International train the trainer neonatal antibiotic stewardship program for South African pharmacists

Hospital‐acquired antimicrobial‐resistant infections are a leading cause of neonatal mortality in South African (SA) neonatal intensive care units (NICU). There is an urgent need for NICU Antibiotic Stewardship Programs (ASP). We describe the development of an international Train‐the‐Trainer (TTT) NICU‐ASP mentoring program for SA pharmacists. A partnership between the South Africa Antimicrobial Stewardship Program (SAASP) and ASP experts from two United States (US) hospitals was formed in 2019. A baseline assessment of four SA NICUs was done to guide the development of a TTT NICU‐ASP mentoring of SA pharmacists utilizing the existing workforce. The program included bilateral site visits. Pre‐post surveys were used to assess SA mentee's NICU experiences, barriers to clinical pharmacy services and confidence to train additional pharmacists in NICU ASP. Four mentees from private (n = 1) and public hospitals (n = 3) completed a 2‐week TTT NICU‐ASP in the US that included; education, patient care rounds, role‐playing, peer‐to‐peer sessions and behavioral interventions followed by ongoing support and mentoring by SAASP mentors. None of the hospitals had pharmacists participating in daily patient care rounds or had multidisciplinary NICU‐ASPs due to lack of NICU trained pharmacists and dedicated time for ASP. Post surveys showed improved confidence to train additional pharmacists in NICU‐ASP. Subsequently, these SA mentees provided NICU‐ASP education to over 700 health care professionals and trained six additional pharmacists in NICU‐ASP. Mentors and mentees developed a comprehensive NICU ASP toolkit for ongoing training of additional pharmacists. A new research collaboration between TTT NICU‐ASP mentors, mentees and physician members of the South Africa National Neonatal Sepsis Task Force has formed and the first national NICU‐ASP study is underway in 12 hospitals. Shared leadership between U.S. and SA mentors led to developing a TTT NICU‐ASP for pharmacists tailored to existing resources and local needs.


Funding information
Pfizer; International Scholars Program at Nationwide Children's Hospital, The Ohio State University Program (SAASP) and ASP experts from two United States (US) hospitals was formed in 2019. A baseline assessment of four SA NICUs was done to guide the development of a TTT NICU-ASP mentoring of SA pharmacists utilizing the existing workforce. The program included bilateral site visits. Pre-post surveys were used to assess SA mentee's NICU experiences, barriers to clinical pharmacy services and confidence to train additional pharmacists in NICU ASP. Four mentees from private (n = 1) and public hospitals (n = 3) completed a 2-week TTT NICU-ASP in the US that included; education, patient care rounds, role-playing, peer-to-peer sessions and behavioral interventions followed by ongoing support and mentoring by SAASP mentors. None of the hospitals had pharmacists participating in daily patient care rounds or had multidisciplinary NICU-ASPs due to lack of NICU trained pharmacists and dedicated time for ASP. Post surveys showed improved confidence to train additional pharmacists in NICU-ASP. Subsequently, these SA mentees provided NICU-ASP education to over 700 health care professionals and trained six additional pharmacists in NICU-ASP.
Mentors and mentees developed a comprehensive NICU ASP toolkit for ongoing training of additional pharmacists. A new research collaboration between TTT NICU-ASP mentors, mentees and physician members of the South Africa National Neonatal Sepsis Task Force has formed and the first national NICU-ASP study is underway in 12 hospitals. Shared leadership between U.S. and SA mentors led to developing a TTT NICU-ASP for pharmacists tailored to existing resources and local needs.

| INTRODUCTION
More than 214 000 infants die each year from multidrug-resistant (MDR) infections. 1 Most of these deaths occur in low-middle income countries (LMIC). In South Africa, neonatal deaths account for approximately 40% of all deaths in children <5 years of age. 1 Data obtained in 2020 from the largest (n = 142 bed) neonatal intensive care unit (NICU) in South Africa found hospital-acquired antimicrobial-resistant infections are the leading cause of late neonatal mortality. 2 The authors recommend implementation of NICU antimicrobial stewardship programs (ASP).
While progress has been made with adult ASPs in South Africa 3,4 NICU-ASPs are largely not present in South African hospitals due to few physicians and pharmacists trained in infectious diseases (ID) and neonatal ASP. The benefit to implementing NICU-ASPs in resource constrained South African hospitals could result in mortality reduction from MDR infections. Large outbreaks of bacterial infections in South Africa NICUs have resulted in the death of many neonates. One hospital reported a 3-fold increase in neonatal deaths from 48 to 140 in 1 year, due to multidrug-resistant Klebsiella pneumonia. 5 Another hospital reported 10 infants died over a 2-month period following an outbreak due to Carbapenem-resistant Enterobacteriaceae (CRE). 6 Factors associated with this outbreak were identified to be overcrowding, understaffing and inadequate infection control practices (ICP).
In 2019, South African physicians launched a new National Neonatal Sepsis Task Force to tackle neonatal sepsis with uniform guidelines and protocols. 7 However the task force did not include a role for pharmacists.
In South Africa, the pharmacists' role in NICUs is primarily for the provision of medications. 8 The need for clinical NICU pharmacy services was identified in a 2017 study. The authors report 9 neonates are three times more likely to experience a medication error than adults, 78% of patients had one or more medication error(s) and anti-infectives (43%) had the most errors. Inadequate knowledge and insufficient training were identified as major causes of medication errors. Implementing NICU-ASPs with pharmacists requires redistributing and retraining the existing pharmacist workforce. The purpose of this paper is to describe the development and impact of an international Train the Trainer (TTT) NICU-ASP for South African pharmacists.

| ASP in South Africa
The South African Antibiotic Stewardship Programme (SAASP) was founded in 2012. A partnership was formed in 2012 between The Ohio State University (OSU) ID pharmacist and SAASP to develop a TTT ASP for South African pharmacists. The program implementation, outcomes and nine-year sustainability were previously described. 10 South African pharmacy schools do not offer ID or neonatal postgraduate training programs. Pharmacists providing NICU clinical pharmacy services are often self-taught or learn on the job.

| NICU-ASP call to action
In response to a 2018 CRE outbreak that resulted in the death of neonates at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, the US Centers for Disease Control and Prevention (CDC) was asked to conduct an infection control practices (ICP) assessment and identify opportunities for improvement. The hospital did not have a NICU-ASP and the pharmacist role was limited to providing ward stock from the pharmacy located three blocks away.
Nurses were responsible for calculating, preparing, and administering all NICU intravenous (IV) medications prepared without a laminar flow hood or consistent proper sterile technique. The CDC identified the urgent need for safe preparation and administration of IV medications and recommended that a pharmacist dedicated solely to the NICU oversee all medication prescriptions, preparation, stock control, and training of healthcare workers on medication safety. In addition, the CDC recommended developing a NICU-ASP to promote the judicious use of antimicrobials. The CDC requested the OSU ID pharmacist TTT-ASP program director to assist in developing NICU-ASP clinical pharmacy services at CHBAH. After discussions with SAASP pharmacist leaders to determine the feasibility and willingness to expand existing ASP efforts by pharmacists to NICU's a collaborative decision was made to provide assistance to CHBAH's NICU using the TTT-ASP model.

| Train the trainer program for NICU-ASP
A partnership was formed in September 2018 between faculty from OSU and Nationwide Children's Hospital (NCH) in Columbus Ohio.
The OSU ID pharmacist TTT program director for adult ASP and an OSU ID physician collaborated with a pediatric ID neonatology physician, NICU ASP pharmacist, and pediatric surgeon to develop the NCH on-site training program for South African pharmacists using similar methodology to the adult TTT-ASP for South African pharmacists. The OSU-NCH faculty partnered with three SAASP pharmacists to co-develop TTT NICU-ASP. The OSU TTT program director received a grant to fund the program.

| Baseline assessment of NICU pharmacy services and NICU ASP
The OSU-NCH mentors worked with SAASP pharmacist mentors in four South African NICUs, one based on the CDC's request and three based on the OSU-SAASP mentor's 9-year involvement with TTT ASP for adult patients. The goal of the visit was to conduct an assessment of NICU pharmacy services, engage with key stakeholders for NICU-ASP and interview pharmacists for TTT NICU-ASP at NCH in Columbus Ohio. Table 1    To address how to start NICU clinical pharmacy services, the mentees met with a retired NICU pharmacist who started NICU clinical pharmacy services at OSU in 1987. 13 The pharmacist described the "baby steps" she took to introduce clinical pharmacy services to neonatologists and nurses, whose only prior experiences were interactions on providing medications. Initially, physicians and nurses had not seen a role for a NICU pharmacist; but she started by documenting medication errors. Her contributions to medication safety broke ground for her to participate in NICU patient care rounds. Notably, this method of implementing NICU clinical pharmacy services in 1987 was successful and sustained over 40 years.
Mentees recorded a podcast about their experience to share on WhatsApp with colleagues. After the mentees returned to South Africa, the US mentors conducted four monthly webinars to continue to advance their NICU knowledge.

| The TTT NICU ASP in South Africa
Upon returning to South Africa, the SAASP mentors continued to support, mentor, and sponsor the mentees. These mentors conducted one-on-one sessions to address challenges and barriers to implementing NICU-ASP. In addition, OSU-NCH and SAASP mentors had monthly calls to discuss each mentees progress and maintain momentum for NICU-ASP.

| RESULTS
Four South African pharmacists came to the US and completed the US component of TTT NICU-ASP.

| Survey-changes in skills and confidence
The pre-survey identified the mentees' greatest fear was approaching a physician to make NICU-ASP recommendations and interventions.
All mentees listed their confidence level to make these interventions as "low," due to lack of NICU-ASP experience or limited knowledge.
Lack of access to publications was identified as a problem by all mentees. Three mentees stated they had a relationship with the neonatologist, but did not have daily patient care interactions due to dispensing responsibilities. All mentees stated they had no experience observing a pharmacist participating in patient care rounds while making recommendations or interventions as part of a multidisciplinary NICU-ASP team.
In the post survey, mentees showed improvement in applying NICU knowledge based on their ability to make appropriate antibiotic recommendations in six patient case scenarios presented by the OSU-NCH mentors. Mentees described improvement in their confidence level to recommend and monitor empiric antimicrobials, assess appropriate antimicrobial durations and make NICU-ASP interventions.
Mentees highly valued the one-on-one role-playing and peer-to-peer sessions with physicians and pharmacist mentors to foster confidence to make NICU-ASP recommendations to physicians. The one-on-one sessions with physician and pharmacist mentors addressed the mentees' fears. Mentors stressed the importance of building a relationship, leveraging the power of face-to-face interactions, and using "handshake stewardship." Physicians shared how trust in the pharmacist accumulates over time based on repeated positive interactions.
All mentees stated this was their first experience to role-play in one- • Implemented stewardship intervention on antibiotic duration of therapy in sepsis. • Increased engagement with neonatologists, more confident with asking questions and making antibiotic recommendations. • Improved credibility with neonatologists and nursesgreater adoption of ideas for improvement in stewardship. • Started a project on reducing "just in case" antibiotic prescriptions at discharge. • Mentored a new pharmacist.
• Completed of Master's thesis on Amikacin peak and trough levels in neonates and submitted the manuscript in collaboration with one of the mentors.
• My increased confidence to contribute in antibiotic stewardship committee meetings resulted in becoming an active member of the stewardship committee and pharmacy and therapeutic committee. • Reviewed empiric antibiotic guidelines for neonates using local antibiograms. • Improved the compliance to our antibiotic guidelines and use of restricted antibiotics. perspective of the pharmacist changed over the following months. Initially nurses told the pharmacist that they were very hesitant to follow the CDC's recommendation to give up medication compounding to the new pharmacist; however, with on-going support from the TTT NICU-ASP mentee the NICU pharmacist's role changed from "provider of ward stock" to an essential NICU team member. The neonatologist co-authored an abstract with the TTT NICU-ASP mentee, NICU pharmacist, OSU mentor and CDC physician that was accepted to the 2020 US Decennial Infectious Diseases Conference. The mentee pharmacist decreased the medication error rate from 17% to 3% over 7 months. When the grant funding expired, the NICU pharmacist position was approved as a permanent post, due to the documented impact of pharmacists on patient care. Based on the high performance of the TTT NICU-ASP mentee, she was promoted to manager of the NICU pharmacist, NICU and pediatric pharmacy services, and ASP.
Additional accomplishments from the TTT NICU-ASP are listed in Table 2.
At DGMAH, the pharmacist mentee applied her new skills to train one pharmacist in NICU-ASP, and mentor pharmacy interns and students during their NICU rotation. Her leadership skills led to an appointment on the outbreak response team for the neonatal and pediatric wards, and input into a quality improvement project for medication safety. Another pharmacist was assigned to assist in dispensing and the mentee had 2 hours daily to provide clinical pharmacy contacted the physician to discuss her joining the task force. The neonatologists not only welcomed the NICU-ASP mentee to the task force, but also asked to collaborate with the SAASP mentor. Table 2 lists additional ways this mentee applied new clinical pharmacy skills she observed while at NCH.
The pharmacist mentee from NFH observed improved credibility with the neonatologists and nurses due to her increased confidence to make NICU-ASP recommendations with acceptance by the physicians. The mentee trained three Netcare pharmacist in NICU-ASP.
The small NICU at NFH had a low incidence of MDR pathogens and low antibiotic use; however, the mentee successfully worked with the neonatologists and implemented the first NICU-ASP intervention to shorten the duration of antibiotic therapy in early-onset sepsis. Additional NICU initiatives by the mentee are listed in Table 2.

| Collaboration to develop the NICU ASP toolkit
Lastly

| Outcome
The  10 We added elements of behavior change science and social determinants of antimicrobial prescribing, since antibiotic stewardship is a highly social interaction influenced by human behaviors. 17,18 The addition of behavior change science to the TTT NICU-ASP was highly valued by each mentee.