Invasive Methicillin-resistant Staphylococcus Aureus Infections Research Articles

Clinical implications of methicillin-resistant Staphylococcus aureus in pregnancy

Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly aggressive and prevalent pathogen in medicine. This pattern has also been noted in obstetrics. This review will delineate the epidemiology and clinical implications of MRSA during pregnancy. Investigations have focused on prevalence of MRSA colonization in obstetrics and the associated morbidity. In addition, some attention has been focused on the neonatal implications of maternal colonization. Overall, the rates of maternal MRSA colonization noted in the United States have been low, in the range of 0.5-4%. The clinical impact of MRSA colonization among pregnant women has also been estimated to be modest. Roughly 357 invasive MRSA infections per 100,000 live births in the United States occur on an annual basis. It is however important to note that published estimates likely underestimate the full scope of MRSA in pregnancy given the lack of formal reporting, importance of related neonatal colonization and morbidity, the complicated treatment implications in pregnant women, the recognized high pathogenicity of MRSA infections, and propensity for recurrent infections among community-acquired MRSA strains. MRSA is an increasingly important pathogen in modern healthcare and in the obstetric population. Continued surveillance and research remains a top priority.

Carriage Rates of Methicillin-resistantStaphylococcus aureusin Neonates with Neonatal Jaundice

Purpose : It is known that carriage rates of Staphylococcus aureus (S. aureus) are highest in newborns and that the asymptomatic carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with invasive MRSA infection with the colonizing strain. This study was carried out to investigate the carriage rates of MRSA in neonates with neonatal jaundice. Methods : We reviewed the medical records of 545 neonates admitted with neonatal jaundice to neonatal intensive care units between January 2006 and December 2010. Nasal and inguinal swab specimens had been taken from them and cultured for the isolation of S. aureus. Antimicrobial susceptibility tests had been done for such isolates to determine methicillinresistance. Results : Out of 545 neonates, 318 (58.3%) were colonized with S. aureus and 214 (39.3%) were colonized with MRSA. Results of the antibiogram analysis showed that 65.7% of MRSA isolates were likely to be community-associated (CA) MRSA. Conclusion : Based on the MRSA carriage rate of 39.3%, a surveillance program for MRSA colonization is considered necessary in neonates transferred from other clinics or hospitals. Out of MRSA isolates, 65.7% were likely to be CA-MRSA. This suggests that CA-MRSA strains were already present in obstetric clinic environments where the neonates were born. It is thought that MRSA surveillance programs in these environments are also necessary.

Combinatorial Phenotypic Signatures Distinguish Persistent from Resolving Methicillin-Resistant Staphylococcus aureus Bacteremia Isolates

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) (positive blood cultures after ≥7 days of therapy) represents a clinically challenging subset of invasive MRSA infections. In this investigation, we examined the potential correlation of specific virulence signatures with PB versus resolving MRSA bacteremia (RB) (negative blood cultures within 2 to 4 days of therapy) strains. Thirty-six MRSA isolates from patients enrolled in a recent multinational clinical trial were studied for (i) susceptibility to host defense cationic peptides (HDPs) (i.e., thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide 1 [hNP-1]); (ii) adherence to host endovascular ligands (fibronectin) and cells (endothelial cells); and (iii) biofilm formation. We found that PB isolates exhibited significantly reduced susceptibilities to tPMPs and hNP-1 (P < 0.001 and P = 0.023, respectively). There was no significant association between the PB outcome and fibronectin binding, endothelial cell binding, or biofilm formation (P = 0.25, 0.97, and 0.064 versus RB strains, respectively). However, multiple logistic regression analysis revealed that the PB outcome was significantly associated with the combination of reduced susceptibilities to HDPs and extent of biofilm formation (P < 0.0001). Similar results were obtained in a second analysis using days of bacteremia as a continuous outcome, showing that reduced HDP susceptibilities and increased biofilm formation cocontributed to predict the duration of bacteremia. Our data indicate that PB isolates have specific pathogenic signatures independent of conventional antimicrobial susceptibility. These combinatorial mosaics can be defined and used to prospectively distinguish PB from RB strains in advance and potentially to predict ultimate clinical outcomes.

Health Care–Associated Invasive MRSA Infections, 2005-2008

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of public health importance; MRSA prevention programs that may affect MRSA transmission and infection are increasingly common in health care settings. Whether there have been changes in MRSA infection incidence as these programs become established is unknown; however, recent data have shown that rates of MRSA bloodstream infections (BSIs) in intensive care units are decreasing. To describe changes in rates of invasive health care-associated MRSA infections from 2005 through 2008 among residents of 9 US metropolitan areas. Active, population-based surveillance for invasive MRSA in 9 metropolitan areas covering a population of approximately 15 million persons. All reports of laboratory-identified episodes of invasive (from a normally sterile body site) MRSA infections from 2005 through 2008 were evaluated and classified based on the setting of the positive culture and the presence or absence of health care exposures. Health care-associated infections (ie, hospital-onset and health care-associated community-onset), which made up 82% of the total infections, were included in this analysis. Change in incidence of invasive health care-associated MRSA infections and health care-associated MRSA BSIs using population of the catchment area as the denominator. From 2005 through 2008, there were 21,503 episodes of invasive MRSA infection; 17,508 were health care associated. Of these, 15,458 were MRSA BSIs. The incidence rate of hospital-onset invasive MRSA infections was 1.02 per 10,000 population in 2005 and decreased 9.4% per year (95% confidence interval [CI], 14.7% to 3.8%; P = .005), and the incidence of health care-associated community-onset infections was 2.20 per 10,000 population in 2005 and decreased 5.7% per year (95% CI, 9.7% to 1.6%; P = .01). The decrease was most prominent for the subset of infections with BSIs (hospital-onset: -11.2%; 95% CI -15.9% to -6.3%; health care-associated community-onset: -6.6%; 95% CI -9.5% to -3.7%). Over the 4-year period from 2005 through 2008 in 9 diverse metropolitan areas, rates of invasive health care-associated MRSA infections decreased among patients with health care-associated infections that began in the community and also decreased among those with hospital-onset invasive disease.

Prediction of vancomycin pharmacodynamics in children with invasive methicillin-resistant Staphylococcus aureus infections: A Monte Carlo simulation

Background: Due to the emergence of community-associated strains, the prevalence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections has increased substantially in pediatric patients. A vancomycin AUC 0–24/MIC index >400 best predicts treatment outcomes for invasive MRSA infection in adults. Data on whether recommended vancomycin doses in children achieve this break point are lacking. Objective: This study aimed to assess the likelihood that currently recommended vancomycin doses in children achieve AUC 0–24/MIC >400. Methods: Vancomycin AUC 0–24/MIC predictions were conducted across a range of dosages (40–70 mg/kg/d) using a Monte Carlo simulation (n = 5000). AUC 0–24 was calculated as daily dose divided by vancomycin clearance, and daily dose was fixed for a given simulation. Three literature-reported estimates in children were used to define vancomycin clearance and its variance. For the MIC distribution of MRSA isolates, susceptibility data were obtained from the University of California, San Francisco Children's Hospital, San Francisco, California (n = 180; 40% ≤0.5 mg/L; 59% = 1 mg/L; and 1% = 2 mg/L). Results: Using the recommended empiric dosage of 40 mg/kg/d, 58% to 66% of children were predicted to achieve AUC 0–24/MIC >400. Increasing the vancomycin dosage to 60 mg/kg/d substantially increased the likelihood (88%–98%) of achieving this pharmacodynamic target. On sensitivity analysis, a dosage of 40 mg/kg/d was more strongly influenced by small changes in MIC compared with 60 mg/kg/d. Conclusions: Recommended empiric vancomycin dosing in children (40 mg/kg/d) was not predicted to consistently achieve the pharmacodynamic target of AUC 0–24/MIC >400 for invasive MRSA infections. A vancomycin dosage of 60 mg/kg/d was predicted to optimize achievement of this target in children.

Invasive Infection Caused by a Community-Associated Methicillin-Resistant Staphylococcus aureus Strain Not Carrying Panton-Valentine Leukocidin in South Korea

Panton-Valentine leukocidin (PVL)-negative, SCCmec type IVa strains are the most common strains of methicillin-resistant Staphylococcus aureus (MRSA) circulating in the community in South Korea. This report describes five elderly patients presenting in 2006 to 2007 with invasive community-associated MRSA infection caused by a PVL-negative, SCCmec type IVa strain with sequence type 72 and spa type t324.

Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?

Invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), particularly those involving persistent bacteraemia, necrotizing pneumonia, osteomyelitis and other deep-seated sites of infections, are associated with high mortality and are often difficult to treat. The response to treatment of severe MRSA infection with currently available antibiotics active against MRSA is often unsatisfactory, leading some physicians to resort to combination antibiotic therapy. Now, with the emergence of community-associated MRSA (CA-MRSA) clones that display enhanced virulence potentially related to up-regulated toxin production, the use of adjuvant protein synthesis-inhibiting antibiotics to reduce toxin production also has been advocated by some experts. In this review, we discuss the limitations of antibiotics currently available for the treatment of serious invasive MRSA infections and review the existing literature that examines the potential role of combination therapy in these infections.

Epidemiologic and Economic Effect of Methicillin-Resistant Staphylococcus aureus in Obstetrics

To quantify the epidemiologic and economic burden of methicillin-resistant Staphylococcus aureus (MRSA) infections in the obstetric population, identify main factors influencing the magnitude of disease, and evaluate the cost-effectiveness of MRSA screening and decolonization. A cost-effectiveness decision analytic model was constructed for estimations from both the societal and third party-payer perspectives. Probabilities were derived from prior studies when available. Cost data came from the Healthcare Cost and Utilization Project, medication wholesale prices, and the Centers for Medicare & Medicaid Services. Sensitivity analysis was conducted to assess the effect of variables across a range of values. Approximately 14,294 pregnant or postpartum women experience an invasive MRSA infection in the United States annually. The majority of invasive MRSA infections are mastitis (n=8,880). The annual economic effect of MRSA infections is projected to be approximately $8.7 million and approximately $8.0 million from the societal and payer perspectives, respectively. Sensitivity analyses demonstrate that the prevalence of MRSA, incidence of mastitis, and rate of cesarean deliveries were key driving factors for the estimations. Methicillin-resistant S aureus is an important emerging pathogen responsible for a modest burden of puerperal infections and associated costs. Universal screening and decolonization efforts do not currently seem to be cost-effective.

Current Recommended Dosing of Vancomycin for Children With Invasive Methicillin-Resistant Staphylococcus aureus Infections Is Inadequate

Vancomycin area-under-the-concentration-time-curve (AUC) for 24 hours divided by the minimum inhibitory concentration (MIC) (AUC24/MIC) >400 optimally treats invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in adults. It is unknown whether recommended vancomycin dosing regimens for children achieve this value. AUC24/MIC was calculated in children using vancomycin doses of 40 and 60 mg/kg/d. AUC24 was calculated as daily dose/vancomycin clearance. Vancomycin clearance in children was estimated by 2 approaches: (1) previously literature-reported vancomycin clearance, and (2) calculated vancomycin clearance using previously derived predictor models and a hypothetical population of healthy children. Representative MIC of hospital MRSA isolates was used (0.5, 1.0, and 2.0 microg/mL). The MIC50/90 for pediatric MRSA isolates in the previous year was 1.0 microg/mL. With a dose of 40 mg/kg/d, both approaches consistently predicted AUC24/MIC <400 when MIC was 1.0 microg/mL. At 60 mg/kg/d, AUC24/MIC >400 was more readily achieved when MIC was 1.0 microg/mL, however, an MIC of 2.0 microg/mL resulted in AUC24/MIC <400 for both dosing regimens. A vancomycin dose of 40 mg/kg/d in children is unlikely to achieve the recommended pharmacodynamic target of AUC24/MIC >400 for invasive MRSA infections even when MIC is 1.0 microg/mL. A starting dose of 60 mg/kg/d should be used in settings where isolates with MIC of 1.0 are common. Alternatives to vancomycin should strongly be considered for patients with MIC > or =2.0 microg/mL.

Characterization of Methicillin-Resistant Staphylococcus aureus Isolates Collected in 2005 and 2006 from Patients with Invasive Disease: a Population-Based Analysis

This study characterizes 1,984 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2005 and 2006 from normally sterile sites in patients with invasive MRSA infection. These isolates represent a convenience sample of all invasive MRSA cases reported as part of the Active Bacterial Core surveillance system in eight states in the United States. The majority of isolates were from blood (83.8%), joints (4.1%), and bone (4.2%). Isolates were characterized by pulsed-field gel electrophoresis (PFGE); SCCmec typing; susceptibility to 15 antimicrobial agents; and PCR analysis of staphylococcal enterotoxin A (SEA) to SEH, toxic shock syndrome toxin 1, and Panton-Valentine leukocidin. Thirteen established PFGE types were recognized among these isolates, although USA100 and USA300 predominated, accounting for 53.2% and 31.4% of the isolates, respectively. As expected, isolates from hospital onset cases were predominantly USA100, whereas those from community-associated cases were predominantly USA300. USA100 isolates were diverse (Simpson's discriminatory index [DI] = 0.924); generally positive only for enterotoxin D (74.5%); and resistant to clindamycin (98.6%), erythromycin (99.0%), and levofloxacin (99.6%), in addition to beta-lactam agents. USA300 isolates were less diverse (DI = 0.566), positive for Panton-Valentine leukocidin (96.3%), and resistant to erythromycin (94.1%) and, less commonly, levofloxacin (54.6%), in addition to beta-lactam agents. This collection provides a reference collection of MRSA isolates associated with invasive disease, collected in 2005 and 2006 in the United States, for future comparison and ongoing studies.

Decreasing MRSA Infections

INVASIVE INFECTIONS WITH METHICILLIN-RESISTANT STAPHYlococcus aureus (MRSA) have become a focus of national attention over the past several years due to their potentially lethal complications and reports indicating that their frequency is on the rise in most US hospitals. Hospitalizations with infections due to MRSA steadily increased between 2000 and 2005, nearly doubling in many areas of the country. Klevens et al estimated that up to 18 650 deaths in the United States in 2005 may have been associated with invasive MRSA infection. These statistics coupled with the increasing number of outbreaks of MRSA infections in community settings have helped ignite a contentious public debate about the best means of control, including calls for increased surveillance for MRSA infections, new prevention activities such as screening of all patients admitted to hospitals to detect colonization with MRSA (universal screening), and public reporting of hospitalacquired MRSA infections. Now amidst this alarm, the report by Burton and colleagues in this issue of JAMA documents decreases in the rate of MRSA-related central line–associated bloodstream infections (CLABSI) in hospitals participating in a voluntary surveillance network. This network was initially known as the National Nosocomial Infection Surveillance system (NNIS, 1997-2004) and later as the National Healthcare Safety Network (NHSN, 2006-2007). Facilities participating in NNIS/NSHN report to the Centers for Disease Control and Prevention (CDC) all health care–acquired infections detected during prospective surveillance in a variety of units. The current report details the experience with MRSA CLABSI in intensive care units (ICUs) from 1997 to 2007 and demonstrates that despite an overall increase in the incidence of MRSA infections, the rate of MRSA CLABSI decreased 49.6% at NNIS/NSHN hospitals. Four types of ICUs (surgical, cardiothoracic, coronary, and medical/surgical without a major teaching affiliation) initially experienced an increase in MRSA CLABSI lasting until 2001, but this was followed by declining rates through 2007. All units, except pediatric ICUs, experienced an overall decline in infections from 2002-2007. Moreover, both the overall rate of CLABSI and methicillin-sensitive S aureus (MSSA) CLABSI showed steady declines from 1997 to 2007 among all types of ICUs. Although the report by Burton et al suggests ICUs are having increasing success limiting the spread of MRSA, the study is not without limitations. The first concern is the dynamic nature of NNIS/NHSN. Fewer than 6% of ICUs in the current study participated in the NNIS/NHSN for the entire 11-year study interval. A large number of hospitals entered the network for the first time in 2007 prompted by mandatory public reporting requirements in many states, highlighting the changing nature of the network and challenging its description as a voluntary, hospital-based reporting system. In addition, although the authors contend that voluntary self-reporting was most likely accurate, it has not been validated since 1998. The accuracy of selfreporting may be an important issue in the upcoming era of mandatory public reporting and increased scrutiny of hospital-acquired infections by regulatory agencies. The study also leaves the unsettling realization that the observed reductions in infection cannot be attributed to any particular intervention. Previous reports from NNISparticipating ICUs have demonstrated reductions in bloodstream infections, ventilator-associated pneumonias, and catheter-associated urinary tract infections. These reports have led to the conclusion that prospective surveillance followed by careful local risk assessment and adoption of interventions that include best practices can be used to reduce hospital-acquired infection rates. It is likely that the reductions in infections reported by Burton et al were related to a range of interventions that have been implemented during the last decade including better hand hygiene practices, adoption of standardized line insertion and care practices, proper barrier precautions, improved catheter technology, and shorter periods of indwelling catheter use in patients. Thus, it is impossible to determine which practices had the greatest effect or even which were implemented by participating ICUs. Can the end be justified by the means, when the means are unknown?

Outbreak of Invasive Methicillin-ResistantStaphylococcus aureusInfection Associated With Acupuncture and Joint Injection

To describe an outbreak of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner. A medical practitioner's office and 4 hospitals in Perth, Western Australia. Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner. We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control audit of the medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner. Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified. This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.

MRSA tricuspid valve infective endocarditis with multiple embolic lung abscesses treated by combination therapy of vancomycin, rifampicin, and sulfamethoxazole/trimethoprim

A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted to our hospital for the treatment of tricuspid valve infective endocarditis (IE) and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We started to treat her with vancomycin (VCM) alone and then in combination with rifampicin (RFP), but her condition did not improve. Then we added sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved rapidly. In Japan, there are very few reports about tricuspid valve IE caused by MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP may be effective for the treatment of severe MRSA infections.

Clinical failures of appropriately-treated methicillin-resistant Staphylococcus aureus infections

Methicillin-resistant Staphylococcus aureus (MRSA) infections can be difficult to treat. We evaluated the rate of clinical failure in appropriately-treated patients and determined risk factors for failure. We retrospectively studied a cohort of patients with invasive MRSA infections who completed recommended therapy at one hospital over a 7 year period. Two-hundred and fifteen cases were included. Vancomycin monotherapy was given in 73%. Failure rates by infection site were as follows: osteomyelitis 37/81 (46%), epidural abscess five/18 (28%), surgical wound four/15 (27%), pneumonia eight/45 (18%), endocarditis five/32 (16%), bloodstream five/42 (12%), joint one/23 (4%), and meningitis zero/one (0%). In multivariate analysis, only a diagnosis of osteomyelitis was independently associated with relapse (p<0.001). We found a high rate of treatment failure in an urban population among patients who completed recommended therapy, largely with vancomycin alone. Failure in osteomyelitis was particularly common. High quality comparative studies of antibiotic regimens for MRSA infections, particularly osteomyelitis, are needed.

Community‐Associated Methicillin‐Resistant Staphylococcus aureus: Continuing to Evolve

In the 2003 issue of The Canadian Journal of Infectious Diseases, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a community-acquired pathogen in Canada was reviewed (1). This followed reports of severe, invasive community-acquired MRSA (CA-MRSA) infections in children in Minnesota and North Dakota (USA), and recognition of its role as a pathogen in several Canadian outbreaks. The emergence of CA-MRSA as a pathogen of epidemiological significance in Canada prompted a meeting in 2005 sponsored by the Public Health Agency of Canada, the Ontario Ministry of Health and Long-Term Care and the Canadian Committee on Antibiotic Resistance, that made recommendations for its prevention and management; it was published in the Journal in 2006 (2). Since then, research has produced evidence that supports previous findings, challenges others and introduces new ones. Of particular interest is the appearance of CA-MRSA as a nosocomial pathogen, and the potential for its genetic intermingling with its hospital-acquired counterpart (HA-MRSA).

Implementation of an intensified infection control program to reduce MRSA transmissions in a German tertiary care hospital

Germany has witnessed increasing national methicillin-resistant Staphylococcus aureus (MRSA) rates during the past 2 decades. In our 900-bed tertiary care community hospital, a similar increase was noted during the period from 1994 to 2002, although single-room isolation and decolonization therapy were the standard of care. An intensified infection control program aimed at the reduction of nosocomial MRSA transmissions was developed in 2002 and translated into clinical practice in 2003. Essential components of the program were a detailed written MRSA standard, acquisition of signal-colored isolation gowns and storage carts facilitating the use of separate supplies for MRSA patients, intensified surveillance and feedback of MRSA data, "flagging" of formerly positive MRSA patients, and a general MRSA screening policy for all newly admitted patients on the surgical intensive care unit (ICU). The effect of the program was monitored by continuous surveillance of MRSA cases on all wards. The transmission index was defined as the ratio between secondary and "imported" MRSA cases. Comparing the preintervention (2002) and postintervention (2005-2006) periods, the total number of MRSA patients, MRSA rates on the ICUs, and invasive MRSA infections on the ICUs were reduced. The MRSA transmission index fell from 2.1 (2002) to 0.8 (2006). The rate of deep incisional and organ/space infections due to MRSA occurring after orthopedic surgery was lowered from 0.74 to 0.15%. Our data indicate that the efficacy of single-room isolation and decolonization therapy can be strongly enhanced by means of a multicomponent, comprehensive MRSA control program. The program was effective despite an increasing "import" of new MRSA cases. Programs of this type may be suited to achieve a downward turn of MRSA figures in Germany.

Invasive Methicillin-Resistant &lt;EMPH TYPE="ITAL"&gt;Staphylococcus aureus&lt;/EMPH&gt; Infections in the United States

As the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed. To describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005. Active, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care-associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA). Incidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains. There were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care-associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100,000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100,000; interval estimate, 92.6-156.9), blacks (66.5 per 100,000; interval estimate, 43.5-63.1), and males (37.5 per 100,000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100,000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care-associated infections in all surveillance areas. Invasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.

Alternatives to Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Vancomycin remains the reference standard for the treatment of systemic infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, as a result of limited tissue distribution, as well as the emergence of isolates with reduced susceptibility and in vitro resistance to vancomycin, the need for alternative therapies that target MRSA has become apparent. New treatment options for invasive MRSA infections include linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. Additionally, a number of new anti-MRSA compounds are in development, including novel glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. The present article will review clinical issues surrounding the newly marketed and investigational agents with activity against MRSA.

The VISA/GISA problem: therapeutic implications

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

Mupirocin Not Really Effective for Eradicating MRSA

Nasal and extranasal colonization by methicillin-resistant Staphylococcus aureus (MRSA), an essential step in invasive MRSA infection, plays a decisive