Background
Antibiotics are the most commonly used medication in neonatal intensive care unit (NICU). Sepsis being the leading cause of mortality and morbidity, globally as well as in India, the treatment and survival of newborn infants, in particular the premature, is hugely dependent on effective antibiotics.1 2 A risk-based approach with low threshold is often used for starting antibiotic in neonatal sepsis, which has been quite successful in lowering its incidence, but increased number of non-infected infants are exposed to antibiotics. Empiric therapy is often extended to five to 5–7 days even in the absence of positive blood cultures.3 Infants commonly present with non-specific systemic signs suggestive of infection, leading to the frequent use of broad-spectrum empirical antibiotics in infants who are subsequently found to be uninfected. Unreliable clinical signs, disastrous outcome in case of delayed start of antibiotic treatment and reluctance to withdraw initiated treatment often result in overuse of antibiotics in NICU.
Antibiotics are powerful, life-saving drugs, but when used inappropriately, they may have serious adverse effects. Prolonged empirical antibiotic use among preterm infants with negative cultures has been associated with an increased risk of mortality and morbidities such as late-onset sepsis (LOS), necrotising enterocolitis (NEC), >stage 3 retinopathy of prematurity, emergence of fungal infections and multidrug-resistant organisms (MDRO), and also poor neurodevelopmental outcomes.4 Antibiotic overuse causes disruption of the microbiome, which may have lasting consequences reflected as dysbiosis, increased carriage of antibiotic resistance genes and MDROs. Each additional day of antibiotic exposure in the absence of positive blood cultures increases the risk of NEC in very low birthweight (VLBW) babies 7%–20%.5
In a recent study, Flannery et al6 demonstrated that 78.6% of VLBW and 87% of extremely low birthweight (ELBW) infants were treated with antibiotics in their first days of life.6 Additionally, as per a meta-analysis, 26·5% of VLBW and 37·8% of ELBW infants received more than 5 days of antibiotic treatment.7
One of the most effective measures to reduce unnecessary antibiotic exposure and its adverse outcomes is by implementation of antibiotic stewardship programmes (ASPs). The WHO identified the development of a national and institutional antibiotic stewardship programmes (ASPs) as a key instrument to tackle this concern.8 This has prompted calls in the USA and the UK for national action plans to combat antibiotic resistance.9 CDC (Centers for Disease Control and Prevention) launched a collaborative QIP (Quality Improvement Programme) with VON (Vermont Oxford Network), the world’s largest neonatal benchmarking organisation.10
However, unlike the paediatric ASP, which has proven to be effective, lack of evidence-based strategies and easy-to-use guidelines at the point of care preclude adoption of best practices for the use of antibiotics in neonates.11 There is lack of a validated antimicrobial guideline that addresses the unique challenges of the NICU environment, such as culture-negative clinical sepsis and empirical treatment of early-onset sepsis (EOS).