Multidrug-resistant Gram-negative bacteria rate and risk factors in the neonatal intensive care unit: A single-center ten-year experience

Abstract

Objective: Multidrug resistance (MDR) in gram-negative neonatal infections is difficult to manage, and the risk factors differ among different studies. We aim to investigate the demographics, mortality, MDR status of gram-negative isolates, and risk factors for MDR gram-negative infections. Material-Methods: We conducted a retrospective single-center study about MDR gram-negative infections in neonates between January 2012-January 2022 at Duzce University Hospital in Turkey. This study evaluates neonates with MDR gram-negative infections' risk factors and clinical features. All analyses were performed using IBM SPSS V23. Univariate analyses and multivariate logistic regression models were studied to determine MDR's risk factors. Results: Of 107 gram-negative bacteria, 41 (38.3%) accounted for Enterobacter, 30 (28%) for Klebsiella pneumonia, and 22 (20.6%) for Escherichia coli. Additionally, 61 (56.5%) were MDR microorganisms. Among the susceptibility tests performed for selected isolates, 41 (77.4%) had resistance to Piperacillin, 57 (75%) showed resistance to amoxiclav, and 16 (72.7%) had cefoxitin resistance. In addition, carbapenemase resistance was found in 24 (43.6%) and meropenem resistance in 13 (36.1%). Colistin, aztreonam, and tigecycline resistances were the least frequent. The following dependent risk factors increased the multidrug resistance risk in gram-negative infections; late-onset sepsis 3.547 fold (p=0.005), use of mechanical ventilation 3.143 fold (p=0.007), blood culture positivity 3.587-fold (p=0.013), bronchopulmonary dysplasia 6.702 fold, (p= 0.015) and total parenteral nutrition 5.591 fold (p=0.001), lower gestational age 1.122 (1/0.891) fold (p=0.026), and birth weight 1.001 (1/0.999) fold, (p=0.013). Similarly, anti-biotherapy duration was significantly higher in the MDR group than in the non-MDR group. Conclusions: The reported risk factors for MDR in gram-negative neonatal infections are all dependent risk factors. Hence clinicians must be alert to all potential risk factors.

Keywords

• gram negative bacterial infections
• neonates
• multidrug resistance

Yenidoğan yoğun bakım ünitesinde çok ilaca dirençli Gram-negatif bakteri oranı ve risk faktörleri: Tek merkezli on yıllık deneyim

Abstract

Amaç: Gram-negatif yenidoğan enfeksiyonlarında çoklu ilaç direncinin (ÇİD) yönetimi zordur ve risk faktörleri farklı çalışmalar arasında farklılık göstermektedir. Bu çalışmanın amacı, gram-negatif izolatların demografik özelliklerini, mortalitesini, ÇİD durumunu ve ÇİD gram-negatif enfeksiyonlar için risk faktörlerini araştırmaktır. Metod: Düzce Üniversitesi Hastanesi'nde Ocak 2012-Ocak 2022 tarihleri arasında yenidoğanlarda ÇİD gram-negatif enfeksiyonlarla ilgili retrospektif tek merkezli bir çalışma yapıldı. Bu çalışmada ÇİD gram-negatif enfeksiyonu olan yenidoğanların risk faktörleri ve klinik özellikleri değerlendirildi. Tüm analizler IBM SPSS V23 kullanılarak gerçekleştirildi. Ayrıca, ÇİD risk faktörlerini belirlemek için tek değişkenli analizler ve çok değişkenli lojistik regresyon modelleri incelenmiştir. Bulgular: Yüzyedi gram-negatif bakterinin 41'ini (%38,3) Enterobacter, 30'unu (%28) Klebsiella pneumonia ve 22'sini (%20,6) Escherichia coli oluşturmuştur. Ayrıca, 61'i (%56,5) ÇİD mikroorganizmalardır. Seçilen izolatlar için yapılan duyarlılık testleri sonucunda 41'inde (%77,4) piperasilin, 57'sinde (%75) amoksiklav ve 16'sında (%72,7) sefoksitin direnci tespit edilmiştir. Ayrıca, 24'ünde (%43,6) karbapenemaz direnci ve 13'ünde (%36,1) meropenem direnci tespit edilmiştir. Kolistin, aztreonam ve tigesiklin dirençleri en az görülen dirençlerdi. Aşağıdaki bağımlı risk faktörleri gram-negatif enfeksiyonlarda çoklu ilaç direnci riskini arttırmıştır; geç başlangıçlı sepsis 3. 547 kat (p=0. 005), mekanik ventilasyon kullanımı 3. 143 kat (p=0. 007), kan kültürü pozitifliği 3. 587 kat (p=0. 013), bronkopulmoner displazi 6. 702 kat, (p=0. 015) ve total parenteral beslenme 5. 591 kat (p=0. 001), düşük gebelik yaşı 1. 122 (1/0. 891) kat (p=0. 026) ve doğum ağırlığı 1. 001 (1/0. 999) kat, (p=0. 013). Benzer şekilde, antibiyoterapi süresi ÇİD grubunda ÇİD olmayan gruba göre anlamlı derecede daha yüksekti. Sonuçlar: Gram-negatif yenidoğan enfeksiyonlarında ÇİD için bildirilen risk faktörlerinin tümü bağımlı risk faktörleridir. Bu nedenle klinisyenler tüm potansiyel risk faktörleri çoklu ilaç direncini öngörmekte önem taşımaktadır.

Keywords

• gram negatif bakteriyel enfeksiyonlar
• yenidoğanlar
• çoklu ilaç direnci

References

1. 1. Wattal C, Kler N, Oberoi JK, Fursule A, Kumar A, Thakur A. Neonatal Sepsis: Mortality and Morbidity in Neonatal Sepsis due to Multidrug-Resistant (MDR) Organisms: Part 1. Indian J Pediatr. 2020.
2. 2. Flannery DD, Chiotos K, Gerber JS, Puopolo KM. Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr Res. 2022;91(2):380-91.
3. 3. Thatrimontrichai A, Premprat N, Janjindamai W, Dissaneevate S, Maneenil G. Multidrug-resistant Gram-negative bacilli sepsis from a neonatal intensive care unit: a case-case-control study. J Infect Dev Ctries. 2019;13(7):603-11.
4. 4. Zou H, Jia X, He X, Su Y, Zhou L, Shen Y,et al. Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis. Front Cell Infect Microbiol. 2021;11:694093.
5. 5. Li JY, Chen SQ, Yan YY, Hu YY, Wei J, Wu QP,et al. Identification and antimicrobial resistance of pathogens in neonatal septicemia in China-A meta-analysis. Int J Infect Dis. 2018;71:89-93.
6. 6. Oliveira PMN, Buonora SN, Souza CLP, Simões Júnior R, Silva TCD, Bom GJT,et al . Surveillance of multidrug-resistant bacteria in pediatric and neonatal intensive care units in Rio de Janeiro State, Brazil. Rev Soc Bras Med Trop. 2019;52:e20190205.
7. 7. Aizawa Y, Shoji T, Ito K, Kasai M, Sakurai H, Toyofuku E,et al. Multidrug-resistant Gram-negative Bacterial Bloodstream Infections in Children's Hospitals in Japan, 2010-2017. Pediatr Infect Dis J. 2019;38(7):653-9.
8. 8. Liu J, Fang Z, Yu Y, Ding Y, Liu Z, Zhang C, et al. Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019. Antimicrob Resist Infect Control. 2021;10(1):121.

9. 9. Zou H, Jia X, He X, Su Y, Zhou L, Shen Y, et al. Emerging Threat of Multidrug-Resistant Pathogens From Neonatal Sepsis. Front Cell Infect Microbiol. 2021;11:694093.
10. 10. Berberian G, Brizuela M, Rosanova MT, Travaglianti M, Mastroiani A,et al. Multidrug-resistant Gram-negative infections in neonatology. Arch Argent Pediatr. 2019;117(1):6-11. English, Spanish.
11. 11. Pokhrel B, Koirala T, Shah G, Joshi S, Baral P. Bacteriological profile and antibiotic susceptibility of neonatal sepsis in neonatal intensive care unit of a tertiary hospital in Nepal. BMC Pediatr. 2018;18(1):208.
12. 12. Solomon S, Akeju O, Odumade OA, Ambachew R, Gebreyohannes Z, Van Wickle K, et al. Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis. PLoS One. 2021;16(8):e0255410.
13. 13. Chiusaroli L, Liberati C, Caseti M, Rulli L, Barbieri E, Giaquinto C, et al. Therapeutic Options and Outcomes for the Treatment of Neonates and Preterms with Gram-Negative Multidrug-Resistant Bacteria: A Systematic Review. Antibiotics (Basel). 2022;11(8):1088.
14. 14. Osei Sekyere J, Reta MA, Bernard Fourie P. Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses. Ann N Y Acad Sci. 2021;1502(1):54-71.
15. 15. Asensio A, Oliver A, González-Diego P, Baquero F, Pérez-Díaz JC, Ros P, et al. Outbreak of a multiresistant Klebsiella pneumoniae strain in an intensive care unit: antibiotic use as risk factor for colonization and infection. Clin Infect Dis. 2000;30(1):55-60.
16. 16. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-81.
17. 17. van Loon K, Voor In 't Holt AF, Vos MC. A Systematic Review and Meta-analyses of the Clinical Epidemiology of Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;62(1):e01730-17.
18. 18. Predic M, Delano JP, Tremblay E, Iovine N, Brown S, Prins C. Evaluation of patient risk factors for infection with carbapenem-resistant Enterobacteriaceae. Am J Infect Control. 2020;48(9):1028-31.
19. 19. Barber KE, Wagner JL, Larry RC, Stover KR. Frequency of and risk factors for carbapenem-resistant Enterobacteriaceae. J Med Microbiol. 2021;70(2):001286.
20. 20. Zhang AR, Wang Q, Zhou CE, Zhang JG, Wang XJ, Zhao JK, et al. [Risk factors and clinical prognosis analysis of carbapenem-resistant Enterobacterales bacteria nosocomial infection]. Zhonghua Yi Xue Za Zhi. 2021;101(21):1572-82.