In 2000, the United Nations prioritized decreasing under-five mortality in the Millennium Development Goals (MDGs), recognizing the critical role of developing local health system capacity in improving childhood morbidity and mortality [1]. Moreover, the sustainable development Goals (SDGs) and specifically, SDG 3.2 set the target of ending preventable death of newborns and children under 5 years of age, all countries aiming to reduce neonatal mortality to at least as low as 12 per 1000 live births and under 5 mortality to at least as low as 25 per 1000 live births by 2030 [2]. Even though Ethiopia was one of the few countries to achieve the MDG of a 67% decrease in under-five year old mortality, gains in neonatal mortality lagged substantially behind other age groups; contrary to the SDG target set, the neonatal mortality is in an increasing trend (increased from 29 per 1000 live births in 2016 to 33 per 1000 live births in 2019) [1,2,3]. Globally, neonatal sepsis accounts for one-third of neonatal deaths and annually, there are estimated over 3 million infants 0-59days old dying, over 500,000 of them being due to possible serious bacterial infections (PSBI) [4].
In infants 0–59 days old, symptoms and signs of serious bacterial infections like sepsis and meningitis are usually non-specific and overlapping, making distinction between the different spectrum of presentations difficult for health care providers. PSBI is defined as the presence of one or more of the below in infants 0–59 days old: fast breathing (respiratory rate of ≥ 60 per minute), movement only when stimulated, not feeding well on observation, temperature greater than or equal to 38 °C or less than 35.5 °C, severe chest in-drawing, convulsions, unable to feed at all, cyanosis, grunting, hypoxemia, lethargy/unconciousness [4,5,6].
The WHO recommendation for the management of PSBI in infants 0-59 days old is hospitalization and treatment with at least 7-days course of antibiotics (with a combination of injectable penicillin and gentamicin). If staphylococcal infection is suspected, a combination of cloxacillin and gentamicin is recommended [4,5,6]. However, inpatient treatment options are not accessible, acceptable or affordable to many infants and families in many of the developing countries. These challenges leave such infants without treatment and hence leading to unnecessary preventable deaths which is against SDG of ending preventable neonatal mortality [2, 5]. In order to overcome these challenges and improve access to the treatment of PSBI in infants 0–59 days old, WHO issued guidance in 2015 [5] which was updated in 2024 [6] for outpatient treatment of PSBI to be used when referral for inpatient treatment is not possible or refused in infants 0-59 days old [5]. The guidance simplifies antibiotic selection for infants 0–59 days of age with PSBI in the absence of clinical microbiological data. Even if different clinical trials have been conducted on these simplified treatment of PSBI in infants 0–59 days old and demonstrated the efficacy and safety of these treatments [7, 8], its implementation in real life has not been conducted. Hence, supported by the WHO, between 2016 and 2017, Jimma and Mekelle Universities, institutions in different regions of Ethiopia, implemented the simplified management of PSBI in infants 0–59 days old when referral is not possible or refused at primary health care unit level using the 2015 WHO treatment guidelines. The implementation studies conducted in the two settings have demonstrated that the simplified treatment was acceptable and feasible from the care givers and health care workers perspectives [9, 10]. The studies used for the development of the guidelines, including the African Neonatal Sepsis Trial (AFRINEST) [7, 8] multicenter trial, have focused almost exclusively on clinical outcomes, including treatment failure and mortality. However, these studies have not assessed the clinical microbiology and antimicrobial susceptibilities of PSBI in outpatient settings, so it remains unclear if the simplified antibiotic regimens recommended in the guidance are appropriate.
Notably, the guidelines are standardized across the globe. Studies from Ethiopia and other low- and middle-income countries (LMICs) have found that the bacterial species responsible for neonatal infection differ from those in high-income countries (HICs), with higher rates of Staphylococcus aureus, Escherichia coli, and Klebsiella species and lower rates of Streptococcus agalactiae or “Group B Strep” in LMICs [11,12,13,14,15]. Despite this discrepancy, in most of these studies, the antibiotics administered for PSBI in the inpatient setting in LMICs were similar to those administered in HICs: ampicillin or penicillin with gentamicin as first-line therapy and a 2nd or 3rd generation cephalosporin as second-line treatment. Some studies included oxacillin or cloxacillin as a first-line treatment, but this was uncommon. Moreover, several studies in Ethiopia and other LMICs have shown high rates of resistance to first- and second-line antimicrobials [11, 14, 15], and a recent review estimated resistance to both first- and second-line antimicrobials to be as high as 43–44% [16]. Taken together, the effectiveness of the guidelines is likely to differ by setting, and likely, not be as effective in LMICs.
Blood culture is the most important diagnostic test for identifying neonatal sepsis, allowing microbial identification and antibiotic susceptibility testing, which guide antibiotic selection. Unfortunately, due to the cost of blood culture, supply chain challenges, and laboratory capacity, many therapeutic decisions in LMICs including the study setting are made empirically using WHO or local guidelines [4]. The most common empiric treatment selections for PSBI were ampicillin and gentamicin, plus cloxacillin or a cephalosporin if there was concern for skin, bone, or joint infection. We aimed to compare the standard of care antibiotics provided per existing protocols to the antibiotic susceptibilities of the isolated microorganisms and develop local antibiogram to ascertain whether the existing WHO guidelines are appropriate for the treatment of PSBI in 0–59 days old infants admitted to Jimma University Hospital from March 2019 to March 2020.