08 Aug 2017
Written by Sandeep Kadam
Antimicrobial resistance (also know as AMR) is a serious global concern resulting in increasing death and chronic disease rates overall, but one group particularly vulnerable is newborn babies.
The burden of early onset or hospital-acquired blood infections, also known as sepsis, is particularly high in neonatal (newborn) intensive care units. This is due to newborns being exposed to multi-drug resistant (MDR) microorganisms because of immature immunity, multiple intervention strategies, and contaminated environments and equipment, such as ventilatory support machines or long lines (catheters). There is a steady rise in multi-drug resistant infections in newborns all over the world in both developed and developing countries which is a major risk associated with the rise of disease rates and death.
Carbapenems are antibiotics often used in hospitals for multi-drug resistant infections. In one tertiary-care hospital in New Delhi, carbapenem-resistance increased from 2% in 2002 to 52% in 2009, to a bacteria called Klebsiellapneumoniae (bacterial pneumonia).
With diminishing options for treating multi-drug resistant Acinetobacter baumannii bacteria, which causes sepsis, meningitis, urinary tract infections and other resistant infections, physicians can use an antibiotic called colistin, but even resistance to colistin is on the rise.
“Given the high death and infection rates, and the subtle symptoms of sepsis, many newborns receive antibiotics on admission to the neonatal unit based on suspicion of sepsis”.
Indian hospitals have reported high gram-negative resistance rates. These are infections, such as E.coli, Klebsiella, Pseudomonas and Acinetobacter, that have high prevalence of Extended Spectrum Beta Lactamases (ESBL), which are bacteria resistant to many penicillin and cephalosporin antibiotics, including carbapenem. As resistance to carbapenem increases, more colistin will be used in patients with infections. Colistin, however, is currently a last line of defense antibiotic, and this increased use creates the possibility of bacteria and, therefore, patients becoming resistant to it too and to other related antibiotics.
A recent study from Delhi has reported that three ‘superbugs’ — Klebsiella, Acinetobacter, and E. coli were associated with 53% of the infections in newborn wards in India, and gram-negative bacteria were responsible for 64% of infections. Acinetobacterspp (22%) was the most common bacteria found, followed by Klebsiella (17%) and E. coli (14%).
High rates of multi-drug resistance were found in all three pathogens, displaying resistance both to commonly used antibiotics and more sparingly-used extended-spectrum cephalosporins and carbapenems.
In a community-based study in rural India, including 85 blood cultures from newborn patients; 69% were identified as gram-negative bacteria, 26% were gram-positive and 3.6% were mixed infections and fungi (Candida sp.). A high level of resistance to penicillin and Ampicillin was found as well as moderate resistance to cephalosporins, and extremely low resistance to the antibiotics gentamicin and amikacin.
Overall, hospital and community-based data in India indicates that sepsis in newborns is predominantly due to drug resistant gram-negative bacteria. These hospital-acquired infections are high in newborns because of their low immunity, skin immaturity, need for invasive devices as part of intensive care support, and suboptimal nutrition with dependence on parenteral nutrition.
The gold standard for diagnosis of sepsis is a blood lab culture, but the yield of blood culture which is essential for the diagnosis is low for newborns. This may be due to an inadequate volume of blood in the culture bottle, prior antibiotic administration to the mother or infant, or a suboptimal method for culture. The end result, therefore, is the overuse of antibiotics due to a fear of missing the diagnosis of sepsis and worsening a newborn’s condition.
What we need in India is a high-specificity test that has a quick turn-around time and which may help a clinician diagnose sepsis. If the test is negative, it would help confidently rule out an infection so a physician could stop using antibiotics preventatively.
“The need for tests with high sensitivity and specificity cannot be overemphasised in the context of misuse of antibiotics in the neonatal intensive care.”
Pending their availability, implementing strategies for reducing the risk of hospital-acquired infections should continue. These include promoting antibiotic stewardship, adhering to strict hand hygiene, aseptic precautions when inserting invasive devices, lines and catheters, early preferential feeding with breast milk to reduce dependence on parenteral nutrition and kangaroo care. Probiotic supplementation has also been shown to reduce the risk of hospital-acquired infections and promote feeding tolerance in preterm newborns who are at the highest risk of prolonged exposure to antibiotics. The importance of environmental cleanliness should also not be forgotten.
A diagnostic test, antibiotic stewardship, probiotics and cleanliness could all go a long way in India, and around the world, to create a brighter future for our next generation of babies to come.
Sandeep Kadam is a Neonatologist at KEM Hospital and Ratna Memorial Hospital in Pune, Maharashtra State, India. He looks after small and sick newborn babies and both hospitals are tertiary care referral units.
Congratulations to the winners of the Longitude Prize on AMR, Sysmex Astrego!
