Incidence of Meningitis in Neonates with Late‑Onset Sepsis at a Tertiary

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[Downloaded free from http://www.jcnonweb.com on Friday, July 12, 2019, IP: 200.121.233.115] Original Article Incidence of Meningitis in Neonates with Late‑onset Sepsis at a Tertiary Care Center in Western India: An Observational Study Sameet Umate, Bhawan Deep Garg, Nandkishor S Kabra

Department of Neonatology, Objective: The objective of this study was to determine the incidence of Surya Children’s Medicare meningitis in neonates with late‑onset sepsis (LOS) in the West India population. Pvt. Ltd., Mumbai, Maharashtra, India Materials and Methods: This prospective observational study enrolled 208 bstract neonates with signs and symptoms suggestive of sepsis with positive C‑reactive A protein at or more than 72 h of postnatal age. Results: Out of total 208 neonates with LOS, 12.5% neonates had meningitis. The incidence of LOS in preterm and low‑birth‑weight neonates were 73.6% and 72.1%, respectively. Most common presenting features in neonates with LOS with or without meningitis were respiratory distress (72.6%), followed by lethargy (68.8%) and refusal to feed (63%). Blood culture was positive in 53.8% neonates who had meningitis. Mortality in neonatal meningitis was 3.84%. Conclusion: This study demonstrated that a significant number of neonates with LOS have coexistent neonatal meningitis. Our study highlights the diagnostic utility of routine lumbar puncture in neonates with clinical features of sepsis.

Keywords: Incidence, late‑onset sepsis, meningitis

Introduction North India.[8] Two other studies from North India[9] and [10] eonatal sepsis is one of the most common Central India reported approximately 17% incidence Ncauses of neonatal mortality.[1] Worldwide, of meningitis in neonates with LOS. However, there is a neonatal mortality accounts for approximately paucity of data from West India. Hence, this study was 5 million deaths each year, 96% of which occurs planned to evaluate the incidence of meningitis in LOS. in developing countries.[2,3] In developing countries, Objective sepsis is responsible for approximately 30%–50% of The main objective of this study was to estimate the the total neonatal deaths.[2] According to the data from incidence of meningitis in LOS at a tertiary care center the National Neonatal‑Perinatal Database (NNPD), in the West Indian population. incidence of neonatal sepsis is 30/1000 live births.[4] Neonatal sepsis is mainly categorized as early‑onset Materials and Methods sepsis and late‑onset sepsis (LOS). LOS presents after This descriptive observational study was conducted at 72 h of age with septicemia, pneumonia, or meningitis.[1] a tertiary level neonatal intensive care unit (NICU) of Neonatal meningitis is a serious consequence of LOS Surya Children’s Hospital, Santacruz West, Mumbai, with a mortality of 33%–48% in developing countries.[2] West India. Ethical Committee of the Institute approved NNPD reported the incidence of meningitis 3/1000 live the study protocol. Neonates, who were born in our births.[1] Incidence of LOS‑associated meningitis ranges Address for correspondence: Dr. Bhawan Deep Garg, [5‑7] from 3% to 30%. Studies in the UK have found that Department of Neonatology, Surya Children’s Medicare Pvt. Ltd., the incidence of meningitis varies from 1.3% to 3.5% S. V. Road, Santacruz West, Mumbai - 400 054, in neonates with LOS.[5] Kaul et al. reported 22.5% Maharashtra, India. E‑mail: [email protected] incidence of meningitis in neonates with suspected clinical sepsis in a tertiary care referral neonatal unit in This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as Access this article online appropriate credit is given and the new creations are licensed under the identical Quick Response Code: terms. Website: www.jcnonweb.com For reprints contact: [email protected]

DOI: How to cite this article: Umate S, Garg BD, Kabra NS. Incidence of 10.4103/jcn.JCN_64_18 meningitis in neonates with late-onset sepsis at a Tertiary Care Center in Western India: An observational study. J Clin Neonatol 2019;8:67-70.

Umate, et al.: Meningitis in late‑onset sepsis

hospital or transferred to the NICU from January as statistically significant. PASW Statistics for Windows, 2015 to December 2016 and presented with signs and Version 18.0. (SPSS Inc., Chicago, USA) was used for symptoms suggestive of sepsis with positive C‑reactive analysis. protein (CRP) at or more than 72 h of postnatal age, were enrolled in the study. Results Sign and symptoms of sepsis were defined as A total of 2039 neonates were admitted during the study the following: lethargy, reduced feeding ability, for various indications. Out of these 2039 neonates, no spontaneous movement, temperature >38°C, 225 neonates were presented with LOS. A total of 208 hypothermia, cyanosis, abdominal distension, increased neonates were eligible for the study after exclusion. The demographic profile of neonates with LOS is prefeed aspirates in preterm/low birth weight (LBW), summarized in Table 1. Out of total 208 neonates pustular lesions, umbilical sepsis, presence of excessive with LOS, 12.5% (n = 26) of neonates had meningitis. crying, high‑pitched cry, bulging fontanelle and/or The incidence of LOS in preterm and LBW neonates occurrence of/or history of convulsions, grunting, flaring, was 73.6% and 72.1%, respectively. Correlation of retractions, tachypnea (respiratory rate >60/min), apnea meningitis with demographic factors is summarized in lasting more than 20 s, tachycardia (heart rate [HR] Table 2, which was not statistically significant. >160/min) or bradycardia (HR <100/min), or capillary refill time >3 s. CRP >10 mg/L was considered positive The most common presenting features in neonates as per our unit protocol. Quantitative CRP estimation with LOS with or without meningitis were respiratory was performed by using turbidimetric immunoassay distress (72.6%), followed by lethargy (68.8%) method. Neonates with neural tube defects, such as and refusal to feed (63%) [Table 3]. Overall blood spina bifida (meningocele, meningomyelocele, and culture was positive in 26% of neonates who lipomeningocele), anencephaly, and very sick neonates presented with LOS. The incidence of blood culture even after initial stabilization, were excluded from the positive rate was significantly higher in neonates study. who had meningitis (53.8%) as compared to no meningitis (22%) [Table 4]. The most common Neonates with positive CRP were undergone organisms isolated in blood culture and CSF culture following investigations: blood culture, urine culture, were Acinetobacter baumannii, followed by Klebsiella and cerebrospinal fluid (CSF) routine microscopic examination and culture. Other blood investigations and neuroimaging as and when required. Meningitis Table 1: Demographic profile of neonates with late‑onset was defined according to the National Neonatology sepsis Forum guidelines 2010.[11] Meningitis was labeled Study group Neonates (n=208), n (%) in a neonate whose CSF findings satisfied all the Male neonates 129 (62.01) following criteria: (1) CSF glucose less than the plasma Term 35 (27.13) Preterm 94 (72.86) glucose (sample to be taken before lumbar puncture) Female neonates 79 (37.98) by ≥50%; (2) CSF white cell count >10/cu mm; (3) CSF Term 26 (32.9) protein >80 mg/dl, and (4) with/without CSF culture Preterm 59 (74.68) positive. Baseline characteristics of the study population Birth weight (kg) were recorded in predesigned pro forma. <1.5 91 (43.75) Study outcomes 1.5–2.499 59 (28.36) >2.5 58 (27.88) 1. To determine the incidence of meningitis in neonates with LOS 2. The outcome of meningitis. Table 2: Correlation of neonatal meningitis with gender, Statistical methods weight, and gestational age Descriptive statistics were used to describe the baseline Meningitis (n=26), No meningitis P n (%) (n=182), n (%) outcome variables. Mean (±standard deviation) and Male 13 (50) 116 (63.73) 0.19 median (interquartile range) were used to analyze Preterm (GA<37 weeks) 19 (73.1) 128 (70.32) 1.00 normally distributed and nonparametric data. Categorical Birth weight (kg) variables were reported as a percentage. Fisher’s <1.5 11 (42.3) 80 (43.95) 0.67 exact test was used to compare categorical data. The 1.5–2.499 9 (34.6) 50 (27.47) Chi‑square test was used for assessing the relationship Chi‑square test used. P<0.05 considered statistically significant. between the two proportions. P < 0.05 was considered GA – Gestational age

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Umate, et al.: Meningitis in late‑onset sepsis

pneumoniae [Tables 5 and 6]. Overall mortality in Table 3: Presenting features in neonates with sepsis with neonates with LOS was 3.36% (n = 7/208). Mortality or without meningitis was not statistically significant in between meningitis Presenting feature Percentage and no meningitis group [Table 7]. Respiratory distress 72.60 Lethargy 68.75 Discussion Refusal to feed 62.98 This study revealed incidence of neonatal meningitis Shock 20.67 in LOS was 12.5%, which was almost similar to other Convulsions 13.94 Indian observational studies such as Bhagat et al.[9] (16%) Fever 10.57 and Mehta[10] (17%). Similar observational studies from Abdominal distention 4.32 Kenya,[12] Brazil,[13] and Asia[14] reported the incidence of meningitis in neonates with LOS were 17.9%, 17%, Table 4: Blood culture in neonates with and without and 17.2%, respectively. However, Kaul et al.[8] reported meningitis a higher incidence of meningitis (22.5%) compared Blood culture Meningitis (n=26), No meningitis P to our study. The minor difference in the incidence n (%) (n=182), n (%) can be attributed to the various epidemiological and Positive 14 (53.84) 40 (21.97) 0.0013* geographical factors in community‑acquired infection in Negative 12 (46.15) 142 (78.02) late‑onset variety of sepsis. *P<0.05 considered statistically significant. Fischer’s exact test used

There was no gender prediction for meningitis in our Table 5: Microorganisms isolated from the blood [8,15,16] study similar to other observational studies. Kaul cultures of neonates with late‑onset sepsis et al. reported male predominance in neonates who Organisms Number (n=54), n (%) had meningitis.[9] Incidence of LOS in preterm and Acinetobacter baumannii 23 (42.59) LBW neonates was 73.6% and 72.1% in our study, Klebsiella pneumoniae 16 (29.62) respectively. Out of neonates having meningitis, 73% and Escherichia coli 5 (9.26) 76.9% were preterm and LBW, respectively. Similarly, Serratia marcescens 3 (5.55) other observational studies reported a high incidence of Staphylococcus epidermidis 1 (1.85) LOS and meningitis in preterm and LBW neonates.[8,9,15] Streptococcus pyogenes 1 (1.85) Major presenting sign and symptoms of LOS with or Sphingomonas paucimobilis 1 (1.85) without meningitis were respiratory distress, lethargy, MRSA 1 (1.85) and refusal to feed in our study. Similar observation was Staphylococcus haemolyticus 1 (1.85) Burkholderia cepacia 1 (1.85) reported by Hoque et al.,[17] Karthikeyan et al.,[18] and Aeromonas hydrophila 1 (1.85) Bhagat et al.[9] MRSA – Methicillin‑resistant Staphylococcus aureus Blood culture was positive in 53.8% cases of meningitis in our study. Bhagat et al.[9] and Mehta[10] reported Table 6: Microorganisms isolated from the cerebrospinal 42.6% and 49.6% positive blood culture in neonates with fluid cultures of meningitic neonates meningitis, respectively. The most common organism Organisms Number (n=12), n (%) recovered from culture was Acinetobacter, followed by Acinetobacter baumannii 5 (41.67) Klebsiella in the present study. Mehta[10] and Bhagat Klebsiella pneumoniae 2 (16.67) et al.[9] reported Klebsiella and methicillin‑resistant Acinetobacter lwoffii 1 (8.33) Staphylococcus aureus most common isolate, Staphylococcus epidermidis 1 (8.33) respectively, in blood culture. The overall mortality Sphingomonas paucimobilis 1 (8.33) in neonatal meningitis was 3.84% which was Serratia marcescens 1 (8.33) comparatively less as reported by other studies such Burkholderia cepacia 1 (8.33) as Mehta[10] (20.6%), Tiskumara et al.[14] (20%), Kaul et al.,[8] (26.1%) and Bhagat et al.[9] (17.6%). This low Table 7: Outcome of meningitis and nonmeningitis cases mortality in our study can be attributed to continuous Outcome Meningitis No meningitis P efforts to improve intensive care facilities. (n=26), n (%) (n=182), n (%) Death 1 (3.84) 6 (3.29) 1.000 (NS) The strength of the study includes adequate sample Recovery 25 (96.1) 176 (96.70) size and strict study protocol. Limitation of our study Fisher’s exact test used. NS – Not significant includes not evaluating the effect of exclusive breast milk feeding on the prognosis of neonates with LOS. on the incidence of neonatal meningitis in the Western Despite this, the present study provides important data Indian population. Moreover, there is an urgent need for

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studies looking at simple and sustainable interventions to late‑onset infection always have a lumbar puncture? Arch Dis reduce the burden of neonatal infection such as adequate Child 2006;91:75‑6. implementation of simple infection control methods, 6. Berger A, Salzer HR, Weninger M, Sageder B, Aspöck C. Septicaemia in an Austrian neonatal intensive care unit: A 7‑year exclusive breastfeeding, restriction of antibiotic use, analysis. Acta Paediatr 1998;87:1066‑9. increasing trend toward noninvasive ventilation, and 7. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, rationalization of admissions to and discharges from Ehrenkranz RA, et al. Late‑onset sepsis in very low birth weight neonatal units. neonates: The experience of the NICHD neonatal research network. Pediatrics 2002;110:285‑91. Conclusion 8. Kaul V, Harish R, Ganjoo S, Mahajan B, Raina SK, Koul D, et al. Importance of obtaining lumbar puncture in neonates with This study demonstrated that a significant number of late onset septicemia a hospital based observational study from neonates with LOS have coexistent neonatal meningitis. North‑West India. J Clin Neonatol 2013;2:83‑7. A vigilant attitude toward the presence of postnatal risk 9. Bhagat R, Hussain SQ, Gattoo IA, Wani SA. Incidence factors associated with an increased risk of mortality of meningitis in late onset sepsis. Int J Contemp Pediatr 2015;2:96‑102. in cases of suspected sepsis can be helpful for early 10. Mehta S. Late onset sepsis in newborns with incidence of treatment initiation. Through the current study, we meningitis. Eur J Pharm Med Res 2017;4:588‑91. would like to recommend that a blood culture should 11. National Neonatology Forum India. Evidence Based Clinical be performed in all cases of suspected sepsis before Practice Guidelines; 2010. Available from: http://www.nnfi.org/ starting antibiotics. In addition, our study highlights the images/pdf/nnf_cpg_consolidated_file‑january102011.pdf. [Last diagnostic utility of routine lumbar puncture in neonates accessed on 2018 May 15]. 12. Laving AM, Musoke RN, Wasunna AO, Revathi G. Neonatal with clinical features of sepsis. bacterial meningitis at the newborn unit of Kenyatta National Financial support and sponsorship Hospital. East Afr Med J 2003;80:456‑62. 13. da Silva LP, Cavalheiro LG, Queirós F, Nova CV, Lucena R. Nil. Prevalence of newborn bacterial meningitis and sepsis during the Conflicts of interest pregnancy period for public health care system participants in Salvador, Bahia, Brazil. Braz J Infect Dis 2007;11:272‑6. There are no conflicts of interest. 14. Tiskumara R, Fakharee SH, Liu CQ, Nuntnarumit P, Lui KM, Hammoud M, et al. Neonatal infections in Asia. Arch Dis Child References Fetal Neonatal Ed 2009;94:F144‑8. 1. Sankar MJ, Agarwal R, Deorari AK, Paul VK. Sepsis in the 15. Jiang JH, Chiu NC, Huang FY, Kao HA, Hsu CH, Hung HY, newborn. Indian J Pediatr 2008;75:261‑6. et al. Neonatal sepsis in the neonatal intensive care unit: 2. Vergnano S, Sharland M, Kazembe P, Mwansambo C, Heath PT. Characteristics of early versus late onset. J Microbiol Immunol Neonatal sepsis: An international perspective. Arch Dis Child Infect 2004;37:301‑6. Fetal Neonatal Ed 2005;90:F220‑4. 16. Gheibi S, Fakoor Z, Karamyyar M, Khashabi J, Ilkhanizadeh B, 3. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Asghari‑Sana F, et al. Coagulase negative Staphylococcus; the Effect of home‑based neonatal care and management of most common cause of neonatal septicemia in Urmia, Iran. Iran sepsis on neonatal mortality: Field trial in rural India. Lancet J Pediatr 2008;18:237‑43. 1999;354:1955‑61. 17. Hoque MM, Ahmed AS, Chowdhury MA, Darmstadt GL, 4. National Neonatal‑Perinatal Database. Report of the National Saha SK. Septicemic neonates without lumbar puncture: What Neonatal Perinatal Database (National Neonatology Forum), are we missing? J Trop Pediatr 2006;52:63‑5. 2002‑2003. Available from: http://www.newbornwhocc.org/pdf/ 18. Karthikeyan G, Premkumar K. Neonatal sepsis: nnpd_report_2002‑03.PDF. [Last accessed on 2016 Oct 15]. Staphylococcus aureus as the predominant pathogen. Indian J 5. Malbon K, Mohan R, Nicholl R. Should a neonate with possible Pediatr 2001;68:715‑7.

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