Rethinking Carbapenems: A Pharmacokinetic Approach for Antimicrobial Selection in Infected Necrotizing Pancreatitis
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Objective: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. Data Sources: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. Study Selection and Data Extraction: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. Data Synthesis: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. Relevance to Patient Care and Clinical Practice: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting. Conclusions: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.Keywords:
Carbapenem
Piperacillin/tazobactam
Antimicrobial Stewardship
Cefepime
Tazobactam
Ertapenem
Doripenem
Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents.
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Background: Infection is a major clinical challenge in ALL treatment. Prompt administration of empirical antibiotic in febrile neutropenic patients has reduced the mortality. Both Cefepime or Piperacillin-Tazobactam has been used as empirical treatment.
Objective: To compare the efficacy and safety between Piperacillin-Tazobactam with Cefepime in febrile neutropenic children with ALL.
Materials and methods: This randomized study was conducted from August 2015 to August 2016 in BSMMU. Sixty one episodes of febrile neutropenia in children with ALL, aged 0 to18 years were included in this study. Patients were randomized into two groups. One group received Piperacilln/Tazobactam and another group received Cefepime and data of 60 febrile neutropenic episodes were analyzed.
Results: Febrile neutropenic episodes in the Piperacillin/Tazobactam group were 28 and in Cefepime group was 32 episodes and 34(57.63%) were male and 25 (42.37%) female. Median age was 5 years and 38(62.3%) neutropenic episodes were in induction phase. Majority had fever without focus 21(35%). Microorganisms isolated in 13 (21.66%) patients and majority 6 (46.15%) had blood infection. Most of the isolated organisms were Gram negative 11(84.61%). Overall treatment success without modification in the Piperacillin/Tazobactam group was 17(60.7%) and in Cefepime group 18 (56.3%) and that comparison was not statistically significant (p= 0.732). Significant difference was also not found comparing the mean duration of fever, neutropenia and hospital stay.
Conclusion: Both Piperacillin/Tazobactam and Cefepime were found effective and safe as an empirical therapy for febrile neutropenic children with ALL.
BANGLADESH J CHILD HEALTH 2021; VOL 45 (2) : 83-88
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To the Editor A recent trial1 comparing the effect of cefepime/enmetazobactam vs piperacillin/tazobactam on complicated urinary tract infection or acute pyelonephritis found that patients receiving cefepime/enmetazobactam had a better primary outcome. We have some concerns about this study.
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To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia.Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7.Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group.We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries.
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Background: To compare the efficacy and safety of piperacillin/tazobactam with cefepime as an empirical monotherapy for adult cancer patients with febrile neutropenia. Method: A prospective, randomized, open-labelled, comparative trial was performed. If clinically preferable, the test article may be changed to oral ciprofloxacin at 72 hours. Clinical and microbiological responses were determined at 72 hours and at the end of therapy. Results: A total of 89 cases were enrolled. 48 patients received piperacillin/tazobactam (PT group) and 41 patients received cefepime (CA group). Demographic and clinical characteristics were similar in two groups (p > 0.05). Clinical success rate at 72 hours in PT group (91.7%) was similar to that in CA group (85.4%) (p = 0.31). At the end of therapy, clinical success rate in PT group (91.7%) was also similar to that in CA group (100%) (p = 0.15). Adverse events including liver dysfunction (21.3%) and renal dysfunction (2.2%) were similar in two groups (p = 0.87). Conclusion: piperacillin/tazobactam monotherapy was as effective and safe as the cefepime as an empirical treatment for cancer patients with febrile neutropenia.
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Previous studies have shown a correlation between acute kidney injury (AKI) and combination antimicrobial therapy comprising piperacillin-tazobactam and vancomycin. In this study, AKIs were compared in patients who received vancomycin plus piperacillin-tazobactam with those who received vancomycin plus cefepime. We found a statistically significant increase in AKI risk in the vancomycin plus piperacillin-tazobactam group when compared to the vancomycin plus cefepime group using both AKI criteria [KDIGO 18.9% vs. 4.5% (p = 0.0012); RIFLE 11.2% vs. 1.8% (p = 0.0029)]. Vancomycin in combination with piperacillin-tazobactam led to an increased risk of AKI in comparison to vancomycin and cefepime.
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Drug utilization evaluation (DUE) is a systematic, criteria-based assessment of medicine that aims to optimize the appropriateness of antibiotic prescription. This study aimed to evaluate the performance of the DUE on prescriptions of two commonly used antibiotics in a pediatric population, cefepime and piperacillin/tazobactam, in a tertiary care hospital.This quasi-experimental study was conducted at the Department of Pediatrics, Ramathibodi Hospital, between March 2020 and August 2021. All hospitalized children aged 1 month to 20 years who received at least one dose of cefepime or piperacillin/tazobactam were enrolled. Before implementing the DUE, cefepime and piperacillin/tazobactam prescriptions were retrospectively evaluated using the DUE criteria. During the 6 month DUE implementation period, physicians voluntarily chose to use DUE to assess the prescriptions' appropriateness. Demographic data, antibiotic use, and clinical data were recorded.There were 304 prescriptions of cefepime and piperacillin/tazobactam, with 108 empirical prescriptions (72 patients) in the DUE group and 158 prescriptions (138 patients) in the non-DUE group. The appropriateness of empirical prescriptions of cefepime and piperacillin/tazobactam was significantly higher in the DUE group (93.5% vs. 83.5%; P = 0.003). Drug utilization evaluation was significantly associated with appropriate empirical prescriptions (adjusted OR 5.32: 95% CI 1.80-15.73; P = 0.003). Prescriptions in critical care wards and urinary tract infections (UTIs) were associated with not fulfilling the DUE criteria for appropriateness.Drug utilization evaluation could improve the appropriateness of empirical use of cefepime and piperacillin/tazobactam in pediatric patients. Patients in critical care units and with UTIs appeared to be associated with inappropriate empirical treatment.
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