Dataset Information

Exposure to ceftobiprole is associated with microbiological eradication and clinical cure in patients with nosocomial pneumonia.

ABSTRACT: 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.

SUBMITTER: Muller AE

PROVIDER: S-EPMC3993259 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exposure to ceftobiprole is associated with microbiological eradication and clinical cure in patients with nosocomial pneumonia.

Muller A E AE Punt N N Mouton J W JW

Antimicrobial agents and chemotherapy 20140210 5

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 determin ...[more]

PMID: 24514085

Similar Datasets

Project description:BackgroundKlebsiella pneumoniae (K. pneumoniae) is a common pathogen associated with hospital and community-onset infections. This study aimed to compare the clinical and microbiological characteristics of nosocomial, healthcare-associated (HCA), and community-acquired (CA) K. pneumoniae infections.MethodsClinical data were extracted from electronic medical records and analyzed retrospectively. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were determined for all identified strains. Carbapenemase and ESBL genes were amplified by PCR. Genotyping of carbapenem-resistant K. pneumoniae (CRKP) and ESBL-producing strains was performed by pulsed-field gel electrophoresis (PFGE).ResultsOf 379 K. pneumoniae infections, 98 (25.9%) were nosocomial, 195 (51.5%) were healthcare-associated, and 86 (22.6%) were community-acquired. Hematological malignancy (OR?=?4.467), and hypertension (OR?=?2.08) and cerebral vascular disease (OR?=?2.486) were associated with nosocomial and HCA infections respectively, when compared to CA infections. Overall, the incidence of antimicrobial resistance for the majority of agents tested was similar between nosocomial and HCA infections (P?>?0.05) and both groups had a higher incidence than CA infections (P?<?0.05). Moreover, 95.1% (78/82) of CRKP strains were isolated from the nosocomial and HCA groups. The blaKPC was the most prevalent carbapenemase gene among CRKP strains (80.5%, 66/82). ESBL-producing strains were prevalent among nosocomial (40.8%), HCA (35.9%) and CA groups (24.4%). The blaCTX-M-9-group and blaCTX-M-1-group genes were predominant in nosocomial (65.0%) and CA strains (66.7%), respectively. PFGE results showed ESBL-producing and CRKP strains were genetically diverse. Identical PFGE profiles were observed among HCA and nosocomial strains.ConclusionsNosocomial and HCA K. pneumoniae infections presented similar clinical features and antimicrobial resistance, and both two types of infections were different to CA infections. CRKP and ESBL-producing strains were disseminated mainly in HCA and nosocomial groups, and showed a clonal diversity. The cross transmission of CRKP was existed among HCA and nosocomial patients. This finding suggests that similar empirical therapy should be considered for patients with nosocomial and HCA K. pneumoniae infections and bacterial resistance surveillance of these infections is necessary.

Dataset Information

Exposure to ceftobiprole is associated with microbiological eradication and clinical cure in patients with nosocomial pneumonia.

Publications

Exposure to ceftobiprole is associated with microbiological eradication and clinical cure in patients with nosocomial pneumonia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets