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Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

ABSTRACT: INTRODUCTION:Preterm birth (PTB) at <37 weeks of gestation is the leading cause of perinatal morbidity and mortality in developed countries. The traditional approach has been based on the assumption that PTB is primarily a result of intrauterine infection, which triggers preterm labour and puts the newborn at risk of early onset sepsis (EOS). We are currently experiencing a rise in prematurity that results from maternal and fetal diseases unrelated to infection. We have designed a systematic review to assess whether chemoprophylaxis should be withheld when the aetiology of preterm birth is non-infectious. METHODS AND ANALYSIS:Our study will focus on studies evaluating EOS in preterm infants. We will conduct a comprehensive search of literature available up to 28 February 2018. An information specialist will search for eligible studies in Medline (Ovid interface, 1948 and onwards), Embase (Ovid interface, 1980 onwards) and the Cochrane Central Register of Controlled Trials (Wiley interface, current issue). We will search databases and registries including records of ongoing research, conference proceedings and thesis (clinical trials, WHO International Clinical Trials Registry Platform). Two authors will independently extract data from eligible studies and assess risk of bias. For continuous outcomes, which follow discrete distribution, mean difference will be calculated. Dichotomous data will be presented using risk ratios, while count data will be expressed using rate ratios. Time-to-event outcomes will be reported as HRs. All estimates will be presented together with 95%?CI. Studies comparable with respect to methodology and reporting the same outcomes will be combined in a meta-analysis. ETHICS AND DISSEMINATION:Our systematic review does not require approval from the research and ethics board. We will use the findings to prepare a future multicentre randomised control trial in order to establish safe and adequate antibiotics policies for preterm infants, based on the aetiology of PTB. PROSPERO REGISTRATION NUMBER:CRD42016029707.

SUBMITTER: Seliga-Siwecka J

PROVIDER: S-EPMC5922463 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

Seliga-Siwecka Joanna J Ansari Mohammed Toseef MT Aschner Judy J Sampson Margaret M Romańska Justyna J

BMJ open 20180427 4

<h4>Introduction</h4>Preterm birth (PTB) at <37 weeks of gestation is the leading cause of perinatal morbidity and mortality in developed countries. The traditional approach has been based on the assumption that PTB is primarily a result of intrauterine infection, which triggers preterm labour and puts the newborn at risk of early onset sepsis (EOS). We are currently experiencing a rise in prematurity that results from maternal and fetal diseases unrelated to infection. We have designed a system ...[more]

PMID: 29703848

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Project description:Frequent use of antibiotics in preterm infants disturbs their gut microbial balance. In this preliminary observational study, we investigated the effect of different antibiotic regimens, administered during the first week of life, on microbial composition and diversity in very low birth weight (VLBW) preterm infants. We performed fecal sampling of breastfed VLBW infants on days 7, 14, and 30. After excluding stool samples from infants who received probiotics or who were administered antibiotics beyond the age of 7 days, we compared gut microbiota profiles between infants receiving a combination of ampicillin and gentamicin for 3 days (AG group, n = 10) and those receiving a combination of ampicillin and cefotaxime for 7 days (AC group, n = 14) using 16S ribosomal DNA community profiling. We also assessed the changes over time in each group. Compared to the AG group, Enterococcus species were significantly more abundant in the AC group (P = 0.002), especially in 7-day samples (12.3 vs. 0.6%, respectively, P = 0.032). No difference was observed at phylum and genus level over time within each group. Species richness in the AC group decreased significantly in the 14-day (P = 0.038) and 30-day (P = 0.03) samples compared to that in the 7-day sample. The same was observed for microbial evenness; in contrast, no significant difference in Shannon index and beta-diversity was detected between the two groups. Controlling for relevant confounding variables did not change the results. In conclusion, different antibiotic regimens affect the early development of gut microbiota in VLBW preterm infants. Prolonged use of ampicillin and cefotaxime might result in overabundance of Enterococcus. However, given that no significant differences were observed in 1-month samples, bacterial genera appear to continue colonizing the gastrointestinal tract despite previous exposure to antibiotics. The clinical relevance of these findings should be elucidated by further studies.

Project description:Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses (I(2) > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval = 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval = 8 to 15]; I(2) = 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.

Project description:BACKGROUND:The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. METHODS AND FINDINGS:We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (? 3) and when applying the three different criteria of evidence the strength of the causality was weak. CONCLUSIONS:Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.

Project description:BackgroundParental sensitivity is the interaction process by which parents (a) recognize cues from their infant, (b) interpret these cues adequately, (c) identify an appropriate response and (d) apply this response in an appropriate time frame. In the neonatal intensive care unit, parents of preterm infants often encounter factors hampering the establishment of their parental sensitivity. Parents report the need to be in proximity to and to participate in their preterm infant's care in order to develop their sensitivity to their newborn infant. To do so, the effectiveness of interventions promoting their parental sensitivity has been evaluated with randomized controlled trials. The purpose of this systematic review is to evaluate the effectiveness of early interventions promoting parental sensitivity of preterm infants' parents.Methods/designA search will be done in the following databases: CINAHL, PubMed in addition to Medline, Embase, PsycInfo, Web of Science, Scopus and ProQuest. No restriction for the years of publication will be considered. Two experts will be conducting independently each step of the review. All studies of randomized controlled trials of early interventions, for parents of preterm infants, implemented in the neonatal intensive care unit before the infant has reached 37 weeks of corrected gestational age, will be considered eligible. Primary outcome is parental sensitivity. Depending on the availability and quality of data, a meta-analysis will be done. Alternatively, a qualitative synthesis of data is planned. The systematic review follows the PRISMA recommendations. Finally, risk of bias and quality of the evidence of included studies will be assessed.DiscussionTo our knowledge, this will be the first systematic review to examine the effect of early interventions that promote parental sensitivity of parents of preterm infants in the neonatal intensive care unit. The results of this review will guide development of best practice guidelines and recommendations for further research and will have implications for neonatal clinical practice.Systematic review registrationPROSPERO CRD42016047083.

Project description:BackgroundEmpiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19.MethodsThis was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics.ResultsA total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes.ConclusionFollowing the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.

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Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

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Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

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