Methicillin-Susceptible Staphylococcus aureus as a Predominantly Healthcare-Associated Pathogen: A Possible Reversal of Roles?

Background

Methicillin-resistant Staphylococcus aureus (MRSA) strains have become common causes of skin and soft tissue infections (SSTI) among previously healthy people, a role of methicillin-susceptible (MSSA) isolates before the mid-1990s. We hypothesized that, as MRSA infections became more common among S. aureus infections in the community, perhaps MSSA infections had become more important as a cause of healthcare-associated infection.

Methods

We compared patients, including children and adults, with MRSA and MSSA infections at the University of Chicago Medical Center (UCMC) from all clinical units from July 1, 2004-June 30, 2005; we also compared the genotypes of the MRSA and MSSA infecting bacterial strains.

Results

Compared with MRSA patients, MSSA patients were more likely on bivariate analysis to have bacteremia, endocarditis, or sepsis (p = 0.03), to be an adult (p = 0.005), to be in the intensive care unit (21.9% vs. 15.6%) or another inpatient unit (45.6% vs. 40.7%) at the time of culture. MRSA (346/545) and MSSA (76/114) patients did not differ significantly in the proportion classified as HA-S. aureus by the CDC CA-MRSA definition (p = 0.5). The genetic backgrounds of MRSA and MSSA multilocus sequence type (ST) 1, ST5, ST8, ST30, and ST59 comprised in combination 94.5% of MRSA isolates and 50.9% of MSSA isolates. By logistic regression, being cared for in the Emergency Department (OR 4.6, CI 1.5-14.0, p = 0.008) was associated with MRSA infection.

Conclusion

Patients with MSSA at UCMC have characteristics consistent with a health-care-associated infection more often than do patients with MRSA; a possible role reversal has occurred for MSSA and MRSA strains. Clinical MSSA and MRSA strains shared genotype backgrounds.     

Staphylococcus aureus Keratitis: A Review of Hospital Cases

Background

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. The study aimed to characterize the patient demographics, clinical features, antibiotic susceptibility, and clinical outcomes of keratitis caused by S. aureus, and to make a comparison between MRSA and methicillin-sensitive S. aureus (MSSA) isolates.

Methodology/Principal findings

Patients (n = 59) with culture-proven S. aureus keratitis treated in Chang Gung Memorial Hospital between January 1, 2006, and December 31, 2010, were included in our study. Patients'' demographic and clinical data were retrospectively reviewed. Twenty-six MRSA (44%) and 33 MSSA (56%) isolates were collected. The MRSA keratitis was significantly more common among the patients with healthcare exposure (P = 0.038), but 46.2% (12/26) of patients with MRSA keratitis were considered to have community-associated infections. All isolates were susceptible to vancomycin. MRSA isolates were significantly more resistant to clindamycin, erythromycin, and sulfamethoxazole/trimethoprim. Ocular surface disease was a significant risk factor for MRSA keratitis (P = 0.011). Visual outcome did not differ significantly between the MRSA and MSSA groups. However, age (B = 0.01, P = 0.035, 95% confidence interval [CI]: 0.001–0.019) and visual acuity at presentation (B = 0.749, P<0.001, 95% CI: 0.573–0.926) were significantly correlated with visual outcome.

Conclusions/Significance

Ocular surface disease is an important predisposing factor for S. aureus keratitis, especially for MRSA infections. Advanced age and poor visual acuity at presentation are important prognostic indicators for poor visual outcome in S. aureus keratitis. Oxacillin resistance may not be a significant prognostic indicator.     

Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis

Introduction

The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens.

Objective

To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis.

Results

Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] = 1.10 [95% confidence intervals: 0.82–1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (OR = 1.71 [1.08–2.70]) and a trend towards better clinical response (OR = 1.55 [0.93–2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR = 2.22 [1.38–3.57]), serious adverse events (OR = 1.53 [1.05–2.24]), and adverse event-related withdrawals (OR = 1.49 [1.14–1.95]) among telavancin recipients.

Conclusion

Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.     

The environment as an unrecognized reservoir for community-associated methicillin resistant Staphylococcus aureus USA300: a case-control study

Background

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are spreading, but the source of infections in non-epidemic settings remains poorly defined.

Methods

We carried out a community-based, case-control study investigating socio-demographic risk factors and infectious reservoirs associated with MRSA infections. Case patients presented with CA-MRSA infections to a New York hospital. Age-matched controls without infections were randomly selected from the hospital''s Dental Clinic patient population. During a home visit, case and control subjects completed a questionnaire, nasal swabs were collected from index respondents and household members and standardized environmental surfaces were swabbed. Genotyping was performed on S. aureus isolates.

Results

We enrolled 95 case and 95 control subjects. Cases more frequently reported diabetes mellitus and a higher number of skin infections among household members. Among case households, 53 (56%) were environmentally contaminated with S. aureus, compared to 36 (38%) control households (p = .02). MRSA was detected on fomites in 30 (32%) case households and 5 (5%; p<.001) control households. More case patients, 20 (21%) were nasally colonized with MRSA than were control indexes, 2 (2%; p<.001). In a subgroup analysis, the clinical isolate (predominantly USA300), was more commonly detected on environmental surfaces in case households with recurrent MRSA infections (16/36, 44%) than those without (14/58, 24%, p = .04).

Conclusions

The higher frequency of environmental contamination of case households with S. aureus in general and MRSA in particular implicates this as a potential reservoir for recolonization and increased risk of infection. Environmental colonization may contribute to the community spread of epidemic strains such as USA300.     

High genetic diversity among community-associated Staphylococcus aureus in Europe: results from a multicenter study

Background

Several studies have addressed the epidemiology of community-associated Staphylococcus aureus (CA-SA) in Europe; nonetheless, a comprehensive perspective remains unclear. In this study, we aimed to describe the population structure of CA-SA and to shed light on the origin of methicillin-resistant S. aureus (MRSA) in this continent.

Methods and Findings

A total of 568 colonization and infection isolates, comprising both MRSA and methicillin-susceptible S. aureus (MSSA), were recovered in 16 European countries, from community and community-onset infections. The genetic background of isolates was characterized by molecular typing techniques (spa typing, pulsed-field gel electrophoresis and multilocus sequence typing) and the presence of PVL and ACME was tested by PCR. MRSA were further characterized by SCCmec typing. We found that 59% of all isolates were associated with community-associated clones. Most MRSA were related with USA300 (ST8-IVa and variants) (40%), followed by the European clone (ST80-IVc and derivatives) (28%) and the Taiwan clone (ST59-IVa and related clonal types) (15%). A total of 83% of MRSA carried Panton-Valentine leukocidin (PVL) and 14% carried the arginine catabolic mobile element (ACME). Surprisingly, we found a high genetic diversity among MRSA clonal types (ST-SCCmec), Simpson’s index of diversity = 0.852 (0.788–0.916). Specifically, about half of the isolates carried novel associations between genetic background and SCCmec. Analysis by BURP showed that some CA-MSSA and CA-MRSA isolates were highly related, suggesting a probable local acquisition/loss of SCCmec.

Conclusions

Our results imply that CA-MRSA origin, epidemiology and population structure in Europe is very dissimilar from that of USA.     

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.     

Differences in Epidemiological and Molecular Characteristics of Nasal Colonization with Staphylococcus aureus (MSSA-MRSA) in Children from a University Hospital and Day Care Centers

Background

Clinical significance of Staphylococcus aureus colonization has been demonstrated in hospital settings; however, studies in the community have shown contrasting results regarding the relevance of colonization in infection by community-associated MRSA (CA-MRSA). In Colombia there are few studies on S. aureus colonization. The aim of this study was to determine the molecular and epidemiological characteristics of nasal colonization by S. aureus (MSSA-MRSA) in children from a university hospital and day care centers (DCCs) of Medellin, Colombia.

Methods

An observational cross-sectional study was conducted in 400 children (200 in each setting), aged 0 months to 5 years, during 2011. Samples were collected from each nostril and epidemiological information was obtained from the parents. Genotypic analysis included spa typing, PFGE, MLST, SCCmec typing, detection of genes for virulence factors and agr groups.

Results

Frequency of S. aureus colonization was 39.8% (n = 159) (hospital 44.5% and DCCs 35.0%) and by MRSA, 5.3% (n = 21) (hospital 7.0% and DCCs 3.5%). Most S. aureus colonized children were older than two years (p = 0.005), the majority of them boys (59.1%), shared a bedroom with a large number of people (p = 0.028), with history of β-Lactamase inhibitors usage (p = 0.020). MSSA strains presented the greatest genotypic diversity with 15 clonal complexes (CC). MRSA isolates presented 6 CC, most of them (47.6%) belonged to CC8-SCCmec IVc and were genetically related to previously reported infectious MRSA strains.

Conclusion

Differences in epidemiological and molecular characteristics between populations may be useful for the understanding of S. aureus nasal colonization dynamics and for the design of strategies to prevent S. aureus infection and dissemination. The finding of colonizing MRSA with similar molecular characteristics of those causing infection demonstrates the dissemination capacity of S. aureus and the risk of infection among the child population.     

Vancomycin heteroresistance is associated with reduced mortality in ST239 methicillin-resistant Staphylococcus aureus blood stream infections

Background

Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI).

Methodology

Consecutive methicillin-resistant S. aureus (MRSA) BSI episodes between 1996 and 2008 were reviewed. Patient demographics, clinical presentation, treatment and overall mortality at 30 days were extracted from the medical records. All isolates underwent vancomycin minimum inhibitory concentration (VMIC) testing by broth microdilution and Etest. hVISA was confirmed by population analysis profiling using the area under the curve method (PAP-AUC).

Principal Findings

401 evaluable MRSA BSI episodes were identified over the 12 years. Of these, 46 (11.5%) and 2 (0.5%) were confirmed as hVISA and VISA by PAP-AUC respectively. hVISA predominantly occurred in ST239-like MRSA isolates with high VMIC (2 mg/L). Compared to VSSA, hVISA was associated with chronic renal failure (p<0.001), device related infections (haemodialysis access) (p<0.001) and previous vancomycin usage (p = 0.004). On multivariate analysis, independent predictors of mortality included age, presence of multiple co-morbidities, principal diagnosis, transit to ICU and severity of illness while infection related surgery and hVISA phenotype were associated with increased survival.

Conclusions/Significance

The presence of hVISA is dependent on the appropriate interplay between host and pathogen factors. hVISA in ST239 MRSA is an independent predictor of survival. Whether these findings would be replicated across all MRSA clones is unknown and warrants further study.     

Quantifying Cost-Effectiveness of Controlling Nosocomial Spread of Antibiotic-Resistant Bacteria: The Case of MRSA

Background

The costs and benefits of controlling nosocomial spread of antibiotic-resistant bacteria are unknown.

Methods

We developed a mathematical algorithm to determine cost-effectiveness of infection control programs and explored the dynamical interactions between different epidemiological variables and cost-effectiveness. The algorithm includes occurrence of nosocomial infections, attributable mortality, costs and efficacy of infection control and how antibiotic-resistant bacteria affect total number of infections: do infections with antibiotic-resistant bacteria replace infections caused by susceptible bacteria (replacement scenario) or occur in addition to them (addition scenario). Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was used for illustration using observational data on S. aureus bacteremia (SAB) in our hospital (n = 189 between 2001–2004, all being methicillin-susceptible S. aureus [MSSA]).

Results

In the replacement scenario, the costs per life year gained range from € 45,912 to € 6590 for attributable mortality rates ranging from 10% to 50%. Using € 20,000 per life year gained as a threshold, completely preventing MRSA would be cost-effective in the replacement scenario if attributable mortality of MRSA is ≥21%. In the addition scenario, infection control would be cost saving along the entire range of estimates for attributable mortality.

Conclusions

Cost-effectiveness of controlling antibiotic-resistant bacteria is highly sensitive to the interaction between infections caused by resistant and susceptible bacteria (addition or replacement) and attributable mortality. In our setting, controlling MRSA would be cost saving for the addition scenario but would not be cost-effective in the replacement scenario if attributable mortality would be <21%.     

Methicillin-Resistant Staphylococcus aureus (MRSA) Is Increasing in Norway: A Time Series Analysis of Reported MRSA and Methicillin-Sensitive S. aureus Cases, 1997–2010

Background

Accurate estimates of the incidence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections are needed to inform public health policies. In Norway, where both MRSA infection and carriage are notifiable conditions, the reported incidence of MRSA is slowly increasing. However, the proportion of MRSA in relation to all S. aureus isolates is unknown, making it difficult to determine if the rising incidence is real or an artifact of an increasing number of tests performed.

Aim

To characterize recent trends in MRSA infections and obtain a more complete understanding of the MRSA level in Norway.

Methods

All reported cases of MRSA and methicillin-sensitive S. aureus (MSSA) from Oslo County (1997–2010) and Health Region East (2008–2008), representing approximately 11% and 36% of the Norwegian population, respectively, were analyzed using a stochastic time series analysis to characterize trends.

Results

In Oslo County, the proportion of methicillin-resistant cases increased from 0.73% to 3.78% during the study period and was well modeled by an exponential growth with a doubling constant of 5.7 years (95% CI 4.5–7.4 years). In Health Region East, the proportion of MRSA cases increased from 0.4% to 2.1% from 2002 to 2008, with a best-fitting linear increase of 0.26% (95% CI 0.21–0.30%) per year. In both cases, the choice of a linear or exponential model for the time trend produced only marginally different model fits. We found no significant changes due to revised national MRSA guidelines published in June 2009. Significant variations in the increasing time trend were observed in the five hospitals within the region. The yearly reported incidence of MSSA was relatively stable in both study areas although we found seasonal patterns with peaks in August.

Conclusion

The level of MRSA is increasing in Norway, and the proportion of methicillin resistance in all S. aureus isolates are higher than the reported proportion of MRSA in invasive infections.     

Recent Emergence of Staphylococcus aureus Clonal Complex 398 in Human Blood Cultures

Background

Recently, a clone of MRSA with clonal complex 398 (CC398) has emerged that is related to an extensive reservoir in animals, especially pigs and veal calves. It has been reported previously that methicillin-susceptible variants of CC398 circulate among humans at low frequency, and these have been isolated in a few cases of bloodstream infections (BSI). The purpose of this study was to determine the prevalence of S. aureus CC398 in blood cultures taken from patients in a geographic area with a high density of pigs.

Methodology/Principal Findings

In total, 612 consecutive episodes of S. aureus BSI diagnosed before and during the emergence of CC398 were included. Three strains (2 MSSA and 1 MRSA) that were isolated from bacteremic patients between 2010–2011 were positive in a CC398 specific PCR. There was a marked increase in prevalence of S. aureus CC398 BSI isolated between 2010–2011 compared to the combined collections that were isolated between 1996–1998 and 2002–2005 (3/157, 1.9% vs. 0/455, 0.0%; p = 0.017).

Conclusions/Significance

In conclusion, in an area with a relative high density of pigs, S. aureus CC398 was found as a cause of BSI in humans only recently. This indicates that S. aureus CC398 is able to cause invasive infections in humans and that the prevalence is rising. Careful monitoring of the evolution and epidemiology of S. aureus CC398 in animals and humans is therefore important.     

High prevalence of EMRSA-15 in Portuguese public buses: a worrisome finding

Background

The nosocomial prevalence of methicillin resistant Staphylococcus aureus (MRSA) in Portugal remains one of the highest in Europe and is currently around 50%. Transmission of S. aureus, including MRSA, occurs principally by direct human-to-human skin contact. However, S. aureus can survive for long periods on inanimate objects, which may represent an important reservoir for dissemination as well.

Methodology/Principal Findings

Between May 2009 and February 2010, handrails of 85 public urban buses circulating in Oporto, Portugal, were screened for the occurrence of MRSA. Twenty-two (26%) buses showed MRSA contamination. The molecular characterization of a total of 55 MRSA, by pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome (SCC) mec typing, spa typing, and multilocus sequence typing (MLST), clustered the isolates into three clonal types. However, the overwhelming majority (n = 50; 91%) of the isolates belonged to a single clone (PFGE A, spa types t747, t032, t025 or t020, ST22, SCCmec type IVh) that exhibits the characteristics of the pandemic EMRSA-15, currently the major lineage circulating in Portuguese hospitals, namely in the Oporto region. Two additional clones were found but in much lower numbers: (i) PFGE B, ST5, spa type t002, SCCmec IVa (n = 3), and (ii) PFGE C, spa type t008, ST8, SCCmec IVa (n = 2). None of the 55 isolates was PVL positive.

Conclusions/Significance

Public buses in Oporto seem to be an important reservoir of MRSA of nosocomial origin, providing evidence that the major hospital-associated MRSA clone in Portugal is escaping from the primary ecological niche of hospitals to the community environment. Infection control measures are urgently warranted to limit the spread of EMRSA-15 to the general population and future studies are required to assess the eventual increase of MRSA in the Portuguese community, which so far remains low.     

Persistence of livestock associated MRSA CC398 in humans is dependent on intensity of animal contact

Introduction

The presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with intensity of animal contact. It is unknown whether the presence of LA-MRSA is a result of carriage or retention of MRSA-contaminated dust. We conducted a longitudinal study among 155 veal farmers in which repeated nasal and throat swabs were taken for MRSA detection. Periods with and without animal exposure were covered.

Methods

Randomly, 51 veal calf farms were visited from June - December 2008. Participants were asked to fill in questionnaires (n = 155) to identify potential risk factors for MRSA colonisation. Nasal and throat swabs were repeatedly taken from each participant for approximately 2 months. Swabs were analysed for MRSA and MSSA by selective bacteriological culturing. Spa-types of the isolates were identified and a ST398 specific PCR was performed. Data were analyzed using generalized estimation equations (GEE) to allow for correlated observations within individuals.

Results

Mean MRSA prevalence was 38% in farmers and 16% in family members. Presence of MRSA in farmers was strongly related to duration of animal contact and was strongly reduced in periods with absence of animal contact (−58%). Family members, especially children, were more often carriers when the farmer was a carrier (OR = 2, P<0.05).Only 7% (n = 11) of the participants appeared to be persistent carriers. A large heterogeneity in spa-types was detected, however 92.7% belonged to LA-MRSA CC398. A surprisingly high fraction of the spa-types (7.3%) did not belong to CC398.

Conclusion

The presence of LA-MRSA in farmers is strongly animal-exposure related. The rapidly decreasing MRSA prevalence during absence of animal contact suggests that LA-MRSA is a poor persistent colonizer in most humans. These results are of relevance for MRSA control strategies.     

Reduced Costs for Staphylococcus aureus Carriers Treated Prophylactically with Mupirocin and Chlorhexidine in Cardiothoracic and Orthopaedic Surgery

Background

A multi centre double-blind randomised-controlled trial (M-RCT), carried out in the Netherlands in 2005–2007, showed that hospitalised patients with S. aureus nasal carriage who were treated prophylactically with mupirocin nasal ointment and chlorhexidine gluconate medicated soap (MUP-CHX), had a significantly lower risk of health-care associated S. aureus infections than patients receiving placebo (3.4% vs. 7.7%, RR 0.42, 95% CI 0.23–0.75). The objective of the present study was to determine whether treatment of patients undergoing elective cardiothoracic or orthopaedic surgery with MUP-CHX (screen-and-treat strategy) affected the costs of patient care.

Methods

We compared hospital costs of patients undergoing cardiothoracic or orthopaedic surgery (n = 415) in one of the participating centres of the M-RCT. Data from the ‘Planning and Control’ department were used to calculate total hospital costs of the patients. Total costs were calculated including nursing days, costs of surgery, costs for laboratory and radiological tests, functional assessments and other costs. Costs for personnel, materials and overhead were also included. Mean costs in the two treatment arms were compared using the t-test for equality of means (two-tailed). Subgroup analysis was performed for cardiothoracic and orthopaedic patients.

Results

An investigator-blinded analysis revealed that costs of care in the treatment arm (MUP-CHX, n = 210) were on average €1911 lower per patient than costs of care in the placebo arm (n = 205) (€8602 vs. €10513, p = 0.01). Subgroup analysis showed that MUP-CHX treated cardiothoracic patients cost €2841 less (n = 280, €9628 vs €12469, p = 0.006) and orthopaedic patients €955 less than non-treated patients (n = 135, €6097 vs €7052, p = 0.05).

Conclusions

In conclusion, in patients undergoing cardiothoracic or orthopaedic surgery, screening for S. aureus nasal carriage and treating carriers with MUP-CHX results in a substantial reduction of hospital costs.     

Molecular Characterization of Staphylococcus aureus from Patients with Surgical Site Infections at Mulago Hospital in Kampala,Uganda

Background

The prevalence of Methicillin resistant Staphylococcus aureus (MRSA) is progressively increasing globally with significant regional variation. Understanding the Staphylococcus aureus lineages is crucial in controlling nosocomial infections. Recent studies on S. aureus in Uganda have revealed an escalating burden of MRSA. However, the S. aureus genotypes circulating among patients are not known. Here, we report S. aureus lineages circulating in patients with surgical site infections (SSI) at Mulago National hospital, Kampala, Uganda.

Methods

A cross-sectional study involving 314 patients with SSI at Mulago National Hospital was conducted from September 2011 to April 2012. Pus swabs from the patients’ SSI were processed using standard microbiological procedures. Methicillin sensitive Staphylococcus aureus (MSSA) and MRSA were identified using phenotypic tests and confirmed by PCR-detection of the nuc and mecA genes, respectively. SCCmec genotypes were determined among MRSA isolates using multiplex PCR. Furthermore, to determine lineages, spa sequence based-genotyping was performed on all S. aureus isolates.

Results

Of the 314 patients with SSI, S. aureus accounted for 20.4% (64/314), of which 37.5% (24/64) were MRSA. The predominant SCCmec types were type V (33.3%, 8/24) and type I (16.7%, 4/24). The predominant spa lineages were t645 (17.2%, 11/64) and t4353 (15.6%, 10/64), and these were found to be clonally circulating in all the surgical wards. On the other hand, lineages t064, t355, and t4609 were confined to the obstetrics and gynecology wards. A new spa type (t10277) was identified from MSSA isolate. On multivariate logistic regression analysis, cancer and inducible clindamycin resistance remained as independent predictors of MRSA-SSI.

Conclusion

SCCmec types I and V are the most prevalent MRSA mecA types from the patients’ SSI. The predominant spa lineages (t645 and t4353) are clonally circulating in all the surgical wards, calling for strengthening of infection control practices at Mulago National Hospital.     

Epidemiology of Staphylococcus aureus Bacteraemia at a Tertiary Children’s Hospital in Cape Town,South Africa

Background

Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa.

Methods

A retrospective study was conducted at a children’s hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared.

Results

Over the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA.  Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality.

Conclusion

The incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa.     

Molecular analysis of repeated methicillin-resistant Staphylococcus aureus infections in children

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections.

Methodology/Principal Findings

Children with multiple MRSA infections during 2004–2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections.

Conclusions/Significance

Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections.     

Nasopharyngeal bacterial colonization and gene polymorphisms of mannose-binding lectin and toll-like receptors 2 and 4 in infants

Background

Human nasopharynx is often colonized by potentially pathogenic bacteria. Gene polymorphisms in mannose-binding lectin (MBL), toll-like receptor (TLR) 2 and TLR4 have been reported. The present study aimed to investigate possible association between nasopharyngeal bacterial colonization and gene polymorphisms of MBL, TLR2 and TLR4 in healthy infants.

Methodology/Principal Findings

From August 2008 to June 2010, 489 nasopharyngeal swabs and 412 blood samples were taken from 3-month-old healthy Finnish infants. Semi-quantitative culture was performed and pyrosequencing was used for detection of polymorphisms in MBL structural gene at codons 52, 54, and 57, TLR2 Arg753Gln and TLR4 Asp299Gly. Fifty-nine percent of subjects were culture positive for at least one of the four species: 11% for Streptococcus pneumoniae, 23% for Moraxella catarrhalis, 1% for Haemophilus influenzae and 25% for Staphylococcus aureus. Thirty-two percent of subjects had variant types in MBL, 5% had polymorphism of TLR2, and 18% had polymorphism of TLR4. Colonization rates of S. pneumoniae and S. aureus were significantly higher in infants with variant types of MBL than those with wild type (p = .011 and p = .024). Colonization rates of S. aureus and M. catarrhalis were significantly higher in infants with polymorphisms of TLR2 and of TLR4 than those without (p = .027 and p = .002).

Conclusions

Our study suggests that there is an association between nasopharyngeal bacterial colonization and genetic variation of MBL, TLR2 and TLR4 in young infants. This finding supports a role for these genetic variations in susceptibility of children to respiratory infections.     

Treatment for Schistosoma japonicum, reduction of intestinal parasite load, and cognitive test score improvements in school-aged children

Background

To determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children, we examined changes in cognitive testscores over 18 months in relation to: (i) treatment-related Schistosoma japonicum intensity decline, (ii) spontaneous reduction of single soil-transmitted helminth (STH) species, and (iii) ≥2 STH infections among 253 S. japonicum-infected children.

Methodology

Helminth infections were assessed at baseline and quarterly by the Kato-Katz method. S. japonicum infection was treated at baseline using praziquantel. An intensity-based indicator of lower vs. no change/higher infection was defined separately for each helminth species and joint intensity declines of ≥2 STH species. In addition, S. japonicum infection-free duration was defined in four categories based on time of schistosome re-infection: >18 (i.e. cured), >12 to ≤18, 6 to ≤12 and ≤6 (persistently infected) months. There was no baseline treatment for STHs but their intensity varied possibly due to spontaneous infection clearance/acquisition. Four cognitive tests were administered at baseline, 6, 12, and 18 months following S. japonicum treatment: learning and memory domains of Wide Range Assessment of Memory and Learning (WRAML), verbal fluency (VF), and Philippine nonverbal intelligence test (PNIT). Linear regression models were used to relate changes in respective infections to test performance with adjustment for sociodemographic confounders and coincident helminth infections.

Principal Findings

Children cured (β = 5.8; P = 0.02) and those schistosome-free for >12 months (β = 1.5; P = 0.03) scored higher in WRAML memory and VF tests compared to persistently infected children independent of STH infections. A decline vs. no change/increase of any individual STH species (β:11.5–14.5; all P<0.01) and the joint decline of ≥2 STH (β = 13.1; P = 0.01) species were associated with higher scores in WRAML learning test independent of schistosome infection. Hookworm and Trichuris trichiura declines were independently associated with improvements in WRAML memory scores as was the joint decline in ≥2 STH species. Baseline coinfection by ≥2 STH species was associated with low PNIT scores (β = −1.9; P = 0.04).

Conclusion/Significance

Children cured/S. japonicum-free for >12 months post-treatment and those who experienced declines of ≥2 STH species scored higher in three of four cognitive tests. Our result suggests that sustained deworming and simultaneous control for schistosome and STH infections could improve children''s ability to take advantage of educational opportunities in helminth-endemic regions.     

Synergy between Vancomycin and Nafcillin against Staphylococcus aureus in an In Vitro Pharmacokinetic/Pharmacodynamic Model

Introduction

Continued pressure from glycopeptide use has led to non-susceptible strains of Staphylococcus aureus including heterogeneously vancomycin-intermediate S. aureus (hVISA). Infections with hVISA are associated with poor patient outcomes, thus incentivizing novel treatments. Evidence suggests that vancomycin and anti-staphylococcal penicillin susceptibility are inversely related which indicates that the use of this combination may be particularly useful against methicillin-resistant S. aureus with reduced susceptibility to vancomycin, such as hVISA. The aim of this study was to evaluate the potential for synergy between vancomycin and nafcillin against hVISA.

Methods

Twenty-five hVISA strains were evaluated for vancomycin and nafcillin minimum inhibitory concentration (MIC) by broth microdilution in duplicate. Potential for synergy was assessed by time-kill at 1/2x MIC in triplicate. Five strains were chosen, representing the range nafcillin MIC’s available in the cohort –4, 16, 64, 128, and 256 µg/mL, and were run in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model in duplicate over 72 hours to evaluate the potential of the combination with simulated human pharmacokinetics. In addition, 4 fully glycopeptide susceptible strains of S. aureus including 2 methicillin-susceptible (MSSA) and 2 methicillin-resistant (MRSA) were run in the PK/PD model for comparison.

Results

In the time-kill, 92% of strains (23 of 25) displayed synergy with the combination of vancomycin and nafcillin. In the PK/PD model, all five strains of hVISA showed an improvement in overall activity (P≤0.004) and organism burden at 72 hours (P≤0.001) with the combination compared to either drug alone. The combination was also successful against both MRSA and MSSA in overall activity (P≤0.009) and organism burden at 72 hours (P≤0.016), though the magnitude of the effect was diminished against MSSA.

Conclusions

The combination of vancomycin and nafcillin significantly improved antibacterial activity against hVISA, MRSA, and MSSA compared to either drug alone.