Prevalence and clinical implications of Staphylococcus aureus with a vancomycin MIC of 4 microg/ml in Korea

In addition to vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus with a vancomycin MIC of 4 microg/ml has been reported to be the cause of therapeutic failure. This study was designed to determine the prevalence of methicillin-resistant S. aureus (MRSA) with a vancomycin MIC of 4 microg/ml and to clarify the clinical characteristics of infections caused by these isolates. During the 8-week period from April to May, 2001, 27 hospitals participated in a nationwide surveillance program for VISA and vancomycin-resistant S. aureus (VRSA) in Korea. After screening on brain-heart infusion agar containing 4 microg/ml of vancomycin as previously described, 100 isolates with confluent growth were tested. The medical records of the patients involved were reviewed. Even though VISA or VRSA was not detected among 3,756 MRSA isolates, 18 (0.5%) had a vancomycin MIC of 4 microg/ml. The infections in 12 of these patients, excluding 5 that were colonized, were 8 chronic osteomyelitis, 1 surgical site infection, 1 pneumonia, 1 intra-abdominal infection, and 1 catheter-related infection. Although 11 cases were exposed to glycopeptides for a long time (median 56 days), the site of infection became culture-negative in only 1 case. Two patients died of their S. aureus infections. MRSA with a vancomycin MIC of 4 microg/ml was rare. Chronic osteomyelitis was the most common type of infection, and prolonged exposure to glycopeptides was associated with reduced susceptibility to vancomycin.     

Application of orange essential oil as an antistaphylococcal agent in a dressing model

ABSTRACT: BACKGROUND: Staphylococcus aureus is the pathogen most often and prevalently involved in skin and soft tissue infections. In recent decades outbreaks of methicillin-resistant S. aureus (MRSA) have created major problems for skin therapy, and burn and wound care units. Topical antimicrobials are most important component of wound infection therapy. Alternative therapies are being sought for treatment of MRSA and one area of interest is the use of essential oils. With the increasing interest in the use and application of natural products, we screened the potential application of terpeneless cold pressed Valencia orange oil (CPV) for topical therapy against MRSA using an in vitro dressing model and skin keratinocyte cell culture model. METHODS: The inhibitory effect of CPV was determined by disc diffusion vapor assay for MRSA and vancomycin intermediate-resistant S. aureus (VISA) strains. Antistaphylococcal effect of CPV in an in vitro dressing model was tested on S. aureus inoculated tryptic soya agar plate. Bactericidal effect of CPV on MRSA and VISA infected keratinocyte cells was examined by enumeration of extra- and intra-cellular bacterial cells at different treatment time points. Cytotoxic effects on human skin cells was tested by adding CPV to the keratinocyte (HEK001) cells grown in serum free KSFM media, and observed by phase-contrast microscope. RESULTS: CPV vapour effectively inhibited the MRSA and VISA strains in both disc diffusion vapour assay and in vitro dressing model. Compared to untreated control addition of 0.1% CPV to MRSA infected keratinocyte decreased the viable MRSA cells by 2 log CFU/mL in 1 h and in VISA strain 3 log10 CFU/mL reduction was observed in 1 h. After 3 h viable S. aureus cells were not detected in the 0.2% CPV treatment. Bactericidal concentration of CPV did not show any cytotoxic effect on the human skin keratinocyte cells in vitro. CONCLUSIONS: At lower concentration addition of CPV to keratinocytes infected with MRSA and VISA rapidly killed the bacterial cells without causing any toxic effect to the keratinocytes. Therefore, the results of this study warrant further in vivo study to evaluate the potential of CPV as a topical antistaphylococcal agent.     

The VISA/GISA problem: therapeutic implications

The emergence of vancomycin intermediate resistant Staphylococcus aureus (VISA) isolates in Japan, USA, France, Hong Kong and Korea among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, is of great concern. Vancomycin has been the drug of choice for the treatment of multiresistant MRSA infections in the last three decades, but the management of invasive MRSA infections will become a serious problem if VISA strains become widespread. VISA isolates reported to date have a vancomycin MIC of 8 mg/L, and were isolated from patients with underlying diseases whose long-term vancomycin treatment apparently failed. Since many VISA isolates also have been resistant to teicoplanin, the term glycopeptide-intermediate S. aureus (GISA) is more appropriate. The frequency of GISA isolates appears to be extremely low; to date, only 10 GISA infections have been reported worldwide. However, heterogeneous resistance to glycopeptides (h-GISA) have been reported in Japan, Europe and Thailand. These h-GISA strains showed vancomycin MICs ranging from 1 to 4 mg/L, but had subpopulations that could grow on agar plates containing 4–8 mg/L, which may represent the first step in the development of GISA strains. Although GISA isolates have shown resistance to many antimicrobials, all GISA isolates remain susceptible to co-trimoxazole and some of them to other common antimicrobials. Currently, there are no recommended therapy guidelines for GISA infections, although in recent studies, several new drugs have shown promising activity against GISA strains. In addition, synergy between glycopeptides and β-lactams against GISA strains was observed in some in vivo and in vitro studies. Specific MRSA/GISA control programs, rational antibiotic policies, including the reduction of glycopeptide use, and rapid laboratory detection of GISA and h-GISA strains are the key measures in preventing the spread of these strains.     

Detection of vancomycin resistant Staphylococcus aureus: a comparative study of three different phenotypic screening methods

The objective of this study was to investigate screening methodologies, to detect Staphylococcus aureus strains with decreased susceptibility to vancomycin. Three methods were used to screen 160 Staphylococcus aureus clinical isolates along with ATCC quality control strains. Subsequently, MIC of all these 160 strains were determined by NCCLS methodology. The MIC of all the 160 clinical isolates was < or = 4 microg/mL and were classified as vancomycin susceptible by NCCLS criteria but 23 strains were positive by Hiramatshu method, two grew on MHA (5 microg/mL vancomycin) while CDC method correctly identified no vancomycin intermediate S.aureus (VISA) or vancomycin resistant S.aureus (VRSA) strains with reference to there MIC. CDC method was found to be the most appropriate screening methodology for detection of VISA or VRSA for diagnostic laboratories.     

Detection of intermediately vancomycin-susceptible and heterogeneous Staphylococcus aureus isolates: comparison of Etest and Agar screening methods

Detection of Staphylococcus aureus isolates with intermediate vancomycin susceptibility (VISA) and heteroresistance (hVISA) remains problematic. The population analysis profile/area under the curve (PAP/AUC) is the gold standard but is cumbersome. We compared the performance of two Etest screening methods (macromethod [MAC] and glycopeptide resistance detection [GRD]) plus brain heart infusion (BHI) agars supplemented with 3 (BHI-V3) or 4 (BHI-V4) mg/liter vancomycin in detecting hVISA and/or VISA phenotypes. Etest hVISA screenings were done in parallel for 485 saved methicillin-resistant S. aureus (MRSA) blood isolates according to the manufacturer's instructions. The PAP/AUC was measured for all isolates according to the modified method. PAP/AUC test isolate/Mu3 ratios of <0.9, 0.9 to 1.3, and >1.3 were considered positive for susceptible MRSA (S-MRSA), hVISA, and VISA, respectively. PAP/AUC revealed seven VISA and 33 hVISA phenotypes. MAC screening was positive for 30 (75.0%) hVISA/VISA and 49 (11.0%) S-MRSA isolates. GRD screening was positive for 28 (70.0%) hVISA/VISA and 63 (14.2%) S-MRSA isolates. Growth on BHI-V3 was noted in all hVISA/VISA and 24 (5.4%) S-MRSA isolates. Growth on BHI-V4 was noted in all VISA and four (12.1%) hVISA isolates. None of the S-MRSA isolates grew on BHI-V4 agar. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were 75.0%, 89.0%, 38.0%, and 97.5% for MAC; 70.0%, 85.8%, 30.8%, and 97.0% for GRD; 100%, 94.6%, 62.5%, and 100% for BHI-V3; and 100, 99.2%, 63.6%, and 100% for BHI-V4 (for detecting VISA). These findings suggest that both Etest screening methods have excellent NPV, but positive results require confirmation. BHI-V3 and BHI-V4 agars provide more precise identification of hVISA and VISA, respectively; they may be reasonable alternatives to PAP/AUC.     

Real-time multiplex PCR for direct detection of methicillin-resistant Staphylococcus aureus (MRSA) in clinical samples enriched by broth culture

A real-time multiplex PCR using the orfX and staphylococcal cassette chromosome (SCC) mec of Staphylococcus aureus was developed. The aim was to achieve a rapid and sensitive high-throughput method for direct detection of heterogeneous methicillin-resistant S. aureus (MRSA) in clinical samples, present in a low-endemic population, such as in Sweden. Consecutive broth enriched pooled clinical screening samples (nares, throat and/or perineum/groin) (n = 541 pools), broth enriched clinical samples showing growth of methicillin-sensitive S. aureus (MSSA) (n = 95 pools), clinical MRSA isolates (n = 173), MRSA reference strains (n = 43) and various coagulase-negative staphylococcal isolates (n = 33) were analyzed. The multiplex PCR detected all heterogeneous MRSA strains (n = 173) obtained in our area as well as all pooled consecutive broth enriched clinical samples with MRSA, i. e. 36 of 541 pools. None of the CoNS were positive. However, 18 out of 541 pools (3.3%) were positive in the multiplex PCR but no growth of MRSA could be detected by subculture and were regarded as false positive. Furthermore, the assay is rapid and reliable negative results can be delivered to the clinician within 18 h that will facilitate the infection control management of patients and hospital staff.     

Clonal spread of Staphylococcus aureus heterogeneously resistant to vancomycin in a university hospital in Korea

Since vancomycin-intermediate Staphylococcus aureus (VISA) was first reported in Japan in 1997, there has been great concern that heterogeneous vancomycin-intermediate S. aureus (hetero-VISA) is the putative precursor of VISA. To investigate the prevalence, clinical significance, and molecular epidemiology of S. aureus with reduced susceptibility to vancomycin, all consecutive isolates of S. aureus isolated from clinical specimens from December 1998 to August 1999 at Asan Medical Center were screened for VISA and hetero-VISA by using brain heart infusion agar containing 4 microg of vancomycin/ml. Screen-positive isolates were confirmed by susceptibility testing and population analysis of subpopulations with reduced susceptibility to vancomycin. The isolates confirmed as hetero-VISA were typed by pulsed-field gel electrophoresis (PFGE). Medical records were reviewed to evaluate the clinical significance and risk factors for the acquisition of hetero-VISA. Of the 4,483 isolates that were tested, 53 were screen positive; no VISA was detected, but 24 isolates (0.54%) from 22 patients were hetero-VISA. All but two strains appeared to be clones of the Korean VISA strain, AMC11094, in the PFGE analysis. A total of 18 patients were in intensive care units, and 16 underwent major surgeries during the same admission. Only 10 of the 22 patients had previous methicillin-resistant S. aureus infections and 11 had previous vancomycin or teicoplanin therapy. Only 7 of the 22 patients from whom hetero-VISA strains were isolated were infected, and the remaining 15 patients were colonized. All seven infected patients were successfully treated with vancomycin. These results suggest that hetero-VISA can be treated with vancomycin, but the spread of hetero-VISA clonal to VISA is of concern, since many believe that VISA can arise from hetero-VISA, although this phenomenon was not observed in this study.     

Effectiveness of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers at hospital admission to prevent hospital-acquired MRSA infections

Screening of potential MRSA-positive patients at hospital admission is recommended in German and international guidelines. This policy has been shown to be effective in reducing the frequency of nosocomial MRSA transmissions in the event of an outbreak, but the influence of screening on reducing hospital-acquired MRSA infections in a hospital setting where MRSA is endemic is not yet well-documented. This study describes the effect of hospital-wide screening of defined risk groups in a 700-bed acute care hospital during a period of 19 months. In a cohort study with a 19-month control period, the frequencies of hospital-acquired MRSA infections were compared with and without screening. In the control period, there were 119 MRSA-positive patients, of whom 48 had a hospital-acquired MRSA infection. On the basis of this frequency, a predicted total of 73.2 hospital-acquired MRSA infections was calculated for the screening period, but only 52% of the expected number (38 hospital-acquired MRSA infections) were observed, i.e., 48% of the predicted number of hospital-acquired MRSA infections were prevented by the screening programme. The screening programme was performed with minimal effort and can therefore be recommended as an effective measure to help prevent hospital-acquired MRSA infections.     

Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus

Of 38 vancomycin-intermediate Staphylococcus aureus (VISA) clinical strains, 27 (71%) possessed a mutation(s) in rpoB encoding the β-subunit of RNA polymerase. Furthermore, 95.6% of the rifampin-resistant mutants obtained from 9 methicillin-resistant S. aureus (MRSA) clinical isolates showed decreased vancomycin susceptibilities. These data indicate the involvement of an rpoB mutation in VISA phenotype expression.     

Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan.

In-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin, linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria were determined using the broth microdilution method for ten blood isolates each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was tested in a time-kill synergism assay of daptomycin combined with oxacillin, imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro bactericidal activity against all the isolates tested, with no tolerance or synergism effects when combined with other agents, except with rifampicin against VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did teicoplanin. Linezolid had the poorest bactericidal activity against the isolates tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90% of the vancomycin-resistant E. faecium isolates.     

Predicting methicillin resistance among community-onset Staphylococcus aureus bacteremia patients with prior healthcare-associated exposure

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7?% and 42.0?% of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3?% to 23.3?%, comparable to that of CA-SAB patients (13.8?%). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection.     

Prevalence and accessory gene regulator (agr) analysis of vancomycin-intermediate Staphylococcus aureus among methicillin-resistant isolates in Taiwan—SMART program, 2003

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in nosocomial staphylococcal infections in Taiwan has exceeded 50% since 2000. However, little relevant data has been available concerning vancomycin-intermediate S. aureus (VISA) and heteroresistant VISA (hVISA). We collected 1,000 MRSA isolates from ten medical center hospitals in Taiwan during 2003. All were initially screened for reduced susceptibility to vancomycin on brain heart infusion (BHI) agar containing 5 mg/L vancomycin. Among 34 MRSA isolates that grew on the screening plates, two VISA isolates (0.2%) and seven hVISA isolates (0.7%) were evident. Vancomycin-resistant S. aureus was not detected. The accessory gene regulator (agr) typing of all 1,000 MRSA strains were typed by multiplex polymerase chain reaction (PCR); 919 strains (91.9%) including the VISA and hVISA isolates belonged to agr group I, 78 strains (7.8%) were agr group II, two strains (0.2%) were agr group III, and one isolate (0.1%) was agr group IV. There was no relationship between sample sites and agr typing. In 2003, the incidence of hVISA and VISA in Taiwan was low. Continued surveillance is recommended, given the implementation of new Clinical and Laboratory Standards Institute (CLSI) criteria for S. aureus and the increasing clinical use of glycopeptides.     

Colonization with vancomycin-intermediate Staphylococcus aureus strains containing the vanA resistance gene in a tertiary-care center in north India

A nasal carriage survey for methicillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit detected four strains of MRSA with reduced susceptibility to vancomycin. The vanA gene was found in two of these vancomycin-intermediate Staphylococcus aureus (VISA) strains. The absence of selective vancomycin pressure might have resulted in reduced expression of the resistant gene.     

Culture-based detection of methicillin-resistant Staphylococcus aureus by a network of European laboratories: an external quality assessment study

Twenty-three hospital laboratories from Europe and Israel participated in an external quality assessment (EQA) of the culture-based detection of methicillin-resistant Staphylococcus aureus (MRSA). Participants also reported the MRSA prevalence in clinical cultures and patient screening specimens, as well as the MRSA screening practices employed at their hospitals. An EQA panel of 18 samples consisting of two MRSA harbouring SCCmec IV and I, and one strain each of methicillin-resistant coagulase-negative S. epidermidis, methicillin-sensitive S. aureus and Escherichia coli as pure strains or in mixtures at 10(7)-1 cfu absolute loads was analysed by the 23 participants. Seventeen (74%) participants identified 17 or more samples correctly. Of these, 15 (88%) utilised a chromogenic medium alone (ChromID, bioMérieux; BBL CHROMagar, BD Diagnostics; MRSA Select, Bio-Rad Laboratories) or combined with a conventional medium and up to three confirmatory tests. Proportions of MRSA among S. aureus isolated from clinical cultures varied widely, even among hospitals within countries, ranging from 11-20% to 61-70%. MRSA carriage rates were less variable (0-20%) between countries. Almost all participants (n=22, 96%) screened patients for MRSA carriage during 2009-2010, of which 15 (68%) screened intensive care unit (ICU) patients alone or combined with other targeted high-risk groups, and 10 (45%) combined nasal screening with another body site.     

In vitro activities of quinupristin/dalfopristin and eight other antimicrobial agents against 360 clinical isolates from Korea

The emergence of multi-drug resistant gram-positive cocci such as methicillin-resistant (MR) staphylococci, vancomycin-resistant (VR) enterococci, and vancomycin-intermediate resistant S. aureus (VISA) has given new urgency to the development of new antimicrobial agents. One of these is quinupristin/dalfopristin (Q/D). We decided to determine the susceptibility of gram-positive cocci isolated at two university hospitals in Seoul to Q/D and compare the results with eight other antimicrobial agents. We investigated 120 isolates of S. aureus including 49 MRSAs and one VISA, 120 isolates of coagulase negative staphylococci (CNS), 64 E. faecalis and 56 E. faecium, including seven strains of VR E. faecium. Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) for several antimicrobials, including vancomycin and Q/D, were determined by broth microdilution. All S. aureus including VISA were susceptible to Q/D. Q/D MIC90 for both methicillin-susceptible S. aureus (MSSA) and MRSA was 0.25 g/mL. 49 (87.5%) of 56 E. faecium including six of seven VR E. faecium were susceptible to Q/D. E. faecalis were not susceptible to Q/D (only 1.5% susceptible), but were inhibited by ampicillin (94% susceptible) or vancomycin (95%). CNS was susceptible to Q/D (96% susceptible) and vancomycin (100% susceptible). One of 38 staphylococci and two of 17 E. faecium were tolerant to Q/D. In conclusion, Q/D showed excellent activity against all species of gram-positive cocci including MRSA, VISA, and VR E. faecium except E. faecalis, and may provide a valuable option for the treatment of infections caused by these emerging nosocomial pathogens of gram-positive cocci.     

Methicillin-resistant Staphylococcus aureus: risk assessment and infection control policies.

The endemic state of methicillin-resistant Staphylococcus aureus (MRSA) occurs through a constant influx of MRSA into the healthcare setting from newly admitted MRSA-positive patients, followed by cross-transmission among inpatients and an efflux of MRSA from the hospital with discharged patients. To date, most MRSA prevention strategies have targeted cross-transmission among hospitalised patients. Intensive concerted interventions that include isolation can reduce the MRSA incidence substantially. However, debate continues about the cost-effectiveness of infection control policies, including screening protocols, to control the influx of MRSA into hospitals. The rationale and cost-effectiveness of wide screening, as compared to targeted screening, should be further studied using appropriate statistical approaches and economic modelling.     

Use of surveillance cultures and enteral vancomycin to control methicillin-resistant Staphylococcus aureus in a paediatric intensive care unit

This study assessed the effects of throat and gut surveillance, combined with enteral vancomycin, on gut overgrowth, transmission of methicillin-resistant Staphylococcus aureus (MRSA), infections and mortality in patients admitted to a paediatric intensive care unit (PICU). A 4-year prospective observational study was undertaken with 1241 children who required ventilation for >or=4 days. Patients identified as MRSA carriers following surveillance cultures of throat and rectum received enteral vancomycin. Twenty-nine (2.4%) children carried MRSA, 19 on admission and nine during treatment in the PICU; one patient was not able to be evaluated. Overgrowth was present in 22 (75%) of the carriers. Ten (0.8%) children developed 21 MRSA infections (15 exogenous infections in eight children at a median of 8 days (IQR 3-10.5); five primary endogenous infections at a median of 3 days (IQR 1-25) in three children when they were in overgrowth status; one child developed both types of infection). Enteral vancomycin reduced gut overgrowth significantly, completely preventing secondary endogenous infections. Transmission occurred on nine occasions over a period of 4 years. Four patients died, two (5.9%) with MRSA infection, giving a mortality (11.8%) similar to the study population (9.8%). No emergence of vancomycin-resistant enterococci or S. aureus with intermediate susceptibility to vancomycin was detected. A policy based on throat and gut surveillance, combined with enteral vancomycin, for critically-ill children who were MRSA carriers was found to be effective and safe, and challenges the recommended guidelines of nasal swabbing followed by topical mupirocin.     

Using a 48-hour delay from admission to the first positive culture without any other consideration: an accurate method to differentiate acquired and imported methicillin-resistant Staphylococcus aureus?

To differentiate imported and acquired strains of methicillin-resistant Staphylococcus aureus (MRSA), a 48-hour delay from hospital admission to the first MRSA-positive culture is usually considered. To assess if taking into account this delay without any other consideration is an accurate method, we defined 3 situations for whom we considered the MRSA acquisition status as questionable. The other situations were defined as either acquired MRSA or imported MRSA. We determined the acquisition status of MRSA (acquired, imported, or questionable) isolated during a 20-month period by considering or not considering screening samples performed on admission. The ratio "imported MRSA/acquired MRSA" (I/A) was calculated according to (1) the consideration of MRSA with questionable status as imported or acquired, and (2) the consideration of screening samples or not in the calculation of the ratio. The acquisition status in our hospital was questionable in 3.6% of patients when all samples were considered and in 12,0% when only clinical samples were taken into account (p = 0,01). The ratio I/A was 4-fold higher by considering both clinical and screening cultures and questionable status as imported than by considering only clinical samples and questionable status as acquired. Using a 48-hour delay without any other consideration is probably an accurate method to differentiate acquired and imported MRSA when a selective screening programme at admission in operational. Conversely, this definition seems to be more hazardous in the absence of screening.     

Analysis of an outbreak of non-phage-typeable methicillin-resistant Staphylococcus aureus by using a randomly amplified polymorphic DNA assay.

A cluster of methicillin-resistant Staphylococcus aureus (MRSA) infections among patients on an intensive care unit (ICU) was detected by routine infection control surveillance. In the period from 5 January to 22 June 1995, 10 patients on the ICU and a further 6 patients (5 on one ward that had received colonized patients transferred from the ICU) were affected by MRSA strains with the same antibiotic susceptibility patterns. Seven (44%) of these 16 colonized patients developed MRSA bacteremia. MRSA isolates with the same characteristics were also found on the hands of one member of the ICU staff. The isolates were untypeable by phage typing, but 15 of 17 outbreak strains analyzed genetically had identical randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) profiles. A single strain of MRSA that was nontypeable by phage typing and that was isolated on the ICU on 1 January and six nontypeable and epidemiologically unrelated MRSA isolates all had RAPD profiles distinct from that of the outbreak strain. Implementation of strict infection control measures stopped the further spread of MRSA on the ICU, the affected general ward, and seven other wards that received MRSA carriers from the ICU. Although nontypeable by phage typing and not previously recognized as an epidemic strain, this strain of MRSA was readily transmissible and highly virulent. RAPD typing was found to be a simple, rapid, and effective method for the epidemiological investigation of this outbreak, and performance of typing by this method was simpler and less time-consuming than that of typing by PFGE. RAPD typing may have more general application for the study of S. aureus infections in hospitals.