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Abstract
The plasmid-mediated quinolone resistance (PMQR) genes have been shown to promote high-level bacterial resistance to fluoroquinolone antibiotics, potentially leading to clinical treatment failures. In Escherichia coli, sub-minimum inhibitory concentrations (sub-MICs) of the widely used fluoroquinolones are known to induce the SOS response. Interestingly, the expression of several PMQR qnr genes is controlled by the SOS master regulator, LexA. During the characterization of a small qnrD-plasmid carried in E. coli, we observed that the aminoglycosides become able to induce the SOS response in this species, thus leading to the elevated transcription of qnrD. Our findings show that the induction of the SOS response is due to nitric oxide (NO) accumulation in the presence of sub-MIC of aminoglycosides. We demonstrated that the NO accumulation is driven by two plasmid genes, ORF3 and ORF4, whose products act at two levels. ORF3 encodes a putative flavin adenine dinucleotide (FAD)-binding oxidoreductase which helps NO synthesis, while ORF4 codes for a putative fumarate and nitrate reductase (FNR)-type transcription factor, related to an O2-responsive regulator of hmp expression, able to repress the Hmp-mediated NO detoxification pathway of E. coli. Thus, this discovery, that other major classes of antibiotics may induce the SOS response could have worthwhile implications for antibiotic stewardship efforts in preventing the emergence of resistance.
Abstract
Introduction: Success rates of external cephalic version (ECV) are heterogenous in the published literature. Some individual factors are already known to be associated with ECV success but probably do not fully explain the differences. The objective of this review is to assess the association between hospitals’ cesarean delivery rates for breech presentations after ECV failure and their ECV success rates.
Material and methods: We performed a review of the literature using the Medline and Cochrane Library computer databases and by searching on clinicaltrials.gov, from 1985 through 2020. This analysis included all studies reporting ECV success rates and cesarean delivery rates for breech presentations. The prognostic factors for successful ECV, such as rates of nulliparity, gestational age at ECV, BMI, and tocolysis use, were also collected and analyzed. Median ECV success rates from the included studies were compared according to these factors. The cesarean rate for persistent breech presentation after ECV failure reported in these studies was considered a proxy indicator of the unit’s policy for breech presentations. The correlation between ECV success rates and cesarean delivery rates was analyzed and is presented as a scatter plot.
Results: This analysis included 22 studies reporting rates of both successful ECV and cesarean deliveries for persistent breech presentation after ECV failure. The ECV success rates ranged from 16.3% to 82.5% with a median of 48.8% (interquartile range: 36.9-62.9). The median ECV success rate was higher in the studies that used tocolysis than in those that did not (51.3% versus 22.0%, P = .001) and in the studies with the highest cesarean rates for breech presentations than in those with the lowest cesarean rates (57.9% versus 36.2%, P = .006). The ECV success rates were significantly correlated with cesarean delivery rates for persistent breech presentations (R = 0.67; P = .001).
Conclusion: The likelihood of successful ECV appears higher in hospitals with policies that generally result in cesarean delivery for persistent breech presentation.
Abstract
Objective: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age.
Design: Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants.
Setting: France, 2011.
Sample: We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes.
Methods: Population-averaged robust Poisson models.
Main outcome measures: Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment.
Results: With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08-1.45] and 1.10 [95 % confidence interval 1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.
Conclusion: In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.
Abstract
The clinical benefits to be expected from intraoperative nociception monitors are currently under investigation. Among these devices, the Analgesia Nociception-Index (ANI) has shown promising results under sevoflurane anesthesia. Our study investigated ANI-guided remifentanil administration under propofol anesthesia. We hypothesized that ANI guidance would result in reduced remifentanil consumption compared with standard management. This prospective, randomized, controlled, single-blinded, bi-centric study included women undergoing elective gynecologic surgery under target-controlled infusion of propofol and remifentanil. Patients were randomly assigned to an ANI or Standard group. In the ANI group, remifentanil target concentration was adjusted by 0.5 ng mL-1 steps every 5 min according to the ANI value. In the Standard group, remifentanil was managed according to standard practice. Our primary objective was to compare remifentanil consumption between the groups. Our secondary objectives were to compare the quality of anesthesia, postoperative analgesia and the incidence of chronic pain. Eighty patients were included. Remifentanil consumption was lower in the ANI group: 4.4 (3.3; 5.7) vs. 5.8 (4.9; 7.1) µg kg-1 h-1 (difference = -1.4 (95% CI, -2.6 to -0.2), p = 0.0026). Propofol consumption was not different between the groups. Postoperative pain scores were low in both groups. There was no difference in morphine consumption 24 h after surgery. The proportion of patients reporting pain 3 months after surgery was 18.8% in the ANI group and 30.8% in the Standard group (difference = -12.0 (95% CI, -32.2 to 9.2)). ANI guidance resulted in lower remifentanil consumption compared with standard practice under propofol anesthesia. There was no difference in short- or long-term postoperative analgesia.
Abstract
Background: The time between symptoms onset and endometriosis diagnosis is usually long. The negative impacts of delayed endometriosis diagnosis can affect patients and health outcomes.
Methods: We conducted a case-control study using clinical symptoms and epidemiological data extracted from a prospective pre-operative patient questionnaire compared between patients with histologically proven endometriosis and patients with no endometriosis at surgical exploration from 2005 to 2018, in a French referral center. We used the beta coefficients of the significant variables introduced in a multiple regression model to devise a score (score 1), evaluated by the area under the curve (or C-index), with three levels, defined by a score between 1 and ≥ 25: (i) highly specific, identifying correctly the patients without the disease; (ii) highly sensitive, identifying the patients with the disease; and (iii) a level maximizing sensitivity and specificity for the best classification of the whole population. To minimize patient self-evaluation of pain, we devised a second score (score 2) with the same method and levels and scores definition, excluding visual analog scale pain scores, except for dysmenorrhea. These scores were validated on an internal and external population.
Findings: Score 1 had a C-index of 0.81 (95% CI [0.79-0.83]). Results for the three score 1 levels were: ≥ 25: specificity of 91% (95% CI [89-93]); < 11: sensitivity of 91% (95% CI [89-93]); ≥ 18: specificity of 75% (95% CI [72-78]) and sensitivity of 73% (95% CI [70-76]). Score 2 had a C-index of 0.75 (95% CI [73-77]). The three levels of score 2 were: ≥ 24: specificity of 82% (95% CI [80-85]); < 7: sensitivity of 92% (95% CI [90-94]); ≥ 17: specificity of 62% (95% CI [58-65]) and sensitivity of 78% (95% CI [75-81]). The two scores were internally and externally validated.
Interpretation: A score based only on a patient questionnaire could allow identification of a population at high risk of endometriosis. This strategy might help referral to specialized radiologists for a non-surgical endometriosis scan.
Abstract
ackground Hygiene measures are recommended to prevent toxoplasmosis during pregnancy, although screening for seroconversion in pregnant women currently are debated and practices vary among countries. Objectives The purpose of this systematic literature review was to assess the effectiveness of hygiene measures during pregnancy to prevent toxoplasmosis infection. Search Strategy We followed the standard MOOSE and PRISMA criteria when conducting this systematic review and reporting the results. Selection criteria A systematic literature search was conducted for studies focused on congenital toxoplasmosis prevention, toxoplasmosis prevention during pregnancy, toxoplasmosis prevention and hygiene measures, which were published between 1970 and August 2020, using the databases of PubMed, Scope Med, EMBASE, and the Cochrane library. Data collection and analysis Our literature search identified 3964 articles, 3757 were excluded after review of title or abstract and 67 studies were considered relevant to the subject. We reviewed risk factors for toxoplasmosis infection during pregnancy and for congenital toxoplasmosis, preventive measures for toxoplasmosis during pregnancy, including: dietary recommendations, pet care measures, environmental measures, knowledge of risk factors and ways to control toxoplasmosis infection, knowledge of risk factors for infection by health professionals, knowledge of primary prevention measures by pregnant women. Conclusion: Hygiene measures are effective and applicable primary prevention to reduce toxoplasmosis and avoid congenital toxoplasmosis and its consequences. Funding No.
Abstract
Context: After 41 weeks, the labor induction term varies according to countries and obstetrical teams. The French recommendations are not to exceed 41 weeks 6 days. However, there are no data on the percentage of nulliparous women with an unfavorable cervix at 41 weeks going into spontaneous labor within five or six days.
Objective: The objective was to establish the rate of spontaneous labor within five days amongst nulliparous women with an unfavorable cervix at 41 weeks, and to identify the maternal and obstetrical factors associated with this spontaneous labor.
Materials and methods: Retrospective study in a University Hospital Maternity between January 1st and December 31st 2017. All nulliparous women with a cephalic fetal presentation and unfavorable cervix at 41 weeks (Bishop ≤ 3) were included. The maximum term for induced labor was set at 41 weeks 5 days. The population was divided into two groups: spontaneous labor and induced labor (induction between 41 weeks and 41 weeks 4 days for medical indications or maternal wish and induction at 41 weeks 5 days for full term). The maternal and obstetrical characteristics of the two groups at 41 weeks were compared as well as the maternal and neonatal outcomes.
Results: The rate of spontaneous labor among the 269 women included was 38.3% (n = 103/269). At 41 weeks, the presence of painful uterine contractions and a Bishop score of 3 were associated with spontaneous labor within five days (p < 0.01). The Bishop score criteria most associated with spontaneous labor were cervical dilation and fetal station. The cesarean delivery rate was 20.4% in the group of women with spontaneous labor versus 41.0% in the group of induced labor (p < 0.01). There were no differences between the two groups in terms of neonatal outcome.
Conclusion: Among nulliparous women with an unfavorable cervix at 41 weeks, almost 40 % will have a spontaneous onset of labor within five days. The only factors found to be associated with this onset of labor are the presence of painful uterine contractions and a higher Bishop score at 41 weeks.
Abstract
Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS).
Study design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores.
Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38).
Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.