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Antibiotic, Clinical tool, Diagnosis, Neonatal sepsis, Procalcitonin, STOPS
Background: Antibiotic therapy is initiated in neonates on suspicion of sepsis. Optimizing therapy is a felt need of clinicians as injudicious prolonged use increases mortality and morbidity risk.
Objective: To evaluate the diagnostic accuracy of clinical tool ‘STOPS’ and serum procalcitonin (PCT) for identifying neonates with early onset neonatal sepsis (EONS) or late onset neonatal sepsis (LONS) and early discontinuation in those with no sepsis.
Methods: The study had a prospective analytical design conducted at a tertiary care hospital. All neonates with suspected EONS or LONS were enrolled. The ‘STOPS’ tool comprising of sensorium, temperature, oxygenation, perfusion, skin color and blood sugar was applied at 6 and 12 hr of enrollment. Serum PCT was sent at 12 hr. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (PLR and NLR) were estimated.
Results: The study enrolled 380 neonates of which 330 were given antibiotics for EONS and 50 for LONS. Temperature recording in the EONS group at 12 hr showed a PPV of 100% and a PLR of 9.1 (7.7 – 18). Perfusion assessment at 12 hr had a PPV of 77% and PLR of 8.25 (2.3 – 29). Skin color assessment at 12 hr it had a PPV of 100% and PLR of 13.5 (9.7 – 27). The diagnostic accuracy of PCT in the EONS group was unremarkable. In the LONS group, skin color at 12 hr had a PPV of 100% and PLR of 11.2 (8.6 – 19.5). The diagnostic accuracy of PCT in the LONS group showed a PPV of 82% and PLR of 7 (1.7 – 29).
Conclusion: Identifying abnormal STOPS parameters was superior to PCT alone in EONS and as good as PCT in LONS. The ‘STOPS’ tool allows early identification of neonates with no sepsis thereby optimizing antibiotic use.
2. Schmatz M, Srinivasan L, Grundmeier RW, Elci OU, Weiss SL, Masino AJ, Tremoglie M, Ostapenko S, Harris MC. Surviving sepsis in a referral neonatal intensive care unit: association between time to antibiotic administration and in-hospital outcomes. J Pediatr 2020;217:59-65.e1.
3. The Young Infants Clinical Signs Study Group. Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet 2008; 371: 135–42.
4. Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sánchez PJ, Ambalavanan N, Benjamin DK Jr; NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123:58–66.
5. Schulfer A, Blaser MJ. Risks of antibiotic exposures early in life on the developing microbiome. PLoS Pathog 2015; 11:e1004903.
6. Connell TG, Rele M, Cowley D, Buttery JP, Curtis N. How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital. Pediatrics 2007; 119:891–6.
7. Buttery JP. Blood cultures in newborn and children: Optimizing an everyday test. Arch Dis Child Fetal Neonatal Ed 2002; 87:F25–F28.
8. Yu Z, Liu J, Sun Q, Qiu Y, Han S, Guo X. The accuracy of the procalcitonin test for the diagnosis of neonatal sepsis: A Meta-analysis. Scand Infect Dis J 2010; 42:723–733.
9. Stocker M, van Herk W, El Helou S, Dutta S, Fontana MS, Schuerman FABA, van den Tooren-de Groot RK, Wieringa JW, Janota J, van der Meer-Kappelle LH, Moonen R, Sie SD, de Vries E, Donker AE, Zimmerman U, Schlapbach LJ, de Mol AC, Hoffman-Haringsma A, Roy M, Tomaske M, Kornelisse RF, van Gijsel J, Visser EG, Willemsen SP, van Rossum AMC; NeoPInS Study Group. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre randomised controlled trial (NeoPIns). Lancet 2017; 390:871–81.
10. The WHO Young Infants Study Group. Clinical prediction of serious bacterial infections in young infants in developing countries. Pediatr Infect Dis J 1999; 18 (10 suppl): S23–31.
11. Lopez Sastre JB, Solis DP, Serradilla VR, Colomer BF, Cotallo GD; Grupo de Hospitales Castrillo. Evaluation of procalcitonin for diagnosis of vertical transmission. BMC Pediatrics 2007; 7:9.
12. Rossi P, Botgross R (eds). Report on the expert meeting on neonatal and pediatric sepsis in the Pediatric committee of the European Medicines Agency. EMA London.2010. EMA/477725/2010.
13. 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 Immunisation (I4) section of the ESPR. Challenges in developing a consensus definition of neonatal sepsis. Pediatr Res 2020;88:14-26.
14. Tuzun F, Ozkan H, Cetinkaya M, Yucesoy E, Kurum O, Cebeci B, Cakmak E, Ozkutuk A, Keskinoglu P, Baysal B, Kumral A, Duman Net al. Is European Medicines Agency (EMA) sepsis criteria accurate for neonatal sepsis diagnosis or do we need new criteria? PLoS One 2019;14:e0218002.
15. National Collaborating Centre for Women's and Children's Health (UK). Antibiotics for Early-Onset Neonatal Infection: Antibiotics for the Prevention and Treatment of Early-Onset Neonatal Infection. London: RCOG Press; 2012.
16. 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
17. Carley S, Dosman S, Jones SR, Harrison M. Simple nomogram to calculate sample size in diagnostic studies. Emerg Med J 2005; 22:180–81.
18. Modi N, Dore CJ, Saraswatula A, Richards M, Bamford KB, Coello R, Holmes A. A case definition for national and international neonatal blood stream infection surveillance. Arch Dis Fetal Neonatal Ed 2009; 94:F8–F12.
19. Tollner U. Early diagnosis of septicemia in the newborn, Clinical studies and sepsis score. Eur J Pediatr 1982; 138:331–37.
20. Bang AT, Bang RA, Reddy MH, Baitule SB, Deshmukh MD, Paul VK, de C Marshal TF. Simple clinical criteria to identify sepsis or pneumonia in neonates in the community needing treatment or referral. Pediatr Infect Dis J 2005; 24:335–41.
21. Ohlin A, Bjorkqvist M, Montgomery SM, Schollin J. Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis. Acta Pediatrica 2010; 99:1635–40.
22. Achten NB, Klingenberg C, Benitz WE, Stocker M, Schlapbach LJ, Giannoni E, Bokelaar R, Driessen GJA, Brodin P, Uthaya S, van Rossum AMC, Plötz FB. Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis. JAMA Pediatr 2019. doi:10.1001/jamapediatrics.2019.2825.
23. Singh SA, Dutta S, Narang A. Predictive Clinical Scores for Diagnosis of Late Onset Neonatal Septicemia. J Trop Pediatr 2003; 49:235–39.
24. Husada D, Chanthavanich P, Chotigeat U, Sunttarattiwong P, Sirivichayakul C, Pengsaa K, Chokejindachai W, Kaewkungwal J. Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand. BMC Infectious Diseases 2020; 20:15. https://doi.org/10.1186/s12879-020-4875-5.
25. Okascharoen C, Sirinavin S, Thakkinstian A, Kitayaporn D, Supapanachart S. A Bedside Prediction-Scoring Model for Late-Onset Neonatal Sepsis. J Perinatol 2005; 25:778–83.
26. Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Iglesias I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB. Early Insulin Therapy in Very-Low-Birth-Weight Infants. New Engl J Med 2008; 359:1873–84.
27. Islam MS, Mia MAH, Akhter KR, Haque M, Malik MA. Glycemic Status and its Effect in Neonatal Sepsis in a Tertiary Care Hospital. Bangladesh J Child Health 2016; 40:21–5.