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Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

ABSTRACT: The current study identified bacterial factors that may improve management of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Isolates were obtained from 386 patients enrolled in a randomized, controlled study of antibiotic efficacy. Isolates were screened for production of virulence factors and for vancomycin susceptibility. After adjustment for host factors such as severity of illness and treatment modality, cytotoxic activity was strongly and inversely associated with mortality; however, it had no effect on clinical cure. Isolates having low cytotoxicity, which were derived largely from healthcare-associated clones, exhibited a greater prevalence of vancomycin heteroresistance, and they were recovered more often from patients who were older and frailer. Additionally, a clone with low cytotoxic activity was associated with death and poor clinical improvement. Clone specificity and attenuated virulence appear to be associated with outcome. To our knowledge, these are the first correlations between MRSA virulence and mortality in nosocomial pneumonia.

SUBMITTER: Rose HR

PROVIDER: S-EPMC4836718 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

Rose Hannah R HR Holzman Robert S RS Altman Deena R DR Smyth Davida S DS Wasserman Gregory A GA Kafer Jared M JM Wible Michelle M Mendes Rodrigo E RE Torres Victor J VJ Shopsin Bo B

The Journal of infectious diseases 20141007 12

The current study identified bacterial factors that may improve management of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Isolates were obtained from 386 patients enrolled in a randomized, controlled study of antibiotic efficacy. Isolates were screened for production of virulence factors and for vancomycin susceptibility. After adjustment for host factors such as severity of illness and treatment modality, cytotoxic activity was strongly and inversely associated with ...[more]

PMID: 25298028

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Project description:BackgroundBacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N1)2009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection.Methodology/principal findingsPatients with community-acquired pneumonia (CAP) caused by co-infection with pandemic A(H1N1)2009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N1)2009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL).Conclusions/significanceClinicians managing patients with pandemic A(H1N1)2009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic A( H1N1) 2009 influenzavirus co-infection.

Project description:Rapid detection and differentiation of methicillin-resistant Staphylococcus aureus (MRSA) are critical for the early diagnosis of difficult-to-treat nosocomial and community acquired clinical infections and improved epidemiological surveillance. We developed a microfluidics chip coupled with surface enhanced Raman scattering (SERS) spectroscopy (532 nm) "lab-on-a-chip" system to rapidly detect and differentiate methicillin-sensitive S. aureus (MSSA) and MRSA using clinical isolates from China and the United States. A total of 21 MSSA isolates and 37 MRSA isolates recovered from infected humans were first analyzed by using polymerase chain reaction (PCR) and multilocus sequence typing (MLST). The mecA gene, which refers resistant to methicillin, was detected in all the MRSA isolates, and different allelic profiles were identified assigning isolates as either previously identified or novel clones. A total of 17 400 SERS spectra of the 58 S. aureus isolates were collected within 3.5 h using this optofluidic platform. Intra- and interlaboratory spectral reproducibility yielded a differentiation index value of 3.43-4.06 and demonstrated the feasibility of using this optofluidic system at different laboratories for bacterial identification. A global SERS-based dendrogram model for MRSA and MSSA identification and differentiation to the strain level was established and cross-validated (Simpson index of diversity of 0.989) and had an average recognition rate of 95% for S. aureus isolates associated with a recent outbreak in China. SERS typing correlated well with MLST indicating that it has high sensitivity and selectivity and would be suitable for determining the origin and possible spread of MRSA. A SERS-based partial least-squares regression model could quantify the actual concentration of a specific MRSA isolate in a bacterial mixture at levels from 5% to 100% (regression coefficient, >0.98; residual prediction deviation, >10.05). This optofluidic platform has advantages over traditional genotyping for ultrafast, automated, and reliable detection and epidemiological surveillance of bacterial infections.

Dataset Information

Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

Publications

Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

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