Plasmid-mediated quinolone resistance genes detected in Ciprofloxacin non-susceptible Escherichia coli and Klebsiella isolated from children under five years at hospital discharge, Kenya.

BACKGROUND: The increasing spread of fluoroquinolone resistant enteric bacteria is a global public health concern. Children recently discharged from the hospital are at high risk of carriage of antimicrobial resistance (AMR) due to frequent exposure to antimicrobials during inpatient stays. This study aimed to determine the prevalence, correlates of ciprofloxacin (CIP) non-susceptibility, and distribution of plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli (E. coli) and Klebsiella spp isolated from children under five years being discharged from two Kenyan Hospitals. METHODS: E. coli and Klebsiella spp were isolated from fecal samples from children discharged from hospital and subjected to antimicrobial susceptibility testing (AST) by disc diffusion and E-test. CIP non-susceptible isolates were screened for seven PMQR genes using multiplex polymerase chain reaction (PCR). Poisson regression was used to determine the association between the carriage of CIP non-susceptible isolates and patient characteristics. RESULTS: Of the 280 CIP non-susceptible isolates: 188 E. coli and 92 Klebsiella spp isolates identified among 266 discharged children, 195 (68%) were CIP-non-susceptible with minimum inhibitory concentrations (MICs) of ≥ 1 µg/mL. Among these 195 isolates, 130 (67%) had high-level CIP MIC = ≥ 32 µg/mL). Over 80% of the isolates had at least one PMQR gene identified: aac(6')lb-cr (60%), qnrB (24%), oqxAB (22%), qnrS (16%), and qepA (6%), however, qnrA was not identified in any isolates tested. Co-carriage of qnrB with acc(6')-lb-cr was the most predominant accounting for 20% of all the isolates. Ceftriaxone use during hospital admission and the presence of extended spectrum beta-lactamase (ESBL) production were significantly associated with the carriage of CIP non-susceptible E. coli and Klebsiella spp. CONCLUSION: CIP non-susceptibility is common among E. coli and Klebsiella spp isolated from hospital discharged children in Kenya. Carriage and co-carriage of PMQR, including the newly identified qepA gene, were frequently observed. These findings suggest that children leaving the hospital may serve as an important reservoir for transmission of resistant E. coli and Klebsiella spp to the community. Enhanced surveillance for AMR determinants is critical to inform interventions to control antimicrobial-resistant bacteria.

Understanding the Relationship Between Social Stressors, Trauma, and Somatic Symptoms Among Latina Immigrant Women.

BACKGROUND: Latina immigrant women are at increased risk for poor mental health. Little is known about factors associated with somatic symptoms, the physical manifestation of distress, in this population. This study examined associations between social stressors, trauma, and somatic symptoms. METHODS: This study used survey data from a community-based sample of Latina immigrant women (n = 154). We determined the frequency of somatic symptoms and used linear regressions to estimate associations of stressors and trauma with physical symptoms. RESULTS: Most participants reported mild or moderate levels of somatic symptom severity. In univariate models, all social stressors and trauma types were significantly associated with higher levels of somatic symptoms. A multivariate model suggested perceived stress was associated with increased somatic symptoms after accounting for other stressors and trauma. DISCUSSION: Future research should examine whether stress and trauma lead to higher levels of somatic symptoms among Latina immigrants.

Antimicrobial resistance including Extended Spectrum Beta Lactamases (ESBL) among E. coli isolated from kenyan children at hospital discharge.

BACKGROUND: Children who have been discharged from hospital in sub-Saharan Africa remain at substantial risk of mortality in the post-discharge period. Antimicrobial resistance (AMR) may be an important factor. We sought to determine the prevalence and risk factors associated with AMR in commensal Escherichia coli (E. coli) from Kenyan children at the time of discharge. METHODOLOGY/PRINCIPLE FINDINGS: Fecal samples were collected from 406 children aged 1-59 months in western Kenya at the time of discharge from hospital and cultured for E. coli. Susceptibility to ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol was determined by disc diffusion according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Poisson regression was used to determine associations between participant characteristics and the presence of extended-spectrum beta-lactamases (ESBL) producing E. coli. Non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of ESBL (44%) was high. Receipt of antibiotics during the hospitalization was associated with the presence of ESBL (aPR = 2.23; 95% CI: 1.29-3.83) as was being hospitalized within the prior year (aPR = 1.32 [1.07-1.69]). Open defecation (aPR = 2.02; 95% CI: 1.39-2.94), having a toilet shared with other households (aPR = 1.49; 95% CI: 1.17-1.89), and being female (aPR = 1.42; 95% CI: 1.15-1.76) were associated with carriage of ESBL E. coli. CONCLUSIONS/SIGNIFICANCE: AMR is common among isolates of E. coli from children at hospital discharge in Kenya, including nearly half having detectable ESBL.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

Azithromycin for the prevention of rehospitalisation and death among Kenyan children being discharged from hospital: a double-blind, placebo-controlled, randomised controlled trial.

BACKGROUND: Mass drug administration of azithromycin to children in sub-Saharan Africa has been shown to improve survival in high-mortality settings. The period after hospital discharge is a time of elevated risk unaddressed by current interventions and might provide an opportunity for targeting empirical azithromycin administration. We aimed to assess the efficacy of azithromycin administered at hospital discharge on risk of death and rehospitalisation in Kenyan children younger than 5 years. METHODS: In this double-blind, placebo-controlled randomised trial, children were randomly assigned (1:1) to receive a 5-day course of azithromycin (oral suspension 10 mg/kg on day 1, followed by 5mg/kg per day on days 2-5) or identically appearing and tasting placebo at discharge from four hospitals in western Kenya. Children were eligible if they were aged 1-59 months at hospital discharge, weighed at least 2 kg, and had been admitted to hospital for any medical reason other than trauma, poisoning, or congenital anomaly. The primary outcome was death or rehospitalisation in the subsequent 6-month period in a modified intention-to-treat population, compared by randomisation group with Cox proportional hazards regression and Kaplan-Meier. Azithromycin resistance in Escherichia coli isolates from a random subset of children was compared by randomisation group with generalised estimating equations. This trial is registered with ClinicalTrials.gov, NCT02414399. FINDINGS: Between June 28, 2016, and Nov 4, 2019, 1400 children were enrolled in the trial at discharge from hospital, with 703 (50·2%) randomly assigned to azithromycin and 697 (49·8%) to placebo. Among the 1398 children included in the modified intention-to-treat analysis (702 in the azithromycin group and 696 in the placebo group), the incidence of death or rehospitalisation was 20·4 per 100 child-years in the azithromycin group and 22·5 per 100 child-years in the placebo group (adjusted hazard ratio 0·91, 95·5% CI 0·64-1·29, p=0·58). Azithromycin resistance was common in commensal E coli isolates from enrolled children before randomisation (37·7% of 406 isolates) despite only 3·7% of children having received a macrolide antibiotic during the hospitalisation. Azithromycin resistance was slightly higher at 3 months after randomisation in the azithromycin group (26·9%) than in the placebo group (19·1%; adjusted prevalence ratio 1·41, 95% CI 0·95-2·09, p=0·088), with no difference observed at 6 months (1·17, 0·78-1·76, p=0·44). INTERPRETATION: We did not observe a significant benefit of a 5-day course of azithromycin delivered to children younger than 5 years at hospital discharge despite the overall high risk of mortality and rehospitalisation. These findings highlight the need for more research into mechanisms and interventions for prevention of morbidity and mortality in the post-discharge period. FUNDING: Eunice Kennedy Shriver National Institute of Child Health & Human Development.

Stress, social support and their relationship to depression and anxiety among Latina immigrant women.

OBJECTIVE: Latina immigrant women in the United States are at increased risk of adverse mental health outcomes due to economic, political, cultural and social stressors related to migration and resettlement. However, few studies have described how stress and social supports are related to depression and anxiety symptoms among Latina immigrant women. METHOD: This cross-sectional study used survey data collected from a community-based sample as part of the Amigas Latinas Motivando el Alma (ALMA) study to describe levels of stress, social support, depression and anxiety among Latina immigrant women (N=153). We also estimated associations between stressors, social supports and mental health. RESULTS: At baseline, 29% of participants reported moderate to severe depressive symptoms and 32% of participants reported moderate to severe anxiety symptoms. In adjusted regression models, stressors including social isolation (ß=0.2, p<0.001), perceived stress (ß=0.6, p<.0001), and law/immigration enforcement stress (ß=0.3, p=0.04) were associated with higher levels of depression symptoms. Perceived stress (ß=0.6, p<0.001) and stress associated with meeting basic needs (ß=0.6, p<0.001) were associated with higher levels of anxiety symptoms, while social support received through positive social interactions was associated with fewer anxiety symptoms (ß=-0.8, p=0.03). CONCLUSIONS: Latina immigrant women experience a number of stressors associated with immigration and their social position, which in turn are associated with increased symptoms of depression and anxiety. Future research should examine how social support, along with programs and policies that reduce stress, can improve mental health outcomes in this population.

A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines.

INTRODUCTION: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. METHODS: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. RESULTS: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. CONCLUSION: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans.

Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient's immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible patients, infections (and the resulting fatalities) can be prevented. Currently, this is done using antimicrobial drugs; to "preserve" drugs for treating infections, we looked for a dietary change to reduce the amount of C. albicans in the gut. Using a mouse model, we showed that adding coconut oil to the diet could become the first drug-free way to reduce C. albicans in the gut. More broadly, this model lets us study the interactions between our diet and the microbes in our body and the reasons why some of those microbes, under certain conditions, cause disease. Podcast: A podcast concerning this article is available.