Correlation of Pharmacokinetic/Pharmacodynamic–Derived Predictions of Antibiotic Efficacy with Clinical Outcomes in Severely Ill Patients with <i>Pseudomonas aeruginosa</i> Pneumonia

Fish, Douglas N.; Kiser, Tyree H.

doi:10.1002/phar.1310

Cited by 8 publications

(7 citation statements)

References 63 publications

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“…Among patients who received ceftazidime-avibactam, favorable microbiological response rates were generally high for infections by Enterobacteriaceae and more variable for those by P. aeruginosa with ceftazidime-avibactam with MICs of Յ8 mg/liter, including ceftazidime-nonsusceptible isolates (Tables 1 and 2). However, consistent with other investigations (45,46), response rates by MIC did not reveal any trends, possibly because few clinical trial isolates had ceftazidime-avibactam MICs of Ͼ8 mg/liter and because MIC-to-outcome correlations may be complicated in [44]). Intra-abdominal cultures required an invasive procedure and were obtained only when clinically indicated; therefore, microbiological responses for patients with cIAI were presumed based on clinical outcomes.…”

supporting

confidence: 84%

Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa

Nichols

Stone

Newell

et al. 2018

Antimicrob Agents Chemother

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Clinical susceptibility breakpoints against and for the ceftazidime-avibactam dosage regimen of 2,000/500 mg every 8 h (q8h) by 2-h intravenous infusion (adjusted for renal function) have been established by the FDA, CLSI, and EUCAST as susceptible (MIC, ≤8 mg/liter) and resistant (MIC, >8 mg/liter). The key supportive data from pharmacokinetic/pharmacodynamic analyses, surveillance, including molecular understanding of relevant resistance mechanisms, and efficacy in regulatory clinical trials are collated and analyzed here.

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supporting

confidence: 84%

Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa

Nichols

Stone

Newell

et al. 2018

Antimicrob Agents Chemother

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“…The PTA goals in our model were conservative and represent optimal pharmacodynamic outcomes to maximize bacterial killing in vitro , but there is a paucity in the current body of literature to support clinical outcomes associated with targeting these optimal pharmacodynamic targets using Monte Carlo simulation, and available published studies are conflicting [ 9 ]. One study conducted by Fish et al compared outcomes predicted by Monte Carlo simulation with actual clinical outcomes in 182 critically ill patients with P. aeruginosa pneumonia [ 27 ]. Both modeling and direct estimation were used to ascertain pharmacodynamic targets.…”

Section: Discussionmentioning

confidence: 99%

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

et al. 2015

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Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.

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“…Both continuous and extended infusions are established methods that may improve the probability of PK/PD target attainment within the critically ill population 8 . Additionally, some studies have suggested that PD targets are different between IA and CEI 41,42 . Loading doses are used in patients with sepsis to achieve target therapeutic drug levels more rapidly and are recommended in this setting by the Surviving Sepsis Campaign Guidelines 38 .…”

Section: What Is New and Conclusionmentioning

confidence: 99%

Loading dose and efficacy of continuous or extended infusion of beta‐lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta‐analysis and meta‐regression analysis

et al. 2020

J Clin Pharm Ther

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What is known and objective The role of continuous/extended beta‐lactam infusions (CEIs) in improving clinical outcomes among critically ill patients remains controversial. Therefore, we aimed to compare the clinical efficacy of CEI versus intermittent administration (IA) of beta‐lactams by performing a systematic review and meta‐analysis. Methods PubMed, the Cochrane Library and Embase were searched from inception until December 2018 for studies comparing clinical outcomes of CEI versus IA in critically ill patients. The meta‐analysis included 18 randomized controlled trials (RCTs) and 13 non‐RCTs. Results and discussion For CEI versus IA, the summary relative risk (RR) for overall mortality and clinical cure was 0.82 (95% confidence interval [CI]: 0.72–0.94) and 1.31 (95% CI: 1.15–1.49), respectively. Subgroup and meta‐regression analyses of the loading dose revealed a significantly increased clinical cure rate in the loading‐dose group (RR: 1.44, 95% CI: 1.22–1.69), which remained significant after adjustments for beta‐lactam type, and association between clinical cure and loading dose for clinical cure (RR: 1.47, 95% CI: 1.20–1.80; p = .001). Subgroup analysis of administration type indicated that both groups had low mortality and high clinical cure rates; however, the heterogeneity analysis did not support an association across continuous infusion and extended infusion groups. Subgroup analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) score was conducted; according to APACHE scores ≥ 16, overall mortality and clinical cure significantly differed between CEI and IA. What is new and conclusion CEIs with loading‐dose treatment may significantly improve the clinical outcomes in critically ill sepsis or septic shock patients.

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Correlation of Pharmacokinetic/Pharmacodynamic–Derived Predictions of Antibiotic Efficacy with Clinical Outcomes in Severely Ill Patients with Pseudomonas aeruginosa Pneumonia

Cited by 8 publications

References 63 publications

Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa

Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Loading dose and efficacy of continuous or extended infusion of beta‐lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta‐analysis and meta‐regression analysis

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