Decolonization of methicillin-resistant Staphylococcus aureus using oral vancomycin and topical mupirocin

The objective of this study was to assess the efficacy and safety of a short course of oral vancomycin and intranasal mupirocin ointment in the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. During an outbreak of MRSA, the colonized subjects received oral vancomycin and topical mupirocin. They were screened for MRSA 1, 3, 6 and 12 months after decolonization. A questionnaire was developed to evaluate the side-effects of oral vancomycin. Thirty-five subjects were treated. Clearance was achieved in all cases, in 24 (69%) subjects after one course of therapy. Twenty-eight (80%) subjects experienced some side-effects, including six (17%) who did not tolerate oral vancomycin. Although oral vancomycin, in combination with topical mupirocin, is effective in the elimination of MRSA colonization, there is a need for further studies to confirm our results and to evaluate the safety of oral vancomycin.     

Costs of healthcare-associated methicillin-resistant Staphylococcus aureus and its control

Methicillin-resistant Staphylococcus aureus (MRSA) clones have caused a huge worldwide epidemic of hospital-acquired infections over the past 20–30 years and continue to evolve, including the advent of virulent community strains. The burden on healthcare services is highly significant, in particular because MRSA has not replaced susceptible staphylococcal infection but is an additional problem. Treatment strategies for MRSA are suboptimal and compromise the care of patients. MRSA is associated with serious morbidity and mortality, both within and without hospitals. Although the literature on the costs of MRSA and its control is suboptimal, it is clear that the control of MRSA is highly desirable and likely to be cost-effective. Any compromises in control are likely to be false economies.     

Emergence and control of an outbreak of infections due to Panton-Valentine leukocidin positive,ST22 methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit

Methicillin resistant Staphylococcus aureus (MRSA) infection can cause significant morbidity and mortality in neonates. We investigated a nosocomial MRSA outbreak in a neonatal intensive care unit (NICU), using a novel typing method. Following two fatal cases, in May 2011, a prospective outbreak investigation was conducted, involving neonates, mothers and healthcare workers in a large tertiary NICU in Sydney. MRSA isolates were characterized by antimicrobial susceptibility testing, a multiplex PCR-based reverse line blot (mPCR/RLB) binary typing system and other molecular typing methods. Over 7 months, 14 neonates were colonized with MRSA and six infected: three with superficial lesions and three with life-threatening disease, including the two index cases, who died despite empirical treatment with vancomycin. Isolates from 15 neonates were indistinguishable by RLB typing and identified as a PVL-producing ST22 SCCmec IV MRSA strain, which was resistant to gentamicin and trimethoprim-sulphamethoxazole. The outbreak strain was also isolated from one healthcare worker, one environmental swab and one father, but the source remained obscure. During the same period several different non-multiresistant and multiresistant MRSA strains were isolated from five neonates, five mothers (including two whose infants were colonized with the outbreak strain), one father, three healthcare workers and two environmental swabs. Rapid turnaround time of typing results allowed us to recognize and define the outbreak and implement targeted infection control interventions. PVL-producing ST22 SCCmec IV MRSA appears to be a virulent and highly transmissible pathogen in the NICU, which was difficult to control.     

Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host,microorganism and therapy

Mortality related to methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA-BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSAstrains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs (V-MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex (CC)5 and carried SCCmecIV and agr2. Microdilution V-MIC50 and V-MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years (HR 1.88), previous fatal disease (HR 2.16), Pitt score >1 (HR 3.45), high-risk source (HR 1.85) and inappropriate initial treatment (HR 1.39) as independent predictive factors for mortality. CC5 and CC22 (HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥ 1.5 did not have a significant impact on mortality, regardless of the method used to assess it.     

Cost-effectiveness of adding decolonization to a surveillance strategy of screening and isolation for methicillin-resistant Staphylococcus aureus carriers

We compared the cost-effectiveness of a methicillin-resistant Staphylococcus aureus (MRSA) programme of active surveillance plus decolonization with the current Veterans Health Administration (VHA) strategy of active surveillance alone, as well as a common strategy of no surveillance. A decision-analytical model was developed for an inpatient stay time horizon, using the VHA's perspective. Model inputs were taken from published literature where available, and supplemented with expert opinion when necessary. Effectiveness outcomes were hospital-acquired MRSA infections and deaths avoided. One-way and two-way sensitivity analyses and Monte Carlo simulations were performed. In the base-case analysis, the strategy of active surveillance plus decolonization dominated (i.e. lower cost and greater effectiveness) both the comparison strategies of active surveillance and no surveillance. In addition, the active surveillance strategy dominated the strategy of no surveillance. One-way and two-way sensitivity analyses demonstrated that at low levels of direct benefit of decolonization (1–4%), the strategy of active surveillance plus decolonization would no longer be dominant. In the probabilistic sensitivity analysis, active surveillance plus decolonization dominated both the other two strategies, and the active surveillance strategy dominated no surveillance in all of 1000 Monte Carlo simulations. These results provide a strong economic argument for adding an MRSA decolonization protocol to the current VHA active surveillance strategy.     

Clonal dissemination of epidemic methicillin-resistant Staphylococcus aureus in Belgium and neighboring countries

Objectives   To determine the diversity of pulsed-field gel electrophoresis (PFGE) types among epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA) recovered in Belgium, France, Germany and The Netherlands over the period 1981–94.
Methods   MRSA strains collected in a multicenter survey in Belgium ( n = 171) and from reference laboratories in neighboring countries ( n = 102) were characterized by PFGE analysis using the Sma I enzyme.
Results   In total, 32 PFGE types were found. Epidemic PFGE type 1, first recognized in 1984, accounted for 82% of Belgian strains (87% of hospitals) and 51% of European MRSA strains. Four other internationally epidemic PFGE types (types 8, 10, 11 and 12) were less widely disseminated and more recently detected (1991–94), each recovered from two or three countries. International spread of two PFGE types was linked to transfer of colonized patients to Dutch hospitals from another country where this type was frequently recovered.
Conclusions   Genotypic analysis indicated widespread distribution of several outbreak-associated MRSA strains over large European regions, which was in some instances related to interhospital patient transfer. These findings underscore the need for standardized international surveillance and control of MRSA transmission between healthcare institutions across Europe.     

Low prevalence of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in Belgian hospitals

Staphylococcus aureus strains with decreased susceptibility to glycopeptides (GISA) have been associated with increased risk of glycopeptide treatment failure. To assess the prevalence of these strains in hospitalised patients in Belgium, 455 methicillin-resistant S. aureus (MRSA) isolates collected in 2001 were screened by two assays: (i) growth on vancomycin agar screen (VAS; brain heart infusion agar (BHI) + vancomycin 6 mg/L); and (ii) a synergy/antagonism test with aztreonam/cefazolin on Mu3 agar (BHI + vancomycin 3 mg/mL). Isolates growing on VAS or Mu3 agar were characterised further by analysis of population susceptibility profiles. MICs of glycopeptides were determined by agar dilution, broth microdilution and Etest (low and high inocula) methods. The isolates were genotyped by pulsed-field gel electrophoresis (PFGE) and determination of staphylococcal cassette chromosome mec (SCCmec) type. No GISA isolates were found. Three (0.7%) hetero-vancomycin intermediate S. aureus (hVISA) and ten (2.2%) hetero-teicoplanin intermediate S. aureus (hTISA) isolates were identified by population analysis. All but one hetero-GISA isolate belonged to either epidemic PFGE group A/SCCmec type I (69%) or PFGE group D/SCCmec type I (23%), both of which were resistant to gentamicin. The sensitivity and specificity for the detection of hetero-GISA by the two assays were 15.4% and 99.8%, respectively, for VAS, and 84.6% and 95.9%, respectively, for Mu3. The data indicated that hetero-GISA strains were uncommon among Belgian MRSA isolates from hospitalised patients. Use of Mu3 agar was more sensitive, but less specific, than VAS as a screening method.     

Outbreak of methicillin-resistant Staphylococcus aureus in general hospital intensive care unit]

Mantes' hospital polyvalent intensive care unit (ICU) experienced an outbreak episode caused by methicillin resistant Staphylococcus aureus (MRSA). Suspicion of physicians was strengthened by observing the weekly reading of multiresistant germs and the significative increase of MRSA carriers incidence rate, compared with the number of admission in the ICU: 5.5% to 11.3%. This outbreak was surprising: it happened immediately after the installation in a new hospital and the reinforcement of nosocomial infection surveillance (systematic screening of every patient admitted to the I.U.C., his isolation if he presents risk factors to multiresistant germs, increasing of handwashing stations). The overlapping period of hospitalisation concerning the 13 patients being reported as SARM carrier, having the same antibiogram, and the epidemic curve suggested a cross contamination. The index case was a MRSA carrier the day of her admission and have had a recent hospitalisation in a high risk unit. MRSA has always been isolated in nasal swab. Six patients among the thirteen carriers developed an infection and have been treated by vancomycin: two systemic infections and four pulmonary infections. The mortality rate was 33% and only one of them seemed to be directly due to MRSA. Area samples were all negative. The clinical staff have been screened with nasal swab. We identified only one nasal MRSA carrier. The pulsed-field gel electrophoresis study showed that 9/11 which have been analysed were identical. This outbreak brought about staff, more sensibilisation to the nosocomial infection and updating of plain hygien rules leaded to its stop five months later.     

Antimicrobial drug use and infection control practices associated with the prevalence of methicillin-resistant Staphylococcus aureus in European hospitals

Major regional variations in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) are observed across Europe. This study investigated hospital MRSA prevalence in relation to patterns of antimicrobial use and infection control policies in an observational, cross-sectional study that used retrospective data from 2001 and linear regression to model relationships. MRSA prevalence (median 20.8%, n = 173 hospitals) and antimicrobial consumption (median 55.2 defined daily doses/100 bed-days, n = 140 hospitals) both varied significantly according to geographical region (p <0.001). MRSA prevalence and antimicrobial consumption data were provided by 128 hospitals, and showed a strong statistical relationship between macrolide use and MRSA prevalence. Use of (i) third-generation cephalosporins, (ii) all antimicrobial agents, and (iii) all antimicrobial agents except glycopeptides was also associated with MRSA prevalence. Up to 146 hospitals provided data on MRSA prevalence and key infection control parameters. Adjusted linear regression modelling provided strong evidence that infection control policy recommendations associated with lower MRSA prevalence rates were (i) use of alcohol-based solutions for hand hygiene (mean difference 10.3%, 99% CI 1.2-10.3), and (ii) placement of MRSA patients in single rooms (mean difference 11.2%, 99% CI 1.4-20.9). Hospitals with problems in implementing isolation policies had higher resistance levels (mean difference 12%, 99% CI 3.8-20.1). Additional recommendations showed less evidence of association with a low MRSA prevalence. Overall, this study highlighted significant associations between MRSA prevalence, antimicrobial use and various key infection control parameters, all of which showed significant individual variations according to geographical region.     

Prevention and control of methicillin-resistant Staphylococcus aureus

Recent efforts to combat infections have focused on pharmaceutical interventions. However, the global spread of antimicrobial resistance calls for the reappraisal of personal and institutional hygiene. Hygiene embodies behavioural and procedural rules that prevent bacterial transmission. Consequently, the chance of spreading bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is significantly reduced. Hygiene is part of the primacy and totality of patient care, ensuring that no harm is done. Any prevention and control strategy must be underpinned by changes in attitude, embraced by all. The major components of preventing and controlling MRSA include hand and environmental hygiene (as part of standard precautions), patient isolation, and patient/staff decolonization. Improving hand hygiene practice is especially important where the risk of infection is highest, e.g. in intensive care. Physical isolation has two advantages: the physical barrier interrupts transmission, and this barrier emphasizes that precautions are required. With limited isolation facilities, risk assessment should be conducted to indicate which patients should be isolated. Environmental hygiene, although important, has a lower priority than standard precautions. When a patient is ready for discharge (home) or transfer (to another healthcare facility), the overall interests of the patient should take priority. All patients should be informed of their MRSA-positive status as soon as possible. Because of increased mupirocin resistance, a selective approach to decolonization should be taken. When MRSA-positive staff are identified, restricting their professional activity will depend on the nature of their work. Finally, politicians and others need to commit to providing the necessary resources to maximize MRSA prevention and control.     

Heterogeneity of disease and clones of community-onset methicillin-resistant Staphylococcus aureus in children attending a paediatric hospital in Belgium

The increase in the number of methicillin-resistant Staphylococcus aureus (MRSA) infections in children has prompted paediatricians to broaden th empirical treatment of common community-onset (CO) infections in children in several countries. Most European countries have reported low rates of CO-MRSA infection, but limited data on paediatric CO-MRSA infections are available. A prospective study was conducted from January 2002 to December 2004 in Brussels. CO-MRSA was defined as MRSA first detected by culture within 48 h of admission or in outpatients. Clinical and epidemiological data were recorded. CO-MRSA strains were genotyped by pulsed-field gel electrophoresis and multilocus sequence typing. Staphylococcal chromosomal cassette mec, toxin (Panton-Valentin leukocidin (PVL), toxic shock syndrome toxin 1, and Eta/b), enterotoxin and antibiotic resistance genes were detected by PCR. The antibiotic resistance phenotype was determined by disk diffusion. S. aureus was isolated in 1681 children. Among these, 107 harboured MRSA. Fifty-one children were colonized or infected by CO-MRSA, 20% of whom had no healthcare exposure. Twelve infants <3 months old and five cystic fibrosis patients were colonized. None of the 22 infected patients (59% with acute otitis media and 36% with skin and soft tissue infections (SSTIs)) required hospitalization. Two-thirds of them failed to respond to empirical antibiotic therapy. The 37 characterized CO-MRSA strains were genetically diverse. Most of them had healthcare-associated genotypes. Only six strains were PVL-positive, all of which were ciprofloxacin-susceptible and more common in children with SSTIs (p 0.001). CO-MRSA remains uncommon in our paediatric population. So far, there is no need to modify the empirical treatment of common S. aureus infections. Monitoring of MRSA rates in S. aureus CO infections remains mandatory, and further investigation is warranted to establish the source of colonization in young infants.     

Screening for methicillin-resistant Staphylococcus aureus in clinical swabs using a high-throughput real-time PCR-based method.

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community is a serious problem. Accordingly, a comprehensive plan has been implemented in the County of Vejle, Denmark, to identify colonised and/or infected individuals and to control the spread of MRSA. Since 2005, all patients and healthcare personnel have been screened for MRSA colonisation, involving analysis of 300-400 samples daily. To deal with this number of samples, a PCR-based method customised for high-throughput analysis and a system for fast reporting of MRSA carrier status were developed. Swab samples were incubated overnight in a selective tryptone soya broth and were analysed by PCR the following day. Using this strategy, non-colonised individuals were identified within 24 h, while MRSA-positive samples were analysed further by traditional microbiological methods to determine the resistance pattern. This is a cost-effective approach, as the greatest expense in hospitals involves the isolation of patients of unknown MRSA status. The method was evaluated by testing 2194 clinical samples, with a sensitivity and specificity of 100% and 94%, respectively. The analytical sensitivity was 97%, with 161 of 166 different MRSA strains and isolates generating positive results according to PCR analysis. Using four control strains, the inter-assay variation was revealed to be a maximum of 2.6%, indicating good reproducibility.     

Body site colonization in patients with community-associated methicillin-resistant Staphylococcus aureus and other types of S. aureus skin infections

Efforts to control spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are often based on eradication of colonization. However, the role of nasal and non-nasal colonization in the pathogenesis of these infections remains poorly understood. Patients with acute S. aureus skin and soft tissue infection (SSTI) were prospectively enrolled. Each subject's nasal, axillary, inguinal and rectal areas were swabbed for S. aureus and epidemiological risk factors were surveyed. Among the 117 patients enrolled, there were 99 patients who had an SSTI and for whom data could be analysed. Sixty-five patients had a CA-MRSA SSTI. Among these patients, MRSA colonization in the nares, axilla, inguinal area and rectum was 25, 6, 11 and 13%, respectively, and 37% overall were MRSA colonized. Most (96%) MRSA colonization was detected using nose and inguinal screening alone. Non-nasal colonization was 25% among CA-MRSA patients, but only 6% among patients with CA-methicillin-susceptible S. aureus (MSSA) or healthcare-associated MRSA or MSSA. These findings suggest that colonization patterns in CA-MRSA infection are distinct from those in non-CA-MRSA S. aureus infections. The relatively high prevalence of non-nasal colonization may play a key role in CA-MRSA transmission and acquisition of infection.     

Prevalence of methicillin-resistant Staphylococcus aureus in infected and uninfected diabetic foot ulcers

This study investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in infected and uninfected diabetic foot ulcers of 84 patients with the two types of diabetes. S. aureus was the most common pathogen among the Gram-positive bacteria isolated from ulcers, and almost 50% of S. aureus isolates were MRSA. The prevalence of MRSA was significantly higher in patients with infected foot ulcers. MRSA infection or colonisation was not associated with factors (previous hospitalisation, use of antibiotics, etc.) known to predispose to MRSA colonisation or infection. The high prevalence of MRSA in patients with foot ulcers may reflect the increased prevalence of MRSA in the community.     

Identification of a methicillin-resistant Staphylococcus aureus inhibitory compound isolated from Serratia marcescens

In this study, we identified an antimicrobial compound produced by the Gram-negative bacterium Serratia marcescens. Colonies of S. marcescens inhibited the growth of nine different methicillin-resistant Staphylococcus aureus (MRSA) isolates and several other tested Gram-positive bacterial species, but not Gram-negative bacteria. Genetic analysis revealed the requirement for the swrW gene which codes for a non-ribosomal peptide synthetase that generates the cyclodepsipeptide antibiotic serratamolide, also known as serrawettin W1. This is the first report describing the anti-MRSA properties of serratamolide.     

Impact of psm-mec in the mobile genetic element on the clinical characteristics and outcome of SCCmec-II methicillin-resistant Staphylococcus aureus bacteraemia in Japan

Over-expression of alpha-phenol-soluble modulins (PSMs) results in high virulence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). The psm-mec gene, located in the mobile genetic element SCCmec-II, suppresses PSMαs production. Fifty-two patients with MRSA bacteraemia were enrolled. MRSA isolates were evaluated with regard to the psm-mec gene sequence, bacterial virulence, and the minimum inhibitory concentration (MIC) of vancomycin and teicoplanin. Fifty-one MRSA isolates were classified as SCCmec-II, and 10 had one point mutation in the psm-mec promoter. We compared clinical characteristics and outcomes between mutant MRSA and wild-type MRSA. Production of PSMα3 in mutant MRSA was significantly increased, but biofilm formation was suppressed. Wild-type MRSA caused more catheter-related bloodstream infections (30/41 vs. 3/10, p 0.0028), whereas mutant MRSA formed more deep abscesses (4/10 vs. 3/41, p 0.035). Bacteraemia caused by mutant MRSA was associated with reduced 30-day mortality (1/10 vs. 13/41, p 0.25), although this difference was not significant. The MIC₉₀ of teicoplanin was higher for wild-type MRSA (1.5 mg/L vs. 1 mg/L), but the MIC of vancomycin was not different between the two groups. The 30-day mortality of MRSA with a high MIC of teicoplanin (≥1.5 mg/L) was higher than that of strains with a lower MIC (≤0.75 mg/L) (6/10 vs. 6/33, p 0.017). Mutation of the psm-mec promoter contributes to virulence of SCCmec-II MRSA, and the product of psm-mec may determine the clinical characteristics of bacteraemia caused by SCCmec-II MRSA, but it does not affect mortality.     

Replacement of methicillin-resistant Staphylococcus aureus clones in Hungary over time: a 10-year surveillance study

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Hungary has been increasing and is now close to 20% among invasive isolates of S. aureus . In order to understand the evolution of MRSA in Hungary, two collections of isolates were studied: 22 representatives of a collection of 238 MRSA isolates recovered between 1994 and 1998, and a collection of 299 MRSA isolates recovered between 2001 and 2004. The isolates were first characterised by pulsed-field gel electrophoresis (PFGE) and were distributed into 19 different PFGE patterns. Representatives of each pattern were further characterised by spa typing, multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCC mec ) typing. The Hungarian clone that was predominant in 1994–1998 (PFGE E, ST239-III) had almost disappeared in 2003–2004, being replaced by the Southern German clone (PFGE B, ST228-I) and the New York/Japan epidemic clone (PFGE A, ST5-II), which represented c.  85% of the 2001–2004 isolates. Thus, this study describes, for the first time, the co-dominance and extensive spread of the New York/Japan clone in a European country.