Fiona M. MacKenzie

Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods.

This article reviews recent findings on the global epidemiology of healthcare-acquired/associated (HA), community-acquired/associated (CA) and livestock-associated (LA) meticillin-resistant Staphylococcus aureus (MRSA) and aims to reach a consensus regarding the harmonisation of typing methods for MRSA. MRSA rates continue to increase rapidly in many regions and there is a dynamic spread of strains across the globe. HA-MRSA is currently endemic in hospitals in most regions. CA-MRSA clones have been spreading rapidly in the community and also infiltrating healthcare in many regions worldwide. To date, LA-MRSA is only prevalent in certain high-risk groups of workers in direct contact with live animals. CA-MRSA and LA-MRSA have become a challenge for countries that have so far maintained low rates of MRSA. These evolutionary changes have resulted in MRSA continuing to be a major threat to public health. Continuous efforts to understand the changing epidemiology of S. aureus infection in humans and animals are therefore necessary, not only for appropriate antimicrobial treatment and effective infection control but also to monitor the evolution of the species. The group made several consensus decisions with regard to harmonisation of typing methods. A stratified, three-level organisation of testing laboratories was proposed: local; regional; and national. The functions of, and testing methodology used by, each laboratory were defined. The group consensus was to recommend spa and staphylococcal cassette chromosome mec (SCCmec) typing as the preferred methods. Both are informative in defining particular strain characteristics and utilise standardised nomenclatures, making them applicable globally. Effective communication between each of the different levels and between national centres was viewed as being crucial to inform and monitor the molecular epidemiology of MRSA at national and international levels.

Antimicrobial drug use and methicillin-resistant Staphylococcus aureus, Aberdeen, 1996-2000.

Relationships between antimicrobial use and MRSA prevalence are analyzed in Aberdeen, Scotland.

An outbreak of multiply-resistant Klebsiella pneumoniae in the Grampian region of Scotland

A predominantly hospital-based outbreak of multiply-resistant Klebsiella pneumoniae capsular type K2 (MRK) expressing expanded spectrum betalactamase (ESBL) activity and fully sensitive only to the carbapenems and amikacin is described. The organism was isolated from 283 patients between March 1992 and September 1995. The outbreak started in the intensive care unit (ICU) of a major acute hospital and spread through surgical wards, a medical ward, a geriatric unit in a separate hospital and various other local hospitals. Environmental screening revealed extensive ward contamination. The decline of the outbreak after the spring of 1995 coincided with the re-emphasis of standard infection control procedures and the launch of a works programme aimed at addressing underlying sites of environmental contamination. Of the 283 cases, 166 (59.0%) were detected through a specially instigated case finding programme. The MRK caused 11 cases of septicaemia, two postoperative intra-abdominal abscesses, one case of postoperative meningitis, 102 cases of urinary tract infection and 28 wound infections and was isolated from the respiratory tracts of five patients with ventilator associated pneumonia. The difficulty in controlling the outbreak is ascribed to heavy environmental contamination, frequent inter- and intra-hospital patient transfers and prolonged carriage of the outbreak strain.

Antibiotic stewardship and consumption: findings from a pan-European hospital study

OBJECTIVES Much has been written about antibiotic stewardship although less is known about the structure and content of antibiotic policies at hospital level. As part of the European Commission Concerted Action Antibiotic Resistance Prevention And Control (ARPAC) Project, data on antibiotic stewardship were collated and relationships investigated by antibiotic consumption in European hospitals. METHODS A questionnaire survey on antibiotic stewardship factors was completed by 170 hospitals from 32 European countries. Data on committees, antibiotic formularies and policies addressing empirical therapy and prophylaxis were collated. Data on antibiotic use, expressed as defined daily doses per 100 occupied bed-days (DDD/100 BD), were provided by 139 hospitals from 30 countries, and 124 hospitals provided both data sets. Six key indicator stewardship variables were analysed by European region, case mix and antibiotic consumption. RESULTS Hospitals from Northern and Western Europe were more likely to convene antibiotic committees or drugs and therapeutic committees compared with those from Southern and South-Eastern Europe (P < 0.001). One-fifth of hospitals had neither an antibiotic committee nor a policy. Hospital antibiotic policies commonly included recommendations on individual drugs, drug choices, dosage, duration and route but were less likely to contain information on side effects and cost. There were no significant differences by median total (J01) antibiotic consumption, although other antibiotic subgroups differed by stewardship indicators. CONCLUSIONS Policies and practices relating to antibiotic stewardship varied considerably across European hospitals. These data provide a benchmark for newer European strategies tackling antibiotic resistance. More work is required to achieve harmonization of recommended practice, particularly in hospitals from Southern Europe.

Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long‐term antibiotic therapy

Long‐term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of protected compartments have elegantly demonstrated their potential in selecting novel variants. However, comparable data from patients have been rare. In this study, extended antibiotic therapy in a single patient suffering from multiple infected liver cysts has provided the opportunity to observe and analyse the molecular evolution of antibiotic resistance. Each isolate has the same basic ompC gene sequence that is distinct from other Escherichia coli isolates, which suggests that they derive from the same founder population. However, the isolates differ in their auxotrophic markers, in the pI values of their dominant β‐lactamase activities and in the mutations in the promoter region of the ampC gene leading to increased expression of the AmpC enzyme. The data provide strong evidence for a single focal infection expanding via parallel pathways of evolution to give a range of antibiotic‐resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.

Meticillin-resistant Staphylococcus aureus (MRSA): screening and decolonisation

Meticillin-resistant Staphylococcus aureus (MRSA) infections are of increasing importance to clinicians, public health agencies and governments. Prevention and control strategies must address sources in healthcare settings, the community and livestock. This document presents the conclusions of a European Consensus Conference on the role of screening and decolonisation in the control of MRSA infection. The conference was held in Rome on 5-6 March 2010 and was organised jointly by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC). In an environment where MRSA is endemic, universal or targeted screening of patients to detect colonisation was considered to be an essential pillar of any MRSA control programme, along with the option of decolonising carriers dependent on relative risk of infection, either to self or others, in a specific setting. Staff screening may be useful but is problematic as it needs to distinguish between transient carriage and longer-term colonisation. The consequences of identification of MRSA-positive staff may have important effects on morale and the ability to maintain staffing levels. The role of environmental contamination in MRSA infection is unclear, but screening may be helpful as an audit of hygiene procedures. In all situations, screening procedures and decolonisation carry a significant cost burden, the clinical value of which requires careful evaluation. European initiatives designed to provide further information on the cost/benefit value of particular strategies in the control of infection, including those involving MRSA, are in progress.

Staphylococcus aureus carriage among participants at the 13th European Congress of Clinical Microbiology and Infectious Diseases.

The aim of this study was to measure the rate of Staphylococcus aureus nasal colonization among attendees of the 13th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), particularly with regard to methicillin-resistant (MRSA) strains. The 31.4% rate of Staphylococcus aureus colonization detected among the participants was in line with colonization rates reported previously for healthcare workers. A statistical difference was found between the rates of Staphylococcus aureus carriage in physicians (37.4%) and non-physicians (21.7%) but not between males (35.0%) and females (28.9%). Only one participant (a Belgian physician) was found to carry MRSA. Surprisingly, the rate of methicillin-susceptible Staphylococcus aureus carriage was significantly higher among participants from countries with a low prevalence of MRSA.

The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals

This observational, cross-sectional study describes the role played by clinical microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals. A total of 170 acute care hospitals from 32 European countries returned a questionnaire on antibiotic policies and practices implemented in 2001. Data on antibiotic use, expressed as Defined Daily Doses per 100 occupied bed-days (DDD/100 BD) were provided by 139 hospitals from 30 countries. A total of 124 hospitals provided both datasets. 121 (71%) of Clinical Microbiology departments and 66 (41%) of Pharmacy departments provided out of hours clinical advice. 70 (41%) of microbiology/infectious disease specialists and 28 (16%) of pharmacists visited wards on a daily basis. The majority of laboratories provided monitoring of blood cultures more than once per day and summary data of antibiotic susceptibility testing (AST) for empiric prescribing (86% and 73% respectively). Most of the key laboratory and pharmacy-led initiatives examined did not vary significantly by geographical location. Hospitals from the North and West of Europe were more likely to examine blood cultures more than once daily compared with other regions (p < 0.01). Hospitals in the North were least likely routinely to report susceptibility results for restricted antibiotics compared to those in the South-East and Central/Eastern Europe (p < 0.01). Hospital wards in the North were more likely to hold antibiotic stocks (100%) compared with hospitals in the South-East which were least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were least likely to dispense antibiotics on an individual patient basis (16%) compared with hospital pharmacies from Southern Europe (60%) (p = 0.01). Hospitals that routinely reported susceptibility results for restricted antibiotics had significantly lower median total antibiotic use in 2001 (p < 0.01). Hospitals that provided prescribing advice outside normal working hours had significantly higher antibiotic use compared with institutions that did not provide this service (p = 0.01). A wide range of antibiotic stewardship measures was practised in the participating hospitals in 2001, although there remains great scope for expansion of those overseen by pharmacy departments. Most hospitals had active antibiotic stewardship programmes led by specialists in infection, although there is no evidence that these were associated with reduced antibiotic consumption. There was also no evidence that pharmacy services reduced the amount of antibiotics prescribed.

Molecular epidemiology of a large outbreak of multiresistant Klebsiella pneumoniae

An outbreak of multiresistant Klebsiella pneumoniae has continued in the Grampian Region of Scotland since 1992. The organism, which generally produces an extended-spectrum beta-lactamase (ESBL), has spread to several hospitals and nursing homes. DNA from 80 possible outbreak isolates was digested with the restriction endonucleases XbaI and SpeI, and the patterns obtained by pulsed-field gel electrophoresis were compared. Restriction patterns of 79 of the isolates were found to be highly similar with both restriction enzymes, whereas one isolate was unrelated. The outbreak isolates were divided into six subtypes with SpeI and 16 subtypes with XbaI. These subtypes were independent of antibiotic susceptibility pattern, date of isolation and ward of origin, but the XbaI subtype did correlate with the SpeI subtype. It was concluded that the Klebsiella isolates of this outbreak were clonally related.

Report of a hospital neonatal unit outbreak of community-associated methicillin-resistant Staphylococcus aureus.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) with the type IV staphylococcal chromosomal cassette mec (SCCmec) is rarely reported as being acquired in hospital. We report a hospital outbreak, in Grampian, Scotland, of eight cases of skin and soft-tissue infections due to such a strain. All patients had been in the labour, delivery and maternity units of a small community hospital during a 7-month period. Typing by pulsed-field gel electrophoresis showed the isolates to be a single strain closely related to the USA800 lineage (paediatric clone) and additional typing confirmed it as ST5-MRSA-IV. Genes for exfoliative toxin A (ETA) and enterotoxin D were detected by PCR in all the isolates although none carried the Panton-Valentine leukocidin gene. Region-wide surveillance of over 6000 MRSA isolates collected from 1998 to 2004 showed that 95 (1.6%) were closely related to the outbreak strain although only 60 carried the ETA gene. The strain has not been seen elsewhere in Scotland.