Update on screening and clinical diagnosis of meticillin-resistant Staphylococcus aureus (MRSA)

Based on the failure of conventional control strategies, some experts and public health officials have promoted active screening to detect asymptomatic carriers of meticillin-resistant Staphylococcus aureus (MRSA) as an effective prevention strategy. Data regarding the (cost-) effectiveness of MRSA screening have recently grown and have produced mixed results. Several clinical studies have not only provided conflicting findings but have also raised numerous issues about the appropriate populations for universal versus targeted screening, screening method(s) and intervention(s). It must also be emphasised that screening alone is not effective. Results should be followed by appropriate interventions to reduce the risk of MRSA transmission and infection. We believe a reasonable approach in most European hospitals with an MRSA on-admission prevalence of <5% is to use targeted rather than universal screening (predominantly with chromogenic media, except for high-risk units and critically ill patients for whom molecular tests could be cost effective), after carefully considering the local MRSA epidemiology, infection control practices and vulnerability of the patient population. This strategy is likely to be cost effective if linked to prompt institution of control measures.     

耐甲氧西林金葡球菌的研究进展

耐甲氧西林金葡球菌(MRSA)在医院和社区获得性感染中具有重要地位,作为出现最频繁的感染性病原菌具有极好的对各种抗菌药物的适应性,并引起耐药.笔者就MRSA的流行病学特征调查和耐药机制研究的进展进行综述,为临床合理用药及新药研发提供参考.     

Preparation of liposomal vancomycin and intracellular killing of meticillin-resistant Staphylococcus aureus (MRSA)

Meticillin-resistant Staphylococcus aureus (MRSA) can persist in alveolar macrophages and contribute to clinical failure of intravenous vancomycin to cure pneumonia. In this study, it was shown that vancomycin in standard solution is unable to kill intracellular MRSA within macrophages. The intracellular viability of MRSA inside macrophages treated with two different formulations of encapsulated liposomal vancomycin prepared using a hydration-dehydration method was then determined. In contrast to the observations with standard vancomycin, treatment with conventional non-pegylated liposomal vancomycin (lacking any surface modification) resulted in a sufficient concentration of antibiotic inside the intracellular compartment of the macrophages to exert a marked bactericidal effect against MRSA. On the other hand, treatment of infected macrophages with surface-pegylated liposomes resulted in no impact on MRSA survival, and this lack of an inhibitory effect may likely reflect delayed phagocytosis owing to the 'stealth' effect by pegylation. This study indicates the potential for a novel liposomal delivery system that may improve clinical vancomycin treatment outcomes by targeting intracellular MRSA infection.     

New insights into meticillin-resistant Staphylococcus aureus (MRSA) pathogenesis, treatment and resistance

Meticillin-resistant Staphylococcus aureus (MRSA) remains one of the principal multiply resistant bacterial pathogens causing serious healthcare-associated and community-onset infections. This paper reviews recent studies that have elucidated the virulence strategies employed by MRSA, key clinical trials of agents used to treat serious MRSA infections, and accumulating data regarding the implications of antibacterial resistance in MRSA for clinical success during therapy. Recent pre-clinical data support a species-specific role for Panton-Valentine leukocidin in the development of acute severe S. aureus infections and have elucidated other virulence mechanisms, including novel modes of internalisation, varying post-invasion strategies (featuring both upregulation and downregulation of virulence factors) and phenotypic switching. Recent double-blind, randomised, phase III/IV clinical trials have demonstrated the efficacy of linezolid and telavancin in hospital-acquired pneumonia (HAP) and complicated skin and skin-structure infections (cSSSIs) caused by MRSA. Tigecycline was non-inferior to imipenem/cilastatin in non-ventilator-associated HAP but was inferior in ventilator-associated pneumonia and has shown a higher rate of death than comparators on meta-analysis. Ceftaroline was clinically and microbiologically non-inferior to vancomycin/aztreonam in the treatment of MRSA cSSSI. Key resistance issues include a rise in vancomycin minimum inhibitory concentrations in MRSA, reports of clonal isolates with linezolid resistance mediated by acquisition of the chloramphenicol/florfenicol resistance gene, and case reports of daptomycin resistance resulting in clinical failure. Novel antimicrobial targets must be identified with some regularity or we will face the risk of untreatable S. aureus infections.     

Activity of ACHN-490 against meticillin-resistant Staphylococcus aureus (MRSA) isolates from patients in US hospitals

The activity of ACHN-490 was evaluated against 493 meticillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2009-2010 from 23 US hospitals. The MIC₅₀ and MIC₉₀ values (minimal inhibitory concentrations for 50% and 90% of the organisms, respectively) for ACHN-490 were 1 and 2 μg/mL compared with 8 and 32 μg/mL for amikacin, 0.5 and 1 μg/mL for gentamicin and 2 and >16 μg/mL for tobramycin. The gene encoding the aminoglycoside-modifying enzyme APH(2″)-Ia/AAC(6′)-Ie was present in 12% of the subset of 84 isolates examined by polymerase chain reaction (PCR), whilst the gene encoding ANT(4′)-Ia was present in 89% of isolates. ACHN-490 activity was not affected by either enzyme.     

Diffusion of meticillin-resistant Staphylococcus aureus USA300 strains in central Italy

Meticillin-resistant Staphylococcus aureus (MRSA) is an outstanding, clonally evolving pathogen that in recent years, under the selective pressure of antibiotics, has acquired the crucial ability to infect people outside of hospitals. MRSA USA300 has progressively become synonymous with severe community-associated staphylococcal disease worldwide. Whilst spreading worldwide, these clones have progressively acquired resistance to several antibiotics and have gained the ability to cause infections in hospital settings. Recently, USA300-related strains showing resistance to several antibiotics have been isolated from community-acquired infections in Italy. This paper reports the high frequency of isolation of USA300-related strains both from community- and hospital-acquired infections in central Italy as well as their genotypic characteristics and antibiotic susceptibility. Analysis of these characteristics by partial least squares discriminant analysis enabled it to be demonstrated that whilst moving from the community to the hospital setting these isolates underwent an adaptive process that generated clones showing distinctive characteristics. These observations further support the hypothesis that the threatening generation of strains combining both resistance and virulence is becoming a reality, and stress the necessity of constant molecular epidemiological surveillance of MRSA.     

Comparison of the effect of ciprofloxacin and Tazocin on the incidence of meticillin-resistant Staphylococcus aureus (MRSA) in an Intensive Care Unit

Meticillin-resistant Staphylococcus aureus (MRSA) is a very significant agent of recalcitrant healthcare-associated infections. A major risk of acquiring such infections is thought to be modulated by the use of particular antimicrobial therapies. The aim of this research was to evaluate prospectively the impact of using either ciprofloxacin or Tazocin (piperacillin+tazobactam) on the incidence of MRSA in an Intensive Care Unit (ICU). The 1-year (2 x 6 months) cross-over study was carried out in a medium-sized (426 beds) teaching hospital. During the first 6-month period, ciprofloxacin was used as the first-line broad-spectrum antibiotic therapy of choice. During the second 6-month period, Tazocin was used as first-line therapy. The incidence of hospital-acquired MRSA (i.e. colonised and/or infected) and rates of compliance of the ICU healthcare workers to optimal hand hygiene practices were recorded throughout the study. The study observed no statistically significant differences (P = 0.1) between MRSA incidence rates in the ICU during the ciprofloxacin (4.4/1000 bed-days) or Tazocin (11.4/1000 bed-days) arms of the study. Interestingly, observing healthcare workers' hand hygiene practices throughout the entire study showed that healthcare workers adhered to these practices 59.2% of the time during the ciprofloxacin arm and 66.0% during the Tazocin arm. The low incidence rates within the unit demonstrated the importance of infection control in limiting the spread of MRSA despite the extensive use of antibiotics in a high-risk setting.     

Prevalence of clinical meticillin-resistant Staphylococcus aureus (MRSA) with high-level mupirocin resistance in Shanghai and Wenzhou,China

A total of 803 clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates obtained from Shanghai and Wenzhou in China were subjected to a screening test by disk diffusion for detection of mupirocin resistance. Among the 803 strains, 53 (6.6%) were mupirocin-resistant. Of these 53 strains, all were discovered by the agar dilution method and polymerase chain reaction (PCR) to be high-level mupirocin-resistant and to harbour the mupA gene. Plasmid DNA hybridisation and curing experiments disclosed that mupA was located on a large plasmid varying in size between 23.0 kb and 52.4 kb in all strains. Susceptibility testing of 10 antibiotics revealed that resistance rates between the Shanghai isolates and the Wenzhou isolates to trimethoprim/sulfamethoxazole and rifampicin differed significantly. Molecular typing by pulsed-field gel electrophoresis (PFGE), staphylococcal chromosomal cassette mec (SCCmec) and staphylococcal protein A (spa) revealed that PFGE A–SCCmec IIIA–spa t030 and PFGE B–SCCmec IIIA–spa t030 represented all of the Wenzhou strains, whereas PFGE N–SCCmec I–spa t318, PFGE P–SCCmec III–spa t037, PFGE I–SCCmec III–spa t037 and PFGE M–SCCmec IIIA–spa t002 were the predominant profiles among Shanghai isolates. These findings indicated that high-level mupirocin resistance mediated by plasmids prevailed in the clinical mupirocin-resistant MRSA from Shanghai and Wenzhou and was mainly related to the transmission of clones.     

Comparison of microbiological and clinical characteristics based on SCCmec typing in patients with community-onset meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia

Molecular identification methods based on the staphylococcal cassette chromosome mec (SCCmec) genotype are more reliable than clinical risk factors and demographic data for differentiating community-acquired and healthcare-associated (HCA) meticillin-resistant Staphylococcus aureus (MRSA). However, patients with community-onset (CO) MRSA infections, defined as a culture-positive sample obtained <48 h after admission and from patients with HCA risk factors, have been infrequently studied. This study compared the clinical profiles of different SCCmec genotypes in this group of patients. From 2004 to 2008, the clinical profiles of 122 non-repetitive patients with CO-MRSA infections at a tertiary medical centre in Taiwan were retrospectively recorded and the molecular characteristics of the isolates were examined. The proportion of SCCmec IV/V genotypes increased from 9.5% to 35.3% from 2004 to 2008. There were no differences in demographic data, underlying diseases, invasive procedures or outcomes between the SCCmec II/III and IV/V groups, except that patients with SCCmec II/III genotypes tended to have more HCA risk factors (3.1 vs. 2.4; P = 0.008). Multivariate logistic regression analysis revealed that having at least four HCA risk factors was independently associated with SCCmec II/III. The sensitivity of recovering SCCmec IV/V genotypes from patients with less than four HCA risk factors was 89.3%. This study revealed the emergence of SCCmec IV/V genotypes in CO-MRSA infections. Although the clinical characteristic boundaries between SCCmec II/III and IV/V diminished, having at least four HCA risk factors made the presence of SCCmec IV/V genotypes less likely in patients with CO-MRSA infections.     

Epidemiology and economic impact of meticillin-resistant Staphylococcus aureus: review and analysis of the literature

In the past 2 decades, meticillin-resistant Staphylococcus aureus (MRSA) has become an increasingly prevalent problem in healthcare, both in acute care institutions and in the community. MRSA is associated with worse outcomes and higher costs for care than meticillin sensitive S. aureus (MSSA). MRSA is a particular problem in several conditions, including hospital-acquired pneumonia (including ventilator-associated pneumonia), skin and soft tissue infections, and diabetic foot infections. Hospitalisation costs associated with MRSA infection are substantially greater than those associated with MSSA infection, and MRSA has wider economic effects that involve indirect costs to the patient and to society. In several countries, infection control programmes have shown potential economic benefits, as savings accruing from strict and effective control have been shown to outweigh the cost of policy implementation. Standard therapy is based on glycopeptide treatment, usually with vancomycin, although resistance to this agent has emerged. Alternative available treatments for MRSA include teicoplanin, tigecycline, daptomycin, quinupristin-dalfopristin and the oxazolidinone, linezolid, which has a higher acquisition cost than vancomycin but is available as intravenous and oral formulations. Despite some limitations of analyses to date, linezolid has been shown to be cost effective in the treatment of MRSA and appears to be related, in part, to the drug's potential for facilitating earlier discharge from hospital. Current opinion favours rational prescribing to maximise therapeutic benefit and minimise the risk of further antibacterial resistance.     

Costs of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) and its control

For most countries badly affected by methicillin-resistant Staphylococcus aureus (MRSA) there have been many years of debate about its relative virulence compared with methicillin-susceptible S. aureus (MSSA) and whether it could be controlled. Now that it is endemic in the majority of hospitals around the world, it is clear that it is at least as virulent as MSSA and is an additional burden of healthcare-acquired infection. There is increasing evidence that, despite this endemicity, control efforts can be successful, although they are often perceived as expensive. In reality, there is a large body of consistent evidence that control is highly cost effective, particularly in the context of the huge societal costs of MRSA and the future ever-greater threats that it poses.