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BMC Infectious Diseases Jun 2020Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in... (Comparative Study)
Comparative Study Meta-Analysis
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.
Topics: Adult; Anti-Bacterial Agents; Critical Illness; Humans; Length of Stay; Piperacillin, Tazobactam Drug Combination; Treatment Outcome
PubMed: 32563242
DOI: 10.1186/s12879-020-05149-6 -
Infection and Drug Resistance 2023infections have gradually emerged as life-threatening nosocomial infections worldwide, accompanied by increasing incidence, multidrug resistance and poor outcomes....
BACKGROUND
infections have gradually emerged as life-threatening nosocomial infections worldwide, accompanied by increasing incidence, multidrug resistance and poor outcomes. However, the epidemiology and clinical features of infection are still limited in mainland China.
METHODS
Patients with infections from 2011 to 2019 in southwestern China were retrospectively analyzed. The clinical features, infection patterns and outcomes were extracted from medical records and analyzed. A comprehensive systematic review was performed in accordance with PRISMA guidelines from conception to August 23, 2021.
RESULTS
Ninety-two patients were ultimately included, with the prevalence rapidly rising from 0 in 2011 to 0.19 per 1000 inpatients in 2019. A total of 93.48% of isolates were multidrug resistant, including 100% resistance to carbapenem. Furthermore, 75% of infections were concomitant with other pathogens. The mortality of our cohort was 36.96%, with risk factors for mechanical ventilation (OR=9.51, P=0.004), male sex (OR=0.27, P=0.031) and more concomitant pathogens. After propensity score matching, central venous catheters, exposure to carbapenem and antifungal drugs, and underlying tumors were associated with infection. Sixteen articles were also summarized, with reported mortality rates ranging from 11.0% to 66.6%. Blood and respiratory tract were the common sources. Piperacillin/tazobactam, trimethoprim/sulfamethoxazole, fluoroquinolone and minocycline were the most sensitive antibiotics. Inappropriate antibiotic treatment was the most commonly reported risk factor for mortality.
CONCLUSION
Nosocomial infection with has become an emerging problem with high mortality in southwestern China. Inappropriate antibiotic treatment and central venous catheters are risk factors for infection and death and should receive adequate attention.
PubMed: 36721634
DOI: 10.2147/IDR.S397051 -
Revista Chilena de Infectologia :... Aug 2021Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment.... (Meta-Analysis)
Meta-Analysis
[Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis].
BACKGROUND
Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment. This systematic review was conducted to evaluate if piperacillin/ tazobactan (PTZ) monotherapy leads to a lower incidence of therapeutic failures than comparators.
METHODS
A literature search was carried out in Embase, and MEDLINE databases using the search terms ('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')), Efficacy endpoint was treatment failure rate. The safety end-point was absence of any adverse effects (AE).
RESULTS
Eleven studies were included. No heterogeneity was detected ( I 2 0%). The risk of failure was not superior for piperacillin/tazobactan to comparators (Global RR: 0.94; IC95% 0.83 a 1.07). Rates of adverse events were similar among studies. No publication bias was detected (p 0.36).
CONCLUSIONS
This systematic review and meta-analysis showed that treating episodes of febrile neutropenia in oncology pediatric patients, the risk of failure for PTZ was not superior to comparators. Adverse events were similar to the comparators.
Topics: Anti-Bacterial Agents; Child; Drug Therapy, Combination; Humans; Neoplasms; Neutropenia; Penicillanic Acid; Piperacillin
PubMed: 34652393
DOI: 10.4067/S0716-10182021000400488 -
BMC Infectious Diseases Aug 2015Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing... (Review)
Review
Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options.
BACKGROUND
Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug-resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam.
METHODS
This systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa.
RESULTS
Clinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded.
CONCLUSIONS
Practitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.
Topics: Anti-Bacterial Agents; Databases, Factual; Gram-Negative Bacterial Infections; Humans; Intraabdominal Infections; Treatment Outcome; Urinary Tract Infections
PubMed: 26243291
DOI: 10.1186/s12879-015-1054-1 -
Scientific Reports Nov 2016It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However,... (Meta-Analysis)
Meta-Analysis Review
It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains of C. difficile in Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenic C. difficile among patients with diarrhoea was 14% (95% CI = 12-16%). In Mainland China, ST-37 and ST-3 were the most prevalent strains; fortunately, hypervirulent strains, such as ST-1 (BI/NAP1/027) and ST-11 (RT 078), have only occurred sporadically to date. The rates of C. difficile resistance to ciprofloxacin (98.3%; 95% CI = 96.9-99.7%), clindamycin (81.7%; 95% CI = 76.1-87.3%) and erythromycin (80.2%; 95% CI = 73.5-86.9%) are higher than in other counties; however, none of the C. difficile isolates reported in Mainland China were resistant to metronidazole (n/N = 0/960), vancomycin (n/N = 0/960), tigecycline (n/N = 0/41) or piperacillin/tazobactam(n/N = 0/288).
Topics: Anti-Bacterial Agents; China; Ciprofloxacin; Clindamycin; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Incidence; Male; Microbial Sensitivity Tests
PubMed: 27897206
DOI: 10.1038/srep37865 -
The Annals of Pharmacotherapy Feb 2012To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for... (Review)
Review
OBJECTIVE
To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for piperacillin/tazobactam, based on clinical and pharmacodynamic outcomes.
DATA SOURCES
MEDLINE (1950-September 2011), EMBASE (1980-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched, using the terms piperacillin, tazobactam, pharmacokinetics, pharmacodynamics, dosing, and infusion. Reference lists from relevant publications were also reviewed.
STUDY SELECTION AND DATA EXTRACTION
Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included. Prespecified clinical outcomes of interest included mortality, clinical cures, and adverse events. The pharmacodynamic endpoint of interest was percent time of unbound drug concentration remaining above the minimum inhibitory concentration.
DATA SYNTHESIS
Twelve studies were included in this review, 7 of which assessed clinical outcomes and 5 that assessed pharmacodynamic endpoints using Monte Carlo simulations. Prolonged or continuous infusions of piperacillin/tazobactam consistently achieved higher pharmacodynamic endpoints than did traditional infusions. The association of prolonged or continuous infusions with improved clinical outcomes, however, is unclear. Two retrospective studies found improved mortality rates with prolonged infusions (1 in a subgroup of patients with higher APACHE II [Acute Physiology and Chronic Health Evaluation II] scores), while another retrospective study found improved clinical cure rates with continuous infusions in patients with ventilator-associated pneumonia. These clinical benefits have not been substantiated in prospective randomized trials. No study has provided evidence of reduced adverse effects with prolonged or continuous infusions.
CONCLUSIONS
The limited evidence available does not firmly support widespread adoption of administering piperacillin/tazobactam as prolonged intermittent or continuous infusions to improve clinical outcomes despite the achievement of higher pharmacodynamic targets in simulated studies. Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies. Well-designed prospective clinical trials are required to confirm potential benefits observed in retrospective studies.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Treatment Outcome
PubMed: 22274145
DOI: 10.1345/aph.1Q378 -
Surgical Infections Aug 2022Zosyn (piperacillin-tazobactam; Pfizer Medical, New York, NY), a valuable antibiotic against gram-negative bacteria, combined with vancomycin (Z+V) is known for its... (Meta-Analysis)
Meta-Analysis
Zosyn (piperacillin-tazobactam; Pfizer Medical, New York, NY), a valuable antibiotic against gram-negative bacteria, combined with vancomycin (Z+V) is known for its high incidence of acute kidney injury (AKI), particularly in the intensive care unit (ICU), leading to the frequent use of alternatives for gram-negative coverage (Alt+V). Because there are limited data describing AKI on these alternative antibiotic agents, a systematic review and meta-analysis was conducted to determine if these regimens were indeed associated with decreased rates of AKI. A literature review was performed electronically from its inception to November 1, 2018, screening for relevant literature by title, abstract and full text according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the following databases: PubMed/Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials. Studies were included if they contained adults who had been admitted to the ICU for treatment and had received a combination of intravenous Z + V or Alt+V as well as had AKI measured during administration of these antibiotic agents. Studies were excluded if they represented pediatric populations, did not receive care in an ICU during their hospital admission, only received monotherapy for antibiotic treatment or received antibiotic treatment for less than 48 hours. Independent extraction was performed by two reviewers. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) methodology for retrospective studies. Random-effects models were used to calculate any differences between rates of AKI after Z + V or Alt + V. Fourteen articles (totaling 30,399 patients) were included. All studies available were retrospective in design. Compared with Alt + V, Z + V was associated with a higher risk ratio of AKI (1.79; 95% confidence interval [CI], 1.46-2.19; p < 0.001). Cefepime (C + V) was the most common alternative to Zosyn, and Z + V was associated with higher rates of kidney injury compared with C + V (1.70; 95% CI, 1.36-2.12; p < 0.00001). However, there was substantial heterogeneity in the data collected as well as high risk of bias. Zosyn plus vancomycin is associated with more risk of AKI compared with Alt+V coverage in ICU adult populations. However, the conclusions were limited by the retrospective nature of the studies, high bias of included articles, and heterogeneity of the included studies.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Child; Critical Illness; Humans; Kidney; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin
PubMed: 35736797
DOI: 10.1089/sur.2022.128 -
BJS Open May 2024Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics.
METHODS
Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000-2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4.
RESULTS
A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien-Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group.
CONCLUSION
Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien-Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice.
Topics: Humans; Pancreaticoduodenectomy; Antibiotic Prophylaxis; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Anti-Bacterial Agents; Piperacillin
PubMed: 38869238
DOI: 10.1093/bjsopen/zrae066 -
The Journal of Antimicrobial... Feb 2006Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam.
METHODS
Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality.
RESULTS
Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality.
CONCLUSIONS
The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.
Topics: Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Enzyme Inhibitors; Fever; Humans; Neutropenia; Penicillanic Acid; Penicillins; Quality Assurance, Health Care; Randomized Controlled Trials as Topic; Tazobactam; Treatment Outcome; beta-Lactamase Inhibitors
PubMed: 16344285
DOI: 10.1093/jac/dki448 -
Antimicrobial Agents and Chemotherapy Sep 2019Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this...
Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.
PubMed: 31591125
DOI: 10.1128/AAC.01572-19