Anaerobic bacteria are part of normal flora of human skin and mucosal membranes. The site of anaerobic infection is commonly the site of normal colonization. The spectrum of infections ranges from local abscesses to life-threatening infections. Anaerobic bacteria differ from aerobic bacteria in their oxygen requirement. Oxygen is toxic to anaerobes which can be explained by the absence of enzymes in the anaerobes of catalase, superoxide dismutase, and peroxidase enzymes. Anaerobes are fastidious organisms and are difficult to grow if proper collection and culture methods are not used. The diagnosis requires clinical suspicion and proper microbiological identification.
Based on oxygen requirement, bacteria can be divided into the following groups:
Obligate aerobes which required oxygen as a terminal electronic acceptor and do not have any other source of energy, such as fermentation.
Obligate anaerobes which obtain energy through fermentation and use organic compounds as a terminal electron acceptor.
Facultative anaerobes which can grow in the presence or absence of oxygen.
The obligate anaerobes can further be subdivided into 2 types based on a percentage of oxygen that can prove toxic. Strict obligate anaerobes which will not survive if there is more than half a percentage in the environment, while moderate obligate anaerobes can still grow in a 2% to 8% oxygen environment.
Common sites of anaerobic infections include oral, abdominal, and pelvic cavities; however, anaerobes can cause infections of other regions such as the head, neck, and skin. Clinically significant anaerobes associated with human infections are as follows:
Gram-Positive, Spore-Forming Bacilli
Clostridium: These are spore-forming anaerobes responsible for some of the more serious human infections. They account for close to 10% of all anaerobic infections. Significant members of this family are Clostridium difficile which causes C. difficile infection. Clostridium perfringens which causes gas gangrene or soft tissue infections. Clostridium septicum which also causes gas gangrene.
Gram-positive, Non-Spore-Forming Bacilli
Actinomyces: These colonize the human gastrointestinal (GI) tract, and infections result from a break in the mucocutaneous barrier. The 3 most common anatomic sites affected by Actinomyces are cervicofacial, thoracic, and abdominal.
Propionibacterium: This species is part of the normal flora of skin and mucosa. The most significant member of this family is Propionibacterium acne which plays a role in the pathogenesis of acne vulgaris.
Bifidobacterium: This is normal flora of intestinal tracts. It is usually non-pathogenic; however, pediatric infections have been documented in the form of chronic otitis media, abdominal abscesses, and peritonitis.
Lactobacillus: These organisms are also normally found in the GI tract and can be recovered from numerous food products. They have low pathogenic potential; however, cases of abdominal abscesses, aspiration pneumonia, and bacteremia, particularly in neonates, have been described.
Peptococcus and Peptostreptococcus: These anaerobes are part of the mouth, GI tract, upper respiratory tract and urogenital tract, as well as the skin. They can be pathogenic and cause numerous infections such as chronic otitis media, chronic sinusitis, aspiration pneumonia, pelvic inflammatory disease including tube-ovarian abscesses.
Other members include Eubacterium, Bifidobacterium, Arcanobacterium, cufflinksa, and microaerophilic Streptococcus (Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius).
Bacteroides: These are most frequently recovered anaerobic pathogens from clinical specimens. They are part of human colonic and normal female genital flora. These organisms are most commonly the cause of intra-abdominal infections particularly abscesses. Majority of these abscesses are mixed infections. They can also cause extra-abdominal infections such as aspiration pneumonia, brain abscesses, among others.
Fusobacterium: One of the species from this group of anaerobes, Fusobacterium necrophorum, is a common cause of peritonsillar abscesses associated with a complication of internal jugular vein thrombosis, known as Lemierre syndrome.
Campylobacter: Is one of the most common causes of acute gastroenteritis.
Prevotella: These are normal flora of human oral cavity and intestinal tract. In children, they are frequently associated with head and neck infections such as peritonsillar abscesses, retropharyngeal abscesses as well as perineal or perianal infections such as a pilonidal abscess.
Veillonella: Occasionally associated with abdominal abscesses and aspiration pneumonia in children.
Anaerobes are part of the indigenous or native flora particularly the oral cavity, human bowel, and female genital tract. The colonization with anaerobes varies with age, organ site, and environmental factors. For example, infants who are exclusively breastfed have gut flora with predominantly Bifidobacterium, with few Bacteroides and Enterococcus species. On the other hand, infants who are fed cow's milk have gut flora similar to that of an adult's which contain gram-negative anaerobes and facultative bacilli.
Anaerobes are part of indigenous flora which resists colonization and invasion from nonindigenous flora. However, infections from anaerobes do occur and usually result from a breakdown of the mucocutaneous barrier or immunosuppression. Anaerobic organ infections include, but are not restricted to, brain abscesses, dental infections, aspiration pneumonia, lung abscesses, bite infections (animal/human), abdominal abscesses, and necrotizing infections of soft tissue.
The pathogenesis of anaerobic infections includes disruption of the mucosal surface and entry of the anaerobic bacteria with the invasion of the deep tissue. The mechanisms of entry include local trauma, surgery, viscus perforation (for example, appendicitis), tissue necrosis, and impaired clearance of a sterile site (chronic sinusitis, pneumonia). The site and the extent of infection is based on the virulence factors of the organism and host immunity.
The virulence factors which assist anaerobic infections are adhesions factors (fimbriae and lectin), invasion factors (phospholipase C, lipopolysaccharides, and proteases), factors involved in tissue destruction (fibrinolysis, acetylglucosaminidase, and collagenase production), capsular resistance to phagocytosis, and others. Serious infections are seen in the immunocompromised host.
When implicated in an abscess, anaerobes are usually part of a polymicrobial infection. Experimental rat models with mixed infections have shown that the growth of anaerobes, as well as anaerobes, is enhanced in polymicrobial infections.
The majority of anaerobic infections in children are local, and bloodstream infections compromise less than 2% of the cases. The approach to anaerobic infections includes the identification of predisposing factors. They are as follows:
Other important clues of anaerobic infection include the presence of a condition predisposing an individual to an anaerobic infection, for example, tissue necrosis, a foul-smelling discharge, infection leading to thrombophlebitis, no improvement with antibiotics in suspected anaerobic activity.
The clinicians should obtain an anaerobic culture when suspicion of an anaerobic infection is present.
Common Organ Site Infections in Anaerobic and Aerobic Infections
Head and neck infection: Anaerobes are commonly implicated in dental infections such as dental abscesses, gingivitis, and periodontitis. Exam findings of dental caries or poor dentition are usually present. Anaerobes are also implicated along with other aerobes in suppurative infections of retropharyngeal abscess, peritonsillar abscess, cervical lymphadenitis, deep neck abscesses, and parotitis. The anaerobe associated with Fusobacterium is linked with a complication of peritonsillar abscess known as Lemierre syndrome. Lemierre syndrome is caused by jugular vein septic thrombophlebitis and metastatic emboli to the lungs and liver.
Anaerobes are also caused by chronic otitis media and chronic sinusitis along with other aerobes such as Staphylococcus aureus and Pseudomonas.
Central nervous system (CNS) infections: Anaerobes are commonly isolated in cultures from brain abscesses which result from a complication of sinusitis, otitis media, dental infections. The 3 anaerobes commonly isolated are Fusobacterium, Prevotella, and Bacteroides. The same organisms are also seen in epidural infections.
Intra-abdominal infections: Damage to intestinal wall as seen in perforated appendix gives enteric anaerobes access to the peritoneal cavity. Over days to weeks, it results in the formation of abdominal abscesses. Abdominal abscesses are almost always mixed infections containing both aerobes and anaerobes. The most common anaerobe implicated in abdominal infections is Bacteroides fragilis followed by Lactobacillus and Clostridium species.
Anaerobes are also a common cause of liver abscesses. The common anaerobes associated are Bacteroides and Fusobacterium species.
Pelvic inflammatory disease: Anaerobes are all are involved in pelvic inflammatory diseases (PID). In a sexually active female with signs and symptoms compatible with pelvic inflammatory disease, empiric antimicrobial therapy against anaerobes and anaerobes is indicated. The common anaerobes involved in PID are Prevotella, Porphyromonas, Clostridium.
Pulmonary infections are seen in children who are unable to control upper airway secretions or lack a normal cough reflex, such as children with cerebral palsy and tracheoesophageal malformations. Aspiration results in pneumonia which can develop into an abscess if untreated. The predominant pathogens involved in aspiration pneumonia are part of the oropharyngeal flora and include Peptostreptococcus, Prevotella, Bacteroides fragilis, and Fusobacterium.
Skin and soft tissue infections: Anaerobes can cause a perirectal abscess or facial abscess in children. Bacteroides fragilis and Clostridium species usually are involved in perirectal infections, and Prevotella, Porphyromonas, and Fusobacterium are involved in oral infectious.
Identification of Serious Anaerobic Infections
Timely identification is important to start empiric therapy. Life-threatening infections such as tetanus, gas gangrene, or infantile botulism are caused by the spore-forming anaerobes, Clostridium tetanus, Clostridium perfringens, or Clostridium botulism respectively.
A history of injury, for example, penetrating nail injury or the presence of a devitalized tissue, should prompt evaluation for tetanus in an immunized child.
Gas gangrene is caused by Clostridium perfringens or Clostridium septicum. It is a medical emergency which requires surgical debridement in addition to antibiotic therapy with penicillin containing antibiotic in combination with clindamycin.
Botulism manifests as descending paralysis, particularly in infants. History of consumption of damaged canned food, use of honey, or living or traveling to endemic regions (high clostridial spore counts) is frequent. Physical examination findings are of an afebrile infant with acute onset of feeding difficulty and bulbar involvement (absence of a gag reflex). For suspected cases, expert review is provided by the California Department of Health (www.infantilebotulism.org). Stool should be sent for to check for Clostridium botulism spores. The mainstay of management is supportive care with or without botulism immunoglobulin (BabyBIG).
In an adolescent with a sore throat, neck pain, and tachycardia out of proportion to fever, Lemierre syndrome should be considered. A neck Doppler ultrasound should be done to look for thrombophlebitis of internal jugular veins and chest x-ray to look for septic emboli.
Local Infections Including Abscesses
Abscesses limited to CNS, head and neck region. The abdominal region can be diagnosed with appropriate anaerobic culture. The specimen should be collected from a sterile site preferably bypassing the normal flora and with needle aspiration or surgical exploration. Tissue or fluid aspirate is preferred over a swab. After collection, the sample should be sent in an anaerobic transport medium, and it should be inoculated in an oxygen-free environment.
Management of anaerobic infection depends on the site of infection, the host, and presence or absence of abscess. As a general rule, an abscess should always be drained, and the culture sent for aerobic and anaerobic culture. Also, surgical debridement of necrotic tissue in clostridium necrotizing fasciitis is crucial in treatment.
After obtaining appropriate cultures, the child should be placed on empiric antibiotics with activity against anaerobes. Following are the choices:
Metronidazole: Has excellent activity against Gram negatives such as Bacteroides fragilis. Its activity against Gram positives is good although less reliable. Metronidazole has excellent bioavailability (100%), and it penetrates well into the tissue including central nervous system and abdominal cavity. Metronidazole gives a metallic taste in the mouth which is frequently cited as the reason for discontinuation.
Clindamycin is active against many anaerobes. The resistance of clindamycin to Bacteroides fragilis is increasing, and it is less reliable as compared to metronidazole, penicillin/beta-lactamase inhibitor, or a carbapenem. Clindamycin whether administered IV or orally penetrates well into the tissue including abscesses, bones, joints. Clindamycin, however, does not enter the central nervous system.
Penicillin/beta-lactamase inhibitor combination: Penicillin alone is active against anaerobes which do not produce beta-lactamase such as Clostridium perfringens. However, most of the gram-negative anaerobes do produce beta-lactamase and combination penicillins such as oral amoxicillin/clavulanate, or intravenous (IV)/intramuscular (IM) ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam.
Second generation cephalosporin: Regarding cephalosporins, the second generation cephalosporins of cefoxitin, cefotetan, and cefmetazole are more active against Bacteroides fragilis. However, given increasing resistance, they are not recommended as an empiric treatment. It is commonly used in surgical prophylaxis.
Carbapenems: Have excellent activity against anaerobes as well as aerobes involved in intra-abdominal and other sites such as CNS. Meropenem is slightly more active than imipenem against gram-negative bacteria.
Quinolones: Have good oral absorption and tissue penetration. However, resistance is increasing, and they should be reserved for children with beta-lactam allergy. Quinolones with activity against anaerobes include levofloxacin and moxifloxacin.
Anaerobic infections are common in both outpatients and in-patients. Because of these infections can affect various organs and present in diverse ways, they are best managed by a multidisciplinary team. It is important for primary care providers, nurse practitioners, and other healthcare workers to consult with an infectious disease expert when faced with an infection which does not respond to conventional antibiotics or has an odd presentation. Anaerobic infections when misdiagnosed do carry a high mortality. 
The prognosis depends upon the type of anaerobic infection.
|||Alauzet C,Lozniewski A,Marchandin H, Metronidazole resistance and nim genes in anaerobes: A review. Anaerobe. 2018 Oct 11 [PubMed PMID: 30316817]|
|||Bula-Rudas FJ,Olcott JL, Human and Animal Bites. Pediatrics in review. 2018 Oct [PubMed PMID: 30275032]|
|||Ghoneim NH,Hamza DA, Epidemiological studies on Clostridium perfringens food poisoning in retail foods. Revue scientifique et technique (International Office of Epizootics). 2017 Dec [PubMed PMID: 30160688]|
|||Shakya N,Sharma D,Newaskar V,Agrawal D,Shrivastava S,Yadav R, Epidemiology, Microbiology and Antibiotic Sensitivity of Odontogenic Space Infections in Central India. Journal of maxillofacial and oral surgery. 2018 Sep [PubMed PMID: 30034150]|
|||Pinnola A,Kuo YH,Sciarretta JD,McIntyre A,Messier R,Davis JM, Bacteriology and Comorbidities in Patients Requiring Surgical Management of Empyema. The American surgeon. 2018 Apr 1 [PubMed PMID: 29712613]|
|||Messbarger N,Neemann K, Role of Anaerobic Blood Cultures in Neonatal Bacteremia. Journal of the Pediatric Infectious Diseases Society. 2018 Aug 17 [PubMed PMID: 29165580]|
|||Jacobs MR,Mazzulli T,Hazen KC,Good CE,Abdelhamed AM,Lo P,Shum B,Roman KP,Robinson DC, Multicenter Clinical Evaluation of BacT/Alert Virtuo Blood Culture System. Journal of clinical microbiology. 2017 Aug [PubMed PMID: 28539343]|
|||Byun JH,Kim M,Lee Y,Lee K,Chong Y, Antimicrobial Susceptibility Patterns of Anaerobic Bacterial Clinical Isolates From 2014 to 2016, Including Recently Named or Renamed Species. Annals of laboratory medicine. 2019 Mar [PubMed PMID: 30430782]|
|||Kheir MM,Tan TL,Ackerman CT,Modi R,Foltz C,Parvizi J, Culturing Periprosthetic Joint Infection: Number of Samples, Growth Duration, and Organisms. The Journal of arthroplasty. 2018 Nov [PubMed PMID: 30093264]|
|||Nyč O,Krůtová M, [Clostridium difficile remains a medical challenge]. Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti. 2017 Fall [PubMed PMID: 29308906]|
|||Lipsky BA,Berendt AR,Cornia PB,Pile JC,Peters EJ,Armstrong DG,Deery HG,Embil JM,Joseph WS,Karchmer AW,Pinzur MS,Senneville E, 2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Journal of the American Podiatric Medical Association. 2013 Jan-Feb [PubMed PMID: 23328846]|
|||Badger VO,Ledeboer NA,Graham MB,Edmiston CE Jr, Clostridium difficile: epidemiology, pathogenesis, management, and prevention of a recalcitrant healthcare-associated pathogen. JPEN. Journal of parenteral and enteral nutrition. 2012 Nov [PubMed PMID: 22577120]|
|||Roje Z,Roje Z,Matić D,Librenjak D,Dokuzović S,Varvodić J, Necrotizing fasciitis: literature review of contemporary strategies for diagnosing and management with three case reports: torso, abdominal wall, upper and lower limbs. World journal of emergency surgery : WJES. 2011 Dec 23 [PubMed PMID: 22196774]|