Reduced Vancomycin Susceptibility Research Articles

Relationship between Vancomycin-Resistant Staphylococcus aureus, Vancomycin-Intermediate S. aureus, High Vancomycin MIC, and Outcome in Serious S. aureus Infections

Vancomycin has been used successfully for over 50 years for the treatment of Staphylococcus aureus infections, particularly those involving methicillin-resistant S. aureus. It has proven remarkably reliable, but its efficacy is now being questioned with the emergence of strains of S. aureus that display heteroresistance, intermediate resistance, and, occasionally, complete vancomycin resistance. More recently, an association has been established between poor outcome and infections with strains of S. aureus with an elevated vancomycin MIC within the susceptible range. This minireview summarizes the definitions, mechanisms, clinical impact, and laboratory identification of reduced vancomycin susceptibility in S. aureus and discusses practical issues for the diagnostic laboratory in testing and interpreting vancomycin susceptibility for S. aureus infections.

Derivation and validation of clinical prediction rules for reduced vancomycin susceptibility in Staphylococcus aureus bacteraemia

Reduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteraemia. We conducted a cohort study of 392 patients with S. aureus bacteraemia within a university health system. The association between RVS, as defined by both Etest [vancomycin minimum inhibitory concentration (MIC) >1·0 μg/ml] and broth microdilution (vancomycin MIC ≥1·0 μg/ml), and patient and clinical variables were evaluated to create separate predictive models for RVS. In total, 134 (34·2%) and 73 (18·6%) patients had S. aureus isolates with RVS by Etest and broth microdilution, respectively. The final model for RVS by Etest included methicillin resistance [odds ratio (OR) 1·51, 95% confidence interval (CI) 0·97-2·34], non-white race (OR 0·67, 95% CI 0·42-1·07), healthcare-associated infection (OR 0·56, 95% CI 0·32-0·96), and receipt of any antimicrobial therapy ≤30 days prior to the culture date (OR 3·06, 95% CI 1·72-5·44). The final model for RVS by broth microdilution included methicillin resistance (OR 2·45, 95% CI 1·42-4·24), admission through the emergency department (OR 0·54, 95% CI 0·32-0·92), presence of an intravascular device (OR 2·24, 95% CI 1·30-3·86), and malignancy (OR 0·51, 95% CI 0·26-1·00). The availability of an easy and rapid clinical prediction rule for early identification of RVS can be used to help guide the timely and individualized management of these serious infections.

Be alert to the alterations in the biological characteristics in heterogeneous vancomycin-intermediate Staphylococcus aureus

The development of reduced vancomycin susceptibility in Staphylococcus aureus in many cases appears to be associated with characteristic changes. These changes may have pitfall of identifying S. aureus by automated testing methods like Vitek 32. In this study, we retested 24 heterogeneous vancomycin-intermediate Staphylococcus haemolyticus (h-VISH) collected in 2008–2010 at the Department of Clinical Microbiology by conventional biochemical tests and polymerase chain reaction (PCR). The heterogeneous vancomycin-intermediate S. aureus (hVISA) reversion test and electron microscopic examination were also used. Six isolates of 24 h-VISH possessed nuc, coa, and 16S rRNA genes, and could be reversed into S. aureus. It suggested that biochemical and morphological changes in hVISA and vancomycin-intermediate S. aureus (VISA) should be considered, and the detection of S. aureus, especially reduced vancomycin susceptibility isolates, requires more attention and different techniques.

Methicillin-resistant Staphylococcus capitis with reduced vancomycin susceptibility causes late-onset sepsis in intensive care neonates.

BackgroundCoagulase-negative staphylococci, mainly Staphylococcus epidermidis, are the most frequent cause of late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) setting. However, recent reports indicate that methicillin-resistant, vancomycin-heteroresistant Staphylococcus capitis could emerge as a significant pathogen in the NICU. We investigated the prevalence, clonality and vancomycin susceptibility of S. capitis isolated from the blood of NICU infants and compared these data to adult patients.Methodology/Principal FindingsWe conducted a retrospective laboratory-based survey of positive blood cultures in NICU infants ≥3 days of age (n = 527) and in adult ICU patients ≥18 years of age (n = 1473) who were hospitalized from 2004 to 2009 in two hospital centers in Lyon, France. S. capitis was the most frequent pathogen in NICU infants, ahead of S. epidermidis (39.1% vs. 23.5% of positive blood cultures, respectively). Conversely, S. capitis was rarely found in adult ICU patients (1.0%) compared to S. epidermidis (15.3%). S. capitis bloodstream isolates were more frequently resistant to methicillin when collected from NICU infants than from adult patients (95.6% vs. 53.3%, respectively). Furthermore, we collected and characterized 53 S. capitis bloodstream isolates from NICU infants and adult patients from six distant cities. All methicillin-resistant S. capitis isolates from NICU infants were clonally related as determined by pulsed-field gel electrophoresis. These isolates harbored a type V-related staphylococcal chromosomal cassette mec element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively).Conclusions/SignificanceA clonal population of methicillin-resistant S. capitis strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting.

Prior Vancomycin Use Is a Risk Factor for Reduced Vancomycin Susceptibility in Methicillin-Susceptible but Not Methicillin-Resistant Staphylococcus aureus Bacteremia

Staphylococcus aureus is a cause of community- and healthcare-acquired infections and is associated with substantial morbidity, mortality, and costs. Vancomycin minimum inhibitory concentrations (MICs) among S. aureus have increased, and reduced vancomycin susceptibility (RVS) may be associated with treatment failure. We aimed to identify clinical risk factors for RVS in S. aureus bacteremia. Case-control. Academic tertiary care medical center and affiliated urban community hospital. Cases were patients with RVS S. aureus isolates (defined as vancomycin E-test MIC >1.0 μg/mL). Controls were patients with non-RVS S. aureus isolates. Of 392 subjects, 134 (34.2%) had RVS. Fifty-eight of 202 patients (28.7%) with methicillin-susceptible S. aureus (MSSA) isolates had RVS, and 76 of 190 patients (40.0%) with methicillin-resistant S. aureus (MRSA) isolates had RVS (P = .02). In unadjusted analyses, prior vancomycin use was associated with RVS (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.00-4.32; P = .046). In stratified analyses, there was significant effect modification by methicillin susceptibility on the association between vancomycin use and RVS (P =.04). In multivariable analyses, after hospital of admission and prior levofloxacin use were controlled for, the association between vancomycin use and RVS was significant for patients with MSSA infection (adjusted OR, 4.02; 95% CI, 1.11-14.50) but not MRSA infection (adjusted OR, 0.87; 95% CI, 0.36-2.13). A substantial proportion of patients with S. aureus bacteremia had RVS. The association between prior vancomycin use and RVS was significant for patients with MSSA infection but not MRSA infection, suggesting a complex relationship between the clinical and molecular epidemiology of RVS in S. aureus.

Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates (‘the MIC Creep’): implications for therapy

Methicillin-resistant S. aureus (MRSA) has emerged as the most common hospital-acquired pathogen and is associated with increased morbidity and mortality compared with other strains. Vancomycin has been the cornerstone of treatment of patients with serious MRSA infections for some decades and while more than 99% of clinical S. aureus isolates remain susceptible to vancomycin, we are beginning to see strains of MRSA with reduced susceptibility. This review discusses this phenomenon, the predictors of infection with such forms of MRSA, and current and future management options.

Daptomycin‐Nonsusceptible, Vancomycin‐Intermediate, Methicillin‐Resistant Staphylococcus aureus Endocarditis

Due to the emergence of Staphylococcus aureus with reduced vancomycin susceptibility, newer antibiotics, including daptomycin, have been used to treat methicillin-resistant S aureus infections. Daptomycin is a cyclic lipopeptide that is approved to treat S aureus bacteremia and right-sided endocarditis, and reports of S aureus with reduced susceptibility to daptomycin are infrequent. To our knowledge, the present report describes the first Canadian case of daptomycin-nonsusceptible, vancomycin-intermediate S aureus infection.

The impact of vancomycin susceptibility on treatment outcomes among patients with methicillin resistant Staphylococcus aureusbacteremia

BackgroundManagement of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia remains a challenge. The emergence of MRSA strains with reduced vancomycin susceptibility complicates treatment.MethodsA prospective cohort study (2005-2007) of patients with MRSA bacteremia treated with vancomycin was performed at an academic hospital. Vancomycin minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for stored MRSA isolates. Cox regression analysis was performed to predict 28-day all-cause mortality.ResultsOne hundred sixty-three patients with MRSA bacteremia were evaluated. One hundred twelve patients (68.7%) had bacteremia due to MRSA with a vancomycin MIC ≥ 2 ug/mL. Among strains with a vancomycin MIC ≥ 2 ug/mL, 10 isolates (8.9%) were vancomycin-intermediate S. aureus (VISA). Thirty-five patients (21.5%) died within 28 days after the diagnosis of MRSA bacteremia. Higher vancomycin MIC was not associated with mortality in this cohort [adjusted hazard ratio (aHR), 1.57; 95% confidence interval (CI), 0.73-3.37]. Vancomycin tolerance was observed in 4.3% (7/162) of isolates and was not associated with mortality (crude HR, 0.62; 95% CI, 0.08-4.50). Factors independently associated with mortality included higher age (aHR, 1.03; 95% CI 1.00-1.05), cirrhosis (aHR, 3.01; 95% CI, 1.24-7.30), and intensive care unit admission within 48 hours after the diagnosis of bacteremia (aHR, 5.99; 95% CI, 2.86-12.58).ConclusionsAmong patients with MRSA bacteremia treated with vancomycin, reduced vancomycin susceptibility and vancomycin tolerance were not associated with mortality after adjusting for patient factors. Patient factors including severity of illness and underlying co-morbidities were associated with the mortality.

Erratum to Endocarditis caused by methicillin-susceptible Staphylococcus aureus with reduced susceptibility to vancomycin: a case report

Staphylococcus aureus is the most common cause of acute infective endocarditis.Recent reports have described heteroresistance to vancomycin associated with methicillin-resistant Staphylococcus aureus. We present the first case report in Argentina of the failure of treatment with vancomycin in endocarditis caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin.We report the case of a 66-year-old Hispanic man with infective endocarditis complicated by septic emboli in the lumbosacral spine and the left iliopsoas muscle. This disease was caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin. He was initially treated with cephalothin and gentamicin but developed a rash caused by beta-lactams and interstitial nephritis. For that reason, the treatment was subsequently switched to vancomycin but he failed to respond. The infection resolved after administration of vancomycin in combination with gentamicin and rifampin.Our case report provides important evidence for the existence of subpopulations of methicillin-susceptible Staphylococcus aureus that have reduced susceptibility to vancomycin which would account for treatment failure. Our case raises an alert about the existence of these strains and highlights the need to determine the vancomycin minimum inhibitory concentration of Staphylococcus aureus to screen for the presence of strains that have reduced vancomycin susceptibility at different infection sites.

Downregulation of RNAIII in vancomycin-intermediate Staphylococcus aureus strains regardless of the presence of agr mutation

Reduced vancomycin susceptibility in Staphylococcus aureus can cause serious problems relating to treatment failure and persistent infection. We investigated vancomycin susceptibility, genetic relationships and transcriptional changes of the accessory gene regulator (agr) in vancomycin-intermediate S. aureus (VISA) strains isolated from South Korea compared with vancomycin-susceptible S. aureus (VSSA) strains. Molecular characterization, population analysis profiling, agr sequencing and transcriptional profiling of RNAIII by real-time RT-PCR were performed. Of 16 VISA strains tested, eight exhibited ST5, agr II and type II SCCmec. The others exhibited ST239, agr I and type III SCCmec. A point mutation in AgrA (Asp8Gly or Ile238Lys) was found in only five VISA strains; no mutations were detected in the other strains. However, RNAIII levels markedly decreased in all VISA strains (mean of 1.39-fold change) compared with the VSSA strains (31.51-fold change) in late-exponential phases (P<0.0001). The downregulation of RNAIII could be an important genetic event in the VISA strains, regardless of the presence or absence of the agr mutation.

Endocarditis caused by methicillin-susceptible Staphylococcus aureus with reduced susceptibility to vancomycin: a case report

IntroductionStaphylococcus aureus is the most common cause of acute infective endocarditis.Recent reports have described heteroresistance to vancomycin associated with methicillin-resistant Staphylococcus aureus. We present the first case report in Argentina of the failure of treatment with vancomycin in endocarditis caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin.Case presentationWe report the case of a 66-year-old Hispanic man with infective endocarditis complicated by septic emboli in the lumbosacral spine and the left iliopsoas muscle. This disease was caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin. He was initially treated with cephalothin and gentamicin but developed a rash caused by beta-lactams and interstitial nephritis. For that reason, the treatment was subsequently switched to vancomycin but he failed to respond. The infection resolved after administration of vancomycin in combination with gentamicin and rifampin.ConclusionOur case report provides important evidence for the existence of subpopulations of methicillin-susceptible Staphylococcus aureus that have reduced susceptibility to vancomycin which would account for treatment failure. Our case raises an alert about the existence of these strains and highlights the need to determine the vancomycin minimum inhibitory concentration of Staphylococcus aureus to screen for the presence of strains that have reduced vancomycin susceptibility at different infection sites.

Impact of rpoB Mutations on Reduced Vancomycin Susceptibility in Staphylococcus aureus

Of 38 vancomycin-intermediate Staphylococcus aureus (VISA) clinical strains, 27 (71%) possessed a mutation(s) in rpoB encoding the β-subunit of RNA polymerase. Furthermore, 95.6% of the rifampin-resistant mutants obtained from 9 methicillin-resistant S. aureus (MRSA) clinical isolates showed decreased vancomycin susceptibilities. These data indicate the involvement of an rpoB mutation in VISA phenotype expression.

Preferential Emergence of Reduced Vancomycin Susceptibility in Health Care-Associated Methicillin-Resistant Staphylococcus aureus Isolates during Continuous-Infusion Vancomycin Therapy in an In Vitro Dynamic Model

Bacterial killing and the development of reduced vancomycin susceptibility during continuous-infusion vancomycin (CIV) therapy were dependent on the area under the concentration-time curve over 24 h divided by the MIC (ƒAUC(24)/MIC), with values of ≥ 240 (equivalent total serum AUC(24)/MICs of ≥ 480) being bactericidal and suppressing emerging resistance in methicillin-resistant Staphylococcus aureus (MRSA). Also, vancomycin therapy was less likely to be bactericidal and 4.4 times more likely to lead to reduced vancomycin susceptibility in health care-associated MRSA than in community-associated MRSA.

Evaluation of the Xpert™ MRSA/SA Blood Culture assay for the detection of Staphylococcus aureus including strains with reduced vancomycin susceptibility from blood culture specimens

The Xpert MRSA/SA Blood Culture (BC) assay (Cepheid, Sunnyvale, CA) was prospectively compared to culture and found to have excellent specificity for both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in BC specimens with a sensitivity of 75% (3/4) and 100% (17/17), respectively. Among 28 heterogeneous vancomycin-intermediate S. aureus (hVISA)/VISA spiked BCs, the assay correctly identified 84.6% VISA and 80% hVISA isolates as MRSA.

Vancomycin Susceptibility Trends and Prevalence of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in Clinical Methicillin-Resistant S. aureus Isolates

Due to the rise in methicillin-resistant Staphylococcus aureus (MRSA) infections and widespread use of vancomycin, MRSA isolates with reduced susceptibility to vancomycin are emerging (i.e., MIC creep). However, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) is unknown due to the difficulty in detecting this phenotype. Recently, Etest glycopeptide resistance detection (GRD) strips have been developed to detect hVISA. This study assessed vancomycin susceptibility in MRSA isolates and determined the prevalence of hVISA by Etest GRD and population analysis profile-area under the curve ratio (PAP-AUC). The genetic backgrounds of 167 MRSA isolates collected from 2000 to 2008 were identified by pulsed-field gel electrophoresis. Vancomycin MICs were determined using Etest and two broth microdilution assays, MicroScan and Sensititre. Etest GRD was performed on all isolates, and those exhibiting a hVISA phenotype were further tested by PAP-AUC. The vancomycin MIC modes remained consistent at 1 μg/ml, as assessed by Sensititre and MicroScan. Etest reported a significant increase (mode MIC = 1.5 μg/ml) in the MIC between 2000 and 2008 (P < 0.01); however, this increase did not reflect a ≥ 2-fold change. In addition, the slight MIC increase did not increase linearly from 2000 to 2008, suggesting biological fluctuation, and is inconsistent with the concept of MIC creep. Etest GRD identified six hVISA isolates, two of which were confirmed to be hVISA by PAP-AUC. In conclusion, reduced vancomycin susceptibility was not detected in our hospital over a 9-year period using three different MIC methodologies, and the hVISA incidence was 1.2%, as determined by Etest GRD and PAP-AUC.

Impacto de la resistencia a la meticilina sobre la mortalidad y vigilancia de la sensibilidad a la vancomicina en bacteriemias causadas por Staphylococcus aureus

Staphylococcus aureus is a major nosocomial pathogen that causes severe morbidity and mortality in many hospitals worldwide. Besides, the incidence of S. aureus bacteremia has significantly increased over the past decades. The aims of this study were to detect the risk factors for methicillin resistance and mortality and to evaluate vancomycin susceptibility in methicillin-resistant isolates. Thus, 39 S. aureus isolates from blood cultures of hospitalized patients with bacteremia were studied in Nueva Clínica Chacabuco Tandil, Buenos Aires, Argentina during 01/2006-12/2008. The overall mortality was 51.3%, which was significantly associated with methicillin resistance (OR: 4.20, IC95%: 1.08-16.32, p: 0.05), even though it was not an independent mortality predictor as it was the mechanical ventilation (OR: 15.99, IC95%: 3.24 - 78.86). Previous surgery (OR: 17.23, IC95%: 1.80-164.60) and hospitalization in intensive care units (OR: 21.12, IC95%: 2.33-191.30) were independent predictors of meticillin-resistance. No isolates were found with reduced vancomycin susceptibility. All the studied isolates were in vitro susceptible to vancomycin with a MIC50 and MIC90 of 0.5 μg/ml.

Management of Staphylococcus aureus bacteremia and endocarditis: progresses and challenges

Staphylococcus aureus is among the leading causes of community-acquired as well as healthcare-associated and hospital-acquired bacteremia and endocarditis. The purpose of this review was to analyze most recent data relevant to the clinical management of S. aureus bacteremia (SAB) and endocarditis. Population-based studies have shown that the incidence of SAB has not decreased in the last years and that healthcare-associated and nosocomial cases continue to account for at least half of SAB. In some areas where methicillin-resistant S. aureus (MRSA) now has become common, MRSA strains with reduced vancomycin susceptibility may have emerged and account for a significant proportion. These strains increase the likelihood of treatment failures, though overall outcomes may often be similarly poor in drug-susceptible S. aureus, which must not be neglected as a pathogen causing potentially lethal infection. Many aspects of drug therapy such as continuous versus intermittent infusion of antibiotics or combination therapy continue to be discussed controversially. Few major progresses in the clinical management have been made in the last few years, but there is evidence that the case fatality can be modestly reduced by efforts focussed on sustained high-quality clinical management. SAB remains a serious, potentially lethal infection, which is too often nosocomial and healthcare-associated. A threat has been the increasing drug resistance of S. aureus seen in many parts of the world and spreading among community isolates. Improved outcomes with new drugs have not been shown convincingly. Large clinical trials assessing the benefits of combination therapies are needed.

New Lipoglycopeptides

Dalbavancin, oritavancin and telavancin are semisynthetic lipoglycopeptides that demonstrate promise for the treatment of patients with infections caused by multi-drug-resistant Gram-positive pathogens. Each of these agents contains a heptapeptide core, common to all glycopeptides, which enables them to inhibit transglycosylation and transpeptidation (cell wall synthesis). Modifications to the heptapeptide core result in different in vitro activities for the three semisynthetic lipoglycopeptides. All three lipoglycopeptides contain lipophilic side chains, which prolong their half-life, help to anchor the agents to the cell membrane and increase their activity against Gram-positive cocci. In addition to inhibiting cell wall synthesis, telavancin and oritavancin are also able to disrupt bacterial membrane integrity and increase membrane permeability; oritavancin also inhibits RNA synthesis. Enterococci exhibiting the VanA phenotype (resistance to both vancomycin and teicoplanin) are resistant to both dalbavancin and telavancin, while oritavancin retains activity. Dalbavancin, oritavancin and telavancin exhibit activity against VanB vancomycin-resistant enterococci. All three lipoglycopeptides demonstrate potent in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis regardless of their susceptibility to meticillin, as well as Streptococcus spp. Both dalbavancin and telavancin are active against vancomycin-intermediate S. aureus (VISA), but display poor activity versus vancomycin-resistant S. aureus (VRSA). Oritavancin is active against both VISA and VRSA. Telavancin displays greater activity against Clostridium spp. than dalbavancin, oritavancin or vancomycin. The half-life of dalbavancin ranges from 147 to 258 hours, which allows for once-weekly dosing, the half-life of oritavancin of 393 hours may allow for one dose per treatment course, while telavancin requires daily administration. Dalbavancin and telavancin exhibit concentration-dependent activity and AUC/MIC (area under the concentration-time curve to minimum inhibitory concentration ratio) is the pharmacodynamic parameter that best describes their activities. Oritavancin's activity is also considered concentration-dependent in vitro, while in vivo its activity has been described by both concentration and time-dependent models; however, AUC/MIC is the pharmacodynamic parameter that best describes its activity. Clinical trials involving patients with complicated skin and skin structure infections (cSSSIs) have demonstrated that all three agents are as efficacious as comparators. The most common adverse effects reported with dalbavancin use included nausea, diarrhoea and constipation, while injection site reactions, fever and diarrhoea were commonly observed with oritavancin therapy. Patients administered telavancin frequently reported nausea, taste disturbance and insomnia. To date, no drug-drug interactions have been identified for dalbavancin, oritavancin or telavancin. All three of these agents are promising alternatives for the treatment of cSSSIs in cases where more economical options such as vancomycin have been ineffective, in cases of reduced vancomycin susceptibility or resistance, or where vancomycin use has been associated with adverse events.

Inducible clindamycin-resistance in clinical staphylococcal isolates with reduced vancomycin susceptibility in a University Teaching Hospital

Inducible clindamycin-resistance in clinical staphylococcal isolates with reduced vancomycin susceptibility in a University Teaching Hospital

The management of methicillin-resistant Staphylococcus aureus infection in Europe

Methicillin-resistant Staphylococcus aureus (MRSA) has been a common nosocomial pathogen since the 1960s and has become a major problem in hospitals worldwide. In 2007, the European Antimicrobial Resistance Surveillance System, a free network that connects more than 600 laboratories in 31 European countries, reported an incidence of MRSA bloodstream infection (BSI) per 100 000 patient-days ranging from 0.2 in Sweden to 24.4 in Portugal [1]. A meta-analysis showed that BSIs due to MRSA are associated with almost two-fold higher mortality than those due to methicillin-susceptible S. aureus [2]. Costs were significantly higher for MRSA BSI than for methicillin-susceptible S. aureus BSI [3]. Therefore, patients and the public increasingly view rates of hospital-acquired MRSA as indicators of quality of patient care. Detection and eradication of MRSA are becoming public health priorities worldwide [4,5]. There has been much debate about the evidence and cost-effectiveness of various infection control policies in controlling MRSA. A multidisciplinary approach should be employed in all settings, including hand hygiene programmes, active surveillance cultures, training of and feedback to healthcare workers, bundles for ventilator-associated pneumonia and central venous catheter-related infections, and environmental programmes [6,7]. A second, even more essential, aspect of the management of MRSA is the treatment of serious infections, which must be prompt and efficacious in order to allow rapid microbiological clearance and successful management of the infection. It is also important to maintain appropriate and constant antibiotic serum concentrations [8–10]. Therapy for MRSA infections has to be decided individually, with consideration of the susceptibility patterns, source of the infection, presence of metastatic sites of infection, comorbidities, and history of patient allergies. A number of questions remain unsolved for the treatment of severe MRSA infections (BSI, endocarditis, osteomyelitis, and pneumonia). Although the glycopeptides still constitute the drugs of choice, there are several concerns about the treatment of MRSA infections: reports of clinical failure with vancomycin treatment regardless of in vitro susceptibility; increasing reports of strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring; and lack of evidence on the efficacy of combination therapy. Moreover, in recent years, pharmaceutical companies have curtailed antibiotic production. Linezolid, daptomycin and tigecycline are the only three really innovative drugs for the treatment of MRSA infections produced in the last 20 years. At present, although the availability of linezolid, daptomycin and tigecycline has definitely improved options for the treatment of MRSA infections, the use of these antibacterials should be carefully monitored, to avoid the future spread of resistance. In addition, the therapeutic roles of the glycopeptides and the relevance of MICs need redefining. The selection of multidrug-resistant MRSA would have significant consequences at the individual level (i.e. increased risk of infection in a colonized patient) and at the institutional level (i.e. increased risk of cross-transmission among hospitalized patients, environmental contamination, and spread of resistance in the community). For the updating of existing guidelines, new trials are needed to compare these new drugs for the treatment of severe infections due to MRSA. Nevertheless, major efforts should be focused on improving specific guidelines for hospital antibiotic use and infection control measures to reduce the nosocomial spread of multidrugresistant MRSA strains. Interestingly, although specific guidelines for the management of MRSA infections have been published in many European countries, there is no common agreement, and treatment is still heterogeneous [11–13]. For certain clinical practices in the management of MRSA, e.g. the use of older drugs, combination therapy, intravenous–oral switch, and duration of treatment, clear evidence does not exist. Therefore, a large survey was proposed to canvass current opinions and practice in the management and treatment of MRSA infection among practitioners across Europe, concentrating on some of these controversial areas. An expert faculty developed a series of questions and gave their own