Hospital-acquired Methicillin-resistant Staphylococcus Aureus Research Articles

Transcriptional analysis of antibiotic resistance and virulence genes in multiresistant hospital-acquired MRSA

The staphylococcal chromosome cassette mec cannot solely explain the multiresistance phenotype or the relatively mild virulence profile of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA). This study reports that several multiresistant HA-MRSA strains differently expressed genes that may support antibiotic resistance, modify the bacterial surface and influence the pathogenic process. Genes encoding efflux pumps (norA, arsB, emrB) and the macrolide resistance gene ermA were found to be commonly expressed by HA-MRSA strains, but not in the archetypal MRSA strain COL. At equivalent cell density, the agr system was considerably less activated in all MRSA strains (including COL) in comparison with a prototypic antibiotic-susceptible strain. These results are in contrast to those observed in recent community-acquired MRSA isolates and may partly explain how multiresistant HA-MRSA persist in the hospital setting.

English

The aim of this study is to investigate the genetic backgrounds of methicillin susceptibleStaphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) isolates isolated from clinical specimens of the patients with verified infections in a Chinese teaching hospital. Macro E test (MET) was used to detect hVISA and multilocus sequence typing (MLST) was used to determine the STs of the selected isolates. The genotypes of SCCmec were determined by multiplex polymerase chain reaction (PCR) in MRSA isolates. Panton-valentine leucocidin (PVL) genes were also detected by PCR. Among 273 S. aureus  isolates, hospital-acquired methicillin-resistant Staphylococcus aureus(HA-MRSA), community-associated methicillin-resistant S. aureus (CA-MRSA), hospital-acquired methicillin susceptible Staphylococcus aureus (HA-MSSA) and community-associated methicillin susceptible Staphylococcus aureus (CA-MSSA) isolates accounted for 55.6, 1.5, 36.3, and 6.6%, respectively. Nine isolates were confirmed as hVISA by MET. Among 60 HA-MRSA isolates, ST239-MRSA-III was the most prevalent clone accounting for 51.7%, followed by ST5-MRSA-II clone. Fifty percentage and 22.2% of CA-MSSA isolates were found to be ST121 and ST88. ST239-MRSA-III was the predominant clone in hVISA isolates. However, no predominant ST type was found in HA-MSSA isolates. Of 9 PVL-positive strains, ST88 was the most prevalent ST (50.0%; 4/8), followed by ST121 (33.3%; 3/9), ST5 (4.5%; 1/22) and ST239 (2.6%; 1/39). In conclusion, ST239- III was the major pandemic clone in hVISA and HA-MRSA and spread in China. ST5-â…¡emerging rapidly in China had remained stable viability.   Key words: Staphylococcus aureus, heterogeneous vancomycin-intermediate Staphylococcus aureus, molecular characteristic.

Clinical Effectiveness and Cost Benefit of Universal versus Targeted Methicillin-Resistant Staphylococcus aureus Screening upon Admission in Hospitals

To conduct an exploratory study to evaluate the clinical effectiveness and cost benefit of universal versus targeted screening for methicillin-resistant Staphylococcus aureus (MRSA) to prevent hospital-acquired MRSA infections. Prospective, interventional study, using a case-control design, difference-in-differences, and cost-benefit analyses. Two community hospitals in Wisconsin. Consecutive sample of 15,049 adult admissions from April 2009 to July 2010. MRSA surveillance performed by polymerase chain reaction (PCR) on samples collected from all adult patients (aged over 18 years) within 30 days before or upon an admission to the hospital. During a 9-month baseline period, targeted screening was conducted at both hospitals. During the 5-month intervention period, all patients admitted to the intervention hospital were screened for MRSA. Infection control measures were consistent at both hospitals. Universal screening was associated with an increase in admission screening of 43.58 percentage points (P< .01), an increase in MRSA detection of 2.95 percentage points (P< .01), and a small, nonsignificant decline in hospital-acquired MRSA infections of 0.12 percentage points (P< .01). The benefit-to-cost ratio was 0.50, indicating that for every dollar spent on universal versus targeted screening, only $0.50 is recovered in avoided costs of hospital-acquired MRSA infection. Compared with targeted screening, universal screening increased the rate of detection of MRSA upon hospital admission but did not significantly reduce the rate of hospital-acquired MRSA infection. Universal screening was associated with higher costs of care and was not cost beneficial.

Evolution of Multidrug-ResistantStaphylococcus aureusInfections in Horses and Colonized Personnel in an Equine Clinic Between 2005 and 2010

A total of 70 Staphylococcus aureus isolates from postoperative infections in hospitalized horses were isolated between January 2005 and January 2011. Among them, 12 isolates were methicillin-susceptible S. aureus (MSSA), 18 were borderline-oxacillin-resistant S. aureus (BORSA), and 40 were methicillin-resistant S. aureus (MRSA). During the same period, the equine clinic personnel were screened for nasal carriage of BORSA and MRSA. Genotyping revealed that BORSA ST1(MLST)-t2863(spa) isolates were responsible for most equine infections and were the main isolates found in colonized members of the personnel between 2005 and 2007, and that in 2007, MRSA ST398-t011-IVa(SCCmec) emerged in infection sites and personnel, replacing BORSA. Besides decreased susceptibility to oxacillin, all MRSA and BORSA of these two major clonal lineages displayed resistance to gentamicin and kanamycin conferred by the aac(6')-Ie-aph(2')-Ia gene and to trimethoprim conferred by dfr(K) in MRSA and dfr(A) in BORSA. All MRSA had additional resistance to tetracycline conferred by tet(M), whereas BORSA generally also display resistance to streptomycin conferred by str. The number of hospital-acquired MRSA infections in horses could be limited after the introduction of basic hygiene measures and personnel decolonization. Two MRSA carriers could not be decolonized using mupirocin, and a year after decolonization, additional members were recolonized with MRSA. Hygiene measures should, therefore, be maintained to limit the transmission of S. aureus between personnel and horses.

Active surveillance culturing impacts methicillin-resistant Staphylococcus aureus acquisition in a pediatric intensive care unit*

To determine whether active surveillance culturing for methicillin-resistant Staphylococcus aureus (MRSA) decreases nosocomial MRSA acquisition in the pediatric intensive care unit. Before and after observational study. A tertiary care, 20-bed, pediatric intensive care unit. All patients admitted to the pediatric intensive care unit. Anterior nares cultures for MRSA were obtained on admission and weekly in the pediatric intensive care unit from January 2007 to December 2009 as part of a hospital quality improvement project. MRSA admission prevalence and nosocomial incidence density were determined retrospectively for 2006 and prospectively for 2007-2009. Nosocomial MRSA incidence density during the intervention period was determined monthly and analyzed by trend analysis by using a general linear model. The correlation of active surveillance culturing compliance with nosocomial acquisition of MRSA was analyzed. Possible confounding by healthcare worker hand hygiene compliance observed during the intervention period was also analyzed by multivariate linear regression analysis. The yearly MRSA incidence density significantly decreased from 2006 to 2009 (6.88 per 1,000 patient days to 1.45 per 1,000 patient days, p < .001) and from 2007 to 2009 (7.32 per 1,000 patient days to 1.45 per 1,000 patient days, p < .001). Trend analysis demonstrated a significant decline in MRSA acquisition over time following the introduction of active surveillance culturing (p < .001). Surveillance culturing was significantly associated with the decline in MRSA acquisition observed in the pediatric intensive care unit by multivariate regression analysis when controlling for hand hygiene (p = .01). Active surveillance culturing resulted in significantly decreased nosocomial acquisition of MRSA in a pediatric intensive care unit setting. Admission and weekly active surveillance culturing appears to be an effective tool to decrease the spread of MRSA in the pediatric intensive care unit, independent of improvement in hand hygiene compliance. The impact on hospital-acquired MRSA infections and the cost benefit of active surveillance culturing require further study.

Reduction of hospital-acquired MRSA as a result of increased use of hydoalcoholic handrub solution: a 7 year follow-up

In the Sint Jan General Hospital, a 900 bed public and teaching hospital, incidence of hospital acquired MRSA (HA-MRSA) increased till 2003 to 5.5/1.000 admissions (adm). In 2004 VigiGerme®, a strategy to fight MRSA by reducing transmission was implemented in collaboration with the University Hospitals of Geneva, in order to reduce the HA-MRSA.

Community-acquired methicillin-resistant Staphylococcus auereus in a Malaysian tertiary centre in year 2009

Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA) is a pathogen recognized to be distinct from hospital-acquired MRSA phenotypically and genotypically. We aimed to identify CA-MRSA cases in UKMMC, their antibiotic susceptibility patterns and genotypic characteristics.

Epidemiology and Risk Factors of Hospital-Acquired Invasive Methicillin Resistant Staphylococcus aureus Infections among Department of Defense Beneficiaries

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of healthcare-associated infection among multidrug-resistant organisms, and is often associated with invasive infection. Studies of hospital-acquired (HA) MRSA infections are typically within the general US population; risk factors from such studies may not be applicable to a subpopulation of Department of Defense (DOD) beneficiaries.

Coming to a practice near you? community-acquired meticillin resistant staphylococcus aureus (ca-mrsa)

Hospital-acquired meticillin resistant Staphylococcus aureus (HA-MRSA) arose in the 1960s, but the last decade saw the emergence of a new entity: community-acquired MRSA (CA-MRSA). Unlike HA-MRSA, patients affected by CA-MRSA have no obvious risk factors and may present with recurrent skin and soft tissue infections (SSTI) or, rarely, severe necrotizing pneumonia. This article provides an overview of CA-MRSA and reinforces the standard infection control procedures required to prevent further spread. The dental team require an awareness of emerging infections, their relevance to dentistry and the infection control procedures necessary to prevent transmission.

Epidemiology and Risk Factors for Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Among Burn Patients

Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial source of morbidity among burn patients. The objectives of this study were to determine the feasibility and efficacy of surveillance cultures and isolation precautions on limiting the transmission of MRSA among burn patients and to determine risk factors for the development of hospital-acquired MRSA (HA-MRSA). All patients admitted to the burn service from January 2007 to June 2009 were screened by nasal swab culture on admission and weekly thereafter. Other sites were cultured based on clinical suspicion. Patients with MRSA were immediately placed on isolation precautions. Community-acquired MRSA (CA-MRSA) and HA-MRSA were defined as identification of the organism <72 hours from admission (CA-MRSA) or ≥72 hours after admission (HA-MRSA). Charts were retrospectively analyzed to identify risk factors for development of HA. Screening compliance was 100%. Seventy MRSA cases were identified in 752 admissions (9% incidence), including 30 cases of CA-MRSA and 40 cases of HA-MRSA. Over the 30-month study period, HA-MRSA incidence decreased according to a significant linear trend. Independent risk factors for the development of HA-MRSA on multivariate analysis included length of stay >7 days (odds ratio [OR] 12.0, 95% confidence interval [CI] 1.6-91), TBSA affected >10% (OR 6.1, CI 2.6-14.2), age >30 years (OR 4.9, CI 2.0-12.0), and inhalation injury (OR 3.5, CI 1.0-11.7). Surveillance cultures with isolation precautions are practical and effective for preventing HA-MRSA among burn patients. Older patients with prolonged hospital stays, large wounds, and inhalation injury are at greatest risk.

Managing an Elusive Pathogen

Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a major problem both within hospitals (hospital-acquired MRSA) and increasingly in community settings (community-acquired MRSA), leading to well-publicized media reports and, as a result, greater public awareness of this problem. Clinically, it is difficult to distinguish between a MRSA and a methicillin-sensitive S. aureus skin and soft tissue infection, and this should be taken into consideration when initiating empiric therapy. There are several oral and intravenous antibiotics available to treat MRSA infections, some of which are inexpensive, whereas others are extremely costly; all have potential adverse effects and possible drug-drug interactions with which the prescriber should be familiar. Careful monitoring of patients who receive outpatient intravenous antibiotics and an understanding of various intravenous devices and their associated possible complications in addition to knowledge of the economics involved are essential to make cost-effective decisions.

Prevalence and molecular epidemiology of meticillin-resistant Staphylococcus aureus in nursing home residents in northern Germany

Nursing home residents are a population at risk for carrying meticillin-resistant Staphylococcus aureus (MRSA). To better guide infection control and healthcare network initiatives, we investigated the point prevalence and molecular epidemiology of MRSA colonisation among nursing home residents in Brunswick, northern Germany. Among the 32 participating nursing homes of the available 34 in the region, 68% of residents (1827 of 2688) were screened for nasal and/or wound colonisation. A total of 139 residents (7.6%; 95% confidence interval: 6.4-8.8%) were identified as MRSA positive, almost six-fold more than the 24 MRSA carriers (0.9%) expected according to the nursing homes' pre-test information. Although known risk factors including urinary tract catheters, wounds, preceding hospital admission, and high grade resident care were confirmed, none was sensitive enough to be considered as the sole determinant of MRSA carriage. spa typing revealed that more than 70% of isolates belonged to the Barnim strain (ST-22, EMRSA-15, CC22) typical for hospital-acquired MRSA in northern Germany. There was no evidence for the presence of community-acquired or livestock-associated S.aureus strains. These data show that in northern Germany MRSA has spread from the hospital environment to other healthcare institutions, which must now be regarded as important reservoirs for MRSA transmission.

World Health Day 2011–Antimicrobial Resistance: No Action Today, No Cure Tomorrow

The World Health Organization (WHO) has recently announced that the global phenomenon of antimicrobial resistance will be the theme of World Health Day 2011.1 The campaign, which aims to safeguard medicines for future generations, will call on governments around the world to implement policies to prevent the emergence of highly resistant “superbugs”.1,2 Asia remains the epicenter of resistant superbugs.3,4 In Taiwan, there is an alarmingly high prevalence of penicillin-resistant Streptococcus pneumoniae, community-acquired and hospitalacquired methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae, multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, as well as penicillinand fluoroquinolone-resistant Neisseria gonorrhoeae. Fluoroquinolone-resistant E coli and Salmonella species, particularly S enterica serotype Choleraesuis, are found not only in humans but also in animals. Azole-resistant Candida species, especially C glabrata, are prevalent in hospitals throughout Taiwan.3,4 In addition, the persistence of multidrug-resistant and the emergence of extensively drug-resistant Mycobacterium tuberculosis pose great challenges to public health.3 Community-acquired MRSA clones including ST59-MRSA-SCCmec type IV-spa type t437, ST30MRSA-SCCmec type IV-spa type t019, and ST72MRSA-SCCmec type IV-spa type t324 predominate in Asian countries. Previously established hospitalacquired MRSA strains including sequence type (ST)239 and ST5 clones have been found among community-acquired MRSA isolates from patients without any risk factors for hospital-acquired MRSA infection. Community-acquired MRSA clones such as ST59, ST30, and ST72 have also been isolated from patients with hospital-acquired infections.5 Various MRSA clones have spread between the community and hospitals as well as between countries.5 A few extensively drug-resistant A baumannii clones have disseminated throughout most hospital settings in Asia.3,4 Even more alarming is the recent emergence in Taiwan of carbapenemresistant Enterobacteriaceae, including those possessing New Delhi metallo-β-lactamase-1 and K pneumoniae carbapenemase.6 Antimicrobial resistance has struck at the core of infectious disease control worldwide.1,2 Although antimicrobial-resistant pathogens can be found throughout the world, antimicrobial resistance is of particular concern in countries where prescription of antimicrobial agents is unregulated and where antibiotics are widely available over the counter. The increased use of antibiotics in the

Increasing Role of Staphylococcus aureus and Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in the United States: A 10-Year Trend of Replacement and Expansion

There is the need to properly characterize the temporal trend of U.S. Staphylococcus aureus infections, including methicillin-resistant S. aureus (MRSA) and community-acquired (CA) MRSA in inpatient and outpatient settings. The study used the Surveillance Network(®) surveillance database (Eurofins Medinet) and the National Hospitalization Discharge Survey for the period 1998-2007. CA-MRSA phenotype was defined by a resistance profile that includes susceptibility to gentamicin and cotrimoxazole, and coresistance to ciprofloxacin/clindamycin. Adjusted rates, rate ratios, and 95% confidence intervals (CIs) were computed using multivariate logistic regression. The study consisted of 1,761,991 S. aureus isolates. Annual MRSA prevalence continuously increased over the 10-year period from 32.7% in 1998 to 53.8% in 2007 (odds ratio 2.4, 95% CI 2.3-2.5). CA-MRSA replaced competing strains by increasing its share of MRSA from 22.3% in 1998 to 66.1% in 2007 (odds ratio 6.7, 95% CI 6.5-6.9). MRSA-related hospitalization rate per 1,000 discharges doubled from 3.5 ± 0.9 in 1998 to 7.6 ± 1.5 in 2007 (RR 2.2, 95% CI 1.8-3.1), whereas CA-MRSA increased from 0.4 ± 0.14 hospitalizations per 1,000 discharges in 1998 to 3.1 ± 0.5 in 2007 (RR 8.1, 95% CI 5.2-14.1), By 2007, 81.5% of all MRSA isolates were categorized as CA-MRSA among children, whereas CA-MRSA represented 48.9% of MRSA isolates from the elderly. MRSA not only replaced methicillin susceptible S. aureus (MSSA) isolates as a percentage of all S. aureus isolates, but its hospitalization rates increased over and above the replacement process. This trend also applies to CA-MRSA over hospital-acquired (HA) MRSA.

Rates of hospital-acquired and healthcare-associated MRSA declined in the USA between 2005 and 2008

Commentary on: AJ Kallen, Y Mu, S Bulens, et al..; Active Bacterial Core surveillance (ABCs) MRSA Investigators of the Emerging Infections Program. Health care-associated invasive MRSA infections, 2005–2008. JAMA2010;304:641–8.

Molecular Characteristics of Community-Acquired Methicillin-ResistantStaphylococcus aureusin Hokkaido, Northern Main Island of Japan: Identification of Sequence Types 6 and 59 Panton-Valentine Leucocidin–Positive Community-Acquired Methicillin-ResistantStaphylococcus aureus

Prevalence and molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were studied in Hokkaido, the main northern island of Japan. Among the 1,015 S. aureus isolates derived from clinical specimens of outpatients collected in 2009, methicillin resistance gene mecA was detected in 189 isolates (18.6%). The most frequent staphylococcal cassette chromosome mec (SCCmec) type in MRSA was II (83.1%), followed by IV (6.9%) and V (3.2%). MRSA with type II-SCCmec showed multiple drug resistance and harbored various toxin and virulence factor genes except for Panton-Valentine leucocidin (PVL) gene. These isolates were mostly classified into sequence type 5 (ST5) (or other STs in CC5) and coagulase genotype II and were thus genetically similar to hospital-acquired MRSA, which have been predominating in Japan (New York/Japan clone). PVL gene was detected in three MRSA strains belonging to ST6 (two strains) and ST59 (one strain), having type IVa- and Vt-SCCmec, respectively, and also in two methicillin-susceptible S. aureus ST121 and ST188. The arcA gene within the arginine catabolic mobile element (ACME) was detected in the two PVL-negative ST5 MRSA strains, which had type IIa- or V-SCCmec. The PVL gene-positive ST6 and ST59 CA-MRSA strains were susceptible to more antimicrobials and had less virulence factor genes than the PVL-negative ST5 MRSA, including the ACME-arcA-positive strains. In the present study, ST6 was identified as a lineage of PVL-positive CA-MRSA, the ACME-arcA was first detected in ST5 MRSA with type V-SCCmec, and ST59 Taiwanese CA-MRSA strain was isolated in Hokkaido for the first time. These findings suggest a potential spread of these emerging CA-MRSA clones in Japan.

Cutaneous community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus

The clinical presentation of methicillin-resistant Staphylococcus aureus (MRSA) infection ranges from asymptomatic colonization to cutaneous and invasive involvement. This review discusses the cutaneous presentations of community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) that one may encounter in the hospital or outpatient setting. Cutaneous CA-MRSA and HA-MRSA are often clinically indistinguishable, although they have different epidemiologic profiles and virulence factors. Bacterial culture is necessary for diagnosis and guides treatment, as infection with CA-MRSA and HA-MRSA require distinct clinical management. Guidelines for surgical interventions and antibiotic treatment of CA-MRSA and HA-MRSA will be discussed. Strategies for MRSA decolonization and prevention of further spread will also be reviewed.

The costs and benefits of hospital MRSA screening

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a significant challenge. Rapid and accurate identification of MRSA in hospital admissions is essential for timely treatment decisions, isolation/bio-burden reduction and reducing potential cross-transmission/acquisition of these infections. Here we present the clinical benefits and cost-effectiveness of a rapid MRSA screening programme, which was implemented at Blackpool Victoria Hospital. The economic advantages of continuing the service despite a 15% cut in overall budget are also presented. In the pre-study period (2007–2008) 20 461 emergency and 21 461 elective admissions were screened and 40 cases of MRSA bacteraemia were reported. Glycopeptide unit days were 4145. During the 12-month pilot, approximately 4% of the PCR emergency screens were positive. Nine MRSA bacteraemias were reported during this period, representing a 78% reduction over the previous year. The cost of service over 12 months was £396 285. Estimated savings from the reduction in bed days and glycopeptide use ranged from 282 266 to 329 117. Hospital-acquired (post 48 hours) MRSA bacteraemias were reduced from 28 to 5. Annual glycopeptide spend was reduced by 50%, from £251 168 (2007–2008) to £124 060 (2008–2009). Rapidly available MRSA results were used to complement clinical decision making and optimize treatment. The cost-effectiveness of any screening programme is proportional to its success. The overall benefits and savings achieved in the current study more than justified the expenditure on rapid screening, and the Trust has since adopted PCR as a regular screening service for emergency admissions.

Effects of Selective Patient Screening for MRSA on Overall MRSA Hospital-Acquired Infection Rates

Determine if implementing a methicillin-resistant Staphylococcus aureus (MRSA) active surveillance program in the intensive care unit (ICU) only would affect hospitalwide transmission of MRSA. Hospital-acquired MRSA rates were collected from January 2007 to December 2009. In July 2008, an active surveillance program was implemented in all ICU areas. The hospital-acquired MRSA rates were compared before and after the implementation of the screening program. The ICU rate of hospital-acquired MRSA reduced from 3.19/1000 patient-days to 1.66/1000 patient-days (P .005). The facility's hospital-acquired MRSA rate was reduced from 0.80/1000 patient-days to 0.38/1000 patient-days (P .0003). Implementing an ICU-only active surveillance program is an effective method of controlling MRSA transmission on a hospitalwide level. Additional high-risk areas to consider include long-term acute care facilities, rehabilitation units, and patients with long-term indwelling medical devices.

Activity of moxifloxacin against intracellular community-acquired methicillin-resistant Staphylococcus aureus: comparison with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular susceptibility breakpoint

Co-trimoxazole, clindamycin and linezolid are used to treat community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but little is known about intracellular activity. Moxifloxacin is active against intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been studied. We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2 hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed in broth and after phagocytosis by THP-1 macrophages or keratinocytes {concentration-dependent experiments [24 h of incubation] to determine relative potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies [E(max) (change in log(10) cfu compared with initial inoculum)] and time-dependent experiments [0-72 h] at human C(max)}. Concentration-dependent experiments: in broth, EC(50) and C(s) were correlated with the MIC for all antibiotics, but moxifloxacin achieved significantly (P < 0.01) greater killing (more negative E(max)) than the comparators; and in THP-1 cells and keratinocytes, moxifloxacin acted more slowly but still reached a near bactericidal effect (2 to 3 log(10) cfu decrease) at 24 h with unchanged EC(50) and C(s) as long as its MIC was ≤0.125 mg/L (recursive partitioning analysis). Clindamycin and linezolid were static, and co-trimoxazole was unable to suppress the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin killed more rapidly and more extensively (≥5 log(10) cfu decrease at 10 h) than clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10) cfu at 72 h). Moxifloxacin is active against both extracellular and intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin, co-trimoxazole and linezolid.