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Background: Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection., Methods: C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow., Results: Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection., Conclusions: These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.

Background: Most pregnant women who self-report penicillin allergy are not truly penicillin-allergic and this misunderstanding often leads to administration of inappropriate antibiotic therapy. Decision algorithms have been developed to guide antibiotic selection but major discrepancies have been reported between guidelines and clinical practice. We aimed to optimize the prescription of antibiotics for pregnant women who self-reported penicillin allergy, using an educational intervention about the classification of penicillin allergies that targeted gynecologists, anesthesiologists and midwives., Methods: This quasi-experimental study assessed the effect of an educational intervention about the classification of penicillin allergy. For six months, a combination of two strategies was used, namely dissemination of printed educational materials and group education. The principal study endpoint was the appropriateness of the antibiotic therapy, defined in advance for each level of allergic risk., Results: The pre-intervention phase included 903 women; one year after its conclusion, the post-intervention phase began and included 892 women. The prevalence of self-reported penicillin allergy was stable over the two periods (6.8% before vs 5.4% after, P=0.24). The clinical classification of penicillin allergies was more often used after the educational intervention (68% vs 100%, P<0.001). The appropriateness of the antibiotic therapy prescribed to self-reported penicillin allergic-women increased significantly between the two periods, from 5/29 (17.2%) to 18/27 (66.7%, P<0.001)., Conclusion: An educational intervention about penicillin allergy classification was associated with an improvement in the choice of appropriate antibiotic therapy among women who had reported penicillin allergy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days. The timing of antibiotic administration relative to CPE exposure may be relevant to infection control and antimicrobial stewardship approaches., (Copyright © 2019 American Society for Microbiology.)

Background: Preterm delivery during pregnancy (<37 weeks' gestation) is a leading cause of perinatal mortality and morbidity. Treating bacterial vaginosis during pregnancy can reduce poor outcomes, such as preterm birth. We aimed to investigate whether treatment of bacterial vaginosis decreases late miscarriages or spontaneous very preterm birth., Methods: PREMEVA was a double-blind randomised controlled trial done in 40 French centres. Women aged 18 years or older with bacterial vaginosis and low-risk pregnancy were eligible for inclusion and were randomly assigned (2:1) to three parallel groups: single-course or triple-course 300 mg clindamycin twice-daily for 4 days, or placebo. Women with high-risk pregnancy outcomes were eligible for inclusion in a high-risk subtrial and were randomly assigned (1:1) to either single-course or triple-course clindamycin. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm birth (22-32 weeks), which we assessed in all patients with delivery data (modified intention to treat). Adverse events were systematically reported. This study is registered with ClinicalTrials.gov, number NCT00642980., Findings: Between April 1, 2006, and June 30, 2011, we screened 84 530 pregnant women before 14 weeks' gestation. 5630 had bacterial vaginosis, of whom 3105 were randomly assigned to groups in the low-risk trial (n=943 to receive single-course clindamycin, n=968 to receive triple-course clindamycin, and n=958 to receive placebo) or high-risk subtrial (n=122 to receive single-course clindamycin and n=114 to receive triple-course clindamycin). In 2869 low-risk pregnancies, the primary outcome occurred in 22 (1·2%) of 1904 participants receiving clindamycin and 10 (1·0%) of 956 participants receiving placebo (relative risk [RR] 1·10, 95% CI 0·53-2·32; p=0·82). In 236 high-risk pregnancies, the primary outcome occurred in 5 (4·4%) participants in the triple-course clindamycin group and 8 (6·0%) participants in the single-course clindamycin group (RR 0·67, 95% CI 0·23-2·00; p=0·47). In the low-risk trial, adverse events were more common in the clindamycin groups than in the placebo group (58 [3·0%] of 1904 vs 12 [1·3%] of 956; p=0·0035). The most commonly reported adverse event was diarrhoea (30 [1·6%] in the clindamycin groups vs 4 [0·4%] in the placebo group; p=0·0071); abdominal pain was also observed in the clindamycin groups (9 [0·6%] participants) versus none in the placebo group (p=0·034). No severe adverse event was reported in any group. Adverse fetal and neonatal outcomes did not differ significantly between groups in the high-risk subtrial., Interpretation: Systematic screening and subsequent treatment for bacterial vaginosis in women with low-risk pregnancies shows no evidence of risk reduction of late miscarriage or spontaneous very preterm birth. Use of antibiotics to prevent preterm delivery in this patient population should be reconsidered., Funding: French Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Bacillus cereus is a ubiquitous telluric organism. B. cereus endocarditis is a rare condition seen mostly in prosthetic heart valves and among intravenous drug users. We report a new case of a patient without risk factors and with a good clinical outcome not requiring valve replacement., Case Report: In October 2014, a 50-year-old woman was referred to the dermatology department of Lille University Hospital for lower-limb wounds developing 6 months earlier. She presented fever without clinical signs of infection, except for the lower-limbs wounds. Blood cultures revealed the presence of B. cereus. Transesophageal echocardiography was performed and revealed two foci of aortic valve vegetation with a diameter of 5mm. After bacterial sensitivity testing, rifampicin and levofloxacin treatment was given for six weeks, with complete remission. A skin graft was performed and good improvement was seen., Discussion: Nineteen cases of B. cereus endocarditis have been described previously, only one of which was without risk factors. We described a case of complete remission after a 6-week course of antibiotics. Our case demonstrates that BC should not be considered as a blood culture contamination, and that treatment may be complex due to antibiotic resistance., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL., Patients and Methods: We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria., Results: We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment., Conclusion: Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.

Objectives: To assess the quality of prescription of fluoroquinolons, aminosids and amoxicillin-clavulanic acids in medicine departments., Methods: Data on target antibiotic prescription were collected on a given day and confronted to local recommendations and literature guidelines. Evaluation of antibiotic therapy was done by assessing molecule choice, administration conditions (dosages, route and administration schedule, treatment duration), reassessment of treatments 48-72 h later, dose adaptation of aminosids depending on serum monitoring., Results: Sixty-three patients were included and 67 "target" antibiotics were prescribed. Prevalence of antibiotic-treated patients was 24.4%, and 14.6% for "target" antibiotic-treated patients. Antibiotic choice was appropriate in 67% of prescriptions. Dosages were adequates in 94% of case and administration schedule in 97% of cases. The oral route administration as soon as possible was applied to half of patients. Treatment duration were respected for 94% of prescriptions. Reassessment of antibiotic therapy 48-72 h later was realized in 66% of cases. Dose adaptation of aminosids, when necessary, was realized on one third of cases. For all the quality criteria assessed, the overall frequency of prescription conformity was 44%., Conclusion: Large diffusion of protocols, systematic reassessment of treatments at 48-72 h, promotion of training sessions for new prescribers in the institution, reinforcing the function of medical correspondents in antibiotic therapy and infectiologists, periodic evaluation of antibiotic therapy, should improve the quality of antibiotic therapy., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)