Undisclosed: the role of aminopenicillins for the treatment of enterococcal UTIs despite in vitro resistance

Reviewed by Jose Lucar, MD; The George Washington University

There is growing interest in the role of aminopenicillins for lower urinary tract infections (UTIs) due to ampicillin-resistant Enterococcus sp. Despite susceptibility testing showing in vitro resistance according to established breakpoints, aminopenicillins reach concentrations in the urine that are likely high enough to achieve bacterial eradication in most patients. Previously, three small retrospective studies evaluating aminopenicillins as treatment for ampicillin-resistant enterococcal urinary tract infections showed similar clinical cure rates with IV ampicillin or oral amoxicillin compared to non-β-lactam antibiotics with in vitro activity2,3,4.

Here, the authors report the findings of a retrospective cohort study of hospitalized adults with symptomatic lower UTIs caused by E. faecium or vancomycin-resistant Enterococcus sp. (VRE) at a multi-hospital health system in Michigan (2013-2021). A key aspect of this study is that starting in 2013, the health system halted routine susceptibility testing on urinary enterococcal isolates, reporting only vancomycin resistance (yes/no) and displaying the following automated comment nudge: “ampicillin IV or amoxicillin orally are predictably reliable for treatment of uncomplicated enterococcal UTI”. Patients were included in this study if they had pyuria or leukocyte esterase on urinalysis and monomicrobial growth of E. faecium or VRE from a urine culture. Key exclusion criteria included definitive identification of E. faecalis, asymptomatic bacteriuria, inability to obtain a review of systems, signs of upper UTI, fever, bacteremia, and renal transplantation.

A database of 790 patients was obtained from which a randomized sample (n=178) was selected. The primary endpoint was 14-day clinical success (composite of 14-day symptom resolution and microbiologic success) comparing those who received definitive therapy with aminopenicillins (n=89) vs non-β-lactams (n=89). Catheter-related infections were comparable in both groups (35% vs 40%). The authors found no significant difference in 14-day clinical success between the groups (83% vs 82%), and no difference was observed either in separate 14-day symptom resolution and 14-day microbiologic success analyses. Similarly, subgroup analyses of definitive E. faecium identification and VRE showed no difference. Interestingly, 93% of patients in the aminopenicillins group had 14-day microbiologic success.

In addition to the limitations of retrospective studies in general, results of retrospective UTI studies need to be interpreted carefully for a number of reasons. These include challenges in discriminating a true UTI vs colonization, high rates of urinary catheterization, utilization of different definitions of clinical and microbiological cure, different inclusion/exclusion criteria, and the fact that lower UTIs can resolve without antibiotic treatment. However, this report not only provides additional evidence to support for the use of aminopenicillins for enterococcal lower UTIs regardless of susceptibility testing results, but also underscores the value of simple behavioral strategies in reporting microbiology results for antimicrobial stewardship.


  1. de Oca JEM, Veve MP, Zervos MJ, Kenney RM. Aminopenicillins versus Non-aminopenicillins for Treatment of Enterococcal Lower Urinary Tract Infections. Int J Antimicrob Agents. 2023 Mar 31:106800. Epub ahead of print. PMID: 37004756.
  2. Richey EM, Waters PW, Jovic M, Rakhman C. Treatment of Ampicillin-Resistant Enterococcus faecium Urinary Tract Infections. Fed Pract. 2015 Jun;32(6):20-23. PMID: 30766068.
  3. Cole KA, Kenney RM, Perri MB, Dumkow LE, Samuel LP, Zervos MJ, Davis SL. Outcomes of Aminopenicillin Therapy for Vancomycin-Resistant Enterococcal Urinary Tract Infections. Antimicrob Agents Chemother. 2015 Dec;59(12):7362-6. Epub 2015 Sep 14. PMID: 26369973.
  4. Shah KJ, Cherabuddi K, Shultz J, Borgert S, Ramphal R, Klinker KP. Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin-resistant Enterococcus spp (VRE): a single-center university hospital experience. Int J Antimicrob Agents. 2018 Jan;51(1):57-61. Epub 2017 Jun 27. PMID: 28666756.
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