Burden of bacterial resistance among neonatal infections in low income countries: how convincing is the epidemiological evidence?

Abstract

Background: Antibiotic resistance is a threat in developing countries (DCs) because of the high burden of bacterial disease and the presence of risk factors for its emergence and spread. This threat is of particular concern for neonates in DCs where over one-third of neonatal deaths may be attributable to severe infections and factors such as malnutrition and HIV infection may increase the risk of death. Additional, undocumented deaths due to severe infection may also occur due to the high frequency of at-home births in DCs.

Methods: We conducted a systematic review of studies published after 2000 on community-acquired invasive bacterial infections and antibiotic resistance among neonates in DCs. Twenty-one articles met all inclusion criteria and were included in the final analysis.

Results: Ninety percent of studies recruited participants at large or university hospitals. The majority of studies were conducted in Sub-Saharan Africa (n=10) and the Indian subcontinent (n=8). Neonatal infection incidence ranged from 2.9 (95% CI 1.9-4.2) to 24 (95% CI 21.8-25.7) for 1000 live births. The three most common bacterial isolates in neonatal sepsis were Staphylococcus aureus, Escherichia coli, and Klebsiella. Information on antibiotic resistance was sparse and often relied on few isolates. The majority of resistance studies were conducted prior to 2008. No conclusions could be drawn on Enterobacteriaceae resistance to third generation cephalosporins or methicillin resistance among Staphylococcus aureus.

Conclusions: Available data were found insufficient to draw a true, recent, and accurate picture of antibiotic resistance in DCs among severe bacterial infection in neonates, particularly at the community level. Existing neonatal sepsis treatment guidelines may no longer be appropriate, and these data are needed as the basis for updated guidelines. Reliable microbiological and epidemiological data at the community level are needed in DCs to combat the global challenge of antibiotic resistance especially among neonates among whom the burden is greatest.

Figure 1

Flowchart of literature search including both the infection incidence and antibiotic resistance branches. *Data was considered not recent if data collection took place principally before 2000.

Figure 2

Incidence and aetiology of neonatal sepsis/bacteremia for 1000 live births in developing countries. Sources; [18,23,27-29] The figure shows point estimates, 95% confidence intervals, and aetiology of neonatal infections along with recruitment strategy and setting. Studies represented in blue were conducted in urban areas. Studies represented in orange were conducted in rural areas. Studies represented by a triangle used hospital recruitment. Studies represented by a circle used community recruitment. GBS (Group B streptococcus). *The Incidence estimate was calculated from the number of isolates and births presented. †CI estimated from data presented in the article. ‡The two estimates were taken from the same study. § Each case had both omphalitis and clinically defined sepsis.