Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

Activity of fosfomycin and amikacin against fosfomycin-heteroresistant Escherichia coli strains in a hollow-fiber infection model.

Objectives:To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM).Materials and methods:Six fosfomycin-heteroresistant E. coli isolates (4 with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. Fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy alone and in combination were assessed using a HFIM.Results:Five isolates were resistant to fosfomycin by AD and BMD, but all susceptible by GSA. All isolates were considered susceptible to amikacin. Antibiotic combinations were synergistic in two isolates and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64mg/L, although, at 307mg/L, only the normomutators and two hypermutators survived. Four isolates survived under 16mg/L amikacin and none at 45mg/L. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilise bacterial cultures, however, fosfomycin and amikacin combination showed a rapid eradication.Conclusions.There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the combination amikacin-fosfomycin can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.

Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study.

Multi-drug-resistant Acinetobacter baumannii isolates are key pathogens that contribute to the global burden of antimicrobial resistance. This study aimed to investigate the phenotypic and molecular characteristics of carbapenem-resistant A. baumannii (CRAB) isolates from the EURECA clinical trial. In total, 228 CRAB clinical strains were recovered from 29 sites in 10 European countries participating in the EURECA study between May 2016 and November 2018. All strains were reconfirmed centrally for identification and antimicrobial susceptibility testing, and were then subjected to DNA isolation and whole-genome sequencing (WGS), with analysis performed using BacPipe v.1.2.6. K and O typing was performed using KAPTIVE. Overall, 226 (99.1%) strains were confirmed as CRAB isolates. The minimum inhibitory concentration (MIC90) results of imipenem and meropenem were >16 mg/L. WGS showed that the isolates mainly harboured blaOXA-23 (n=153, 67.7%) or blaOXA-72 (n=70, 30.1%). Four blaOXA-72 isolates from Serbia co-harboured blaNDM-1. An IS5 transposase family element, ISAba31, was found upstream of the blaOXA-72 gene harboured on a small (~10-kb) pSE41030-EUR plasmid. The majority of isolates (n=178, 79.1%) belonged to international clone II. Strains belonging to the same sequence type but isolated in different countries or within the same country could be delineated in different clusters by core-genome multi-locus sequence typing (MLST). Whole-genome/core-genome MLST showed high diversity among the isolates, and the most common sequence type was ST2 (n=153, 67.7%). The EURECA A. baumannii strain collection represents a unique, diverse repository of carbapenem-resistant isolates that adds to the existing knowledge of A. baumannii epidemiology and resistance genes harboured by these strains.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade.

OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Interplay among Different Fosfomycin Resistance Mechanisms in Klebsiella pneumoniae.

The objectives of this study were to characterize the role of the uhpT, glpT, and fosA genes in fosfomycin resistance in Klebsiella pneumoniae and evaluate the use of sodium phosphonoformate (PPF) in combination with fosfomycin. Seven clinical isolates of K. pneumoniae and the reference strain (ATCC 700721) were used, and their genomes were sequenced. ΔuhpT, ΔglpT, and ΔfosA mutants were constructed from two isolates and K. pneumoniae ATCC 700721. Fosfomycin susceptibility testing was done by the gradient strip method. Synergy between fosfomycin and PPF was studied by checkerboard assay and analyzed using SynergyFinder. Spontaneous fosfomycin mutant frequencies at 64 and 512 mg/liter, in vitro activity using growth curves with fosfomycin gradient concentrations (0 to 256mg/liter), and time-kill assays at 64 and 307 mg/liter were evaluated with and without PPF (0.623 mM). The MICs of fosfomycin against the clinical isolates ranged from 16 to ≥1,024 mg/liter. The addition of 0.623 mM PPF reduced fosfomycin MIC between 2- and 8-fold. Deletion of fosA led to a 32-fold decrease. Synergistic activities were observed with the combination of fosfomycin and PPF (most synergistic area at 0.623 mM). The lowest fosfomycin-resistant mutant frequencies were found in ΔfosA mutants, with decreases in frequency from 1.69 × 10-1 to 1.60 × 10-5 for 64 mg/liter of fosfomycin. In the final growth monitoring and time-kill assays, fosfomycin showed a bactericidal effect only with the deletion of fosA and not with the addition of PPF. We conclude that fosA gene inactivation leads to a decrease in fosfomycin resistance in K. pneumoniae The pharmacological approach using PPF did not achieve enough activity, and the effect decreased with the presence of fosfomycin-resistant mutations.

A comparative study between real-time PCR and loop-mediated isothermal amplification to detect carbapenemase and/or ESBL genes in Enterobacteriaceae directly from bronchoalveolar lavage fluid samples.

OBJECTIVES: To evaluate and compare the efficacy of real-time PCR (Xpert Carba-R) and loop-mediated isothermal amplification (Eazyplex® SuperBug CRE) for detecting carbapenemase carriage in Enterobacteriaceae directly from bronchoalveolar lavage (BAL). METHODS: Negative BAL samples were spiked with 21 well-characterized carbapenemase-producing Enterobacteriaceae strains to a final concentration of 102-104 cfu/mL. Xpert Carba-R (Cepheid, Sunnyvale, CA, USA), which detects five targets (blaKPC, blaNDM, blaVIM, blaOXA-48 and blaIMP-1), and the Eazyplex® SuperBug CRE system (Amplex-Diagnostics GmbH, Germany), which detects seven genes (blaKPC, blaNDM, blaVIM, blaOXA-48, blaOXA-181, blaCTXM-1 and blaCTXM-9), were evaluated for the detection of these genes directly from BAL samples. RESULTS: Xpert Carba-R showed 100% agreement with carbapenemase characterization by PCR and sequencing for all final bacteria concentrations. Eazyplex® SuperBug CRE showed 100%, 80% and 27% agreement with PCR and sequencing when testing 104, 103 and 102 cfu/mL, respectively. False negative results for Eazyplex® SuperBug CRE matched the highest cycle threshold values for Xpert Carba-R. Hands-on time for both assays was about 15 min, but Eazyplex® SuperBug CRE results were available within 30 min, whereas Xpert Carba-R took around 50 min. CONCLUSIONS: We here describe the successful use of two commercial diagnostic tests, Xpert Carba-R and Eazyplex® SuperBug CRE, to detect bacterial carbapenem resistance genes directly in lower respiratory tract samples. Our results could be used as proof-of-concept data for validation of these tests for this indication.

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections.

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS: Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

OBJECTIVES: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. METHODS: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. RESULTS: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = -0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = -1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = -0.2%, p 0.605). CONCLUSIONS: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.

Current options for the treatment of infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in different groups of patients.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are a frequent cause of invasive infections worldwide. Carbapenems are nowadays the most used drugs to treat these infections. However, due to the increasing rates of resistance to these antimicrobials, carbapenem-sparing alternatives are being investigated. OBJECTIVES AND SOURCES: The aim of this narrative literature review is to summarize the published information on the currently available antibiotics for the treatment of ESBL-E infections, providing specific information on three subgroups of patients: Group 1, patients with severe infections or infections from high-risk sources or in severely immunocompromised patients; Group 2, patients with non-severe infections from intermediate-risk source; and Group 3, patients with non-severe urinary tract infection. CONTENT AND IMPLICATIONS: For patients in Group 1, the current data would support the use of carbapenems. For milder infections, however, particularly urinary tract infections, other non-carbapenem antibiotics can be considered in selected cases, including beta-lactam/beta-lactam inhibitor combinations, cephamycins, temocillin and aminoglycosides. While specific studies should be performed in these situations, individualized decisions may be taken in order to avoid overuse of carbapenems.

Rates, predictors and mortality of community-onset bloodstream infections due to Pseudomonas aeruginosa: systematic review and meta-analysis.

BACKGROUND: Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional. OBJECTIVES: To assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy. DATA SOURCE: A systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases. Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered. INTERVENTION: Empiric antimicrobial therapy for CO-BSI-PA. METHODS: A systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model. RESULTS: Twelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52-141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12-2.98l p 0.02). CONCLUSIONS: CO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.

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.

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.

Development and validation of baseline, perioperative and at-discharge predictive models for postsurgical prosthetic joint infection.

OBJECTIVES: To develop and validate baseline, perioperative and at-discharge risk-scoring systems for postsurgical prosthetic joint infection (PJI) in patients undergoing arthroplasty. METHODS: A multicentre prospective cohort study of patients undergoing hip and knee arthroplasty was performed. Patients were randomly assigned (2:1) to a derivation cohort (DC) or a validation cohort (VC). Multivariable predictive models of PJI were constructed at baseline (preoperative period), perioperative (adding perioperative variables) and at-discharge (adding wound state at discharge). The predictive ability of the models and scores was evaluated by area under the receiving operating characteristic curves (AUROC). RESULTS: The DC and VC included 2324 and 1245 patients, respectively. Baseline model included total hip arthroplasty (THA), revision arthroplasty (RA), Charlson index and obesity. The AUROC for the score was 0.75 and 0.78 in the DC and VC, respectively. Perioperative model included THA, RA, obesity, National Nosocomial Infections Surveillance (NNIS) index ≥2, significant wound bleeding and superficial surgical site infection; the AUROC was 0.81 and 0.77 in the DC and VC, respectively. The at-discharge model included THA, RA, obesity, NNIS index ≥2, superficial surgical site infection and high-risk wound; the AUROC was 0.82 and 0.84 in the DC and VC, respectively. A score ≥8 points provided 99% negative predictive values for all models. CONCLUSIONS: Simple scores for predicting PJI at three different moments of care in patients undergoing arthroplasty were developed and validated. The scores allow early and accurate identification of high-risk individuals in whom enhanced preventive measures and follow-up may be needed. Further external validation is needed.