Effectiveness and Safety of Beta-Lactam Antibiotics with and without Therapeutic Drug Monitoring in Patients with Pseudomonas aeruginosa Pneumonia or Bloodstream Infection

Abstract

This objective of this study was to compare clinical outcomes in hospitalized patients with Pseudomonas aeruginosa pneumonia (PNA) or bloodstream infection (BSI) receiving beta-lactam antibiotic (BLA) infusions with and without the guidance of therapeutic drug monitoring (TDM). A retrospective, parallel cohort study was conducted at two academic medical centers between December 2015 and January 2020, UF Shands Gainesville, which uses BLA TDM for select patients (BLA TDM), and UF Health Jacksonville, which does not use BLA TDM (No-BLA TDM).

Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies

“…In two studies, the PK/PD target was 100% f T > 4xMIC 16 , 18 . In another publication, both 100% f T > MIC and 100% f T > 4 × MIC were considered as targets, and no sufficient data were provided for the comparison group that could have allowed their extraction 19 . In three publications, multiple PK/PD targets were employed 20 – 22 (Table 1 ).…”

“…Data on clinical cure from the infection were extracted from five studies including 616 patients 15 – 19 . Significantly higher odds of clinical cure were identified in the intervention group in the analysis of the pooled results [OR 2.22; 95% CI 1.78–2.76; I 2 = 0%], as well as in the subgroup analysis of the observational studies [OR 2.10; 95% CI 1.47–3.00; I 2 = 0%] and of the randomized controlled trials [OR 2.58; 95% CI 1.60–4.15; I 2 = 0%, Fig.…”

“… Author and year of publication Definitions of outcomes De Waele et al 2013 15 Clinical resolution: disappearance of all signs and symptoms associated with infection Improvement: marked or moderate reduction in severity and/or number of signs and symptoms of infection Failure: insufficient lessening of signs and symptoms of infection to qualify as improvement, including death Microbiological eradication: response to therapy was also evaluated by bacterial persistence on day 7 Fournier et al 2018 22 Clinical cure: ND Improvement: ND Failure: ND Microbiological eradication: ND Hagel et al 2022 16 Resolution: disappearance of signs and symptoms and no addition of antimicrobial therapy and no requirement for additional antibiotic treatment (except as part of de-escalation strategy) for the disease to be examined AND no initiation of antibiotic treatment for the disease to be investigated within 48 h after completion of the study drug Improvement: marked to moderate improvement in signs and symptoms and no addition of antimicrobial therapy and no initiation of antimicrobial therapy in 48 h after cessation of antibiotics Failure: signs and symptoms of infection persist or increase in comparison to baseline, or additional antibiotic treatment becomes necessary for the disease to be investigated Microbiological eradication: documented: elimination of the putative pathogen from repeated cultures of the site of infection presumed: disappearance of acute signs and symptoms related to the infection and no culture results available Fournier et al 2015 20 ND McDonald et al 2016 17 Resolution: antibiotic cessation due to microbiological control or de-escalation to narrower spectrum antibiotic triggered by clinical improvement and new microbiology data Treatment failure: escalation of antibiotic therapy with additional agents Aldaz et al 2021 18 Clinical remission: absence of all signs and symptoms suggestive of infection including the normalization of temperature, C-reactive protein (CRP) and procalcitonin (PCT) levels in the absence of known sepsis markers. Normal CRP and PCT levels were defined ≤ 0.5 mg/L and ≤ 0.5 ng/mL, respectively Microbiological remission: cultures with no bacterial growth Nikolas et al 2021 21 ND Kunz Coyne et al 2022 19 Clinical cure: absence of all-cause in-hospital mortality, escalation and...…”

Comprehensive guidance for antibiotic dosing in obese adults: 2022 update

“…21,22 A recent retrospective study with 31% obese patients (BMI > 30 kg/m 2 ) in the cohort demonstrated a benefit in clinical outcomes with β-lactam TDM versus no TDM and controlled for obesity. 23 Cefepime and piperacillin-tazobactam were the most commonly used β-lactams in both cohorts for treatment…”

“…European guidelines and workgroups have recommended that TDM be routinely performed when β‐lactam antibiotics are used in critically ill patients, but include no recommendations for dosing in obesity 21,22 . A recent retrospective study with 31% obese patients (BMI > 30 kg/m 2 ) in the cohort demonstrated a benefit in clinical outcomes with β‐lactam TDM versus no TDM and controlled for obesity 23 . Cefepime and piperacillin–tazobactam were the most commonly used β‐lactams in both cohorts for treatment of P. aeruginosa pneumonia or bloodstream infection.…”