Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

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  

 

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. Chambers HF. Carbapenem and monobactams. In Mandell GL et al. eds. Principles and practice of infectious diseases. 2010, pp 341-45.
  6. Cunha CB, Cunha BA. Antibiotic essentials. 2017, pp 689-91.
  7. Meropenem.http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7253?searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dmeropenem%26t%3Dname
  8. 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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Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

Should I be concerned about piperacillin-tazobactam nephrotoxicity in the absence of vancomycin?

Nephrotoxicity associated with piperacillin-tazobactam (PT) combined with vancomycin (V) has been increasingly reported1,2,  with  some recommending that an alternative to V be used when PT is also on board 2. However, there are several reasons why the nephrotoxic potential of PT either alone or with antibiotics other than V also deserves further study before such recommendations can be widely embraced3.

First, most studies of VPT combination do not include comparative V or PT alone arms making it difficult to assess the relative contribution of these 2 antibiotics to kidney injury when used in combination. A small study that did include a PT-only  arm reported a similar rate of acute kidney injury (AKI) in PT and VPT arms ( 15.4% and 18.8% , respectively), both significantly higher that than of  V-only group (4%).4

 Other reasons not to readily dismiss PT as a cause of nephrototoxicity include the  lack of association between higher V trough levels and AKI in patients receiving VPT2, the association of PT with lower rates of renal function recovery in critically ill patients when compared to other selected β-lactams5,  and higher magnesium and potassium renal tubular loss with the use of PT compared to selected cephalosporins and ciprofloxacin6.  As with other penicillins, PT-associated acute interstitial nephritis may also occur7-8.

In short, even in the absence of V, nephrotoxic potential of PT should not be automatically dismissed.

 

Disclosure: Ref 3 was also authored by the creator of this pearl.

References

  1. Hammond DA, Smith MN, Chenghui Li, et al. Systematic review and meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam. Clin Infect Dis 2017;64:666-74.
  2. Navalkele B, Pogue JM, Karino S, et al. Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime. Clin Infect Dis 2017;64:116-123.
  3. Manian FA. Should we revisit the nephrotoxic potential of piperacillin-tazobactam as well? Clin Infect Dis 2017; https://doi.org/10.1093/cid/cix321
  4. Kim T, Kandiah S, Patel M, et al. Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. BMC Res Notes 2015;8:579.
  5. Jensen J-U S, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomized trial. BMJ Open 2012;2:e000635. http://bmjopen.bmj.com/content/2/2/e000635
  6. Polderman KH, Girbes ARJ. Piperacillin-induced magnesium and potassium loss in intensive care unit patients. Intensive Care Med 2002;28:530-522.
  7. Muriithi AK, Leung N, Valeri AM, et al. Clinical characteristics, causes and outcomes of acute interstitial nephritis in the elderly. Kidney International 2015;87:458-464.
  8. Soto J, Bosch JM, Alsar Ortiz MJ, et al. Piperacillin-induced acute interstitial nephritis. Nephron 1993;65:154-155. 
Should I be concerned about piperacillin-tazobactam nephrotoxicity in the absence of vancomycin?