Risk of hospitalization and death within 2 years after methicillin-resistant Staphylococcus aureus (MRSA) diagnosis in persons colonized or infected with livestock and non-livestock-associated MRSA-A nationwide register-based cohort study.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) CC398 has emerged in humans throughout Europe and the USA during the last decade and is associated with the spread of LA-MRSA CC398 in production animals. In this study, we investigated the risk of subsequent hospitalization with an S. aureus-related diagnosis and death within the first 2 years after MRSA diagnosis. The study included 7,521 carriers of MRSA, an age-matched reference population of 376,041 individuals and 7,607 patients infected with MRSA. Hazard ratios (HR) for hospitalization with an S. aureus-related diagnosis were 4.09 (95% CI: 2.78-6.00) and for death 1.21 (95% CI: 0.80-1.83) in LA-MRSA CC398 carriers compared with the reference population. Comparing carriers of LA-MRSA CC398 and non-CC398 MRSA, HR for hospitalization was 0.61 (95% CI: 0.37-0.99) and death 0.25 (95% CI: 0.16-0.40), respectively. Patients initially diagnosed with LA-MRSA CC398 or non-CC398 MRSA infection differed from MRSA carriers in terms of older age, higher Charlson comorbidity index score and longer hospital stays. HR for subsequent hospitalization and death was similar regardless having infection with LA-MRSA CC398 or non-CC398 MRSA at the time of MRSA diagnosis. We established that MRSA CC398 carriers have a lower risk of hospitalization and death up to 2 years after MRSA diagnosis than non-CC398 MRSA carriers do. In contrast, MRSA carriage, regardless the MRSA strain is a burden in terms of hospitalization and death when compared to the background reference population. Further, we established that there are no differences in risk of subsequent hospitalization and death in patients initially diagnosed with MRSA CC398 or non-CC398 MRSA infection. We suggest that public health surveillance of MRSA clearly needs to distinguish between carriage and infection as well as strain type before any inference from number of cases to disease burden is made.

Evolution and Population Dynamics of Clonal Complex 152 Community-Associated Methicillin-Resistant Staphylococcus aureus.

Since the late 1990s, changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) were recognized with the emergence of community-associated MRSA (CA-MRSA). CA-MRSA belonging to clonal complex 152 (CC152), carrying the small staphylococcal cassette chromosome mec (SCCmec) type V and encoding the Panton-Valentine leukocidin (PVL), has been observed in Europe. The aim of this study was to investigate its origin, evolution, and dissemination. Whole-genome sequencing was performed on a global collection of 149 CC152 isolates spanning 20 years (93 methicillin-susceptible S. aureus [MSSA] and 56 MRSA isolates). Core genome phylogeny, Bayesian inference, in silico resistance analyses, and genomic characterization were applied. Phylogenetic analysis revealed two major distinct clades, one dominated by MSSA and the other populated only by MRSA. The MSSA isolates were predominately from sub-Saharan Africa, whereas MRSA was almost exclusively from Europe. The European MRSA isolates all harbored an SCCmec type V (5C2&5) element, whereas other SCCmec elements were sporadically detected in MRSA from the otherwise MSSA-dominated clade, including SCCmec types IV (2B), V (5C2), and XIII (9A). In total, 93% of the studied CC152 isolates were PVL positive. Bayesian coalescent inference suggests an emergence of the European CC152-MRSA in the 1990s, while the CC152 lineage dates back to the 1970s. The CA-MRSA CC152 clone mimics the European CC80 CA-MRSA lineage by its emergence from a PVL-positive MSSA ancestor from North Africa or Europe. The CC152 lineage has acquired SCCmec several times, but acquisition of SCCmec type V (5C2&5) seems associated with expansion of MRSA CC152 in Europe.IMPORTANCE Understanding the evolution of CA-MRSA is important in light of the increasing importance of this reservoir in the dissemination of MRSA. Here, we highlight the story of the CA-MRSA CC152 lineage using whole-genome sequencing on an international collection of CC152. We show that the evolution of this lineage is novel and that antibiotic usage may have the potential to select for the phage-encoded Panton-Valentine leukocidin. The diversity of the strains correlated highly to geography, with higher level of resistance observed among the European MRSA isolates. The mobility of the SCCmec element is mandatory for the emergence of novel MRSA lineages, and we show here distinct acquisitions, one of which is linked to the successful clone found throughout Europe today.

Genomic identification of cryptic susceptibility to penicillins and ß-lactamase inhibitors in methicillin-resistant Staphylococcus aureus.

Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly all ß-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with ß-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/ß-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/ß-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.

Increased risk of diabetes mellitus five years after an episode of Staphylococcus aureus bacteraemia.

Background: Diabetes mellitus is a risk factor for infection with Staphylococcus aureus, but it is unclear whether S. aureus infection is a prediabetic condition. Methods: Nationwide population-based matched cohort study. Incidence rate and ratio with 95% confidence interval of diabetes were estimated by negative binomial regression. Results: Of 19,988 individuals with S. aureus bacteraemia and 185,579 population comparators, 667 and 4974 had a primary diagnose of diabetes within five years after discharge of S. aureus bacteraemia corresponding to a more than double risk of diabetes (adjusted incidence rate ratio 2.28 (95% confidence interval: 2.10-2.46)). Other factors associated with an increased risk of diabetes during follow-up were male sex, increasing age and level of comorbidity. Of the S. aureus bacteraemia and population cohort, 422 (2.11%) and 4048 (2.18%), respectively, developed diabetes without complications, while 245 (1.23%) and 926 (0.50%), respectively, developed diabetes with complications. Rates of diabetes without complication were increased for individuals in the S. aureus bacteraemia cohort compared to the population cohort within the first two years after which rates were comparable while rates of diabetes with complications remained higher throughout the five year follow-up period compared to the population cohort. Conclusions: The risk of diabetes was markedly increased up to five years after S. aureus bacteraemia compared to a population cohort. In addition to screening for diabetes during hospital admittance, screening cases of S. aureus bacteraemia for diabetes in the years following S. aureus bacteraemia may allow for earlier detection of diabetes.

Characterization of Staphylococcus aureus from Human Immunodeficiency Virus (HIV) patients in Accra, Ghana.

INTRODUCTION: The aims of this study were to: a) determine the nasal carriage prevalence of Stahpylococcus aureus among HIV patients, b) to characterize S. aureus strains isolated. METHODOLOGY: Characterization of S. aureus isolates was done by antibiotyping, spa typing, and detection of Panton-Valentine leukocidin (PVL) genes. RESULTS: S. aureus isolated (10/124; 8%)  belonged to spa types t084 (n = 3), t10828 (n = 2), t311, t304, t774, t645, and t091. The isolates were resistant to penicillin (100%), tetracycline (40%), rifampicin (10%), fucidic acid (10%), norfloxacin (10%), erythromycin (10%), and sulfamethoxazole trimethoprim (10%). Multidrug resistance (MDR) was detected in 30% of the isolates. CONCLUSION: The finding of MDR S. aureus among HIV-positive patients suggests that surveillance of antimicrobial resistant S. aureus among this patient group could be considered as an infection control measure in the hospital.

Rapid increase of genetically diverse methicillin-resistant Staphylococcus aureus, Copenhagen, Denmark.

In Copenhagen, methicillin-resistant Staphylococcus aureus (MRSA) accounted for <15 isolates per year during 1980-2002. However, since 2003 an epidemic increase has been observed, with 33 MRSA cases in 2003 and 110 in 2004. We analyzed these 143 cases epidemiologically and characterized isolates by pulsed-field gel electrophoresis, Staphylococcus protein A (spa) typing, multilocus sequence typing, staphylococcal chromosome cassette (SCC) mec typing, and detection of Panton-Valentine leukocidin (PVL) genes. Seventy-one percent of cases were community-onset MRSA (CO-MRSA); of these, 36% had no identified risk factors. We identified 29 spa types (t) and 16 sequence types (STs) belonging to 8 clonal complexes and 3 ST singletons. The most common clonal types were t024/ST8-IV, t019/ST30-IV, t044/ST80-IV, and t008/ST8-IV (USA300). A total of 86% of isolates harbored SCCmec IV, and 44% had PVL. Skin and soft tissue infections dominated. CO-MRSA with diverse genetic backgrounds is rapidly emerging in a low MRSA prevalence area.