Dominique L. Monnet

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided.

Clostridium difficile infection in Europe: a hospital-based survey

BACKGROUND Little is known about the extent of Clostridium difficile infection in Europe. Our aim was to obtain a more complete overview of C difficile infection in Europe and build capacity for diagnosis and surveillance. METHODS We set up a network of 106 laboratories in 34 European countries. In November, 2008, one to six hospitals per country, relative to population size, tested stool samples of patients with suspected C difficile infection or diarrhoea that developed 3 or more days after hospital admission. A case was defined when, subsequently, toxins were identified in stool samples. Detailed clinical data and stool isolates were collected for the first ten cases per hospital. After 3 months, clinical data were followed up. FINDINGS The incidence of C difficile infection varied across hospitals (weighted mean 4·1 per 10,000 patient-days per hospital, range 0·0-36·3). Detailed information was obtained for 509 patients. For 389 of these patients, isolates were available for characterisation. 65 different PCR ribotypes were identified, of which 014/020 (61 patients [16%]), 001 (37 [9%]), and 078 (31 [8%]) were the most prevalent. The prevalence of PCR-ribotype 027 was 5%. Most patients had a previously identified risk profile of old age, comorbidity, and recent antibiotic use. At follow up, 101 (22%) of 455 patients had died, and C difficile infection played a part in 40 (40%) of deaths. After adjustment for potential confounders, an age of 65 years or older (adjusted odds ratio 3·26, 95% CI 1·08-9·78; p=0·026), and infection by PCR-ribotypes 018 (6·19, 1·28-29·81; p=0·023) and 056 (13·01; 1·14-148·26; p=0·039) were significantly associated with complicated disease outcome. INTERPRETATION PCR ribotypes other than 027 are prevalent in European hospitals. The data emphasise the importance of multicountry surveillance to detect and control C difficile infection in Europe. FUNDING European Centre for Disease Prevention and Control.

Clinical and Economic Impact of Common Multidrug-Resistant Gram-Negative Bacilli

During the last decade, the efforts to combat multidrug-resistant (MDR) microorganisms mainly focused on gram-positive bacteria, namely, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. While a large number of hospitals have implemented more rigorous infection

Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes.

We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries. Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004). Streptococcal resistance is directly associated with antibiotic selection pressure on a national level.

Self-medication with antimicrobial drugs in Europe

Antimicrobial drug self-medication occurs most often in eastern and southern Europe and least often in northern and western Europe.

Carbapenemase-producing Enterobacteriaceae in Europe: A survey among national experts from 39 countries, February 2013

The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to healthcare delivery, although its extent differs substantially from country to country. In February 2013, national experts from 39 European countries were invited to self-assess the current epidemiological situation of CPE in their country. Information about national management of CPE was also reported. The results highlight the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection control measures.

Critical shortage of new antibiotics in development against multidrug-resistant bacteria—Time to react is now ☆

Two commercial databases (Pharmaprojects and Adis Insight R&D) were queried for antibacterial agents in clinical development. Particular attention was given to antibacterial agents for systemic administration. For each agent, reviewers were requested to indicate whether its spectrum of activity covered a set of selected multidrug-resistant bacteria, and whether it had a new mechanism of action or a new target. In addition, PubMed was searched for antibacterial agents in development that appeared in review articles. Out of 90 agents that were considered to fulfil the inclusion criteria for the analysis, 66 were new active substances. Fifteen of these could be systemically administered and were assessed as acting via a new or possibly new mechanism of action or on a new or possibly new target. Out of these, 12 agents were assessed as having documented in vitro activity against antibiotic-resistant Gram-positive bacteria and only four had documented in vitro activity against antibiotic-resistant Gram-negative bacteria. Of these four, two acted on new or possibly new targets and, crucially, none acted via new mechanisms of action. There is an urgent need to address the lack of effective treatments to meet the increasing public health burden caused by multidrug-resistant bacteria, in particular against Gram-negative bacteria.

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

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

Epidemiology of Emerging Methicillin-Resistant Staphylococcus aureus (MRSA) in Denmark: a Nationwide Study in a Country with Low Prevalence of MRSA Infection

ABSTRACT Strict infection control measures introduced during the 1970s have kept the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections extremely low in Denmark. Nevertheless, similarly to other countries, MRSA infections began to appear in the community in the late 1990s. A nationwide surveillance program has collected and stored all MRSA isolates since 1988 and, since 1999, clinical information has been also recorded. We used this information and isolates in a detailed epidemiological and molecular analysis of the 81 MRSA infections identified in Denmark in 2001. MRSA isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, multilocus sequence typing, and SCCmec typing. Comparison of the 45 community-onset MRSA (CO-MRSA) infections with the 36 hospital-acquired MRSA (HA-MRSA) infections showed several striking contrasts. Most CO-MRSA were recovered from skin and soft tissue infections caused by isolates carrying the Panton-Valentine leucocidin toxin genes, and the majority (84%) of isolates belonged to a single clonal type, ST80-IV, which has been found in the community in other European countries. Clone ST80-IV could be traced in Denmark back to 1993. ST80-IV was rarely found in HA-MRSA infections, which belonged to a large number of clonal types, including some pandemic MRSA clones. The low number of HA-MRSA infections and the diversity of MRSA clones in Danish hospitals may be the result of successful infection control measures that prevent spread of clones in hospitals. The mechanism of spread of the ST80-IV clone in the Danish community is not known, and new control measures are needed to control further spread of this and other CA-MRSA clones.

Modelling and forecasting antimicrobial resistance and its dynamic relationship to antimicrobial use: a time series analysis

To investigate the relationship between antimicrobial use and resistance in our hospital, we collected antimicrobial susceptibility and use data from existing microbiology laboratory and pharmacy databases for the period July 1st, 1991-December 31, 1998. The data was analyzed as time series and autoregressive integrated moving average (Box-Jenkins) and transfer function models were built. By using this method, we were able to demonstrate a temporal relationship between antimicrobial use and resistance, to quantify the effect of use on resistance and to estimate the delay between variations of use and subsequent variations in resistance. The results obtained for two antimicrobial-microorganism combinations: ceftazidime-gram-negative bacilli and imipenem-Pseudomonas aeruginosa, are shown as examples.