Current and future treatment options for community-associated MRSA infection.

INTRODUCTION: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia. AREAS COVERED: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic. EXPERT OPINION: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.

Future trends in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection: An in-depth review of newer antibiotics active against an enduring pathogen.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major public health problem. Vancomycin and teicoplanin have been in clinical use for several decades but their drawbacks are well described. In the last 10 years, several antibiotics have been made available for clinical use. Daptomycin and linezolid have been extensively used during this period. Other agents such as ceftaroline, ceftobiprole, dalbavancin, oritavancin, tedizolid and telavancin have been approved by regulatory agencies since 2009. Many others, such as the newer tetracyclines, fluoroquinolones, oxazolidinones and pleuromutilins, are in various stages of development. In addition, an ongoing multicentre trial is investigating the role of combination of vancomycin or daptomycin with ß-lactam antibiotics. This review discusses the role of the newer antibiotics, reflecting the views of the 6th MRSA Consensus Conference meeting of the International Society of Chemotherapy MRSA Working Group that took place in 2016.

An international cross-sectional survey of antimicrobial stewardship programmes in hospitals.

OBJECTIVES: To report the extent and components of global efforts in antimicrobial stewardship (AMS) in hospitals. METHODS: An Internet-based survey comprising 43 questions was disseminated worldwide in 2012. RESULTS: Responses were received from 660 hospitals in 67 countries: Africa, 44; Asia, 50; Europe, 361; North America, 72; Oceania, 30; and South and Central America, 103. National AMS standards existed in 52% of countries, 4% were planning them and 58% had an AMS programme. The main barriers to implementing AMS programmes were perceived to be a lack of funding or personnel, a lack of information technology and prescriber opposition. In hospitals with an existing AMS programme, AMS rounds existed in 64%; 81% restricted antimicrobials (carbapenems, 74.3%; quinolones, 64%; and cephalosporins, 58%); and 85% reported antimicrobial usage, with 55% linking data to resistance rates and 49% linking data to infection rates. Only 20% had electronic prescribing for all patients. A total of 89% of programmes educated their medical, nursing and pharmacy staff on AMS. Of the hospitals, 38% had formally reviewed their AMS programme: reductions were reported by 96% of hospitals for inappropriate prescribing, 86% for broad-spectrum antibiotic use, 80% for expenditure, 71% for healthcare-acquired infections, 65% for length of stay or mortality and 58% for bacterial resistance. CONCLUSIONS: The worldwide development and implementation of AMS programmes varies considerably. Our results should inform and encourage the further evaluation of this with a view to promoting a worldwide stewardship framework. The prospective measurement of well-defined outcomes of the impact of these programmes remains a significant challenge.

A cross-sectional survey of antimicrobial stewardship strategies in UK hospitals.

WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship programmes describe strategies to optimize antimicrobial prescribing and utilization, minimize resistance and improve patient outcomes. Strategies in hospitals are usually implemented by multidisciplinary antimicrobial teams (AMTs). The objective of this study was to describe the profile and activities of AMTs within hospitals in the United Kingdom (UK). METHOD: All hospitals within the UK (n = 836) were included, and a prepiloted questionnaire was mailed to the 'Director of Pharmacy'. Non-respondents were mailed up to two reminder questionnaires at two-weekly intervals. Main outcome measures are as follows: existence and remit of the AMTs; availability of antimicrobial-prescribing policies, aims, scope and methods of dissemination; and monitoring and feedback provided on antimicrobial policy adherence. RESULTS: Response rate was 33% (n = 273). Completed questionnaires analysed were n = 226. Eighty-two (n = 186) of respondents indicated the presence of an AMT within the hospital, with 95% of these (n = 177) reporting an antimicrobial pharmacist as part of the team. All AMTs (n = 186) were involved in development of an antimicrobial policy and almost all (99% n = 184) promoted adherence and restricting use of specific antimicrobials (97% n = 180). Ninety-eight per cent of respondents (n = 222) reported the availability of a local antimicrobial-prescribing policy within the hospital with this disseminated mainly through the hospital intranet (98% n = 217). Adherence to policy was measured mainly through audits measuring the appropriateness of antimicrobial use against the local policy (76% n = 169). Hospitals in England (P = 0·010), tertiary care hospitals (P = 0·021) and bed capacity >500 (P < 0·001) were more likely to have an AMT, as were hospitals with an accident and emergency department (P < 0·001), an infectious diseases unit (P = 0·019) and a microbiology department (P < 0·001). Audits to measure policy adherence were more likely (P < 0·001) if an AMT was present. The only variable retained in bivariate logistic regression was the presence of a microbiology unit, with an odds ratio of 14·1 (95% CI 6·02-33·33, P < 0·001). WHAT IS NEW AND CONCLUSIONS: Although most respondents reported an antimicrobial-prescribing policy, less had an AMT. Despite recent government and regional initiatives, further improvements in antimicrobial stewardship are still required.

MDRO Beijing Consensus Meeting Report: Global burden of multidrug-resistant organisms' current antimicrobial resistance problems in Asia-Pacific.

The International Society of Chemotherapy's Working Groups on Antibiotic Resistance and Antibiotic Stewardship convened a half-day workshop on the burden of multidrug-resistant organisms in the Asia-Pacific. This short review is a summary of their discussion and conclusions.

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Methicillin-resistant Staphylococcus aureus (MRSA) infection continues to be a substantial global problem with significant associated morbidity and mortality. This review summarises the discussions that took place at the 4th MRSA Consensus Conference in relation to the current treatment options for serious MRSA infections and how to optimise whichever therapy is embarked upon. It highlights the many challenges faced by both the laboratory and clinicians in the diagnosis and treatment of MRSA infections.

Treatment of bacteraemia: meticillin-resistant Staphylococcus aureus (MRSA) to vancomycin-resistant S. aureus (VRSA).

Around the world, Staphylococcus aureus remains a dominant cause of bacteraemia. Whilst meticillin resistance remains the major phenotype of concern, various levels of reduced glycopeptide susceptibility are emerging with increasing frequency. The most common MRSA phenotypes now have raised vancomycin MICs within the susceptible range (MICs of 1-2mg/L). This phenomenon, known as MIC creep, is hotly contested and often denied. Key to detecting MIC creep may be to examine isolates fresh, as freezing can allow reversion to wild-type MIC, presumably by loss of mutations. Treatment failure is common with vancomycin and it is uncertain whether higher doses are beneficial. At the other extreme, when enough mutations have accumulated, full VISA status is achieved, although this can also be unstable on storage. Heteroresistant and VISA strains can be considered the inevitable end result of continued MIC creep and are even more likely to fail glycopeptide treatment. Currently full vancomycin resistance is uncommon, with only approximately 20 strains described and confirmed worldwide. Empirical treatment for patients with undefined Gram-positive sepsis can undoubtedly be improved by knowledge of MRSA status, so this is a potential advantage of hospital admission screening. If a patient is risk-assessed or screen-positive for MRSA, and infection is not serious, then vancomycin or teicoplanin is appropriate empirical therapy, providing loading doses are given to achieve therapeutic concentrations immediately (trough 15 mg/L). For life-threatening infections, the glycopeptides are inadequate unless the isolate is likely to be fully susceptible (Etest<1.5mg/L). If not, daptomycin (8-10mg/L) can be used as monotherapy but the MIC should be measured as soon as possible.

Vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infection: End of an era?

Infection with meticillin-resistant Staphylococcus aureus (MRSA) continues to have significant morbidity and mortality. Vancomycin, which has been the mainstay of treatment of invasive MRSA infections, has several drawbacks related to its pharmacological properties as well as varying degrees of emerging resistance. These resistant subpopulations are difficult to detect, making therapy with vancomycin less reliable. The newer agents such as linezolid, daptomycin, ceftaroline, and the newer glycopeptides telavancin and oritavancin are useful alternatives that could potentially replace vancomycin in the treatment of certain conditions. By summarising the discussions that took place at the III MRSA Consensus Conference in relation to the current place of vancomycin in therapy and the potential of the newer agents to replace vancomycin, this review focuses on the challenges faced by the laboratory and by clinicians in the diagnosis and treatment of MRSA infections.

Antimicrobial stewardship: lessons from human healthcare.

This paper focuses on antimicrobial stewardshipin human healthcare, and some concepts possibly transferable to veterinary medicine. Antimicrobial stewardship is a multidisciplinary effort to reduce antimicrobial resistance in human pathogens, when future drug development is dwindling. These strategies encourage healthcare staff to use antimicrobials prudently and, when needed, for as short a duration and with as narrow a spectrum as possible. Various methods are involved in stewardship within the healthcare setting, often implemented simultaneously, which sometimes makes evaluation of specific measures difficult. All healthcare workers must accept responsibility for stewardship, although the role of infectious diseases physicians, microbiologists, pharmacists and infection control practitioners is crucial, as are appropriate surveillance systems and information technology. Support from management and government is also beneficial. Considering the frequent use of antimicrobials in animals, it would seem sensible to apply a similarly critical approach to conserve the efficacy of the antimicrobials still available, now and in the future.

Combination antimicrobial susceptibility testing of multidrug-resistant Stenotrophomonas maltophilia from cystic fibrosis patients.

Stenotrophomonas maltophilia is increasingly being isolated from the respiratory tract of individuals with cystic fibrosis, and, because of its multidrug-resistant nature, the selection of suitable treatment regimens can be problematical. Etest methodology was used to facilitate MIC and antimicrobial combination testing on 80 isolates of S. maltophilia cultured from the respiratory tract of Scottish individuals with cystic fibrosis between 2001 and 2010. The overall rate of susceptibility for the 1,410 MIC tests was 23.1%, and resistance was 68.9%. The most active antimicrobials were minocycline, co-trimoxazole, and doxycycline, with 92.4%, 87.3%, and 58.8% of isolates being susceptible, respectively. Of the 517 combinations, 13.2% were synergistic, with the most synergistic being ticarcillin/clavulanate plus aztreonam (91.7% synergistic), ticarcillin/clavulanate plus colistin (40%), and ticarcillin/clavulanate plus levofloxacin (19.4%). Colistin plus tobramycin was the only antagonistic combination (0.2%). By the median susceptible breakpoint index, the most active combinations were minocycline plus co-trimoxazole (median index, 20), minocycline plus piperacillin-tazobactam (median, 20), and co-trimoxazole plus ceftazidime (median, 16.5). The increasing problem of multidrug resistance in organisms recovered from the respiratory tracts of individuals with cystic fibrosis is not going to go away. Current susceptibility testing methods do not address the slow-growing organisms associated with chronic infection, and interpretive standards are based on achievable blood levels of antimicrobials. Addressing these issues specifically for organisms recovered from the respiratory tracts of individuals with cystic fibrosis should lead to better therapeutic outcomes and improved wellbeing of individuals with cystic fibrosis.

Is vancomycin MIC "creep" method dependent? Analysis of methicillin-resistant Staphylococcus aureus susceptibility trends in blood isolates from North East Scotland from 2006 to 2010.

This study investigated "creep" in vancomycin and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood cultures over a 5-year period in a hospital in the United Kingdom, using different susceptibility testing methods. Trends in vancomycin and daptomycin susceptibility were evaluated by using Etest performed prospectively on isolates in routine clinical practice from December 2007 to December 2010 (n = 102). Comparison was made to results from prospective testing of subcultures at the Scottish MRSA Reference Laboratory, using an automated system (Vitek 2) and retrospective testing (Etest and CLSI reference broth microdilution [BMD] method) of stored isolates from 2006 to 2010 (n = 208). Spearman's rank correlations revealed a significant increase in vancomycin MIC (P = 0.012) and a significant decrease in daptomycin MIC (P = 0.03) by year of study for Etest results from the time of isolation. However, neither trend was replicated in MICs from automated or retrospective testing. The Friedman test revealed a significant difference between vancomycin MICs obtained from the same samples by different testing methods (χ(2) [3 degrees of freedom] = 97; P < 0.001). MICs from automated testing and Etest analysis of stored isolates were significantly lower than those from Etest analysis at the time of isolation for both antibiotics (P < 0.001). Effects of storage on the MIC appeared within the first 6 months of storage. Inconsistent evidence on vancomycin MIC creep and the relevance of the MIC to clinical outcome may arise from differences in susceptibility testing methods, including storage of isolates. There is a need to standardize and streamline susceptibility testing of vancomycin against MRSA.

Universal screening for meticillin-resistant Staphylococcus aureus in acute care: risk factors and outcome from a multicentre study.

BACKGROUND: A Health Technology Assessment (HTA) model on effectiveness of meticillin-resistant Staphylococcus aureus (MRSA) screening in Scotland suggested that universal screening using chromogenic agar was the preferred option in terms of effectiveness and cost. AIM: To test the model's validity through a one-year pilot-study. METHOD: A large one-year prospective cohort study of MRSA screening was carried out in six acute hospitals in NHS Scotland, incorporating 81,438 admissions. Outcomes (MRSA colonization and infection rates) were subjected to multivariable analyses, and trends before and after implementation of screening were compared. FINDINGS: The initial colonization prevalence of 5.5% decreased to 3.5% by month 12 of the study (P < 0.0001). Colonization was associated with the number of admissions per patient, specialty of admission, age, and source of admission (home, other hospital or care home). Around 2% of all admissions with no prior history of MRSA infection or colonization tested positive. Those who were screen positive on admission and not previously known positive were 12 times more likely than those who screened negative to develop infection, increasing to 18 times if they were both screen positive and previously known positive. MRSA infections (7.5 per 1000 inpatient-days overall) also reduced significantly over the study year (P = 0.0209). CONCLUSION: The risk factors identified for colonization and infection indicate that a universal clinical risk assessment may have a role in MRSA screening.

Diagnosis and management of skin and soft-tissue infections (SSTI): a literature review and consensus statement on behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges and resulting in significant morbidity and mortality among patients as well as increased healthcare costs. eight members of the SSTI working group of the Italian Society of infectious Diseases prepared a draft of the statements, grading the quality of each piece of evidence after a careful review of the current literature using MEDLINE database and their own clinical experience. Statements were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America (IDSA). The manuscript was successively reviewed by seven members of the SSTI working group of the international Society of Chemotherapy, and ultimately re-formulated by all e xperts. the microbiological and clinical aspects together with diagnostic features were considered for uncomplicated and complicated SSTIs. Antimicrobial therapy was considered as well -both empirical and targeted to methicillin-resistant Staphylococcus aureus (MRSA) and/or other main pathogens.

A retrospective cohort study into acquisition of MRSA and associated risk factors after implementation of universal screening in Scottish hospitals.

OBJECTIVE: To estimate the proportion of patients who acquire methicillin-resistant Staphylococcus aureus (MRSA) while in hospital and to identify risk factors associated with acquisition of MRSA. DESIGN: Retrospective cohort study. PATIENTS: Adult patients discharged from 36 general specialty wards of 2 Scottish hospitals that had implemented universal screening for MRSA on admission. METHODS: Patients were screened for MRSA on discharge from hospital by using multisite body swabs that were tested by culture. Discharge screening results were linked to admission screening results. Genotyping was undertaken to identify newly acquired MRSA in MRSA-positive patients on admission. RESULTS: Of the 5,155 patients screened for MRSA on discharge, 2.9% (95% confidence interval [CI], 2.43-3.34) were found to be positive. In the subcohort screened on both admission and discharge (n = 2,724), 1.3% of all patients acquired MRSA while in hospital (incidence rate, 2.1/1,000 hospital bed-days in this cohort [95% CI, 1.5-2.9]), while 1.3% remained MRSA positive throughout hospital stay. Three risk factors for acquisition of MRSA were identified: age above 64 years, self-reported renal failure, and self-reported presence of open wounds. On a population level, the prevalence of MRSA colonization did not differ between admission and discharge. CONCLUSIONS: Cross-transmission of MRSA takes place in Scottish hospitals that have implemented universal screening for MRSA. This study reinforces the importance of infection prevention and control measures to prevent MRSA cross-transmission in hospitals; universal screening for MRSA on admission will in itself not be sufficient to reduce the number of MRSA colonizations and subsequent MRSA infections.

Epidemiology and management of candidaemia--a retrospective, multicentre study in five hospitals in the UK.

Candidaemia is associated with high mortality. Despite the fact that Candida species account for close to 10% of all nosocomial bloodstream infections, relatively few studies have investigated the management of candidaemia in hospitals. Our objective was to find out how candidaemia is managed in hospitals. Data relating to all episodes of candidaemia for the year 2008 were retrospectively collected in five centres in Scotland and Wales. A total of 96 candidaemic episodes were recorded in the year 2008, yielding 103 isolates of Candida. Fifty candidaemic episodes were caused by Candida albicans. Fluconazole was the most common agent prescribed for the treatment of candidaemia. There was great variation in the prescribed dose of fluconazole. Forty per cent of patients who survived received <2 weeks of systemic antifungal therapy. Central venous catheters (CVC) were removed in 57% of patients. CVC removal was not associated with better survival. The overall mortality was 40.4%. Management of candidaemia varies between the UK centres and is often inadequate. There is need to have consensus on the dosages of antifungal agents and the duration of therapy. The current guidance on removal of CVC in all cases of candidaemia should be reviewed.