Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa Treated With Ceftolozane/Tazobactam.

BACKGROUND: Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible P. aeruginosa. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-P. aeruginosa considering the C/T MIC. METHODS: This was a multicenter retrospective study of 90 patients with LRI caused by resistant P. aeruginosa who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. RESULTS: The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with P. aeruginosa strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; P = .041). Multivariate analysis identified septic shock (P < .001), C/T MIC >2 mg/L (P = .045), and increasing Charlson Comorbidity Index (P = .019) as independent predictors of mortality. CONCLUSIONS: The effectiveness of C/T in P. aeruginosa LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.

Noninvasive ventilation during the weaning process in chronically critically ill patients.

Chronically critically ill patients often undergo prolonged mechanical ventilation. The role of noninvasive ventilation (NIV) during weaning of these patients remains unclear. The aim of this study was to determine the value of NIV and whether a parameter can predict the need for NIV in chronically critically ill patients during the weaning process. We conducted a prospective study that included chronically critically ill patients admitted to Spanish respiratory care units. The weaning method used consisted of progressive periods of spontaneous breathing trials. Patients were transferred to NIV when it proved impossible to increase the duration of spontaneous breathing trials beyond 18 h. 231 chronically critically ill patients were included in the study. 198 (85.71%) patients achieved weaning success (mean weaning time 25.45±16.71 days), of whom 40 (21.4%) needed NIV during the weaning process. The variable which predicted the need for NIV was arterial carbon dioxide tension at respiratory care unit admission (OR 1.08 (95% CI 1.01-1.15), p=0.013), with a cut-off point of 45.5 mmHg (sensitivity 0.76, specificity 0.67, positive predictive value 0.76, negative predictive value 0.97). NIV is a useful tool during weaning in chronically critically ill patients. Hypercapnia despite mechanical ventilation at respiratory care unit admission is the main predictor of the need for NIV during weaning.