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Scope: This European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing?, Methods: An expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria. For each main question for the four topics, a systematic review was performed, including randomized controlled trials and observational studies. Both clinical outcomes and stewardship process outcomes related to antibiotic use were deemed relevant. The literature searches were conducted between May 2021 and March 2022. In April 2022, the panel members were formally asked to suggest additional studies that were not identified in the initial searches. Data were summarized in a meta-analysis if possible or otherwise summarized narratively. The certainty of the evidence was classified according to the Grading of Recommendations Assessment, Development and Evaluation criteria. The guideline panel reviewed the evidence per topic critically appraising the evidence and formulated recommendations through a consensus-based process. The strength of the recommendations was classified as strong or weak. To substantiate the implementation process, implementation trials or observational studies describing facilitators/barriers for implementation were identified from the same searches and were summarized narratively., Recommendations: The recommendations on the use of biomarkers and rapid pathogen diagnostic tests focus on the initiation of antibiotics in patients admitted through the ED. Their effect on the discontinuation or de-escalation of antibiotics during hospital stay was not reported, neither was their effect on hospital infection prevention and control practices. The recommendations on watchful waiting (i.e. withholding antibiotics with some form of follow-up) focus on specific infectious syndromes for which the primary care literature was also included. The recommendations on blood cultures focus on the indication in three common infectious syndromes in the ED explicitly excluding patients with sepsis or septic shock. Most recommendations are based on very low and low certainty of evidence, leading to weak recommendations or, when no evidence was available, to best practice statements. Implementation of these recommendations needs to be adapted to the specific settings and circumstances of the ED. The scarcity of high-quality studies in the area of antimicrobial stewardship in the ED highlights the need for future research in this field., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies., (© 2021. The Author(s).)

Estimating whether the individual probability of being infected by a fluoroquinolone resistant isolate is higher than 10% may help to choose the empirical treatment of pyelonephritis. We aimed to model the risk of fluoroquinolone resistance in women with community-onset pyelonephritis. Women with non-severe community-onset pyelonephritis were prospectively recruited in 4 French emergency departments of 2 districts. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated through multivariate logistic regression. Among 190 patients, 19 (10%) were infected by a fluoroquinolone resistant isolate. Fluoroquinolone resistance was more frequent in district #2 (17%) than in district #1 (3%). Independent risk factors for fluoroquinolone resistance were district (adjusted OR, 7.0 (2.2-31.9)), and in the 6 previous months, urinary tract infection (UTI, aOR, 3.9 (1.3-11.5)) and vesical catheterization (aOR, 4.7 (0.5-33.3)). A specific model was derived to identify district #2 patients with a low (10% or lower) probability of being infected by a fluoroquinolone resistant isolate. Independent risk factors were residency in long-term care facility (aOR, 3.3 (0.7-13.5)), and in the 6 previous months, UTI (adjusted OR, 3.1 (0.9-10.7)) and home nursing care (aOR, 3.4 (0.6-17.0)). For 63 (67%) patients, the predicted probability of fluoroquinolone resistance was 0.10; among these patients, 6 (10%) actually had a fluoroquinolone resistant isolate. Locally derived predictive models may be used to identify patients with a low probability of fluoroquinolone resistance and guide the empirical antimicrobial therapy of non-severe community-onset pyelonephritis.

Background: Although the interest of antibiotics is well known, antibiotics prescription is associated with side effect, especially in patients with multiples comorbidities. One way to reduce the incidence of side effects is to respect antibiotics prescriptions guidelines. Our objective was to investigated the factors associated with guidelines adherence in elderly patients with multiples comorbidities., Methods: From October 2015 to December 2016, antibiotics prescription and guidelines adherence were analyzed in two post-acute care and rehabilitation services of a 2600-bed, university-affiliated center., Results: One hundred and twenty-eight patients were included, fifty-nine (46%) patients had antibiotics prescription according to guidelines. In Multivariable logistic regression analysis, prescription of 2 antibiotics or more (OR = 0.168, 95% IC = 0.037-0.758, p < 0.05), 85 years of age and more (OR = 0.375, 95% IC = 0.151-0.931, p < 0.05) and the Charlson comorbidity index score (OR = 0.750, 95% IC = 0.572-0.984, p < 0.05) were negatively associated with antibiotics prescriptions according to guidelines., Conclusions: High comorbidity in the elderly was negatively associated with the guidelines adherence of antibiotiсs prescriptions. These criteria should be considered to optimize antibiotics prescriptions in elderly patients.

Study Objective: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia., Methods: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population., Results: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively)., Conclusion: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess recent trends in susceptibility to antibiotics among urinary isolates isolated in European emergency departments (EDs) and to identify isolates with a high (90% or more) predicted probability of susceptibility to fluoroquinolones or third-generation cephalosporins (3GCs)., Methods: In this cross-sectional study, we included urine cultures obtained from adult patients between 2010 and 2016 in 24 European EDs. Temporal trends were assessed using time-series analysis and multivariate logistic models. Multivariate logistic models were also used to predict susceptibility to fluoroquinolones or 3GCs from patient age and sex, year, month and ED., Results: We included 88242 isolates. Time-series analysis found a significant increase in susceptibility to fluoroquinolones and no significant trend for susceptibility to 3GCs. Adjusting for patient age and sex, ED and organism, multivariate models showed that susceptibility to 3GCs decreased from 2014 to 2016, while susceptibility to fluoroquinolones increased in 2015 and 2016. Among isolates from 2016, multivariate models predicted high probability of susceptibility to fluoroquinolones in 11% of isolates (positive predictive value 91%) and a high probability of susceptibility to 3GCs in 35% of isolates (positive predictive value 94%)., Conclusions: Susceptibility of ED urinary isolates to fluoroquinolones increased from 2014, while susceptibility to 3GCs decreased from 2015. Predictive models identified isolates with a high probability of susceptibility to fluoroquinolones or 3GCs. The ability of such models to guide the empirical treatment of pyelonephritis in the ED remains to be determined., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to assess whether treatment with ceftriaxone/cefotaxime is associated with lower in-hospital mortality than amoxicillin-clavulanate in pati0ents hospitalized in medical wards for community-onset pneumonia., Methods: We conducted a retrospective and multicentre study of patients hospitalized in French medical wards for community-onset pneumonia between 2002 and 2015. Treatments with ceftriaxone/cefotaxime or amoxicillin-clavulanate were defined by their start in the emergency department for a duration of 5 days or more with no other β-lactam. A logistic regression analysis was performed on the overall population, and a propensity score analysis was restricted to patients treated with either ceftriaxone/cefotaxime or amoxicillin-clavulanate., Results: 1698 patients (median age, 80 y) were included, of which 716 and 198 were treated with amoxicillin-clavulanate and ceftriaxone/cefotaxime, respectively. In-hospital mortality was 10% (9-12%). In multivariate analysis, factors associated with in-hospital mortality were treatment with ceftriaxone/cefotaxime (aOR 2.9; (1.4-5.7)), pneumonia severity index class 4 or 5 (aOR 7.8 (4.3-15.7)), do-not-resuscitate order (aOR 8.7 (5.2-14.6)) and fluid therapy (aOR 6.3 (2.5-15.1)). The propensity score analysis was performed on 178 patients treated with ceftriaxone/cefotaxime matched with 178 patients treated with amoxicillin-clavulanate; no significant association between treatment with ceftriaxone/cefotaxime and in-hospital mortality was found (OR 1.5 (0.7-3.0))., Conclusion: In the largest study aiming to compare amoxicillin-clavulanate and ceftriaxone/cefotaxime in community-onset pneumonia, ceftriaxone/cefotaxime was not associated with lower in-hospital mortality than amoxicillin-clavulanate. Our results suggest that ceftriaxone/cefotaxime should not be preferred over amoxicillin-clavulanate for patients hospitalized in medical wards with community-onset pneumonia., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aims: Amoxicillin-clavulanate is extensively used in European hospitals. Whether the hospital use of amoxicillin-clavulanate is associated with nonsusceptibility to third-generation cephalosporins (3GC) in Klebsiella pneumoniae is unknown. Our aim was to assess the relationship between the hospital use of amoxicillin-clavulanate and 3GC nonsusceptibility in K. pneumoniae and Escherichia coli., Methods: Yearly data of antibiotic use and 3GC nonsusceptibility in K. pneumoniae and E. coli were obtained from 33 French hospitals between 2011 and 2016. Decreased susceptibility to 3GC and Extended-Spectrum Beta-Lactamase (ESBL) production were modelled from antibiotic use with linear mixed models on years 2011 to 2015, and validated on year 2016., Results: Nonsusceptibility to 3GC increased in K. pneumoniae and E. coli. In a multivariable model that included year and use of 3GC and fluoroquinolones as explanatory variables, amoxicillin-clavulanate use was protective against 3GC nonsusceptibility in K. pneumoniae (incidence rate ratio [IRR], 0.992 [0.988-0.997]), and with ESBL production in K. pneumoniae (IRR, 0.989 [0.985-0.992]). The correlation coefficient between observed and predicted numbers of 3GC-nonsusceptible K. pneumoniae in 2016 was 0.95 (95% confidence interval, 0.89-0.98). There was no significant association between amoxicillin-clavulanate use and 3GC nonsusceptibility in E. coli., Conclusion: Amoxicillin-clavulanate hospital use was protective against nonsusceptibility to 3GC in K. pneumoniae. Conversely, it was not associated with susceptibility to 3GC in E. coli. To decrease the hospital use of 3GC and fluoroquinolones, and 3GC nonsusceptibility in K. pneumoniae, it may be acceptable to increase the hospital use of amoxicillin-clavulanate. Interventional studies are necessary to confirm this hypothesis.

We previously found that the hospital use of tetracyclines is associated with quinolone resistance in hospital isolates of Enterobacteriaceae. Tetracyclines are heavily used in the community. Our aim was to assess whether their use in the community favors quinolone resistance in community isolates of Escherichia coli. Monthly data of community antibiotics use and E. coli quinolone resistance in a 1.3 million inhabitant French area were obtained from 2009 to 2014, and were analyzed with autoregressive integrated moving average (ARIMA) models. Quinolone use decreased from 10.1% of the total antibiotic use in 2009 to 9.3% in 2014 (trend, - 0.016; p-value < 0.0001), while tetracycline use increased from 16.5% in 2009 to 17.1% in 2014 (trend, 0.016; p < 0.0001). The mean (95% confidence interval) monthly proportions of isolates that were non-susceptible to nalidixic acid and ciprofloxacin were 14.8% (14.2%-15.5%) and 9.5% (8.8%-10.1%), respectively, with no significant temporal trend. After adjusting on quinolone use, tetracycline use in the preceding month was significantly associated with nalidixic acid non-susceptibility (estimate [SD], 0.01 [0.007]; p-value, 0.04), but not with ciprofloxacin non-susceptibility (estimate [SD], 0.01 [0.009]; p-value, 0.23). Tetracycline use in the community may promote quinolone non-susceptibility in E. coli. Decreasing both tetracycline and quinolone use may be necessary to fight against the worldwide growth of quinolone resistance.

Objectives: Third-generation cephalosporins and fluoroquinolones are particularly prone to promoting bacterial resistance. Their use in Emergency Departments (EDs) is poorly known. Our objectives were to assess the use of antibacterial agents in French EDs., Methods: This study is a retrospective study of antibiotics delivered to the adult units of 11 EDs of French academic centres in 2012, and to six of these EDs between 2009 and 2012., Results: The total antibiotic use was 66.4 defined daily doses (DDD)/1000 ED visits in 2012, and it increased between 2009 and 2012 (yearly estimate, +1.8±0.9 DDD/1000 ED visits, P=0.048). The 3GC-FQ class, which grouped third-generation cephalosporins and fluoroquinolones, accounted for 39.2% of the total antibiotic use, and the use of this class of antibiotics was highly variable among EDs (range, 31.6-49.5% of total antibiotic use). The aminopenicillin and β-lactamase inhibitor/3GC-FQ ratio varied among EDs [median (range), 0.91 (0.52-1.25)]. Between 2009 and 2012, there was a significant decrease in the use of the 3GC-FQ class (yearly estimate, -0.8±0.4% of total antibiotic use), antipneumococcal fluoroquinolones (-0.8±0.3%) and other fluoroquinolones (-0.9%±0.3%), and there was a significant increase in the use of third-generation cephalosporins (+0.7±0.3%), aminoglycosides (+0.4±0.1%), imidazole derivatives (+0.4±0.1%) and lincosamides (+0.1±0.0%)., Conclusion: Fluoroquinolones and third-generation cephalosporins are widely used in the ED. Their use is highly variable among EDs. Third-generation cephalosporins were increasingly used between 2009 and 2012, whereas the use of fluoroquinolones decreased. Reduced use of cephalosporins in the ED, without increasing fluoroquinolone use, should be aimed at through antibiotic stewardship programs.

Because of the high prevalence of amoxicillin resistance among uropathogens, amoxicillin is not recommended as an empirical treatment of urinary tract infections (UTIs). Quick detection of an amoxicillin-susceptible Escherichia coli (ASEC) would allow prescribing amoxicillin without preliminary broad-spectrum empirical treatment in uncomplicated pyelonephritis. To quickly diagnose UTIs due to ASEC, we developed a real-time PCR that detects in fresh uncultured urine the E. coli-specific gene yccT as well as the blaTEM and blaCTX-M genes. The ASEC rapid test was considered positive if the PCR was positive for the yccT gene but negative for blaTEM and blaCTX-M. The test was compared with culture and susceptibility testing. Among 200 patients with a suspected community-acquired UTI, 61 (30.5%) had a monobacterial UTI due to ASEC. The ASEC rapid test result was obtained in 3 h 13 [95% confidence interval (CI) 3 h 12-3 h 15] and was positive for 43 patients (21.5%). Specificity and sensitivity were 97.8% (95% CI 95.8-99.8%) and 65.6% (95% CI 59.0-72.1%), respectively. Positive and negative predictive values were 93.0% (95% CI 89.5-96.5%) and 86.6% (95% CI 81.9-91.3%), respectively. Owing to its high specificity and positive predictive value, the ASEC rapid test allows the diagnosis of UTI due to ASEC only 3 h after urine sampling. A positive ASEC rapid test may be used to treat uncomplicated pyelonephritis with amoxicillin from the start, without preliminary broad-spectrum empirical treatment. The ASEC rapid test is a promising tool to spare fluoroquinolones and third-generation cephalosporins in UTIs., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: Fluoroquinolones and 3rd-generation cephalosporins that are prescribed for pneumonia may be avoided and replaced by a penicillin in some cases. We aimed to determine if the proportion of patients treated for pneumonia with a cephalosporin, a fluoroquinolone or both varies among Emergency Departments (EDs), and to estimate the proportion of avoidable prescriptions., Methods: This was a retrospective study of patients treated for pneumonia in eight French EDs, and subsequently hospitalized in non-ICU wards. Third-generation cephalosporins or respiratory fluoroquinolones were presumed unavoidable if they met both criteria: (1) age ≥65 years or comorbid condition; and (2) allergy or intolerance to penicillin, or failure of penicillin, or previous treatment with penicillin, or for fluoroquinolones only, suspected legionellosis., Results: We included 832 patients. Thirty-four percent (95 % CI, 31-38 %) of patients were treated with a cephalosporin, a respiratory fluoroquinolone or both (range among EDs 19-44 %). Four EDs were independent risk factors for prescription of a cephalosporin, a fluoroquinolone or both [adjusted OR, 2.27 (1.64-3.15)], as were immune compromise [aOR 2.54 (1.56-4.14)], antibacterial therapy started before arrival in the ED [aOR 3.32 (2.30-4.81)], REA-ICU class III or IV [aOR 1.93 (1.15-3.23)], PSI class V [aOR 1.49 (1.00-2.20)], fluid resuscitation [aOR 3.98 (2.49-6.43)] and non-invasive ventilation in the ED [aOR, 7.18 (1.7-50.1)]. Treatment with a cephalosporin, a fluoroquinolone or both was avoidable in 67 % (62-73 %) of patients., Conclusion: Cephalosporins and fluoroquinolones use in pneumonia is highly variable among EDs. The majority of these prescriptions are avoidable. Antibiotic stewardship programs should be implemented to restrict their use in EDs.

The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extended-spectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link estimate ± SE, 0.0066 ± 0.0033), lincosamides (0.0093 ± 0.0029), and other antibacterial agents (0.0050 ± 0.0023) were associated with an increased incidence, while nitrofurantoin (-0.0188 ± 0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (-0.0078 ± 0.0031) were associated with a decreased incidence. In a multivariate model including 3rd- and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd- and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020 ± 0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance.

The increasing bacterial resistance to antibiotics has become a major public health concern bringing the threat of therapeutic impasses. In this context, control of the spread of highly-resistant bacteria emerging antibiotics (BHRe), such as glycopeptide-resistant enterococci (VRE) and Enterobacteriaceae producing carbapenemases (CPE), is based on a dual strategy of reducing the prescription of antibiotics to limit the pressure selection and preventing the spread from carriers. Prevention strategy is based on three different levels such as standard precautions for all patients with a particular focus on the management of excreta, and additional precautions for BHRe carriers. What makes it difficult is that carriage is usually completely asymptomatic, enterobacteria and enterococci are normal commensal of gut microbiota. Explosive dissemination of Enterobacteriaceae producing extended spectrum beta-lactamases in hospital and community heralds the emergence of CPE whose import by patients with a history of hospitalization in abroad may be the main source of spread in France., (Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Ciprofloxacin and cotrimoxazole are recommended to treat uncomplicated pyelonephritis and uncomplicated cystitis, respectively, provided that local resistance rates of uropathogens do not exceed specified thresholds (10 and 20 %, respectively). However, Escherichia coli resistance rates in Emergency Departments (ED) remain poorly described. Our objectives were to assess E. coli ciprofloxacin and cotrimoxazole resistance rates in EDs of a French administrative region, and to determine if resistance rates differ between EDs. This was a retrospective study of E. coli urine isolates sampled in ten EDs between 2007 and 2012. The following risk factors for resistance were tested using logistic regression: ED, sex, age, sampling year, sampling month. A total of 17,527 isolates were included. Ciprofloxacin local resistance rates (range, 5.3 % [95 % CI, 4.0-7.1 %] to 11.7 % [95 % CI, 5.2-23.2 %]) were ≤10 % in nine EDs in 2012. Five EDs were risk factors for ciprofloxacin resistance, as were male sex, age and sampling in April or October. Cotrimoxazole local resistance rates (range, 13.3 % [95 % CI, 6.3-25.1 %] to 20.4 % [95 % CI, 18.9-22.0 %]) were ≤20 % in seven EDs in 2012. Five EDs were risk factors for cotrimoxazole resistance, as were age, sampling between October and December, and sampling in 2011 and 2012. We found a significant variability of E. coli ciprofloxacin and cotrimoxazole resistance rates among EDs of a small region. These differences impact on the feasibility of empirical treatment of urinary tract infections with ciprofloxacin or cotrimoxazole in a given ED. Continuous local survey of antibacterial resistance in ED urinary isolates is warranted to guide antibacterial therapy of urinary tract infections.

Fluoroquinolones and third-generation cephalosporins are particularly prone to select bacterial resistance to antibiotics. We aimed to assess the temporal trends of antibiotic use in the emergency department adults unit of an academic hospital between 2002 and 2012. Antibiotic use was converted in defined daily doses (DDD). The total antibiotic consumption tended to decrease, from 53.1±8.5 to 48.6±11.9 DDD/1000 patient visits (estimate decrease per year, -0.9±0.5 DDD/1000 visits, P=0.07). Use of third-generation cephalosporins increased significantly, from 9.7% of total antibiotic use to 22.6% (estimate per year, 1.2±0.2%, P<0.0001), whereas use of fluoroquinolones decreased from 19.5 to 12.3% (estimate per year, -0.7±0.2%, P<0.003). Given their ability to select bacterial resistance, especially extended-spectrum β-lactamases, particular attention should be paid to increasing use of third-generation cephalosporins in the emergency department.

Third-generation cephalosporins are used to treat inpatients with community-acquired pneumonia. Some of these prescriptions may be avoided, i.e. replaced by agents less likely to promote ESBL-mediated resistance. Our objectives were to assess the recent trend of third-generation cephalosporins use for pneumonia in the emergency department, and the proportion of avoidable prescriptions. This was a retrospective study of patients treated for community-acquired pneumonia in an emergency department, and subsequently hospitalized in non ICU wards. Third-generation cephalosporin prescriptions were presumed unavoidable if they met both criteria: (i) age ≥ 65 yr or comorbid condition, and (ii) allergy or intolerance to penicillin, or failure of penicillin first-line therapy, or treatment with penicillin in three previous months. Prescriptions were otherwise deemed avoidable. The proportion of patients treated with a third generation cephalosporin increased significantly from 13.9 % (6.9-24.1 %) in 2002 to 29.5 % (18.5-42.6 %) in 2012 (OR = 1.07 [1.01-1.14] , P = 0.02). This increase was independent from other factors associated with the prescription of a third-generation cephalosporin (immunocompromising condition, antibacterial therapy in three previous months, fluid resuscitation and REA-ICU class). Treatment with third-generation cephalosporin was avoidable in 118 out of 147 patients (80.3 % [72.7-86.2 %]). On day 7 after admission in the ED, treatment with third-generation cephalosporins was stopped or de-escalated in, respectively, 17 % and 32 % of patients. Antibiotic stewardship programs should be implemented to restrict the third-generation cephalosporins use for pneumonia in the emergency department.

Bacteremia remains a major cause of life-threatening complication in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture have been reported in cancer patients over the past years. The aim of our systematic review was to inventory the recent trends in epidemiology and antibiotic resistance of microorganisms causing bacteremia in cancer patients. Data for this review was identified by searches of Medline, Scopus and Cochrane Library for indexed articles and abstracts published in English since 2008. The principal search terms were: "antimicrobial resistance", "bacteremia", "bacterial epidemiology", "bloodstream infection", "cancer patients", "carbapenem resistance", "Escherichia coli resistance", "extended-spectrum β-lactamase producing E. coli", "febrile neutropenia", "fluoroquinolone resistance", "neutropenic cancer patient", "vancomycin-resistant Enterococcus", and "multidrug resistance". Boolean operators (NOT, AND, OR) were also used in succession to narrow and widen the search. Altogether, 27 articles were selected to be analyzed in the review. We found that Gram-negative bacteria were the most frequent pathogen isolated, particularly in studies with minimal use of antibiotic prophylaxis. Another important trend is the extensive emergence of antimicrobial-resistant strains associated with increased risk of morbidity, mortality and cost. This increasing incidence of antibiotic resistance has been reported in Gram-negative bacteria as well as in Gram-positive bacteria. This exhaustive review, reporting the recent findings in epidemiology and antibiotic resistance of bacteremia in cancer patients, highlights the necessity of local continuous surveillance of bacteremia and stringent enforcement of antibiotic stewardship programs in cancer patients.

Background: The relationship between the hospital use of various classes of antibiotics and resistance of Escherichia coli to quinolones remains debated. Our aim was to study the relationship between the hospital use of 16 classes of antibacterial agents and the incidence of quinolone-resistant E. coli isolates., Methods: Antibiotic use and resistance data were collected from 36 hospitals. Incident rate ratios (IRR) were assessed using negative binomial regression., Results: The incidence of quinolone-resistant isolates was independently associated with the consumption of tetracyclines (IRR 1.139, 95% CI 1.030-1.259), first- and second-generation cephalosporins (IRR 1.007, 95% CI 1.002-1.013), third-generation cephalosporins (IRR 1.029, 95% CI 1.010-1.048), and quinolones (IRR 1.007, 95% CI 1.000-1.014). These associations were independent from the type of patient served., Conclusions: The level of hospital use of quinolones influences the incidence of quinolone resistance in E. coli hospital isolates. The consumption of two other classes of antibiotics, cephalosporins and tetracyclines, is also associated with quinolone resistance., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the frequency of de-escalation in inpatients treated for community-acquired urinary tract infection and the frequency of conditions legitimating not de-escalating therapy., Methods: A retrospective study of inpatients (age >15 years) at a large academic hospital who were empirically treated for urinary tract infections due to Escherichia coli susceptible to at least one of the following antibacterial agents: amoxicillin, co-amoxiclav, and cotrimoxazole. De-escalation was defined as the replacement of the empirical broad-spectrum therapy by amoxicillin, co-amoxiclav, or cotrimoxazole., Results: Eighty patients were included. De-escalation was prescribed for 32 of 69 patients for whom it was possible from both a bacteriological and clinical point of view (46 %, 95 % CI, 34-59 %). Initial treatment was switched to amoxicillin (n = 21), co-amoxiclav (n = 2), or cotrimoxazole (n = 8). Thirteen conditions justifying not de-escalating antibacterial therapy were detected in 11 of 48 patients who were not de-escalated (23 %, 95 % CI, 12-37 %): shock, n = 5; renal abscess, n = 1; obstructive uropathy, n = 4; bacterial resistance or clinical contraindication to both cotrimoxazole and β-lactams, n = 3., Conclusions: De-escalation is under-prescribed for urinary tract infections. Omission of de-escalation is seldom legitimate. Interventions aiming to de-escalate antibacterial therapy for UTIs should be actively implemented.

Background: The difficulty to diagnose community-acquired pneumonia (CAP) and the lack of scientific data regarding the optimal duration of antibiotic therapy are responsible for overprescribing antibiotics., Objective: The authors had for objective to perform a systematic review of the international medical literature on strategies aimed at reducing antibiotic consumption for CAP., Methods: We performed a Pubmed search using the keywords CAP, antibiotic use, duration of antibiotic therapy, procalcitonin, short-course treatment, and biomarkers. We then made a critical review of the selected articles., Results: Our review identified two strategies used to reduce antibiotic consumption for CAP. The first one was based on procalcitonin (PCT) use. This strategy, even though reducing the duration of antibiotic therapy, does not seem optimal since it is associated with longer antibiotic treatment than recommended by the Infectious Diseases Society of America. Moreover, this strategy is associated with an increased cost in biochemical tests. The other strategy is based on a 2-step clinical reassessment: 1) during the first 24 hours of hospitalization, to confirm the diagnosis of CAP and 2) during hospitalization, to shorten the duration of antibiotic therapy according to the patient's clinical status., Conclusion: Clinical reassessment, currently little studied compared to PCT guidance algorithm, seems to be promising to reduce antibiotic consumption for CAP. Especially since it was never compared to PCT guidance strategy in a randomized clinical trial., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Infrared microspectroscopy was used to show that vancomycin alters infrared spectra of endocarditis vegetation bacteria, and that vancomycin effects on bacterial biochemical contents are unevenly distributed between peripheral and central areas of bacterial masses. Infrared microspectroscopy is useful to study the activity of antibacterial agents against bacteria in tissues., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to compare the in vivo activities of the new antistaphylococcal drugs ceftaroline fosamil, daptomycin and tigecycline at projected human therapeutic doses against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains in a rabbit model of endocarditis., Methods: The efficacy of therapeutic regimens in our model was evaluated following 4 days of treatment by determining colony counts of infected vegetations. Emergence of resistant variants during therapy was assessed., Results: Using this model of infective endocarditis, ceftaroline fosamil and daptomycin demonstrated high bactericidal in vivo activity (reduction of >5 log(10) cfu/g of vegetation) after a 4 day treatment against MSSA, MRSA and GISA strains. Both drugs were more efficacious than tigecycline, which showed moderate activity but failed to exhibit a bactericidal effect. Ceftaroline was superior to daptomycin in terms of sterilization of the vegetations. Emergence of resistant variants during daptomycin therapy was observed in two animals (one in the MSSA group and one in the MRSA group) but was not observed in ceftaroline- or tigecycline-treated animals., Conclusions: The novel β-lactam agent ceftaroline fosamil was the most active bactericidal drug in this model and is a promising therapeutic option for the treatment of severe S. aureus infections, including those caused by MRSA and GISA strains.

Objectives: To evaluate the activity of a new cephalosporin, ceftaroline, in comparison with other antistaphylococcal drugs (linezolid and vancomycin) at projected human therapeutic doses against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains., Methods: Using a rabbit experimental model of acute osteomyelitis, efficacy was assessed following 4 days of treatment by colony counts of infected bone tissues (joint fluid, femoral bone marrow and bone)., Results: Although vancomycin remains the standard treatment for MRSA osteomyelitis, it was ineffective against the MRSA strain and poorly active against GISA infections in this model. Ceftaroline and linezolid demonstrated significant activity in bone marrow and bone, and were significantly better than vancomycin treatment. However, ceftaroline was the only drug to exhibit significant activity against MRSA in infected joint fluid., Conclusions: The present study supports ceftaroline as a promising therapeutic option for the treatment of severe MRSA infections, including osteomyelitis.

We assessed the in vitro and in vivo efficacy of the novel parenteral broad-spectrum cephalosporin ceftaroline against Enterococcus faecalis in time-kill experiments and in a rabbit endocarditis model with simulated human dosing. Ceftaroline was more active than either vancomycin or linezolid against vancomycin-sensitive and -resistant isolates of E. faecalis.

We compared the efficacy of quinupristin/dalfopristin versus vancomycin, alone or in combination with rifampicin, in a rabbit model of methicillin-resistant Staphylococcus aureus-induced arthritis. Vancomycin, alone or in combination with rifampicin, and quinupristin/dalfopristin+rifampicin were significantly more effective than quinupristin/dalfopristin alone.

Serum concentrations of beta-lactams that continuously exceed the minimum inhibitory concentration may improve therapeutic outcomes for immunosuppressed patients. The trough serum levels of ceftazidime (CAZ), cefepime (FEP) or imipenem (IMP) were prospectively determined on days 1 and 3 of treatment in cancer patients. Seventy-eight episodes of suspected infection were analysed. Trough serum levels were higher than 4 mg/L in 62%, 24% and 0% of cases in the CAZ, FEP and IMP groups, respectively, and were higher than 20 mg/L in 24% of cases in the CAZ group compared with 0% both in the FEP and IMP groups. For suspected infectious episodes in cancer patients, the traditional intermittent regimen of beta-lactams does not appear to be appropriate for the pharmacokinetic/pharmacodynamic properties of these antibiotics.

The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

Incubation in CO(2) resulted in higher (> or =3 doubling dilution) MICs of telithromycin than those found in ambient air for 31.2% of 346 Streptococcus pneumoniae ermB-positive strains. An increased telithromycin MIC in CO(2) was not correlated with loss of its activity in the murine sepsis/peritonitis model.

Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log(10) CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.