Academic journal article Journal of Health Population and Nutrition

Extended-Interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Academic journal article Journal of Health Population and Nutrition

Extended-Interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Article excerpt


Global importance of neonatal infections

An estimated four million neonatal deaths occur around the world every year (1). Approximately 99% of these deaths occur in developing countries (1-3). Serious bacterial infections are the single most important cause of morbidity and mortality among newborns (1,4-6). An estimated 20% of all children born in developing countries, or 30 million annually, develop an infection during the neonatal period, and infectious diseases account for 36% of all neonatal deaths (1,7-9). Recent data suggest that approximately one-half of neonatal deaths in highmortality settings are due to infections (1,4,10).

For the treatment of serious bacterial infections in neonates, the World Health Organization (WHO) recommends intramuscular injections of an aminoglycoside and penicillin antibiotics for at least 10 days (11). The recommendations of WHO were designed for infants aged seven days to two months and include gentamicin dosed at 7.5 mg/kg intramuscularly once daily (11). Gentamicin is a potent aminoglycoside antibiotic with bactericidal activity against gram-negative bacteria. The combination of gentamicin and a penicillin, such as ampicillin, also produces synergistic activity against several principal gram-positive pathogens in neonates. In addition to the use of gentamicin in combination with an injectable penicillin, alternative treatment regimens, such as combining gentamicin with administration of oral antibiotics, including co-trimoxazole, may be life-saving (10). However, until further studies are available which provide evidence for efficacy of oral antibiotic treatment of neonates with suspected sepsis, or perhaps a subset with low-risk indications, every attempt should be made to provide a full course of parenteral antibiotics. Thus, a primary variable in treatment regimens that may potentially be altered to simplify dosing is the duration of the interval between administrations of doses.

The case-fatality rate due to neonatal sepsis in developing countries is estimated at 40%, based largely on data for infants treated in hospitals (9,12). When neonatal infections occur, many deaths can be avoided if the signs are recognized early and the disease is treated promptly and adequately (3,13- 15). In rural India and Bangladesh, for example, 66- 75% and 88-90% of births, respectively, take place at home, and acceptance of delivery in a health facility by rural women is still minimal (16-21). Since signs of illness due to infections are most likely to manifest while the infant is at home, and families in many societies are reluctant to take newborns outside the home, even when they are ill (20), an important strategy for reducing neonatal mortality will be to improve the ability of caregivers in the family and community to recognize danger signs and to promptly seek care. The ability of first-line health workers to prevent, recognize, and provide initial case management of infectious diseases in the home and community, or at health facilities, will also need to be improved (10,22-24).

For the treatment of neonatal sepsis in resourcepoor, high-mortality settings in developing countries where most neonatal deaths occur (1), simplified regimens are needed which ideally would allow for extended-interval dosing of parenteral antibiotics no more frequently than once a day. Although extended-interval dosing with parenteral antibiotics is desirable in developed countries, it is essential in developing-country community settings. Homevisits by community health workers to administer parenteral antibiotics, or alternatively, visits to the health facility by patients to receive injectable antibiotics generally are not feasible more than once per day. Extended-interval dosing in health facilities could also potentially reduce costs associated with antibiotic treatment, including demands on staff time, reduce demands on logistic and supply systems, and minimize chances for iatrogenic problems associated with antibiotic administration. …

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