Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis

Abstract

Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28-1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55-0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference − 1.27, 95% Confidence Interval − 2.45-0.08, P = 0.04) in critically ill patients. Conclusion: Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy.

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study

“…After the DALI-study revealed that underdosing of beta-lactam antimicrobials was common in critically ill patients, several dose optimization strategies, such as higher maintenance doses and the use of continuous infusions, were developed and implemented [ 25 ]. These strategies were also used during this study, resulting in almost all samples attaining the minimum—conservative—clinical target set forward by the joint ESICM/IATDMCT/ISAC position paper for beta-lactam antimicrobials given by continuous infusion: a measured steady state concentration above the BP [ 4 ].…”

Extended infusion of piperacillin–tazobactam versus intermittent infusion in critically ill egyptian patients: a cost-effectiveness study

“…On the other hand, a recent systematic review and meta-analysis evaluated articles published between 1998 to 2019 showed that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion 25 . Also, Yang et al in their meta-analysis study showed a superior clinical success rate for the continuous infusion (being used over 24 h) than the conventional intermittent approach (over 30 min.…”

Piperacillin-tazobactam: prospects for use in real-world practice

“…Клинические исследования подтверждают результаты, полученные в эксперименте. Так, метаанализ результатов 23 клинических исследований эффективности пролонгированных инфузий пиперациллина/тазобактама (Fawaz S. et al, 2020), включавший в общей сложности 3828 взрослых пациентов в критическом состоянии, продемон-стрировал, что непрерывные/длительные инфузии у пациентов в критическом состоянии статистически достоверно увеличивали частоту клинического излечения (отношение шансов (ОШ) 1,56, 95 % ДИ 1,28-1,90, р=0,0001), снижали показатели смертности (ОШ 0,68, 95 % ДИ 0,55-0,84, р=0,0003), увеличивали вероятность микробиологического излечения (ОШ 1,52, 95 % ДИ 1,10-2,11, р=0,01) и приводили к сокращению сроков госпитализации (средняя разница -1,27 дня, 95 % ДИ 2,45-0,08, р=0,04) [35].…”