Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

Prospective clinical trial evaluating spironolactone in Doberman pinschers with congestive heart failure due to dilated cardiomyopathy.

INTRODUCTION/OBJECTIVES: Whether the aldosterone antagonist spironolactone has beneficial survival effects in dogs with dilated cardiomyopathy (DCM) is not known. The primary objective of the study was to evaluate the effect of spironolactone, when added to conventional therapy, on survival time in Doberman pinschers with congestive heart failure (CHF) due to DCM. ANIMALS: Sixty-seven client-owned Doberman pinschers with CHF due to DCM. MATERIALS AND METHODS: The trial design was prospective, randomized, blinded, and placebo controlled. Dogs were randomized to receive 50-75 mg of spironolactone twice daily (n = 34) or a placebo (n = 33), in addition to standard CHF therapy. Follow-up visits were targeted every one-six weeks until endpoint. Quality-of-life questionnaire and physical examination were performed at every visit, while renal biochemistry, ECG, echocardiography, and thoracic radiography were reassessed as needed. The primary endpoint was time to cardiac death, defined as death or euthanasia from CHF or sudden death. RESULTS: Median time to primary endpoint in the spironolactone group (183 days) was not statistically significantly different than that for the placebo group (124 days) (P = 0.254). The development of atrial fibrillation (AF) was significantly less frequent in the spironolactone group (n = 7) than the placebo group (n = 15, P = 0.037). CONCLUSIONS: While median time to cardiac death in the spironolactone group was not statistically significantly different than that in the placebo group, adding spironolactone to conventional therapy resulted in reduced occurrence of AF.

Perioperative Prophylaxis for Total Artificial Heart Transplantation.

BACKGROUND: Practice variation regarding perioperative antimicrobial prophylaxis in total artificial heart transplantations (TAH-t) across institutions is unknown. The aim of our survey was to assess the current practices for prevention of infection in TAH-t recipients among different programs. METHODS: An electronic survey was sent to programs that implant Syncardia TAH (Syncardia Systems, Tuscon, Ariz, USA). Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. RESULTS: The majority of centers (80.8%) had a formal surgical infection prophylaxis protocol. For non-penicillin-allergic patients, five (20.1%) institutions reported using a 4-drug regimen, seven (29.2%) used a 3-drug regimen, five (20.1%) used a 2-drug regimen, and seven (29.2%) used a cephalosporin alone. Similar data was seen in the penicillin-allergic patients. Infections were reported to occur postoperatively in 52.2% centers. During the first month after TAH-t, bacteremia represented 27.3%, driveline infections 27.2%, pulmonary infections 9%, and mediastinal infections 18.2%. The most common organisms seen within the first month were Candida spp., Escherichia coli, and Pseudomonas aeruginosa (21.4%). In 65% of centers, the mean rate of death post-TAH-t due to infection was 14.5% (SD, 22.3%). The mean rate of patients surviving until orthotopic heart transplantation was 58.6% (SD, 27.7%). CONCLUSIONS: Preventing infections post-TAH-t is key to decreasing morbidity and mortality. All institutions administered perioperative prophylaxis for TAH-t with significant variation among the centers. The majority of the centers have a formal perioperative prophylactic protocol.

White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs.

Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents.

Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center.

Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.

Development of an occupational airborne chemical exposure matrix.

BACKGROUND: Population-based studies of the occupational contribution to chronic obstructive pulmonary disease generally rely on self-reported exposures to vapours, gases, dusts and fumes (VGDF), which are susceptible to misclassification. AIMS: To develop an airborne chemical job exposure matrix (ACE JEM) for use with the UK Standard Occupational Classification (SOC 2000) system. METHODS: We developed the ACE JEM in stages: (i) agreement of definitions, (ii) a binary assignation of exposed/not exposed to VGDF, fibres or mists (VGDFFiM), for each of the individual 353 SOC codes and (iii) assignation of levels of exposure (L; low, medium and high) and (iv) the proportion of workers (P) likely to be exposed in each code. We then expanded the estimated exposures to include biological dusts, mineral dusts, metals, diesel fumes and asthmagens. RESULTS: We assigned 186 (53%) of all SOC codes as exposed to at least one category of VGDFFiM, with 23% assigned as having medium or high exposure. We assigned over 68% of all codes as not being exposed to fibres, gases or mists. The most common exposure was to dusts (22% of codes with >50% exposed); 12% of codes were assigned exposure to fibres. We assigned higher percentages of the codes as exposed to diesel fumes (14%) compared with metals (8%). CONCLUSIONS: We developed an expert-derived JEM, using a strict set of a priori defined rules. The ACE JEM could also be applied to studies to assess risks of diseases where the main route of occupational exposure is via inhalation.

Clostridium difficile and cytomegalovirus colitis co-infection: search for the hidden 'bug'.

Few cases of co-infection with cytomegalovirus (CMV) and Clostridium difficile colitis have been reported previously. We describe 2 cases of CMV and C. difficile colitis, and review 7 previously published reports. We aim to raise awareness of possible CMV-C. difficile co-infection, especially in refractory cases of C. difficile colitis.

Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus.

Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P<0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P<0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

Relationship between susceptibility to daptomycin in vitro and activity in vivo in a rabbit model of aortic valve endocarditis.

Daptomycin is approved for treatment of Staphylococcus aureus bacteremia and right-sided endocarditis. Increases in daptomycin MICs have been associated with failure. A rabbit model of aortic valve endocarditis was used to determine whether MIC correlates with activity in vivo and whether a higher daptomycin dose can improve efficacy. Two related clinical S. aureus strains, one with a daptomycin MIC of 0.5 microg/ml and the other with a MIC of 2 microg/ml, were used to establish aortic valve endocarditis in rabbits. Daptomycin was administered once a day for 4 days at 12 mg/kg of body weight or 18 mg/kg to simulate doses in humans of 6 mg/kg and 10 mg/kg, respectively. Endocardial vegetations, spleens, and kidneys were harvested and quantitatively cultured. The strain with a MIC of 2 microg/ml had a survival advantage over the strain with a MIC of 0.5 microg/ml with >100 times more organisms of the former in endocardial vegetations at the 12-mg/kg dose in a dual-infection model. Both the 12-mg/kg dose and the 18-mg/kg dose completely eradicated the strain with a MIC of 0.5 from vegetations, spleens, and kidneys. The 12-mg/kg dose was ineffective against the strain with a MIC of 2 in vegetations; the 18-mg/kg dose produced a reduction of 3 log(10) units in CFU in vegetations compared to the controls, although in no rabbit were organisms completely eliminated. Increasing the dose of daptomycin may improve its efficacy for infections caused by strains with reduced daptomycin susceptibility.

MRI measurement of the canine auditory pathways and relationship with brainstem auditory evoked responses.

The objective of this study was to determine direct measurements of auditory pathways by magnetic resonance imaging (MRI) during the growth period of healthy Beagles, and to discover how canine brainstem auditory evoked response (BAER) latencies vary in relation to these MRI measurements. Eighty healthy Beagles were tested at eight, 16 and 52 weeks of age (stages 1, 2, 3, respectively) with BAER and brain MRI. The BAER interpeak latency (IPL) II-V and brain MRI neural generators of BAER waves II and V were identified. A linear distance was calculated in millimeters in order to determine the approximate length of auditory pathways. Sensory nerve conduction velocity (SNCV) of the auditory pathway between peak II and peak V was calculated for each group. A significant difference was observed between brain MRI distances among the three stages. Mean BAER IPL II-V were not significantly different between the three stages. The progressive growth of the skull and brain witnessed by the progressive increased distance of the MRI auditory pathways between peak II and peak V was not associated with a progressive maturation of the BAER IPL II-V. The SNCV of the auditory pathway between peak II and peak V was 6.14 m/sec for group 1; 6.76 m/sec for group 2; and 7.32 m/sec for group 3.

Ceftobiprole: in-vivo profile of a bactericidal cephalosporin.

Resistance to antimicrobials is a significant and growing problem, limiting treatment options, especially for serious Gram-positive infections. Ceftobiprole is a novel broad-spectrum cephalosporin that is active in vitro against streptococci and staphylococci, including penicillin-resistant strains of pneumococci and methicillin-resistant Staphylococcus aureus (MRSA). It maintains the activity of extended-spectrum cephalosporins against Gram-negative bacteria, including Enterobacteriaceae. The in-vivo activity of ceftobiprole has been demonstrated in mouse sepsis and subcutaneous abscess models of infection. Its activity also has been examined in several discriminative models of infection that mimic specific diseases in humans and permit testing of antimicrobial activity under a variety of defined pharmacokinetic conditions. These include experimental pneumonia in mice, a tissue cage model of foreign body infection in rats, and endocarditis models in rats and rabbits. In these models, ceftobiprole exhibits activity equivalent or superior to that of comparators against MRSA, including vancomycin-intermediate strains. These models also confirm the in-vivo activity of ceftobiprole against Gram-negative bacteria that are susceptible in vitro. The results from animal models support the evaluation of the clinical efficacy of ceftobiprole in humans and also predict clinical efficacy in the empirical treatment of severe infections. The broad spectrum of activity may allow ceftobiprole to be used as monotherapy for serious hospital-acquired infections where combination therapy would otherwise be required.

Clinical utility of the Duncan-Ely test for rectus femoris dysfunction during the swing phase of gait.

The Ely Test (or Duncan-Ely test) has been accepted as a clinical tool to assess rectus femoris spasticity by passively flexing the knee rapidly while the patient lies prone in a relaxed state. In this retrospective review, patients' dynamic knee range of motion (ROM) during gait and an electromyogram (EMG) were compared with the results of the Ely test. Data for 70 patients (44 males, 26 females; 104 limbs) were included. Mean age of patients was 13 years, SD 9 years, range 4 years 5 months to 54 years. All patients were diagnosed with cerebral palsy (spastic diplegia, n = 42; spastic quadriplegia, n = 15, and hemiplegia, n = 13). All patients were ambulatory (50 independent, 20 with assistive devices). A standard matrix was used to calculate sensitivity and specificity of the Ely test as well as its positive and negative predictive value. For the gait variables examined (decreased dynamic knee ROM, timing of peak knee flexion, and abnormal EMG in swing) the sensitivity of the Ely test ranged from 56 to 59% and the specificity ranged from 64 to 85%. For the same variables the positive predictive value ranged from 91 to 98% and the negative predictive value ranged from 4 to 19%. The Ely test was shown to have a good positive predictive value (i.e. the certainty about the presence of rectus spasticity in patients with a positive Ely test result) for rectus femoris dysfunction during gait.

Pre-conception and antenatal screening for the fragile site on the X-chromosome.

BACKGROUND: Fragile X is the most common cause of mental retardation after Down syndrome. It is the commonest inherited cause of mental retardation, and results from a dynamic mutation in a gene on the long arm of the X chromosome. Various strategies are used for prenatal screening. OBJECTIVES: To determine whether pre-conceptual or antenatal screening for Fragile X carrier status in apparently low risk women confers any additional benefit over the existing practice of offering testing to women thought to be at increased risk. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2001), the Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1980 to 2001), and reference lists of articles. SELECTION CRITERIA: Randomised clinical trials comparing women being tested regardless of family history (intervention group) with women tested only when there is a family history of either fragile X and/or other undiagnosed mental illness/impairment (control group). DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed trial quality and extracted data. MAIN RESULTS: No trials were included. REVIEWER'S CONCLUSIONS: No information is available from randomised trials to indicate whether routine pre-conceptual or antenatal screening for fragile X carrier status confers any benefit over testing women thought to be at increased risk.

Botulinum toxin type a neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial.

BACKGROUND: Focal spasticity of the gastrocnemius-soleus muscles causes equinus gait in children with cerebral palsy (CP). Botulinum toxin type A (BTX-A), a neuromuscular blocking agent, reduces muscle tone/overactivity in dystonia, stroke, and CP. OBJECTIVE: A prospective, open-label, multicenter clinical trial evaluated the long-term safety and efficacy of repeated intramuscular injections of BTX-A on equinus gait in CP children. METHODS: Nine centers enrolled 207 children. BTX-A injections (4 U/Kg) were given approximately every 3 months (maximum dose 200 U per treatment). Outcome measures included a Physician Rating Scale of gait, ankle range of motion measurements, and the incidence and profile of adverse events. RESULTS: One hundred fifty-five (75%) of 207 children completed at least 1 year with a total of 302 patient years of BTX-A treatment. The mean duration of BTX-A exposure was 1.46 years per patient. Dynamic gait pattern on the Physician Rating Scale improved in 46% of patients (86/185) at first follow-up. The response was maintained in 41% to 58% of patients for 2 years. Both gait pattern and ankle position improved at every visit. The most common treatment-related adverse events included increased stumbling, leg cramps, leg weakness, and calf atrophy in 1% to 11% of patients. No treatment-related serious adverse events were reported. Only 6% (7/117) of patients with pre- and postantibody samples had both detectable antibodies and a subsequent treatment failure. CONCLUSION: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait.

Perinatal and postneonatal mortality among Indigenous and non-Indigenous infants born in Western Australia, 1980-1998.

OBJECTIVE: To describe cause-specific perinatal and postneonatal mortality for Indigenous and non-Indigenous infants using a new classification system. DESIGN: Total population retrospective cohort study. PARTICIPANTS AND SETTING: All registered births in Western Australia of birthweight greater than 399 g from 1980 to 1998, inclusive. MAIN OUTCOME MEASURES: Rates and time trends for all births 1980-1998, and cause-specific rates for births 1980-1993 of fetal, neonatal and postneonatal mortality among Indigenous and non-indigenous infants, using a classification system designed for use in perinatal, postneonatal and childhood deaths. RESULTS: For Indigenous infants born 1980-1998, the mortality rate before the first birthday was 2.7 times (95% CI, 2.5-2.9 times) that for non-Indigenous infants. Indigenous infants born 1980-1993 had a higher mortality rate in all cause-of-death categories. The highest relative risk was for deaths attributable to infection (8.1; 95% CI, 6.5-10.0) which occurred primarily in the postneonatal period; the source of the infection was less likely to be identified in Indigenous deaths. From 1980-1998, the rate of neonatal deaths decreased at a greater rate for Indigenous than for non-Indigenous infants. However, while stillbirth and sudden infant death syndrome rates for non-Indigenous births fell, they remained static for Indigenous births. CONCLUSIONS: The new classification system, which considers the underlying rather than immediate cause of death, enables investigation of the causes of all deaths, from stillbirths to childhood. This system has highlighted the comparative importance of infection as a cause of death for Indigenous infants, particularly in the postneonatal period.

Identifying pulmonary tuberculosis in patients with negative sputum smear results.

BACKGROUND: Clinicians need to decide whether to begin empiric therapy for patients who are suspected of having tuberculosis (TB) but have negative sputum smear results. Culture results may take weeks, and delaying treatment may allow further transmission of disease. STUDY OBJECTIVE: To identify the clinical, demographic, and radiographic characteristics that identify smear-negative patients who have TB, and to create a TB prediction rule. DESIGN: Retrospective chart review. SETTING: University-affiliated public hospital in San Francisco, CA, between 1993 and 1998. PATIENTS: Forty-seven patients with TB and 141 control patients who were hospitalized with a suspicion of pulmonary TB; all had negative sputum smear results. MEASUREMENTS AND RESULTS: Demographic, clinical, and radiographic variables were determined by chart review. In multivariate analysis, a positive tuberculin skin test result (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.0 to 11.9) was independently associated with an increased risk of a positive TB culture finding. A radiographic pattern not typical of pulmonary tuberculosis (OR, 0.3; 95% CI, 0.1 to 0.7) and expectoration with cough (OR, 0.3; 95% CI, 0.1 to 0.6) were predictive of a decreased risk. An interaction between HIV seropositivity and mediastinal lymphadenopathy on the chest radiograph was also associated with a positive TB culture result (OR, 7.2; 95% CI, 1.4 to 36.0). The TB prediction score (TPS) was created with widely ranging likelihood ratios that could affect the posterior probability of TB by 30-fold. CONCLUSION: The TPS put into context with the overall prevalence of TB in a given area may help clinicians decide if a patient with negative sputum smear results should start empiric antituberculous therapy or wait for culture results. These results need prospective validation.

Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis.

Although the protective cellular immune response to Mycobacterium tuberculosis requires recruitment of macrophages and T lymphocytes to the site of infection, the signals that regulate this trafficking have not been defined. We investigated the role of C-C chemokine receptor 2 (CCR2)-dependent cell recruitment in the protective response to M. tuberculosis. CCR2(-/-) mice died early after infection and had 100-fold more bacteria in their lungs than did CCR2(+/+) mice. CCR2(-/-) mice exhibited an early defect in macrophage recruitment to the lung and a later defect in recruitment of dendritic cells and T cells to the lung. CCR2(-/-) mice also had fewer macrophages and dendritic cells recruited to the mediastinal lymph node (MLN) after infection. T cell migration through the MLN was similar in CCR2(-/-) and CCR2(+/+) mice. However, T cell priming was delayed in the MLNs of the CCR2(-/-) mice, and fewer CD4(+) and CD8(+) T cells primed to produce IFN-gamma accumulated in the lungs of the CCR2(-/-) mice. These data demonstrate that cellular responses mediated by activation of CCR2 are essential in the initial immune response and control of infection with M. tuberculosis.

Supracondylar fractures of the humerus associated with ipsilateral forearm fractures in children: a report of forty-seven cases.

Supracondylar fractures of the humerus associated with ipsilateral forearm fractures are uncommon and treatment recommendations are controversial. The purpose of this study was to determine whether pin fixation of both fracture components, humerus and forearm, would improve the outcome. In a two-center trial, 884 children sustaining supracondylar fractures of the humerus were retrospectively reviewed, and 47 (5.3%) showed associated ipsilateral forearm fractures. Of those, 29 underwent Kirschner-wire fixation of the forearm fracture, and 18 of the forearm fractures were treated with casting alone. Three of the 18 forearm fractures with casting alone reangulated. There were no reangulations in the patients who had pin fixation of their fractures. There were no complications due to pin fixation in the humerus or the forearm. In unstable supracondylar humerus and forearm fractures, stabilization with pin fixation to prevent reangulation should be considered.

The changing epidemiology of Staphylococcus aureus?

Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.