Continuing Education Activity
Hospital-acquired infections (healthcare-associated infections) are nosocomially acquired infections that are not present or incubating at the time of admission to a hospital. These infections include catheter-associated urinary tract infections, central line-associated bloodstream infections, surgical site infections, ventilator-associated pneumonia, hospital-acquired pneumonia, and Clostridium difficile infections. Symptoms that favor an infection include productive cough, shortness of breath, abdominal pain, rebound tenderness, altered mental status, palpitations, suprapubic pain, polyuria, dysuria, and costovertebral angle tenderness. This activity outlines the evaluation and management of hospital-acquired infections and reviews the role of the interprofessional team in improving care for patients with this condition.
- Describe the pathophysiology of hospital-acquired infections.
- Review the laboratory tests used in the evaluation of hospital-acquired infections.
- Summarize the management of hospital-acquired infections.
- Outline the importance of improving care coordination among the interprofessional team to prevent transmission of infections and enhance the delivery of care for patients affected by hospital-acquired infections.
Hospital-acquired infections, also known as healthcare-associated infections (HAI), are nosocomially acquired infections that are typically not present or might be incubating at the time of admission. These infections are usually acquired after hospitalization and manifest 48 hours after admission to the hospital. The infections are monitored closely by agencies such as the National Healthcare Safety Network (NHSN) of the Center for Disease Control and Prevention (CDC).  This surveillance is done to prevent HAI and improve patient safety. HAI infections include central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), surgical site infections (SSI), Hospital-acquired Pneumonia (HAP), Ventilator-associated Pneumonia (VAP), and Clostridium difficile infections (CDI). 
For the last few decades, hospitals have taken the hospital-acquired infections seriously. Several hospitals have established infection tracking and surveillance systems in place, along with robust prevention strategies to reduce the rate of hospital-acquired infections.  The impact of hospital-acquired infections is seen not just at an individual patient level, but also at the community level as they have been linked to multidrug-resistant infections. Identifying patients with risk factors for hospital-acquired infections and multidrug-resistant infections is very important in the prevention and minimization of these infections.
Based on the guidelines from both the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS), the definitions of Pneumonia have been changed to better identify patients at risk for multidrug-resistant (MDR) pathogens. This, in turn, is aimed at avoiding the overuse of antibiotics. Healthcare-acquired Pneumonia or HCAP, which was widely used previously, has been made obsolete. The term Hospital-acquired Pneumonia or HAP has replaced HCAP. As per the IDSA guidelines, Hospital-acquired Pneumonia is defined as "pneumonia that occurs 48 hours or more after admission to the hospital and did not appear to be incubating at the time of admission".  According to IDSA, Ventilator-associated pneumonia or VAP is defined as "pneumonia that develops more than 48 to 72 hours after endotracheal intubation".  Both HAP and VAP are associated with poorer outcomes and significant morbidity and mortality worldwide. 
The risk for hospital-acquired infections is dependent on the infection control practices at the facility, the patient's immune status, and the prevalence of the various pathogens within the community. The risk factors for HAI include immunosuppression, older age, length of stay in the hospital, multiple underlying comorbidities, frequent visits to healthcare facilities, mechanical ventilatory support, recent invasive procedures, indwelling devices, and stay in an intensive care unit (ICU).  Receipt of intravenous antibiotics within the last 90 days is one of the major risk factors for developing antimicrobial resistance to multiple drugs.  While hospitalizations play a major role in the management of acute illnesses, and they also enhance the risk of susceptible patients for multiple nosocomial and often antimicrobial-resistant pathogens. These pathogens can be acquired from other patients, hospital staff, or the hospital facility. The risk is higher among patients in ICU. In a point prevalence study that included 231,459 patients across 947 hospitals concluded that about 19.5% of patients in ICU had at least one HAI. 
Clostridium difficile is the organism that causes Clostridium difficile colitis (CDI). Common organisms for CLABSI are candida spp (adult ICU), Enterobacteriaceae (adult wards, pediatric ICU and wards, and oncology wards), and staph aureus.  Common pathogens that are known to cause CAUTI are Enterococcus, staphylococcus aureus, Pseudomonas, proteus, Klebsiella, and Candida.  According to the National Healthcare Safety Network, the common causative organisms for SSI include (in descending order) staph aureus, coagulase-negative staphylococcus, Enterococcus, E Coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella pneumoniae.  The most common pathogens for HAP and VAP are staph aureus and pseudomonas aeruginosa, while E Coli and Klebsiella pneumoniae can be seen in higher proportions among pediatric populations. 
In 2014, the CDC published a multistate point prevalence survey of healthcare-associated infections involving 11,282 patients from 183 US hospitals.  According to this report, about 4% of hospitalized patients suffered from at least one of the HAI. In absolute numbers, in 2011, an estimated 648,000 hospitalized patients suffered from 721,800 infections.  The dominant infections (in descending order) include Pneumonia (21.8%), surgical site infections (21.8%), gastrointestinal infections (17.1%), urinary tract infections or UTIs (12.9%), and primary bloodstream infection (9.9%, and include Catheter-associated bloodstream infections).  Among the pathogens causing HAI, C. difficile (12.1%) is the leading pathogen and is closely followed by Staphylococcus aureus (10.7%), Klebsiella (9.9%), and Escherichia coli (9.3%).  Skin and surgical site infections are usually caused by Staphylococcus aureus and sometimes include Methicillin-resistant staphylococcus aureus (MRSA). The SENIC study (Study on Efficacy of Nosocomial Infection Control) pointed out the possibility of reducing infections by a third by combining infection tracking and infection control programs.  Due to greater awareness and robust preventative measures undertaken in the hospital settings, there has been some reduction in the incidence of certain HAI. The implementation of robust infection surveillance and prevention practices has resulted in some success in the prevention of HAI. According to the CDC, the rates of CLABSI have decreased by 46% between 2008 to 2013. 
Transmission of pathogens in a health care environment is complex and can occur through direct contact with the healthcare workers or the surrounding contaminated environment.
Risk factors for the development of CDI are well known. These include recent antibiotic use, gastric acid suppresants, nonselective non-steroidal anti-inflammatory drugs (NSAIDs), and some comorbidities. 
Risk factors for SSI include both patient factors such as age, diabetes, obesity, nutritional status, colonization, co-existing infections, and operative factors such as duration of the procedure, skin antisepsis, surgical technique, antimicrobial prophylaxis.  Some pathogens possess a tendency to colonize in areas with warmth and moisture. These areas are typically located in the inguinal and perineal region, axilla, and trunk. Certain bacteria and fungi thrive in such environments.
Some of the proposed mechanisms of CAUTI are intraluminal colonization, retrograde intraluminal ascent, extraluminal peri urethral spread, and biofilms adherent to the urinary catheters.  Some organisms, such as Pseudomonas species and Proteus species, can form tough biofilms around catheters. Sometimes, these pathogens produce enzymes that inactivate the antimicrobial agents, making it harder to treat these infections. 
Mechanisms of infection in central line-associated bloodstream infections include colonization, biofilm formation, and extraluminal migration. The femoral site is associated with an increased risk of infections and should be avoided if possible.  Staphylococcus aureus and Staphylococcus epidermidis are common organisms associated with biofilm formation on catheters.  Coagulase-negative staphylococci (CoNS), commonly found in skin flora, is a common cause of colonization of central lines and thereby central line-associated bloodstream infections.
Multidrug-resistant (MDR) pathogens are also a significant cause of infections in hospitals, particularly in the intensive care unit. Infections with MDR organisms are associated with an increase in the length of stay (LOS), mortality indicators, and increased costs of care.  MDR pathogens are resistant to at least one antibiotic from three different classes or with different mechanisms of action. 
MDR organisms are often suspected of HAP and VAP. The use of intravenous antibiotics within the past 90 days is an important risk factor for MDR infections.  Other risk factors for MDR VAP include the presence of septic shock at the time of VAP onset and duration of hospitalization, Acute respiratory distress syndrome, and acute renal replacement therapy before the onset of VAP. 
Pharmacokinetics and pharmacodynamics change during an acute illness, especially during sepsis. For a given drug, the volume of distribution varies depending on the phase of the illness or recovery. This is an important concept and must be considered when determining dosing medication dosings, especially for drugs like aminoglycosides and beta-lactams. Another important determinant of the dosing of renal-excreted medications is the estimated glomerular filtration rate (eGFR), which may be impaired in sepsis. The IDSA and ATS recommend selecting antibiotic dosing based on pharmacokinetics and pharmacodynamics for critically ill patients with ventilator-associated Pneumonia.  An antibiotic's efficacy may be concentration-dependent (fluoroquinolones and aminoglycosides), time-dependent (beta-lactams), or a combination of both (Vancomycin). Time-dependent drugs are typically administered as extended infusions to maintain concentrations typically within four times of minimum inhibitory concentrations, whereas concentration-dependent drugs are dosed targeting one high peak (with a onetime high dose) or multiple peaks with intermittent dosing.
History and Physical
Obtaining thorough details in history and performing a comprehensive physical examination is important in determining whether the infection was acquired before admission or whether it is a hospital-acquired infection. Important pieces of history, such as subjective fever, chills, and night sweats, may indicate that the infection was not hospital-acquired. Common infectious symptoms include fever, chills, altered mental status, productive cough, shortness of breath, palpitations, abdominal pain, flank pain, suprapubic pain, polyuria, dysuria, and diarrhea. Vital signs can reflect signs of systemic inflammatory response or sepsis. These include hypothermia or hyperthermia, tachypnea, tachycardia, and hypotension. Examination of external devices such as tracheostomies, endotracheal tubes, foley catheters, intravascular lines, insulin pumps, and pacemakers/ defibrillators is essential. Supplementing the examination of external devices is the information on the location and placement of the device (duration and setting).
Central lines placed hastily during emergencies need to be re-evaluated and possibly replaced within 24 hours to 48 hours, especially in the context of aseptic conditions during placement of the line or a new fever during hospitalization. Central venous catheters are considered the primary source of hospital-acquired bloodstream infections. The other sources of bloodstream infections are catheter-associated urinary tract infections and ventilator-associated Pneumonia. The surgical sites and breaches in skin integrity should be examined daily for any signs of evolving infection. Thorough and serial examinations go a long way in identifying brewing infections in early phases, containing the infections, and minimizing complications. Careful examination of abdomen and stool samples is often needed in evaluation for clostridium difficile infection.
Laboratory testing complements the history and clinical examination in elucidating the possible source of infection and revealing evidence of organ dysfunction. Serum levels of lactic acid, liver transaminases, prothrombin time, blood urea nitrogen (BUN), and serum creatinine can support clinical findings of hypoperfusion. Other important lab findings include low or elevated white cell counts, elevated bands, thrombocytopenia, hypoglycemia, hyperglycemia, and reduced mixed venous blood saturation. Obtaining samples for cultures before initiation of antibiotics is vital in early identification of the pathogen and the antimicrobial susceptibility pattern. Both the pathogen and the antibiotic susceptibility help narrow down from broad-spectrum antibiotics to specific agents targeted towards the pathogens. Investigations that do not alter clinical decision making or the clinical course are not usually recommended. If the pretest probability is high for a HAI such as ventilator-associated pneumonia/ VAP, then tests such as C-reactive protein (CRP) and procalcitonin are considered ancillary and not indicated. For patients with HAP/ VAP, recent IDSA guidelines recommend noninvasive sampling with tracheal aspirates as they have been shown to have non-inferior yield when compared to invasive samplings such as quantitative tracheal lavage or bronchoscopy. 
Treatment / Management
Management of hospital-acquired infections follows standard goal-directed therapy if sepsis, antibiotics, fluid resuscitation, and close monitoring for organ dysfunction. Fluid resuscitation should be followed by serial assessments of the clinical and hemodynamic responses. The selection and timing of initiation of antibiotics are critical. Empiric antibiotics should be selected based on risk factors for MDR pathogens and clinical stability of the patient. Antibiotics should be started early within an hour if possible, and if central line-associated bloodstream infection is suspected, two sets of blood cultures, one from a peripheral venous site and the other from the central venous catheter site, should be obtained before initiation of antibiotic therapy. In case of hypotension, hypoperfusion, or organ dysfunction, the catheter must be removed without delay, and the tip should be sent for culture.
When suspecting catheter-associated urinary tract infections, the old catheter must be removed, and a urine sample from the newly placed catheter must be obtained, preferably before initiating antibiotics. These measures have been shown to enhance the yield of microbiological specimens. As part of the stand precautions, all catheters (including central lines and urinary catheters) should be removed if they are no longer indicated.  For catheter-associated UTIs, seven days of antibiotics are typically recommended. However, in case of a delayed response or bacteremia, the antibiotic course could be extended to 10 - 14 days. Reducing usage, minimizing dwelling, antimicrobial catheters, and antibiotic prophylaxis in certain situations help in the prevention of CAUTI. 
The usual duration of the antibiotic regimen in HAP or VAP is seven days unless a longer duration is clinically indicated.  Antibiotic regimens typically include activity against staph aureus and Pseudomonas aeruginosa.  MDR pathogens need different antibiotics than the usual antibiotics.
CLABSI incidence has decreased in the US over the years due to increasing awareness and implementation of evidence-based preventive strategies such as aseptic precautions at the time of insertion, removal of unnecessary catheters, chlorhexidine baths, antimicrobial dressings, and catheter lock solutions.  The antibiotic duration for central line-associated bloodstream infections is dependent on whether the infection is complicated or uncomplicated and whether the catheter is retained or removed. Determinants of complicated central line-associated bloodstream infections include suppurative thrombophlebitis, osteomyelitis, endocarditis, persistent positive cultures after 72 hours, and active malignancy or immunosuppression. 
For Clostridium difficile infections, oral vancomycin is usually the drug of choice and sometimes might need altering the underlying antibiotics regimen for primary infection. Metronidazole is an alternative medication. Newer medications include fidaxomicin.  Other options, such as teicoplanin, among other antibiotics, are being explored.  Fecal microbiota transplantation is reserved for severe refractory cases.
Proper hand hygiene and appropriate infection prevention strategies need to be followed while caring for surgical sites postoperatively. Also, antibiotic prophylaxis and skin decontamination are important factors in the prevention of SSI.  Antibiotics to cover common pathogens in case of surgical site infections need to be employed early and later adjusted per reports from cultures. Antibiotics to cover staphylococcus aureus and other organisms such as Pseudomonas are usually initiated, depending upon the clinical scenario. Sometimes, antibiotics with activity against MDR pathogens such as MRSA and carbapenemase-producing Enterobacteria need to be considered. 
Universal standard (infection control) measures, such as handwashing with soap and water or using alcohol-based disinfectant before and after each patient visit, are vital in reducing rates of transmission of MDR pathogens. In a study, the use of gloves and gowns did not prevent contamination and conclusively did not seem enough to prevent the spread of infections. 
- Bacterial sepsis
- Clostridium Difficile Colitis
- Enterococcal infections
- Viral hepatitis
Pearls and Other Issues
Over the years, various preventive strategies have been employed to reduce hospital-acquired infections. The major principles of prevention include hand hygiene, contact precautions when indicated, antibiotic stewardship to avoid the rise of MDR organisms, appropriate antimicrobial prophylaxis, particularly for surgeries, patient positioning, subglottic suction to avoid aspiration, strict asepsis when placing a central line, limiting unnecessary use of external devices, removal of catheters as soon as no longer indicated, and decontamination with chlorhexidine bathing for patients in the intensive care unit.
Enhancing Healthcare Team Outcomes
An Interprofessional Approach to Healthcare-Associated Infections
Healthcare-associated infections have very high morbidity and mortality, costing the healthcare system billions of dollars each year. Over the years, many guidelines have been developed for monitoring, performing and monitoring central lines, and isolation of infected patients. Only a concerted effort by all healthcare teams can have an impact. The primary strategy employed in hospitals is to prevent transmission of infectious agents among patients and healthcare providers. Nurses play a vital role in prevention as they are often the first to encounter infected patients. Washing hands and ensuring that everyone follows the established rules for infection prevention are key. Several category 1A recommendations, including education of healthcare workers about infection control procedures, hand washing, using aseptic techniques when performing invasive procedures, and securing catheters.  Further, the disinfection of hospital rooms and decreasing environmental contamination is also encouraged. Finally, with a rise in antibiotic resistance organisms, a hospital committee consisting of a pharmacist should be established to ensure that the empirical use of antibiotics is not routine and ensuring that certain antibiotics cannot be used without prior approval from the committee.
Healthcare-associated infections are known to increase the length of stay, health care costs, and mortality. Each year the top 5 healthcare-associated infections result in about $9.8 billion costs, with surgical site infections leading the pack.  Healthcare costs are known to occur in every medical and surgical department, including the ICU. However, with more awareness and better guidelines, both sepsis and central line infections appear to be declining. Best practices have now been established in most hospitals for the insertion of central lines and wound care. All members in all disciplines of the interprofessional healthcare team must have involvement in this process.