Etiology of Bacterial Sepsis and Isolate Resistance Patterns in Hospitalized Neonates in Zambia.

BACKGROUND: The Sepsis Prevention in Neonates in Zambia study is a prospective cohort study that evaluated an infection prevention and control (IPC) bundle in the University Teaching Hospital neonatal intensive care unit (NICU) in Lusaka, Zambia. We present here the etiologies, antimicrobial resistance profiles, and associated mortality of bloodstream infections (BSI) in this cohort. METHODS: Venous blood was collected from neonates with clinically suspected sepsis and cultured with an automated blood culture system. Organism identification and susceptibility testing were done using the Vitek II system. We used the CDC National Health Safety Network criteria to define pathogens and commensals. RESULTS: There were 1120 blood cultures performed for 1060 neonates with suspected sepsis. Overall, 38% (424/1120) of cultures were positive of which 72% (306/424) grew pathogens. Blood cultures obtained after, as compared to before, 2 days of hospitalization were more likely to yield a pathogen (77% vs. 65%; P < 0.001). Klebsiella pneumoniae was the most prevalent organism, accounting for 74% (225/306) of all pathogens . K. pneumoniae isolates were highly resistant: 98% (221/225) were extended-spectrum beta-lactamase (ESBL)-positive, while 81% were resistant to gentamicin (182/225) and fluoroquinolones (177/219). Only one isolate was carbapenem resistant. Observed mortality rate was 32% (122/380); 61% (75/122) of the deaths was related to Klebsiella BSI. CONCLUSIONS: Multidrug-resistant ESBL-producing Klebsiella species were the main organisms responsible for BSI and were associated with increased mortality. BSI risk increased with prolonged hospitalization, underscoring the importance of IPC measures in the NICU.

Healthcare worker perceptions of the implementation context surrounding an infection prevention intervention in a Zambian neonatal intensive care unit.

BACKGROUND: Infants in the neonatal intensive care unit (NICU) are particularly susceptible to healthcare-associated infections (HAIs). NICUs in low- and middle income countries face additional challenges to HAI prevention. There is a need to better understand the role of the implementation context surrounding infection prevention interventions in low- and middle income countries. AIM: The aim of this study was to identify NICU healthcare worker perceptions of an intervention to reduce bloodstream infections in a large Zambian NICU. METHODS: Semi-structured interviews were conducted with NICU staff during a prospective cohort study examining the impact of an infection prevention bundle on bloodstream infections. Interviews were analyzed using an integrated approach, combining inductive theme generation with an application of the Consolidated Framework for Implementation Research (CFIR). RESULTS: Interviews were conducted with 17 NICU staff (5 physicians and 12 nurses). Respondents believed the bundle elements were easy to use, well-designed and facilitated improved performance. Four organizational characteristics that facilitated HAI transmission were identified - (1) lack of NICU admission protocols; (2) physical crowding; (3) understaffing; and (4) equipment shortages. Respondents suggested that NICU resource constraints reflected a societal ethos that devalued the medical care of infants. Despite the challenges, respondents were highly motivated to prevent HAIs and believed this was an achievable goal. They enthusiastically welcomed the bundle but expressed serious concern about sustainability following the study. CONCLUSIONS: By eliciting healthcare worker perceptions about the context surrounding an infection prevention intervention, our study identified key organizational and societal factors to inform implementation strategies to achieve sustained improvement.

Preventing Bloodstream Infections and Death in Zambian Neonates: Impact of a Low-cost Infection Control Bundle.

BACKGROUND: Sepsis is a leading cause of neonatal mortality in low-resource settings. As facility-based births become more common, the proportion of neonatal deaths due to hospital-onset sepsis has increased. METHODS: We conducted a prospective cohort study in a neonatal intensive care unit in Zambia where we implemented a multifaceted infection prevention and control (IPC) bundle consisting of IPC training, text message reminders, alcohol hand rub, enhanced environmental cleaning, and weekly bathing of babies ≥1.5 kg with 2% chlorhexidine gluconate. Hospital-associated sepsis, bloodstream infection (BSI), and mortality (>3 days after admission) outcome data were collected for 6 months prior to and 11 months after bundle implementation. RESULTS: Most enrolled neonates had a birth weight ≥1.5 kg (2131/2669 [79.8%]). Hospital-associated mortality was lower during the intervention than baseline period (18.0% vs 23.6%, respectively). Total mortality was lower in the intervention than prior periods. Half of enrolled neonates (50.4%) had suspected sepsis; 40.8% of cultures were positive. Most positive blood cultures yielded a pathogen (409/549 [74.5%]), predominantly Klebsiella pneumoniae (289/409 [70.1%]). The monthly rate and incidence density rate of suspected sepsis were lower in the intervention period for all birth weight categories, except babies weighing <1.0 kg. The rate of BSI with pathogen was also lower in the intervention than baseline period. CONCLUSIONS: A simple IPC bundle can reduce sepsis and death in neonates hospitalized in high-risk, low-resource settings. Further research is needed to validate these findings in similar settings and to identify optimal implementation strategies for improvement and sustainability. CLINICAL TRIALS REGISTRATION: NCT02386592.

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children.

Importance: ß-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other ß-lactam antibiotic. However, few studies have evaluated the safety of this combination for children. Objective: To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal ß-lactam antibiotic throughout the first week of hospitalization. Design, Setting, and Participants: This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal ß-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.). Main Outcomes and Measures: The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal ß-lactam antibiotic. Results: A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal ß-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal ß-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14). Conclusions and Relevance: Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Daptomycin Use in United States Children's Hospitals.

We described 1035 pediatric hospitalizations with daptomycin use in 794 patients since 2004. Daptomycin use was uncommon but increased over time. A minority of hospitals accounted for the majority of use. This variability of daptomycin use highlights the need for future studies to assess the efficacy and safety of daptomycin in children.

The burden of pediatric diarrhea: a cross-sectional study of incurred costs and perceptions of cost among Bolivian families.

BACKGROUND: Worldwide, acute gastroenteritis represents an enormous public health threat to children under five years of age, causing one billion episodes and 1.9 to 3.2 million deaths per year. In Bolivia, which has one of the lower GDPs in South America, an estimated 15% of under-five deaths are caused by diarrhea. Bolivian caregiver expenses related to diarrhea are believed to be minimal, as citizens benefit from universal health insurance for children under five. The goals of this report were to describe total incurred costs and cost burden associated with caregivers seeking treatment for pediatric gastroenteritis, and to quantify relationships among costs, cost burden, treatment setting, and perceptions of costs. METHODS: From 2007 to 2009, researchers interviewed caregivers (n=1,107) of pediatric patients (<5 years of age) seeking treatment for diarrhea in sentinel hospitals participating in Bolivia's diarrheal surveillance program across three main geographic regions. Data collected included demographics, clinical symptoms, direct costs (e.g. medication, consult fees) and indirect costs (e.g. lost wages). RESULTS: Patient populations were similar across cities in terms of gender, duration of illness, and age, but familial income varied significantly (p<0.05) when stratified on appointment type. Direct, indirect, and total costs to families were significantly higher for inpatients as compared to outpatients of urban (p<0.001) and rural (p<0.05) residence. Consult fees and indirect costs made up a large proportion of total costs. Forty-five percent of patients' families paid ≥1% of their annual household income for this single diarrheal episode. The perception that cost was affecting family finances was more frequent among those with higher actual cost burden. CONCLUSIONS: This study demonstrated that indirect costs due to acute pediatric diarrhea were a large component of total incurred familial costs. Additionally, familial costs associated with a single diarrheal episode affected the actual and perceived financial situation of a large number of caregivers. These data serve as a baseline for societal diarrheal costs before and immediately following the implementation of the rotavirus vaccine and highlight the serious economic importance of a diarrheal episode to Bolivian caregivers.