Antibiotic and antimicrobial resistance

We describe three cases of bloodstream infection caused by colistin-resistant Escherichia coli in patients in a tertiary hospital in Italy, between August 2016 and January 2017. Whole genome sequencing detected the mcr-1 gene in three isolated strains belonging to different sequence types (STs). This occurrence of three cases with mcr-1-positive E. coli belonging to different STs in six months suggests a widespread problem in settings where high multidrug resistance is endemic such as in Italy.

As antibiotic consumption rates between hospitals can vary depending on the characteristics of the patients treated, risk-adjustment that compensates for the patient-based variation is required to assess the impact of any stewardship measures. The aim of this study was to investigate the usefulness of patient-based administrative data variables for adjusting aggregate hospital antibiotic consumption rates. Data on total inpatient antibiotics and six broad subclasses were sourced from 34 acute hospitals from 2006 to 2014. Aggregate annual patient administration data were divided into explanatory variables, including major diagnostic categories, for each hospital. Multivariable regression models were used to identify factors affecting antibiotic consumption. Coefficient of variation of the root mean squared errors (CV-RMSE) for the total antibiotic usage model was very good (11%), however, the value for two of the models was poor (> 30%). The overall inpatient antibiotic consumption increased from 82.5 defined daily doses (DDD)/100 bed-days used in 2006 to 89.2 DDD/100 bed-days used in 2014; the increase was not significant after risk-adjustment. During the same period, consumption of carbapenems increased significantly, while usage of fluoroquinolones decreased. In conclusion, patient-based administrative data variables are useful for adjusting hospital antibiotic consumption rates, although additional variables should also be employed.

We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad-spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing.

This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003–2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003–2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003–2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden.

Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012–15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.

Recently, the plasmid-mediated colistin resistance gene mcr-1 was found in Enterobacteriaceae from humans, pigs and retail meat in China. Several reports have documented global presence of the gene in Enterobacteriaceae from humans, food animals and food since. We screened several well-characterised strain collections of Enterobacteriaceae, obtained from retail chicken meat and hospitalised patients in the Netherlands between 2009 and 2015, for presence of colistin resistance and the mcr-1 gene. A total of 2,471 Enterobacteriaceae isolates, from surveys in retail chicken meat (196 isolates), prevalence surveys in hospitalised patients (1,247 isolates), clinical cultures (813 isolates) and outbreaks in healthcare settings (215 isolates), were analysed. The mcr-1 gene was identified in three (1.5%) of 196 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from retail chicken meat samples in 2009 and 2014. Two isolates were obtained from the same batch of meat samples, most likely representing contamination from a common source. No mcr-1-positive isolates were identified among 2,275 human isolates tested. All mcr-1-positive isolates were colistin-resistant (minimum inhibitory concentration (MIC) > 2 mg/L). Our findings indicate that mcr-1-based colistin-resistance currently poses no threat to healthcare in the Netherlands. They indicate however that continued monitoring of colistin resistance and its underlying mechanisms in humans, livestock and food is needed.

Colistin resistance was investigated in 1,696 isolates collected from 2007 to 2014 within the frame of the French livestock antimicrobial resistance surveillance programme. The mcr-1 gene was detected in all commensal Escherichia coli isolates with a minimum inhibitory concentration to colistin above the 2 mg/L cut-off value (n=23). In poultry, mcr-1 prevalence was 5.9% in turkeys and 1.8% in broilers in 2014. In pigs, investigated in 2013, this prevalence did not exceed 0.5%. These findings support that mcr-1 has spread in French livestock.

Antimicrobial resistance is recognised as a growing problem that seriously threatens public health and requires prompt action. Concerns have therefore been raised about the potential harmful effects of making antibiotics available without prescription. Because of the very serious concerns regarding further spread of resistance, the over-the-counter (OTC) availability of antibiotics was analysed here. Topical and systemic OTC antibiotics and their indications were determined across 26 European Union (EU) countries and Norway by means of a European survey. We identified a total of 48 OTC products containing 20 different single antibiotics and three antibiotic combinations as active substances, used mainly as topical preparations in short treatment courses. Given the relevance of these medicines and the increasing risk of antimicrobial resistance, it is important to limit the availability of OTC antibiotics and to monitor their use.