New York State Infection Control

Earn CME/CE in your profession:


Continuing Education Activity

Infection control refers to the policy and procedures implemented to control and minimize the dissemination of infections in hospitals and other healthcare settings, with the main purpose of reducing infection rates. The primary purpose of infection control programs has been to focus on the surveillance of hospital-acquired infections and understand the epidemiology of the risk factors. In more recent times, healthcare epidemiology is characterized by consumer demands for more transparency and accountability, increasing scrutiny and regulation, and expectations for rapid reductions in HAIs rates. The role of infection control is to prevent and reduce the risk of hospital-acquired infections. This can be achieved by implementing infection control programs in the forms of surveillance, isolation, outbreak management, environmental hygiene, employee health, education, and infection prevention policies and management. This activity reviews the New York State requirements in educating healthcare professionals in regards to infection control.

Objectives:

  • Review the risk factors for developing a hospital-acquired infection.

  • Identify the most common morbidity and mortality associated with a hospital-acquired infection.

  • Summarize key education points a health professional should impart to their staff regarding preventing hospital-acquired infections.

Introduction

Infection control refers to the policy and procedures implemented to control and minimize the dissemination of infections in hospitals and other healthcare settings, with the main purpose of reducing infection rates. Infection control as a formal entity was established in the early 1950s in the United States. By the late 1950s and 1960s, a small number of hospitals began to recognize healthcare-associated infections (HAIs) and implemented some of these infection control concepts. The primary purpose of infection control programs was to focus on the surveillance for HAIs and in-cooperate the basic understandings of epidemiology to elucidate risk factors for HAIs.[1] However, most of the infection control programs were organized and managed by large academic centers rather than public health agencies, which lead to sporadic efficiency and suboptimal outcomes. It was not until the late 19th and early 20th century when the new era in infection control was started through three pivotal events. These events included the Institute of Medicine’s 1999 report on errors in health care, the 2002 Chicago Tribune representation on HAIs, and the 2004/2006 publications of the significant reductions in bloodstream infection rate through the standardization of central venous catheter insertion process.[2][3][4] 

This new era in healthcare epidemiology is characterized by consumer demands for more transparency and accountability, increasing scrutiny and regulation, and expectations for rapid reductions in HAIs rates.[5] The role of infection control is to prevent and reduce the risk of hospital-acquired infections. This can be achieved by implementing infection control programs in the forms of surveillance, isolation, outbreak management, environmental hygiene, employee health, education, and infection prevention policies and management.[6]

Function

The significance and function of infection control are substantial. There are almost 2 million hospital-acquired infections annually, and of these, nearly 100,000 people die annually.[6] Due to the significance of the problem, New York State implemented Chapter 768, which requires health professionals to take two hours of New York State Department of Education continuing education every four years covering CDC standards of infection control and the possibility of unprofessional conduct due to lack of compliance with the law. This course meets the New York State State Chapter 768 mandatory requirement.

The state law requires professionals to be familiar with the following elements of infection control in the healthcare setting:

  1. Adhere to scientifically accepted principles and practices of infection control and monitor the performance of professionals for whom the health professional is responsible.
  2. Understand the modes and mechanisms of transmission of pathogenic organisms and strategies for control and prevention.
  3. Use engineering and work practice controls to reduce the opportunity for patient and worker exposure to potentially infectious material.
  4. The use and selection of barriers and/or personal protective equipment for preventing patient and healthcare worker contact with potentially infectious material.
  5. The creation and maintenance of a safe environment for patient care through the application of infection control practices and principles for cleaning, disinfection, and sterilization.
  6. The prevention and management of infectious or communicable diseases in healthcare workers.
  7. Sepsis awareness and education.

Health professionals should take the New York statute seriously as the consequences are potentially severe:

  • Evidence of completion of training must be submitted to the State Department of Health or the Education Department.
  • Health professionals with hospital privileges are required to present documentation of training to the hospital during the renewal of hospital privileges.
  • Virtually all professionals, including physicians, physician assistants, and podiatrists (including students and residents), nurses, nurse practitioners, dentists, and dental hygienists, must complete and maintain training.
  • Exemptions are available from the Department of Health if a health professional has completed equivalent course work or their practice does not require infection control or barrier precautions.
  • The statute establishes minimum rules for compliance and consequences for non-compliance for facilities, which includes a possible citation, fine, and other disciplinary action.
    • Employee or patient complaints concerning poor infection control practices may result in an investigation by the Department of Education or the Department of Health.
  • Healthcare professionals who fail to use appropriate infection control techniques, are aware of violations, or are responsible for lax staff compliance and education may be charged with professional misconduct and receive disciplinary action. 

Required Documentation

Physicians, Physician Assistants, and Specialist Assistants

  • When the course is completed, retain the Certificate of Completion.
  • If affiliated with a hospital, submit a copy of the Certificate of Completion to your hospital personnel office or administration. Hospitals are required to verify completion prior to credentialing health professionals.
  • If not affiliated with a hospital, submit the Certificate of Completion to the Department of Health.
  • Retain a copy of the Certificate of Completion for at least 6 years.

Nurses, Dentists, Dental Hygienists, Podiatrists, and Optometrists

  • When the course is completed, retain the Certification of Completion.
  • Maintain a copy of the Certificate of Completion in the event you are asked to submit it.
  • Attest to completing this requirement to the State Education Department on the initial licensure/registration application and each subsequent registration.

Issues of Concern

Element 1. Adhere to scientifically accepted principles and practices of infection control and monitor the performance of professionals for whom the health professional is responsible.

Hospital-acquired infections are a significant cause of morbidity and mortality and cost billions of dollars annually. The most common hospital-acquired infections include the urinary tract, surgical sites, pneumonia, and bloodstream infections. According to the Center for Disease Control, the following table describes the most common pathogens. Health professionals should be aware of each disease, how to avoid spread.

Acinetobacter 

Acinetobacter bacteria is commonly found in soil and water and can cause infection in the blood, lungs, urinary tract, and wounds. I can colonize a patient and be found in respiratory secretions and wounds. It causes thousands of infections in hospitalized patients and hundreds of deaths. High-risk patients include those with indwelling catheters or open wounds, those on ventilators, and any patient with a prolonged stay. Those with weak immune systems are more susceptible. It is spread on environmental surfaces, especially if they are not properly cleaned or through person-to-person contact such as contaminated hands. Spread can be avoided by handwashing with soap and water or using alcohol-based hand sanitizer, cleaning medical devices, and rigorous environmental cleaning. Acinetobacter is often carbapenem-resistant and usually multidrug-resistant. Treatment is usually selected after culture, and a sensitivity report is obtained from the laboratory.[7]

Burkholderia cepacia

Burkholderia cepacia can be found in soil and water. It is rarely found in immunocompromised patients, particularly those with chronic lung diseases such as cystic fibrosis, and hospitalized patients. It is transmitted via contaminated medicines such as mouthwash, over-the-counter nasal spray, contaminated medical devices, and person-to-person contact. B. cepacia may be resistant to most antibiotics. Treatment of B. cepacia is made on a case-by-case basis.[8]

Clostridioides difficile

Clostridioides difficile causes life-threatening diarrhea, fever, nausea, and abdominal pain, and lost appetite. It is commonly a side-effect of taking antibiotics. High-risk individuals are over the age of 65, live in nursing homes or hospitals for extended periods, and those with weak immune systems. It is spread person-to-person. Effective prevention of C. difficile infection includes early detection of the disease, placing the patient under isolation with a dedicated toilet and contact precautions, promoting hygiene measures such as improved hand hygiene and environmental cleaning. It is evaluated by stool examination for C. difficile toxins, or toxigenic C. difficile bacillus is the commonly used diagnostic test. The management of C. difficile infection includes discontinuing inciting antibiotics, isolating the patient, and administering an antibiotic based on the severity of the infection. The antibiotics usually used in the treatment of C. difficile infection are vancomycin or fidaxomicin. Asymptomatic patients do not require treatment. Intravenous metronidazole can be used in a patient who suffers from ileus, where the delivery of orally administered antibiotics will be delayed.[9]

Clostridium sordellii is a rare bacterium that causes arthritis, bacteremia, peritonitis, endocarditis, pneumonia, myonecrosis, and sepsis. Women are at the highest risk of infection following the end of pregnancy. Symptoms include diarrhea, nausea, vomiting, and abdominal pain without fever. It is not known how C. sordellii is spread. C. sordellii is treated with supportive measures such as IV fluids and susceptible to beta-lactam, clindamycin, chloramphenicol, and tetracycline, while resistant to aminoglycosides and sulfonamides. 

Carbapenem-resistant Enterobacteriaceae (CRE) and Carbapenemase-producing CRE (CP-CRE)

Enterobacteriaceae are bacteria found in the gastrointestinal tract that cause infections both in healthcare and community settings. CRE can cause bloodstream infections, ventilator-associated pneumonia, intra-abdominal abscesses, and urinary tract, often in people who have a urinary catheter or have urinary retention. Enterobacteriaceae are a common cause of fatal infections in both community and healthcare settings. CP-CRE is thought to be primarily responsible for the spread of CRE in the United States and has been targeted for aggressive prevention. Enterobacteriaceae that are resistant to at least one of the carbapenem antibiotics or produce the enzyme carbapenemase that makes them resistant to carbapenem antibiotics are called CRE. When found in culture, CRE can represent an infection or chronic colonization. The main risk factors for CRE is exposure to the healthcare-related risk factors, including help with activities of daily living, exposure to an intensive care unit, and mechanical ventilation. Several antibiotics have been associated with getting CRE, including carbapenems, cephalosporins, fluoroquinolones, and vancomycin. CRE is transmitted from person to person and contaminated medical equipment. Prevent CRE by placing patients currently or previously colonized in a private room and dedicated noncritical equipment. Personnel should wear a gown and gloves and use hand hygiene. Avoid long-term use of urinary catheters. Predictors of prolonged CRE carriage have been found to include: antibiotic exposure, invasive device use, high Charlson's co-morbidity score, frequent hospital admission, and long-term care facility. Surveillance and long-term contact precautions of 3 to 6 months may decrease the spread of CRE.[10]

ESBL-producing Enterobacteriaceae

Enterobacteriaceae very commonly cause infections and death in both the healthcare settings and in communities. Examples include Escherichia coli and Klebsiella pneumoniae. These infections commonly occur with exposure to healthcare; however, ESBL-producing Enterobacteriaceae can also cause infections in otherwise healthy people, such as those with urinary tract infections. Enterobacteriaceae can produce enzymes called extended-spectrum beta-lactamases (ESBLs), which break down and destroy commonly used antibiotics, including penicillins and cephalosporins, and make these drugs ineffective. As a result, even common infections, such as urinary tract infections caused by ESBLs, require complex treatments such as intravenous carbapenem antibiotics. Enterobacteriaceae can be spread from one person to another in healthcare settings through contaminated hands and surfaces and contaminated food or water. Hand-hygiene, after using the bathroom and before eating, reduces the spread of these infections. Treatment is hospitalization and IV carbapenem antibiotics, which are typically reserved for highly resistant ESBL-producing Enterobacteriaceae infections.[10]

Gram-negative Bacteria

Gram-negative bacteria (GNB) are a significant public health problem due to their high resistance to antibiotics, and hospitalized patients are at a high risk of morbidity and mortality.[1][2] The gram-negative bacteria can reach almost all systems such as the digestive system, nervous system, urinary system, and the bloodstream, causing gastroenteritis and meningitis. Infection is particularly dangerous in immunocompromised individuals those that acquire a multiresistant infection. Cultures and gram-stain are the only way to determine the organism.[25]  Treatment options for gram-negative drug-resistant infections are limited. Overuse of antimicrobials is one of the key causes. Hand-hygiene may reduce the incidence.[10]

Hepatitis A

Healthcare-associated hepatitis A virus is rare. It is spread by the fecal-oral route, and transmission to healthcare personnel usually occurs a patient is fecally incontinent or has diarrhea. Other risk factors include eating or drinking in patient care areas, not washing hands after handling an infected infant, and sharing food, beverages, or cigarettes.[11]

Hepatitis B

Hepatitis B can cause lifelong infection, cirrhosis of the liver, liver cancer, liver failure, and death. It is spread in healthcare settings when body fluids from an infected person enter a non-infected individual primarily through contaminated needles, syringes, or other sharp instruments.[11]

Hepatitis C

Hepatitis C causes lifelong infection, cirrhosis, or liver cancer. It is spread by contact with the blood. It is uncommonly spread in the healthcare setting primarily through contaminated needles, syringes, or other sharp instruments.[11]

Human Immunodeficiency Virus (HIV)

Human immunodeficiency virus (HIV) can result in acquired immune deficiency syndrome (AIDS). HIV destroys CD4+ T cells, which are crucial to fighting disease resulting in a weakened immune system and the risk for many different types of infections. The transmission of HIV in healthcare settings is rare. Proper sterilization and disinfection procedures are required to minimize risks. Most exposures do not result in infection. The best prevention is to follow universal precautions, including protective practices and personal protective equipment.[12]

Klebsiella

Klebsiella is a Gram-negative bacterium that causes healthcare-associated infections, including bacteremia, pneumonia, meningitis, surgical site, and wound infections. Klebsiella has developed antimicrobial resistance to the carbapenems. In healthcare settings, patients who require a ventilator, intravenous catheters, and chronic antibiotics are most at risk. Klebsiella is spread through person-to-person contact. To prevent spreading Klebsiella infections, healthcare workers should practice hand hygiene and wear gowns and gloves when caring for infected patients. Klebsiella infections that are not drug-resistant are treated with antibiotics.[13]

MRSA

Methicillin resistance in S. aureus is an oxacillin minimum inhibitory concentration greater than or equal to 4 micrograms/mL. It is a common cause of hospital-acquired and community-acquired infections associated with significant morbidity, mortality, length of stay, and cost burden. Risk factors include prolonged hospitalization, ICU admission, nursing home or hospitalization, recent antibiotic use, MRSA colonization, procedures, HIV infection, open wounds, hemodialysis, central venous access, or long-term indwelling urinary catheter placement. Healthcare workers in contact with MRSA patients are at high risk. MRSA causes skin infections, osteomyelitis, meningitis, pneumonia, lung abscess, and empyema.[4][5][6] Clinical suspicion in patients with risk factors is crucial in early diagnostic and therapeutic intervention. Confirmation should not delay treatment with empiric antibiotics. Clinicians should send samples from suspected infection sources for analysis, including blood, sputum, urine, or wound scraping.[10][6][8] The selection of empiric antibiotic therapy depends on the type of disease, local S. aureus resistance patterns, availability of the drug, side effect profile, and individual patient profile.[11][12][13] Prevention and control are with strict hand hygiene and adequate contact precautions. Contact precautions include the use of gowns, gloves, and possibly masks during clinical encounters. Infection control includes keeping patients in isolated rooms who have MRSA infections.[14]

Nontuberculous 

Nontuberculous mycobacteria (NTM) is also referred to as atypical mycobacteria, mycobacteria other than tuberculosis (MOTT), or environmental mycobacteria. NTM are opportunistic pathogens placing those with underlying lung disease or depressed immune systems at risk. Infections may be induced in the lungs, soft tissue, lymph nodes, blood, and medical devices. Symptoms are often nonspecific, such as fever, weight loss, night sweats, decreased appetite, and loss of energy. Diagnostic tests such as acid-fast bacilli stain and culture should be ordered, but results make take weeks. NTM are intrinsically resistant to most antibiotics; therapy is individualized to susceptibility and the body site and frequently requires a combination of 2 to 3 antimicrobial agents for 6 months to a year.[15]

Norovirus

Noroviruses cause gastroenteritis with acute onset of vomiting, diarrhea, and stomach cramping. Norovirus illness is usually brief, but in young children, the elderly, and those immunocompromised, the infection has a higher risk of morbidity and mortality. Healthcare facilities and other institutional settings are at-risk for outbreaks because of increased person-to-person contact. Treatment is supportive with fluids. Transmission is through feces and vomit, and it is very contagious if there is direct contact, sharing food or drinks, or touching surfaces. Prevention includes private rooms, hand-hygiene, gowns and gloves, and cleaning and disinfection.[16]

Pseudomonas aeruginosa

Pseudomonas is a bacteria found commonly in soil and water. The most common type of Pseudomonas aeruginosa causes infections in the blood, lungs, and wounds. Multidrug-resistant Pseudomonas aeruginosa is a frequent cause of morbidity and mortality in the hospital, particularly in those on ventilators, patients with indwelling catheters, and burn victims. Resistant strains can be spread from one person to another through contaminated hands, equipment, or surfaces. Spread can be decreased by hand-hygiene, daily room cleaning, and infection control practices. Pseudomonas aeruginosa infections are becoming more difficult to treat with antibiotics due to antibiotic resistance. Culture and sensitivity will help in making an appropriate antibiotic selection.[17]

Staphylococcus aureus

Staphylococcus aureus is common in many individual's noses and is usually does not cause any harm; however, staph in healthcare settings can cause serious or fatal infections, including:

  • Bacteremia or sepsis
  • Endocarditis
  • Osteomyelitis 
  • Pneumonia, particularly if on a ventilator

Staph causes several different types of infections, including:

  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Methicillin-susceptible Staphylococcus aureus (MSSA)
  • Vancomycin-intermediate Staphylococcus aureus (VISA)
  • Vancomycin-resistant Staphylococcus aureus (VRSA)

Populations at risk for Staphylococcus aureus infection include those with chronic conditions such as diabetes, cancer, vascular disease, eczema, lung disease, IV drug abusers, patients with weak immune systems, in the ICU, post-surgery, and if they have an inserted medical device. Routine cultures will typically reveal the diagnosis; however, RT-PCR for 16S rRNA genes may be necessary in some cases. Drug susceptibility testing often is required to guide treatment.[4] Treatment depends largely on the type of infection as well as the presence or absence of drug-resistant strains.[6] When antimicrobial therapy is needed, the duration and mode of therapy are largely dependent on the infection type and other factors.[6] In general, penicillin remains the drug of choice if isolates are sensitive and vancomycin for MRSA strains.[3] In some cases, alternative therapy is necessary in addition to antimicrobial therapy.[6] Prevention relies on infection control methods such as hospital decontamination procedures, handwashing, and MRSA transmission prevention guidelines. Topical antimicrobials such as mupirocin can be used to eliminate nasal colonization in some nasal carriers. 

Tuberculosis

Transmission of Mycobacterium tuberculosis is a risk to patients and healthcare personnel. Transmission is more likely if pulmonary or larynx-related TB. Transmission is associated with close contact, particularly during cough-inducing procedures, as it can be spread through the air. Signs and symptoms include chronic cough, weight loss, fever, night sweats, exposure, and blood in the sputum. Cases of multidrug-resistant TB have been recognized and are difficult to treat. Tuberculosis is a preventable and treatable infectious disease. Respiratory precautions should be in effect if a patient is at risk.[18]

VISA/VRSA

Vancomycin intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) are specific types of antimicrobial-resistant bacteria. Persons who develop this type of staph infection usually have underlying health conditions and recent exposure to vancomycin and other antimicrobial agents. Staph bacteria can get into the bloodstream and cause serious morbidity and mortality from bacteremia or sepsis, pneumonia, endocarditis, and osteomyelitis. Staph bacteria are classified as VISA if the MIC for vancomycin is 4 to 8µg/ml and classified as VRSA if the vancomycin MIC is ≥16µg/ml. The condition is treated with antibiotics. The use of appropriate infection control practices, including hand hygiene and wearing gloves, can reduce VISA and VRSA spread.[19]

Vancomycin-resistant Enterococci (VRE) in Healthcare Settings

VRE causes infections in patients in hospitals. Enterococci are bacteria normally present in the human intestines and the female genital tract and can cause infections resulting in significant morbidity and mortality. At-risk patients include those treated with vancomycin, recent surgery or ICU placement, indwelling medical devices, and immunocompromised. VRE can spread from one person to another through contact and via contaminated surfaces or equipment. It can be reduced by hand-hygiene, frequent cleaning, and wearing gloves when in contact with VRE patients. VRE is treated with antibiotics based on sensitivity tests. Chronically colonized patients do not require treatment.[20][21]

Healthcare professionals do not always follow the principles and practices of infection control due to rushing, sloth, or lack of education. Health professionals have a duty to "first do no harm." As such, they have an ethical responsibility to adhere to scientifically accepted or evidence-based practices of infection control. New York State has been very proactive and has included the legal responsibility to adhere to such principles. Legal requirements include both performing safe practices and training staff in safe practices, including the following:

  • Failure to be aware of common healthcare-related infections and how to decrease their incidence
  • Failure to practice appropriate hand hygiene
  • Failure to practice safe injection
  • Failure to sterilize instruments correctly
  • Failure to use the sharps containers
  • Failure to wear gloves or use personal protective equipment

Element 2: Understand the modes and mechanisms of transmission of pathogenic organisms and control and prevention strategies.

Clinicians need to understand the pathophysiology of infection to better prevent and treat infections. There are four types of pathogens: bacteria, fungi, parasites, and viruses. Transmission requires adequate minimum numbers to cause disease and environmental factors conducive to the growth and spread of the pathogen. If the pathogen has an environment conducive to growth, it may result in active disease or a chronically colonized patient. Locations of growth in humans include the alimentary tract, blood, body fluids, genitourinary tract, integument, respiratory tract, and transplacental. Transmission of a pathogen occurs through three routes contact (direct and indirect), droplet, and airborne.[22]

Contact Transmission

Direct: When microorganisms are transferred from one person to person without a contaminated intermediate. 

Indirect: When the transfer occurs through a contaminated intermediate person or object. 

Droplet Transmission

Respiratory droplets transmit the infection from the respiratory tract to susceptible mucosal surfaces of the recipient, commonly from coughing, sneezing, intubation, or suctioning.

Airborne Transmission

Distribution of airborne droplet nuclei or small particles containing infectious agents that remain in the air over time and distance. The dispersion may occur by air currents over long distances.

Element III: Use engineering and work practice controls to reduce the opportunity for patient and worker exposure to potentially infectious material.

Infection control refers to the policy and procedures implemented to control and minimize the dissemination of infections in hospitals and other healthcare settings, with the main purpose of reducing infection rates. Infection control as a formal entity was established in the early 1950s in the United States. By the late 1950s and 1960s, a small number of hospitals began to recognize healthcare-associated infections (HAIs) and implemented some of the infection control concepts. The primary purpose of infection control programs was to focus on the surveillance of HAIs and in-cooperate the basic understandings of epidemiology to elucidate risk factors for HAIs.[1] However, most of the infection control programs were organized and managed by large academic centers rather than public health agencies, which lead to sporadic efficiency and suboptimal outcomes. It was not until the late 19th and early 20th century when the new era in infection control was started through three pivotal events. These events included the Institute of Medicine’s 1999 report on errors in health care, the 2002 Chicago Tribune representation on HAIs, and the 2004/2006 publications of the significant reductions in bloodstream infection rate through the standardization of central venous catheter insertion process.[2][3][4] This new era in healthcare epidemiology is characterized by consumer demands for more transparency and accountability, increasing scrutiny and regulation, and expectations for rapid reductions in HAIs rates.[2][3][2][5] The role of infection control is to prevent and reduce the risk of hospital-acquired infections. This can be achieved by implementing infection control programs in surveillance, isolation, outbreak management, environmental hygiene, employee health, education, and infection prevention policies and management.

The infection control program has the main purpose of preventing and stopping the transmission of infections. Specific precautions are needed to prevent infection transmission depending on the microorganism.

The following are examples of indications for transmission-based precautions:

  • Standard precautions: Used for all patient care. It includes hand hygiene, personal protective equipment, appropriate patient placement, cleaning and disinfects patient care equipment, textiles and laundry management, safe injection practices, proper disposal of needles and other sharp objects.
  • Contact precaution: Used for patients with known or suspected infections that can be transmitted through contact. Standard precautions are needed for those patients, plus limit transport and movement of patients, use disposable patient care equipment, and thorough cleaning and disinfection strategies. Patients with acute infectious diarrhea such as Clostridium difficile, vesicular rash, respiratory tract infection with a multidrug-resistant organism, abscess, or draining wound that cannot be covered need to be under contact precautions.
  • Droplet precautions: Used for patients with known or suspected infections that can transmit by air droplets through the mechanism of a cough, sneeze, or talking. In such cases, it is vital to control the source by placing a mask on the patient, use standard precautions plus limitations on transport and movement. Patients with respiratory tract infection in infants and young children, a petechial or ecchymotic rash with fever, and meningitis are placed under droplet precautions.
  • Airborne precautions: Use for patients with known or suspected infections are transmittable by the airborne route. Those patients require to be in an airborne infection isolation room with all the previously mentioned protections. The most important pathogens that need airborne precautions are tuberculosis, measles, chickenpox, and disseminated herpes zoster. Patients with suspected vesicular rash, cough/fever with pulmonary infiltrate, a maculopapular rash with cough/coryza/fever need to be under airborne precaution.

Multiple of those indications might require more than one precaution to ensure the efficient standard and transmission-based precautions. For example, patients with suspected C. difficile need to be under contract and standard precautions; tuberculosis patients need to be under airborne, contact, and standard precautions.

Equipment

Healthcare facilities must have the necessary equipment to implement the standard precautions for all patients. The most significant precaution that is effective in preventing infection transmission is hand hygiene. This is achieved by washing hands with soap and warm water and/or by hand rubbing with alcohol or nonalcohol based hand sanitizer. Gloves can also be used as a standard precaution; new gloves must be used for each patient and disposed of after each patient interaction. Other personal protective equipment includes facial protection (procedure/surgical masks, goggles, face shield) and gown before entering the patient's room. Infection control equipment also includes the housekeeping tools where adequate and routine disinfection of surfaces and floors are implemented. Also, linens have to be handled and transported in a manner that prevents skin and mucous exposure by using the appropriate personal protective equipment.

Personnel

Hospitals need to attain hospital epidemiologists, infection preventionists, and an infection control committee to organize a well-structured and implemented infection control program. The hospital epidemiologist must interface with many hospital departments and administrators to discuss their responsibilities, expectations, and available resources. The epidemiologist generally oversees the infection prevention program and, in some cases, the quality improvement program. A physician with a subspecialty in infectious disease usually holds the position.[23] A registered nurse with a background in clinical practice, epidemiology, and basic microbiology typically holds the infection preventionist title. Hospitals can have multiple infection preventionists depending on the number of beds available, mix of patients, and the Center for Disease Control and Prevention (CDC) recommendations.[24] The last aspect of a functioning infection control program is the infection control committee, which consists of an interprofessional group of clinicians, nurses, administrators, epidemiologists, infection preventionists, and other representatives from the laboratory, pharmacy, operating rooms, and central services. The responsibilities of this committee are to generate, implement, and maintain policies related to infection control.[24]

Technique

To achieve a successful and functioning infection control program, a hospital can implement the following measures:

Surveillance: The primary aim of surveillance programs is to assess the rate of infections and endemic likelihood. Generally, hospitals target surveillance for HAIs in areas where the highest rate of infection is, including intensive care units (ICUs), hematology/oncology, and surgery units. However, surveillance has expanded in recent years to include hospital-wide based surveillance as it is becoming a mandatory requirement by the public health authorities in multiple states.[25] This change has also been empowered by the wide implementation of electronic health records in most hospitals in the United States. It is now easy for any medical provider to access the electronic records at patients’ bedside and assess risks and surveillance data for each patient. Most hospitals have developed sophisticated algorithms in their electronic health systems that could streamline surveillance and identify patients at the highest risk for HAIs. Hence, hospital-wide surveillance targeting a specific infection could be implemented relatively easily. Public health agencies require that hospitals report some specific infections to strengthen the public health surveillance system.[26]

Isolation: The main purpose of isolation is to prevent the transmission of microorganisms from infected patients to others. Isolation is an expensive and time-consuming process; therefore, it should only be utilized if necessary. On the other hand, if isolation is not implemented, we risk an increase in morbidity and mortality, thereby increasing overall healthcare costs. Hospitals that operate based on single-patient per room can implement isolation efficiently; however, significant facilities still have a substantial number of double-patient rooms, which is challenging for isolation.[27] The CDC and the Healthcare Infection Control Practice Advisory Committee have issued a guideline to outline the approaches to enhance isolation. These guidelines are based on standard and transmission-based precautions. The standard precaution refers to the assumption that all patients are possibly colonized or infected with microorganisms; therefore, precautions are applied to all patients, at all times and in all departments. The main elements for standard precautions include hand hygiene (before and after patient contact), personal protective equipment (for contact with any body fluid, mucous membrane, or nonintact skin), and safe needle practices (use one needle per single-dose medication per single time, then dispose of it is a safe container).[28] Other countries such as the United Kingdom have also adopted the bare below the elbows initiative that requires all healthcare providers to wear short-sleeved garments with no accessories, including rings, bracelets, and wristwatches. As for the transmission-based precautions, a cohort of patients is selected based on their clinical presentations, diagnostic criteria, or confirmatory tests with specific indication of infection or colonization of microorganisms to be isolated. In these cases, a requirement for airborne/droplet/contact precautions is necessary. These precautions are designed to prevent the transmission of disease based on the type of microorganism.[29]

Outbreak Investigation and Management: Microorganisms outbreaks can be identified through the surveillance system. Once a particular infection monthly rate crosses the 95% confidence interval threshold, an investigation is warranted for a possible outbreak. Also, clusters of infections can be reported by the healthcare providers of laboratory staff, which should be followed by an initial investigation to assess if this cluster is indeed an outbreak. Usually, clusters of infections involve a common microorganism that can be identified using the pulsed-field gel electrophoresis or the whole-genome sequencing, which provides more detailed tracking of the microorganism. Most outbreaks are a result of direct or indirect contact involving multidrug-resistant organisms. Infected patients require separation, isolation if needed, and the implementation of the necessary contact precautions, depending on the suspected cause of infection. These measures must be enforced to control such outbreaks.[30]

Education: Healthcare professionals need to be educated and periodically reinforce their knowledge through seminars and workshops to ensure a high understanding of how to prevent communicable disease transmission. The hospital might develop an infection prevention liaison program by appointing a healthcare professional who could disseminate the infection prevention information to all hospital members.

Employee Health: It is essential for the infection control program to work closely with employee health services. Both teams need to address important topics related to employees' well-being and infection prevention, including managing exposure to bloodborne communicable diseases and other communicable infections. Generally, all new employees undergo a screening by the employee health service to ensure that they are up-to-date with their vaccinations and have adequate immunity against some common communicable infections such as hepatitis B, rubella, and mumps, measles, tetanus, pertussis, and varicella. Moreover, healthcare employees should always be encouraged to take the annual influenza vaccination. Also, a periodic test for latent tuberculosis should be performed to assess for any new exposure. Employ health service should develop proactive campaigns and policies to engage employees in their wellbeing and prevent infections.

Antimicrobial Stewardship: Antimicrobials are widely used in the inpatient and outpatient settings. Antimicrobial usage widely varies between hospitals. Commonly, a high percentage of patients admitted to hospitals are administered antibiotics. Hospitals are increasingly adopting antimicrobial stewardship programs to control antimicrobial resistance, improve outcomes, and reduce healthcare costs. Antimicrobial stewardship should be programmed to monitor antimicrobial susceptibility profiles to anticipate and assess any new antimicrobial resistance patterns. These trends need to be correlated with the antimicrobial agents used to evaluate susceptibility.[31] Antimicrobial stewardship programs can be designed to be active and/or passive and target pre-prescription or post-prescription periods. An active program includes prescription restrictions and preauthorization in the pre-prescription period, while passive initiatives include education, guidelines, and antimicrobial susceptibility reports. On the other hand, an active post-prescription program would focus on a real-time feedback provision to physicians regarding antibiotic usage, dose, bioavailability, and susceptibility with automatic conversion of intravenous to oral formulations, while passive post-prescription involves the integration of the electronic medical records to generate alerts for prolonged prescriptions and antibiotic-microorganism mismatch.[32]

Policy and Interventions: The main purpose of the infection control program is to develop, implement, and evaluate policies and interventions to minimize the risk of HAIs. The hospital’s infection control committee usually develops policies to enforce procedures that are generalizable to the hospital or certain departments. These policies are developed based on the hospital’s needs and evidence-based practice. Interventions that impact infection control can be categorized into two categories; vertical and horizontal interventions. The vertical intervention involves the reduction of risk from a single pathogen. For example, the surveillance cultures and subsequent isolation of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Whereas horizontal intervention targets multiple different pathogens transmitted via the same mechanism, such as handwashing hygiene, clinicians must wash their hands before and after any patient contact, which will prevent the transmission of multiple different pathogens. Vertical and horizontal interventions can be implemented simultaneously and are not mutually exclusive. However, vertical interventions might be more expensive and would not impact the other drug-resistant pathogens, while horizontal interventions might be a more affordable option with more impactful results if implemented appropriately.[33]

Environmental Hygiene: As the inpatient population becomes more susceptible to infections, the emphasis on environmental hygiene has increased. Hospital decontamination through the traditional cleaning methods is notoriously inefficient. Newer methods, including steam, antimicrobial surfaces, automated dispersal systems, sterilization techniques, and disinfectants, have a better effect in limiting the transmission of pathogens through the surrounding environment.[34] The CDC has published guidelines that emphasize the collaboration between federal agencies and hospital engineers, architectures, public health, and medical professionals to manage a safe and clean environment within hospitals, including air handling, water supply, and construction.[35]

Clinical Significance

Infection control clinically translates to identifying and containing infections to minimize its dissemination. Clinicians play a significant role in infection control by identifying patients' signs and symptoms suspicious for a transmissible infection such as tuberculosis. Precaution orders have to be placed and implemented even before a confirmatory diagnosis is reached to avoid the possible transmission of the infectious pathogen. Clinically, an efficient infection control program results in fewer infection rates and a lower risk of developing multidrug-resistant pathogens. Hospital-acquired infections are one of the most common healthcare complications. Therefore simple standard precautions such as hand hygiene can prove to be highly effective. In fact, the most effective and least expensive way for clinicians to also apply infection control principles is by washing hands before and after any patient interaction.[36] Hence, hospitals need to promote handwashing by providing reminders at all bedsides and having sinks or hand sanitizer stations available at the entrance to each room in the hospital. Another simple measure can be to educate patients to always try to use their forearm to block their cough or sneeze to avoid the transmission of droplets and the direct contamination of their hands by which pathogens can be transferred to other surfaces.

Enhancing Healthcare Team Outcomes

Infection control has many challenges, especially with the increasing number of hospitalized patients, a greater prevalence of invasive technologies, and a higher prevalence of immunocompromised patients.[37] Poor infection control programs lead to increased rates of infections, increase the likelihood of multidrug-resistant bacterias, and increases the risk of outbreaks in specific departments that might disseminate to the entire hospital and community. Resources are one of the major limitations in achieving an optimal infection control program; hospital epidemiologists should consider the balance between cost, clinical outcomes, patient satisfaction, and economic impact when considering new interventions. Hospital epidemiologists also need to assess the latest evidence-based literature to ensure that all infection control policies are up-to-date and monitor newly emerging multidrug-resistant pathogens. The major direct complication of an inappropriately managed infection control program is infection risk for the patient. Patients might be at risk for bacterial, viral, fungal, or parasitic infection. If the infection is severe, it can spread to the bloodstream leading to sepsis and possible septic shock, which are life-threatening. All healthcare workers have a duty to prevent infection and maintain an aseptic environment when possible. Nursing is on the front lines of this issue since they routinely have the highest level of contact with the patient and have access to all aspects of the facility; their observations and recommendations should be taken seriously by all interprofessional healthcare team members. The most basic preventive method is by washing hands. 

Element 4: The use and selection of barriers and/or personal protective equipment for preventing patient and healthcare worker contact with potentially infectious material.

In a world of evolving disease, accidental industrial or commercial contamination, as well as foreign and domestic terrorism, providers must be able to provide safe and efficient care to patients while wearing personal protective equipment (PPE). The most common schema for PPE is the United States Occupational Safety and Health Administrations' (OSHA) PPE protection levels A, B, C, and D.[38]

OSHA defines PPE as specialized clothing or equipment worn for protection against infectious or other hazardous materials. Selection of PPE equipment is based on:

  • Anticipated exposure type - contact, splash, and/or spray.
  • Category of isolation precaution required.
  • Durability and appropriateness, durability, and fit for the task.

OSHA requires appropriate PPE for employees, appropriate disposal, and, if reusable, appropriately cleaned after each use. 

The nature of evolving viruses that cause Ebola, severe acute respiratory syndrome (SARS), COVID-19, and Middle Eastern respiratory syndrome (MERS) has required the use of PPE by providers to avoid natural or nosocomial inoculation from airborne or contact means.[39] Indication for resuscitation with PPE is the need to care for patients at risk of spreading infectious diseases.[40][41]

Equipment

  • Gloves - protect the hands.
  • Aprons and gowns - protect skin and clothing.
  • Face shields - protect eyes, face, mouth, and nose.
  • Goggles - protect the eyes.
  • Masks - protect the mouth/nose.
  • Respirators - protect the respiratory tract from airborne infections.

Providers require PPE so they can safely enter the rooms of infected patients. A risk-benefit analysis chooses equipment for PPE levels of protection. The benefits increase with more restrictive PPE levels, but also proportionally increases the risk from physiological stress. The appropriate PPE needs to be chosen for the right task or hazard. Equipment is based on United States Occupational Safety and Health Administration (OSHA) standards.

  • Level A offers the highest level of protection and is best used for unknown threats. Level A protects operators from liquids, vapors, and gases. Level A equipment encompasses a positive pressure full face mask connected to a self-contained breathing apparatus (SCBA), a totally encapsulated suit, outer chemical resistant gloves, inner chemical resistant gloves, and chemical-resistant boots.
  • Level B offers protection from liquids, gases, but not vapors. Level B consists of positive-pressure, full-faced, self-contained breathing apparatus (SCBA), hooded chemical-resistant clothing, outer chemical-resistant gloves, inner chemical-resistant gloves, chemical resistant-boots, boot covers, and face shield. 
  • Level C is most commonly used in healthcare facilities and consists of a full or half-face mask, air-purifying respirator, chemical hooded resistant clothing, outer and inner chemical-resistant gloves, chemical-resistant boots, boot covers, and face shield. 
  • Level D provides the least amount of protection and entails a work uniform, gloves, boots, safety glasses, and a face shield.[42] These modes of PPE protect against a plethora of threats when used appropriately.

Key Steps

  1. Work from "clean" to "dirty."
  2. Hand-hygiene and then don PPE before contact
  3. Don, before entering the room in order:
    • Gown
    • Mask or respiratory
    • Goggles or face shield
    • Gloves
  4. Continue use of PPE during contact.
    • Keep hands away from the face.
    • Limit surfaces touches.
    • Change when heavily contaminated.
  5. When contact completed, remove at the doorway or immediately outside the room, and discard PPE avoiding contamination, in order:
    1. Gloves
    2. Goggles or face shield
    3. Gown
    4. Mask or respiratory
  6. Post-hand-hygiene

Clean Areas

  • Inside, outside back including ties; areas of PPE not in contact with infectious organisms.

Contaminated Areas

  • Outside front of the PPE, contact with body sites, or environmental surfaces

Gloving and Degloving

  • Locate correct size
  • Insert hand into gloves over isolation gown
  • Avoid touching yourself with contaminated gloves.
  • Change gloves after each use.
  • Remove at the doorway, before leaving the room, peel away from hand, turning gloves inside out without touching the contaminated area, discard appropriately, never reuse

Aprons and Gowns Donning and Removing

  • Locate the correct apron or gown type and size for the isolation and protection required
  • The opening is in the back with secure ties at the neck and waist; two gowns may be worn if too small (one in the front and one in the back); don front to back.
  • Remove front to back, turning contaminated region outside to the inside, discard appropriately, never reuse

Mask/Respirator Donning and Removing

  • Mask or respirator should fit snuggly over the nose and mouth.
  • Place mask over the nose, mouth, and chin with nose piece of the bridge of the nose and secure ties or elastic band
  • To remove, grasp bottom tie, then top tie and remove, avoid touching the contaminated area, discard appropriately, never reuse

Goggles/Face Shields Donning and Removing

  • Goggles should fit snuggly around the eyes; a face shield should cover the forehead and extend below the chin.
  • Position over eyes and face and secure using the earpieces or headband, adjusting for a snug fit.
  • Remove with a clean ungloved hand, lift away from the face, avoid touching the contaminated area, discard appropriately, never reuse.

Respiratory Protection Donning and Removing

  • Respiratory respirator PPE types include particulate, elastomeric, powered air-purifying
  • Select a fit-tested respirator and place over the nose, mouth, and chin; secure and adjust on the head; perform a fit-check (Inhale, the respirator should collapse; exhale, no leakage)
  • Removing by lifting the bottom elastic first of head, lift the elastic, discard appropriately

Element 5. The creation and maintenance of a safe environment for patient care by applying infection control practices and principles for cleaning, disinfection, and sterilization.

Health professionals should understand infection control practices and the principles of cleaning, disinfection, and sterilization. To do so, the following provides a review of terms that should be understood.[43][44]

Contamination - The presence of microorganisms on a surface.

Cleaning - scrubbing of visible soil and foreign materials from objects and surfaces using water, soaps, detergents, or enzymatic products.

Disinfection - a process using chemicals or wet pasteurization that eliminates pathogenic microorganisms.

  • High-level - disinfectant that kills all organisms except bacterial spores and is an approved chemical germicide sterilant.
  • Intermediate - disinfectant that destroys all vegetative bacteria but not bacterial spores and is classified as a tuberculocidal.
  • Low-level - disinfectant that destroys all vegetative bacteria but not bacterial spores and is classified as a disinfectant.

Decontamination - a process using chemicals or physical techniques to destroy, inactivate, or remove a pathogenic microorganism on a surface.

Sterilization - chemical or physical destruction or removal of pathogenic microorganisms and their spores using dry heat, hydrogen peroxide gas plasma, steam under pressure, EtO gas, or liquid chemicals.

Sterilization might be achieved by heat, chemicals, irradiation, high pressure, steam filtration under pressure, dry heat, ultraviolet radiation, gas vapor sterilants, and chlorine dioxide gas. Effective sterilization techniques are essential, and failure could lead to significant morbidity and mortality. The four commonly employed techniques are the following:

Heat Method: Heat is used to kill microbes.

Wet Heat/Steam: Autoclaves use steam heated to 121 to 134 degrees C under pressure. This kills or deactivates all microbes, bacterial spores, and viruses. Autoclaving kills microbes by hydrolysis and coagulation of proteins in cells using intense heat and water.

Dry Heat: Bacteria are exposed to high temperatures by flaming, incineration, or a hot air oven. It is typically used for needles, scalpels, and scissors.

Filtration: Filtering with a pore size that is too small for microbes to pass through is used to remove bacteria; however, it will not remove viruses and phage are smaller than bacteria.

Radiation: Exposing packed materials to radiation (UV, X-rays, gamma rays) for sterilization. UV radiation is safer but has low penetration. X-rays are used for sterilizing large packages and pallet loads of medical devices. Gamma radiation has high penetration and is used to sterilize disposable medical equipment, such as syringes, needles, cannulas and IV sets, and food.

Chemical: Reliable method to kill microbes, but it can damage the material to be sterilized. 

Gas: Used be gases penetrate quickly into the material like steam, but there is a danger of explosion, and it is expensive. Commonly used gases for sterilization are a combination of ethylene oxide and carbon-dioxide. 

Health professionals should understand and know how to apply OSHA, CDC, and WASTE general guidelines concerning the level and potential for contamination, disinfection strategies, reprocessing, and appropriate medical waste management.

OSHA AND GENERAL GUIDELINES

The OSHA standards are designed to limit bloodborne pathogen occupational exposure. All equipment and working surfaces must be cleaned and decontaminated with an appropriate disinfectant after contact with infectious materials or blood. OSHA considers EPA-registered disinfectants labeled as effective against HIV and HBV as appropriate disinfectants provided the surfaces have not become contaminated with concentrations of an agent(s) for which a higher level of disinfection is recommended. In general, for smaller spills, OSHA requires the use of EPA-registered tuberculocidal disinfectants or hypochlorite solution (diluted 1:10 or 1:100 with water), and for larger spills, a 1:10 final dilution of EPA-registered hypochlorite solution should be used to inactivate bloodborne viruses.[45][46][47]

Contamination Level

  • Cross-contamination potential
  • Microorganism type
  • Microorganisms numbers

Contamination Potential

  • Composition, configuration, and design, or configuration 
  • Internal and external
  • Device, equipment, instrument, or surface
  • Frequency of hand contact 
  • Risk level

General Cleaning and Disinfecting Strategies [48][49]

  • Avoid high-level disinfectants for disinfection of noncritical instruments and devices.
  • Select EPA-registered disinfectants in accordance with the manufacturer's instructions.
  • Use the recommended cleaning and maintenance of noncritical medical equipment.

Cleaning Frequency, Procedures, Principles, and Reprocessing 

  • Avoid exposing immunocompromised and infants to cleaning and aerosolization of potential contaminants.
  • Avoid cleaning methods that aerosolize contaminants in patient-care areas.
  • Change the mop head daily and more frequently if used on a large spill.
  • Clean and disinfect high-touch surfaces frequently.
  • Clean floors, tabletops, walls, and tabletops frequently.
  • Clean noncritical medical equipment surfaces with a detergent or disinfectant.
  • Consult an infection control expert for cleaning and disinfecting if known or suspected prion disease.
  • Do not use alcohol to disinfect large environmental surfaces.
  • Do not disinfectant with fogging in patient-care areas.
  • Do not use mats with tacky surfaces in or near operating rooms of ICU.
  • Do not use phenolics or chemical germicide to disinfect bassinets or incubators while the infant is present. When using phenolic disinfectants, prepare solutions in accordance with manufacturers' instructions.
  • Devices, equipment, and instruments should be managed and reprocessed according to recommended methods.
  • Follow proper procedures for effective uses of cloths and mops.
  • Instructions should be readily available for cleaning and disinfection of devices, equipment, and instruments.
  • Prepare cleaning solutions daily.
  • Use vacuums with HEPA filters.
  • Use barrier protective coverings noncritical surfaces that are commonly contaminated, challenging to clean, or touched frequently.
  • Use an EPA-registered hospital detergent or disinfectant designed for one-step housekeeping purposes.
  • When using a disinfectant wipe, make sure the surface remains visibly wet.

Reprocessing

  1. Frequent cleaning solution changes
  2. Pre-cleaning internal and external surfaces removing debris and soilage.
  3. Clean with brushes, scrubbing, and automated washers.
  4. For disinfection, sufficient contact time with the chemical solution is necessary.
  5. For sterilization, sufficient exposure time to chemicals, heat, or gases is necessary.

Reprocessing Sequence Based On Manufacturer and Use

Manufacturer

  • Compatibility among equipment
  • Heat and pressure tolerance
  • Time and temperature requirements

Use

  • Low-level disinfection for noncritical instruments and devices
  • High-level disinfection for semi-critical instruments and devices
  • Sterilization required for critical instruments and devices

Reprocessing Effectiveness

  • Prior cleaning and removal of organic matter and biofilms
  • Selection and use of disinfectants and sterilization techniques
  • Monitoring activity and stability of disinfectant, contact time, and usage
  • Post-disinfection/sterilization handling, packaging, and storage

Potential Sources of Cross-contamination

Surfaces which require cleaning between proceduresPractices that contribute to hand contaminationReuse of devices, equipment, and instruments

CDC GUIDELINES

Health professionals should be aware of the OSHA Guidelines and the CDC Guidelines that use the Spaulding classification*, depending on the need for disinfection or sterilization and the categories of critical, semicritical, or non-critical items.[35]

Non-critical Patient Care

Items that contact the skin but not mucous membranes; as the skin blocks access to most microorganisms, sterility of items in contact with intact skin is "not critical" (i.e., crutches, stethoscope, blood pressure cuffs, toilet, sink, and bedpans). Noncritical reusable items may be decontaminated where they are used. Environmental Protection Agency registered disinfectants may be used following directions for dilution, compatibility, safe use, shelf life, storage, and disposal.

Noncritical Environmental Surfaces

Noncritical environmental surfaces often touched by hands such as tables, bed rails, phones, television controls can contribute to the transmission of healthcare workers or medical equipment that contacts patients. Frequent cleaning and use of single-use disposable towels impregnated with a disinfectant will minimize transmission risk.

Semicritical

Items free of all microorganisms with rare bacterial spores may contact mucous membranes or nonintact skin, such as anesthesia equipment, cystoscopes, endoscopes, and anorectal manometry catheters, esophageal manometry probes, laryngoscope blades, and vaginal specula. Semicritical items require chemical disinfectants such as hydrogen peroxide, glutaraldehyde, ortho-phthalaldehyde, and peracetic acid with hydrogen peroxide are acceptable.

Critical

If a catheter, central line, or surgical instrument enters the vascular system or body cavity, it must be sterile. Cleaning must proceed using liquid chemical sterilants, using appropriate sterility and concentration, contact time, pH, and temperature guidelines. Options for sterilization include:

  • Ethylene oxide (EtO)
  • Hydrogen peroxide gas plasma
  • 0.2% peracetic acid
  • 0.08% peracetic acid with 1.0% hydrogen peroxide
  • 2.4% glutaraldehyde-based formulations
  • 0.95% glutarldehyde with 1.54% phenol/phenate
  • 7.35% hydrogen peroxide with 0.23% peracetic acid
  • 7.5% stabilized hydrogen peroxide

*The CDC guidelines recognize limitations of the Spaulding classification system with some medical equipment, particularly those in the semi-critical category, that may have challenges due to potential damage to the instrument.

WASTE MANAGEMENT GUIDELINES

Disposal Plan and Personal

  • Individual(s) should be designated and trained to establish and monitor the collection, handling, treatment, and disposal of wastes.

Waste Categories

  • Body fluids
  • Laboratory microbial
  • Pathology tissues
  • Sharps 

Waste Handling, Transporting, Storing, Treatment, and Disposal

  • Educate staff in the appropriate handling, transportation, treatment, and disposal method, with a particular focus on sharp use and disposal.[50]
  • Leadership position in managing the handling and disposal of regulated wastes:
    • Treat regulated medical wastes by an approved method by the appropriate authority.
      • Sanitary sewers may be used for human tissues provided that local and state discharge requirements are met.
      • Laboratories that isolate clinical specimens need to comply with federal regulations concerning the receipt, transfer, management, and disposal.
        • Biosafety Laboratory
          • Levels 1 and 2 should inactivate amplified microbial cultures and stocks onsite using an approved inactivation method such as autoclaving.
          • Level 3 should inactivate microbiologic waste onsite with autoclaving, incineration, or other approved methods before disposal in a sanitary landfill.
          • Level 4 should inactivate microbiologic waste onsite by using autoclaving or other approved methods before disposal in a sanitary landfill.

Element 6: The prevention and management of infectious or communicable diseases in healthcare workers.

Healthcare workers are at particular risk of acquiring institutionally related infections such as hepatitis B, HIV, influenza, measles, mumps, rubella, and varicella. This risk can be mitigated by using appropriate immunizing agents and rapid response to unexpected exposure, such as a needlestick. At-risk healthcare workers should receive vaccination for preventable illnesses and education and training regarding methods to minimize exposure to bloodborne pathogens and infectious diseases. Exposure prevention and post-exposure prophylaxis are the key elements in reducing related morbidity and mortality. Healthcare facilities should have established policies and procedures to prevent exposure, reporting, evaluation, counseling, and treatment.[51]

Healthcare workers must be properly trained in avoiding needlestick and sharp injuries, as percutaneous exposure is a common cause of HIV/AIDS. If a healthcare worker is exposed to bodily fluids, the site should be washed with soap and water immediately. If a mucous membrane is exposed, it should be flushed with water immediately. Healthcare workers should be educated to report occupational exposures immediately as treatment is more effective when administered immediately after the exposure. Any exposure should be recorded in the healthcare worker's medical records. Healthcare facilities should have a planned 24-hour a day available post-exposure prophylaxis provider available for education and administration of hepatitis B immunoglobulin, HBV vaccine, and HIV antiretroviral agents.[52]

The CDC recommendations for postexposure prophylaxis include*:

Less Severe Exposure (Percutaneous Injury)

  • HIV+, Class 1
    • 2-drug postexposure 
  • HIV+, Class 
    •  3-drug postexposure prophylaxis
  • HIV Status Unknown 
    •  Consider 2-drug postexposure prophylaxis if HIV risk factors

Small Volume (Mucous Membrane and Nonintact skin) 

  • HIV+, Class 1
    • Consider 2-drug postexposure prophylaxis
  • HIV+, Class 
    •  Recommend 2-drug postexposure prophylaxis
  • HIV Status Unknown 
    •  Generally not recommended postexposure prophylaxis

More Severe Exposure (Percutaneous Injury)

  • HIV+, Class 1
    • 3 drug postexposure prophylaxis
  • HIV+, Class 2
    •  3 drug postexposure prophylaxis
  • HIV Status Unknown 
    •  Consider 2 drug postexposure prophylaxis if HIV risk factors

Large Volume (Mucous Membrane and Nonintact skin) 

  • HIV+, Class 1
    • Recommend 2-drug postexposure prophylaxis
  • HIV+, Class 2
    •  Recommend 3-drug postexposure prophylaxis
  • HIV Status Unknown 
    •  Consider 2 drug postexposure prophylaxis if HIV risk factors

 *If postexposure prophylaxis is taken and the source is found to be HIV-negative, treatment should be discontinued. 

Element 7. Sepsis Awareness. 

Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its tissues and organs. Due to its significant morbidity and mortality and increased incidence in institutional settings, all health professionals should know the signs, symptoms, and treatment.

The development of antiseptic measures, the germ theory of disease, and bacteriology have led to the widely held belief that sepsis was a systemic infection resulting from a pathogenic organism invading the host that spreads via the bloodstream (i.e., septicemia). It was not until the further widespread use of antibiotics and the discovery of endotoxin that suggested the pathophysiology of sepsis was far more complex.[53][54]

Despite the increased understanding of this complex disease process, mortality from sepsis remains the most common cause of death in the non-coronary intensive care unit.[55] In the hopes of allowing earlier therapeutic intervention, an international consensus meeting in 1991 created and defined terms, such as systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock (known now as Sepsis-1). SIRS describes the inflammatory process, independent of cause based on a combination of vital signs and blood work.

SIRS

SIRS includes 2 or more of the following:

  • Temperature greater than 38 C or less than 36 C
  • Heart rate greater than 90 beats per minute
  • Tachypnea greater than 20 breaths per minute or PaCO2 less than 32 mm Hg
  • White blood cell (WBC) count greater than 12,000 per cubic millimeter or fewer than 4000 per cubic millimeter, or greater than 10% immature (band) forms

Sepsis

  • SIRS as the result of an infection

Severe Sepsis

  • Sepsis associated with organ dysfunction (1 or more), hypo-perfusion abnormality, or sepsis-induced hypotension
  • Hypo-perfusion abnormalities may include but are not limited to lactic acidosis, oliguria, or acute change in mental status.

Septic Shock

  • Sepsis-induced hypotension despite adequate fluid resuscitation

Multi-Organ Dysfunction Syndrome 

Multi-organ dysfunction syndrome (MODS) is the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

Sepsis-3 redefined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is important to note that not all patients who present with SIRS have an infection. Also, not all patients who have an infection are septic. Sepsis is differentiated from infection by a dysregulated host response and the presence of end-organ dysfunction.[56] Sepsis and its sequelae represent a continuum of clinical and pathophysiologic severity, resulting in progressive physiologic failure of several inter-dependent organ systems.

The Surviving Sepsis Campaign (SSC) and its accompanying treatment bundle were developed with the intention of rapid identification and treatment of septic patients. In 2001, Rivers et al. showed the benefits of a specific protocol termed early goal-directed therapy (EGDT) versus standard therapy, resulting in a significant decrease in mortality.[57] EGDT was subsequently incorporated into the first iteration of the 6hr resuscitation bundle of the Surviving Sepsis Campaign guidelines.[58] These guidelines have changed since their first publication with revisions in 2008, 2012, and finally 2016.[59] Heightened scrutiny of these guidelines and recommendations resulted from the Centers for Medicare and Medicaid Services(CMS) using the bundled care as a hospital quality measure. These were initially adopted by the National Quality Forum 0-500 and subsequently became the Sepsis CMS Core measures known as SEP-1. These measures have come under criticism primarily for the assumption that bundled and structured care is superior to individualized treatment guided by the bedside clinician.[60] In addition to the numerous criticisms of the measures or the evidence supporting them, their mortality benefit remains a point of controversy for many clinicians.

Etiology

The inflammatory response that leads to clinical syndromes such as sepsis is triggered by conditions that threaten the functional integrity of the host, in this case, microbial invasion. Both pro-inflammatory responses and anti-inflammatory responses characterize the host response. The extent of this process depends entirely on both pathogen factors (load, virulence, and pathogen-associated molecular pattern) and host factors (environment, genetics, age, other illnesses, and medications).

At its onset, the host cell will recognize the pathogen leading to a perpetuation of inflammation starting with leukocyte activation, complement activation, and coagulation activation, ultimately resulting in necrotic cell death. Normally, leukocyte activation, primarily neutrophils, are activated early in the inflammatory response cycle and undergo a respiratory burst, consuming lots of oxygen to create toxic metabolites of oxygen. Neutrophils also use their myeloperoxidase enzyme to convert hydrogen peroxide to hypochlorite, a powerful germicidal agent (the active ingredient in bleach). These metabolites are stored in cytoplasmic granules and are released during neutrophil degranulation. This necrotic cell death releases further toxic metabolites, which causes further inflammatory pathway activation and further collateral tissue damage. This cascade can become a self-sustaining process if left unchecked.

Pro-inflammatory mechanisms are kept in check by the immune system via the humoral, cellular, and neural mechanisms. Regulation by the humoral mechanism is characterized by an impaired immune cell function with the expansion of regulatory T cells and myeloid suppressor cells that further reduce inflammation. Regulation by the neural mechanism involves the hypothalamic-pituitary-adrenal axis and vagus nerve stimulating the spleen to release norepinephrine and acetylcholine secretion by CD4 T cells, which helps to suppress the release of pro-inflammatory cytokines. On the cellular level, there is inhibition of pro-inflammatory gene transcription.

The damage inflicted by the inflammatory process is largely due to oxidation, where the production of oxidants overwhelms the body’s endogenous antioxidant defenses. This collateral damage can result from inadequate antioxidant protection and is the basis behind newer research geared towards replacing endogenous antioxidants.[54]

Epidemiology

Sepsis is associated with high morbidity and mortality and has recently been identified as affecting nearly 1.7 million US adults every year. Before 2000, mortality was noted to be as high as 50% in severe sepsis and septic shock patients.[57][61] Even with new technologies and treatments, the mortality remains around 20% to 25% nationwide, with 1 in 3 patients who die in the hospital succumbing to sepsis. Given the reported increasing prevalence of sepsis, a large amount of importance has been placed on treating and recognizing this disease process early, with the most recent budget reported at around $23.7 billion in 2013.[62][63][64]

Pathophysiology

Sepsis progressing to septic shock and multi-organ failure results from a worsening circulatory insufficiency characterized by hypovolemia, myocardial depression, increased metabolic demands, and vasoregulatory perfusion abnormalities. Classically, septic shock and inflammatory shock have been described as primarily systemic vasodilatation of both arteries and veins. This dilation reduces ventricular preload as well as afterload by decreasing systemic vascular resistance. The typical hemodynamic pattern in septic shock consists of low cardiac filling pressures, or low central venous pressures (CVP), and low systemic vascular resistance (SVR). With low preload and afterload, cardiac output (CO) must increase to compensate, typically with increased heart rate (CO = Stroke Volume x Heart Rate).  This is also why sepsis is thought of as a distributive shock and is also known as hyper-dynamic or warm shock.

The vascular changes resulting in systemic vasodilatation can be attributed largely to the dysfunction of the vascular endothelium and mitochondria. Part of the inflammatory process can be attributed to the enhanced production of nitric oxide (NO), which is a free radical and is produced in the vascular endothelial cells. In addition to the inflammatory processes, sepsis is also associated with microvascular thrombosis. This is caused by activation of the clotting cascade with tissue factor and exacerbated by decreased anti-coagulation and impaired fibrinolysis. This leads to increased thrombus formation and therefore worsening tissue hypoperfusion. With thrombus formation and tissue hypoperfusion, the vascular endothelial cells also experience a loss of function with cadherin. Tight junctions are disrupted, leading to further capillary leak and increased interstitial edema. To worsen this effect, red blood cells (RBC) have been shown to have decreased deformability during this inflammatory phase and will further contribute to poor tissue oxygenation. Vasodilation, disruption of the vascular endothelium, decreased RBC deformability, with the ensuing hypotension all contribute to worsening tissue oxygenation.[54][65]

Impaired tissue oxygenation will also cause mitochondrial dysfunction and lead to the shunting of pyruvate away from the Kreb cycle, which, when it accumulates, will be converted to lactate as a means of continuing metabolism in the critically ill. Hyperlactatemia in sepsis is the result of multiple metabolic adjustments, not simply tissue hypoperfusion. Conditions known to favor lactate production include systemic hypoperfusion necessitating anaerobic metabolism, regional hypoperfusion, and microcirculatory dysfunction. Additionally, increased aerobic glycolysis can produce an excess of pyruvate that overwhelms pyruvate dehydrogenase used to take the pyruvate into the Kreb cycle for aerobic metabolism. With the excess pyruvate present, a portion will be shunted to lactate conversion and accumulate in the cytoplasm before dispersing in the bloodstream. This occurs in white blood cells, which rely on anaerobic metabolism, especially when activated during periods of infection or inflammation, and have been shown to contribute to increased blood levels of lactic acid. This increased production and decreased clearance of lactate results in hyperlactatemia.[66][67]

As this disease process progresses, further inflammatory cytokines are released, resulting in effects seen in both cardiac activity and splanchnic vasculature. Further depression of cardiac contractility, in both systolic and diastolic phases, results from these circulating inflammatory cytokines. Splanchnic blood flow is also affected and primarily shunted to other organs, especially once hypotension is present. This creates an increased risk for translocation of enteric pathogens and endotoxin across the bowel mucosa and into the systemic circulation, further aggravating the inciting condition.

Alternatively, this process has been described in terms of oxygen demands and consumption. At its earliest manifestation, sepsis creates an increased need for oxygen locally, accompanied closely by a critical decrease in systemic oxygen delivery, limiting tissue oxygenation as described via various mechanisms above. This is followed by an increase in the systemic oxygen extraction ratio and an accompanying decrease in central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2). When the limits for how much oxygen can be extracted from blood are reached, cellular metabolism switches to anaerobic metabolism, further contributing to lactate production, as noted above. The failure to increase the oxygen extraction ratio and thus increase systemic oxygen consumption is secondary to impairment of microvascular oxygen perfusion as well as mitochondrial dysfunction. This is the basis for following increasing lactate levels or decreasing venous oxygen saturation as a marker for disease severity and prognosis.[65]

Histopathology

The cellular and tissue changes induced by a shock are essentially those also seen in hypoxic injury states. As oxygen tension within the cell decreases, there is a loss of oxidative phosphorylation and decreased ATP generation. The sodium pump fails, and potassium is lost with a concurrent influx of sodium and water, causing the cell to swell in size. With worsening hypoxia, there is a progressive loss of glycogen and decreased protein synthesis. As hypoxic injury continues, the cytoskeleton will disperse, and “blebs” will appear. Mitochondria will also exhibit swelling at this stage while the endoplasmic reticulum (ER) remains dilated. If oxygen is restored, a lot of these processes and injury can be reversed. If hypoxia persists, irreversible injury and cellular necrosis will ensue. Cells at this stage exhibit severe swelling of mitochondria, extensive damage to plasma membranes, and swelling of lysosomes. Cellular death is mainly by necrosis. However, apoptosis also contributes as the mitochondria are believed to leak pro-apoptotic enzymes with swelling. Apoptosis is a pathway of cellular death that is induced by a tightly regulated program that uses its own enzymes to degrade the rest of the cell in the hopes of limiting collateral tissue damage.

In sepsis and more specifically septic shock, these changes typically are more evident in tissues that are heavily dependent on blood flow and the elimination of cellular by-products, i.e., brain, heart, lungs, kidneys, adrenals, and gastrointestinal (GI) tract. Biopsies from septic patients reveal a wide range of findings concerning the kidneys, with “non-specific morphologic changes,” not acute tubular necrosis, being the most commonly reported finding.[68][69] The lungs are another very commonly affected organ in septic shock as it is known to be somewhat resistant to hypoxic injury. However, in septic shock, diffuse alveolar damage may develop; as a result, notably findings of interstitial and intra-alveolar edema, inflammation, and fibrin deposition. These findings are also associated with the dreaded complication of disseminated intravascular coagulation (DIC), which will show further fibrin deposition, as a part of these micro-thrombi, in nearly all the vascular territories of the organs named above. During DIC, the petechial appearance on the skin is often secondary to the consumption of platelets and clotting factors that are a part of the micro-thrombi. When viewed in isolation, these changes are reversible; however, once a patient reaches a state where multiple organ systems are involved, the patient usually dies before they have a chance to recover.

History and Physical

The history and physical exam will vary widely depending on where they fall on the continuum from SIRS to septic shock. Important considerations when taking a history in a patient with suspected sepsis are geared toward assessing those risk factors associated with increased mortality or higher incidence of sepsis and inquiring about possible sources of infection. Comorbidities associated with morbidity and mortality in sepsis include active cancer, diabetes, chronic lung disease, congestive heart failure, renal insufficiency, and liver disease (cirrhosis). Age, specifically older than 65 years old, is an independent predictor of mortality in sepsis. This is because of the association of increasing age with a decrease in the adaptive immune system with B and T cells showing impaired functionality. Alternatively, gender does not seem to play a role in sepsis mortality, as studies focusing on this subject are conflicting.[70] The presence of any of these comorbidities should heighten your suspicion for the patient developing sepsis and prompt an earlier intervention if possible.

Gathering information geared toward finding an infectious source will help tailor further intervention and management. Notably, a patient’s recent history, hospitalization, and exposure to drug-resistant organisms may help direct what treatment to initiate. Retrospectively, infection sources have been shown to be in the order of prevalence: pneumonia, intra-abdominal infections, and urinary tract infections.[56] However, the mortality rate is not related to the site of infection or the causative organism, including multi-drug-resistant organisms.[71] Even with this caveat, finding a suspected source of infection is critical in the early stages of a patient’s presentation.

The physical portion of the exam will provide critically important vital signs, allowing for utilization of clinical screening tools.  There has been criticism on utilizing the SIRS criteria for this purpose because its specificity in sepsis remains low. However, the basic tenets of observing vital sign abnormalities and systemic response to infection remain valid. The differences and reliability of these clinical scores are discussed in further detail below. Clinical conditions that are associated with inflammatory injury are best grouped as organ systems related to their condition in order of prevalence:

  • Lungs manifesting as acute respiratory distress syndrome (ARDS)
  • Cardiovascular as septic shock (hypotension)
  • Kidneys as acute kidney injury (AKI)
  • The brain as septic encephalopathy
  • Bone marrow as anemia of critical illness
  • Skeletal muscle as critical illness myopathy
  • Peripheral nerves as critical illness polyneuropathy

The physical exam should be focused on quickly assessing the patient with initial vitals. If there is suspicion for sepsis, a thorough physical exam looks for a potential infectious source, including a pelvic exam if indicated.

Evaluation

With the increased emphasis placed on earlier detection of sepsis, several clinical scores have been proposed to help further predict which patients are septic and which patients will ultimately have a worse outcome. As defined above, SIRS has been criticized for being too general, and while being very sensitive, it is also not very specific. The SIRS criteria were developed to identify this systemic response based on vital signs and lab work, not the source of infection.  However, when comparing even newer clinical tools such as the qSOFA score (quick sepsis-related organ failure assessment), the SIRS criteria were still more sensitive.[72][73] Ultimately, the difficulty in validating and finding a clinical tool that will detect a septic patient 100% of the time is that no gold standard for diagnosing sepsis exists. 

To diagnose sepsis in a patient, we still rely on three clinical and laboratory data groups, namely, general systemic manifestations, manifestations of organ dysfunction/failure, and finally, microbiological documentation. The general systemic manifestations are taken into account with the SIRS criteria. Manifestations of organ failure or dysfunction can be seen in changes of platelets, bilirubin, INR, creatinine, and lactic acid, among many other surrogate markers.[72] Microbiological documentation commonly includes blood cultures; however, they can include urine, peritoneal, synovial, respiratory secretions, and potentially cerebrospinal fluid(CSF). The downside is that in over one-third of clinical cases of sepsis and septic shock, the blood cultures are negative, and contaminants can complicate the picture.[54]

Sepsis-2 Criteria (2001) defined parameters of both physical and laboratory findings present with organ dysfunction, heavily influencing the Surviving Sepsis Campaign and CMS Core Measure (SEP-1). Organ dysfunction as noted in SEP-1, are as follows: SBP less than 90 mm Hg, MAP less than 65 mm Hg, Acute respiratory failure (need for invasive or non-invasive mechanical ventilation), creatinine greater than 2.0, urine output less than 0.5 ml/kg per hour (for 2 consecutive hours), total bilirubin greater than 2 mg/dl, platelet count fewer than 100,000, INR greater than 1.5, or aPTT greater than 60 seconds, or lactate greater than 2 mmol/L. Evaluation for sepsis as the underlying process should be evaluated with these markers of end-organ dysfunction in mind.

With a high index of suspicion for sepsis, investigation typically includes:

  • Complete blood count (CBC)with differential
  • Comprehensive metabolic profile (CMP)
  • Lactate
    • A critical value of greater than 2 mmol/L
  • INR/aPTT
    • Elevated acutely as a result of end-organ dysfunction
  • Chest x-ray and urinalysis
    • Either can be ordered to investigate for possible sources of infection.
  • Blood Cultures with or without other potential source cultures
    • At least 2 blood cultures are recommended before administering antibiotics.
  • Optional workup of uncertain benefit
    • Procalcitonin
    • C-reactive protein
    • Lipase
    • Venous blood gas
    • DIC panel (fibrinogen, D-dimer, fibrin degradation products)
    • TSH
    • Rapid flu, respiratory virus panel
    • CT head with ot without lumbar puncture
    • CT chest/abdomen/pelvis
    • MRI cervical/thoracic/lumbar spines (epidural abscess)

Treatment and Management

The treatment and management of sepsis have evolved consistently since it has been recognized as a disease entity. These advances can be credited for the mortality improvement with septic patients that have been seen over the last 2 decades. However, with mortality from sepsis still approaching 20% to 25%, there are improvements still needed to treat and manage these complex patients. Therapies are directed at the basic elements of sepsis as a syndrome of infection, the host response, and organ dysfunction. The initial management of infection requires forming a probable diagnosis, obtaining cultures, and initiating appropriate and timely empirical anti-microbial therapy and source control. Attenuating the host response and accompanying organ dysfunction are both parts of ongoing cardiopulmonary resuscitation. 

The initial resuscitation period was previously goal-directed, bundled care, something the Surviving Sepsis Campaign guidelines promote. Three large trials subsequently have shown no mortality benefit over usual care, which likely reflects the improvement of care, in general, with more of a trend toward early goal-directed therapies.[57][74][75][76] Despite the numerous trials and recommendations evaluating the components of this resuscitation, it remains a subject of debate and the source of ongoing clinical trials. Because of its complexities, the management has been grouped into 2 bundles of care, a 3 and 6-hour acute sepsis bundle, and a 24-hour sepsis management bundle.

Components of Acute Sepsis Bundle

Three-Hour Bundle

  • Obtain appropriate cultures before administration of antibiotics
  • Obtain plasma lactate level
  • Administer appropriate broad-spectrum antibiotics
  • Begin administration of crystalloid at 30 ml/kg for hypotension or lactate level greater than or equal to 4 mmol/L, within the first 3 hours

Six-Hour Bundle

  • Start vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain a mean arterial pressure level greater than or equal to 65 mmHg
  • In the event of persistent hypotension after initial fluid administration, or if initial lactate greater than 4 mmol/L, reassess volume status and tissue perfusion and document findings
  • Re-measure lactate if initial lactate was elevated

Components of the Sepsis Management Bundle (to be completed in the next 24 hours)

  • Administer low-dose steroid if indicated: Hydrocortisone at a dose of 200 mg per day
  • Maintain blood glucose levels less than 180 mg/dL
  • Maintain plateau airway pressure at less than 30 cm H2O in ventilator-dependent patients: Employ a lung-protective ventilator strategy.
  • Reassess antibiotic therapy daily for de-escalation when appropriate
  • Early Initiation of enteral feeding rather than complete fast or parenteral nutrition
  • Perform source control, where indicated, within 12 hours of identification
  • Administer prophylaxis for deep vein thrombosis
  • Administer stress-ulcer prophylaxis to prevent upper gastrointestinal (GI) bleeding

Antimicrobial therapy is strongly recommended to be started as soon as possible after diagnosing severe sepsis, or septic shock has been made.  Delays in initiating antibiotic therapy have been associated with increased mortality. Recommendations have been made for initiating therapy within 1 hour of diagnosis; however, there appears to be some dispute about the importance of this timing.[77] Despite the observation that sepsis mortality is not related to the site of infection or the causative organism, including multi-drug resistant organisms, the delay in administering appropriate antibiotics does affect mortality.[78] For this reason, broad-spectrum antibiotics targeting the suspected source are recommended, not necessarily the most appropriate antimicrobial agent.

Obtaining appropriate cultures is intended to influence care after this acute resuscitation phase has already passed. Lots of emphasis has been placed in the past on the timing and technique by which to obtain a blood culture with the greatest likelihood of returning a true positive result.  There has been no correlation between the timing of a blood culture draw and detecting significant bacteremia.  Recommendations from the Infectious Disease Society of America (IDSA) emphasize drawing them in a sterile manner from at least two different locations, with the volume of the blood cultured being emphasized rather than timing.[79]

Volume resuscitation, in the acute phase, is recommended as 30 ml/kg of crystalloid fluids. This fixed number was taken as the average volume of fluid given to patients in the PROCESS, ARISE, and PROMISE trials.[74][75][76][75][74] The volume of intravenous fluids to give in early resuscitation is still a point of contention and debate, as half of those patients in the study did not receive 30 ml/kg, and half of those patients required more. The ideal fluid to administer is also a contested point, with a general recommendation for "crystalloid fluids" such as normal saline, Ringer's lactate, or plasmalyte from the most recent Surviving Sepsis Campaign guidelines.[59] Recent large trials and reviews on the subject report some benefit with buffered crystalloid solutions (plasmalyte or Ringer’s lactate) over normal saline.[80][81] The guidelines for treating and managing sepsis do not reflect these findings.

Vasopressors are indicated in septic shock if the condition fails to respond to the intravenous fluid bolus as recommended above.  Vasopressors provide additional vascular contraction to help maintain beneficial blood pressure, with a target MAP of greater than 65 mm Hg.[82] The vasopressor choice initially should be norepinephrine, with vasopressin added if norepinephrine after titration dose fails to improve blood pressure by itself. Epinephrine should be used as a second-line agent to norepinephrine.  Recommendations at this point are to avoid the use of dopamine except in carefully selected patients. If there is evidence of myocardial dysfunction, recommendations support the addition of a dobutamine infusion to ongoing vasopressor therapy. Vasopressors should be administered through a central venous catheter as soon as placement is possible.[59]

Re-evaluation is critically important to guide the management of these patients after the initial resuscitation period. This typically includes a thorough clinical examination and the concurrent variables of heart rate, blood pressure, urine output, respiratory rate, among others. There have been multiple attempts at clearly defining these goals for acute resuscitation, and have included at different times measuring central venous pressure (CVP), mixed venous oxygen saturation (SvO2), trending lactic acid, stroke volume measurements, mean arterial pressure (MAP), and urine output. CVP measurements have been fraught with imprecision and did not demonstrate usefulness in predicting whether or not a patient will respond to additional intravenous fluid administration. Mean arterial pressure is the force behind perfusion in the peripheral organs and tissues and should be the goal for both fluid and vasopressor administration. While not directly a result of tissue perfusion, especially in sepsis, an elevated lactic acid has been directly related to increased mortality. Lactate clearance has also been suggested as a goal for early resuscitation. A decrease of only 10% in the first 6 hours corresponded to an 11% decrease in the likelihood of mortality compared to patients who were unable to achieve this.[66][67] However, there is weak evidence of a reduction in mortality when lactate guided resuscitation is employed over usual care.[59] For compliance with CMS core measures as noted in the guidelines above, documented reassessment of volume status and tissue perfusion should include vital signs, cardiopulmonary, capillary refill, pulse, and skin findings.

The widely held belief in sepsis that tissue hypoxia was the problem led to liberal transfusions of packed red blood cells to increase oxygen delivery in the early years of sepsis management. This, however, has since been disproven with the transfusion requirements in septic shock trials addressing mortality with a lower threshold transfusion of 7 g/dL versus a 9 g/dL. Targeting a lower transfusion threshold of 7 g/dL in septic patients is the current recommendation unless there are signs of critical coronary disease, myocardial ischemia, or acute hemorrhage.[59][83]

Corticosteroids have two important implications in severe sepsis and septic shock: they have anti-inflammatory activity and magnify the vaso-constricting response to catecholamines. The conflicting support for the routine use of steroids in severe sepsis and septic shock has led to inconsistent recommendations for its use, despite more than 50 years of trials looking at its benefit in septic shock. Recently the CORTICUS and ADRENAL trials, focusing on this point, have failed to show a direct mortality benefit. However, there was a decreased length of ICU stay and days on vasopressors in survivors.[84][85] In contrast, the APROCCHSS trial looked at a fludrocortisone and hydrocortisone combination did show a mortality benefit in septic shock patients without an increase in adverse events.[86] Currently, the recommendations support its use in refractory septic shock that has not responded to intravenous fluids and vasopressor therapy as well a low dose prolonged course should be continued while the patient is on vasopressor therapy. Hydrocortisone is the preferred corticosteroid because of its mineralocorticoid effects.

Mechanical ventilation is an important component of the management of the respiratory system. Predominantly the lungs are the most commonly affected organ in severe sepsis and septic shock. If the patient experiences acute lung injury that progresses to ARDS requiring mechanical ventilation, a lung-protective strategy is needed. In the landmark ARDSNet trial, patients receiving mechanical ventilation and developed ARDS had lower mortality and decreased ventilator-dependent days with a lung-protective strategy. This strategy employed a lower tidal volume strategy of 6 ml/kg of predicted body weight and kept plateau pressures under 30 cm H2O.[87]

Targeted treatments at different intersections in the newer sepsis models have been continually developed and usually have been unsuccessful at providing any mortality benefit routinely. Drotrecogin alfa, which is recombinant human activated protein C, was approved by the FDA in 2001 and was thought to promote fibrinolysis and inhibit thrombosis, which would have a significant impact on the pro-inflammatory state and complications involved in sepsis and septic shock. This was not the case as it was withdrawn from the market after further studies were published, showing no benefit and potentially worse outcomes. Further efforts were made to look at the administration of monoclonal antibodies against TNF, blocking IL-1 activity, granulocyte colony-stimulating factor (filgrastim), NO inhibitors, anti-thrombin, N-acetylcysteine, and using antibodies to endotoxin; however, these too failed to demonstrate efficacy.  Despite these failures, further development of other immunomodulating agents and the proposed "metabolic cocktail" continue to be pursued, as mortality even with newer therapies remains unacceptably high.[70][88]

Clinical Significance

Infectious diseases result in significant morbidity and mortality in healthcare works and patients. Drug-resistant and rapidly spreading emerging infectious diseases such as recently seen with COVID-19 have dramatically increased the cost of care. New York State has been proactive in making sure each healthcare worker is familiar with current standards of infection control practices and can assist and have an obligation to educate their staff. Through education, surveillance, and research, improved outcomes will be achieved.

Enhancing Healthcare Team Outcomes

Over 100 years of data show improved patient outcomes, regardless of the disease process, when healthcare professionals collaborate, acting as an interprofessional team.[89] The prevention and management of infectious diseases involve nearly every aspect of healthcare. With the implementation of bundled care, communication between physicians, nursing staff, respiratory therapists, and pharmacists becomes more important as these interventions must be implemented swiftly and correctly. With later identification of infectious diseases resulting in increased morbidity and mortality, the emphasis on prevention has become more important.

Multiple curriculums and recommendations for addressing these interprofessional teams' development to manage the prevention and treatment of infectious diseases have been put forth.[90] Developing a successful strategy for preventing, managing, and treating infectious diseases requires an interprofessional team approach, which will result in better outcomes. [Level 2]


Details

Author

Ted Louie

Author

Asif Noor

Updated:

7/31/2023 8:34:08 PM

References


[1]

Forder AA. A brief history of infection control - past and present. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2007 Nov:97(11 Pt 3):1161-4     [PubMed PMID: 18250929]


[2]

Melker RJ. The Institute of Medicine report on medical errors. The New England journal of medicine. 2000 Aug 31:343(9):664-5     [PubMed PMID: 10979813]


[3]

Berenholtz SM, Pronovost PJ, Lipsett PA, Hobson D, Earsing K, Farley JE, Milanovich S, Garrett-Mayer E, Winters BD, Rubin HR, Dorman T, Perl TM. Eliminating catheter-related bloodstream infections in the intensive care unit. Critical care medicine. 2004 Oct:32(10):2014-20     [PubMed PMID: 15483409]


[4]

Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C. An intervention to decrease catheter-related bloodstream infections in the ICU. The New England journal of medicine. 2006 Dec 28:355(26):2725-32     [PubMed PMID: 17192537]


[5]

Edmond M, Eickhoff TC. Who is steering the ship? External influences on infection control programs. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2008 Jun 1:46(11):1746-50. doi: 10.1086/587987. Epub     [PubMed PMID: 18419420]


[6]

Habboush Y, Yarrarapu SNS, Guzman N. Infection Control. StatPearls. 2023 Jan:():     [PubMed PMID: 30085559]


[7]

Brady MF, Jamal Z, Pervin N. Acinetobacter. StatPearls. 2023 Jan:():     [PubMed PMID: 28613535]


[8]

Oliveira J, Reygaert WC. Gram-Negative Bacteria. StatPearls. 2023 Jan:():     [PubMed PMID: 30855801]


[9]

Tiwari A, Nagalli S. Clostridium botulinum Infection. StatPearls. 2023 Jan:():     [PubMed PMID: 31971722]


[10]

Ramirez D, Giron M. Enterobacter Infections. StatPearls. 2023 Jan:():     [PubMed PMID: 32644722]


[11]

Mehta P, Reddivari AKR. Hepatitis. StatPearls. 2023 Jan:():     [PubMed PMID: 32119436]


[12]

Gooch CM, Wadhwa R. Body Fluid Exposures. StatPearls. 2023 Jan:():     [PubMed PMID: 32496730]


[13]

Hu Y, Anes J, Devineau S, Fanning S. Klebsiella pneumoniae: Prevalence, Reservoirs, Antimicrobial Resistance, Pathogenicity, and Infection: A Hitherto Unrecognized Zoonotic Bacterium. Foodborne pathogens and disease. 2021 Feb:18(2):63-84. doi: 10.1089/fpd.2020.2847. Epub 2020 Oct 30     [PubMed PMID: 33124929]


[14]

Siddiqui AH, Koirala J. Methicillin-Resistant Staphylococcus aureus. StatPearls. 2023 Jan:():     [PubMed PMID: 29489200]


[15]

Bethencourt Mirabal A, Ferrer G. Lung Nontuberculous Mycobacterial Infections. StatPearls. 2023 Jan:():     [PubMed PMID: 31869064]


[16]

Capece G, Gignac E. Norovirus. StatPearls. 2023 Jan:():     [PubMed PMID: 30020637]


[17]

Wilson MG, Pandey S. Pseudomonas aeruginosa. StatPearls. 2023 Jan:():     [PubMed PMID: 32491763]


[18]

Jilani TN, Avula A, Zafar Gondal A, Siddiqui AH. Active Tuberculosis. StatPearls. 2023 Jan:():     [PubMed PMID: 30020618]


[19]

Holubar M, Meng L, Alegria W, Deresinski S. Bacteremia due to Methicillin-Resistant Staphylococcus aureus: An Update on New Therapeutic Approaches. Infectious disease clinics of North America. 2020 Dec:34(4):849-861. doi: 10.1016/j.idc.2020.04.003. Epub 2020 Sep 30     [PubMed PMID: 33011050]


[20]

Kirkizlar TA, Akalin H, Kirkizlar O, Ozkalemkas F, Ozkocaman V, Kazak E, Ozakin C, Bulbul EN, Ozboz ES, Ali R. Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia. Leukemia research. 2020 Dec:99():106463. doi: 10.1016/j.leukres.2020.106463. Epub 2020 Oct 18     [PubMed PMID: 33130331]


[21]

Miller WR, Murray BE, Rice LB, Arias CA. Resistance in Vancomycin-Resistant Enterococci. Infectious disease clinics of North America. 2020 Dec:34(4):751-771. doi: 10.1016/j.idc.2020.08.004. Epub     [PubMed PMID: 33131572]


[22]

Douedi S, Douedi H. Precautions, Bloodborne, Contact, and Droplet. StatPearls. 2023 Jan:():     [PubMed PMID: 31855382]


[23]

Wright SB, Ostrowsky B, Fishman N, Deloney VM, Mermel L, Perl TM. Expanding roles of healthcare epidemiology and infection control in spite of limited resources and compensation. Infection control and hospital epidemiology. 2010 Feb:31(2):127-32. doi: 10.1086/650199. Epub     [PubMed PMID: 20039800]


[24]

O'Boyle C, Jackson M, Henly SJ. Staffing requirements for infection control programs in US health care facilities: Delphi project. American journal of infection control. 2002 Oct:30(6):321-33     [PubMed PMID: 12360140]


[25]

Assanasen S, Edmond M, Bearman G. Impact of 2 different levels of performance feedback on compliance with infection control process measures in 2 intensive care units. American journal of infection control. 2008 Aug:36(6):407-13. doi: 10.1016/j.ajic.2007.08.008. Epub     [PubMed PMID: 18675146]


[26]

Dudeck MA, Horan TC, Peterson KD, Allen-Bridson K, Morrell G, Pollock DA, Edwards JR. National Healthcare Safety Network (NHSN) Report, data summary for 2010, device-associated module. American journal of infection control. 2011 Dec:39(10):798-816. doi: 10.1016/j.ajic.2011.10.001. Epub     [PubMed PMID: 22133532]


[27]

Detsky ME, Etchells E. Single-patient rooms for safe patient-centered hospitals. JAMA. 2008 Aug 27:300(8):954-6. doi: 10.1001/jama.300.8.954. Epub     [PubMed PMID: 18728270]


[28]

Bauer TM, Ofner E, Just HM, Just H, Daschner FD. An epidemiological study assessing the relative importance of airborne and direct contact transmission of microorganisms in a medical intensive care unit. The Journal of hospital infection. 1990 May:15(4):301-9     [PubMed PMID: 1972946]

Level 2 (mid-level) evidence

[29]

Boyce JM, Pittet D, Healthcare Infection Control Practices Advisory Committee, HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2002 Oct 25:51(RR-16):1-45, quiz CE1-4     [PubMed PMID: 12418624]


[30]

Snitkin ES, Zelazny AM, Thomas PJ, Stock F, NISC Comparative Sequencing Program Group, Henderson DK, Palmore TN, Segre JA. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Science translational medicine. 2012 Aug 22:4(148):148ra116. doi: 10.1126/scitranslmed.3004129. Epub     [PubMed PMID: 22914622]


[31]

Polk RE, Hohmann SF, Medvedev S, Ibrahim O. Benchmarking risk-adjusted adult antibacterial drug use in 70 US academic medical center hospitals. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011 Dec:53(11):1100-10. doi: 10.1093/cid/cir672. Epub 2011 Oct 13     [PubMed PMID: 21998281]


[32]

MacDougall C, Polk RE. Variability in rates of use of antibacterials among 130 US hospitals and risk-adjustment models for interhospital comparison. Infection control and hospital epidemiology. 2008 Mar:29(3):203-11. doi: 10.1086/528810. Epub     [PubMed PMID: 18257689]


[33]

Wenzel RP, Edmond MB. Infection control: the case for horizontal rather than vertical interventional programs. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2010 Oct:14 Suppl 4():S3-5. doi: 10.1016/j.ijid.2010.05.002. Epub 2010 Sep 18     [PubMed PMID: 20851010]

Level 3 (low-level) evidence

[34]

Dancer SJ. Controlling hospital-acquired infection: focus on the role of the environment and new technologies for decontamination. Clinical microbiology reviews. 2014 Oct:27(4):665-90. doi: 10.1128/CMR.00020-14. Epub     [PubMed PMID: 25278571]


[35]

Sehulster L, Chinn RY, CDC, HICPAC. Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2003 Jun 6:52(RR-10):1-42     [PubMed PMID: 12836624]


[36]

Mathur P. Hand hygiene: back to the basics of infection control. The Indian journal of medical research. 2011 Nov:134(5):611-20. doi: 10.4103/0971-5916.90985. Epub     [PubMed PMID: 22199099]


[37]

Edmond MB. Getting to zero: is it safe? Infection control and hospital epidemiology. 2009 Jan:30(1):74-6. doi: 10.1086/592411. Epub     [PubMed PMID: 19067600]


[38]

Borron SW. Introduction: Hazardous materials and radiologic/nuclear incidents: lessons learned? Emergency medicine clinics of North America. 2015 Feb:33(1):1-11. doi: 10.1016/j.emc.2014.09.003. Epub 2014 Nov 15     [PubMed PMID: 25455659]


[39]

Greenland KB, Tsui D, Goodyear P, Irwin MG. Personal protection equipment for biological hazards: does it affect tracheal intubation performance? Resuscitation. 2007 Jul:74(1):119-26     [PubMed PMID: 17353076]


[40]

Patrick A, Murphy P, Pryor R, Cooper K, Godbout E, Stevens MP, Doll M, Hemphill RR, Bearman G. Nurse survey, knowledge gaps and the creation of an environmental hygiene protocol for patient transport and removing linen from patient rooms. American journal of infection control. 2020 Sep:48(9):1113-1115. doi: 10.1016/j.ajic.2019.12.012. Epub 2020 Jan 9     [PubMed PMID: 31926759]

Level 3 (low-level) evidence

[41]

Hanage WP, Testa C, Chen JT, Davis L, Pechter E, Seminario P, Santillana M, Krieger N. COVID-19: US federal accountability for entry, spread, and inequities-lessons for the future. European journal of epidemiology. 2020 Nov:35(11):995-1006. doi: 10.1007/s10654-020-00689-2. Epub 2020 Nov 2     [PubMed PMID: 33136249]


[42]

Holland MG, Cawthon D. Personal protective equipment and decontamination of adults and children. Emergency medicine clinics of North America. 2015 Feb:33(1):51-68. doi: 10.1016/j.emc.2014.09.006. Epub 2014 Nov 15     [PubMed PMID: 25455662]


[43]

Scarano A, Inchingolo F, Lorusso F. Environmental Disinfection of a Dental Clinic during the Covid-19 Pandemic: A Narrative Insight. BioMed research international. 2020:2020():8896812. doi: 10.1155/2020/8896812. Epub 2020 Oct 28     [PubMed PMID: 33145359]


[44]

Violante T, Violante FS. Surgical masks vs respirators for the protection against coronavirus infection: state of the art. La Medicina del lavoro. 2020 Oct 31:111(5):365-371. doi: 10.23749/mdl.v111i5.9692. Epub 2020 Oct 31     [PubMed PMID: 33124607]


[45]

Hamel KD. How to keep waste in its place. Occupational health & safety (Waco, Tex.). 2013 Jul:82(7):30-1     [PubMed PMID: 23951840]


[46]

Olorunnishola OA, Kidd-Taylor A, Byrd L. Occupational injuries and illnesses in the solid waste industry: a call for action. New solutions : a journal of environmental and occupational health policy : NS. 2010:20(2):211-23. doi: 10.2190/NS.20.2.f. Epub     [PubMed PMID: 20621885]


[47]

Hamel KD. Use good practices throughout your facility. Occupational health & safety (Waco, Tex.). 2010 Dec:79(12):32, 34     [PubMed PMID: 21243951]


[48]

Gutterman E, Jorgensen L, Mitchell A, Fua S. Adverse staff health outcomes associated with endoscope reprocessing. Biomedical instrumentation & technology. 2013 Mar-Apr:47(2):172-9. doi: 10.2345/0899-8205-47.2.172. Epub     [PubMed PMID: 23600361]


[49]

Alvarado C. Reconciliation of FDA and societal guidelines for endoscope reprocessing. Gastrointestinal endoscopy clinics of North America. 2000 Apr:10(2):275-81     [PubMed PMID: 10683214]


[50]

Parida A, Capoor MR, Bhowmik KT. Knowledge, attitude, and practices of Bio-medical Waste Management rules, 2016; Bio-medical Waste Management (amendment) rules, 2018; and Solid Waste Rules, 2016, among health-care workers in a tertiary care setup. Journal of laboratory physicians. 2019 Oct-Dec:11(4):292-299. doi: 10.4103/JLP.JLP_88_19. Epub     [PubMed PMID: 31929693]


[51]

Tsang KK, Mertz D, O'Neill C, Khan S. Silver linings of the coronavirus disease 2019 (COVID-19) pandemic from an infection prevention and control perspective. Infection control and hospital epidemiology. 2021 Nov:42(11):1408-1409. doi: 10.1017/ice.2020.1310. Epub 2020 Nov 4     [PubMed PMID: 33143783]

Level 3 (low-level) evidence

[52]

Territo H, Vaqar S, Justiz Vaillant AA. HIV Prophylaxis. StatPearls. 2023 Jan:():     [PubMed PMID: 30521273]


[53]

Funk DJ, Parrillo JE, Kumar A. Sepsis and septic shock: a history. Critical care clinics. 2009 Jan:25(1):83-101, viii. doi: 10.1016/j.ccc.2008.12.003. Epub     [PubMed PMID: 19268796]


[54]

Angus DC, van der Poll T. Severe sepsis and septic shock. The New England journal of medicine. 2013 Nov 21:369(21):2063. doi: 10.1056/NEJMc1312359. Epub     [PubMed PMID: 24256390]


[55]

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun:101(6):1644-55     [PubMed PMID: 1303622]

Level 3 (low-level) evidence

[56]

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23:315(8):801-10. doi: 10.1001/jama.2016.0287. Epub     [PubMed PMID: 26903338]

Level 3 (low-level) evidence

[57]

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine. 2001 Nov 8:345(19):1368-77     [PubMed PMID: 11794169]


[58]

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM, Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Critical care medicine. 2004 Mar:32(3):858-73     [PubMed PMID: 15090974]


[59]

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive care medicine. 2017 Mar:43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18     [PubMed PMID: 28101605]


[60]

Spiegel R, Farkas JD, Rola P, Kenny JE, Olusanya S, Marik PE, Weingart SD. The 2018 Surviving Sepsis Campaign's Treatment Bundle: When Guidelines Outpace the Evidence Supporting Their Use. Annals of emergency medicine. 2019 Apr:73(4):356-358. doi: 10.1016/j.annemergmed.2018.06.046. Epub 2018 Sep 4     [PubMed PMID: 30193754]


[61]

Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time. Critical care medicine. 1998 Dec:26(12):2078-86     [PubMed PMID: 9875924]


[62]

Novosad SA, Sapiano MR, Grigg C, Lake J, Robyn M, Dumyati G, Felsen C, Blog D, Dufort E, Zansky S, Wiedeman K, Avery L, Dantes RB, Jernigan JA, Magill SS, Fiore A, Epstein L. Vital Signs: Epidemiology of Sepsis: Prevalence of Health Care Factors and Opportunities for Prevention. MMWR. Morbidity and mortality weekly report. 2016 Aug 26:65(33):864-9. doi: 10.15585/mmwr.mm6533e1. Epub 2016 Aug 26     [PubMed PMID: 27559759]


[63]

Dantes RB, Epstein L. Combatting Sepsis: A Public Health Perspective. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Sep 28:67(8):1300-1302. doi: 10.1093/cid/ciy342. Epub     [PubMed PMID: 29846544]

Level 3 (low-level) evidence

[64]

Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ, Kadri SS, Angus DC, Danner RL, Fiore AE, Jernigan JA, Martin GS, Septimus E, Warren DK, Karcz A, Chan C, Menchaca JT, Wang R, Gruber S, Klompas M, CDC Prevention Epicenter Program. Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014. JAMA. 2017 Oct 3:318(13):1241-1249. doi: 10.1001/jama.2017.13836. Epub     [PubMed PMID: 28903154]


[65]

Rivers EP, Katranji M, Jaehne KA, Brown S, Abou Dagher G, Cannon C, Coba V. Early interventions in severe sepsis and septic shock: a review of the evidence one decade later. Minerva anestesiologica. 2012 Jun:78(6):712-24     [PubMed PMID: 22447123]


[66]

Okorie ON, Dellinger P. Lactate: biomarker and potential therapeutic target. Critical care clinics. 2011 Apr:27(2):299-326. doi: 10.1016/j.ccc.2010.12.013. Epub     [PubMed PMID: 21440203]


[67]

Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Critical care medicine. 2004 Aug:32(8):1637-42     [PubMed PMID: 15286537]


[68]

Parmar A, Langenberg C, Wan L, May CN, Bellomo R, Bagshaw SM. Epidemiology of septic acute kidney injury. Current drug targets. 2009 Dec:10(12):1169-78     [PubMed PMID: 19715542]


[69]

Kosaka J, Lankadeva YR, May CN, Bellomo R. Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data. Critical care medicine. 2016 Sep:44(9):e897-903. doi: 10.1097/CCM.0000000000001735. Epub     [PubMed PMID: 27058465]

Level 1 (high-level) evidence

[70]

Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, Remick DG. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiological reviews. 2013 Jul:93(3):1247-88. doi: 10.1152/physrev.00037.2012. Epub     [PubMed PMID: 23899564]

Level 3 (low-level) evidence

[71]

Zahar JR, Timsit JF, Garrouste-Orgeas M, Français A, Vesin A, Descorps-Declere A, Dubois Y, Souweine B, Haouache H, Goldgran-Toledano D, Allaouchiche B, Azoulay E, Adrie C. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Critical care medicine. 2011 Aug:39(8):1886-95. doi: 10.1097/CCM.0b013e31821b827c. Epub     [PubMed PMID: 21516036]


[72]

Serafim R, Gomes JA, Salluh J, Póvoa P. A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality: A Systematic Review and Meta-Analysis. Chest. 2018 Mar:153(3):646-655. doi: 10.1016/j.chest.2017.12.015. Epub 2017 Dec 28     [PubMed PMID: 29289687]

Level 1 (high-level) evidence

[73]

Freund Y, Lemachatti N, Krastinova E, Van Laer M, Claessens YE, Avondo A, Occelli C, Feral-Pierssens AL, Truchot J, Ortega M, Carneiro B, Pernet J, Claret PG, Dami F, Bloom B, Riou B, Beaune S, French Society of Emergency Medicine Collaborators Group. Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department. JAMA. 2017 Jan 17:317(3):301-308. doi: 10.1001/jama.2016.20329. Epub     [PubMed PMID: 28114554]


[74]

ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. The New England journal of medicine. 2014 May 1:370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18     [PubMed PMID: 24635773]

Level 1 (high-level) evidence

[75]

ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. The New England journal of medicine. 2014 Oct 16:371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1     [PubMed PMID: 25272316]


[76]

Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Tan JC, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock. Health technology assessment (Winchester, England). 2015 Nov:19(97):i-xxv, 1-150. doi: 10.3310/hta19970. Epub     [PubMed PMID: 26597979]

Level 1 (high-level) evidence

[77]

Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis. Critical care medicine. 2015 Sep:43(9):1907-15. doi: 10.1097/CCM.0000000000001142. Epub     [PubMed PMID: 26121073]

Level 1 (high-level) evidence

[78]

Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. The New England journal of medicine. 2017 Jun 8:376(23):2235-2244. doi: 10.1056/NEJMoa1703058. Epub 2017 May 21     [PubMed PMID: 28528569]


[79]

Riedel S, Bourbeau P, Swartz B, Brecher S, Carroll KC, Stamper PD, Dunne WM, McCardle T, Walk N, Fiebelkorn K, Sewell D, Richter SS, Beekmann S, Doern GV. Timing of specimen collection for blood cultures from febrile patients with bacteremia. Journal of clinical microbiology. 2008 Apr:46(4):1381-5. doi: 10.1128/JCM.02033-07. Epub 2008 Feb 27     [PubMed PMID: 18305133]


[80]

Finfer S, Myburgh J, Bellomo R. Intravenous fluid therapy in critically ill adults. Nature reviews. Nephrology. 2018 Sep:14(9):541-557. doi: 10.1038/s41581-018-0044-0. Epub     [PubMed PMID: 30072710]


[81]

Semler MW, Self WH, Rice TW. Balanced Crystalloids versus Saline in Critically Ill Adults. The New England journal of medicine. 2018 May 17:378(20):1951. doi: 10.1056/NEJMc1804294. Epub     [PubMed PMID: 29768150]


[82]

Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Hervé F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P, SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. The New England journal of medicine. 2014 Apr 24:370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18     [PubMed PMID: 24635770]


[83]

Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettilä V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Müller RG, Møller MH, Steensen M, Tjäder I, Kilsand K, Odeberg-Wernerman S, Sjøbø B, Bundgaard H, Thyø MA, Lodahl D, Mærkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A, TRISS Trial Group, Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. The New England journal of medicine. 2014 Oct 9:371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1     [PubMed PMID: 25270275]


[84]

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J, CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. The New England journal of medicine. 2008 Jan 10:358(2):111-24. doi: 10.1056/NEJMoa071366. Epub     [PubMed PMID: 18184957]


[85]

Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, Billot L, Correa M, Glass P, Harward M, Joyce C, Li Q, McArthur C, Perner A, Rhodes A, Thompson K, Webb S, Myburgh J, ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. The New England journal of medicine. 2018 Mar 1:378(9):797-808. doi: 10.1056/NEJMoa1705835. Epub 2018 Jan 19     [PubMed PMID: 29347874]


[86]

Annane D, Renault A, Brun-Buisson C, Megarbane B, Quenot JP, Siami S, Cariou A, Forceville X, Schwebel C, Martin C, Timsit JF, Misset B, Ali Benali M, Colin G, Souweine B, Asehnoune K, Mercier E, Chimot L, Charpentier C, François B, Boulain T, Petitpas F, Constantin JM, Dhonneur G, Baudin F, Combes A, Bohé J, Loriferne JF, Amathieu R, Cook F, Slama M, Leroy O, Capellier G, Dargent A, Hissem T, Maxime V, Bellissant E, CRICS-TRIGGERSEP Network. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. The New England journal of medicine. 2018 Mar 1:378(9):809-818. doi: 10.1056/NEJMoa1705716. Epub     [PubMed PMID: 29490185]


[87]

Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The New England journal of medicine. 2000 May 4:342(18):1301-8     [PubMed PMID: 10793162]


[88]

Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun:151(6):1229-1238. doi: 10.1016/j.chest.2016.11.036. Epub 2016 Dec 6     [PubMed PMID: 27940189]

Level 2 (mid-level) evidence

[89]

Frenk J, Chen L, Bhutta ZA, Cohen J, Crisp N, Evans T, Fineberg H, Garcia P, Ke Y, Kelley P, Kistnasamy B, Meleis A, Naylor D, Pablos-Mendez A, Reddy S, Scrimshaw S, Sepulveda J, Serwadda D, Zurayk H. Health professionals for a new century: transforming education to strengthen health systems in an interdependent world. Lancet (London, England). 2010 Dec 4:376(9756):1923-58. doi: 10.1016/S0140-6736(10)61854-5. Epub 2010 Nov 26     [PubMed PMID: 21112623]


[90]

Chung HO, Medina D, Fox-Robichaud A. Interprofessional sepsis education module: a pilot study. CJEM. 2016 Mar:18(2):143-5. doi: 10.1017/cem.2015.42. Epub 2015 Jun 11     [PubMed PMID: 26063312]

Level 3 (low-level) evidence