Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

Methicillin-resistant Staphylococcus aureus (MRSA) transmission in the hospital setting has been a frequent subject of investigation using bacterial genomes, but previous approaches have not yet fully utilised the extra deductive power provided when multiple pathogen samples are acquired from each host. Here, we used a large dataset of MRSA sequences from multiply-sampled patients to reconstruct colonisation of individuals in a high-transmission setting in a hospital in Thailand. We reconstructed transmission trees for MRSA. We also investigated transmission between anatomical sites on the same individual, finding that this either occurs repeatedly or involves a wide transmission bottleneck. We examined the between-subject bottleneck, finding considerable variation in the amount of diversity transmitted. Finally, we compared our approach to the simpler method of identifying transmission pairs using single nucleotide polymorphism (SNP) counts. This suggested that the optimum threshold for identifying a pair is 39 SNPs, if sensitivities and specificities are equally weighted

Staphylococcus aureus Bacteraemia in a Tropical Setting: Patient Outcome and Impact of Antibiotic Resistance

Background: Most information on invasive Staphylococcus aureus infections comes from temperate countries. There are considerable knowledge gaps in epidemiology, treatment, drug resistance and outcome of invasive S. aureus infection in the tropics. Methods: A prospective, observational study of S. aureus bacteraemia was conducted in a 1000-bed regional hospital in northeast Thailand over 1 year. Detailed clinical data were collected and final outcomes determined at 12 weeks, and correlated with antimicrobial susceptibility profiles of infecting isolates. Principal Findings: Ninety-eight patients with S. aureus bacteraemia were recruited. The range of clinical manifestations was similar to that reported from temperate countries. The prevalence of endocarditis was 14%. The disease burden was highest at both extremes of age, whilst mortality increased with age. The all-cause mortality rate was 52%, with a mortality attributable to S. aureus of 44%. Methicillin-resistant S. aureus (MRSA) was responsible for 28% of infections, all of which were healthcare-associated. Mortality rates for MRSA and methicillin-susceptible S. aureus (MSSA) were 67% (18/27) and 46% (33/71), respectively (p = 0.11). MRSA isolates were multidrug resistant. Only vancomycin or fusidic acid would be suitable as empirical treatment options for suspected MRSA infection. Conclusions: S. aureus is a significant pathogen in northeast Thailand, with comparable clinical manifestations and a similar endocarditis prevalence but higher mortality than industrialised countries. S. aureus bacteraemia is frequently associated with exposure to healthcare settings with MRSA causing a considerable burden of disease. Further studies are required to define setting-specific strategies to reduce mortality from S. aureus bacteraemia, prevent MRSA transmission, and to define the burden of S. aureus disease and emergence of drug resistance throughout the developing world. © 2009 Nickerson et al

Feasibility of Modified Surviving Sepsis Campaign Guidelines in a Resource-Restricted Setting Based on a Cohort Study of Severe S. Aureus Sepsis

[This corrects the article on p. e29858 in vol. 7.]

Hemodynamic support and adjunctive therapy of severe sepsis in a resource-limited setting.

<p>Hemodynamic support and adjunctive therapy of severe sepsis in a resource-limited setting.</p

Other supportive therapy in a resource-limited setting.

<p>Other supportive therapy in a resource-limited setting.</p

Management and outcome of 72 patients with severe sepsis.

<p>When not shown the patient denominator is 72. Where the denominator differs from this for a particular question, these are shown.</p

Diagnostic criteria used for organ dysfunction.

<p>Criteria were from the literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029858#pone.0029858-Bone1" target="_blank">[1]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029858#pone.0029858-Levy1" target="_blank">[2]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029858#pone.0029858-Goldstein1" target="_blank">[27]</a> to fit the available data. Acute oliguria was determined from 24-hour urine because hourly urine output was infrequently monitored. Diagnostic criteria of arterial hypoxaemia (PaO₂/FiO₂<300), ileus, and clinical signs of tissue hypoperfusion (decrease capillary refill or mottling) were not used as data were not recorded in the patient records. Laboratory testing for lactate level was not available in the hospital. The Glasgow Coma Score was not documented in patient records.</p

<i>S. aureus</i> attributable deaths occur more rapidly than non-attributable deaths.

<p>Kaplan-Meier survival curves comparing <i>S. aureus</i> attributable deaths and non-attributable deaths (p = 0.001).</p