Papara

International Journal of Antimicrobial Agents 36 (2010) 391–400

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International Journal of Antimicrobial Agents
journal homepage: http://www.elsevier.com/locate/ijantimicag

Review

Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options
Tobias Welte ∗ , Mathias W. PletzDepartment of Pulmonary Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

a r t i c l e
Keywords: Pneumonia MRSA Antimicrobials

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a b s t r a c t
Meticillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of nosocomial pneumonia. Inadequate or inappropriate antimicrobial therapy, often caused by antimicrobial resistance, is associated withincreased mortality for these infections. Agents currently recommended for the treatment of MRSA pneumonia include vancomycin and linezolid in the USA, and vancomycin, linezolid, teicoplanin and quinupristin/dalfopristin in Europe. Antimicrobials such as tigecycline and daptomycin, although approved for the treatment of some MRSA infections, have not demonstrated efficacy equivalent to the approvedagents for MRSA pneumonia. Further agents lack data from randomised controlled trials (e.g. fosfomycin, fusidic acid or rifampicin in combination with vancomycin). Antimicrobial agents that have recently been approved or are being investigated as treatments for MRSA infections include the lipoglycopeptides telavancin (approved for the treatment of complicated skin and skin-structure infections inthe USA and Canada), dalbavancin and oritavancin, the cephalosporins ceftobiprole and ceftaroline, and the dihydrofolate reductase inhibitor iclaprim. To be an effective treatment for MRSA pneumonia, antimicrobial agents must have activity against antimicrobial-resistant S. aureus, penetrate well into the lung, have a low potential for resistance development and have a good safety profile. Here,the available data for current and potential future MRSA pneumonia antimicrobials are reviewed and discussed. © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

1. Introduction Pneumonia is a common infection in communities and healthcare facilities, with mortality rates as high as 76% reported under some circumstances in ventilated patients [1,2]. Currentlyaccepted categories of pneumonia include community-acquired pneumonia (CAP) and nosocomial pneumonia, the latter encompassing healthcare-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). CAP is defined as pneumonia occurring outside of the hospital or within 48 h of hospital admission in patients with no prior contact with the healthcaresystem. HCAP is defined as pneumonia acquired outside of the hospital by patients with certain risk factors for infection with pathogens of nosocomial origin [3,4]. Patients are required to have at least one of the following risk factors for a diagnosis of HCAP: hospitalisation for >2 days in the previous 90 days in an acute care facility; residence in a nursing home or other long-term care facility;previous antibiotic therapy, chemotherapy or wound care in the previous 30 days; haemodialysis in a hospital or clinic; home infusion therapy or wound care; or a family member infected with a multidrug-resistant (MDR) pathogen [1]. HAP is defined as

∗ Corresponding author. Tel.: +49 511 532x3530. E-mail address: welte.tobias@mh-hannover.de (T. Welte).

pneumonia occurring after 48 h followinghospital admission and, similarly, VAP is defined as pneumonia occurring at least 48 h after endotracheal intubation [1]. Nosocomial pneumonia is associated with increased disease severity, mortality, length of hospital stay and hospital costs compared with CAP [4]. HCAP is more similar to HAP and VAP in terms of causative organisms, treatment requirements and prognosis than it is to CAP [4]. A...