Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review

BackgroundMultidrug-resistant (MDR) microorganism development in the gut is frequently the result of inappropriate antibiotic use. Faecal microbiota transplantation (FMT) restores normal gut microbiota in patients with Clostridium difficile infection. We hypothesized that it may help in decolonizing MDR organisms (MDROs) and in preventing recurrent MDR infections.ObjectivesTo assess FMT efficacy (eradication rate) for decolonizing MDROs and preventing recurrent MDR infections.Data sourcesMedline, Embase and Web of Science (inception through 11 February 2019).Study eligibility criteriaClinical trials, retrospective studies, case reports and case series.ParticipantsPatients with MDR infections or MDRO colonization treated with FMT.InterventionsFMT.MethodsSystematic review.ResultsTwenty-one studies (one randomized clinical trial, seven uncontrolled clinical trials, two retrospective cohort studies, two case series, nine case reports) assessing 192 patients were included. Three studies assessed FMT efficacy in preventing MDR infections; 16 assessed its effect on MDRO colonization; two assessed both. Data from 151 patients were included in the final analyses. In studies with low to moderate risk of bias, the eradication rate was 37.5% to 87.5%. Efficacy was similar in studies looking at infection or colonization and did not differ by length of follow-up. No serious adverse events from FMT were reported. Seven patients died of other causes.ConclusionsFMT could be used as a treatment for eradicating MDR colonization and possibly preventing recurrent MDR infections, once more supporting efficacy and safety data are available. Larger well-designed randomized controlled trials are needed to further explore this therapy.     

The tripartite insurance model (TIM): a financial incentive to prevent outbreaks of infections due to multidrug-resistant microorganisms in hospitals

Healthcare-associated infections caused by multidrug-resistant organisms (MDROs) constitute a major challenge worldwide, but care providers are often not sufficiently incentivized to implement recommended infection prevention measures to prevent the spread of such infections. We propose a new approach which creates incentives for hospitals, external laboratories and insurers to collaborate on preventing MDRO outbreaks by testing more and implementing infection prevention measures. This tripartite insurance model (TIM) redistributes the costs of preventing and combating MDRO outbreaks in a way that all parties benefit from reducing the number of outbreaks.     

Healthcare personnel intestinal colonization with multidrug-resistant organisms

ObjectivesThis study aims to assess the association between patient contact and intestinal carriage of multidrug-resistant organisms (MDRO) by sampling healthcare personnel (HCP) and staff without patient contact.MethodsFor this observational study, we recruited 400 HCP who worked in our 200-bed research hospital and 400 individuals without patient contact between November 2013 and February 2015. Participants submitted two self-collected perirectal swabs and a questionnaire. Swabs were processed for multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci (VRE). Questionnaires explored occupational and personal risk factors for MDRO carriage.ResultsAmong 800 participants, 94.4% (755/800) submitted at least one swab, and 91.4% (731/800) also submitted questionnaires. Extended spectrum β-lactamase-producing organisms were recovered from 3.4% (26/755) of participants, and only one carbapenemase-producing organism was recovered. No VRE were detected. The potential exposure of 68.9% (250/363) of HCP who reported caring for MDRO-colonized patients did not result in a rate of MDRO carriage among HCP (4.0%; 15/379) significantly higher than that of staff without patient contact (3.2%; 12/376; p 0.55).ConclusionsThis is the largest US study of HCP intestinal MDRO carriage. The low colonization rate is probably reflective of local community background rates, suggesting that HCP intestinal colonization plays a minor role in nosocomial spread of MDROs in a non-outbreak setting.Trial Registration. clinicaltrials.gov Identifier: NCT01952158.     

How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection

BackgroundVulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.ObjectivesTo describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints.SourcesExpert guidelines and peer-reviewed clinical studies are encompassed and discussed.ContentIMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case.ImplicationsFuture research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.     

Global epidemiology of antimicrobial resistance in commensal Neisseria species: A systematic review

BackgroundCommensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin.MethodsPubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp.ResultsA total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp.ConclusionThe MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.     

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis

BackgroundCOVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.ObjectiveWe aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.Data sourceA search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.Study eligibilityStudies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.MethodsPooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.ResultsOf 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67–1.47) or proportion (risk ratio 0.91, 95% CI: 0.55–1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92–2.92; risk ratio 1.08, 95% CI: 0.91–1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03–1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).ConclusionThe COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.     

Rapid molecular tests for detection of antimicrobial resistance determinants in Gram-negative organisms from positive blood cultures: a systematic review and meta-analysis

BackgroundTimely detection of antimicrobial (cephalosporin/carbapenem) resistance (AMR) determinants is crucial to the clinical management of bloodstream infections caused by Gram-negative bacteria (GNB).ObjectivesTo review and meta-analyse the evidence for using commercially available molecular tests for the direct detection of AMR determinants in GNB-positive blood cultures (PBCs).Data sourcesPubMed, Scopus and ISI Web of Knowledge.Study eligibility criteriaClinical studies evaluating the performance of two major commercial systems, namely the Verigene® and FilmArray® systems, for rapid testing of GNB-PBCs, in comparison with the phenotypic or genotypic methods performed on GNB-PBC isolates.MethodsLiterature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria and, for meta-analysis of sensitivity and specificity of both systems, bivariate random-effects model.ResultsTwenty studies were identified (3310 isolates) from 2006 to 2019. Nine studies were conducted in East Asia. In 15 studies using phenotypic comparators (1930 isolates), 1014 (52.5%) isolates were Escherichia coli, and 287 (14.9%) of all the isolates displayed AMR phenotypes. In five studies using genotypic comparators (1380 isolates), 585 (42.4%) were E. coli, and 100 (7.2%) of all the isolates displayed AMR genotypes. Pooled sensitivity and specificity estimates for detection of AMR determinants by the Verigene (i.e. CTX-M, IMP, KPC, NDM, OXA and VIM) and/or FilmArray (i.e. KPC) systems were 85.3% (95% CI 79.9%–89.4%) and 99.1% (95% CI 98.2%–99.5%), respectively, across the 15 studies, and 95.5% (95% CI 89.2%–98.2%) and 99.7% (95% CI 99.1%–99.9%), respectively, across the five studies.ConclusionsOur findings show that the Verigene and FilmArray systems may be a valid adjunct to the conventional microbiology (phenotypic or genotypic) methods used to identify AMR in GNBs. The FilmArray system detects only one AMR genotype, namely KPC, limiting its use. Both Verigene and FilmArray systems can miss important cephalosporin/carbapenem resistance phenotypes in a minority of cases. However, the sensitivity and specificity of both systems render them valuable clinical tools in timely identification of resistant isolates. Further studies will establish the prominence of such rapid diagnostics as standard of care in individuals with bloodstream infections.     

Prevalence of multidrug-resistant tuberculosis in prisons: Systematic review and meta-analysis

BackgroundIn the context of prisons, multidrug-resistant tuberculosis (MDR-TB) is a major problem. In this article, we estimate the prevalence of MDR-TB among the population deprived of freedom from countries in South America, Europe, Asia and Africa.MethodsThe articles were retrieved through systematic search at four databases (EMBASE, CINAHL, LILACS and MEDILINE). The meta-analysis was developed by the random effect model, using the Mantel-Haenszel method, with presentation of the aggregated results through the forest plot. The degree of heterogeneity between the studies was verified using Cochran's Q test and I².ResultsOf the 102 articles analyzed, 21 were included in this systematic review. The analysis showed heterogeneity indicated by the Q test (P ?< ?0.001) and I² statistics (I² ?= ?50.52%). The funnel graph and Egger test (P ?< ?0.830) showed symmetry between investigations. The grouped prevalence of MDR-TB was 0.48% (95% CI: 0.02 to 1.32), advancing to 1.15 (95% CI: 0.15 to 2.73) when culture and sensitivity test were considered by the authors. No specific characteristics were significantly associated with differences in prevalence rates in the population deprived of freedom.ConclusionThe study reaffirms the magnitude of MDR-TB in the population deprived of freedom in the world context. Political and technical-scientific efforts should be mobilized to mitigate TB and MDR-TB in prisons and for successful national and international disease control programs.     

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

ScopeThe aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.MethodsThese 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.RecommendationsThe 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.     

Machine learning for microbial identification and antimicrobial susceptibility testing on MALDI-TOF mass spectra: a systematic review

BackgroundThe matrix assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI-TOF MS) technology has revolutionized the field of microbiology by facilitating precise and rapid species identification. Recently, machine learning techniques have been leveraged to maximally exploit the information contained in MALDI-TOF MS, with the ultimate goal to refine species identification and streamline antimicrobial resistance determination.ObjectivesThe aim was to systematically review and evaluate studies employing machine learning for the analysis of MALDI-TOF mass spectra.Data sourcesUsing PubMed/Medline, Scopus and Web of Science, we searched the existing literature for machine learning-supported applications of MALDI-TOF mass spectra for microbial species and antimicrobial susceptibility identification.Study eligibility criteriaOriginal research studies using machine learning to exploit MALDI-TOF mass spectra for microbial specie and antimicrobial susceptibility identification were included. Studies focusing on single proteins and peptides, case studies and review articles were excluded.MethodsA systematic review according to the PRISMA guidelines was performed and a quality assessment of the machine learning models conducted.ResultsFrom the 36 studies that met our inclusion criteria, 27 employed machine learning for species identification and nine for antimicrobial susceptibility testing. Support Vector Machines, Genetic Algorithms, Artificial Neural Networks and Quick Classifiers were the most frequently used machine learning algorithms. The quality of the studies ranged between poor and very good. The majority of the studies reported how to interpret the predictors (88.89%) and suggested possible clinical applications of the developed algorithm (100%), but only four studies (11.11%) validated machine learning algorithms on external datasets.ConclusionsA growing number of studies utilize machine learning to optimize the analysis of MALDI-TOF mass spectra. This review, however, demonstrates that there are certain shortcomings of current machine learning-supported approaches that have to be addressed to make them widely available and incorporated them in the clinical routine.     

Predictors of poor treatment outcomes in multidrug-resistant tuberculosis patients: a retrospective cohort study

ObjectivesWe aimed to determine the characteristics, treatment outcomes and risk factors for poor treatment outcomes among multidrug-resistant (MDR) tuberculosis (TB) patients in Khyber Pakhtunkhwa province, Pakistan.MethodsA retrospective cohort study including all patients with MDR-TB who sought care at the MDR-TB unit in Peshawar was conducted between January 2012 and April 2014. Patients were followed until an outcome of TB treatment was recorded as successful (cured or completed) or unsuccessful. Binary logistic regression was used to identify predictors of poor outcome, i.e. unsuccessful treatment outcomes.ResultsOverall, 535 patients were included. The proportion of female subjects was relatively higher (n = 300, 56.1%) than male subjects. The mean (standard deviation) age of patients was 30.37 (14.09) years. Of 535 patients for whom treatment outcomes were available, 402 (75.1%) were cured, 4 (0.7%) completed therapy, 34 (6.4%) had disease that failed to respond to therapy, 93 (17.4%) died and two (0.4%) defaulted; in total, 129 (24.1%) had an unsuccessful outcome. We found three significant predictors of unsuccessful treatment during multivariate logistic regression: being married (odds ratio (OR) = 2.17, 95% confidence interval (CI) 1.01, 4.66), resistance to second-line drugs (OR = 2.61, 95% CI 1.61, 4.21) and presence of extensively drug-resistant TB (OR = 7.82, 95% CI 2.90, 21.07).ConclusionsApproximately 75% of the treatment success rate set by the Global Plan to Stop TB was achieved. Resistance to second-line drugs and presence of extensively drug-resistant TB are the main risk factors for poor treatment outcomes.     

A systematic review of antimicrobial susceptibility testing as a tool in clinical trials assessing antimicrobials against infections due to gram-negative pathogens

BackgroundAntimicrobial susceptibility testing (AST) is the standard of care for treating bacterial infections. In randomized clinical trials of new antimicrobials, AST might not be performed or reported in real time.ObjectivesTo determine local, real-time laboratory AST performance, its usage in the trial flow, quality control (QC) of the local testing, central AST performance and the effect of using AST categorization on the trials' primary outcomes.Data sourcesWe systematically searched PubMed, Embase, PsychINFO and Web of Science.Eligibility criteriaWe included registered randomized controlled trials published in journals between January 2015 and December 2019.Participants and interventionsWe included trials comparing different antibiotics for the treatment of infections caused predominantly by Gram-negative bacteria.MethodsPrimary outcomes for different trial populations were extracted and differences between trial arms were compared for patients with infections caused by susceptible versus non-susceptible bacteria. Results are described narratively.ResultsOf 32 randomized trials, 25 trials reported that local AST was performed, 1312 reported the local laboratory AST methods, no trial reported QC, but post-hoc referral for AST at a reference laboratory was common. Patients' outcomes were superior when patients with infections due to susceptible and non-susceptible pathogens were compared post hoc (median difference 14%, interquartile range 8%–24%) in trials allowing this comparison (seven antimicrobials), except for colistin, where 14-day mortality was 9% higher when patients were treated with colistin for colistin-susceptible versus colistin-resistant carbapenem-resistant Acinetobacter baumannii. When excluding patients with pathogens that were non-susceptible to either antimicrobial in the trials, the difference in the primary outcome between the trial arms was reduced in five out of six trials.ConclusionsTrials should perform AST to guide patient inclusion or exclusion from the study and consider the impact of the central laboratory susceptibility results on the study outcomes when using post-hoc reference testing.     

Risk factors for carbapenem-resistant Gram-negative bacterial infections: a systematic review

BackgroundRapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions.ObjectivesWe aimed to identify risk factors for CR Gram-negative infection through a systematic literature review.Data sourcesWe searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials.Study eligibility criteriaProspective or retrospective cohort and case–control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible.ParticipantsStudies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters).MethodsSearches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor.ResultsIn total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection.ConclusionsSeveral variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors.     

The antimicrobial potential of algicolous marine fungi for counteracting multidrug-resistant bacteria: phylogenetic diversity and chemical profiling

Marine fungi represent an important but still largely unexplored source of novel and potentially bioactive secondary metabolites. The antimicrobial activity of nine sterile mycelia isolated from the green alga Flabellia petiolata collected from the Mediterranean Sea was tested on four antibiotic-resistant bacterial strains using extracellular and intracellular extracts obtained from each fungal strain. The isolated fungi were identified at the molecular level and assigned to one of the Dothideomycetes, Sordariomycetes or Eurotiomycetes classes. Following assessment of inhibition of bacterial growth (IC₅₀), all crude extracts were subjected to preliminary ¹H NMR and TLC analysis. According to preliminary pharmacologic and spectroscopic/chromatographic results, extracts of fungal strains MUT 4865, classified as Beauveria bassiana, and MUT 4861, classified as Microascacea sp.2, were selected for LC–HRMS analysis. Chemical profiling of antibacterial extracts from MUT 4861 and MUT 4865 by LC HRMS allowed identification of the main components of the crude extracts. Several sphingosine bases were identified, including a compound previously unreported from natural sources, which gave a rationale to the broad spectrum of antibacterial activity exhibited.     

Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review

BackgroundMost of the antimicrobial stewardship (AMS) literature has focused on antimicrobial consumption for the treatment of infections, for the prophylaxis of surgical site infection and for the prevention of endocarditis. The role of AMS for medical antibiotic prophylaxis (AP) has not been adequately addressed.AimsTo identify targets for AMS interventions for medical AP in adult patients.SourcesTargeted searches were conducted in PubMed.ContentThe various indications for medical AP and relevant evidence from practice guidelines are outlined. The following were identified as potential targets for AMS interventions: (a) addressing under-utilization of antibiotic-sparing strategies (e.g. for recurrent urinary tract infections, recurrent soft-tissue infections, recurrent exacerbations associated with bronchiectasis or chronic obstructive pulmonary disease), (b) reducing unnecessary AP beyond recommended indications (e.g. for acute pancreatitis, bite wounds, or urinary catheter manipulations), (c) reducing the use of AP with a broader spectrum than necessary, (d) reducing the use of AP for longer than the recommended duration (e.g. AP for prevention of osteomyelitis in open fractures or AP in high-risk neutropenia), (e) evaluating the role of antibiotic cycling to prevent the emergence of resistance during prolonged AP (e.g. in recurrent urinary tract infections or prophylaxis for spontaneous bacterial peritonitis), and (f) addressing research gaps regarding appropriate indications or antibiotic regimens for medical prophylaxis.ImplicationsThis review summarizes current trends in AP and proposes targets for AMS interventions.     

The methodology of surveillance for antimicrobial resistance and healthcare-associated infections in Europe (SUSPIRE): a systematic review of publicly available information

ObjectivesSurveillance is a key component of any control strategy for healthcare-associated infections (HAIs) and antimicrobial resistance (AMR), and public availability of methodologic aspects is crucial for the interpretation of the data. We sought to systematically review publicly available information for HAIs and/or AMR surveillance systems organized by public institutions or scientific societies in European countries.MethodsA systematic review of scientific and grey literature following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed. Information on HAIs and/or AMR surveillance systems published until 31 October 2016 were included.ResultsA total of 112 surveillance systems were detected; 56 from 20 countries were finally included. Most exclusions were due to lack of publicly available information. Regarding AMR, the most frequent indicator was the proportion of resistant isolates (27 of 34 providing information, 79.42%); only 18 (52.9%) included incidence rates; the data were only laboratory based in 33 (78.5%) of the 42 providing this information. Regarding HAIs in intensive care units, all 22 of the systems providing data included central line–associated bloodstream infections, and 19 (86.3%) included ventilator-associated pneumonia and catheter-associated urinary tract infections; incidence density was the most frequent indicator. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22, 95.5%).ConclusionsPublicly available information about the methods and indicators of the surveillance system is frequently lacking. Despite the efforts of European Centre for Disease Control and Prevention (ECDC) and other organizations, wide heterogeneity in procedures and indicators still exists.     

Reduced susceptibility to chlorhexidine disinfectant among New Delhi metallo-beta-lactamase-1 positive Enterobacteriaceae and other multidrug-resistant organisms: Report from a tertiary care hospital in Karachi,Pakistan

We analysed susceptibility of multidrug-resistant organisms (MDROs) including New Delhi metallo-beta-lactamase-1 positive Enterobacteriaceae to chlorhexidine and compared results to their susceptible counterparts. Susceptibilities of chlorhexidine digluconate in a standard (CHX-S) preparation and two commercial disinfectants containing different CHX concentrations (2% w/v and 4% w/w) were performed. MDROs had narrower range of higher CHX-S minimum inhibitory concentrations (MICs) as compared to pan-sensitive organisms. The MIC values for commercial disinfectants products for MDROs were many folds higher (20–600 times), than CHX-S for in vitro use. Increasing antibiotic resistance among bacterial isolates can be an indirect marker of reduced susceptibility to chlorhexidine in hospital setting.     

Clofazimine improves clinical outcomes in multidrug-resistant tuberculosis: a randomized controlled trial

Objectives

We carried out a randomized multicentre study in China to investigate whether the clofazimine would improve the efficacy of the standardized regimen in patients with multidrug-resistant tuberculosis (MDR-TB).

The quality of studies evaluating antimicrobial stewardship interventions: a systematic review

BackgroundAntimicrobial stewardship aims to optimize antibiotic use and minimize selection of antimicrobial resistance. The methodological quality of published studies in this field is unknown.AimsOur objective was to perform a comprehensive systematic review of antimicrobial stewardship research design and identify features which limit validity and translation of research findings into clinical practice.SourcesThe following online database was searched: PubMed.Study eligibility criteriaStudies published between January 1950 and January 2017, evaluating any antimicrobial stewardship intervention in the community or hospital setting, without restriction on study design or outcome.ContentWe extracted data on pre-specified design quality features and factors that may influence design choices including (1) clinical setting, (2) age group studied, (3) when the study was conducted, (4) geographical region, and (5) financial support received. The initial search yielded 17 382 articles; 1008 were selected for full-text screening, of which 825 were included. Most studies (675/825, 82%) were non-experimental; 104 (15%) used interrupted time series analysis, 41 (6%) used external controls, and 19 (3%) used both. Studies in the community setting fulfilled a median of five out of 10 quality features (IQR 3–7) and 3 (IQR 2–4) in the hospital setting. Community setting studies (25%, 205/825) were significantly more likely to use randomization (OR 5.9; 95% CI 3.8–9.2), external controls (OR 5.6; 95% CI 3.6–8.5), and multiple centres (OR 10.5; 95% CI 7.1–15.7). From all studies, only 48% (398/825) reported clinical and 23% (190/825) reported microbiological outcomes. Quality did not improve over time.ImplicationsOverall quality of antimicrobial stewardship studies is low and has not improved over time. Most studies do not report clinical and microbiological outcome data. Studies conducted in the community setting were associated with better quality. These limitations should inform the design of future stewardship evaluations so that a robust evidence base can be built to guide clinical practice.