New approaches to preventing, diagnosing, and treating neonatal sepsis

Karen Edmond, Anita Zaidi, Karen Edmond, Anita Zaidi

Abstract

Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Pathogenesis of congenital and neonatal…
Figure 1. Pathogenesis of congenital and neonatal infections.
Figure 2. Example of “lab on a…
Figure 2. Example of “lab on a chip” point-of-care device.

References

    1. Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr Infect Dis J. 2009;28:S3–9.
    1. Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: when? Where? Why? Lancet. 2005;365:891–900.
    1. Darmstadt GL, Bhutta ZA, Cousens S, Adam T, Walker N, et al. Evidence-based, cost-effective interventions: how many newborn babies can we save? Lancet. 2005;365:977–988.
    1. Bahl R, Martines J, Ali N, Bhan MK, Carlo W, et al. Research priorities to reduce global mortality from newborn infections by 2015. Pediatr Infect Dis J. 2009;28:S43–48.
    1. Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, et al. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics. 2000;105:21–26.
    1. Zaidi AK, Thaver D, Ali SA, Khan TA. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009;28:S10–18.
    1. Stoll BJ. The global impact of neonatal infection. Clin Perinatol. 1997;24:1–21.
    1. Zaidi AK, Huskins WC, Thaver D, Bhutta ZA, Abbas Z, et al. Hospital-acquired neonatal infections in developing countries. Lancet. 2005;365:1175–1188.
    1. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med. 2002;347:240–247.
    1. Seale AC, Mwaniki M, Newton CR, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect Dis. 2009;9:428–438.
    1. Tiskumara R, Fakharee SH, Liu CQ, Nuntnarumit P, Lui KM, et al. Neonatal infections in Asia. Arch Dis Child Fetal Neonatal Ed. 2009;94:F144–148.
    1. Schrag SJ, Hadler JL, Arnold KE, Martell-Cleary P, Reingold A, et al. Risk factors for invasive, early-onset Escherichia coli infections in the era of widespread intrapartum antibiotic use. Pediatrics. 2006;118:570–576.
    1. Menezes EV, Yakoob MY, Soomro T, Haws RA, Darmstadt GL, et al. Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy. BMC Pregnancy Childbirth. 2009;9(Suppl 1):S4.
    1. Stiehm ER, Fudenberg HH. Serum levels of immune globulins in health and disease: a survey. Pediatrics. 1966;37:715–727.
    1. Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007;7:379–390.
    1. Levy O, Martin S, Eichenwald E, Ganz T, Valore E, et al. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics. 1999;104:1327–1333.
    1. Levy O. Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J Endotoxin Res. 2005;11:113–116.
    1. Angelone DF, Wessels MR, Coughlin M, Suter EE, Valentini P, et al. Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr Res. 2006;60:205–209.
    1. Marodi L. Neonatal innate immunity to infectious agents. Infect Immun. 2006;74:1999–2006.
    1. Kramer MS. Balanced protein/energy supplementation in pregnancy. Cochrane Database Syst Rev. 2000:CD000032.
    1. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2006:CD004905.
    1. Healy CM, Baker CJ. Maternal immunization. Pediatr Infect Dis J. 2007;26:945–948.
    1. Demicheli V, Barale A, Rivetti A. Vaccines for women to prevent neonatal tetanus. Cochrane Database Syst Rev. 2005:CD002959.
    1. Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. 2008;359:1555–1564.
    1. Sinha A, Lieu TA, Paoletti LC, Weinstein MC, Platt R. The projected health benefits of maternal group B streptococcal vaccination in the era of chemoprophylaxis. Vaccine. 2005;23:3187–3195.
    1. Quiambao BP, Nohynek H, Kayhty H, Ollgren J, Gozum L, et al. Maternal immunization with pneumococcal polysaccharide vaccine in the Philippines. Vaccine. 2003;21:3451–3454.
    1. Bhutta ZA, Darmstadt GL, Hasan BS, Haws RA. Community-based interventions for improving perinatal and neonatal health outcomes in developing countries: a review of the evidence. Pediatrics. 2005;115:519–617.
    1. Rhee V, Mullany LC, Khatry SK, Katz J, LeClerq SC, et al. Maternal and birth attendant hand washing and neonatal mortality in southern Nepal. Arch Pediatr Adolesc Med. 2008;162:603–608.
    1. Meegan ME, Conroy RM, Lengeny SO, Renhault K, Nyangole J. Effect on neonatal tetanus mortality after a culturally-based health promotion programme. Lancet. 2001;358:640–641.
    1. Biran A, Schmidt WP, Wright R, Jones T, Seshadri M, et al. The effect of a soap promotion and hygiene education campaign on handwashing behaviour in rural India: a cluster randomised trial. Trop Med Int Health. 2009;14:1303–1314.
    1. Luby SP, Agboatwalla M, Painter J, Altaf A, Billhimer WL, et al. Effect of intensive handwashing promotion on childhood diarrhea in high-risk communities in Pakistan: a randomized controlled trial. JAMA. 2004;291:2547–2554.
    1. Curtis VA, Danquah LO, Aunger RV. Planned, motivated and habitual hygiene behaviour: an eleven country review. Health Educ Res. 2009;24:655–673.
    1. McClure EM, Goldenberg RL, Brandes N, Darmstadt GL, Wright LL, et al. The use of chlorhexidine to reduce maternal and neonatal mortality and morbidity in low-resource settings. Int J Gynaecol Obstet. 2007;97:89–94.
    1. Lumbiganon P, Thinkhamrop J, Thinkhamrop B, Tolosa JE. Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV). Cochrane Database Syst Rev. 2004:CD004070.
    1. Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2009:CD007467.
    1. Early-onset and late-onset neonatal group B streptococcal disease–United States, 1996-2004. MMWR Morb Mortal Wkly Rep. 2005;54:1205–1208.
    1. accessed 3rd September 2009.
    1. Mullany LC, Darmstadt GL, Khatry SK, Katz J, LeClerq SC, et al. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet. 2006;367:910–918.
    1. Mullany LC, Darmstadt GL, Tielsch JM. Safety and impact of chlorhexidine antisepsis interventions for improving neonatal health in developing countries. Pediatr Infect Dis J. 2006;25:665–675.
    1. Darmstadt GL, Saha SK, Ahmed AS, Chowdhury MA, Law PA, et al. Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial. Lancet. 2005;365:1039–1045.
    1. Siegrist CA. Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants. Vaccine. 2003;21:3406–3412.
    1. Bhandari N, Bahl R, Mazumdar S, Martines J, Black RE, et al. Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial. Lancet. 2003;361:1418–1423.
    1. Edmond KM, Zandoh C, Quigley MA, Amenga-Etego S, Owusu-Agyei S, et al. Delayed breastfeeding initiation increases risk of neonatal mortality. Pediatrics. 2006;117:e380–386.
    1. Edmond KM, Kirkwood BR, Amenga-Etego S, Owusu-Agyei S, Hurt LS. Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana. Am J Clin Nutr. 2007;86:1126–1131.
    1. Mullany LC, Katz J, Li YM, Khatry SK, LeClerq SC, et al. Breast-feeding patterns, time to initiation, and mortality risk among newborns in southern Nepal. J Nutr. 2008;138:599–603.
    1. Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev. 2007:CD000501.
    1. Gogia S, Sachdev HS. Neonatal vitamin A supplementation for prevention of mortality and morbidity in infancy: systematic review of randomised controlled trials. BMJ. 2009;338:b919.
    1. English M, Ngama M, Mwalekwa L, Peshu N. Signs of illness in Kenyan infants aged less than 60 days. Bull World Health Organ. 2004;82:323–329.
    1. Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet. 2008;371:135–142.
    1. Cromwell D, Joffe T, Hughes R, Murphy D, Dhillon C, et al. The local adaptation of national recommendations for preventing early-onset neonatal Group B Streptococcal disease in UK maternity units. J Health Serv Res Policy. 2008;13(Suppl 2):52–57.
    1. Buhimschi CS, Bhandari V, Hamar BD, Bahtiyar MO, Zhao G, et al. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med. 2007;4:e18. doi: .
    1. Buhimschi CS, Dulay AT, Abdel-Razeq S, Zhao G, Lee S, et al. Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth. BJOG. 2009;116:257–267.
    1. Neal PR, Kleiman MB, Reynolds JK, Allen SD, Lemons JA, et al. Volume of blood submitted for culture from neonates. J Clin Microbiol. 1986;24:353–356.
    1. Benjamin DK, Jr, Miller W, Garges H, Benjamin DK, McKinney RE, Jr, et al. Bacteremia, central catheters, and neonates: when to pull the line. Pediatrics. 2001;107:1272–1276.
    1. Kurlat I, Stoll BJ, McGowan JE., Jr Time to positivity for detection of bacteremia in neonates. J Clin Microbiol. 1989;27:1068–1071.
    1. Darmstadt GL, Batra M, Zaidi AK. Parenteral antibiotics for the treatment of serious neonatal bacterial infections in developing country settings. Pediatr Infect Dis J. 2009;28:S37–42.
    1. Peters RP, van Agtmael MA, Danner SA, Savelkoul PH, Vandenbroucke-Grauls CM. New developments in the diagnosis of bloodstream infections. Lancet Infect Dis. 2004;4:751–760.
    1. Moisi JC, Saha SK, Falade AG, Njanpop-Lafourcade BM, Oundo J, et al. Enhanced diagnosis of pneumococcal meningitis with use of the Binax NOW immunochromatographic test of Streptococcus pneumoniae antigen: a multisite study. Clin Infect Dis. 2009;48(Suppl 2):S49–56.
    1. Jordan JA, Durso MB. Comparison of 16S rRNA gene PCR and BACTEC 9240 for detection of neonatal bacteremia. J Clin Microbiol. 2000;38:2574–2578.
    1. Jordan JA, Durso MB. Real-time polymerase chain reaction for detecting bacterial DNA directly from blood of neonates being evaluated for sepsis. J Mol Diagn. 2005;7:575–581.
    1. Jordan JA, Durso MB, Butchko AR, Jones JG, Brozanski BS. Evaluating the near-term infant for early onset sepsis: progress and challenges to consider with 16S rDNA polymerase chain reaction testing. J Mol Diagn. 2006;8:357–363.
    1. Weile J, Knabbe C. Current applications and future trends of molecular diagnostics in clinical bacteriology. Anal Bioanal Chem. 2009;394:731–742.
    1. Andrade SS, Bispo PJ, Gales AC. Advances in the microbiological diagnosis of sepsis. Shock. 2008;30(Suppl 1):41–46.
    1. Jordan JA, Jones-Laughner J, Durso MB. Utility of pyrosequencing in identifying bacteria directly from positive blood culture bottles. J Clin Microbiol. 2009;47:368–372.
    1. Verboon-Maciolek MA, Thijsen SF, Hemels MA, Menses M, van Loon AM, et al. Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy. Pediatr Res. 2006;59:457–461.
    1. Franz AR, Steinbach G, Kron M, Pohlandt F. Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics. 1999;104:447–453.
    1. Edgar JD, Wilson DC, McMillan SA, Crockard AD, Halliday MI, et al. Predictive value of soluble immunological mediators in neonatal infection. Clin Sci (Lond) 1994;87:165–171.
    1. Yager P, Edwards T, Fu E, Helton K, Nelson K, et al. Microfluidic diagnostic technologies for global public health. Nature. 2006;442:412–418.
    1. Zhang Y, Ozdemir P. Microfluidic DNA amplification–a review. Anal Chim Acta. 2009;638:115–125.
    1. Stevens DY, Petri CR, Osborn JL, Spicar-Mihalic P, McKenzie KG, et al. Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage. Lab Chip. 2008;8:2038–2045.
    1. Thaver D, Ali SA, Zaidi AK. Antimicrobial resistance among neonatal pathogens in developing countries. Pediatr Infect Dis J. 2009;28:S19–21.
    1. Darmstadt GL, Batra M, Zaidi AK. Oral antibiotics in the management of serious neonatal bacterial infections in developing country communities. Pediatr Infect Dis J. 2009;28:S31–36.
    1. Bhutta ZA, Zaidi AK, Thaver D, Humayun Q, Ali S, et al. Management of newborn infections in primary care settings: a review of the evidence and implications for policy? Pediatr Infect Dis J. 2009;28:S22–30.
    1. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet. 1999;354:1955–1961.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever