Mark D. King

Emergence of Community-Acquired Methicillin-Resistant Staphylococcus aureus USA 300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections

Context In community outbreaks of methicillin-resistant Staphylococcus aureus (MRSA), 2 clones predominate in the United States: USA 300 and USA 400. Little is known about these infections in the nonoutbreak setting. Contribution This study evaluated nonoutbreak community-acquired S. aureus skin and soft-tissue infections in patients in a large urban setting. Almost three quarters of the soft-tissue infections were caused by MRSA, and these were predominantly the USA 300 type. No MRSA USA 300 isolate was resistant to trimethoprimsulfamethoxazole or vancomycin, while most were resistant to erythromycin in addition to -lactams. Implications Antibiotic choice for serious nonoutbreak community-acquired skin and soft-tissue infection should consider high rates of MRSA in some communities. The Editors Methicillin-resistant Staphylococcus aureus (MRSA) infections have usually been associated with exposure to health care settings, but they have recently been recognized in persons without traditional risk factors. These infections have been called community-acquired or community-associated MRSA (1). Most cases have been associated with skin and soft-tissue infection and have been reported among selected populations, including correctional facility inmates, homosexual men, and sports teams (2-5). Molecular typing studies in the United States and Australia have demonstrated that most community-acquired MRSA infections are caused by one of several clones or pulsed-field types (6, 7). In the United States, 2 clones, designated as USA 300 and USA 400 by the Centers for Disease Control and Prevention (CDC), have been identified as the primary types that cause community-acquired MRSA infections (6). The outbreaks of MRSA skin and soft-tissue infections observed in correctional facilities and among athletes have been associated with the USA 300 pulsed-field type, while outbreaks associated with severe and fatal disease in children, as well as skin and soft-tissue infections in Native American populations, have been associated with the USA 400 pulsed-field type (6). The community-acquired MRSA clones have frequently been associated with the PantonValentine leukocidin virulence factor and the presence of staphylococcal chromosome cassette mec (SCCmec) type IV allele (1, 6-9). In contrast, hospital-acquired or health careassociated MRSA strains usually lack genes for PantonValentine leukocidin and are associated with other SCCmec alleles (for example, SCCmec type II) (1, 6, 7). In addition to PantonValentine leukocidin and SCCmec type IV, the community-acquired MRSA USA 300 and USA 400 genotypes have usually demonstrated resistance to -lactams and erythromycin while retaining susceptibility to clindamycin, trimethoprimsulfamethoxazole, and fluoroquinolones, whereas health careassociated genotypes are often multidrug-resistant (1, 6). Although increasingly reported as a cause of outbreaks of skin and soft-tissue infection, the proportion of S. aureus skin and soft-tissue infections caused by community-acquired MRSA in nonoutbreak settings remains poorly defined. We sought to determine the proportion of infections caused by community-acquired MRSA, the clinical characteristics associated with community-acquired MRSA, and the molecular epidemiology of community-acquired MRSA among persons with community-onset S. aureus skin and soft-tissue infection who were receiving care at a large hospital and its affiliated clinics in urban Atlanta, Georgia. Methods Laboratory Surveillance for Community-Onset S. aureus Skin and Soft-Tissue Infection We conducted active, prospective laboratory surveillance from 1 August 2003 to 15 November 2003 to identify S. aureus isolates of patients with skin and soft-tissue infections at the Grady Health System. The Grady Health System includes Grady Memorial Hospital, a 1000-bed public inner-city hospital, and its affiliated outpatient clinics. We limited surveillance to S. aureus isolates that were obtained from patients with a community-onset skin and soft-tissue infection (isolates designated either as an exudate or a body fluid culture). We defined community-onset S. aureus by positive test results from cultures that were obtained within 72 hours of admission or at an outpatient visit. An investigator classified community-onset S. aureus before we performed molecular typing studies or before we reviewed antimicrobial susceptibility results other than methicillin susceptibility. We identified S. aureus and tested antimicrobial susceptibility for all isolates in the Grady Memorial Hospital Clinical Microbiology Laboratory in accordance with the National Committee for Clinical Laboratory Standards (10). Study Sample and Data Collection The Emory University Institutional Review Board and the Grady Research Oversight Committee approved the study. Grady Memorial Hospital provides medical care for a primarily medically indigent inner-city population, approximately 80% of whom are African American, residing within inner-city Atlanta (Fulton County and DeKalb County). The hospital serves as a teaching hospital for both Emory University School of Medicine and Morehouse School of Medicine. The referral pattern for the hospital and its affiliated clinics is primarily patient self-referral on the basis of place of residence (that is, residence within DeKalb or Fulton Counties) or indigent status, with some patients referred for tertiary academic medical care. We retrospectively reviewed computerized medical and laboratory records to document patient demographic characteristics, HIV status, presence of end-stage renal disease, hospitalization within the previous 12 months, and any history of MRSA infection or colonization. The reviewer completed the abstraction process blinded to the molecular typing results of MRSA isolates. We documented the need for hospitalization for managing the S. aureus skin and soft-tissue infection. We obtained S. aureus antimicrobial susceptibility profiles from the hospitals microbiology laboratory, and we categorized infections as due to either methicillin-susceptible S. aureus (MSSA) or MRSA. We reviewed computerized pharmacy records to document the antimicrobial agent therapy that was used to treat the patients skin and soft-tissue infection. We considered antimicrobial agent therapy to be adequate if the prescribed antimicrobial agent had in vitro activity against the isolated S. aureus strain. Molecular Typing and Genetic Analyses We performed pulsed-field gel electrophoresis (PFGE) using SmaI as a restriction endonuclease on all available MRSA isolates, as described by Bannerman and colleagues (11). We digitized gels and saved them as an image for analysis with BioNumerics software (Applied Maths, Sint-Martens-Latem, Belgium). We performed cluster analysis by using the unweighted pair-group method based on Dice coefficients. We defined pulsed-field type clusters by using a similarity coefficient of at least 80% and the criteria of Tenover and colleagues (12). By using the nomenclature outlined by McDougal and colleagues (6), we categorized MRSA isolates into 1 of 8 lineages: USA 100 through USA 800. For some isolates, we determined SCCmec type by using polymerase chain reaction (PCR)typing of the mec gene complex as described by Okuma and colleagues (7). Similarly, we assessed the presence of PantonValentine leukocidin genes in selected MRSA isolates by using PCR as previously described by Lina and colleagues (13). Classification of Community-Onset S. aureus Skin and Soft-Tissue Infections We classified community-onset S. aureus skin and soft-tissue infections into 3 groups on the basis of either molecular typing results (pulsed-field type) of MRSA isolates or antimicrobial susceptibility pattern in cases in which the MRSA isolate was not available for PFGE. The 3 groups were 1) the community-acquired MRSA USA 300/USA 400 group, 2) the other MRSA group, and 3) the MSSA group. The community-acquired MRSA USA 300/USA 400 group was defined by MRSA skin and soft-tissue infections caused by a MRSA isolate that either demonstrated a USA 300 or USA 400 pulsed-field type (6) or had an antimicrobial susceptibility profile demonstrating resistance only to -lactams and erythromycin while retaining susceptibility to clindamycin, levofloxacin, trimethoprimsulfamethoxazole, and vancomycin. The other MRSA group was defined by MRSA skin and soft-tissue infections caused by a MRSA isolate that either demonstrated a pulsed-field type other than USA 300 or USA 400 (for example, USA 100, USA 500, or USA 800 [which have all been described as health careassociated pulsed-field types]) or had an antimicrobial susceptibility profile demonstrating resistance to -lactams, erythromycin, and at least 1 additional antibiotic. We defined the MSSA group by skin and soft-tissue infections caused by MSSA. Statistical Analysis We performed data management and statistical analyses by using Microsoft Excel 2000 software (Microsoft Corp., Redmond, Washington) and SAS software, version 8.2 (SAS Institute, Cary, North Carolina). We assessed risk factors for community-acquired MRSA skin and soft-tissue infection in 2 separate analyses. Our first analysis compared the community-acquired MRSA USA 300/USA 400 group with the MSSA group, and our second analysis compared the community-acquired MRSA USA 300/USA 400 group with the other MRSA group. In addition, we repeated each analysis using data that were limited to those skin and soft-tissue infections in which a MRSA isolate was available for PFGE to account for any potential misclassification bias introduced when skin and soft-tissue infections were classified according to antimicrobial susceptibility profile. We initially identified potential risk factors for community-acquired MRSA skin and soft-tissue infection by univariate analysis. We calculated prevalence ratios and the corresponding 95% CIs. Multivariable log-binomial regression models included variables that were

Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Genotype as a Major Cause of Health Care—Associated Blood Stream Infections

BACKGROUND Whether community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream infections (BSIs) and health care-associated infections has been poorly defined. METHODS Consecutive MRSA isolates recovered from patients with BSIs were prospectively collected at an urban public hospital. Molecular typing studies were performed. Prevalence and risk factors for the MRSA USA300 genotype were assessed. RESULTS One hundred thirty-two cases of MRSA BSI were documented over 7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were available for genotyping. Characteristics of the 116 evaluable cases included: a mean age 47 years; 62% were male, 82% were African American, and 22% were HIV seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%), there was contact with a health care facility within the year prior to infection, and a nosocomial infection (defined as positive blood culture results obtained >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39 (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42 (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health care-associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis, isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67; 95% CI, 1.10-12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08-16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01-0.82) and those who were treated with antimicrobials in the prior year were less likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02-0.49). CONCLUSIONS MRSA USA300 genotype, the predominant cause of community-associated MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause of health care-associated and nosocomial BSI. MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.

Risk Factors for Colonization with Methicillin-Resistant Staphylococcus aureus (MRSA) in Patients Admitted to an Urban Hospital: Emergence of Community-Associated MRSA Nasal Carriage

BACKGROUND Surveillance cultures performed at hospital admission have been recommended to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) but require substantial resources. We determined the prevalence of and risk factors for MRSA colonization at the time of hospital admission among patients cared for at a public urban hospital. METHODS Anterior nares cultures were obtained within 48 h after admission during a 1-month period. A case-control study and molecular typing studies were performed. RESULTS A total of 53 (7.3%) of 726 patients had a nares culture positive for MRSA, and 119 (16.4%) had a nares culture that was positive for methicillin-susceptible S. aureus. In multivariate analysis, risk factors for MRSA colonization included antibiotic use within 3 months before admission (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.0), hospitalization during the past 12 months (OR, 4.0; 95% CI, 2.0-8.2), diagnosis of skin or soft-tissue infection at admission (OR, 3.4; 95% CI, 1.5-7.9), and HIV infection. A total of 47 (89%) of 53 case patients colonized with MRSA had at least 1 of these independent risk factors, in contrast to 343 (51%) of 673 control patients (OR, 7.5; 95% CI, 3.2 -17.9). Molecular typing demonstrated that 16 (30%) of 53 MRSA nares isolates (2.2% of the 726 isolates) belonged to the USA300 community-associated MRSA (CA-MRSA) genotype. CONCLUSION The prevalence of MRSA colonization at the time of patient admission was high (>7%). Limiting surveillance cultures to patients with >or=1 of the identified risk factors may allow for targeted screening. The emergence of CA-MRSA colonization represents a new, unrecognized reservoir of MRSA within hospitals, potentially increasing the risk for horizontal transmission.

Human Papillomavirus–Associated Oral Warts among Human Immunodeficiency Virus–Seropositive Patients in the Era of Highly Active Antiretroviral Therapy: An Emerging Infection

Oral warts are a manifestation of human papillomavirus infection that have been noted infrequently in persons with human immunodeficiency virus (HIV). A nested case-control study was conducted to assess rates of and risk factors for oral warts among a cohort of HIV-seropositive patients. From 1997 through 1999, 56 patients with oral warts were identified among 2194 HIV-positive patients attending an urban oral health center (prevalence, 2.6%). Incident cases of oral warts were significantly more likely to have been diagnosed in 1999 than they were in 1997-1998 (P=.001). Multivariate analysis indicated that the risk of oral warts was associated with a >/=1-log(10) decrease in HIV RNA level in the 6 months before diagnosis of oral warts (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.08-5.11) and with serologic evidence of chronic or previous infection with hepatitis B virus (OR, 2.66; 95% CI, 1.31-5.41). The incidence of oral warts in HIV-seropositive patients appears to be increasing in the era of highly active antiretroviral therapy. Oral warts were associated with reductions in virus load, which suggests that this may in part be related to immune reconstitution.

Impact of an antimicrobial utilization program on antimicrobial use at a large teaching hospital: a randomized controlled trial.

BACKGROUND Multidisciplinary antimicrobial utilization teams (AUTs) have been proposed as a mechanism for improving antimicrobial use, but data on their efficacy remain limited. OBJECTIVE To determine the impact of an AUT on antimicrobial use at a teaching hospital. DESIGN Randomized controlled intervention trial. SETTING A 953-bed, public, university-affiliated, urban teaching hospital. PATIENTS Patients who were given selected antimicrobial agents (piperacillin-tazobactam, levofloxacin, or vancomycin) by internal medicine ward teams. INTERVENTION Twelve internal medicine teams were randomly assigned monthly: 6 teams to an intervention group (academic detailing by the AUT) and 6 teams to a control group that was given indication-based guidelines for prescription of broad-spectrum antimicrobials (standard of care), during a 10-month study period. MEASUREMENTS Proportion of appropriate empirical, definitive (therapeutic), and end (overall) antimicrobial usage. RESULTS A total of 784 new prescriptions of piperacillin-tazobactam, levofloxacin, and vancomycin were reviewed. The proportion of antimicrobial prescriptions written by the intervention teams that was considered to be appropriate was significantly higher than the proportion of antimicrobial prescriptions written by the control teams that was considered to be appropriate: 82% versus 73% for empirical (risk ratio [RR], 1.14; 95% confidence interval [CI], 1.04-1.24), 82% versus 43% for definitive (RR, 1.89; 95% CI, 1.53-2.33), and 94% versus 70% for end antimicrobial usage (RR, 1.34; 95% CI, 1.25-1.43). In multivariate analysis, teams that received feedback from the AUT alone (adjusted RR, 1.37; 95% CI, 1.27-1.48) or from both the AUT and the infectious diseases consultation service (adjusted RR, 2.28; 95% CI, 1.64-3.19) were significantly more likely to prescribe end antimicrobial usage appropriately, compared with control teams. CONCLUSIONS A multidisciplinary AUT that provides feedback to prescribing physicians was an effective method in improving antimicrobial use. Trial registration. ClinicalTrials.gov identifier: NCT00552838.

Paradoxical recurrent meningitis following therapy of cryptococcal meningitis: an immune reconstitution syndrome after initiation of highly active antiretroviral therapy

We report a case of paradoxical recurrent meningitis in response to initiation of highly active antiretroviral therapy in a patient receiving maintenance fluconazole for a previous diagnosis of cryptococcal meningitis. We describe the unusual radiographic and histopathologic findings which are consistent with an immune reconstitution induced paradoxical inflammatory response to residual cryptococcal infection.

Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Cost-Effectiveness Analysis Based on a Multicenter Clinical Trial

Two months of treatment with rifampin-pyrazinamide (RZ) and 9 months of treatment with isoniazid are both recommended for treatment of latent tuberculosis infection in adults without human immunodeficiency virus infection, but the relative cost-effectiveness of these 2 treatments is unknown. We used a Markov model to conduct a cost-effectiveness analysis to assess the impact on life expectancy and costs based on the results of a recent clinical trial that compared the rates of adverse events and completion of the 2 treatment regimens. Compared with no treatment, both regimens increased life expectancy by 1.2 years, but RZ cost 273 dollars more per patient. Sensitivity analyses showed that, assuming equal efficacy between the 2 regimens, there was no threshold completion rate for RZ at which the 2 treatments would be of equal net cost. Under most circumstances, treatment of latent tuberculosis infection with isoniazid is cost-saving than treatment with RZ.

Dapsone-Induced Hypersensitivity Pneumonitis Mimicking Pneumocystis carinii Pneumonia in a Patient with AIDS

Interstitial pneumonitis, often related to infectious etiologies, occurs commonly in HIV-infected patients. However, hypersensitivity pneumonitis from noninfectious etiologies, including environmental stimuli or drug exposure, is an unusual etiology of interstitial pneumonitis in HIV-infected patients. We report a patient with AIDS who developed a dapsone-induced hypersensitivity pneumonitis mimicking Pneumocystis carinii (PCP) pneumonia. We believe drug-induced hypersensitivity pneumonitis should be considered in the differential diagnosis of interstitial pneumonia in HIV-infected patients in whom infectious etiologies have been ruled out.

A multicenter study on optimizing piperacillin-tazobactam use: lessons on why interventions fail.

We examined interventions to optimize piperacillin-tazobactam use at 4 hospitals. Interventions for rotating house staff did not affect use. We could target empiric therapy in only 35% of cases. Because prescribing practices seemed to be institution specific, interventions should address attitudes of local prescribers. Interventions should target empiric therapy and ordering of appropriate cultures.

299 EMERGENCE OF COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS USA300 GENOTYPE IN HEALTH CARE-ASSOCIATED BLOODSTREAM INFECTIONS

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen and recently there has been the emergence of community-acquired MRSA (CA-MRSA). The impact of CA-MRSA genotypes (e.g. USA300) as a cause of bacteremia and nosocomial infections is poorly understood. Purpose of Study To determine the molecular epidemiology of MRSA bloodstream infections (BSI) in a large urban hospital. Methods Between January 1, 2004 and April 7, 2004, MRSA isolates recovered from blood of patients were collected. Pulsed field gel electrophoresis (PFGE) was performed on extracted DNA after SmaI-digestion. DNA fingerprints were compared to established pulsed-field type (PFT) clusters. Epidemiologic data were recorded. Results A total of 49 patients had a MRSA BSI during the study period, for a rate of 5.7 per 1,000 patient admissions. The demographic and clinical characteristics of patients included mean age of 51 years (range 6 months-92 years); 25 (51%) were male; 44 (90%) were African-American; 14 (29%) were HIV-seropositive; and 15 (31%) had a current or prior history of substance abuse. The mean length of stay was 25.6 days (range 2-131 days), and 13 (27%) died during their hospitalization. Age was independently associated with an increased risk of death (OR 1.07 per year, 95% CI 1.01-1.12). Community-onset disease, defined by positive cultures within 48 hours of admission, occurred in 25 (51%) of the patients; nosocomial infections, defined by a positive culture > 48 hours after admission, occurred in 24 (49%). However, 48 (98%) of 49 patients had health care-associated infections as all but 1 with “community onset” had previous contact with health care facilities (e.g., dialysis, antibiotic use, surgery, and residence in long-term care facility within 1 year prior to admission). Molecular typing revealed that 21 (43%) of 49 MRSA isolates were PFT USA100, 16 (33%) were USA500, and 12 (24%) were USA300, which has been associated with CA-MRSA infections. Conclusions MRSA is a common cause of bacteremia at our institution and is primarily health care-associated, even if the onset occurred in the community. The MRSA USA300 genotype, usually associated with skin and soft tissue infection, has emerged as a significant cause of nosocomial and health care-associated MRSA BSI in our institution, accounting for nearly one-fourth of all infections. The emergence of MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.