Prevalence of Gram-negative Bacteria and Their Antibiotic Resistance in Neonatal Sepsis in Iran: a Systematic Review and Meta-analysis

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2023 Aug 15

PMID 37582726

Authors

Nazila Moftian

Peyman Rezaei-Hachesu

Morteza Arab-Zozani

Taha Samad-Soltani

Atefeh Esfandiari

Mohammad Saleh Tabib

Kayvan Mirnia

Affiliations

Soon will be listed here.

Abstract

Background: Neonatal sepsis, particularly gram-negative (GN) bacteria-induced, is a significant cause of morbidity and mortality in newborns. Healthcare professionals find this issue challenging because of antibiotic resistance. This study aims to combine findings to identify the prevalence of GN bacteria and their antibiotic resistance in Iranian neonates with sepsis.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed through international databases, including (PubMed/MEDLINE, EMBASE, Scopus, and Web of Science), Iranian local databases (Magiran, Iranmedex, Irandoc, Scimed, and SID), and the first 100 records of Google Scholar. Analytical cross-sectional study checklist from the Joanna Briggs Institute (JBI) was used for the quality assessment of included studies. Comprehensive Meta-Analysis Software Version 2 was used to conduct the meta-analysis. The between-study heterogeneity was investigated by I statistics.

Results: The prevalence of GN bacteria was estimated to be 53.6% [95% CI: 45.9- 61.1: P = 0.362] in Iranian neonates with sepsis, based on 31 studies with a sample size of 104,566. klebsiella pneumoniae (K.pneumonia) (23.2% [95% CI: 17.5-30.0, P < 0.001]) followed by Escherichia coli (E.coli) (13.5% [95% CI: 9.4-18.9, P < 0.001]) were more prevalent among GN bacteria. The highest resistance in K.pneumoniae was observed in Cefixime (80.6%, [95% CI: 56.3-93.1, P = 0.018]). E.coli showed greater resistance to Ampicillin (61.8%, [95% CI: 44.2-76.5, P = 0.188]. The prevalence of GN bacteria in Iranian neonates with sepsis has a decreasing trend based on the year, as shown by a meta-regression model (P < 0.0004).

Conclusion: GN pathogens, particularly K.pneumoniae, and E.coli, are the leading cause of neonatal sepsis in Iran. GN bacteria showed the highest resistance to Third-generation cephalosporin and Aminoglycosides.

Citing Articles

Virulence genes, efflux pumps, and molecular typing of Klebsiella pneumoniae isolates from North Iran.

Birgani A, Goli H, Siadat S, Fateh A, Nikbin V, Sakhaee F AMB Express. 2025; 15(1):36.

PMID: 40045145 PMC: 11883068. DOI: 10.1186/s13568-025-01845-1.

16 S rRNA-based molecular identification of coagulase-negative Staphylococcus species in neonates with sepsis and their antibiotic resistance patterns in Ahvaz, Iran.

Malakian A, Dehghan S, Abbasi Montazeri E, Aramesh M, Dehdashtian M, Aletayeb S BMC Microbiol. 2025; 25(1):114.

PMID: 40033203 PMC: 11874690. DOI: 10.1186/s12866-025-03809-8.

A mixed-method study on antimicrobial resistance infection drivers in neonatal intensive care units: pathways, risks, and solutions.

Yeshiwas A, Bayeh G, Tsega T, Tsega S, Gebeyehu A, Asmare Z Antimicrob Resist Infect Control. 2025; 14(1):15.

PMID: 39985102 PMC: 11846396. DOI: 10.1186/s13756-025-01520-x.

Prevalence and pathogen profiles of bacteremia in neonates hospitalized for clinical Sepsis in Ethiopia: a systematic review and meta-analysis.

Geleta D, Abebe G, Tilahun T, Ahmed H, Workneh N, Beyene G BMC Infect Dis. 2024; 24(1):1424.

PMID: 39695487 PMC: 11654219. DOI: 10.1186/s12879-024-10312-4.

Clinical features and risk factors of Klebsiella pneumoniae infection in premature infants: a retrospective cohort study.

Wei X, Liang J, Zhang H, Yan C, Lu X, Chen Y BMC Infect Dis. 2024; 24(1):1311.

PMID: 39550549 PMC: 11569604. DOI: 10.1186/s12879-024-10201-w.

References

Amuka J, Asogwa F, Ugwuanyi R, Onyechi T . Neonatal deaths and challenges of public health: Where do We need urgent intervention in developing countries?. Health Care Women Int. 2019; 41(2):227-237. DOI: 10.1080/07399332.2019.1691213. View

Randolph A, McCulloh R . Pediatric sepsis: important considerations for diagnosing and managing severe infections in infants, children, and adolescents. Virulence. 2013; 5(1):179-89. PMC: 3916372. DOI: 10.4161/viru.27045. View

Tsai M, Wu I, Lee C, Chu S, Lien R, Huang H . Neonatal gram-negative bacillary late-onset sepsis: A case-control-control study on a prospectively collected database of 5,233 admissions. Am J Infect Control. 2015; 44(2):146-53. DOI: 10.1016/j.ajic.2015.09.009. View

Wen S, Ezure Y, Rolley L, Spurling G, Lau C, Riaz S . Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis. PLoS Med. 2021; 18(9):e1003787. PMC: 8478175. DOI: 10.1371/journal.pmed.1003787. View

Schlapbach L, Straney L, Alexander J, MacLaren G, Festa M, Schibler A . Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study. Lancet Infect Dis. 2014; 15(1):46-54. DOI: 10.1016/S1473-3099(14)71003-5. View

Laxminarayan R, Matsoso P, Pant S, Brower C, Rottingen J, Klugman K . Access to effective antimicrobials: a worldwide challenge. Lancet. 2015; 387(10014):168-75. DOI: 10.1016/S0140-6736(15)00474-2. View

Akbarian-Rad Z, Riahi S, Abdollahi A, Sabbagh P, Ebrahimpour S, Javanian M . Neonatal sepsis in Iran: A systematic review and meta-analysis on national prevalence and causative pathogens. PLoS One. 2020; 15(1):e0227570. PMC: 6980642. DOI: 10.1371/journal.pone.0227570. View

Moftian N, Samad Soltani T, Mirnia K, Esfandiari A, Tabib M, Rezaei Hachesu P . Clinical Risk Factors for Early-Onset Sepsis in Neonates: An International Delphi Study. Iran J Med Sci. 2023; 48(1):57-69. PMC: 9843461. DOI: 10.30476/IJMS.2022.92284.2352. View

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

10.

Porritt K, Gomersall J, Lockwood C . JBI's Systematic Reviews: Study selection and critical appraisal. Am J Nurs. 2014; 114(6):47-52. DOI: 10.1097/01.NAJ.0000450430.97383.64. View

11.

Karambin M, Zarkesh M . Entrobacter, the most common pathogen of neonatal septicemia in rasht, iran. Iran J Pediatr. 2012; 21(1):83-7. PMC: 3446115. View

12.

Mahallei M, Rezaee M, Mehramuz B, Beheshtirooy S, Abdinia B . Clinical symptoms, laboratory, and microbial patterns of suspected neonatal sepsis cases in a children's referral hospital in northwestern Iran. Medicine (Baltimore). 2018; 97(25):e10630. PMC: 6024470. DOI: 10.1097/MD.0000000000010630. View

13.

Marzban A, Samaee H, Mosavinasab N . Changing trend of empirical antibiotic regimen: experience of two studies at different periods in a neonatal intensive care unit in Tehran, Iran. Acta Med Iran. 2011; 48(5):312-5. View

14.

Rajabi Z, Mehdi Soltan Dallal M . Study on Bacterial Strains Causing Blood and Urinary Tract Infections in the Neonatal Intensive Care Unit and Determination of Their Antibiotic Resistance Pattern. Jundishapur J Microbiol. 2015; 8(8):e19654. PMC: 4601293. DOI: 10.5812/jjm.19654v2. View

15.

Almohammady M, Eltahlawy E, Reda N . Pattern of bacterial profile and antibiotic susceptibility among neonatal sepsis cases at Cairo University Children Hospital. J Taibah Univ Med Sci. 2020; 15(1):39-47. PMC: 7033391. DOI: 10.1016/j.jtumed.2019.12.005. View

16.

Peterside O, Pondei K, Akinbami F . Bacteriological Profile and Antibiotic Susceptibility Pattern of Neonatal Sepsis at a Teaching Hospital in Bayelsa State, Nigeria. Trop Med Health. 2015; 43(3):183-90. PMC: 4593775. DOI: 10.2149/tmh.2015-03. View

17.

Rabie Shehab El-Din E, El-Sokkary M, Bassiouny M, Hassan R . Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt. Biomed Res Int. 2015; 2015:509484. PMC: 4471255. DOI: 10.1155/2015/509484. View

18.

Zelellw D, Dessie G, Mengesha E, Shiferaw M, Mela Merhaba M, Emishaw S . A Systemic Review and Meta-analysis of the Leading Pathogens Causing Neonatal Sepsis in Developing Countries. Biomed Res Int. 2021; 2021:6626983. PMC: 8203353. DOI: 10.1155/2021/6626983. View

19.

Azami M, Jaafari Z, Masoumi M, Shohani M, Badfar G, Mahmudi L . The etiology and prevalence of urinary tract infection and asymptomatic bacteriuria in pregnant women in Iran: a systematic review and Meta-analysis. BMC Urol. 2019; 19(1):43. PMC: 6543660. DOI: 10.1186/s12894-019-0454-8. View

20.

You T, Zhang H, Guo L, Ling K, Hu X, Li L . Differences in clinical characteristics of early- and late-onset neonatal sepsis caused by pneumoniae. Int J Immunopathol Pharmacol. 2020; 34:2058738420950586. PMC: 7444108. DOI: 10.1177/2058738420950586. View