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Early improvement in severely ill patients with pneumonia treated with ceftobiprole: a retrospective analysis of two major trials.

ABSTRACT: BACKGROUND:Patients with pneumonia who are elderly or severely ill are at a particularly high risk of mortality. This post hoc retrospective analysis of data from two Phase III studies evaluated early improvement outcomes in subgroups of high-risk patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia [VAP]). METHODS:One study included hospitalised CAP patients randomised to ceftobiprole or ceftriaxone ± linezolid treatment. The other study included HAP patients, who were randomised to ceftobiprole or ceftazidime plus linezolid treatment. The primary outcome was rate of early clinical response (Day 3 in CAP and Day 4 in HAP patients). Additional outcome measures included clinical cure at a test-of-cure visit, 30-day all-cause mortality and safety. RESULTS:The overall high-risk group comprised 398 CAP patients and 307 HAP patients with risk factors present at baseline. The rate of early response was numerically higher in ceftobiprole-treated patients vs comparator-treated patients in the following high-risk groups: CAP patients aged ?75?years (16.3% difference, 95% confidence interval [CI]: 1.8, 30.8); CAP patients with COPD (20.1% difference, 95% CI: 8.8, 31.1); all high-risk HAP patients (12.5% difference, 95% CI: 3.5, 21.4); HAP patients with >10 baseline comorbidities (15.3% difference, 95% CI: 0.3, 30.4). CONCLUSIONS:Previous studies show that ceftobiprole is an efficacious therapy for patients with pneumonia who are at high risk of poor outcomes. This post hoc analysis provides preliminary evidence that ceftobiprole treatment may have advantages over other antibiotics in terms of achieving early improvement in high-risk patients with HAP (excluding VAP) and in some subgroups of high-risk CAP patients. TRIAL REGISTRATION:NCT00210964 : registered September 21, 2005; NCT00229008 : registered September 29, 2005; NCT00326287 : registered May 16, 2006.

SUBMITTER: Scheeren TWL

PROVIDER: S-EPMC6390565 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Early improvement in severely ill patients with pneumonia treated with ceftobiprole: a retrospective analysis of two major trials.

Scheeren Thomas W L TWL Welte Tobias T Saulay Mikael M Engelhardt Marc M Santerre-Henriksen Anne A Hamed Kamal K

BMC infectious diseases 20190226 1

<h4>Background</h4>Patients with pneumonia who are elderly or severely ill are at a particularly high risk of mortality. This post hoc retrospective analysis of data from two Phase III studies evaluated early improvement outcomes in subgroups of high-risk patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia [VAP]).<h4>Methods</h4>One study included hospitalised CAP patients randomised to ceftobiprole or ceftriaxone ± lin ...[more]

PMID: 30808293

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Project description:BackgroundVery old patients (≥ 80 years-old, VOP) are increasingly admitted to intensive care units (ICUs). Community-acquired pneumonia (CAP) is a common reason for admission and the best strategy of support for respiratory failure in this scenario is not fully known. We evaluated whether noninvasive ventilation (NIV) would be beneficial compared to invasive mechanical ventilation (IMV) regarding hospital mortality.MethodsMulticenter cohort study of VOPs admitted with CAP in need of IMV or NIV to 11 Brazilian ICUs from 2009 through 2012. We used logistic regression models to evaluate the association between the initial ventilatory strategy (NIV vs. IMV) and hospital mortality adjusting for confounding factors. We evaluated effect modification with interaction terms in pre-specified sub-groups.ResultsOf 369 VOPs admitted for CAP with respiratory failure, 232 (63%) received NIV and 137 (37%) received IMV as initial ventilatory strategy. IMV patients were sicker at baseline (median SOFA 8 vs. 4). Hospital mortality was 114/232 (49%) for NIV and 90/137 (66%) for IMV. For the comparison NIV vs. IMV (reference), the crude odds ratio (OR) was 0.50 (95% CI, 0.33-0.78, p = 0.002). This association was largely confounded by antecedent characteristics and non-respiratory SOFA (adjOR = 0.70, 95% CI, 0.41-1.20, p = 0.196). The fully adjusted model, additionally including Pao2/Fio2 ratio, pH and Paco2, yielded an adjOR of 0.81 (95% CI, 0.46-1.41, p = 0.452). There was no strong evidence of effect modification among relevant subgroups, such as Pao2/Fio2 ratio ≤ 150 (p = 0.30), acute respiratory acidosis (p = 0.42) and non-respiratory SOFA ≥ 4 (p = 0.53).ConclusionsNIV was not associated with lower hospital mortality when compared to IMV in critically ill VOP admitted with CAP, but there was no strong signal of harm from its use. The main confounders of this association were both the severity of respiratory dysfunction and of extra-respiratory organ failures.

Project description:BackgroundPhysician-staffed helicopter emergency medical services (HEMS) are dispatched to a variety of incidents, ranging from less serious to life-threatening. The skillset of a physician may be important to provide appropriate care for the most critically ill and severely injured patients. A better understanding of these patients may therefore be important to optimize dispatch criteria, training, and equipment setups for HEMS units. The aim of this study was to describe the characteristics of patients with the national advisory committee on aeronautics (NACA) score 5 and 6, primarily by diagnostic group and interventions performed.MethodsRetrospective cohort study on aggregated data from the HEMS-base in Trondheim, Norway. All patients with NACA score 5 and 6 in the 10-year period from 2013 to 2022 were included. Patients with return of spontaneous circulation (ROSC) after successful cardiopulmonary resuscitation were described separately from non-cardiac arrest patients.ResultsOut of 9546 patient encounters, 2598 patients were included, with 1640 in the NACA 5 and 958 in NACA 6 group. Patient age was median 63 (interquartile range 45-74) and 64% of the patients were male. Post-ROSC patients accounted for 24% of patients. Of the non-cardiac arrest patients, the most frequent aetiology was trauma (16%), cardiac (15%), neurologic (14%) and respiratory (11%). The most common physician-requiring advanced interventions were general anaesthesia (22%), intubation (21%), invasive blood pressure monitoring (21%) and ventilator treatment (18%). The mean number of advanced interventions per mission were consistent during the study period (1,78, SD 0,25).ConclusionTwenty-seven percent of all HEMS dispatches were to NACA 5 and 6 patients. Twenty-four percent of these were post-ROSC patients. Sixty-three percent of all patients received at least one advanced physician-requiring intervention and the average number of interventions were consistent during the last 10 years. Hence, the competence a physician-staffed HEMS resource provide is utilized in a high number of critically ill and injured patients.

Project description:The percentage of the dosing interval that the non-protein-bound plasma concentration is above the MIC (%fT>MIC) for cephalosporins has been shown to correlate with microbiological outcomes in preclinical studies. However, clinical data are scarce. Using data from a randomized double-blind phase 3 clinical trial, we explored the relationship of ceftobiprole exposure with microbiological and clinical outcomes in patients with nosocomial pneumonia. The individual ceftobiprole exposure was determined for different pharmacokinetic (PK)/pharmacodynamic (PD) indices using individual pharmacokinetic data and a previously published population model. The MICs used in the analysis were the highest MICs for any bacterium cultured at baseline or the end of treatment (EOT). Outcomes were microbiological cure at EOT and clinical cure at test of cure (TOC). Multiple logistic regression (MLR) and classification and regression tree (CART) analyses were applied to determine the relationships among exposure, patient characteristics, and outcomes. MLR indicated that the %fT>MIC of ceftobiprole was the best predictor for both microbiological eradication and clinical cure. CART analysis showed a breakpoint value of 51.1% (n = 159; P = 0.0024) for clinical cure, whereas it was 62.2% (n = 251; P < 0.0001) for microbiological eradication. Other factors also contributed, particularly to clinical outcome. These included the difference between VAP and non-VAP patients, systemic inflammatory response syndrome (SIRS), creatinine clearance, the use of anti-Pseudomonas combination therapy, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. There is a strong correlation between microbiological eradication and clinical cure with exposure to ceftobiprole. The %fT>MIC required to result in a favorable clinical outcome is >51% of the dosing interval, which is in line with the values found for microbiological eradication, the comparator ceftazidime, and preclinical models.

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Early improvement in severely ill patients with pneumonia treated with ceftobiprole: a retrospective analysis of two major trials.

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Early improvement in severely ill patients with pneumonia treated with ceftobiprole: a retrospective analysis of two major trials.

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