Frequency of bystander exposure to antibiotics for enteropathogenic bacteria among young children in low-resource settings

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.

Antibiotic use causes selection pressure for antimicrobial resistance (AMR), a growing global public health crisis that threatens to render antibiotics ineffective against many high-burden infections (1). Most of the concern is placed on the development of resistance in the target pathogen of treatment (i.e., the pathogen causing the treated illness). However, systemic treatment also results in antibiotic exposure for commensal bacteria and pathogens carried asymptomatically at the time of treatment (2). Selective pressure for resistance among organisms that are not the target pathogen has been called “bystander selection” (3, 4). While the public health relevance of resistance in nonpathogenic commensal organisms is less clear, bystander selection among pathogens carried asymptomatically at the time of treatment has direct consequences for the development of resistance in those pathogens (4). This type of selection has the potential to promote antibiotic-resistant disease in settings where subclinical carriage of pathogens is common.Children in low-resource settings frequently carry enteric pathogens in the absence of diarrheal symptoms (5). Enteroaggregative Escherichia coli (EAEC), for example, was detected in nearly half (49%) of nondiarrheal stools collected in the first 2 y of life in the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) birth cohort study conducted in South America, South Asia, and sub-Saharan Africa (6). Campylobacter and Shigella, which are on the World Health Organization priority pathogen list for concern for AMR (7), were detected in 28% (5) and 10% (8) of nondiarrheal stools, respectively. Antibiotic treatment is also highly common in these populations, with approximately five treatment courses per child-year observed in MAL-ED (9). Children were treated with more than one antibiotic course per child year for diarrhea alone (10), despite treatment guidelines that only recommend treatment for dysentery (11), which comprised less than 5% of diarrheal episodes (10). For these reasons, children in low-resource settings represent a unique population in which the burden of bystander selection on enteric pathogens could be particularly high.Antimicrobial stewardship interventions to prevent antibiotic overuse and interventions to prevent illnesses that prompt antibiotic treatment, such as vaccines, could have the ancillary benefit of reducing bystander selection (12). However, the magnitude of this potential impact is unknown. A prior study quantified the proportion of antibiotic exposures for specific pathogens that were not related to the treatment of that pathogen based on modeled data from unrelated sources (3). The observational birth cohort study, MAL-ED, provides a unique opportunity to characterize bystander antibiotic exposure directly since testing for enteric pathogen carriage was conducted monthly in nondiarrheal stools from birth to 2 y of age, and antibiotic use was comprehensively documented during twice-weekly surveillance visits. Here, we aimed to quantify the absolute frequency of bystander antibiotic exposures for enteric bacterial pathogens carried asymptomatically at the time of treatment among children in MAL-ED. We compared the frequency of antibiotic exposures that occurred when the bacteria were the target pathogen to when they were bystanders and attributed bystander exposure to specific indications for treatment. We also identified child characteristics that were associated with bystander antibiotic exposures. Finally, we assessed the association between bystander antibiotic exposure and resistance both at the individual and the community level using E. coli as a model organism.     

Effect of sumac extract on serum oxidative status,RANKL/OPG system and alveolar bone loss in experimental periodontitis in rats

Objectives

Sumac (Rhus coriaria L.) is widely used spice which has several properties such as antioxidant, anti-inflammatory and antimicrobial. The purpose of this animal study was to evaluate the effects of sumac extract on levels of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG) expression, serum oxidative status, and alveolar bone loss in experimental periodontitis.

Material and Methods

Twenty-four Wistar rats were separated into three groups: non-ligated (NL, n=8), ligature only (LO, n=8), and ligature and treated with sumac extract (S, n=8) (20 mg/kg per day for 11 days). A 4/0 silk suture was placed around the mandibular right first molars subgingivally; after 11 days, the rats were sacrificed, and alveolar bone loss was histometrically measured. The detection of RANKL and OPG were immunohistochemically performed. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed.

Results

Alveolar bone loss was significantly greater in the LO group compared to the S and NL groups (p<0.05). The number of inflammatory cell infiltrate (ICI) and osteoclasts in the LO group was significantly higher than that of the NL and S groups (p<0.05). The number of osteoblasts in the LO and S groups was significantly higher than that of the NL group (p<0.05). There were significantly more RANKL-positive cells in the LO group than in the S and NL groups (p<0.05). OPG-positive cells were higher in S group than in LO and NL groups (p<0.05). TOS and OSI levels were significantly reduced in S group compared to LO group (P<0.05) and TAS levels were similar in S and NL group (p>0.05).

Conclusions

The present study showed that systemic administration of sumac extract may reduce alveolar bone loss by affecting RANKL/OPG balance, TOS and OSI levels in periodontal disease in rats.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

A Prospective,Randomized Comparison of Modified Pulmonary Vein Isolation Versus Conventional Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation

Modified Pulmonary Vein Isolation in AF Ablation. Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high‐frequency AF nests may have a higher efficacy. Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0–1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy‐guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time‐domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow‐up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log‐rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155–1162, November 2012)     

银屑病和日光性角化病皮损应用氨基-γ-酮戊酸荧光染色后肉眼荧光强度与原卟啉Ⅸ含量的相互关系

应用5-氨基-γ-酮戊酸（ALA）诱导的卟啉荧光诊断（FDAP）中，肉眼可观察到原卟啉IX（PpIX）沉积。因操作重复性低，且涉及PpIX肿瘤选择的机制知之甚少，所以解释荧光数据仍有些困难。本研究中，作者要研究FDAP后银屑病和日光性角化病（AK）患者皮损的PpIX沉积情况。基于此目的，将患者脱屑区皮损和无皮损正常皮肤用20％ALA油孵育3h，进行FDAP，取强荧光区皮损和无皮损处皮肤活检。从活检标本中提取PpIX、蛋白质和双链DNA行荧光分光光度法定量，用图像分析软件分析由FDAP获得的数字图像。     

1型糖尿病患儿的课堂注意力：稳定血糖的效果

目的:观察评估通过使用胰岛素泵以稳定血糖,是否可以改善1型糖尿病患儿的课堂注意力。试验设计:对4例患有1型糖尿病且血糖水平不稳定的患儿在课堂中的表现进行为期10d的观察。在放置胰岛素泵,控制血糖后再观察10d。利用改良多基线设计血糖控制水平是否与患儿专注于功课和走神行     

Prevalence of behaviour disorders in low birthweight infants

OBJECTIVE--To determine the prevalence of behaviour disorders in low birthweight infants. DESIGN--Children of birth weight < or = 2000 g born to mothers resident in Merseyside in 1980-1 assessed using the Rutter parent and teacher behaviour questionnaires and the Conner modification of the Rutter teacher questionnaire. Children attending normal schools were assessed with controls matched for age, sex, and class in school. Children attending special schools were assessed unmatched. SUBJECTS--233 matched case-control pairs attending normal primary schools and 46 unmatched children attending special schools. SETTING--Primary and special schools. MAIN OUTCOME MEASURES--Emotional, conduct, and undifferentiated behaviour disorders and hyperactivity. RESULTS--On the parental questionnaire screen, 36% of the cases and 22% of the controls had a behaviour disorder and on the teacher questionnaire the proportions were 27% and 12% respectively. Hyperactivity was significantly more common among male cases than their controls (21% v 5.0%) but differed little among female cases and controls (9% v 7%). CONCLUSIONS--Improving neonatal survival of low birthweight infants is accompanied by a higher prevalence of behaviour disorders. The long term implications for psychiatric morbidity and other adult disease must be monitored.     

Regional cerebral blood flow and oxygen metabolism during migraine with and without aura

Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO₂) and oxygen extraction (rOER) were measured during baseline ( n =11), aura ( n = 6), headache ( n = 10) and after treatment with sumatriptan ( n = 4). Data were analysed using and ROI-based approach from 26 different anatomically defined regions, and also an exploratory approach whereby all subjects were normalized to a stereotactic brain atlas; t -maps were constructed by depicting significant changes between states. The exploratory approach revealed a region corresponding to the primary visual cortex with significant reductions in rCBF (23.1%) and rCMRO₂ (22.5%), but no change in rOER during the headache phase compared to baseline. These data suggest that cerebral ischemia was not the primary cause of the attacks in these cases.