Polymicrobial Infections Among Patients with Vascular Q Fever, France, 2004-2020.

We report 5 cases of vascular Q fever complicated by polymicrobial superinfection in patients who had no risk factors for acute Q fever. Q fever was diagnosed by serologic and molecular assays for Coxiella burnetii. We confirmed additional infections using conventional graft cultures.

Increased ß-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study.

BACKGROUND: Augmented renal clearance (ARC) is recognized as a leading cause of ß-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased ß-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP). METHODS: In this single-center, retrospective study, every ARC patient treated by ß-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome. RESULTS: During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period. CONCLUSIONS: Higher than licensed dosing regimens of ß-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of ß-lactams administered by continuous infusion: a prospective observational study.

This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose ß-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored ß-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CLCr measurements and therapeutic drug monitoring. The main outcome was the rate of ß-lactam underdosing, defined as a free drug concentration <4 × MIC of the known pathogen. Secondary outcomes were rates of subexposure for ß-lactams and therapeutic failure. The performance of CLCr in predicting underdosing was assessed by a ROC curve, and multivariable logistic regression was performed to determine risk factors for subexposure and therapeutic failure. A total of 79 patients were included and 235 samples were analysed. The rate of underdosing<4×MIC was 12%, with a significant association with CLCr (P <0.0001). A threshold of CLCr ≥ 170 mL/min had a sensitivity and specificity of 0.93 (95% CI 0.77-0.99) and 0.65 (95% CI 0.58-0.71) for predicting ß-lactam underdosing<4×MIC. Mean CLCr values ≥170 mL/min were significantly associated with subexposure<4xMIC [OR = 10.1 (2.4-41.6); P = 0.001]. Patients with subexposure<4×MIC presented higher rates of therapeutic failure [OR = 6.3 (1.2-33.2); P = 0.03]. Mean CLCr values ≥170 mL/min remain a risk factor for subexposure to ß-lactams despite high doses of ß-lactams administered continuously. ß-Lactam subexposure was associated with higher rates of therapeutic failure in septic critically ill patients.