Neonatal outcomes associated with antimicrobial resistance: A retrospective cross-sectional study
Published:  Jan 17, 2023DOI: 10.7324/JAPS.2023.120166
Neonatal sepsis (NS) is a leading cause of morbidity and mortality requiring immediate admission and prolonged neonatal intensive care unit (NICU) stay. This study attempts to identify factors associated with NS and its outcomes. A total of 186 NS case records (January 2017 to September 2019) were analyzed retrospectively. Multiple logistic regression and linear regression were employed to determine the factors associated with mortality, length of NICU stay, and treatment cost with a significance level of p ≤ 0.05. The mean neonatal age was 6.8 ± 9.5 days. Culture reports identified Klebsiella pneumonia (69%) as the major pathogen. Forty-four percent of neonates died, of whom 57% and 44% suffered early-onset sepsis and late-onset sepsis respectively. Logistic regression showed that mortality was significantly associated with platelet count (OR = 0.998; 95% CI =0.996–1.000) and very low birth weight (LBW) (OR = 2.427; 95% CI = 1.103–5.342). Linear regression showed that the number of definitive antibiotics used was associated with prolonged length of NICU stay. Also, length of NICU stay, number of definitive antibiotics, seizures, and heart disease, were significantly associated with overall cost. Mortality was higher with early-onset of sepsis than with late-onset of sepsis. The study could help policymakers and clinical practitioners to develop and implement targeted interventions that potentially reduce the global prevalence of NS.
Chandra P, Iqbal F, Unnikrishnan MK, Jayashree P, Shenoy PA, Elstin Anburaj S, Rajesh V, Surulivelrajan M, Lewis LE. Neonatal outcomes associated with antimicrobial resistance: A retrospective cross-sectional study. J Appl Pharm Sci, 2023. https://doi.org/10.7324/JAPS.2023.120166
Aerts C, Leahy S, Mucasse H, Lala S, Bramugy J, Tann CJ, Madhi SA, Bardají A, Bassat Q, Dangor Z, Lawn JE, Jit M, Procter SR. Quantifying the acute care costs of neonatal bacterial sepsis and meningitis in Mozambique and South Africa. Clin Infect Dis Off Publ Infect Dis Soc Am, 2022; 74:S64-9; https://doi.org/10.1093/cid/ciab815 https://doi.org/10.1093/cid/ciab815
Ahuja A. Despite improved infant and child mortality rates and feeding practices, malnutrition has increased in Kerala: NFHS-5. NDTV, 2021. Available via https://swachhindia.ndtv.com/despite-improved-infant-and-child-mortality-rates-and-feeding-practices-malnutrition-has-increased-in-kerala-nfhs-5-55455/ (Accessed 15 March 2022).
Ananya19b. Multicollinearity: problem, detection and solution. Analytics Vidhya. 2021. Available via https://www.analyticsvidhya.com/ blog/2021/02/multicollinearity-problem-detection-and-solution/ (Accessed 29 April 2022)
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 Lond Engl, 1999; 354:1955-61; https://doi.org/10.1016/S0140-6736(99)03046-9 https://doi.org/10.1016/S0140-6736(99)03046-9
Bang A, Deshmukh M, Baitule S, Duby J. Decline in the incidence of neonatal sepsis in rural Gadchiroli, India during the twenty-one years (1998-2019) following the home-based neonatal care field-trial. Pediatr Infect Dis J, 2021; 40:1029-33; https://doi.org/10.1097/ INF.0000000000003248 https://doi.org/10.1097/INF.0000000000003248
Bhaskar S. 2021. Despite improved infant and child mortality rates and feeding practices, malnutrition has increased in Kerala: NFHS- 5. NDTV-Dettol Banega Swasth Swachh India. Available via https:// swachhindia.ndtv.com/despite-improved-infant-and-child-mortality-rates-and-feeding-practices-malnutrition-has-increased-in-kerala-nfhs-5-55455/ (Accessed 4 April 2022).
Boerma T, Ronsmans C, Melesse DY, Barros AJ, Barros FC, Juan L, Moller AB, Say L, Hosseinpoor AR, Yi M, Neto DDLR, Temmerman M. Global epidemiology of use of and disparities in caesarean sections. Lancet, 2018; 392(10155):1341-8. https://doi.org/10.1016/S0140-6736(18)31928-7
Bora JK, Saikia N. Neonatal and under-five mortality rate in Indian districts with reference to sustainable development goal 3: an analysis of the national family health survey of India (NFHS), 2015-2016. Plos One, 2018; 13:e0201125; https://doi.org/10.1371/journal.pone.0201125 https://doi.org/10.1371/journal.pone.0201125
Boverman G, Perez C, Vij S, Tgavalekos K, Ravindranath S, Antonescu C, Chambers-Hawk B. Neonatal ICU antibiotic use trends within an integrated delivery network. Antimicrob Resist Infect Control, 2022; 11:21; https://doi.org/10.1186/s13756-022-01057-3 https://doi.org/10.1186/s13756-022-01057-3
Cantey JB, Pyle AK, Wozniak PS, Hynan LS, Sánchez PJ. Early antibiotic exposure and adverse outcomes in preterm, very low birth weight infants. J Pediatr, 2018; 203:62-7; https://doi.org/10.1016/j. jpeds.2018.07.036 https://doi.org/10.1016/j.jpeds.2018.07.036
Chandra P, Rajesh V, Surulivelrajan M, Shastry CS, Unnikrishnan MK. Multidrug-resistant Acinetobacter baumannii infections: looming threat in the Indian clinical setting. Expert Rev Anti Infect Ther, 2022; 20:721-32; https://doi.org/10.1080/14787210.2022.2016393 https://doi.org/10.1080/14787210.2022.2016393
Cortese F, Scicchitano P, Gesualdo M, Filaninno A, De Giorgi E, Schettini F, Laforgia N, Ciccone MM. Early and late infections in newborns: where do we stand? A review. Pediatr Neonatol, 2016; 57:265-73; https:// doi.org/10.1016/j.pedneo.2015.09.007 https://doi.org/10.1016/j.pedneo.2015.09.007
Dadgostar P. Antimicrobial resistance: implications and costs. Infect Drug Resist, 2019; 12:3903-10; https://doi.org/10.2147/IDR. S234610 https://doi.org/10.2147/IDR
Dall. Report highlights the deadly impact of bacterial infections. CIDRAP, 2022. Available via https://www.cidrap.umn.edu/antimicrobial-stewardship/report-highlights-deadly-impact-bacterial-infections (Accessed 24 November 2022).
Dewez JE, Chellani H, Nangia S, Metsis K, Smith H, Mathai M, van den Broek N. Healthcare workers' views on the use of continuous positive airway pressure (CPAP) in neonates: a qualitative study in Andhra Pradesh, India. BMC Pediatr, 2018; 18:347; https://doi.org/10.1186/ s12887-018-1311-8 https://doi.org/10.1186/s12887-018-1311-8
Duke T. CPAP: a guide for clinicians in developing countries. Paediatr Int Child Health, 2014; 34:3-11; https://doi.org/10.1179/2046905 513Y.0000000102 https://doi.org/10.1179/2046905513Y.0000000102
Fenny AP, Otieku E, Labi KAK, Asante FA, Enemark U. Costs and extra length of stay because of neonatal bloodstream infection at a teaching hospital in Ghana. PharmacoEcon Open, 2020; 5:111-20; https:// doi.org/10.1007/s41669-020-00230-x https://doi.org/10.1007/s41669-020-00230-x
Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, Tröndle M, Savova Y, Kissoon N, Schlattmann P, Reinhart K, Allegranzi B, Eckmanns T. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child, 2021; 106:745-52; https://doi.org/10.1136/archdischild-2020-320217 https://doi.org/10.1136/archdischild-2020-320217
Gastmeier P, Geffers C, Schwab F, Fitzner J, Obladen M, Rüden H. Development of a surveillance system for nosocomial infections: the component for neonatal intensive care units in Germany. J Hosp Infect, 2004; 57:126-31; https://doi.org/10.1016/j.jhin.2003.12.038 https://doi.org/10.1016/j.jhin.2003.12.038
Gondwe T, Betha K, Kusneniwar GN, Bunker CH, Tang G, Simhan H, Haggerty CL. Adverse infant outcomes associated with caesarean section delivery in India. Int Health, 2020; 12(5):411-6. https://doi.org/10.1093/inthealth/ihz111
The World Bank. GDP per capita (current US$). 2021. Available via https://data.worldbank.org/indicator/NY.GDP.PCAP.CD (Accessed 30 March 2022).
Hassuna NA, AbdelAziz RA, Zakaria A, Abdelhakeem M. Extensively-drug resistant Klebsiella pneumoniae recovered from neonatal sepsis cases from a major NICU in Egypt. Front Microbiol, 2020; 11:1375. https://doi.org/10.3389/fmicb.2020.01375
Hayes R, Hartnett J, Semova G, Murray C, Murphy K, Carroll L, Plapp H, Hession L, O'Toole J, McCollum D, Roche E, Jenkins E, Mockler D, Hurley T, McGovern M, Allen J, Meehan J, Plötz FB, Strunk T, de Boode WP, Polin R, Wynn JL, Degtyareva M, Küster H, Janota J, Giannoni E, Schlapbach LJ, Keij FM, Reiss IKM, Bliss J, Koenig JM, Turner MA, Gale C, Molloy EJ, Infection, Inflammation, Immunology and Immunization (I4) section of the European Society for Paediatric Research (ESPR). Neonatal sepsis definitions from randomized clinical trials. Pediatr Res, 2021; https:// doi.org/10.1038/s41390-021-01749-3 https://doi.org/10.1038/s41390-021-01749-3
Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK, Smith PB, Manzoni P, Jacqz-Aigrain E, Kaguelidou F, Cohen-Wolkowiez M. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev, 2012; 88(Suppl 2):S69-74; https://doi.org/10.1016/S0378-3782(12)70019-1 https://doi.org/10.1016/S0378-3782(12)70019-1
Johnson TJ, Patel AL, Jegier BJ, Engstrom JL, Meier PP. Cost of morbidities in very low birth weight infants. J Pediatr, 2013; 162:243-9; https://doi.org/10.1016/j.jpeds.2012.07.013 https://doi.org/10.1016/j.jpeds.2012.07.013
Kamath BD, Todd JK, Glazner JE, Lezotte D, Lynch AM. Neonatal outcomes after elective cesarean delivery. Obst Gynecol, 2009; 113(6):1231. https://doi.org/10.1097/AOG.0b013e3181a66d57
Kesarwani R. Estimation of life expectancy from infant mortality rate at districts level. Int Res J Soc Sci, 2015; 4:52-63.
Leal YA, Álvarez-Nemegyei J, Velázquez JR, Rosado-Quiab U, Diego-Rodríguez N, Paz-Baeza E, Dávila-Velázquez J. Risk factors and prognosis for neonatal sepsis in southeastern Mexico: analysis of a four-year historic cohort follow-up. BMC Pregnancy Childbirth, 2012; 12:48; https://doi.org/10.1186/1471-2393-12-48 https://doi.org/10.1186/1471-2393-12-48
Li G, Bielicki JA, Ahmed ASMNU, Islam MS, Berezin EN, Gallacci CB, Guinsburg R, da Silva Figueiredo CE, Santarone Vieira R, Silva AR, Teixeira C, Turner P, Nhan L, Orrego J, Pérez PM, Qi L, Papaevangelou V, Triantafyllidou P, Iosifidis E, Roilides E, Sarafidis K, Jinka DR, Nayakanti RR, Kumar P, Gautam V, Prakash V, Seeralar A, Murki S, Kandraju H, Singh S, Kumar A, Lewis L, Pukayastha J, Nangia S, KNY, Chaurasia S, Chellani H, Obaro S, Dramowski A, Bekker A, Whitelaw A, Thomas R, Velaphi SC, Ballot DE, Nana T, Reubenson G, Fredericks J, Anugulruengkitt S, Sirisub A, Wong P, Lochindarat S, Boonkasidecha S, Preedisripipat K, Cressey TR, Paopongsawan P, Lumbiganon P, Pongpanut D, Sukrakanchana PO, Musoke P, Olson L, Larsson M, Heath PT, Sharland M. Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network. Arch Dis Child, 2020; 105:26-31; https://doi.org/10.1136/archdischild-2019-316816 https://doi.org/10.1136/archdischild-2019-316816
Liyakat H, Khan M, Tahirkheli N, Bader -u-Nisa, Ashfaq M. Bacteriological profile and antibiogram of neonatal sepsis. J Dow Univ Health Sci JDUHS, 2021; 15:130-5; https://doi.org/10.36570/ jduhs.2021.3.1240 https://doi.org/10.36570/jduhs.2021.3.1240
Maternal and Neonatal Health in Madhya Pradesh: Trends, Insights and Scope. (2022). India Health Action Trust (IHAT). Available via https://www.ihat.in/resources/mnh-in-madhya-pradesh-trends-insights-and-scope/ (Accessed 29 April 2022)
McGovern M, Giannoni E, Kuester H, Turner MA, van den Hoogen A, Bliss JM, Koenig JM, Keij FM, Mazela J, Finnegan R, Degtyareva M, Simons SHP, de Boode WP, Strunk T, Reiss IKM, Wynn JL, Molloy EJ, Infection, Inflammation, Immunology and Immunization (I4) section of the ESPR. Challenges in developing a consensus definition of neonatal sepsis. Pediatr Res, 2020; 88:14-26; https://doi.org/10.1038/ s41390-020-0785-x https://doi.org/10.1038/s41390-020-0785-x
Micormedex NeoFax Essentials 2014 (1).pdf. (2014). Available via http://ypeda.com/attachments/fil/Micormedex%20NeoFax%20 Essentials%202014%20(1).pdf (Accessed 04 April 2022).
Milton R, Gillespie D, Dyer C, Taiyari K, Carvalho MJ, Thomson K, Sands K, Portal EAR, Hood K, Ferreira A, Hender T, Kirby N, Mathias J, Nieto M, Watkins WJ, Bekele D, Abayneh M, Solomon S, Basu S, Nandy RK, Saha B, Iregbu K, Modibbo FZ, Uwaezuoke S, Zahra R, Shirazi H, Najeeb SU, Mazarati JB, Rucogoza A, Gaju L, Mehtar S, Bulabula ANH, Whitelaw AC, Walsh TR, Chan GJ, BARNARDS Group. Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study. Lancet Glob Health, 2022; 10(5):e661-72.
Murthy S, Godinho MA, Guddattu V, Lewis LES, Nair NS. Risk factors of neonatal sepsis in India: a systematic review and meta-analysis. Plos One, 2019; 14:e0215683; https://doi.org/10.1371/journal. pone.0215683 https://doi.org/10.1371/journal.pone.0215683
Niknajad A, Ghojazadeh M, Sattarzadeh N, Bashar Hashemi F, Dezham Khoy Shahgholi F. Factors affecting the neonatal intensive care unit stay duration in very low birth weight premature infants. J Caring Sci, 2012; 1:85-92; https://doi.org/10.5681/jcs.2012.013
Panigrahi P, Chandel DS, Hansen NI, Sharma N, Kandefer S, Parida S, Satpathy R, Pradhan L, Mohapatra A, Mohapatra SS, Misra PR, Banaji N, Johnson JA, Morris JG, Gewolb IH, Chaudhry R. Neonatal sepsis in rural India: timing, microbiology and antibiotic resistance in a population-based prospective study in the community setting. J Perinatol Off J Calif Perinat Assoc, 2017; 37:911-21; https://doi.org/10.1038/jp.2017.67 https://doi.org/10.1038/jp.2017.67
Pokhrel B, Koirala T, Shah G, Joshi S, Baral P. Bacteriological profile and antibiotic susceptibility of neonatal sepsis in neonatal intensive care unit of a tertiary hospital in Nepal. BMC Pediatr, 2018; 18:208; https:// doi.org/10.1186/s12887-018-1176-x https://doi.org/10.1186/s12887-018-1176-x
Prinja S, Manchanda N, Mohan P, Gupta G, Sethy G, Sen A, van den Hombergh H, Kumar R. Cost of neonatal intensive care delivered through district level public hospitals in India. Indian Pediatr, 2013; 50:839-46; https://doi.org/10.1007/s13312-013-0234-6 https://doi.org/10.1007/s13312-013-0234-6
Ree IMC, Fustolo-Gunnink SF, Bekker V, Fijnvandraat KJ, Steggerda SJ, Lopriore E. Thrombocytopenia in neonatal sepsis: incidence, severity and risk factors. Plos One, 2017; 12:e0185581; https://doi. org/10.1371/journal.pone.0185581 https://doi.org/10.1371/journal.pone.0185581
Salman O, Procter SR, McGregor C, Paul P, Hutubessy R, Lawn JE, Jit M. Systematic review on the acute cost-of-illness of sepsis and meningitis in neonates and infants. Pediatr Infect Dis J, 2020; 39:35-40; https://doi.org/10.1097/INF.0000000000002500 https://doi.org/10.1097/INF.0000000000002500
Schober P, Boer C, Schwarte LA. Correlation coefficients: appropriate use and interpretation. Anesth Analg, 2018; 126:1763-8; https://doi.org/10.1213/ANE.0000000000002864 https://doi.org/10.1213/ANE.0000000000002864
Shah S, Zemichael O, Meng HD. Factors associated with mortality and length of stay in hospitalized neonates in Eritrea, Africa: a cross-sectional study. BMJ Open, 2012; 2:e000792; https://doi.org/10.1136/ bmjopen-2011-000792 https://doi.org/10.1136/bmjopen-2011-000792
Shelar J. Indian neonates highly resistant to first-line antibiotics. The Hindu. 2019 (Accessed 18 November 2022)
Shrestha P, Das BK, Bhatta NK, Jha DK, Das B, Setia A, Tiwari A. Clinical and bacteriological profiles of blood culture positive sepsis in newborns. J Nepal Paediatr Soc, 2007; 27:64-7; https://doi.org/10.3126/ jnps.v27i2.1411 https://doi.org/10.3126/jnps.v27i2.1411
Singh S, Charani E, Devi S, Sharma A, Edathadathil F, Kumar A, Warrier A, Shareek PS, Jaykrishnan AV, Ellangovan K. A road-map for addressing antimicrobial resistance in low- and middle-income countries: lessons learnt from the public private participation and co-designed antimicrobial stewardship programme in the State of Kerala, India. Antimicrob Resist Infect Control, 2021; 10:32; https://doi.org/10.1186/ s13756-020-00873-9 https://doi.org/10.1186/s13756-020-00873-9
Singh M, Alsaleem M, Gray CP. Neonatal sepsis. In: StatPearls. StatPearls Publishing, Treasure Island, FL, 2022.
Sundaram V, Kumar P, Dutta S, Mukhopadhyay K, Ray P, Gautam V, Narang A. Blood culture confirmed bacterial sepsis in neonates in a North Indian tertiary care center: changes over the last decade. Jpn J Infect Dis, 2009; 62:46-50.
Thomson KM, Dyer C, Liu F, Sands K, Portal E, Carvalho MJ, Barrell M, Boostrom I, Dunachie S, Farzana R, Ferreira A, Frayne F, Hassan B, Jones E, Jones L, Mathias J, Milton R, Rees J, Chan GJ, Bekele D, Mahlet A, Basu S, Nandy RK, Saha B, Iregbu K, Modibbo F, Uwaezuoke S, Zahra R, Shirazi H, Syed NU, Mazarati JB, Rucogoza A, Gaju L, Mehtar S, Bulabula ANH, Whitelaw A, van Hasselt JGC, Walsh TR, BARNARDS Group. Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS). Lancet Infect Dis, 2021; 21:1677-88; https://doi.org/10.1016/S1473-3099(21)00050-5 https://doi.org/10.1016/S1473-3099(21)00050-5
Thukral A, Sankar MJ, Chandrasekaran A, Agarwal R, Paul VK. Efficacy and safety of CPAP in low- and middle-income countries. J Perinatol, 2016; 36:S21-8; https://doi.org/10.1038/jp.2016.29 https://doi.org/10.1038/jp.2016.29
Tsai MH, Hsu JF, Chu SM, Lien R, Huang HR, Chiang MC, Fu RH, Lee CW, Huang YC. Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J, 2014; 33:e7-13; https://doi.org/10.1097/INF.0b013e3182a72ee0 https://doi.org/10.1097/INF.0b013e3182a72ee0
UNICEF. Neonatal mortality. UNICEF DATA. 2021. Available via https://data.unicef.org/topic/child-survival/neonatal-mortality/ (Accessed 29 April 2022)
WHO. Newborns: improving survival and well-being. Available via https://www.who.int/news-room/fact-sheets/detail/newborns-reducing-mortality (Accessed 15 May 2022)
Ye J, Zhang J, Mikolajczyk R, Torloni MR, Gülmezoglu AM, Betran AP. Association between rates of caesarean section and maternal and neonatal mortality in the 21st century: a worldwide population-based ecological study with longitudinal data. BJOG Int J Obst Gynaecol, 2016; 123(5):745-53. https://doi.org/10.1111/1471-0528.13592
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