PHARMACOEPIDEMIOLOGY OF ANTIMICROBIAL AGENTS IN NEONATOLOGY: RESULTS OF THE RETROSPECTIVE CROSS-SECTIONAL STUDY

Background. Infectious diseases remain the leading causes of morbidity and mortality worldwide. Against the background of ever-increasing resistance of bacteria, it is necessary to develop effective measures aimed at the structure optimization of consumption of antimicrobial agents. Therefore, the pharmacoepidemiological data describing either the consumption of antimicrobial agents or the resistance level to them is required.

Objective: Our aim was to assess the antimicrobial load in term and preterm newborns during their stay in the maternity wards and/or in the intensive care units (ICU).

Methods. A retrospective cross-sectional study has been carried out. The analysis included data of 419 newborns from 5 medical centers. The study has been carried out as part of a multi-purpose program on antibiotic resistance containment being held in St. Petersburg from 2014.

Results. The antimicrobial load on the child's body expressed in days of the antimicrobial therapy was 1,838 per 1,000 patient-days in children staying in the ICU for not more than 16 days, and 1,434 per 1,000 patient-days when staying in the ICU for more than 16 days. The average duration of the antimicrobial therapy is 28 days in the ICU and 5 days out the ICU (department for newborns, physiological departments). The most commonly, the children were treated with ampicillin — 384 (92%), gentamicin — 254 (61%), and fluconazole — 150 (36%). The prevalence of off-label prescriptions was 41% (of 1,557 analyzed prescriptions), unlicensed prescriptions — 10%. Congenital infections were the main reasons for prescription of antimicrobial drugs — 225 (62%).

Conclusion. The high anti-bacterial load in newborns has been established. The indicator 'days of antimicrobial therapy' in the ICU is 4 times higher than that in the United States. The prevalence of off-label and unlicensed prescriptions is comparable with foreign data.

1. Савинова Т.А., Сидоренко Н.Б., Буданов С.В., Грудинина С.А. Динамика распространения резистентности к беталактамным антибиотикам среди Streptococcus pneumoniae и ее клиническая значимость // Антибиотики и химиотерапия. — 2010. — Т. 55. — № 1–2. — C.12–20. [Savinova TA, Sidorenko SV, Budanov SV, Grudinina SA. Dynamics of beta-lactams resistance distribution in Streptococcus pneumoniae and its clinical significance. Antibiot Khimioter. 2010,55(1–2):12–20. (In Russ).]

2. Сидоренко С.В., Резван С.П., Еремина Л.В. и др. Этиология и антибиотикочувствительность возбудителей тяжелых госпитальных инфекций в отделениях реанимации // Антибиотики и химиотерапия. — 2005. — Т. 50. — № 2–3 — C. 33–41. [Sidorenko SV, Rezvan SP, Eremina LV, et al. Etiology of severe hospital infections in intensive care units and antibiotic resistance of the pathogens. Antibiot Khimioter. 2005,50(2–3):33–41. (In Russ).]

3. I ntroduction to drug utilization research [Internet]. Oslo: WHO, 2003. 49 p. [cited 2016 Sep 9]. Available from: http://apps.who.int/medicinedocs/en/d/Js4876e/.

4. Hamad B. The antibiotics market. Nat Rev Drug Discov. 2010,9(9):675–676. doi: 10.1038/nrd3267.

5. Donadio S, Maffioli S, Monciardini P, et al. Antibiotic discovery in the twenty-first century: current trends and future perspectives. J Antibiot (Tokyo). 2010,63(8):423–430. doi: 10.1038/ja.2010.62.

6. Шабалов Н.П. Неонатология. Учебное пособие. В 2-х томах. 5-е изд., испр. и доп. — М.: МЕДпресс-информ, 2009. [Shabalov NP. Neonatologiya. Uchebnoe posobie. In 2 Volumes. 5th ed., enlarged. Moscow: MEDpress-inform, 2009. (In Russ).]

7. Р уководство по перинатологии / Под ред. Иванова Д.О. — СПб.: Информ-Навигатор, 2015. — 1216 с. [Rukovodstvo po perinatologii. Ed by Ivanov D.O. St. Petersburg: Inform-Navigator, 2015. 1216 p. (In Russ).]

8. Cantey JB, Wozniak PS, Sanchez PJ. Prospective surveillance of antibiotic use in the neonatal intensive care unit: results from the SCOUT study. Pediatr Infect Dis J. 2015,34(3):267–72. doi: 10.1097/INF.0000000000000542.

9. Turner S. Unregistered and off-label drug use in paediatric inpatients. Aust J Hosp Pharm.1999,29(5):265–268. doi: 10.1002/jppr1999295265.

10. Patefield WM. Algorithm AS 159: an efficient method of generating random R C tables with given row and column totals. J R Stat Soc Ser C Appl Stat. 1981,30(1):91–97. doi: 10.2307/2346669.

11. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B. 1995,57(1):289–300.

12. grls.rosminzdrav.ru [интернет]. Государственный реестр лекарственных средств РФ. [Gosudarstvennyi reestr lekarstvennykh sredstv RF. (In Russ).] [доступ от 04.10.2016]. Доступ по ссылке http://grls.rosminzdrav.ru/Default.aspx.

13. Kimberlin DW, Brady MT, Jackson MA, Long SS, editors. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. American academy of pediatrics, 2015. 1151 p.

14. Федеральное руководство по использованию лекарственных средств (формулярная система). Выпуск XVII. — М.: Видокс, 2016. — 1045 с. [Federal’noe rukovodstvo po ispol’zovaniyu lekarstvennykh sredstv (formulyarnaya sistema). Vypusk XVII. Moscow: Vidoks, 2016. 1045 p. (In Russ).]

15. Vaniya HV, Agrawal JM, Patel NM, et al. Antimicrobial drug utilization pattern in neonatal sepsis in a tertiary care hospital. Journal of Clinical and Experimental Research. 2014,2(2):110–114. doi: 10.5455/jcer.201422.

16. Patel Brijal S, KubavatAmita R, Sondarva Divyesh B, Piparva Kiran G. Drug utilization study in neonatal intensive care unit at tertiary care hospital, Rajkot, Gujarat: a prospective study. World Journal of Pharmacy and Pharmaceutical Sciences. 2015,4(7):2034–2042.

17. Stevenson DK, Verter J, Fanaroff AA, et al. Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed. 2000,83(3):F182–F185. doi: 10.1136/fn.83.3.f182.

18. nice.org.uk [Internet]. Neonatal infection (early onset): antibiotics for prevention and treatment. Clinical guideline of NICE. 2012. [cited 2016 Sep 9]. Available from: https://www.nice.org.uk/guidance/cg149.

19. Yang YN, Tseng HI, Yang SN, et al. A strategy for reduction of antibiotic use in new patients admitted to a neonatal intensive care unit. Pediatr Neonatol. 2012,53(4):245–251. doi: 10.1016/j.pedneo.2012.06.009.

20. Suryawanshi S, Pandit V, Suryawanshi P, Panditrao A. Antibiotic prescribing pattern in a tertiary level neonatal intensive care unit. J Clin Diagn Res. 2015,9(11):FC21–FC24. doi: 10.7860/jcdr/2015/14764.6807.

21. Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med. 2015,7(307):307ra152. doi: 10.1126/scitranslmed.aab2271.

22. Barlow GM, Yu A, Mathur R. Role of the gut microbiome in obesity and diabetes mellitus. Nutr Clin Pract. 2015,30(6):787–797. doi: 10.1177/0884533615609896.

23. Bradley JS, Nelson JD. Nelsons pediatric antimicrobial therapy. 22nd ed. American Academy of Pediatrics, 2016. 278 p.

24. Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed. 1999,80(2):142–145. doi: 10.1136/fn.80.2.f142.

25. O’Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics. 2002,110(5):e52. doi: 10.1542/peds.110.5.e52.

26. Колбин А.С., Шабалов Н.П., Карпов О.И. Фармако эпи де миология противоинфекционных средств у недоношенных новорожденных // Педиатрия. Журнал имени Г.Н. Сперанского. — 2004. — Т. 83. — № 5 — С. 69–73. [Kolbin AS, Shabalov NP, Karpov OI. Pharmacoepidemiology of anti-infectious medicaments in premature born neonates. Pediatriia. 2004,83(5):69–73. (In Russ).]

27. Зырянов С.К. Использование нерекомендованных лекарств в педиатрии // Педиатрия. Журнал имени Г.Н. Сперанского. — 2005. — Т.84. — №5 — С. 19–22. [Zyryanov SK. Usage of non-recommended drugs in pediatric practice. Pediatriia. 2005,84(5):19–22. (In Russ).]