Antibiotic consumption in French nursing homes between 2018 and 2022: A multicenter survey.

OBJECTIVES: Monitoring antibiotic consumption is a key component to steer antimicrobial stewardship programs, including in nursing homes. We analyzed changes in antibiotic consumption in French nursing homes during 5 years, including the COVID-19 pandemic, to identify potential priorities for improvement. DESIGN: A multicenter survey was conducted between 2018 and 2022. SETTING: The study was conducted across 220 French nursing homes with on-site pharmacies. METHOD: Antibiotic consumption data were collected from pharmacy records and are expressed as defined daily doses per 1,000 resident days. Antibiotic indicators promoted by health authorities were calculated from quantitative data to evaluate the quality of prescribing. RESULTS: Antibiotic consumption significantly decreased between 2018 and 2022, particularly during the coronavirus disease 2019 (COVID-19) pandemic, despite a slight increase in 2022. During the study period, the most used antibiotic classes were penicillins (61.9% in 2022) followed by cephalosporins (10.5%), macrolides-lincosamides-streptogramins (7.3%) then fluoroquinolones (7.0%). Amoxicillin-clavulanic acid was the most consumed antibiotic; amoxicillin and ceftriaxone ranked second and third. Azithromycin consumption increased from 2020, as did the indicator regarding broad-spectrum antibiotics. CONCLUSIONS: The decreasing trend in antibiotic use and control of fluoroquinolone use over the study period suggest compliance with antibiotic use guidelines. However, changes in the use of broad-spectrum antibiotics and the substantial use of amoxicillin-clavulanic acid, although it is rarely a first-line antibiotic, highlight the need for antimicrobial stewardship activities and the usefulness of antibiotic consumption surveillance to identify priorities.

Do Different Sutures with Triclosan Have Different Antimicrobial Activities? A Pharmacodynamic Approach.

(1) Background: Three antimicrobial absorbable sutures have different triclosan (TS) loads, triclosan release kinetics and hydrolysis times. This in vitro study aims to analyse and compare their antimicrobial pharmacodynamics. (2) Methods: Time-kill assays were performed with eight triclosan-susceptible microorganisms common in surgical site infections (SSIs) and a segment of each TS. Microbial concentrations were measured at T0, T4, T8 and T24 h. Similar non-triclosan sutures (NTS) were used as controls. Microbial concentrations were plotted and analysed with panel analysis. They were predicted over time with a double-exponential model and four parameters fitted to each TS × microorganism combination. (3) Results: The microbial concentration was associated with the triclosan presence, timeslot and microorganism. It was not associated with the suture material. All combinations shared a common pattern with an early steep concentration reduction from baseline to 4-8 h, followed by a concentration up to a 24-h plateau in most cases with a mild concentration increase. (4) Conclusions: Microorganisms seem to be predominantly killed by contact or near-contact killing with the suture rather than the triclosan concentration in the culture medium. No significant in vitro antimicrobial pharmacodynamic difference between the three TS is identified. Triclosan can reduce the suture microbial colonisation and SSI risk.

Do Triclosan Sutures Modify the Microbial Diversity of Surgical Site Infections? A Systematic Review and Meta-Analysis.

Randomised controlled clinical trials (RCTs) report a lower incidence rate of surgical site infections (SSIs) with triclosan sutures (TSs) compared with non-triclosan sutures (NTSs). Do triclosan sutures modify the microbial diversity of culture-confirmed SSIs (ccSSIs)? If so, this would support the association between TS antimicrobial activity and the SSI incidence rate. This prospective systematic literature review (PROSPERO CRD42019125099) was conducted according to PRISMA. RCTs that compared the incidence of SSIs with TSs and NTSs and reported microbial counts from SSI cultures per suture group were eligible. The microbial species were grouped by genus, and the association between genera and sutures was tested. The pooled relative risk (RR) of ccSSIs was also calculated. Twelve RCTs were eligible. No publication bias was identified. The microorganism count was 180 in 124 SSIs with TSs versus 246 in 199 SSIs with NTSs. No significant difference in microbial diversity was found, but statistical power was low for test results to support or challenge the association between the antimicrobial activity of TSs and the reduced rate of SSIs. The RR of the ccSSIs was significant and consistent with comprehensive meta-analyses. The certainty of the pooled RR was moderate.

Systematic review of factors promoting behaviour change toward antibiotic use in hospitals.

BACKGROUND: Antimicrobial stewardship (AMS) programmes include actions to improve antibiotic use. OBJECTIVES: This study aimed to identify factors of AMS interventions associated with behaviour change toward antibiotic use in hospitals, applying behavioural sciences. DATA SOURCES: PubMed and Scopus online databases were searched. STUDY ELIGIBILITY CRITERIA: Studies published between January 2015 and December 2020 were included. The required study outcomes were as follows: effect of the intervention reported in terms of antibiotic consumption, antibiotic costs, appropriateness of prescription, duration of therapy, proportion of patients treated with antibiotics, or time to appropriate antibiotic therapy. PARTICIPANTS: Participants included health care professionals involved in antibiotic prescription and use in hospitals and patients receiving or susceptible to receiving antibiotics. INTERVENTIONS: Studies investigating AMS interventions in hospitals were included. METHODS: Risk of bias was determined using the integrated quality criteria for review of multiple study designs tool. A systematic review of AMS interventions was conducted using the behaviour change wheel to identify behaviour changes functions of interventions; and the action, actor, context, target, and time framework to describe how they are implemented. Relationships between intervention functions and the action, actor, context, target, and time domains were explored to deduce factors for optimal implementation. RESULTS: Among 124 studies reporting 123 interventions, 64% were effective in reducing antibiotic use or improving the quality of antibiotic prescription. In addition, 91% of the studies had a high risk of bias. The main functions retrieved in the effective interventions were enablement, environmental restructuring, and education. The most common subcategories were audit and feedback and real-time recommendation for enablement function, as well as material resources, human resources, and new tasks for environmental restructuring function. Most AMS interventions focused on prescriptions, targeted prescribers, and were implemented by pharmacists, infectious diseases specialists, and microbiologists. Interventions focusing on specific clinical situation were effective in 70% of cases. CONCLUSIONS: Knowledge of factors associated with behaviour changes will help address local barriers and enablers before implementing interventions.

Adverse drug reactions induced by cotrimoxazole: Still a lot of preventable harm.

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance center (France) during a 5-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommendations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring.

Pulmonary tuberculosis and management of contact patients in a Department of Nephrology and Kidney Transplantation.

OBJECTIVES: To describe the investigation, follow-up, management, and outcomes in a cohort of chronic kidney disease (CKD) and kidney transplant recipients (KTR) exposed to a case of pulmonary tuberculosis (TB). METHODS: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with evidence of latent TB infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. RESULTS: A total of 130 patients with CKD and 180 KTR were identified as contacts and followed-up over a 2-year period. Few vulnerable high-priority contacts received anti-TB treatment, including the two (100%) highly exposed patients in circle 1, 11/78 (14.1%) CKD patients and 4/142 (2.8%) KTR in circle 2, and 10/52 (19.2%) CKD patients and 2/36 (5.6%) KTR in circle 3; all had a positive interferon-gamma release assay result. No incident cases of TB disease occurred. CONCLUSIONS: These findings suggest that latent TB treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2, with a negative interferon-gamma release assay and in countries with low prevalence of TB.

Corrigendum to: A Major Regional Measles Outbreak: Description of Hospitalized Cases in 2017-2018 at Bordeaux University Hospital, France.

[This corrects the article DOI: 10.1093/ofid/ofaa332.].

Establishment of a French surveillance system of Clostridiodes difficile infection: Comparison of patient's characteristics with other national and European data.

INTRODUCTION: The magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. METHODS: DIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions. A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database. RESULTS: From January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%). The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study. Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DISCUSSION: These results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.

Do Contact Precautions Reduce the Incidence of Intensive Care Unit-Acquired Pseudomonas aeruginosa Infections? The DPCPYO (Detection and Contact Precautions for Patients With P. aeruginosa) Cluster-Randomized Crossover Trial.

BACKGROUND: The issue of contact precautions as contributory factors for reducing Pseudomonas aeruginosa (Pa) infections in intensive care units (ICUs) remains questioned. We evaluated the impact of the addition of contact precautions to standard precautions for Pa-positive patients on incidence of ICU-acquired Pa infections. METHODS: In this multicenter, cluster-randomized crossover trial, 10 French ICUs were randomly assigned (1:1) to sequence 0-1 (6-month control period [CP]/3-month washout period/6-month intervention period [IP]) or sequence 1-0 (6-month IP/3-month washout period/6-month CP). A surveillance screening program for Pa was implemented. Competing-risks regression models were built with death and discharge without the occurrence of ICU-acquired Pa infection (the primary outcome) as competing events. Models were adjusted for within-ICU correlation and patient- and ICU-level covariates. The Simpson diversity index (SDI) and transmission index (TI) of Pa isolates were derived from pulsed-field gel electrophoresis typing. RESULTS: Within recruited ICUs, the cumulative incidence and incidence rate of ICU-acquired Pa infections were 3.38% (55/1625) versus 3.44% (57/1658) and 3.31 versus 3.52 per 1000 patient-days at risk during the CP and IP, respectively. Multivariable models indicated that the intervention did not significantly change the cumulative incidence (subdistribution hazard ratio, .91; 95% confidence interval [CI], .49-1.67; P = .76) or rate (cause-specific hazard ratio, 1.36; 95% CI, .71-2.63; P = .36) of the primary outcome. SDI and TI did not significantly differ between CP and IP. CONCLUSIONS: The addition of contact precautions to standard precautions for Pa-positive patients with a surveillance screening program does not significantly reduce ICU-acquired Pa infections in non-outbreak situations. Clinical Trials Registration. ISRCTN92710225.

Randomized study of antiseptic application technique in healthy volunteers before vascular access insertion (TApAS trial).

BACKGROUND: In France about 32% of hospitalized patients have a vascular access placement. However, a common complication associated with these is catheter-related bloodstream infection (CRBI) due to the introduction of microorganisms from the skin during catheter insertion. There is no consensus on the best way to clean the skin prior to catheter insertion, which could be a key element of CRBI prevention. The two techniques most commonly used to apply antiseptic to the skin are the concentric circle and back-and-forth techniques, but these have not been compared in clinical trials. Hence, this study conducted this comparison. METHODS: This single-center, non-comparative, randomized, matched pilot study investigated the levels of cutaneous microorganisms before and after antiseptic application using both techniques in a population of healthy French volunteers. The two application methods were used on each participant's arms at the elbow fold, with randomization for the application side (right or left). Quantification of cutaneous microorganisms was performed in a blinded manner with regard to the technique used. FINDINGS: From April 8 to July 17, 2019, 132 healthy volunteers participated in the study. For the whole study population, the mean initial colonization level was 2.68 log10 colony forming units (CFU)/mL (SD 0.82) before the back-and-forth technique, and 2.66 log10 CFU/mL (SD 0.85) before the concentric circle technique. The mean differences in number of microorganisms between the initial sample and the final sample were 2.45 log10 CFU/mL (95% CI: 2.29 to 2.61) for the back-and-forth technique and 2.43 log10 CFU/mL (95% CI: 2.27 to 2.59) for the concentric circle technique. The mean difference in reduction in microorganisms between the back-and-forth technique and the concentric circle technique was 0.02 log10 CFU/mL (95% CI: -0.11 to 0.15). INTERPRETATION: There was no clinically difference in reduction of microorganisms between the concentric circle and back-and-forth techniques at the bend of the healthy volunteer's elbow, after the 30 s of drying of the antiseptic. These findings have a significant impact on time required to achieve antiseptic application before catheter insertion because there is yet no argument to justify application for 30 s, because a single concentric circle pass was much faster with similar results. Future studies should investigate the impact of skin application technique on the prevention of infectious risk associated with catheter insertion on admission to health care facilities (conventional, outpatient, or emergency) and throughout the period of stay in a health care facility.

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.

Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review.

BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU. METHODS: Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy. RESULTS: Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting. CONCLUSION: Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.

Molecular epidemiology of Pseudomonas aeruginosa isolated from infected ICU patients: a French multicenter 2012-2013 study.

Although Pseudomonas aeruginosa has a non-clonal epidemic population structure, recent studies have provided evidence of the existence of epidemic high-risk clones. The aim of this study was to assess the molecular epidemiology of P. aeruginosa isolates responsible for infections in French ICUs, regardless of resistance patterns. For a 1-year period, all non-duplicate P. aeruginosa isolated from bacteremia and pulmonary infections in ten adult ICUs of six French university hospitals were characterized by antimicrobial susceptibility testing and genotyping (MLST and PFGE). We identified ß-lactamases with an extended spectrum phenotypically and by sequencing. The 104 isolates tested were distributed in 46 STs, of which 7 epidemic high-risk (EHR) clones over-represented: ST111, ST175, ST235, ST244, ST253, ST308, and ST395. Multidrug-resistant (MDR) isolates mostly clustered in these EHR clones, which frequently spread within hospitals. Only one ST233 isolate produced the carbapenemase VIM-2. PFGE analysis suggests frequent intra-hospital cross-transmission involving EHR clones. For ST395 and ST308, we also observed the progression from wild-type to MDR resistance pattern within the same PFGE pattern. Molecular epidemiology of P. aeruginosa in French ICUs is characterized by high clonal diversity notably among antimicrobial susceptible isolates and the over-representation of EHR clones, particularly within MDR isolates, even though multidrug resistance is not a constant inherent trait of EHR clones.

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.

Epidemiology and microbiological profile comparison between community and hospital acquired infections: A multicenter retrospective study in Lebanon.

BACKGROUND: The objective of this study is to identify and characterize the species resistance of different pathogens between community acquired and hospital acquired infections pointing at patients' related independent co-morbidities and socio-demographic factors. METHODS: It was a retrospective cohort, multicenter study from five private hospitals located in Beirut and Mount Lebanon. Two hundred fifty-eight adult patients were included. RESULTS: 110 Gram negative pathogens and 26 Gram positive pathogens were implicated in hospital acquired infections. The Gram-negative bacteria that showed a positive correlation regarding patient's type of infection were Pseudomonas aeruginosa (12%), Klebsiella pneumoniae (6.2%) and Acinetobacter baumannii (3.1%). These bacteria were more frequent in patients with hospital acquired infections (P=0.002, 0.013 and 0.017 respectively). The ratio of methicillin resistant Staphylococcus aureus, Extended Spectrum Beta Lactamase producing Escherichia coli and K. pneumoniae and multi drug P. aeruginosa showed high significance in hospital acquired infections. The logistic regression, showed a significant relationship between resistant bacteria and age (p<0.001, ORa=5.680, CI [2.344; 13.765]) and immunosuppressed state (p=0.003, ORa=3.137, CI [1.485; 6.630]) and an inverse relationship for Chronic Obstructive Pulmonary Disease (COPD) (p=0.006, ORa=0.403, CI [0.212; 0.765]). CONCLUSION: Our results confirm that hospital acquired infections/bacteria have higher rates of resistance when compared to community acquired; these rates increase with age, immunosuppression and are inversely proportional with COPD. Therefore, physicians should be aware of patients' comorbidities to properly guide initial therapy.

Outbreak in newborns of methicillin-resistant Staphylococcus aureus related to the sequence type 5 Geraldine clone.

We describe the first nosocomial outbreak of a toxic shock syndrome-positive methicillin-resistant Staphylococcus aureus (MRSA) sequence type 5 Geraldine clone. Infection control interventions that are usually successful were implemented to control the outbreak. Spread of this virulent MRSA strain highlights the need to be vigilant to MRSA antibiotic susceptibilities.

Control of extended-spectrum ß-lactamase-producing Enterobacteriaceae nosocomial acquisition in an intensive care unit: A time series regression analysis.

BACKGROUND: This study was undertaken to determine the temporal relationship between implementation of different interventions in an intensive care unit (ICU) and control of endemic nosocomial acquisition of extended-spectrum ß-lactamase Enterobacteriaceae (ESBLE). METHODS: This was a prospective observational study with time-series analysis of the monthly incidence of ESBLE and its predictors. In November 2007, after a 14-month baseline period, an intervention consisting of restriction of third-generation cephalosporins (3 GC) and increased use of alcohol-based hand rubs was implemented. In January 2008, an increased health care worker (HCW):patient ratio was also implemented. In March 2010, the ICU was closed, and patients were moved to a clean ICU. RESULTS: The first intervention resulted in global reduction in 3 GC and increased use of alcohol-based hand rub. A significant change in ESBLE incidence was observed in a full segmented univariate regression analysis (mean change in level, -0.91 ± 0.19; P < .0001). After ICU closure, there was a dramatic reduction in ESBLE acquisition. According to the multivariate model, the ICU closure was the main protective factor. Before ICU closure, an increase in the HCW:patient ratio of 0.1 point tended to be associated with a decreased risk of ESBLE acquisition (relative risk, 0.28; 95% confidence interval, 0.06-1.25; P = .09). CONCLUSIONS: This study shows that ICU closure was associated with, but not necessarily the reason for, control of ESBLE cross-transmission in a nonoutbreak setting. Environmental ESBE sources may play a role in cross-transmission.

Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.

Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the determination of Cmax and an intermediate aminoglycoside assay before minimum plasma concentration) and the Bayesian method were both classified as high-intensity TDM programmes. Given the mean cost of aminoglycoside nephrotoxicity, these programmes may be cost-effective if its prevalence is above 10 %. However, none of these high-intensity TDM programmes have demonstrated a reduction of aminoglycoside-associated nephrotoxicity in patients with septic shock. Therefore, the questions remain as to, first, whether a TDM programme is relevant and, second, what intensity of TDM is achievable in the ICU, i.e. how it can be practically applied in the ICU setting where urgent care and high workload are substantial obstacles to a sophisticated, optimized aminoglycoside administration.

Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

OBJECTIVES: To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). METHODS: This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). RESULTS: A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. CONCLUSIONS: Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.