In this episode, I’ll discuss an article about using piperacillin-tazobactam for the treatment of ESBL pyelonephritis.
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Lead author: Sima L Sharara
Published in Clinical Infectious Diseases December 2019
As a carbapenem sparing strategy, there has always been considerable interest in using piperacillin-tazobactam for ESBL infections in the urinary tract. The prevalence of ESBL infection is only increasing, making the need to maximize non-carbapenem antibiotics greater.
We know from the MERINO study that if bacteremia is present, piperacillin-tazobactam results in higher mortality than carbapenems, so the focus of investigators has been to look at the effectiveness of piperacillin-tazobactam against ESBL in non-bacteremic urinary infections.
Previous studies of this topic have not clearly outlined whether patients had cystitis or pyelonephritis. The investigators of this study sought to focus on non-bacteremic pyelonephritis patients with ESBL infection to determine just how far this carbapenem-sparing intervention can be pushed
This was a multi-center observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving piperacillin-tazobactam vs the carbapenems ertapenem or meropenem. The inclusion criteria required all of the following to be true:
1. The patient had urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL.
2. An ESBL gene was identified.
3. Pyuria was present, defined as ≥10 white blood cells per high powered field in the urine.
4. Dysuria and fever plus at least 1 of the following symptoms were present: emesis, rigors, hypotension, or flank pain.
A total of 186 patients were evaluated; 45 who received piperacillin-tazobactam and 141 who received a carbapenem.
The cohort was not bacteremic but did have significant disease as one-quarter were admitted to the intensive care unit and nearly half were immunocompromised, and nearly half also had underlying urologic abnormalities.
There were no statistically significant differences between groups in any of the clinical measures of efficacy including re-infection, resolution of symptoms, or mortality.
The authors concluded:
Piperacillin-tazobactam may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.
Although this study does not expand the use of piperacillin-tazobactam for ESBL urinary infections with bacteremia, it is important in that it clarifies the appropriateness of this strategy even in pyelonephritis.
A quarter of the patient in the study were even admitted to the ICU for at least 24 hours.
The most commonly prescribed doses in the study were as follows: piperacillin-tazobactam 3.375 grams IV every 6 hours (81%) or 4.5 grams IV every 6 hours (19%). It should be noted that towards the end of the study period, the institution’s recommended dose of piperacillin-tazobactam for ESBL urinary infection was raised to a minimum of 4.5 grams IV every 6 hours, and the 3.375 g dose was abandoned.
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