C-2 derivatized 8-sulfonamidoquinolines as antibacterial compounds.

A series of C-2 derivatized 8-sulfonamidoquinolines were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc (50 µM ZnSO4). The vast majority of compounds tested were demonstrated to be significantly more active against S. uberis when in the presence of supplementary zinc (MICs as low as 0.125 µg/mL were observed in the presence of 50 µM ZnSO4). Compounds 5, 34-36, 39, 58, 79, 82, 94 and 95 were shown to display the greatest antibacterial activity against S. aureus (MIC ≤ 8 µg/mL; both in the presence and absence of supplementary zinc), while compounds 56, 58 and 66 were demonstrated to also exhibit activity against E. coli (MIC ≤ 16 µg/mL; under all conditions). Compounds 56, 58 and 66 were subsequently confirmed to be bactericidal against all three mastitis pathogens studied, with MBCs (≥3log10 CFU/mL reduction) of ≤ 32 µg/mL (in both the presence and absence of 50 µM ZnSO4). To validate the sanitizing activity of compounds 56, 58 and 66, a quantitative suspension disinfection (sanitizer) test was performed. Sanitizing activity (>5log10 CFU/mL reduction in 5 min) was observed against both S. uberis and E. coli at compound concentrations as low as 1 mg/mL (compounds 56, 58 and 66), and against S. aureus at 1 mg/mL (compound 58); thereby validating the potential of compounds 56, 58 and 66 to function as topical sanitizers designed explicitly for use in non-human applications.

Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds.

A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, 12 and 13 were demonstrated to have MICs of 0.0625 µg/mL against S. uberis in the presence of 50 µM ZnSO4. Against S. aureus compounds 9g (MIC 4 µg/mL) and 11d (MIC 8 µg/mL) showed the greatest activity, whereas all compounds were found to be inactive against E. coli (MIC > 256 µg/mL); again in the presence of 50 µM ZnSO4. All compounds were demonstrated to be significantly less active in the absence of supplementary zinc. Compound 9g was subsequently confirmed to be bactericidal, with an MBC (≥3log10 cfu/mL reduction) of 0.125 µg/mL against S. uberis in the presence of 50 µM ZnSO4. To validate the sanitising activity of compound 9g in the presence of supplementary zinc, a quantitative suspension disinfection (sanitizer) test was performed. In this preliminary test, sanitizing activity (>5log10 reduction of CFU/mL in 5 min) was observed against S. uberis for compound 9g at concentrations as low as 1 mg/mL, validating the potential of this compound to function as a topical sanitizer against the major environmental mastitis-causing microorganism S. uberis.

The 2016 Garrod Lecture: The role of the healthcare epidemiologist in antimicrobial chemotherapy-a view from the USA.

Antimicrobial chemotherapy now spans 80 years and four generations. The healthcare epidemiologist has an important role to play in this field. Efforts focus in three areas: (i) minimizing the transmission of antimicrobial-resistant bacteria in healthcare settings (infection control); (ii) optimizing use of currently available antibacterial drugs (antibiotic stewardship); and (iii) recognizing and responding to opportunities for new drug development. For each area, the epidemiologist provides data that address four practical questions-'What is the problem?', 'What should be done?', 'Is it being done?' and 'Is it working?'. A team approach is crucial to acting on the epidemiological data. Examples are presented to illustrate different roles of the epidemiologist, and tools and measures that have been developed to address some problems of current importance. Monitoring of quality, integrity and security of data remains a major focus. The epidemiologist will continue to have a key role in antimicrobial chemotherapy.

Comparison of typing results obtained for methicillin-resistant Staphylococcus aureus isolates with the DiversiLab system and pulsed-field gel electrophoresis.

We compared the results of typing methicillin-resistant Staphylococcus aureus (MRSA) isolates using the DiversiLab system (DL) to the results obtained using pulsed-field gel electrophoresis (PFGE). One hundred five MRSA isolates of PFGE types USA100 to USA1100 and the Brazilian clone, from the Centers for Disease Control and Prevention (CDC) and Project ICARE strain collections, were typed using DL. In addition, four unique sets of MRSA isolates from purported MRSA outbreaks that had been previously typed by DL, each consisting of six isolates (where five isolates were classified as indistinguishable by DL and one was an unrelated DL type) were typed by PFGE. DL separated the 105 MRSA isolates of known USA types into 11 clusters and six unique banding patterns. DL grouped most of the USA100, USA200, and USA1100 isolates into unique clusters. Multilocus sequence type 8 isolates (i.e., USA300 and USA500) often clustered together at >95% similarity in DL dendrograms. Nevertheless, USA300 and USA500 DL patterns could be distinguished using the pattern overlay function of the DL software. Among the hospital outbreak clusters, PFGE and DL identified the same "unrelated" organism in three of four sets. However, PFGE showed more pattern diversity than did DL, suggesting that two of the sets were less likely to represent true outbreaks. In summary, DL is useful for screening MRSA isolates to rule out potential outbreaks of MRSA in hospitals, but PFGE provides better discrimination of potential outbreak strains and is more useful for confirming strain relatedness and specific USA types.

Identification of plasmid-mediated AmpC beta-lactamases in Escherichia coli, Klebsiella spp., and proteus species can potentially improve reporting of cephalosporin susceptibility testing results.

The goal of this study was to determine if the interpretations of extended-spectrum and advanced-spectrum cephalosporins (ESCs and ASCs, respectively) for isolates of Enterobacteriaceae would be impacted by the results of aminophenylboronic acid (APBA) testing. Fifty-three isolates of Escherichia coli, 21 Klebsiella species, and 6 Proteus species that were resistant to at least one ESC were tested by disk diffusion with ceftazidime and cefotetan disks with and without APBA. Ceftazidime disks with and without clavulanic acid (CLAV) were also tested to confirm extended-spectrum beta-lactamase (ESBL) carriage. Twenty-nine (36.3%) isolates were only APBA test positive, 27 were only CLAV test positive, 2 were positive with both substrates, and 22 were negative with both substrates. Thirteen (41.9%) of the 31 APBA-test-positive isolates (all E. coli) tested susceptible to cefotaxime, ceftriaxone, or ceftazidime. Since clinical data suggest that AmpC-producing isolates should be reported as resistant to all ESCs, APBA testing can be helpful in identifying such organisms. Screening for AmpC-producing organisms using nonsusceptibility to cefoxitin and amoxicillin-clavulanate was less specific than APBA testing; it identified ESBL as well as AmpC-producing organisms. Only 18 of 31 APBA-positive isolates were positive by PCR for an AmpC beta-lactamase gene. Thus, testing with APBA could improve the accuracy of reporting ESCs, especially for E. coli. However, results of APBA and CLAV testing did not correlate well for isolates containing both AmpC beta-lactamases and ESBLs. Thus, additional data are needed before formal recommendations can be made on changing the reporting of ASC test results.

Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes--proceedings of the HCAP Summit.

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.

High rate of mobilization for blaCTX-Ms.

We constructed a phylogenetic analysis of class A beta-lactamases and found that the blaCTX-Ms have been mobilized to plasmids approximately 10 times more frequently than other class A beta-lactamases. We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer. Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted. That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

Cytomegalovirus seroprevalence and childhood sources of infection: A population-based study among pre-adolescents in the United States.

BACKGROUND: Among pre-adolescents, the importance of different sources of cytomegalovirus (CMV) infection is unclear. OBJECTIVE: To assess the importance of several CMV sources among pre-adolescent children. STUDY DESIGN: We used data from a United States population-based sample conducted from 1988 to 1994: 4-10-year-old participants (n=3386) of the Third National Health and Nutrition Examination Survey. We tested available sera for CMV-specific-IgG and assessed CMV prevalence differences by surrogates for exposure to childhood CMV sources (maternal CMV serostatus, breast-feeding, older sibling CMV serostatus, and child care center attendance). RESULTS: CMV infection was more prevalent (70%) among Mexican American children with foreign-born householders than among children with native-born householders (31% non-Hispanic White, 39% non-Hispanic Black, and 37% Mexican American children). Child's serostatus was associated with their mother's (prevalence difference range (PDR)=33-40%) and older sibling's serostatus (PDR=39-50%). Breast-feeding was associated with CMV in some racial/ethnic and householder groups (PDR=-5.1% to 22.7%). There was little difference in CMV seroprevalence by child care center attendance (PDR=-6.5% to -0.4%). CONCLUSIONS: This study expands understanding of CMV by identifying the importance of householder nativity and demonstrating the importance of family transmission among the general population of pre-adolescents.

Importance of bacterial burden among methicillin-resistant Staphylococcus aureus carriers in a long-term care facility.

OBJECTIVE: To evaluate the prevalence and transmission of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization, as well as risk factors associated with MRSA carriage, among residents of a long-term care facility (LTCF). DESIGN: Prospective, longitudinal cohort study. SETTING: A 100-bed Veterans Administration LTCF. PARTICIPANTS: All current and newly admitted residents of the LTCF during an 8-week study period. METHODS: Nasal swab samples were obtained weekly and cultured on MRSA-selective media, and the cultures were graded for growth on a semiquantitative scale from 0 (no growth) to 6 (heavy growth). Epidemiologic data for the periods before and during the study were collected to assess risk factors for MRSA carriage. RESULTS: Of 83 LTCF residents, 49 (59%) had 1 or more nasal swab cultures that were positive for MRSA; 34 (41%) were consistently culture-negative (designated "noncarriers"). Of the 49 culture-positive residents, 30 (36% of the total of 83 residents) had all cultures positive for MRSA (designated "persistent carriers"), and 19 (23% of the 83 residents) had at least 1 culture, but not all cultures, positive for MRSA (designated "intermittent carriers"). Multivariate analysis showed that participants with at least 1 nasal swab culture positive for MRSA were likely to have had previous hospitalization (odds ratio, 3.9) or wounds (odds ratio, 8.2). Persistent carriers and intermittent carriers did not differ in epidemiologic characteristics but did differ in mean MRSA growth score (3.7 vs 0.7; P<.001). CONCLUSIONS: Epidemiologic characteristics differed between noncarriers and subjects with at least 1 nasal swab culture positive for MRSA. However, in this LTCF population, only the degree of bacterial colonization (as reflected by mean MRSA growth score) distinguished persistent carriers from intermittent carriers. Understanding the burden of colonization may be important when determining future surveillance and control strategies.

Antimicrobial resistance: international control strategies, with a focus on limited-resource settings.

Microorganisms resistant to multiple anti-infective agents have increased worldwide. These organisms threaten both optimal care of patients with infection as well as the viability of current healthcare systems. In addition, antimicrobials are valuable resources that enhance both prevention and treatment of infections. As resistance diminishes this resource, it is a societal goal to minimise resistance and therefore to reduce forces that produce resistance. This review considers strategies for minimising resistance that are needed at several different levels of responsibility, ranging from the patient care provider to international agencies. It then describes responses that might be appropriate according to the resources available for control, focusing on limited-resource settings. Antimicrobial resistance represents an international concern. Response to this problem demands concerted efforts from multiple sectors both in developed and developing countries, as well as the strengthening of multinational/international partnerships and regulations. Both medical and public health agencies should be in the forefront of these efforts.

Antimicrobial resistance prevention initiative--an update: proceedings of an expert panel on resistance.

Antimicrobial resistance is a growing problem that complicates the treatment of important nosocomial and community-acquired infections. It is a worldwide problem that spans the range of human pathogens, including bacteria, fungi, and viruses. This update from the Antimicrobial Resistance Prevention Initiative (ARPI) provides a review of some important trends in antibiotic, antifungal, and antiviral resistance. Areas of focus include multidrug-resistant bacteria in the hospital setting; the growing problem of community-acquired methicillin-resistant Staphylococcus aureus; triazole and polyene resistance in nosocomial infections caused by non-Candida albicans or Aspergillus species, and the utility of in vitro susceptibility testing for these fungal infections; antiviral resistance in alpha- or beta-herpesviruses causing genital herpes or cytomegalovirus infection in immunocompromised hosts; and concerns about a possible pandemic involving avian influenza A and the importance of minimizing emergence of resistant strains of this highly pathogenic virus. The challenges in each area are different, but the general keys to addressing the growing problem of antimicrobial resistance continue to be responsible antimicrobial stewardship and the development of newer antimicrobial agents.

Effect of multiple interventions on community health workers' adherence to clinical guidelines in Siaya district, Kenya.

Evaluation of a community health worker (CHW) programme in Siaya district, Kenya, showed CHWs commonly made errors in managing childhood illness. We assessed the effect of multiple interventions on CHW healthcare practices. A sample of 192 ill-child consultations performed by 114 CHWs in a hospital outpatient department between February and March 2001 were analysed. The mean percentage of assessment, classification and treatment procedures performed correctly for each child was 79.8% (range 13.3-100%). Of the 187 children who required at least one treatment or referral to a health facility, only 38.8% were prescribed all treatments (including referral) recommended by the guidelines. Multivariate analyses found no evidence that the intervention-related factors studied (refresher training, supervision, involvement of community women in the CHW selection process, adequacy of medicine supplies, and use of a guideline flipchart during consultations) were significantly associated with overall or treatment-specific guideline adherence. A multivariate linear regression analysis revealed that several non-intervention-related factors, such as patient characteristics, were significantly associated with overall guideline adherence. Given that our study was cross-sectional and our measurement of exposure to several interventions was based on CHW recall, the estimated effects of the interventions should be interpreted with caution. Despite these limitations, however, our results raise questions about the effectiveness, in the setting of Siaya district, of several interventions commonly used to improve the quality of care given by CHWs.

Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum.

Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting.

Investigation of inducible clindamycin and telithromycin resistance in isolates of beta-hemolytic streptococci.

We evaluated the accuracy of an erythromycin-clindamycin double-disk test (D-zone test) and an erythromycin-telithromycin D-zone test for detection of inducible resistance in isolates of beta-hemolytic streptococci with erythromycin resistance. The results of these tests were compared to results of a broth microdilution (BMD) induction test using combinations of erythromycin and either clindamycin or telithromycin. Of 29 erythromycin-resistant, clindamycin-susceptible isolates, 16 were positive by the erythromycin-clindamycin D-zone test; all of these demonstrated inducible clindamycin resistance by BMD. Twelve isolates were D-zone test-negative, did not demonstrate inducible resistance by BMD, and were positive for a mef determinant. Of 39 erythromycin-resistant, telithromycin-susceptible isolates, 13 were erythromycin-telithromycin D-zone test-positive, 19 questionably positive (unclear blunting of the zone), and 7 were D-zone test-negative. The erythromycin-telithromycin D-zone test result did not correlate with inducible resistance by BMD or the presence of an erm or mef gene. These results demonstrate that the erythromycin-clindamycin D-zone and BMD induction tests accurately detect inducible clindamycin resistance, but the erythromycin-telithromycin D-zone test is not reliable for detecting inducible telithromycin resistance.

Adherence to infectious diseases society of America guidelines for empiric therapy for patients with community-acquired pneumonia in a commercially insured cohort.

BACKGROUND: There is little published research addressing how the 2003 Infectious Diseases Society of America (IDSA) guidelines for empiric therapy of community-acquired pneumonia (CAP) are implemented in clinical practice. OBJECTIVE: This study was designed to describe antibiotic treatment patterns among patients with CAP treated in ambulatory settings in light of the IDSA guidelines. METHODS: Health insurance claims data from a large managed care organization with -30 million enrollees located in geographically diverse regions of the United States were analyzed. Patients > or =18 years of age with CAP who received a prescription for any antibiotic in an ambulatory setting during 2004 were identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes for diagnosis (481-486). Recent antibiotic use was defined as receipt of any antibiotics <90 days before the date of diagnosis. Antibiotics were identified through National Drug Codes and from outpatient medical claims data with the use of J codes. Individuals were classified, per IDSA guidelines, as previously healthy without recent antibiotic use (group 1); previously healthy with recent antibiotic use (group 2); with comorbidities and without recent antibiotic use (group 3); and with comorbidities and recent antibiotic use (group 4). The guideline adherence was calculated using the number of patients receiving recommended treatment divided by the total number of patients in each group. RESULTS: Of 34,342 patients identified, 76.5% had no reported comorbidities. Among group-1 patients, 52.0% received the recommended empiric therapy (macrolide or doxycycline). In group-2 patients, 42.5% received the recommended therapy (respiratory quinolone alone or advanced-generation macrolide plus amoxicillin or amoxicillin-clavulanate). A high rate of compliance with recommended empiric therapy (advanced-generation macrolides or respiratory quinolones) was observed in group-3 patients (81.5%). In group-4 patients, 43.4% received the recommended therapy (respiratory quinolone or advanced-generation macrolide plus ss-lactam). Patients whose therapy was adherent with the guidelines had fewer respiratory-infection-related hospital admissions within 30 days after initiation of antibiotic treatment (overall, relative risk = 0.81 [95% CI, 0.71-0.94]). CONCLUSION: Although these data reflect a period shortly after the 2003 IDSA guidelines were published, they suggest that there is room for improvement with regard to choice of empiric antibiotic therapy among these patients with CAP treated in ambulatory settings.

In vitro activities of Daptomycin, Linezolid, and Quinupristin-Dalfopristin against a challenge panel of Staphylococci and Enterococci, including vancomycin-intermediate staphylococcus aureus and vancomycin-resistant Enterococcus faecium.

We assessed the in vitro activities of daptomycin, linezolid, and quinupristin-dalfopristin (QD) against a contemporary challenge panel of 88 staphylococcal and 90 enterococcal isolates. The staphylococci selected included vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant S. aureus, and coagulasenegative staphylococci. Enterococcal isolates included vancomycin-resistant Enterococcus faecium (VREF) containing either vanA, vanB1, or vanD. The MICs of daptomycin, linezolid, and QD were determined using commercial broth microdilution panels. All three VISA isolates were susceptible to daptomycin, linezolid, and QD. QD was the most active agent against staphylococcal isolates (MIC50 < or = 0.5 microg/ml and MIC90 = 1 microg/ml), including those with decreased susceptibility to vancomycin. QD was also the most active agent against VREF (MIC90 < or = 0.5 microg/ml). No differences were seen for susceptibility of vanA, vanB1, and vanD VREF strains for daptomycin, linezolid, or QD. Daptomycin was the most effective against E. faecalis. On the basis of manufacturer-suggested interpretive criteria, 92% of isolates were susceptible (MIC90 = 4 microg/ml). All isolates tested were susceptible to at least one antimicrobial agent for which interpretive criteria have been defined. Population analysis of three S. aureus isolates for which the daptomycin MICs were 8 microg/ml showed a pattern of homogeneous resistance.

Patterns of health care resource utilization after macrolide treatment failure: results from a large, population-based cohort with acute sinusitis, acute bronchitis, and community-acquired pneumonia.

BACKGROUND: Macrolide antibiotics are used as first-line therapy for the treatment of respiratory tract infections. The recent emergence of macrolide-resistant pathogens is a major concern. OBJECTIVE: This study quantifies the frequency of macrolide treatment failure in respiratory infections and examines its impact on health care use. METHODS: Patients with respiratory infections treated with macrolides in outpatient clinics from January to December 2002 were identified from a health insurance claims database. Macrolide treatment failure was defined as the receipt of a second antibiotic, different from the first, within 4 weeks after the initial macrolide. The end points were numbers of hospitalizations and emergency department and office visits within 1 month after the initial macrolide. We examined diagnostic codes on claim forms for posttreatment hospitalizations and visits to identify those most likely to be related to treatment failure as opposed to other causes. Utilization data were analyzed by Poisson regression to control for confounding variables. RESULTS: The patients were divided into acute sinusitis (n = 111,135), acute bronchitis (n = 157,360), and community-acquired pneumonia (n = 36,212). Of these respective groups, 11,285 (10.2%), 15,498 (9.9%), and 4144 (11.4%) received a second antibiotic within 4 weeks. This subgroup with macrolide treatment failure was older, included more women, and had used more medical care before the index visit compared with patients with treatment success. After adjustment for age, sex, and previous health care use, patients experiencing treatment failure were more likely to be admitted to the hospital or to use emergency department or outpatient care after the index visit. This association was strongest for admissions and visits pertaining to the care of respiratory infections. CONCLUSIONS: By our definition, about 10% of patients with respiratory infections who were treated with macrolide antibiotics experienced treatment failure within 4 weeks. Macrolide treatment failure was associated with increased health care utilization.

Risk factors for methicillin-resistance among patients with Staphylococcus aureus bacteremia at the time of hospital admission.

BACKGROUND: Community-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) seem to be increasing. Characteristics permitting recognition of patients with such strains would aid infection control efforts and choice of empiric therapy pending culture and susceptibility results. METHODS: Retrospective review of medical records for all adults seen in the Emergency Care Center at Grady Memorial Hospital, Atlanta, Georgia, whose blood cultures taken within 24 hours of entry yielded S. aureus. Risk factors for the presence of methicillin resistance in S. aureus isolates recovered from patients with staphylococcal bacteremia were assessed. RESULTS: S. aureus isolates from 118 (40%) of 297 study patients with bacteremia at the time of admission were methicillin-resistant. Multivariate analysis identified hospitalization in the 6 months preceding admission [odds ratio (OR) = 4.4; 95% CI, 2.0-9.8], receipt of antimicrobial agents in the past 3 months (OR = 5.6; 95% CI, 2.6-11.9], presence of indwelling urinary catheter (OR = 7.3; CI, 2.5-20.9), and nursing home residence (OR = 9.9; 95% CI, 3.9-25.6) to be independently associated with the presence of methicillin resistance. All but 4 of the 118 patients with methicillin-resistant strains had at least 1 of these factors and the proportion of resistant isolates progressively increased as more of these features were present. CONCLUSIONS: The presence of these risk factors should be considered when making decisions about isolation and other infection control procedures as well as empiric antimicrobial therapy with vancomycin for patients with suspected staphylococcal infection at the time of hospital admission. Similar studies could guide practices for dealing with such patients in other centers, because the occurrence of MRSA infections at the time of admission may vary widely by geographic area.