Although traditionally 7 to 14 days of antibiotic therapy has been recommended for Gram-negative bacteremia, more recent studies suggest that shorter antibiotic treatment courses are as effective as longer treatments for a variety of infections, particuarly those due to Enterobacteriaceae (eg, E. Coli, Klebsiella sp) in patients with low severity illness (1).
A 2019 randomized-controlled study involving primarily patients with bacteremia caused by E. Coli or Klebsiella sp. (~75%) with most cases associated with UTI (~70%) found that 7 days was as effective as 14 days of treatment in hemodynamically stable patients who are afebrile for at least 48 hours without an ongoing focus of infection (1). More specifically, there was no significant difference between the 2 groups in the rates of relapse of bacteremia or mortality at 14 or 28 days.
An accompanying editorial concluded that “7 days of treatment may be sufficient for hospitalized, non-critically ill patients with Gram-negative bacteremia and with signs of early response to treatment” (2). Again, the accent should be on hemodynamically stable patients who respond rapidly to treatment.
These articles reflect a recent overall trend in antibiotic therapy that favors shorter courses of therapy for many common infections, as nicely summarized by a 2016 article (3).
• Community-acquired pneumonia 3-5 days (vs 7-10 days)
• Nosocomial pneumonia 8 days or less (vs 10-15 days)
• Pyelonephritis 5-7 days (vs 10-14 days)
• Intraabdominal infection 4 days (vs 10 days)
• COPD acute exacerbation 5 days or less (vs >6 days)
• Acute bacterial sinusitis 5 days (vs 10 days)
• Cellulitis 5-6 days (vs 10 days)
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1. Yahav D, Franceschini E, Koppel F, et al. Seven versus 14 days of antibiotic therapy for uncomplicated Gram-negative bacteremia: A noninferiority randomized controlled trial. Clin Infect Dis 2019; 69:1091-8. https://academic.oup.com/cid/article/69/7/1091/5237874
2. Daneman D, Fowler RA. Shortening antibiotic treatment durations for bacteremia. Clin Infect Dis 2019;69:1099-1100. https://academic.oup.com/cid/article-abstract/69/7/1099/5237877?redirectedFrom=fulltext
3. Spellberg B. The new antibiotic mantra: “ Shorter is better”. JAMA Intern Med 2016;176:1254-55. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2536180
Although meropenem is a broad spectrum antibiotic that covers many gram-negative and gram-positive organisms as well as anaerobes, its activity against enterococci is generally poor and leaves much to be desired.
In a study of ampicillin-sensitive E. faecalis isolates from hospitalized patients, only 36% of isolates were considered susceptible (MIC≤4 mg/L); activity against E. faecium isolates was similarly poor.1 Several other studies have reported the suboptimal activity of meropenem against both E. faecalis and E. faecium, 2-4 with susceptibility rates as low as 8.6% depending on the MIC break point used.3
A popular textbook and a handbook on infectious diseases also do not recommend the use of meropenem for treatment of enterococcal infections. 5,6
Of interest, the package insert states that meropenem is indicated for complicated skin and soft tissue infections due to a variety of organisms, including E. faecalis (vancomycin-susceptible isolates only), but not for complicated intra-abdominal infections or meningitis due this organism.7
In our patient with intraabdominal infection, we may consider piperacillin-tazobactam instead. Piperacillin-tazobactam is a broad spectrum antibiotic with excellent coverage against anaerobes and ampicillin-susceptible E. faecalis.1,8
- Endtz HP, van Dijk WC, Verbrugh HA, et al. Comparative in-vitro activity of meropenem against selected pathogens from hospitalized patients in the Netherlands. J Antimicrob Chemother 1997;39:149-56. https://www.ncbi.nlm.nih.gov/pubmed/9069534
- Pfaller MA, Jones RN. A review of the in vitro activity of meropenem and comparative antimicrobial agents tested against 30,254 aerobic and anaerobic pathogens isolated world wide. Diag Microbiol Infect Dis 1997;28:157-63. https://www.ncbi.nlm.nih.gov/pubmed/9327242
- Hallgren A, Abednazari H, Ekdahl C, et al. Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems. J Antimicrob Chemother 2001;48:53-62. https://www.ncbi.nlm.nih.gov/pubmed/11418512
- Hoban DJ, Jones RN, Yamane N, et al. In vitro activity of three carbapenem antibiotics comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide. Diag Microbiol Infect Dis 993;17:299-305.https://www.ncbi.nlm.nih.gov/pubmed/8112045
- Chambers HF. Carbapenem and monobactams. In Mandell GL et al. eds. Principles and practice of infectious diseases. 2010, pp 341-45.
- Cunha CB, Cunha BA. Antibiotic essentials. 2017, pp 689-91.
- Perry CM, Markham A. Piperacillin/tazobactam. Drugs 1999;57:805-43. https://link.springer.com/article/10.2165%2F00003495-199957050-00017
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