One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients.

Letermovir is the first approved drug for cytomegalovirus (CMV) infection prophylaxis in adult patients who are CMV positive undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Because CMV infection risk varies from patient to patient, we evaluated whether a risk-based strategy could be effective. In this single-center study, all consecutive adult patients who were CMV positive and underwent allo-HCT between 2015 and 2021 were included. During period 1 (2015-2017), letermovir was not used, whereas during period 2 (2018-2021), letermovir was used in patients at high risk but not in patients at low risk, except in those receiving corticosteroids. In patients at high risk, the incidence of clinically significant CMV infection (csCMVi) in period 2 was lower than that in period 1 (P < .001) by week 14 (10.5% vs 51.6%) and week 24 (16.9% vs 52.7%). In patients at low risk, although only 28.6% of patients received letermovir in period 2, csCMVi incidence was also significantly lower (P = .003) by week 14 (7.9% vs 29.0%) and week 24 (11.2% vs 33.3%). Among patients at low risk who did not receive letermovir (n = 45), 23 patients (51.1%) experienced transient positive CMV DNA without csCMVi, whereas 17 patients (37.8%) experienced negative results. In both risk groups, the 2 periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and nonrelapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in patients at high risk but allows some patients at low risk to not use letermovir.

Evolution of antibiotic treatments for healthcare-associated infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae in France.

BACKGROUND: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) remain a public health challenge. AIM: We traced the evolution of antibiotics prescribed for patients with ESBLE-healthcare associated infections (ESBLE-HAI) between 2012 and 2017, with a specific focus on treatments for lower urinary tract infections (LUTI). METHODS: We used the 2012 and 2017 French point prevalence survey data. Patients with ESBLE-HAI were defined as those diagnosed with at least one Enterobacteriaceae with ESBL production. Patients with LUTI caused by ESBLE (ESBLE-LUTI) were defined as those with LUTI as the reported infection site and diagnosed with ESBLE. We only analysed treatments intended for HAI. RESULTS: In 2017, more than half of treatments for ESBLE-HAIs were ß-lactams. While from 2012 to 2017 the proportion of carbapenem treatments decreased from 30% to 25%, penicillin treatments doubled. Among patients treated for ESBLE-LUTI, a larger proportion received a single antibiotic in 2017. The most frequently prescribed antibiotics for these infections were amoxicillin/clavulanic acid, nitrofurantoin and ofloxacin. More than one out of six treatments lasted for more than 7 days. Carbapenem use was halved between 2012 and 2017, and decreases were likewise observed for aminoglycosides. CONCLUSION: In accordance with French recommendations, comparison of the two most recent French point prevalence surveys showed an evolution in ESBLE-HAI treatment, especially for ESBLE-LUTI. However, treatment durations remained longer than recommended. Data from the 2022 survey should provide insights on the future evolution of prescription trends.

A case of subacute bowel obstruction revealing slowly-evolutive gastro-intestinal mucormycosis following allogeneic hematopoietic cell transplantation.

Gastro-intestinal mucormycosis (GIMM) is a highly lethal invasive fungal disease partly because of a challenging diagnosis. An allogeneic hematopoietic cell transplant recipient experienced bowel obstruction caused by slowly-evolutive gastro-intestinal mucormycosis and was successfully treated with surgery and antifungal therapy. Pathological findings revealed a granuloma without angio-invasion, which is unusual in this fungal disease and has incomplete similarities with an immune reconstitution inflammatory syndrome. Mucorales-specific PCR in both serum and resected tissue was positive and helped assessing the diagnosis. GIMM should be considered in front of unexplained granulomatosis or bowel obstruction in immunocompromised patients.

Practical checklist for implementation of antifungal stewardship programmes.

Introduction. Antifungal stewardship programmes are needed in healthcare facilities to limit the overuse or misuse of antifungals, which are responsible for an increase in antifungal resistance.Hypothesis/Gap Statement. Core recommendations for antifungal stewardship were published by the Mycoses Study Group Education and Research Consortium, while the Centers for Disease Control and Prevention (CDC) provided a Core Elements of Hospital Antibiotic Stewardship Programs checklist. The recommendations offer global core elements for best practices in antifungal stewardship, but do not provide a framework for the implementation of antifungal stewardship programmes in healthcare facilities.Aim. In line with the recommendations, it is of the utmost importance to establish a practical checklist that may be used to implement antifungal stewardship programmes.Methodology. The practical checklist was established by a national consensus panel of experts involved in antifungal stewardship activities. A preliminary checklist was sent to all experts. The final document was approved by the panel after discussion and the resolution of any disagreements by consensus.Results. The final checklist includes the following items: leadership support; actions to support optimal antifungal use; actions to monitor antifungal prescribing, use and resistance; and an education programme.Conclusion. This antifungal stewardship checklist offers opportunities for antifungal resistance containment, given that antifungal stewardship activities promote the optimal use of antifungals.

Clinical Decision Support Systems for Antibiotic Prescribing: An Inventory of Current French Language Tools.

Clinical decision support systems (CDSSs) are increasingly being used by clinicians to support antibiotic decision making in infection management. However, coexisting CDSSs often target different types of physicians, infectious situations, and patient profiles. The objective of this study was to perform an up-to-date inventory of French language CDSSs currently used in community and hospital settings for antimicrobial prescribing and to describe their main characteristics. A literature search, a search among smartphone application stores, and an open discussion with antimicrobial stewardship (AMS) experts were conducted in order to identify available French language CDSSs. Any clinical decision support tool that provides a personalized recommendation based on a clinical situation and/or a patient was included. Eleven CDSSs were identified through the search strategy. Of the 11 CDSSs, only 2 had been the subject of published studies, while 9 CDSSs were identified through smartphone application stores and expert knowledge. The majority of CDSSs were available free of charge (n = 8/11, 73%). Most CDSSs were accessible via smartphone applications (n = 9/11, 82%) and online websites (n = 8/11, 73%). Recommendations for antibiotic prescribing in urinary tract infections, upper and lower respiratory tract infections, and digestive tract infections were provided by over 90% of the CDSSs. More than 90% of the CDSSs displayed recommendations for antibiotic selection, prioritization, dosage, duration, route of administration, and alternative antibiotics in case of allergy. Information about antibiotic side effects, prescription recommendations for specific patient profiles and adaptation to local epidemiology were often missing or incomplete. There is a significant but heterogeneous offer for antibiotic prescribing decision support in French language. Standardized evaluation of these systems is needed to assess their impact on antimicrobial prescribing and antimicrobial resistance.

Inflammation and infection in plasma cell disorders: how pathogens shape the fate of patients.

The role of infection and chronic inflammation in plasma cell disorders (PCD) has been well-described. Despite not being a diagnostic criterion, infection is a common complication of most PCD and represents a significant cause of morbidity and mortality in this population. As immune-based therapeutic agents are being increasingly used in multiple myeloma, it is important to recognize their impact on the epidemiology of infections and to identify preventive measures to improve outcomes. This review outlines the multiple factors attributed to the high infectious risk in PCD (e.g. the underlying disease status, patient age and comorbidities, and myeloma-directed treatment), with the aim of highlighting future prophylactic and preventive strategies that could be implemented in the clinic. Beyond this, infection and pathogens as an entity are believed to also influence disease biology from initiation to response to treatment and progression through a complex interplay involving pathogen exposure, chronic inflammation, and immune response. This review will outline both the direct and indirect role played by oncogenic pathogens in PCD, highlight the requirement for large-scale studies to decipher the precise implication of the microbiome and direct pathogens in the natural history of myeloma and its precursor disease states, and understand how, in turn, pathogens shape plasma cell biology.

Does 18F-FDG PET/CT add value to conventional imaging in clinical assessment of chronic disseminated candidiasis?

Background: Chronic disseminated candidiasis (CDC) classically occurs after profound and prolonged neutropenia. The aim of the CANHPARI study was to assess the clinical value of adding 18F-fluorodeoxyglucose PET/CT to conventional radiology for initial and subsequent evaluations of CDC. Materials and methods: A pilot prospective study was conducted in 23 French onco-hematological centers from 2013 to 2017 (NCT01916057). Patients ≥ 18 y.o. suspected for CDC on abdominal conventional imaging (CT or MRI) were included. PET/CT and conventional imaging were performed at baseline and month 3 (M3). Follow-up was assessed until M12. The primary outcome measure was the global response at M3, i.e., apyrexia and complete response to PET/CT. The secondary outcome measure consists in comparison between responses to PET/CT and conventional imaging at diagnosis and M3. Results: Among 52 included patients, 44 were evaluable (20 probable and 24 possible CDC); 86% had acute leukemia, 55% were male (median age 47 years). At diagnosis, 34% had fever and conventional imaging was always abnormal with microabscesses on liver and spleen in 66%, liver in 25%, spleen in 9%. Baseline PET/CT showed metabolic uptake on liver and/or spleen in 84% but did not match with lesion localizations on conventional imaging in 32%. M3 PET/CT showed no metabolic uptake in 13 (34%) patients, 11 still having pathological conventional imaging. Global response at M3 was observed in eight patients. Conclusion: Baseline PET/CT does not replace conventional imaging for initial staging of CDC lesions but should be performed after 3 months of antifungal therapy. Clinical trial registration: [www.clinicaltrials.gov], identifier [NCT01916057].

Antifungal Stewardship in Hematology: Reflection of a Multidisciplinary Group of Experts.

We have presented a practical guide developed by a working group of experts in infectious diseases and hematology to summarize the different recommendations issued by the different international groups on antifungal agents used for hematology patients. In addition, a working group of experts in the domains of nephrology, hepatology, and drug interactions have reported their different recommendations when administering antifungal agents, including dose adjustments, monitoring, and management of their side effects. This guide will enable prescribers to have a document available that will allow for better and optimal use of antifungal agents for hematology patients with consideration of the toxicity and interactions adjusted to each indication.

How to measure hospital antibiotic consumption: comparison of two methods from data surveillance in France.

BACKGROUND: Antibiotic use (ABU) surveillance in healthcare facilities (HCFs) is essential to guide stewardship. Two methods are recommended: antibiotic consumption (ABC), expressed as the number of DDD/1000 patient-days; and prevalence of antibiotic prescription (ABP) measured through point prevalence surveys. However, no evidence is provided about whether they lead to similar conclusions. OBJECTIVES: To compare ABC and ABP regarding HCF ranking and their ability to identify outliers. METHODS: The comparison was made using 2012 national databases from the antibiotic surveillance network and prevalence study. HCF rankings according to each method were compared with Spearman's correlation coefficient. Analyses included the ABU from entire HCFs as well as according to type, clinical ward and by antibiotic class and specific molecule. RESULTS: A total of 1076 HCFs were included. HCF rankings were strongly correlated in the whole cohort. The correlation was stronger for HCFs with a higher number of beds or with a low or moderate proportion of acute care beds. ABU correlation between ABC or ABP was globally moderate or weak in specific wards. Furthermore, the two methods did not identify the same outliers, whichever HCF characteristics were analysed. Correlation between HCF ranking varied according to the antibiotic class. CONCLUSIONS: Both methods ranked HCFs similarly overall according to ABC or ABP; however, major differences were observed in ranking of clinical wards, antibiotic classes and detection of outliers. ABC and ABP are two markers of ABU that could be used as two complementary approaches to identify targets for improvement.

Low to medium-low risk perception for dengue, chikungunya and Zika outbreaks by infectious diseases physicians in France, Western Europe.

BACKGROUND: Many tropical countries are currently experiencing dengue (DEN), chikungunya (CHIK) and also more recently Zika (ZIKA) epidemics (particularly in Latin America). Although the risk of transmission and spread of these infections in temperate regions remains a controversial issue, vector-borne diseases have been widely reported in the media and have been the focus of preventive strategies by national and international policy-makers and public health authorities. In this context, we wanted to determine the extent of risk perception in infectious diseases (ID) physicians of the current and future risk of arboviral disease introduction, autochthonous case development and epidemic scenarios in France, Western Europe. METHODS: To this aim, we developed an original standardized questionnaire survey which was disseminated by the French Infectious Diseases Society to ID physician members. RESULTS: We found that ID physicians perceived the risk of introduction and outbreak development of DEN, CHIK and ZIKA in France to be low to medium-low. Generalized Linear Model(s) identified medical school training, the extent of professional experience, and awareness of the French national plan regarding arboviral infections as significant predictors for lower risk perception among respondents. CONCLUSION: Despite the fact that arboviral diseases are increasingly being imported into France, sometimes resulting in sporadic autochtonous transmission, French ID physicians do not perceive the risk as high. Better communication and education targeting health professionals and citizens will be needed to enhance the effectiveness of the French national plan to prepare against arboviral diseases.

Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort.

OBJECTIVES: Antibiotics for febrile neutropenia (FN) in acute myeloid leukaemia (AML) patients undergoing intensive chemotherapy are usually maintained until neutropenia resolution, because of the risk of uncontrolled sepsis in this vulnerable population. This leads to unnecessarily prolonged antimicrobial therapy. METHODS: Based on ECIL-4 recommendations, we modified our management strategy and discontinued antibiotics after a pre-established duration in patients treated for a first episode of FN between August 2014 and October 2017. RESULTS: Antibiotics were stopped during 62 FN episodes, and maintained in the control group (n = 13). Median age of patients was 54 years. A total of 39 (63%) patients received induction and 23 (37%) consolidation chemotherapy; 36 (58%) patients had fever of unknown origin. Median neutropenia length was 26 days (IQR 24-30). Antibiotics were started at day 9 (IQR 5-13). Most patients received piperacillin-tazobactam (56%) or cefepime (32%). Antimicrobial therapy was longer in the control group than in the policy compliant group, 10 (IQR 7-16) vs. 19 days (IQR 15-23), P = 0.0001. After antibiotics discontinuation, 20% patients experienced fever recurrence, within 5.5 days (IQR 3-7.5). None of these febrile episodes were severe and 80% patients remained afebrile, with neutrophil recovery occurring within 5 days (IQR 2-8.5). Overall, 287 antibiotics days were spared; this represents 49% of all days with antibiotics. No patient had died at day 30 from intervention; six died during late follow-up, two from graft-versus-host disease and four from relapsed or refractory leukaemia. CONCLUSIONS: Discontinuing antibiotics in neutropenic AML patients treated for a first episode of FN is safe, and results in significant antibiotic sparing.

Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey).

BACKGROUND: Bloodstream infections (BSIs) are severe infections that can be community or hospital acquired. Effects of time to appropriate treatment and impact of antimicrobial management team are discussed in terms of outcome of BSI. We sought to evaluate the impact of initial BSI management on short-term mortality. PATIENTS AND METHODS: A prospective, multicenter survey was conducted in 121 French hospitals. Participants declaring BSI during a 1-month period were included consecutively. Data on patient comorbidities, illness severity, BSI management, and resistance profile of bacterial strains were collected. Predictors of 10-day mortality were identified by multivariate regression for overall BSI, health care-related and hospital-acquired BSI. RESULTS: We included 1,952 BSIs. More than a third of them were hospital acquired (39%). Multidrug resistance was identified in 10% of cases, mainly in health care-related BSI. Empirical therapy and targeted therapy were appropriate for 61% and 94% of cases, respectively. Increased 10-day mortality was associated with severe sepsis, septic shock, increasing age, and any focus other than the urinary tract. Decreased mortality was associated with receiving at least one active antibiotic within the first 48 hours. Intervention of antimicrobial management team during the acute phase of BSI was associated with a decreased mortality at day 10 in the overall population and in health care-related BSI. CONCLUSION: Optimizing BSI management by increasing rapidity of appropriate treatment initiation may decrease short-term mortality, even in countries with low rate of multidrug-resistant organisms. Early intervention of antimicrobial management team is crucial in terms of mortality.

Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study.

Background: The ongoing extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs), medical and surgical wards between 2009 and 2013. Methods: This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011. Results: Over the study period, carbapenem consumption in ICUs (n = 85), medical (n = 227) and surgical wards (n = 181) was equal to 73.4, 6.2 and 5.4 defined daily doses per 1000 patient-days, respectively. Release of guidelines was followed by a significant decrease in carbapenem use within ICUs and medical wards, and a slowdown in use within surgical wards. The following factors were independently associated with a higher probability of reducing carbapenem use: location in Eastern France, higher initial carbapenem prescribing profile and reductions in consumption of fluoroquinolones, glycopeptides and piperacillin/tazobactam. In parallel, factors independently associated with a lower probability of reducing carbapenem use were ICUs, ward size increase, wards of cancer centres, higher initial third-generation cephalosporin (3GC) prescribing profile and location in high-risk regions for ESBL-PE. Conclusions: Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.

Explicit definitions of potentially inappropriate prescriptions of antibiotics in older patients: a compilation derived from a systematic review.

Potentially inappropriate prescriptions (PIPs) of antibiotics (antibiotic-PIPs) are generally detected by applying implicit definitions based on expert opinion. Explicit definitions are less frequently used, even though this approach would enable the automated detection of antibiotic-PIPs in electronic health records. Here, explicit definitions of antibiotic-PIPs used in studies of older adults were systematically reviewed. The MEDLINE®, Scopus® and Web of ScienceTM core collection databases were searched with a combination of three terms and their synonyms: 'potentially inappropriate prescription' AND 'antibiotic treatment' AND 'older patients'. Following standardised selection of publications, explicit definitions of antibiotic-PIPs were extracted and were classified into infectious diseases domains and subdomains. A total of 600 search queries identified 4270 records, 93 of which were selected for review. A total of 160 mentions of antibiotic-PIPs were found, corresponding to 62 distinct definitions in 19 infectious diseases domains. Nearly one-half of the definitions were related to upper respiratory tract infections (n = 11 definitions; 17.7%), lower respiratory tract infections (n = 8; 12.9%) and drug-drug interactions (n = 11; 17.7%). Almost 75% of definitions (n = 46) were mentioned in a single study only. Only three definitions concerned critically important antibiotics such as third-generation cephalosporins and fluoroquinolones. This systematic review identified 62 explicit definitions of antibiotic-PIPs. Most of the definitions were not found in more than one study and they varied in the degree of precision. We advocate the implementation of an expert consensus on explicit definitions of antibiotic-PIPs that correspond to today's challenges in public health.

Carbapenem use in French hospitals: A nationwide survey at the patient level.

The objective of this study was to evaluate the characteristics of carbapenem use in French healthcare settings in order to guide future actions. Healthcare facilities voluntarily participated in a nationwide cross-sectional survey in 2011. Medical data and reasons for carbapenem treatment (CPR) and discontinuation were recorded for all patients treated with carbapenems. A total of 2338 patients were recorded by 207 facilities. The median duration of CPR was 8 days, and 31.4% of patients received CPR for >10 days. An antibiotic consultant was involved in the initial choice of CPR in 36.8% of cases. CPR was chosen on an empirical (EP) basis for 1229 patients (52.6%), mainly because of severe sepsis (48.6%) or a perceived risk of bacterial resistance (33.7%). Among EP patients, de-escalation was more frequent in the case of intervention of an antibiotic consultant (35.1%) than without intervention (22.9%) (P<0.01). Among the 1109 patients receiving CPR initially based on bacteriological results, 607 (54.7%) had ESBL-producing Enterobacteriaceae and 397 (35.8%) had Gram-negative bacilli susceptible to at least one ß-lactam other than carbapenems or to fluoroquinolones. Among the latter, de-escalation was performed in 59 cases (14.9%). The intervention of an antibiotic consultant did not favour de-escalation in this group. In conclusion, carbapenems are frequently used for treating suspected or confirmed multidrug-resistant bacteria, and overall CPR duration is long. De-escalation is frequently not implemented despite isolates being susceptible to other drugs. More frequent antibiotic consultant intervention may help to decrease carbapenem use in the case of EP treatment.

Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial.

BACKGROUND: Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. METHODS: In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) or 5% povidone iodine-69% ethanol (povidone iodine-alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. FINDINGS: Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine-alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine-alcohol (580 patients with scrubbing, 588 without). Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol; hazard ratio 0·15, 95% CI 0·05-0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol (27 [3%] patients vs seven [1%] with povidone iodine-alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. INTERPRETATION: For skin antisepsis, chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. FUNDING: University Hospital of Poitiers, CareFusion.