ceftobiprole-medocaril and Pneumonia--Ventilator-Associated

Hospital-acquired pneumonia (HAP) and health-care-associated pneumonia (HCAP) are leading causes of death, morbidity, and resource utilization in hospitalized patients, and are associated with a broad range of Gram-positive and Gram-negative pathogens. Here, we discuss the different definitions of HAP and HCAP, review current guidelines regarding the treatment of these conditions, highlight the shortcomings of current therapeutic options, and discuss new antibiotic treatments. To optimize therapeutic outcomes in patients with HAP/HCAP, initial antimicrobial treatment must be appropriate and should be given as soon as possible; inappropriate or delayed therapy greatly increases morbidity and mortality. Selection of the most appropriate antimicrobial agent depends on the causative pathogen(s); initial broad-spectrum therapy is commonly recommended and should cover all pathogens that may be present. Treatment selection should also take into consideration the following factors: knowledge of underlying local risk factors for antimicrobial resistance, disease staging, and risk factors related to specific pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus (MRSA). Guidelines consistently emphasize the importance of treating HAP and HCAP with early and appropriate broad-spectrum antibiotics, and recent developments in this field have resulted in the availability of several additional treatment options. Telavancin shows potent activity against Gram-positive bacteria including MRSA and can be administered once daily; it was approved in the USA and European Union for the treatment of HAP after demonstrating non-inferiority to vancomycin. Ceftobiprole medocaril exhibits rapid antimicrobial activity against a broad range of both Gram-positive and Gram-negative pathogens, including MRSA. It was approved for the treatment of HAP (excluding ventilator-associated pneumonia) and community-acquired pneumonia in Europe in 2013. These new treatments may offer effective alternative therapeutic options for the management of HAP.. Basilea Pharmaceutica Ltd., Basel, Switzerland.

Topics: Anti-Bacterial Agents; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Humans; Pneumonia, Ventilator-Associated; Risk Factors; Severity of Illness Index

Ceftobiprole is a cephalosporin with activity against methicillin-resistant Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa with a promising role in the treatment of hospital-acquired pneumonia (HAP). Cure rates, however, with ceftobiprole at the doses studied may be inferior to conventional treatment in the ventilator-acquired subset of HAP.. Literature was sought using PubMed and through abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy (2006 - 2012) and the European Congress of Clinical Microbiology and Infectious Diseases (2007 - 2012). The authors used the search terms "ceftobiprole," "BAL9141," "RO63-9141," "BAL5788," and 'RO5788." The article discusses the activity, mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), and clinical trials of ceftobiprole in HAP. The article also provides discussion of how PK/PD parameters play a role in the outcome of HAP treatment and how dosing in ventilator-associated pneumonia (VAP) should be reconsidered in light of altered PK/PD.. In patients with normal PK and non-VAP, ceftobiprole is effective for the treatment of HAP in the recommended doses, ceftobiprole is unlikely to achieve the desired PD targets when PK parameters are altered in VAP (e.g., increased volume of distribution and clearance). In these settings, off-label use at higher doses may overcome these limitations; but in the presence of alternative therapies, it cannot be currently recommended.

Topics: Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Cross Infection; Dose-Response Relationship, Drug; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome