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Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

ABSTRACT: Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators.We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test.625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 microg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129).Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings.ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).

SUBMITTER: Kollef MH

PROVIDER: S-EPMC2911715 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

Kollef Marin H MH Nathwani Dilip D Merchant Sanjay S Gast Christopher C Quintana Alvaro A Ketter Nzeera N

Critical care (London, England) 20100510 3

<h4>Introduction</h4>Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators.<h4>Methods</h4>We assessed durations ...[more]

PMID: 20459721

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Project description:IntroductionThe aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria.MethodsThis was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011).ResultsThe study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0).ConclusionsAmong patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome.Trial registrationClinicalTrials.gov: NCT00589693.

Project description:IntroductionSelective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for.MethodsNine reviews were used to source 45 observational (benchmark) groups and 137 component (control and intervention) groups of studies of SDD and studies of three non-antimicrobial methods of VAP prevention. The logit VAP-IP data were summarized by meta-analysis using random effects methods and the associated heterogeneity (tau2) was measured. As group level predictors of logit VAP-IP, the mode of VAP diagnosis, proportion of trauma admissions, the proportion receiving prolonged ventilation and the intervention method under study were examined in meta-regression models containing the benchmark groups together with either the control (models 1 to 3) or intervention (models 4 to 6) groups of the prevention studies.ResultsThe VAP-IP benchmark derived here is 22.1% (95% confidence interval; 95% CI; 19.2 to 25.5; tau2 0.34) whereas the mean VAP-IP of control groups from studies of SDD and of non-antimicrobial methods, is 35.7 (29.7 to 41.8; tau2 0.63) versus 20.4 (17.2 to 24.0; tau2 0.41), respectively (P < 0.001). The disparity between the benchmark groups and the control groups of the SDD studies, which was most apparent for the highest quality studies, could not be explained in the meta-regression models after adjusting for various group level factors. The mean VAP-IP (95% CI) of intervention groups is 16.0 (12.6 to 20.3; tau2 0.59) and 17.1 (14.2 to 20.3; tau2 0.35) for SDD studies versus studies of non-antimicrobial methods, respectively.ConclusionsThe VAP-IP among the intervention groups within the SDD evidence base is less variable and more similar to the benchmark than among the control groups. These paradoxical observations cannot readily be explained. The interpretation of the SDD evidence base cannot proceed without further consideration of this contextual effect.

Project description:IntroductionThis retrospective analysis compares the probability of target attainment (PTA) for ceftriaxone, levofloxacin and ceftaroline fosamil against Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in a representative patient population with moderate-to-severe community-acquired pneumonia (CAP).MethodsPublished pharmacokinetic (PK) models for levofloxacin and ceftriaxone, and an existing model for ceftaroline, were used with standard dosage regimens for simulating individual PK data with covariates representative of patients with CAP (5000 patients/drug regimen). PTA for clinically relevant pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated from steady state PK profiles for a range of minimum inhibitory concentrations (MICs). Cumulative fractions of response (CFRs) were also calculated using MIC distributions from 2012 to 2017 global surveillance data.ResultsCeftaroline fosamil (600 mg q12 h) achieved > 90% PTA at all exposure targets for each pathogen at European Committee on Antimicrobial Susceptibility Testing (EUCAST)/Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints, and CFRs were > 99%. Ceftriaxone, but not levofloxacin, achieved 100% PTA and > 90% CFR against S. pneumoniae. Both levofloxacin and ceftriaxone achieved high PTA and CFR against H. influenzae. Levofloxacin achieved PTAs < 90% at EUCAST/CLSI breakpoints and ceftriaxone achieved PTAs < 90% at MICs up to 2 mg/L against S. aureus; both agents produced generally low CFRs against S. aureus (except levofloxacin against methicillin-sensitive S. aureus), reflecting the lack of activity of these agents against methicillin-resistant S. aureus.ConclusionCeftaroline fosamil demonstrated higher overall PTA rates than levofloxacin and ceftriaxone, in particular against S. aureus. These results provide insight regarding the potential comparative efficacy of the described antibiotics for moderate-to-severe CAP.FundingPfizer.

Project description:BackgroundAlthough induction of labor of low-risk nulliparous women at 39 weeks reduces the risk of cesarean delivery compared with expectant management, concern regarding more frequent use of labor induction remains, given that this intervention historically has been thought to incur greater resource utilization.ObjectiveThe objective of the study was to determine whether planned elective labor induction at 39 weeks among low-risk nulliparous women, compared with expectant management, was associated with differences in health care resource utilization from the time of randomization through 8 weeks postpartum.Study designThis is a planned secondary analysis of a multicenter randomized trial in which low-risk nulliparous women were assigned to induction of labor at 39 weeks or expectant management. We assessed resource utilization after randomization in 3 time periods: antepartum, delivery admission, and discharge through 8 weeks postpartum.ResultsOf 6096 women with data available, those in the induction of labor group (n = 3059) were significantly less likely in the antepartum period after randomization to have at least 1 ambulatory visit for routine prenatal care (32.4% vs 68.4%), unanticipated care (0.5% vs 2.6%), or urgent care (16.2% vs 44.3%), or at least 1 antepartum hospitalization (0.8% vs 2.2%, P < .001 for all). They also had fewer tests (eg, sonograms, blood tests) and treatments (eg, antibiotics, intravenous hydration) prior to delivery. During the delivery admission, women in the induction of labor group spent a longer time in labor and delivery (median, 0.83 vs 0.57 days), but both women (P = .002) and their neonates (P < .001) had shorter postpartum stays. Women and neonates in both groups had similar frequencies of postpartum urgent care and hospital readmissions (P > .05 for all).ConclusionWomen randomized to induction of labor had longer durations in labor and delivery but significantly fewer antepartum visits, tests, and treatments and shorter maternal and neonatal hospital durations after delivery. These results demonstrate that the health outcome advantages associated with induction of labor are gained without incurring uniformly greater health care resource use.

Project description:IntroductionHospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP) are associated with significant healthcare resource utilization (HCRU). This a priori, exploratory, secondary analysis from the ASPECT-NP clinical trial evaluated resource utilization among patients with ventilated HABP (vHABP)/VABP treated with ceftolozane/tazobactam or meropenem.MethodsThis analysis used data from the randomized, double-blind, noninferiority phase 3 ASPECT-NP trial of patients with vHABP/VABP randomized to receive ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) or meropenem 1 g for 8-14 days. Day 28 outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, and time to mechanical ventilation extubation in the microbiological intention-to-treat (mITT) population and in an HCRU population. The HCRU population, a subset of patients from the mITT population that were alive at day 28, was used to remove resource use bias influenced by mortality rates.ResultsCeftolozane/tazobactam-treated versus meropenem-treated patients, respectively, had fewer deaths (20.1% vs. 25.5%), fewer hospital discharges (30.7% vs. 32.4%), and higher ICU discharges (60.0% vs. 58.3%) and extubations (51.9% vs. 48.2%) by day 28. In the HCRU population, adjusted LOS differences (95% confidence intervals) for ceftolozane/tazobactam compared with meropenem were 0.1 (- 1.4 to 1.6) hospitalization days, - 1.4 (- 2.9 to 0.2) ICU days, and - 0.9 (- 2.4 to 0.7) mechanical ventilation days. Patterns were similar among the VABP and Pseudomonas aeruginosa subgroups.ConclusionSimilar 28-day resource utilization outcomes were observed between ceftolozane/tazobactam and meropenem in the mITT population of patients from ASPECT-NP with vHABP/VABP due to gram-negative pathogens. ASPECT-NP was not powered to detect differences in resource utilization outcomes between treatment groups; however, numerical differences in ICU LOS and duration of mechanical ventilation were noted. Further study is needed to assess resource utilization in the real-world practice setting, especially among patients excluded from ASPECT-NP, including those with resistant P. aeruginosa infections.Trial registrationsClinicalTrials.gov: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

Dataset Information

Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

Publications

Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

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