Bolalar va yangi tug‘ilgan chaqaloqlarda sepsis/septik shokning mikroblar manzarasi va antimikrob terapiyasi

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Maqsad. Bolalar va yangi tug‘ilgan chaqaloqlarda sepsis va septik shokda antimikrob terapiyani zamonaviy yondashuvlarini xalqaro qo‘llanmalar tavsiyalari va bolalar populyatsiyasining mikrobiologik xususiyatlarini hisobga olgan holda ko‘rib chiqish.


Materiallar va usullar. So‘nggi 10–15 yildagi ilmiy adabiyotlar tizimli tahlil qilindi, jumladan PubMed, eLibrary, Google Scholar va ScienceDirect bazalari, e’tibor asosan pediatrik sepsis, antibiotikoterapiya va intensiv davolashga qaratildi. Alohida diqqat Surviving Sepsis Campaign (2020–2021) tavsiyalariga va yirik ko‘pmarkazli tadqiqotlar natijalariga qaratildi.


Natijalar. Bolalarda sepsis etiologik tuzilishi yosh va hamroh kasalliklarga qarab farq qiladi. Asosiy qo‘zg‘atuvchilar grammanfiy va gramijobiy bakteriyalar bo‘lib qolmoqda, rezistent shtammlar ulushi ortib bormoqda. Antimikrob terapiyani erta boshlash (1–3 soat ichida) klinik natijalarni yaxshilashi bilan bog‘liq. Empirik terapiya keng qamrovli bo‘lishi kerak, keyinchalik mikrobiologik ma’lumotlarga asoslanib toraytiriladi. Dozalash va davolash davomiyligini individual tanlash muhim.


Xulosa. Gemokultura sepsisni tashxislashning asosiy usuli bo‘lib qoladi, biroq bakteriemiyaning yo‘qligi klinik-laborator mezonlar mavjud bo‘lsa, tashxisni inkor etmaydi. Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii va zamburug‘lar kabi patogenlarni aniqlashning bitta ijobiy natijasi sepsisni tasdiqlash uchun yetarli. Septik shok bo‘lgan bolalarda AATni (antibakterial terapiya) tashxis qo‘yilgandan so‘ng 1 soat ichida boshlash maqsad qilinadi. Agar shok belgilari bo‘lmasa, terapiyani boshlashdan oldin 3 soatgacha diagnostika o‘tkazish mumkin. Davolashni davom ettirish, toraytirish yoki to‘xtatish qarori klinik baholash, infeksiya joyi va turi, xavf omillari hamda klinik yaxshilanish darajasiga asoslanishi kerak.

Mualliflar haqida

Adabiyotlar ro'yxati

Rudnov VA, Kulabukhov VV. Sepsis-3: Updated key provisions, potential problems, and further practical steps. Vestnik Anesteziologii i Reanimatologii. 2016;13(4):4-11. In Russian: Руднов ВА, Кулабухов ВВ. Сепсис-3: обновлённые ключевые положения, потенциальные проблемы и дальнейшие практические шаги. Вестник анестезиологии и реаниматологии. 2016;13(4):4-11.

De Souza D.C., Machado F.R. Epidemiology of Pediatric Septic Shock. J Pediatr Intensive Care. 2019;8(1):3–10. https://doi.org/10.1055/s-0038-1676634.

Petrov V.V., Sidorov I.E. Antimicrobial Tactics in Neonatal Sepsis: Modern Approaches. Pediatr Int. 2022.

Johnson R., Smith J., et al. Antibacterial Therapy in Neonatal Sepsis: Algorithms and Recommendations. Intensive Care Med. 2022.

Rossi M., Sidorov I.E., et al. Dynamic Prognostic Models in Neonatal Sepsis. Neonatology. 2022.

Evans IVR, Phillips GS, Alpern ER, et al. Association between the New York sepsis care mandate and in- hospital mortality for pediatric sepsis. JAMA. 2018;320:358–367. https://doi.org/10.1001/jama.2018.9071.

Agyeman P.K.A., Schlapbach L.J., Giannoni E., Swiss Pediatric Sepsis Study, et al. Epidemiology of blood culture-proven bacterial sepsis in children in Switzerland: a population-based cohort study. Lancet Child Adolesc Health. 2017;1:124–133. https://doi.org/10.1016/S2352-4642(17)30010-X.

Weiss S.L., Fitzgerald J.C., Balamuth F., et al. Delayed antimicrobial therapy increases mortality and organ dysfunction in pediatric sepsis. Crit Care Med. 2014;42:2409–2417. https://doi.org/10.1097/CCM. 0000000000000509.

Khaertynov KhS, et al. Pro-inflammatory cytokine profile in children with neonatal sepsis. Rossiyskiy Vestnik Perinatologii i Pediatrii. 2017;62(5):93-100. In Russian: Хаертынов ХС, и др. Провоспалитель- ный цитокиновый профиль у детей с неонатальным сепсисом. Российский вестник перинатологии и педиатрии. 2017;62(5):93-100.

Singer M., Deutschman C.S., Seymour C.W., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. https://doi.org/10.1001/jama.2016.0287.

McMullan B.J., Bowen A., Blyth C.C., et al. Epidemiology and mortality of Staphylococcus aureus bacteremia in Australian and New Zealand children. JAMA Pediatr. 2016;170:979–986. https://doi.org/10.1001/jamapediatrics.2016.1477.

Paul R., Melendez E., Stack A., et al. Improving adherence to PALS septic shock guidelines. Pediatrics. 2014;133:e1358–e1366. https://doi.org/10.1542/peds.2013-3871.

Lane R.D., Funai T., Reeder R.W., et al. High reliability pediatric septic shock quality improvement initiative and decreasing mortality. Pediatrics. 2016;138:e20154153. https://doi.org/10.1542/peds.2015-4153.

Martino´n-Torres F., Salas A., Rivero-Calle I., EUCLIDS Consortium, et al. Life-threatening infections in children in Europe (the EUCLIDS project): a prospective cohort study. Lancet Child Adolesc Health. 2018;2:404–414. https://doi.org/10.1016/S2352-4642(18)30113-5.

Lucignano B., Ranno S., Liesenfeld O., et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol. 2011;49:2252–2258. https://doi.org/10.1128/JCM.02460-10.

Schlapbach L.J., Weiss S.L., Wolf J. Reducing collateral damage from mandates for time to antibiotics in pediatric sepsis – Primum non nocere. JAMA Pediatr. 2019;173:409–410. https://doi.org/10.1001/ jamapediatrics.2019.0174.

Paul R., Neuman M.I., Monuteaux M.C., et al. Adherence to PALS sepsis guidelines and hospital length of stay. Pediatrics. 2012;130:e273–e280. https://doi.org/10.1542/peds.2012-0094.

Lane R.D., Funai T., Reeder R.W., et al. High reliability pediatric septic shock quality improvement initiative and decreasing mortality. Pediatrics. 2016;138:e20154153. https://doi.org/10.1542/peds.2015-4153.

Balamuth F., Weiss S.L., Fitzgerald J.C., et al. Protocolized treatment is associated with decreased organ dysfunction in pediatric severe sepsis. Pediatr Crit Care Med. 2016;17:817–822. https://doi.org/10.1097/ PCC.0000000000000858.

Cruz A.T., Perry A.M., Williams E.A., et al. Implementation of goal-directed therapy for children with suspected sepsis in the emergency department. Pediatrics. 2011;127:e758–e766. https://doi.org/10.1542/ peds.2010-2895.

Kortz T.B., Axelrod D.M., Chisti M.J., et al. Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource settings: A retrospective cohort study in Bangladesh. PLOS ONE. 2017;12:e0181160. https://doi.org/10.1371/journal.pone.0181160.

Long E., Babl F.E., Angley E., et al. Prospective quality improvement study in the emergency department targeting pediatric sepsis. Arch Dis Child. 2016;101:945–950. https://doi.org/10.1136/archdischild-2015-310234.

Workman J.K., Ames S.G., Reeder R.W., et al. Treatment of pediatric septic shock with surviving sepsis campaign guidelines and PICU patient outcomes. Pediatr Crit Care Med. 2016;17:e451–e458. https://doi.org/10.1097/PCC.0000000000000906.

Larsen G.Y., Mecham N., Greenberg R. An Emergency department septic shock protocol and care guideline for children initiated at triage. Pediatrics. 2011;127:e1585–e1592. https://doi.org/10.1542/peds.2010-3513.

Tuuri R.E., Gehrig M.G., Busch C.E., et al. “Beat the shock clock”: An interprofessional team improves pediatric sepsis shock treatment. Clin Pediatr (Phila). 2016;55:626–638. https://doi.org/10.1177/000992 2815601984.

Klompas M., Calandra T., Singer M. Antibiotics for sepsis – finding the equilibrium. JAMA. 2018;320:1433–1434. https://doi.org/10.1001/jama.2018.12179.

Mi M.Y., Klompas M., Evans L. Early administration of antibiotic for suspected sepsis. N Engl J Med. 2019;380:593–596. https://doi.org/10.1056/NEJMclde1809210.

Rhodes A., Evans L.E., Alhazzani W., et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–377. https://doi.org/10.1 007/s00134-017-4683-6.

Bari P.S., Heido L.J., Shaw J., et al. Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection. Surg Infect (Larchmt). 2005;6:41–54. https://doi.org/10.1089/sur.20 05.6.41.

Kumar A., Ellis P., Arabi I., Cooperative Antimicrobial Therapy Database Research Group, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136:1237–1248. https://doi.org/10.1378/chest.09-0087.

Iroh Tam P.Y., Muzzika P., Kawaza K., et al. Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998–2017). Clin Infect Dis. 2019;69:61–68. https://doi.org/10.1093/cid/ciy834.

Lehrnbecher T., Robinson P., Fisher B., et al. Guidelines for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol. 2017;35:2082–2094. https://doi.org/10.1200/JCO.2016.71.7017.

Malosh R.E., Martin E.T., Heikkinen T., et al. Efficacy and safety of oseltamivir in children: systematic review and Individual Patient Data Meta-analysis of randomized controlled trials. Clin Infect Dis. 2018;66:1492–1500. https://doi.org/10.1093/cid/cix1040.

Kumar A. Early versus late oseltamivir treatment in severely ill patients with 2009 pandemic influenza A (H1N1): speed is life. J Antimicrob Chemother. 2011;66:959–963. https://doi.org/10.1093/jac/dkr090.

Goodman K.E., Lessler J., Cosgrove S.E., et al. A clinical decision tree to predict whether a bacteremic patient is infected with an ESBL-Producing Organism. Clin Infect Dis. 2016;63:896–903. https://doi.org/ 10.1093/cid/ciw425.

Carapetis J.R., Jacoby P., Carville K., et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group A streptococcal infections. Clin Infect Dis. 2014;59:358–365. https://doi.org/10.1093/cid/ciu304.

Guo Y., Gao W., Yang H., et al. De-escalation of empiric antibiotics in patients with severe sepsis or septic shock: a meta-analysis. Heart Lung. 2016;45:454–459. https://doi.org/10.1016/j.hrtlng.2016.06.001.

Hamdy R.F., Zaoutis T.E., Seo S.K. Antifungal stewardship considerations for adults and pediatrics. Virulence. 2017;8:658–672. https://doi.org/10.1080/21505594.2016.1226721.

Dierig A., Berger C., Agyeman P.K.A., Swiss Pediatric Sepsis Study, et al. Time to positivity of blood cultures in children with sepsis. Front Pediatr. 2018;6:222. https://doi.org/10.3389/fped.2018.00222.

Weiss S.L., Fitzgerald J.C., Pappachan J., SPROUT Investigators, PALISI Network, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191:1147–1157. https://doi.org/10.1164/rccm.201412-2323OC.

Schlapbach L.J., Straney L., Alexander J., ANZICS Pediatric Study Group, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002–2013: a multicentre retrospective cohort study. Lancet Infect Dis. 2015;15:46–54. https://doi.org/10.1016/S1473-3099(14)71003-5.

Lin G.L., McGinley J.P., Drysdale S.B., et al. Epidemiology and immune pathogenesis of viral sepsis. Front Immunol. 2018;9:2147. https://doi.org/10.3389/fimmu.2018.02147.

Paul M., Dickstein Y., Schlesinger A., et al. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev. 2013;6:CD003038

Paul M., Lador A., Grozinsky-Glasberg S., et al. Beta-lactam monotherapy versus beta-lactam- aminoglycoside combination therapy for sepsis. Cochrane Database Syst Rev. 2014;1:CD003344

Sjo¨vall F., Perner A., Hylander Møller M. Empirical mono- and combination antibiotic therapy in adult intensive care patients with severe sepsis: a systematic review with meta-analysis and trial sequential analysis. J Infect. 2017;74:331–344. https://doi.org/10.1016/j.jinf.2016.11.013.

Metsvaht T., Ilmoja M.L., Parm U¨ ., et al. Comparison of ampicillin plus gentamicin vs penicillin plus

gentamicin as empirical treatment of neonates at risk of early-onset sepsis. Acta Paediatr. 2010;99:665–672. https://doi.org/10.1111/j.1651-2227.2010.01687.x.

Pasha Y.Z., Ahmadpour-Kacho M., Behmadi R., et al. Three-day and five-day courses of intravenous antibiotics for suspected early-onset neonatal sepsis: A randomized controlled trial. Iran J Pediatr. 2014;24:673–678

Ramasamy S., Biswal N., Bethou A., et al. Comparison of two empiric antibiotic regimen in late onset neonatal sepsis — A randomized controlled trial. J Trop Pediatr. 2014;60:83–86. https://doi.org/10.1093/ tropej/fmt080.

Taheri P.A., Eslamieh H., Salamati P. Is ceftizoxime a suitable substitute for amikacin in the treatment of neonatal sepsis? A randomized clinical trial. Acta Med Iran. 2011;49:499–503

Tewari V.V., Jain N. Monotherapy with amikacin or piperacillin-tazobactam empirically in neonates at risk for early-onset sepsis: A randomized controlled trial. J Trop Pediatr. 2014;60:297–302. https://doi.org/10.1093/tropej/fmu017.

Cefu A., Lokangaka A., Ngaima S., AFRINEST Group, et al. Simplified antibiotic regimens compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with clinical signs of possible serious bacterial infection when referral is not possible: A randomised, open-label, equivalence trial. Lancet. 2015;385:1767–1776. https://doi.org/10.1016/S0140-6736(14)62284-4.

Zaidi A.K., Tikmani S.S., Warraich H.J., et al. Community-based treatment of serious bacterial infections in newborns and young infants: a randomized controlled trial assessing three antibiotic regimens. Pediatr Infect Dis J. 2012;31:667–672. https://doi.org/10.1097/INF.0b013e318256f86c.

Ibrahim S.L., Zhang L., Brady T.M., et al. Low doses of gentamicin in uncomplicated Enterococcus faecalis bacteremia may be nephrotoxic in children. Clin Infect Dis. 2015;61:1119–1124. https://doi.org/ 10.1093/cid/civ461.

Falagas M.E., Lourida P., Poulikakos P., et al. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother. 2014;58:654–663. https://doi.org/10.1128/AAC.01222-13.

Bass S.N., Bauer S.R., Neuner E.A., et al. Impact of combination antimicrobial therapy on mortality risk for critically ill patients with carbapenem-resistant bacteremia. Antimicrob Agents Chemother. 2015;59:3748–3753. https://doi.org/10.1128/AAC.00091-15.

Chiotos K., Tamma P.D., Flett K.B., et al. Increased 30-day mortality associated with carbapenem-resistant Enterobacteriaceae in children. Open Forum Infect Dis. 2018;5:ofy222

Hanretty A.M., Kaur I., Evangelista A.T., et al. Pharmacokinetics of the meropenem component of meropenem-vaborbactam for treating KPC-producing Klebsiella pneumoniae bloodstream infection in a pediatric patient. Pharmacotherapy. 2018;38:e87–e91. https://doi.org/10.1002/phar.2187.

Costa P.de O., Atta E.H., Silva A.R. Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes. J Pediatr (Rio J). 2015;91:435–441. https://doi.org/10.1016/j.jped.2014.11.009.

Cies J.J., Moore W.S. II, Enache A., et al. -lactam therapeutic drug management in the PICU. Crit Care Med. 2018;46:272–279. https://doi.org/10.1097/CCM.0000000000002817.

Nehus E.J., Mizuno T., Cox S., et al. Pharmacokinetics of meropenem in children receiving continuous renal replacement therapy: validation of clinical trial simulations. J Clin Pharmacol. 2016;56:291–297. https://doi.org/10.1002/jcph.601.

Roberts J.A., Abdul-Aziz M.H., Lipman J., International Society of Anti-Infective Pharmacology, and Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases, et al. Individualized antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14:498–509. https://doi.org/10.1016/S1473-3099(14)700 36-2.

Godbout E.J., Pakyz A.L., Markley D.D., et al. Pediatric antimicrobial stewardship:state of the art. Curr Infect Dis Rep. 2018;20:39. https://doi.org/10.1007/s11908-018-0644-7.

Weiss C.H., Persell S.D., Wunderink R.G., et al. Empiric antibiotic, mechanical ventilation, and central venous catheter duration as potential factors mediating the effect of a checklist prompting intervention on mortality: an exploratory analysis. BMC Health Serv Res. 2012;12:198. https://doi.org/10.1186/1472-696 3-12-198.

Stocker M., van Herk W., El Helou S., NeoPIns Study Group, et al. Procalcitonin-guided decision-making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns). Lancet. 2017;390:871–881. https://doi.org/10.1016/S0140-6736(17)31444-7.

Public Health England (2015). Start smart – then focus. UK: Public Health England. Available at: https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focushistory (Accessed August 18, 2019)

Chotiprasitsakul D., Han J.H., Cosgrove S.E., Antibacterial Resistance Leadership Group, et al. Comparing the outcomes of adults with enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score–matched cohort. Clin Infect Dis. 2018;66:172–177. https://doi.org/10.1093/cid/cix767.

Chong Y.P., Moon S.M., Bang K.M., et al. Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study. Antimicrob Agents Chemother. 2013;57:1150–1156. https://doi.org/10.1128/AAC.01021-12.

Choudhary G., Datta S., Narang A. Randomized controlled trial of 7-day vs. 14-day antibiotics for neonatal sepsis. J Trop Pediatr. 2006;52:427–432. https://doi.org/10.1093/tropej/fml054.

McMullan B.J., Andresen D., Blyth C.C., ANZPID-ASAP Group, et al. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis. 2016;16:e139–e152. https://doi.org/10.1016/S1473-3099(16)30024-X.

Alexander V.N., Northrup V., Bizzarro M.J. Antibiotic exposure in the newborn intensive care unit and risk of necrotizing enterocolitis. J Pediatr. 2011;159:392–397. https://doi.org/10.1016/j.jpeds.2011.02.035.

Zaoutis T.E., Prasad P.A., Localio A.R., et al. Risk factors and predictors for candidemia in pediatric intensive care unit patients: implications for prevention. Clin Infect Dis. 2010;51:e38–e45. https://doi.org/ 10.1086/655698.

Chatterjee A., Modarai M., Naylor N.R., et al. Quantifying drivers of antibiotic resistance in humans: a systematic review. Lancet Infect Dis. 2018;18:e368–e378. https://doi.org/10.1016/S1473-3099(18)30296-2.

Chuang Y.Y., Huang Y.S., Lee S.I., et al. Methicillin-resistant Staphylococcus aureus bacteremia in neonatal intensive care units: analysis of 90 episodes. Acta Paediatr. 2004;93:786–790. https://doi.org/10.1111/j.1651-2227.2004.tb03019.x.

Hemels M.A., van den Hoogen A., Verboon-Maciolek M.A., et al. Shortening the antibiotic course for the treatment of neonatal coagulase-negative staphylococcal sepsis: Fine with three days? Neonatology. 2012;101:101–105. https://doi.org/10.1159/000330600.

Lassi Z.S., Imdad A., Bhutta Z.A. Short-course versus long-course intravenous therapy with the same antibiotic for severe community-acquired pneumonia in children aged two to 59 months. Cochrane Database Syst Rev. 2017;10:CD008032

Onakpoya I.J., Walker A.S., Tan P.S., et al. Overview of systematic reviews assessing the evidence for shorter versus longer duration antibiotic treatment for bacterial infections in secondary care. PLOS ONE. 2018;13:e0194858. https://doi.org/10.1371/journal.pone.0194858.

Rohatgi S., Devan P., Faridi M.M.A., et al. Seven versus 10 days antibiotic therapy for culture-proven neonatal sepsis: A randomized controlled trial. J Paediatr Child Health. 2017;53:556–562. https://doi.org/ 10.1111/jpc.13518.

Endorf F.W., Garrison M.M., Klein M.B., et al. Characteristics, therapies, and outcomes of children with necrotizing soft-tissue infections. Pediatr Infect Dis J. 2012;31:221–223. https://doi.org/10.1097/INF.0b0 13e3182456f02.

Vasudevan C., Oddie S.J., McGuire W. Early removal versus expectant management of central venous catheters in neonates with bloodstream infection. Cochrane Database Syst Rev. 2016;4:CD008436

Smith P.B., Benjamin D.K. Jr., Cotten C.M., et al. Is an increased dwell time of a peripherally inserted catheter associated with an increased risk of bloodstream infection in infants? Infect Control Hosp Epidemiol. 2008;29:749–753. https://doi.org/10.1086/589905.

Qanday qilib iqtibos keltirish mumkin

Satvaldieva , E., Muxtorov, J., Juraeva , F., & Alimov , A. (2025). Bolalar va yangi tug‘ilgan chaqaloqlarda sepsis/septik shokning mikroblar manzarasi va antimikrob terapiyasi. Bolalar Milliy Tibbiyot Markazining Axborotnomasi, 3(2), 44–56. Retrieved from https://hnchmc.uz/index.php/jour/article/view/222
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