A Tricky Enterococcus

Enterococci are commensal bacteria inhabiting GI tract of animals and humans. It typically emerges in debilitated patients exposed to broad-spectrum antibiotics and as part of polymicrobial infections (especially, GI and/or urogenital). Enterococci are usually part of mixed aerobic and anaerobic flora, and antimicrobial regimens with minimal in vitro anti-enterococcal activity are often effective in treating mixed infections; therefore, the pathogenicity of enterococci in this setting is questionable. These and other factors limit the ability of investigators to determine the independent contribution of enterococcal infections to mortality and morbidity.

It is not uncommon to see a positive enteroccocal growth in patients with septic abdomen. Unfortunately, these bacteria commonly possess inherited and acquired resistance to multiple classes of antibiotics (multidrug resistant, MDR). For example, E. faecium has inherited resistance to penicillinase-susceptible penicillin (low level), penicillinase-resistant penicillins, cephalosporins, nalidixic acid, aztreonam, macrolides, and low levels of clindamycin and aminoglycosides (Fraser et al. 2018). It commonly acquires resistance to chloramphenicol, tetracyclines, rifampin, fluoroquinolones, aminoglycosides (high levels), and even vancomycin (Vancomycin Resistant Enterococcus, VRE). Aminopenicillins arrest their growth but do not kill the bacteria; Enterococci promptly produce B-lactamases after exposure to the betalactamase inhibitors. The combination of aminoglycosides or ceftriaxone and aminopenicillins may be used to enhance their individual effects (Fernández-Hidalgo et al. 2013) against E.faecalis but not E.faecium. Besides vancomycin and beta-lactam/aminoglycoside combination, enterococci may be sensitive to doxycycline, rifampin and chloramphenicol.

In my clinical practice, it is very common when a dog receives a definitive surgical treatment for a septic abdomen, starts to improve in the first 2-3 days after surgery, and the initial abdominal fluid culture comes back positive for Enterococci in combination with E.coli or other polymicrobial flora. E.faecium is usually MDR and chloramphenicol or rifampin are only antibiotics that this bacterium is sensitive to on the standard culture/sensitivity report. The question arises whether we should ignore the enterococcal growth since the patient is improving and its virulence has been questioned in the human and veterinary literature or we should treat this bacterium? The guideline below was created by myself after reviewing human and veterinary literature.

This guideline can be used in all patients with a positive culture growing Enterococcus spp (most common in septic abdomen secondary to GI perforation, wounds, and urogenital infections). Since the Enterococcus spp. (especially, E. faecium) has an extensive inherited and acquired antibiotic resistance and the virulence of this bacterium is controversial and not always implicated in a syndrome of sepsis, the treatment of positive Enterococcal cultures is not always warranted.

Step 1: Determine the risk of not treating Enterococcus infection.

Low risk patients

  • Hemodynamically stable
  • No new organ dysfunctions
  • Immunocompetent, not receiving immunosuppressive therapy

High risk patients

  • Patients with septic shock
  • Worsening clinical status, development of a new organ dysfunction
  • Immunocompromised patients (neutropenic, undergoing chemotherapy, receiving immunosuppressive drugs)
  • Patients with persistent intra-abdominal fluid collections without clinical improvement and in whom definitive source control cannot be achieved;
  • Patients with suspected bacterial endocarditis

Step 2: If the patient is considered a low risk for developing complications secondary to Enterococcus infection and the source control is achieved (e.g. an abscess is drained, septic abdomen is surgerized, etc), you may consider:

  1.  Not treat Enterococcus + treat other bacteria (in case of polymicrobial culture results) + continue monitoring the patient; if the patient becomes a high risk, it is recommended to consider starting antibiotic therapy specific for Enterococcus;
  2. Perform a blood culture from at least 2 different veins; if the culture is negative and the patient remains a low risk, do not treat Enterococcus; if the Enterococcal bacteremia is confirmed on the blood culture, start anti-enterococcal therapy (step 3) (Claeys et al. 2016).

Step 3: In general, if the patient is a high risk (see step 1) and has a positive Enterococcal growth, the treatment of this infection is likely warranted (Chatterjee et al 2007).

  1. Start the specific anti-enterococcal therapy once the culture/sensitivity results are back
  2. Choose the antibiotic with the least toxic potential (most common antibiotics that E.faecium remains sensitive to include doxycycline, chloramphenicol and rifampin)
  3. If E.faecium is resistant to mentioned-above antibiotics and the patient remains a high risk, vancomycin can be considered as a last resort option, however the antibiotic use committee should be consulted prior to its use. Vancomycin-resistant Enterococcus (VRE) is an emergent pathogen that is becoming more prevalent in human medicine.

References

Arias CA, Murray BE. The rise of the Enterococcus: beyond vancomycin resistance Nat Rev Microbiol. 2012;10:266–278

Hardie JM, Whiley RA. Classification and overview of the genera Streptococcus and Enterococcus. J Appl Microbiol. 1997;83:1S–11S

de Perio MA, Yarnold PR, Warren J, et al. Risk factors and outcomes associated with non-Enterococcus faecalis, non-Enterococcus faecium enterococcal bacteremia. Infect Control Hosp Epidemiol. 2006 Jan. 27(1):28-33

Chatterjee I, Iredell JR, Woods M, et al. The implications of enterococci for the intensive care unit. Crit Care Resusc. 2007 Mar. 9(1):69-75

Claeys KC, Zasowski EJ, Lagnf AM, Rybak MJ. Comparison of outcomes between patients with single versus multiple positive blood cultures for Enterococcus: Infection versus illusion?. Am J Infect Control. 2016 Jan 1. 44 (1):47-9

Fernández-Hidalgo N, Almirante B, Gavaldà J, Gurgui M, Peña C, de Alarcón A, et al. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis. Clin Infect Dis. 2013 May. 56(9):1261-8

Susan L Fraser, MD et al. Enterococcal Infections Treatment & Management. Medscape 2018.

Author: Igor Yankin

Igor is the creator of VetEmCRIT.com. He is a clinical assistant professor of Veterinary Emergency and Critical Care Medicine at the Texas A&M University.

3 thoughts on “A Tricky Enterococcus”

  1. Great post! I think that another article to consider which supports the confusion regarding this issue and the general idea that if the source of contamination is addressed, antibiotic selection may be less important is Kalafut JAAHA 2018 Comparison of Initial and Postlavage Bacterial Culture Results of Septic Peritonitis in Dogs and Cats”

    “Positive culture pre- or postlavage and appropriate antimicrobial selection did not significantly affect survival. For individual animals, culture results differed between pre- and postlavage samples, although no definitive effect of peritoneal lavage was seen for the population as a whole. Antimicrobials most commonly effective against isolates were Cefotaxime, Ceftazidime, and Imipenem. If prompt surgical source control is employed, antibiotic choice may not affect clinical outcome.”

    It can be really frustrating if the patient is not improving clinically and then deciding to reach for a “big gun” versus waiting for blood culture results..no easy answers! I would also say that progression of cytology of the abdominal fluid can be helpful while waiting for other diagnostics.

  2. Even though that the analysis may show sensitivity to a certain antimicrobial medicines in vivo, enterococcus can still be resistant to them in vitro. This is super bacteria that can over-live us all and can grow in acetic environment, in the presence of high salt concentration and survives prolonged fasting. Therefore, some sort of special approach should be used to treat the bacteria. Certainly, only pathogen strains should be treated.

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