<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>AIM: </strong>The aim of this study was to identify NICU healthcare worker perceptions of an intervention to reduce bloodstream infections in a large Zambian NICU.</p>

<p><strong>METHODS: </strong>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).</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

<p><strong>INTRODUCTION: </strong>Sepsis is the leading cause of infectious morbidity and mortality among hospitalized neonates. In high-resource pediatric and adult intensive care units, use of aqueous chlorhexidine (CHG) solution has been associated with reduced risk of bloodstream infections (BSI).</p>

<p><strong>OBJECTIVES: </strong>To assess the impact of bathing of neonates with 2% CHG on BSI, suspected sepsis, and mortality in a low-income country neonatal care unit.</p>

<p><strong>METHODS: </strong>We conducted a secondary analysis of data from the Sepsis Prevention in Neonates in Zambia (SPINZ) study, a prospective observational cohort study performed at a large public referral hospital in Lusaka, Zambia. The SPINZ study assessed the impact of an infection control bundle (consisting of alcohol hand rub, SMS hygiene reminders, enhanced environmental cleaning, and CHG baths for babies ≥1.5 kg) on sepsis, BSI, and all-cause mortality. Episodic shortages in study staffing resulted in some enrolled babies not receiving a CHG bath. Using Longitudinal Targeted Maximum Likelihood Estimation and Cox proportional hazards regression to adjust for observed confounding, we estimated the causal effect of receiving a CHG bath within the first 3 days of life on suspected sepsis, BSI, and death among inborn babies enrolled during the study implementation and intervention phases.</p>

<p><strong>RESULTS: </strong>The majority of inborn, enrolled babies ≥1.5 kg received a CHG bath within 3 days of NICU admission (864 of 1233, 70%). We found that CHG bathing reduced the hazard rate of BSI among inborn babies ≥1.5 kg by a factor of 0.58 (p = 0.10, 95% CI: 0.31, 1.11), corresponding to an absolute risk reduction of 9.6 percentage points within a week of admission (p = 0.002, 95% CI: 3.4-15.7 percentage points). We did not find a statistically significant effect of CHG bathing on culture-negative sepsis (p = 0.54) or death (p = 0.85).</p>

<p><strong>CONCLUSION: </strong>In our single center study, CHG bathing at admission was associated with a reduced risk of BSI due to a pathogenic organism after adjusting for potential confounding. Our results suggest that CHG may be an effective intervention for preventing neonatal sepsis in high-risk, low-income country settings.</p>

<p><strong>Background: </strong>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.</p>

<p><strong>Methods: </strong>We conducted a prospective cohort study in a neonatal intensive care unit in Zambia where we implemented a multi-faceted 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 (&gt;3 days after admission) outcome data were collected for 6 months prior to and 11 months after bundle implementation.</p>

<p><strong>Results: </strong>Most enrolled neonates had a birthweight ≥1.5 kg (2131/2669, 79.8%). Hospital-associated mortality was lower during the intervention than baseline period (18.0% vs 23.6%). 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 birthweight categories, except babies weighing &lt;1.0 kg. The rate of BSI with pathogen was also lower in the intervention than baseline period.</p>

<p><strong>Conclusions: </strong>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.</p>

<p><strong>Importance: </strong>β-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 β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.</p>

<p><strong>Objective: </strong>To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal β-lactam antibiotic throughout the first week of hospitalization.</p>

<p><strong>Design, Setting, and Participants: </strong>This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal β-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.).</p>

<p><strong>Main Outcomes and Measures: </strong>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 β-lactam antibiotic.</p>

<p><strong>Results: </strong>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 56 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal β-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 β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).</p>

<p><strong>Conclusions and Relevance: </strong>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.</p>

<p>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.</p>