ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers.

SCOPE: The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. METHODS: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. RECOMMENDATIONS: The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.

OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers

The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. Methods: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporinresistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same timepoints and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.

Views and experiences with regard to antibiotic use of hospitalized patients in five European countries: a qualitative descriptive study.

OBJECTIVES: To explore inpatients experiences and views with regard to antibiotics in five European hospitals. METHODS: Qualitative study where a patient-centred framework was used to explore inpatients' experiences concerning antibiotic treatment. A purposeful sample of inpatients treated with antibiotics in five hospitals participated in interviews (all centres) and focus groups (Switzerland only). RESULTS: A total of 31 interviews (five in Belgium, ten in Croatia, nine in France, five in the Netherlands and two in Switzerland) and three focus groups (in Switzerland, 11 participants) were performed. The median age of participants was 61 years (range 33-86 years). The following main themes emerged: (a) patients trust doctors to take the best decisions for them even though communication concerning different antibiotic-related aspects is often insufficient, (b) patients feel that doctors do not prioritize communication due to time constraints and do not seem to adapt information based on patients' preferences, (c) patients differ in their wish to be informed but overall want to be informed on the main aspects in an understandable way, (d) patients often find reassurance in sharing information about their antibiotic treatment with close family, (e) professionals should explore patients' preferences to be involved or not in shared decision making for antibiotic treatment. CONCLUSION: Inpatients often doubt their ability to understand medical information and trust their physicians to take the best decisions for them. Tailored strategies that inform hospitalized patients, acknowledging their concerns and preferences, may be useful to promote patient involvement and to improve communication regarding antibiotic use.

Patient-related determinants of antibiotic use: a systematic review.

OBJECTIVES: We aimed to assess patient-related determinants potentially influencing antibiotic use. METHODS: Studies published in MEDLINE until 30 September 2015 were searched. We included: qualitative studies describing patients' self-reported determinants of antibiotic use; and quantitative studies on either self-reported or objectively assessed determinants associated with antibiotic use. Whenever possible, reported determinants were categorized as 'barriers' or 'facilitators' of responsible antibiotic use. RESULTS: A total of 87 studies from 33 countries were included. Seventy-five (86.2%) were quantitative and described self-reported (45/75, 60.0%), objectively assessed (20/75, 26.7%) or self-reported and objectively assessed (10/75, 13.3%) patient-related determinants. Twelve (12/87, 13.8%) were qualitative studies or had a qualitative and quantitative component. Eighty-six of the studies (98.8%) concerned the outpatient setting. We identified seven broad categories of determinants having an impact on different aspects of antibiotic use (in descending order of frequency): demographic and socio-economic characteristics, patient-doctor interactions (e.g. counselling), treatment characteristics (e.g. administration frequency), attitudes (e.g. expecting antibiotics), access to treatment (e.g. patients' direct costs), characteristics of the condition for which the antibiotic was prescribed (e.g. duration of symptoms), knowledge (e.g. regarding indications for treatment). Most determinants were classified as 'barriers' to responsible antibiotic use. CONCLUSION: A large variety of patient-related determinants impact antibiotic use. The most easily 'modifiable' determinants concern patient-doctor interactions, treatment characteristics and knowledge. Data from the inpatient setting and low- and middle-income countries were underrepresented. Further studies should develop and test interventions that take these determinants into account with the ultimate aim of improving responsible use of antibiotics.

Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study.

OBJECTIVES: We quantified the impact of antibiotics prescribed in primary care for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin-resistant (CIP-RE) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE), while accounting for household clustering. METHODS: Prospective cohort study from January 2011 to August 2013 at primary care sites in Belgium, Poland and Switzerland. We recruited outpatients requiring antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients), outpatients not requiring antibiotics (non-exposed patients), and one to three household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL-PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2 (S3). RESULTS: We included 300 households (205 exposed, 95 non-exposed) with 716 participants. Most exposed patients received nitrofurans (86; 42%) or fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples from 202 (28%) participants. Fluoroquinolone treatment caused transient suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE (aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of samples from 71 (10%) participants, with colonization not associated with antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95% CI 1.3-9.0), respectively. CONCLUSIONS: These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae.