Association between Antibiotic Prescribing in Pregnancy and Cerebral Palsy or Epilepsy in Children Born at Term: A Cohort Study Using The Health Improvement Network.

Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network

Risk factors for Haemophilus influenzae and pneumococcal respiratory tract colonization in CVID

To the Editor: Disease-specific studies focused on infection risk in common variable immune deficiencies (CVIDs) are needed to define strategies for controlling respiratory infections predominantly due to bacteria such as Streptococcus pneumoniae and Haemophilus influenzae.1 Little information is available on the rate of airway bacterial carriage and its consequence in hypogammaglobulinemias. Despite IgG replacement, recurrent respiratory infections are common in CVID, possibly leading to chronic lung damage2 and poor quality of life.3 Thus, patients are often prescribed antibiotics and/or long-term antimicrobial prophylactic regimens. Several regimens are used including rotation or periodically changing antibiotics.4 However, antibiotics influence antimicrobial resistance among airway microbiota. In a recent meta-analysis on patients with chronic lung diseases, 30% of S pneumoniae showed resistance to macrolides.

Transfer of antibiotic resistance in Staphylococcus aureus

Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic elements and occurs primarily by conjugation or bacteriophage transduction, with the latter traditionally being perceived as the primary route. Recent work on conjugation and transduction suggests that transfer by these mechanisms may be more extensive than previously thought, in terms of the range of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen

Consumption of antibiotics within ambulatory care in Malta

Background: Antibiotic use is recognised as the most important driver for the development of antimicrobial resistance in community pathogens. Surveillance is therefore critical for improvement programmes. Methods: Antimicrobial distribution data for the years 2007 to 2009 were collected retrospectively by the National Antibiotic Committee from all licensed wholesale distributors (WSL) in Malta and analysed according the World Health Organization Anatomical Therapeutic Chemical classification (ATC) level 4 criteria. Results: Overall consumption increased from 18.6 defined-daily-doses/1000-inhabitant-days (DID) in 2007 to 22.7 DID in 2008 and reached 24.4 DID in 2009 - an increase of more than 30% over the three years, Penicillins with beta-lactamase inhibitor increased in volume (7.1 to 8.8 DID) but decreased in proportion (38.4% to 36.0%) between 2007 and 2009. On the other hand, second generation cephalosporins increased in both volume and proportion (2.8 to 5.4 DID; 15.0% to 22.0%). The proportion for macrolides remained stable at approximately 16% but the volume of use again increased (2.9 DID to 3.9 DID). Fluoroquinolone proportion decreased from 9.1% to 6.8%, maintaining a stable volume of use in the region of 1.7 DID. Conclusions: Antibiotic consumption in Malta has shown a consistent increasing trend over the past three years, despite a reduction in over-the-counter acquisition. Furthermore, there is evidence of a strong, and possibly unjustified, prescription of wide spectrum antibacterials. This is potentially an important driver for documented resistance in Streptococcus pneumoniae and Escherichia coli and needs to be addressed at a national level.peer-reviewe

Characteristics of demand for antibiotics in primary care: an almost ideal demand system approach

We model demand for different classes of antibiotics used for respiratory infections in outpatient care using a linear approximate almost ideal demand system approach. We compute elasticities to socioeconomic determinants of consumption and own- and cross- price elasticities between different groups of antibiotics. We find significant elasticities between newer/more expensive generations and older/less expensive generations of antibiotics. The larger use of more expensive antibiotics is also associated with the self-dispensing status of practices, ceteris paribus.Antibiotic use, Demand equations, Demand elasticities, Almost Ideal Model, Self-dispensing

Influence of chronic azithromycin treatment on the composition of the oropharyngeal microbial community in patients with severe asthma

Background: This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbationprone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbationprone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo. Results: A total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads. We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment. Conclusions: Despite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in half of the patients

Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine

Background Antimicrobial resistance has become a major challenge in veterinary medicine, particularly in the context of bacterial pathogens that play a role in both humans and animals. Objectives This review serves as an update on acquired resistance mechanisms in bacterial pathogens of human and animal origin, including examples of transfer of resistant pathogens between hosts and of resistance genes between bacteria. Results Acquired resistance is based on resistance-mediating mutations or on mobile resistance genes. Although mutations are transferred vertically, mobile resistance genes are also transferred horizontally (by transformation, transduction or conjugation/mobilization), contributing to the dissemination of resistance. Mobile genes specifying any of the three major resistance mechanisms – enzymatic inactivation, reduced intracellular accumulation or modification of the cellular target sites – have been found in a variety of bacteria that may be isolated from animals. Such resistance genes are associated with plasmids, transposons, gene cassettes, integrative and conjugative elements or other mobile elements. Bacteria, including zoonotic pathogens, can be exchanged between animals and humans mainly via direct contact, but also via dust, aerosols or foods. Proof of the direction of transfer of resistant bacteria can be difficult and depends on the location of resistance genes or mutations in the chromosomal DNA or on a mobile element. Conclusion The wide variety in resistance and resistance transfer mechanisms will continue to ensure the success of bacterial pathogens in the future. Our strategies to counteract resistance and preserve the efficacy of antimicrobial agents need to be equally diverse and resourceful. This article is based on a State of the Art presentation at the 8th World Congress of Veterinary Dermatology held May 2016 in Bordeaux, France

Resistance decay in individuals after antibiotic exposure in primary care: A systematic review and meta-analysis

Abstract Background Antibiotic resistance is an urgent global problem, but reversibility is poorly understood. We examined the development and decay of bacterial resistance in community patients after antibiotic use. Methods This was a systematic review and meta-analysis. PubMed, EMBASE and CENTRAL (from inception to May 2017) were searched, with forward and backward citation searches of the identified studies. We contacted authors whose data were unclear, and of abstract-only reports, for further information. We considered controlled or times-series studies of patients in the community who were given antibiotics and where the subsequent prevalence of resistant bacteria was measured. Two authors extracted risk of bias and data. The meta-analysis used a fixed-effects model. Results Of 24,492 articles screened, five controlled and 20 time-series studies (total 16,353 children and 1461 adults) were eligible. Resistance in Streptococcus pneumoniae initially increased fourfold after penicillin-class antibiotic exposure [odds ratio (OR) 4.2, 95% confidence interval (CI) 3.5–5.4], but this fell after 1 month (OR 1.7, 95% CI 1.3–2.1). After cephalosporin-class antibiotics, resistance increased (OR 2.2, 95%CI 1.7-2.9); and fell to (OR 1.6, 95% CI 1.2-2.3) at 1 month. After macrolide-class antibiotics, resistance increased (OR 3.8, 95% CI 1.9–7.6) and persisted for 1 month (OR 5.2, 95% CI 2.6–10.3) and 3 months (OR 8.1, 95% CI 4.6–14.2, from controlled studies and OR 2.3, 95% CI 0.6–9.4, from time-series studies). Resistance in Haemophilus influenzae after penicillins was not significantly increased (OR 1.3, 95% CI 0.9–1.9) initially but was at 1 month (OR 3.4, 95% CI 1.5–7.6), falling after 3 months (OR 1.0, 95% CI 0.5–2.2). Data were sparse for cephalosporins and macrolides. Resistance in Enterobacter increased post-exposure (OR 3.2, 95% CI 0.9–10.8, from controlled studies and OR 7.1, 95% CI 4.2–12, from time-series studies], but was lower after 1 month (OR 1.8, 95% CI 0.9–3.6). Conclusions Resistance generally increased soon after antibiotic use. For some antibiotic classes and bacteria, it partially diminished after 1 and 3 months, but longer-term data are lacking and urgently needed. Trial registration PROSPERO CRD42015025499