Episode #34 – Febrile Digest – Enterococcus in IAI, Pharmageddon

Our Guest

Scott Crabtree, MD, MPH

Scott Crabtree is an Assistant Professor at UC Davis in Sacramento, CA.  He completed residency with the Air Force in San Antonio, and he then completed his infectious diseases fellowship at Dartmouth-Hitchcock in NH.  He completed his military service commitment and has been in UC Davis ever since.  He is a general ID clinician and has a special interest in antimicrobial stewardship and infection prevention.

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Consult Notes

In this Febrile Digest, we discussed the questions of when do we treat Enterococcus in intra-abdominal infections.  Some would focus on treating it when isolated from a sterile site, while others might not target it for treatment at all.  You can find more references below that were mentioned in the podcast.

Here are the prior IDSA IAI Guidelines (archived; from 2010):  Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America [published correction appears in Clin Infect Dis. 2010 Jun 15;50(12):1695. Dosage error in article text]. Clin Infect Dis. 2010;50(2):133-164. doi:10.1086/649554

• Text from IDSA guidelines regarding treatment of Enterococcus:
  • Empiric coverage of Enterococcus is not necessary in patients with community-acquired IAI (A-I)
  • Antimicrobial therapy for enterococci should be given when enterococci are recovered from patients with health care– associated infection (B-III).
  • Empiric anti-enterococcal therapy is recommended for patients with health care–associated intra-abdominal infection, particularly those with postoperative infection, those who have previously received cephalosporins or other antimicrobial agents selecting for Enterococcus species, immunocompromised patients, and those with valvular heart disease or prosthetic intravascular materials (B-II).
  • Initial empiric anti-enterococcal therapy should be directed against Enterococcus faecalis. Antibiotics that can potentially be used against this organism, on the basis of susceptibility testing of the individual isolate, include ampicillin, piperacillintazobactam, and vancomycin (B-III).
  • Empiric therapy directed against vancomycin-resistant Enterococcus faecium is not recommended unless the patient is at very high risk for an infection due to this organism, such as a liver transplant recipient with an intra-abdominal infection originating in the hepatobiliary tree or a patient known to be colonized with vancomycin-resistant E. faecium (B-III).

There are additional guidelines from the Surgical Infection Society (SIS), which were published in 2017: Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017;18(1):1-76. doi:10.1089/sur.2016.261

Here are an additional set of guidelines for management from the World Society for Emergency Surgery (WSES): Sartelli M, Chichom-Mefire A, Labricciosa FM, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections [published correction appears in World J Emerg Surg. 2017 Aug 2;12 :36]. World J Emerg Surg. 2017;12:29. Published 2017 Jul 10. doi:10.1186/s13017-017-0141-6

We mentioned prior trials that have compared regimens active against routine isolates for Enterococcus for community acquired infection.  None of these demonstrated a clear advantage for treatment of Enterococci.  These papers are cited in the IDSA guidelines above.

•  Cohn SM, Lipsett PA, Buchman TG, et al. Comparison of intravenous/ oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections. Ann Surg 2000; 232:254–62.
  • Multicenter, randomized trial of patients with complicated intra-abdominal infection who clinically improved on IV therapy and were switched to oral therapy after 48 hrs
  • 131 patients received piperacillin-tazobactam vs 151 patients who received ciprofloxacin + metronidazole >> results favored cipro/metro arm
  • Of 29 patients on cipro/metro and with cultures with Enterococcus, 72% had good bacteriologic response (despite no effective enterococcal therapy)
    • Authors did not stratify failures by presence of Enterococcus
• Ohlin B, Cederberg A, Forssell H, Solhaug JH, Tveit E. Piperacillin/ tazobactam compared with cefuroxime/ metronidazole in the treatment of intra-abdominal infections. Eur J Surg 1999; 165:875–84.
  • 140 PTZ vs 129 cefuroxime-metro, no diff in outcomes
  • 1/15 pts with Enterococcal infection given cipro+metro had clinical failure (due to complication of abscess)
• Polk HC Jr, Fink MP, Laverdiere M, et al. Prospective randomized study of piperacillin/tazobactam therapy of surgically treated intra-abdominal infection. The Piperacillin/Tazobactam Intra-Abdominal Infection Study Group. Am Surg 1993; 59:598–605.
  • 331 pts, pip-tazo combo favored over clindamycin + gentamicin
•  Sirinek KR, Levine BA. A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Surg Gynecol Obstet 1991; 172(Suppl):30–5.
  • Ticaricillin-clavulanate vs clindamycin-gentamicin, equivalent
• Walker AP, Nichols RL, Wilson RF, et al. Efficacy of a b-lactamase inhibitor combination for serious intraabdominal infections. Ann Surg 1993; 217:115–21.
  • Ampicillin-sulbactam vs cefoxitin, no difference

We also talked a bit about whether patients with Enterococcus in intra-abdominal infection cultures at risk for treatment failure or death?

• Groups at particular high risk of poor outcomes include
  • Immunocompromised hosts
  • Healthcare associated pos-top peritonitis
  • Severe sepsis of abd origin who have previously received cephalosporins and other broad-spectrum antibiotics selecting for Enterococcus spp
  • Pts with peritonitis and valvular heart disease or prosthetic intravascular material, which place them at higher risk for endocarditis
• Isolation has been reported as risk factor for treatment failure and death 
  • Burnett RJ, Haverstock DC, Dellinger EP, et al. Definition of the role of enterococcus in intraabdominal infection: analysis of a prospective randomized trial. Surgery 1995; 118:716–21.
    • Patients with Enterococcus had more treatment failure (28% v 14%) 
    • Enterococus was associated with failure in multivariate analysis
  • Sitges-Serra A, Lopez MJ, Girvent M, Almirall S, Sancho JJ. Postoperative enterococcal infection after treatment of complicated intra-abdominal sepsis. Br J Surg 2002; 89:361–7.
    • Post-operative enterococcal infections associated with high mortality (21 vs 4%)
• Although other more recent papers suggest there is no difference in severity/complications
  • Sanders JM, Tessier JM, Sawyer R, et al. Does Isolation of Enterococcus Affect Outcomes in Intra-Abdominal Infections?. Surg Infect (Larchmt). 2017;18(8):879-885. doi:10.1089/sur.2017.121
    • Post hoc analysis of the STOP-IT trial, stratified into two groups based on isolation of enterococcus. Not associated with number or severity of complications
  • Marcus G, Levy S, Salhab G, et al. Intra-abdominal Infections: The Role of Anaerobes, Enterococci, Fungi, and Multidrug-Resistant Organisms. Open Forum Infect Dis. 2016;3(4):ofw232. Published 2016 Dec 20. doi:10.1093/ofid/ofw232
  • Fabre V, Nemati K, Avdic E, Cosgrove SE, Amoah J, Tamma PD. The Role of Ertapenem for the Treatment of Complicated Intra-abdominal Infections With a Positive Culture for Enterococcus faecalis. Open Forum Infect Dis. 2018;6(1):ofy339. Published 2018 Dec 15. doi:10.1093/ofid/ofy339
    • Multicenter observational study comparing clinical outcomes of patients with complicated IAI growing E.faecalis who received ertapenem or pip-tazo
  • Zhang J, Yu WQ, Chen W, et al. Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Anti-Enterococcal Therapy for Intra-Abdominal Infection. Surg Infect (Larchmt). 2021;22(2):131-143. doi:10.1089/sur.2020.001

Transcript