A REVIEW OF ANTIBIOTIC USED IN SUSPECTED EARLY-ONSET NEONATAL SEPSIS FROM MALAYSIAN PERSPECTIVE: WHICH ONES TO CHOOSE AND HOW LONG TO GIVE?
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i1.29489Keywords:
Neonate, Early onset sepsis, Guideline, Treatment, DurationAbstract
Objective: Suspected early-onset sepsis is a common diagnosis among neonates which warrants admission to the neonatal intensive care unit. Prolonged empiric antibiotic is the biggest concern and treatment duration is still controversial. Antimicrobial stewardship (AMS) program promotes early antibiotic de-escalation to reduce unnecessary antibiotic exposure and its implementation in the intensive care setting seems to be feasible. The primary objective of this review was to compare the existing guidelines and review the literature regarding choice and duration of empiric antibiotic in managing suspected early-onset neonatal sepsis.
Methods: Two Malaysian Ministry of Health guidelines were compared with guidelines from America (n=1), Australia (n=1), and United Kingdom (n=2). The literature search was conducted from January to June 2017 through open access journal and databases available at the author's institution library (EBSCOHost, Ovid and Science Direct).
Results: All guidelines recommended similar antibiotics range and suggested to review treatment at 36– 72 h post antibiotic exposure. A total of 113 abstracts and full articles were identified, and only 11 full-text articles published in English were related to the subject of interest. All studies show differences either in study design, choice of antibiotics, treatment duration or outcome measures; thus, a meta-analysis was not possible to be conducted.
Conclusion: From this review, we found the potential to performed early empiric antibiotic de-escalation especially in clinically well-appearance neonates, and it is best to customize our guidelines based on local evidence which justify the need for more local research in this area.
Downloads
References
WHO. Antibiotic Use for Sepsis in Neonates and Children: 2016 Evidence Update. Geneva: WHO; 2016.
WHO. Neonatal and Perinatal Mortality, Country, Regional and Global Estimates. Geneva: WHO; 2006.
Cordero L, Ayers LW. Duration of empiric antibiotics for suspected early-onset sepsis in extremely low birth weight infants. Infect Control Hosp Epidemiol 2003;24:662-6.
Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr 2016;28:141-9.
WHO. Collaborating Centre for Training and Research in Newborn Care. Sepsis in Newborn. Geneva: WHO; 2014.
Mtitimila EI, Cooke RW. Antibiotic regimens for suspected early neonatal sepsis. Cochrane Database Syst Rev 2004;4:CD004495.
Shah BA, Padbury JF. Neonatal sepsis: An old problem with new insights. Virulence 2014;5:170-8.
Cortese F, Scicchitano P, Gesualdo M, Filaninno A, De Giorgi E, Schettini F, et al. Early and late infections in newborns: Where do we stand? A Review. Pediatr Neonatol 2016;57:265-73.
Chan GJ, Lee Anne CC, Baqui AH, Tan, Black RE. Prevalence of early-onset neonatal infection among newborns of mothers with bacterial infection or colonization: A systematic review and meta-analysis. BMC Infect Dis 2015;15:118.
Wortham JM, Hansen NI, Schrag SJ, Hale E, Meurs KV, Sánchez PJ, et al. Chorioamnionitis and culture confirmed, early-onset neonatal infections. J Pediatr 2016;137:e20152323.
Kiser C, Nawab U, McKenna K, Aghai ZH. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics 2014;133:992-8.
Cummings JJ. The well-appearing newborn at risk for early-onset sepsis: We can do better. J Pediatr 2017;139:e20164211.
Kuhn P, Dheu C, Bolender C, Chognot D, Keller L, Demil H, et al. Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics. Paediatr Perinat Epidemiol 2010;24:479-87.
Le Doare K, O’Driscoll M, Turner K, Seedat F, Russell NJ, Seale AC, et al. Intrapartum antibiotic chemoprophylaxis policies for the prevention of group B streptococcal disease worldwide: Systematic review. Clin Infect Dis 2017;65:S143-S151.
Schrag JS, Hadler JL, Arnold KE, Martell-Cleary P, Reingold A, Schuchat A. Risk factors for invasive, early onset Escherichia coli infections in the era of widespread intrapartum antibiotic use. J Pediatr 2006;118:570-6.
Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia coli sepsis and the ampicillin resistance in the era of intrapartum antibiotic prophylaxis. J Pediatr 2008;121:689-96.
Rønnestad A, Abrahamsen TG, Medbø S, Reigstad H, Lossius K, Kaaresen PI, et al. Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants. J Pediatr 2005;115;262.
Ballot DE, Nana T, Sriruttan C, Cooper PA. Bacterial blood stream infections in neonates in a developing country. Int Sch Res Net 2012;2012:6.
Ibrahim NA, Manan MM. Early onset neonatal sepsis pathogens in Malaysian hospitals: Determining empiric antibiotic. Int J Pharm Pharm Sci 2014;8:686-90.
Al-Taiar A, Hammoud MS, Thalib L, Isaacs D. Pattern and etiology of culture-proven early-onset neonatal sepsis: A five-year prospective study. Int J Infect Dis 2011;15:e631-4.
Fjalstad JW, Stensvold HJ, Bergseng H, Simonsen GS, Salvesen B, Rønnestad AE, et al. Early-onset sepsis and antibiotic exposure in term infants: A Nationwide population-based study in Norway. Pediatr Infect Dis J 2016;35:1-6.
Benitz WE, Gould JB, Druzin ML. Antimicrobial prevention of early-onset Group B streptococcal sepsis: Estimates of risk reduction based on a critical literature review. J Pediatr 1999;103:e78.
Duvoisina G, Fischera C, Maucort-Boulch D, Giannonia E. Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment. Swiss Med Wkly 2014;144:13981.
Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016;28:135-40.
Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. J Pediatr 2006;117:67-74.
Metsvaht T, Ilmoja ML, Parm Ü, Maipuu L, Merila M, Lutsar I, et al. Comparison of ampicillin plus gentamicin vs. Penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis. Acta Paediatr 2010;99:665-72.
Awaisu A, Syed A, Mohamed I, Saad A. Antimicrobials utilization and outcomes of neonatal sepsis among patients admitted to a university teaching hospital in Malaysia. East J Med 2007;12:6-14.
Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: Data from a large national data set. J Pediatr 2006;117:1979.
Shinde AR, Mohite RV, Shinde RV. Pattern of antibiotics utilization in neonatal septicemia: A cross-sectional study from rural tertiary care hospital western Maharashtra, India. Int J Pharm Pharm Sci 2017;9:60-3.
Polin RA. Management of neonates with suspected or proven early-onset bacterial sepsis guidance for the clinician in rendering pediatric care. J Pediatr 2012;2012:129.
Cotten CM, Smith PB. Duration of empiric antibiotic therapy for infants suspected of early-onset sepsis. Curr Opin2013;25:167-71.
Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis – A systematic review. Infect Dis (Lond) 2015;47:117-24.
Kaye KS. Antimicrobial de-escalation strategies in hospitalized patients with pneumonia, intra-abdominal infections, and bacteremia. J Hosp Med 2012;7:S13-21.
Ministry of Health. Protocol on Antimicrobial Stewardship Program in Healthcare Facilities. Malaysia: Ministry of Health; 2014.
Patel SJ, Saiman L. Antibiotic resistance in neonatal intensive care unit pathogens: Mechanisms, clinical impact, and prevention including antibiotic stewardship. Clin Perinatol 2010;37:547-63.
Khasawneh FA, Karim A, Mahmood T, Ahmed S, Jaffri SF, Mehmood M, et al. Safety and feasibility of antibiotic de-escalation in bacteremic pneumonia. Infect Drug Resist 2014;7:177-82.
Njoku JC, Hermsen ED. Antimicrobial stewardship in the intensive care unit: A focus on potential pitfalls. J Pharm Pract 2010;23:50-60.
Gonzalez L, Cravoisy A, Barraud D, Conrad M, Nace L, Lemarié J, et al. Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients. Crit Care 2013;17:R140.
Masterton RG. Antibiotic de-escalation. Crit Care Clin 2011;27:149-62.
Garnacho-Montero J, Escoresca-Ortega A, Fernández-Delgado E. Antibiotic de-escalation in the ICU: How is it best done? Curr Opin Infect Dis 2015;28:193-8.
Camargo LF. The ‘‘De-escalation concept’’ and antibiotic de-escalation: A missed opportunity? Shock 2013;39:29-31.
Khan RA, Aziz ZZ. Antibiotic de-escalation therapy in neurosurgical patients with ventilator - Associated pneumonia in intensive care unit: A retrospective observational study. Indian J Pharm Edu Res 2017;51:144-9.
Montravers P, Augustin P, Grall N, Desmard M, Allou N, Marmuse JP, et al. Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections. Crit Care 2016;20:83.
Viasus D, Simonetti AF, Garcia-Vidal C, Niubó J, Dorca J, Carratalà J, et al. Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia. J Antimicrob Chemother 2017;72:547-53.
Ohji G, Doi A, Yamamoto S, Iwata K. Is de-escalation of antimicrobials effective? A systematic review and meta-analysis. Int J Infect Dis 2016;49:71-9.
Leone M, Bechis C, Baumstarck K, Lefrant JY, Albanèse J, Jaber S, et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: A multicenter non-blinded randomized noninferiority trial. Intensive Care Med 2014;40:1399-408.
Krzyzaniak N, Bajorek B. A global perspective of the roles of the pharmacist in the NICU. Int J Pharm Pract 2017;25:107-20.
Samiya NK, Siby J, Sasidharan P. A study of clinical pharmacist-initiated intervention for the optimal use of medications in a neonatal intensive care unit (NICU) of a tertiary care hospital, South India. Int J Pharm Pharm Sci 2016;8:23-6.
Ministry of Health. Pediatric Protocol. 3rd ed. Malaysia: Ministry of Health; 2013.
Ministry of Health. National Antibiotic Guideline. 2nd ed. Malaysia: Ministry of Health; 2014.
Government of South Australia. South Australian Perinatal Practice Guideline: Neonatal sepsis. Australia: Government of South Australia; 2014.
National Institute for Health and Care Excellence. Neonatal infection (Neonatal infection (early onset): Antibiotics for Pre-antibiotics for Prevention and Treatment Clinical Guideline. United Kingdom: National Institute for Health and Care Excellence (NICE); 2012.
Prevention, Diagnosis and Treatment of Early-onset Neonatal Bacterial Infection: Neonatal Clinical Guideline. Royal Cornwall Hospitals NHS; 2015.
Tewari VV, Jain N. Monotherapy with amikacin or piperacillin-tazobactum empirically in neonates at risk for early-onset sepsis: A randomized controlled trial. J Trop Pediatr 2014;60:297-302.
Chong E, Reynolds J, Shaw J, Forur P, Delmore P, Uner H, et al. Result of a two-center, before and after study of piperacillin-tazobactam versus ampicillin and gentamicin as empiric therapy for suspected sepsis at birth in neonates ≤ 1500g. J Perinatol 2013;33:529-32.
Pasha YZ, Ahmadpour-Kacho M, Behmadi R, Jahangir T 3-day versus 5-day course of intravenous antibiotics for suspected early onset neonatal sepsis: A Randomized controlled trial. Iran J Pediatr 2014;24:673-8.
Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sanchez PJ, et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. J Pediatr 2009;123:58-66.
Labenne M, Michaut F, Gouyon B, Ferdynus C, Gouyon JB. A population-based observational study of restrictive guidelines for antibiotic therapy in early-onset neonatal infections. Pediatr Infect Dis J 2007;26:593-9.
Ibrahim NA, Manan MM, Aziz NA. The effectiveness of empiric antibiotic therapy in the prevention of early onset sepsis. Int J Curr Res 2014;6:6258-65.
Oliver EA, Reagan PB, Slaughter JL, Buhimschi CS, Buhimschi IA. Patterns of empiric antibiotic administration for presumed early-onset neonatal sepsis in neonatal intensive care units in the United States. Am J Perinatol 2017;34:640-7.
Weintraub AS, Ferrara L, Deluca L, Moshier E, Green RS, Oakman E, et al. Antenatal antibiotic exposure in preterm infants with necrotizing enterocolitis. J Perinatol 2012;32:705-9.
Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin DK Jr. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth weight infants. J Pediatr 2006;118:717-21.
Seale AC, Obiero CW, Berkley JA. Rational development of guidelines for management of neonatal sepsis in developing countries. Curr Opin Infect Dis 2015;28:225-30.
Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin North Am 2004;51:939-59, 8-9.
Chauhan N, Tiwari S, Jain U. Potential biomarkers for effective screening of neonatal sepsis infections: An overview. Microb Pathog 2017;107:234-42.
Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatric Infect Dis Soc 2014;3:234-45.
Ottolini MC, Lundgren K, Mirkinson LJ, Cason S, Ottolini MG. Utility of complete blood count and blood culture screening to diagnose neonatal sepsis in the asymptomatic at risk newborn. Pediatr Infect Dis J 2003;22:430-4.
Mukhopadhyay S, Puopolo KM. Clinical and microbiologic characteristics of early-onset sepsis among very low birth weight infants: Opportunities for antibiotic stewardship. Pediatr Infect Dis J 2017;36:477-81.
Cantey JB, Baird SD. Ending the culture of culture-negative sepsis in the neonatal ICU. Pediatrics 2017;140:e20170044.
Ganesan P, Shanmugam P, Sattar SB, Shankar SL. Evaluation of IL-6, CRP and hs-CRP as early markers of neonatal sepsis. J Clin Diagn Res 2016;10:DC13-7.
Jefferies AL. Management of term infants at increased risk for early-onset bacterial sepsis. Paediatr Child Health 2017;22:223-8.
Rubin LG, Sánchez PJ, Siegel J, Levine G, Saiman L, Jarvis WR. Evaluation and treatment of neonates with suspected late-onset sepsis: A survey of neonatologists’ practices. J Pediatr 2002;110:e42.
Naher BS, Mannan MA, Noor K, Shahidullah M. Role of procalcitonin and C-reactive protein in the diagnosis of neonatal sepsis. Bangladesh Med Res Counc Bull 2011;37:40-6.
Mukhopadhyay S, Puopolo KM. Risk assessment in neonatal early onset sepsis. Semin Perinatol 2012;36:408-15.
Cotten CM. Antibiotic stewardship: Reassessment of guidelines for management of neonatal sepsis. Clin Perinatol 2015;42:195-206, x.
Mithal LB, Palac HL, Yogev R, Ernst LM, Mestan KK. Cord blood acute phase reactants predict early onset neonatal sepsis in preterm infants. PLoS One 2017;12:e0168677.
Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A, Corcia-Palomo Y, Fernández-Delgado E, Herrera-Melero I, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 2014;40:32-40.
Cohen-Wolkowiez M, Moran C, Benjamin DK, Cotten CM, Clark RH, Benjamin DK Jr., et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009;28:1052-6.
Touw DJ, Westerman EM, Sprij AJ. Therapeutic drug monitoring of aminoglycosides in neonates. Clin Pharmacokinet 2009;48:71-88.
Nestaas E, Bangstad HJ, Sandvik L, Wathne KO. Aminoglycoside extended interval dosing in neonates is safe and effective: A meta-analysis. Arch Dis Child Fetal Neonatal Ed 2005;90:F294-300.
Polin RA, Watterberg K, Benitz W, Eichenwald E. The conundrum of early-onset sepsis. J Pediatr 2014;133:1122-3.
Grant CH, Arnott A, Brook T, Horne A, Hurst W, Kelly S, et al. Reducing antibiotic exposure in suspected neonatal sepsis. Clin Pediatr (Phila) 2018;57:76-81.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
