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This pilot prospective study assessed the association between the faecal relative abundance of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) and the occurrence of ESBL-PE related infections. Twenty-four patients were included. The median ESBL relative abundance was 32.4%. The mean ESBL-PE relative abundance (ESBL-PE-RA) was more than five-fold higher in patients exposed during the last three months to antibiotics (P = 0.002). Furthermore, the mean ESBL relative abundance was more than two-fold higher in patients colonized with non-E. coli strains (P = 0.044). The mean ESBL-PE-RA was more than 10-fold higher for the concordant patients than for the discordant patients (59.1% vs 4.9%; P < 0.001)., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of β-lactamases or by deregulation of natural genetically-encoded β-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC β-lactamases. AmpC can be overproduced as a response to β-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: A variety of microorganisms can cause infective endocarditis (IE), with Staphylococci and Streptococci accounting for the majority of cases. Streptococci are a common cause of community-acquired IE but few studies have focused on this subgroup of endocarditis., Methods: A retrospective multicentre study was conducted between 2012 and 2017 in 12 hospital centres in France. Data were extracted from the local diagnosis-related group database and matched with microbiological results. After identification, the records were retrospectively analysed., Results: A total of 414 patients with streptococcal endocarditis were included. The patients were predominantly male (72.8%) and the median age was 73.2 years (interquartile range [IQR] 61.3-80.9). The majority of patients (70.6%) had native valve endocarditis. Embolic complications were seen in 38.8% of patients. Viridans group Streptococci (VGS) and bovis-equinus group Streptococci (BGS) accounted for 52.4% and 34.5% of isolated strains, respectively. Minimum inhibitory concentrations (MICs) of amoxicillin were <0.125, 0.125-2 and >2 mg/L for 59.6%, 27% and 1% of isolates, respectively. In-hospital mortality for patients with Streptococci-related IE was 17.8%. In multivariate analysis, the only factor associated with in-hospital mortality was MIC for amoxicillin between 0.25 and 2 mg/L (P = 0.04; OR = 2.23 [95% confidence interval (CI) 1.03-4.88]) whereas performance of cardiac surgery for IE was a protective factor (P = 0.001, OR = 0.23 [95% CI 0.1-0.56])., Conclusions: IE remains a serious and deadly disease despite recent advances in diagnosis and treatment. Adaptation of antibiotic doses to MICs for amoxicillin and surgery may improve patient outcome., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The aim of this work was to issue clinical practice guidelines on antibiotic prophylaxis in urodynamics (urodynamic studies, UDS)., Materials and Methods: Clinical practice guidelines were provided using a formal consensus method. Guidelines proposals were drew up by a multidisciplinary experts group (pilot group = steering group), then rated by a panel of 12 experts (rating group) using a formal consensus method, and then peer reviewed by a reviewing/reading group of experts (different from the rating group)., Results: Urine (bacterial) culture with antimicrobial susceptibility testing is recommended for all patients before UDS (strong agreement). In patients with no neurologic disease, the risk factors for tract urinary infection (UTI) after UDS are age > 70 years, recurrent UTI, and post-void residual volume > 100ml. In patients with neurologic disease, the risk factors for UTI after UDS are recurrent UTI, vesicoureteral reflux, and intermicturition pressure > 40cmH 2 O. If the urine culture is negative before UDS and there is no risk factor for UTI, antibiotic prophylaxis is not recommended (Strong agreement). If the urine culture is negative before UDS, but there are one or more risk factors for UTI, antibiotic prophylaxis is optional. If antibiotic prophylaxis is initiated, a single oral dose (3g) of fosfomycin-tromethamine two hours before UDS is recommended (Strong agreement). If there is bacterial colonization on UCB before UDS, antibiotic therapy is optional (Undecided). If prescribed, it should be adapted to the antimicrobial susceptibility of the identified bacterium or bacteria, started the day before and stopped after UDS (except for fosfomycin-tromethamine: a single dose the day before UDS is necessary and sufficient) (Strong agreement). In the event of UTI before UDS, the UTI should be treated and UDS postponed (Strong agreement). The proposed recommendations should not be changed for patients with a hip or knee replacement (Strong agreement). No antibiotic prophylaxis of bacterial endocarditis is necessary, including in high-risk patients with valvular heart disease (Strong agreement)., Conclusion: These new guidelines should help to harmonize clinical practice and limit exposure to antibiotics., Level of Evidence: 4., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Urinary tract infection (UTI) is one of the most frequent community-acquired infection. Escherichia coli resistance has been on the rise since 2000s., Methods: We conducted a prospective multicenter cohort study including adults who had a positive urine cytobacteriological examination (UCBE) performed in our Parisian suburb laboratory platform from October 2014 to March 2015., Results: A total of 1223 patients were included: 995 (81.4%) women and 228 (18.6%) men. Gram-negative bacilli were isolated in 91% of cases: E. coli accounted for 69.4% of cases. Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) prevalence was 4.2%. Resistance of ESBL-producing E. coli strains to amoxicillin, fluoroquinolones, nitrofurantoin, and fosfomycin was respectively 100%, 80%, <5%, and <10%. Risk factors for bacteriuria caused by ESBL-PE were older age (OR=3.7 [1.99-14.4]; P=0.02), recurrent UTI (OR=3.7 [1.9-7.2]; P=0.05), immunosuppression (OR=9.2 [4.1-19.47]; P=0.01), recent hospitalization within the last three months (OR=4.5 [2.3-8.3]; P=0.05), and recent antibiotic therapy (OR=13.4 [6.29-31.9]; P<0.01)., Conclusion: The prevalence of ESBL-PE bacteriuria seems to be 4%. Older age, immunosuppression, recurrent UTI, recent hospitalization, and antibiotic therapy are the main risk factors associated with ESBL-PE community-acquired UTI., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: To avoid the use of carbapenems, alternatives such as cephamycin, piperacillin-tazobactam, and others are suggested for the treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections. The aim of this study was to evaluate the frequency and the feasibility of antimicrobial de-escalation for ESBL-PE-related infections., Methods: A prospective observational, bi centric cohort study was conducted. All patients with ESBL-PE infections were included. De-escalation was systematically suggested if patients were clinically stable and the isolate was susceptible to possible alternatives., Results: Seventy-nine patients were included: 36 (45.6%) were children, 27 (34.1%) were hospitalized in intensive care units, and 37 (47%) were immunocompromised. Urinary tract infections, pneumonia, and catheter-related bloodstream infections accounted for 45.6%, 19%, and 10%, respectively, of the cohort. Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were the three most frequent causative organisms isolated. On day 5, 47 (59.2%) of the patients were still receiving carbapenems. Antimicrobial resistance (44.7%), infection relapse (26.9%), and clinical instability (19.2%) were the most important reasons for not prescribing alternatives. E. coli-related infections appeared to be a protective factor against maintaining the carbapenem prescription (odds ratio 0.11, 95% confidence interval 0.041-0.324; p=0.0013)., Conclusions: In clinical practice, less than 50% of patients with ESBL-PE-related infections were de-escalated after empirical treatment with carbapenems., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Empirical broad spectrum antimicrobial therapy prescribed in life-threatening situations should be de-escalated to mitigate the risk of resistance emergence. Definitions of de-escalation (DE) vary among studies, thereby biasing their results. The aim of this study was to provide a consensus definition of DE and to establish a ranking of β-lactam according to both their spectra and their ecological consequences. Twenty-eight experts from intensive care, infectious disease and clinical microbiology were consulted using the Delphi method (four successive questionnaires) from July to November 2013. More than 70% of similar answers to a question were necessary to reach a consensus. According to our consensus definition, DE purpose was to reduce both the spectrum of antimicrobial therapy and the selective pressure on microbiota. DE included switching from combination to monotherapy. A six-rank consensual classification of β-lactams allowing gradation of DE was established. The group was unable to differentiate ecological consequences of molecules included in group 4, i.e. piperacillin/tazobactam, ticarcillin/clavulanic acid, fourth-generation cephalosporin and antipseudomonal third-generation cephalosporin. Furthermore, no consensus was reached on the delay within which DE should be performed and on whether or not the shortening of antibiotic therapy duration should be included in DE definition. This study provides a consensual ranking of β-lactams according to their global ecological consequences that may be helpful in future studies on DE. However, this work also underlines the difficulties of reaching a consensus on the relative ecological impact of each individual drug and on the timing of DE., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.)

Objective: We wanted to describe the clinical features associated with urinalysis positive for ESBL-producing Escherichia coli and their impact on antibiotic use., Methods: We performed a prospective observational study in 13 French hospitals of the Paris area for 3 consecutive months. We included all patients with urine cultures positive for ESBL-producing E. coli., Results: One hundred and seventeen of the 218 patients (54%) presented with asymptomatic bacteriuria, 31 (14%) with cystitis, and 70 (32%) with a parenchymal infection. Nineteen patients with asymptomatic bacteriuria (16%) received antibiotics. Forty-one with parenchymal infections (59%) received a carbapenem. A carbapenem alternative could have been used in every patient treated with a carbapenem, according to antibiotic susceptibility testing results., Conclusions: Urinary tract infections accounted for 46% of E. coli ESBL positive urinalysis. Fifty percent of parenchymal infections were treated with a carbapenem., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The fight against multi-drug resistant Gram-negative bacilli (MDRGNB), especially extended-spectrum β-lactamase producing Enterobacteriaceae, is about to be lost in our country. The emergence of new resistance mechanisms to carbapenems in these Enterobacteriaceae exposes patients to a risk of treatment failure without any other therapeutic options. This dramatic situation is paradoxical because we are well aware of the 2 major factors responsible for this situation: 1) MDRO cross-transmission, associated with a low compliance to standard precautions, especially hand hygiene, and 2) overexposure of patients to antibiotics. The implementation of a "search and isolate" policy, which was justified to control the spread of some MDRO that remained rare in the country, was not associated with a better adherence to standard precautions. The antibiotic policy and the measures implemented to control antibiotic consumptions have rarely been enforced and have shown inconsistent results. Notably, no significant decrease of antibiotic consumption has been observed. There is no excuse for these poor results, because some authors evaluating the effectiveness of programs for the control of MDRO have reported their positive effects on antimicrobial resistance without any detrimental effects. It is now urgent to deal with the 2 major factors by establishing an educational and persuasive program with quantified and opposable objectives. Firstly, we have to improve the observance of hand hygiene above 70%. Secondly, we have to define and reach a target for the reduction of antibiotic consumption both in community and in hospital settings., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Cefoxitin could be an alternative to carbapenems in extended-spectrum-beta-lactamase-producing Escherichia coli (ESBL-EC) infections. However, pharmacological and clinical data regarding cefoxitin are limited. Using a recent pharmacological model and the MICs of ESBL-EC collected from pyelonephritis, we determined the probabilities to reach four pharmacological targets: free cefoxitin concentrations above the MIC during 50% and 100% of the administration interval (T>MIC = 50% and T>MIC = 100%, respectively) and free cefoxitin concentrations above 4× MIC during 50% and 100% of the administration interval (T>4MIC = 50% and T>4MIC = 100%, respectively). Cefoxitin could be used to treat ESBL-EC pyelonephritis, but administration modalities should be optimized according to MICs in order to reach pharmacological targets., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Purpose: Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB)., Patients and Methods: We conducted a multicenter prospective descriptive study including patients with CA-GNB., Results: Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138) and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P<0.001), the origin of the patient (Paris region or West of France) (P=0.006), and home health care (P<0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively., Conclusions: Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The use of intravenously administered antibiotics has several disadvantages including hospitalization costs, infectious risk, and patient discomfort. The objective of this study was to estimate the proportion of children receiving intravenous antibiotic therapy (IV), for whom there was a switch to an oral route conforming to the criteria established by the American Pediatric Surgical Association (APSA). A cohort of 100 children hospitalized for acute appendicitis with generalized peritonitis or abscess were analyzed. In this study, we compared the criteria of switching to an oral route as recommended by the APSA (disappearance of the pain, normalization of white blood cells, afebrile for 48 hours, return to bowel function) and by reports from the literature (afebrile, tolerating regular diet). In 47.5% of the children, there was a switch to an oral route conforming to the APSA recommendations. In children having a late switch, the average duration of the IV treatment was of 7.6 ± 3.6 days associated with 62 days of avoidable IV antibiotics. The duration of hospitalization and antibiotic treatment was significantly higher in children having a late switch (P=0.04; P=0.01, respectively). Concerning the criteria reported in the literature, 14.5% of children were not switched to an oral route. Meeting the criteria from the literature would have resulted in 199 days of avoidable IV antibiotics. A significant number of days of IV antibiotics could have been avoided. However, the large number of exclusion criteria in the APSA analysis suggests that practitioners do not follow these recommendations or objective criteria. The criteria proposed in the literature could decrease the duration of IV antibiotics and the associated hospitalization costs., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Vancomycin is still the cornerstone of antibiotic therapy for patients with suspected or proven invasive methicillin resistant Staphylococcus aureus infections. However, clinical and pharmacodynamic studies underline that appropriate doses depend on the infection site, the patient's weight, his renal function, and the bacterial susceptibility., Objective and Method: In this prospective study made in a Paris teaching hospital, our two goals were to describe the modalities of infusion and serum concentration obtained during therapy, in our pediatrics and adults population., Results: In our hospital, vancomycin was administered every eight hours in 83 % (97/102) of the cases and the doses used were 30 mg/kg per day in 67 % of cases (68/102). Serum trough levels reached 15 mcg/ml and 20 mcg/ml in 36 % and 18 % of cases respectively. Moreover, despite adequate doses, trough levels of 15 mcg/ml were obtained in only 40 % of cases., Conclusion: Vancomycin infusion use could be optimized, by defining optimal serum concentrations and monitoring made by a mobile team of infectious diseases specialists., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Objective: Members of the genus Bacillus are Gram-positive bacilli, ubiquitous in the environment. When isolated in clinical practice, it is frequently considered as due to environmental contamination. Bacillus cereus is the most frequent species isolated in clinical practice, nevertheless other Bacillus spp. are sometimes isolated. Bacillus bacteremia is uncommon, the affected patients are severely ill and frequently immunocompromised with hematological malignancies., Study Design: Two cases of bloodstream infection due to Bacillus species rarely described before are described, one due to Bacillus macerans and the other to Bacillus pumilus. Both patients presented with severe bacteremia and were immunodepressed after recent chemotherapy. They died a few days after admission to our ICU., Conclusion: The initial report of Bacillus spp. isolated in blood culture in oncohematological patients indicates a potentially severe infection.