piperacillin--tazobactam-drug-combination and Pneumonia--Ventilator-Associated

Ventilator-associated pneumonia (VAP) is one of the most important problems of intensive care units. Eighty-four neurologic patients with acute stroke (Glasgow Coma Score ≤8) were entered into a double-blind clinical trial. Patients in the intervention group received piperacillin-tazobactam 4 g/0.5 g at the time of intubation and 12 h later. The incidences of early-onset (within four days of intubation) and late-onset VAP were 9.2 and 26.9 episodes per 1000 days of mechanical ventilation in the intervention and control groups, respectively (odds ratio: 0.217; 95% confidence interval: 0.056-0.085; P = 0.028). Administration of prophylactic piperacillin-tazobactam may reduce early-onset VAP, but the benefit does not extend to late-onset VAP.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Double-Blind Method; Female; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Treatment Outcome; Young Adult

The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. In previous studies, we found a higher rate of clinical cure of ventilator-associated pneumonia (VAP) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime. Therefore, the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam (PIP/TAZ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure. Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Cohort Studies; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome

Both cefoperazone-sulbactam (CFP-SUL) and piperacillin-tazobactam (PIP-TAZ) are β-lactam/β-lactamase inhibitor antibiotics and have a similar antimicrobial spectrum. However, comparative clinical efficacy and safety of CFP-SUL and PIP-TAZ for the treatment of pneumonia remain largely unknown, especially in elderly patients.. Based on a multi-centre registry database, patients aged ≥65 years, diagnosed with severe community-acquired pneumonia (SCAP), hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), and given empirical therapy with CFP-SUL or PIP-TAZ were included in the analysis. The primary outcome of interest was the proportion of patients achieving clinical cure. Multi-variate logistic regression was conducted to compare odds ratios (OR) for the outcome between patients who received CFP-SUL and patients who received PIP-TAZ.. In total, 941 elderly patients (624 with SCAP, and 317 with either HAP or VAP) were included in this study. Overall in-hospital mortality for the entire cohort was 19%. Clinical cure was achieved in 81% and 83% of patients with SCAP and HAP/VAP, respectively. Multi-variate logistic regression analysis showed similar odds for clinical cure for patients receiving CFP-SUL or PIP-TAZ among those with SCAP [adjusted OR 1.10, 95% confidence interval (CI) 0.71-1.70] or HAP/VAP (adjusted OR 0.72, 95% CI 0.30-1.76). Regarding safety, both CFP-SUL and PIP-TAZ were generally well tolerated with few reported adverse events.. Among elderly patients with SCAP or HAP/VAP, empirical therapy with CFP-SUL is a viable alternative to PIP-TAZ, while considering antibiotic heterogeneity in the antimicrobial stewardship context.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefoperazone; Cohort Studies; Community-Acquired Infections; Female; Frail Elderly; Healthcare-Associated Pneumonia; Humans; Male; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Treatment Outcome

To compare the rate of therapeutic failure in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacterales pulmonary infections.. Over a 4-year period, all adult patients treated for a wild-type AmpC-producing Enterobacterales pulmonary infection were retrospectively included. Two groups of patients were compared according to the definitive antibiotic therapy (3GCs or PTZ) considered after <48 h of empirical antibiotic therapy. The main outcome was the rate of therapeutic failure (impaired clinical response under treatment and/or a relapse of pulmonary infection). The secondary outcome was a secondary acquisition of 3GCs resistance.. Over the study period, 244 patients were included; 56 (23%) experienced therapeutic failure. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, p = .011 and 13 vs. 5%, p = .035, respectively). In the propensity score-matched population, the use of 3GCs was associated with higher rates of therapeutic failure (HR = 1.61 [1.27-2.07]). The secondary de-escalation to 3GCs after 48 h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance.. Our study confirms that 3GCs should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacterales pulmonary infections.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cephalosporins; Critical Illness; Cross Infection; Enterobacter; Family Characteristics; Female; Hospitals; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Penicillanic Acid; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Retrospective Studies; Ventilators, Mechanical

Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial. A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for. Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.

Topics: Aged; Anti-Bacterial Agents; Blood Platelet Disorders; Cross Infection; Humans; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by

Topics: Anti-Bacterial Agents; COVID-19; Drug Resistance, Multiple, Bacterial; Humans; Lung; Lymphocyte Activation; Male; Meropenem; Metagenomics; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Recurrence; Respiration, Artificial; SARS-CoV-2; T-Lymphocytes

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Intensive Care Units; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; United States

Topics: Aged; Amikacin; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Immunocompromised Host; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Ventilators, Mechanical

Ventilator-associated pneumonia (VAP) is an important hospital-acquired infection with substantial mortality. Only a few studies are available from India addressing the microbiological aspects of VAP, which have been done with small study populations. This study was carried out in the intensive care units (ICUs) of a tertiary care hospital to assess the profile of pathogens and to determine the pattern of antimicrobial resistance.. This was a retrospective study of clinically suspected cases of VAP. Over a three year period, a total of 247 cases in 2011, 297 in 2012 and 303 in 2013 admitted in ICUs on mechanical ventilation with clinical evidence of VAP were included in our study. The endotracheal aspirate samples from these suspected cases were subjected to quantitative culture technique, and colony count of ≥10[5] colony forming units/ml was considered significant. Antimicrobial susceptibility test for the isolates was done.. VAP rates of 44.1, 43.8 and 26.3 were seen in 2011, 2012 and 2013, respectively. In all the three years, non-fermentative Gram-negative bacilli were the predominant organisms, followed by Pseudomonas spp. and Klebsiella spp. Staphylococcus aureus exhibited a downwards trend in prevalence from 50.0 per cent in 2011 to 34.9 per cent in 2013. An increase in vancomycin-resistant enterococci was seen from 4.3 per cent in 2012 to 8.3 per cent in 2013, while methicillin resistance amongst the S. aureus crossed the 50 per cent mark in 2013. An increasing trend in resistance was shown by Pseudomonas spp. for piperacillin-tazobactam (PTZ), amikacin and imipenem (IPM). For the non-fermenters, resistance frequency remained very high except for IPM (33.1%) and polymyxin-B (2.4%).. Our findings show VAP as an important problem in the ICU setting. The incidence of multidrug-resistant pathogens was on the rise. The resistance pattern of these pathogens can help an institution to formulate effective antimicrobial policy. To have a comprehensive pan-India picture, multicentric studies are needed.

Topics: Amikacin; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; India; Intensive Care Units; Klebsiella; Methicillin Resistance; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas; Staphylococcus aureus; Tertiary Care Centers; Vancomycin-Resistant Enterococci

Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA(lys) recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.

Topics: Anti-Bacterial Agents; Clindamycin; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Rearrangement; Genetic Variation; Genome, Bacterial; Genomic Islands; Humans; Longitudinal Studies; Molecular Typing; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA

Ventilator-associated pneumonia (VAP) occurs in nearly one-third of mechanically ventilated patients in the Intensive Care Unit. Piperacillin/tazobactam (TZP) is currently recommended in the empirical treatment of VAP, but intermittent dosing may result in inadequate serum concentrations. The efficacy and costs of continuous infusion (CI) of TZP, using therapeutic drug monitoring for real-time dose adjustment, was assessed in a prospective pilot study of 16 patients with VAP. TZP was given as a loading dose of 2.0/0.25 g followed by a CI of 10.0/1.25g daily. Rapid antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration (MIC) of the pathogens. TZP concentrations were determined by high-pressure liquid chromatography before and at 1, 6, 12, 24, 48, 72 and 96 h after the onset of administration. Dosages were adjusted to maintain piperacillin concentrations four-fold above the MIC (T>4 × MIC) of the pathogen, with a maximum dose of 16.0/2.0 g. The cost of the total TZP administered was compared with the cost of a standard TZP regimen (16.0/2.0 g) if given over the same period of time. The median MIC for TZP was 1 μg/mL (range 0.025-32 μg/mL). TZP concentrations were adequate for 71% of pathogens on the first day of therapy. Clinical cure was achieved in 9/10 patients who had adequate drug concentrations and in 3/6 patients with insufficient levels. The daily dose of TZP received by CI was 37.5% less than that of a standard regimen, which corresponds to a saving of €15 on daily therapy costs compared with the standard regimen. In conclusion, CI of TZP achieved optimal drug concentrations in most patients with VAP, with a favourable impact on costs. Adequate drug concentrations were achieved for MIC ≤ 4 μg/mL, but higher dosages should be considered for the treatment of pathogens with low susceptibility thresholds.

Topics: Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Drug Monitoring; Female; Health Care Costs; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasma; Pneumonia, Ventilator-Associated; Treatment Outcome

Initial treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is usually empirical. The use of a broad-spectrum antibiotic regimen to treat NP-VAP that is active against suspected multidrug-resistant pathogens maximizes the likelihood of a favorable outcome. In a post hoc analysis of pooled data from 2 prospective, randomized, open-label, phase 3 NP-VAP trials, doripenem, a new broad-spectrum carbapenem with antipseudomonal activity, demonstrated noninferiority to standard comparator regimens (imipenem and piperacillin-tazobactam) with regard to clinical and microbiological outcomes. In subgroup analyses, doripenem continued to show noninferiority to the comparator drugs in achieving clinical and microbiological cures in populations at high risk of multidrug-resistant infection, such as patients with late-onset VAP (defined as patients who develop VAP >5 days after intubation) or those with NP-VAP caused by Pseudomonas aeruginosa or complicated by bacteremia. Overall, the clinical data indicate that doripenem has the potential to be an important option in the treatment of NP, including VAP.

Topics: Carbapenems; Cross Infection; Doripenem; Humans; Imipenem; Infusions, Intravenous; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated