Morbidity and mortality rates in premature infants treated with aminoglycosides in neonatal intensive care units: A comparative study
Main Article Content
Keywords
Aminoglycosides, Length of stay, Mortality, Morbidity, Vancomycin, Meropenem, Ventilation, NICU
Abstract
Objective: Aminoglycosides are used as first-line defense antibiotics in the Neonatal Intensive Care Unit (NICU) for the treatment of sepsis, meningitis, neonatal pneumonia, and endocarditis. However, they pose negative side effects such as ototoxicity, nephrotoxicity, and the neuromuscular blockade effect resulting from acetylcholine inhibition. In contrast to other antibiotics (such as vancomycin or meropenem), delayed weaning and weaning failure from artificial ventilation may be linked to neuromuscular blocking in neonates treated with aminoglycosides. However, the used dosing regimen and therapeutic guideline of aminoglycosides may provide optimal clinical outcomes. Methods: Data were obtained for 582 NICU patients with sepsis, birth asphyxia, respiratory distress syndrome, birth defects, infections or others, and who needed artificial ventilation. Included patients were divided into four groups: A, treated with amikacin; B, treated with gentamicin; C, treated with meropenem; and D, treated with vancomycin. The weaning duration, weaning failure rate, mortality rate, and length of hospital stay were compared. Results: Gentamicin showed the most positive effects in reducing the length of hospital stay and ventilation period of neonates with improved health conditions. In addition, the mortality rate was lowest in neonates treated with gentamicin as compared to other treatments. Conclusion: Our data elucidated that aminoglycosides, particularly gentamicin, with guidance was effective in improving the neonatal mortality and morbidity through reducing length of hospital stay and ventilation period without producing neuromuscular blocking action.
References
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28. Renna G, Siro-Brigiani G, Cuomo V. Comparative evaluation of the neuromuscular blocking activity of three new aminoglycoside antibiotics in rats. Toxicology letters. 1981;9(2):107-12.
29. Potter JM, Edeson R, Campbell R, Forbes A. Potentiation by gentamicin of non-depolarizing neuromuscular block in the cat. Anaesthesia and Intensive Care. 1980;8(1):20-5.
30. Regazzi M, Berardi A, Picone S, Tzialla C. Pharmacokinetic and pharmacodynamic considerations of antibiotic use in neonates. Antibiotics. 2023;12(12):1747.
31. Simeoli R, Cairoli S, Decembrino N, Campi F, Dionisi Vici C, Corona A, et al. Use of antibiotics in preterm newborns. Antibiotics. 2022;11(9):1142.
32. Butranova OI, Ushkalova EA, Zyryanov SK, Chenkurov MS. Developmental pharmacokinetics of antibiotics used in neonatal ICU: focus on preterm infants. Biomedicines. 2023;11(3):940.
33. Vella-Brincat JW, Begg EJ, Robertshawe BJ, Lynn AM, Borrie TL, Darlow BA. Are gentamicin and/or vancomycin associated with ototoxicity in the neonate? A retrospective audit. Neonatology. 2011;100(2):186-93.
34. Iosifidis E, Evdoridou I, Agakidou E, Chochliourou E, Protonotariou E, Karakoula K, et al. Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: epidemiology, molecular analysis and risk factors. American journal of infection control. 2013;41(10):857-61.
35. Clock SA, Ferng Y-H, Tabibi S, Alba L, Patel SJ, Jia H, et al. Colonization with antimicrobial-resistant gram-negative bacilli at neonatal intensive care unit discharge. Journal of the Pediatric Infectious Diseases Society. 2017;6(3):219-26.
36. Hasvold J, Bradford L, Nelson C, Harrison C, Attar M, Stillwell T. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis. Journal of neonatal-perinatal medicine. 2013;6(2):173-7.
37. Zhao R, Yu K, Zhang J, Zhang G, Huang J, Ma L, et al. Deciphering the mobility and bacterial hosts of antibiotic resistance genes under antibiotic selection pressure by metagenomic assembly and binning approaches. Water research. 2020;186:116318.
38. Friedland I, Funk E, Khoosal M, Klugman K. Increased resistance to amikacin in a neonatal unit following intensive amikacin usage. Antimicrobial agents and chemotherapy. 1992;36(8):1596-600.
39. Rodrigues D, Baldissera GS, Mathos D, Sartori A, Zavascki AP, Rigatto MH. Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity. Brazilian Journal of Microbiology. 2021;52(4):1913-9.
40. HU W, YANG Q, WANG X, TAN B, CHEN Y, SUN H. Amikacin therapy and management of premature infants infected with carbapenem-resistant Klebsiella pneumoniae. Chinese Journal of Clinical Pharmacology and Therapeutics. 2024;29(12):1401.
41. Bor M, Ilhan O. Carbapenem-resistant Klebsiella pneumoniae outbreak in a neonatal intensive care unit: risk factors for mortality. Journal of Tropical Pediatrics. 2021;67(3):fmaa057.
42. El Desoky E, Sheikh A, Al Hammadi A. Aminoglycoside and vancomycin serum concentration monitoring and mortality due to neonatal sepsis in Saudi Arabia. Journal of clinical pharmacy and therapeutics. 2003;28(6):479-83.
43. Hughes KM, Johnson PN, Anderson MP, Sekar KC, Welliver RC, Miller JL. Comparison of amikacin pharmacokinetics in neonates following implementation of a new dosage protocol. The Journal of Pediatric Pharmacology and Therapeutics. 2017;22(1):33-40.
44. Siddiqi A, Khan D, Khan F, Razzaq A. Therapeutic drug monitoring of amikacin in preterm and term infants. Singapore medical journal. 2009;50(5):486.
45. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics. 2006;117(1):67-74.
46. Millar M, MacKay P, Levene M, Langdale V, Martin C. Enterobacteriaceae and neonatal necrotising enterocolitis. Archives of disease in childhood. 1992;67(1 Spec No):53-6.
47. Furuno JP, Perencevich EN, Johnson JA, Wright M-O, McGregor JC, Morris Jr JG, et al. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization. Emerging infectious diseases. 2005;11(10):1539.
48. Weinstein RA, Fridkin SK. Vancomycin-intermediate and-resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clinical Infectious Diseases. 2001;32(1):108-15.
49. Dua’A A, Xu S, Luig M, Kim HY, Alffenaar J-W. Dosing of vancomycin and target attainment in neonates: a systematic review. International Journal of Antimicrobial Agents. 2022;59(2):106515.
50. Kato H, Hagihara M, Okudaira M, Asai N, Koizumi Y, Yamagishi Y, et al. Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk. International Journal of Antimicrobial Agents. 2021;58(2):106393.
51. Lignieres G, Rybak A, Levy C, Birgy A, Bechet S, Bonacorsi S, et al. Meningitis caused by extended-spectrum β-lactamase–producing Escherichia coli in infants in France: a case series. JAC-Antimicrobial Resistance. 2023;5(2):dlad042.
2. Young LS, Hewitt WL. Activity of five aminoglycoside antibiotics in vitro against gram-negative bacilli and Staphylococcus aureus. Antimicrobial Agents and Chemotherapy. 1973;4(6):617-25.
3. Donowitz LG. Nesocomial infection in neonatal intensive care units. American journal of infection control. 1989;17(5):250-7.
4. Hollander EM, van Tuinen EL, Schölvinck EH, Bergman KA, Bourgonje AR, Gracchi V, et al. Evaluation of Dosing Guidelines for Gentamicin in Neonates and Children. Antibiotics. 2023;12(5):810.
5. Hartman SJ, Orriëns LB, Zwaag SM, Poel T, de Hoop M, de Wildt SN. External validation of model-based dosing guidelines for vancomycin, gentamicin, and tobramycin in critically ill neonates and children: a pragmatic two-center study. Pediatric Drugs. 2020;22:433-44.
6. Muller-Pebody B, Johnson A, Heath P, Gilbert R, Henderson K, Sharland M, et al. Empirical treatment of neonatal sepsis: are the current guidelines adequate? Archives of Disease in Childhood-Fetal and Neonatal Edition. 2011;96(1):F4-F8.
7. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatric Clinics. 2013;60(2):367-89.
8. Chen C, Chen Y, Wu P, Chen B. Update on new medicinal applications of gentamicin: evidence-based review. Journal of the Formosan Medical Association. 2014;113(2):72-82.
9. Mingeot-Leclercq M-P, Tulkens PM. Aminoglycosides: nephrotoxicity. Antimicrobial agents and chemotherapy. 1999;43(5):1003-12.
10. Tulkens PM. Nephrotoxicity of aminoglycoside antibiotics. Toxicology letters. 1989;46(1-3):107-23.
11. Le TA, Hiba T, Chaudhari D, Preston AN, Palowsky ZR, Ahmadzadeh S, et al. Aminoglycoside-related nephrotoxicity and ototoxicity in clinical practice: a review of pathophysiological mechanism and treatment options. Advances in therapy. 2023;40(4):1357-65.
12. Rosenberg CR, Fang X, Allison KR. Potentiating aminoglycoside antibiotics to reduce their toxic side effects. PLoS One. 2020;15(9):e0237948.
13. Selimoglu E. Aminoglycoside-induced ototoxicity. Current pharmaceutical design. 2007;13(1):119-26.
14. Webster CM, Shepherd M. A mini-review: environmental and metabolic factors affecting aminoglycoside efficacy. World Journal of Microbiology and Biotechnology. 2023;39(1):7.
15. Jospe-Kaufman M, Siomin L, Fridman M. The relationship between the structure and toxicity of aminoglycoside antibiotics. Bioorganic & medicinal chemistry letters. 2020;30(13):127218.
16. Kotze A, Bartel P, Sommers DK. Once versus twice daily amikacin in neonates: prospective study on toxicity. Journal of paediatrics and child health. 1999;35(3):283-6.
17. Lundergan FS, Glasscock B, F G, Kim EH, Cohen RS. Once-daily gentamicin dosing in newborn infants. Pediatrics. 1999;103(6):1228-34.
18. Bhargava V, Malloy M, Fonseca R. The association between vancomycin trough concentrations and acute kidney injury in the neonatal intensive care unit. BMC pediatrics. 2017;17:1-6.
19. Parini R, Rusconi F, Cavanna G, Vigliani E, Cornacchia L, Assael B. Evaluation of the renal and auditory function of neonates treated with amikacin. Developmental pharmacology and therapeutics. 1982;5(1-2):33-46.
20. Endo A, Nemoto A, Hanawa K, Maebayashi Y, Hasebe Y, Kobayashi M, et al. Relationship between amikacin blood concentration and ototoxicity in low birth weight infants. Journal of Infection and Chemotherapy. 2019;25(1):17-21.
21. Jansen D, Heemskerk S, Koster-Kamphuis L, Bouw T, Van Heijst A, Pickkers P. Urine biomarkers for gentamicin-induced acute kidney injury in the nicu. Pediatric Research. 2011;70(5):764-.
22. Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp J-H, Schelonka RL, Randolph DA, et al. Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections. Clinical infectious diseases. 2012;55(11):1495-502.
23. Sahni M, Richardson CJ, Jain SK. Sustained neuromuscular blockade after vecuronium use in a premature infant. American Journal of Perinatology Reports. 2015;5(02):e121-e3.
24. Sizar O, Rahman S, Sundareshan V. Amikacin. StatPearls [Internet]: StatPearls Publishing; 2023.
25. Korang SK, Safi S, Nava C, Gordon A, Gupta M, Greisen G, et al. Antibiotic regimens for early‐onset neonatal sepsis. Cochrane Database of Systematic Reviews. 2021 (5).
26. Korang SK, Safi S, Nava C, Greisen G, Gupta M, Lausten-Thomsen U, et al. Antibiotic regimens for late‐onset neonatal sepsis. Cochrane Database of Systematic Reviews. 2021 (5).
27. JAYESH VARIA RP, VANDANA M DESAI, VASAV D DESAI. Adverse Drug Reaction following Injection of Amikacin Sulphate in a Cluster of Preterm Newborns. Indian Journal of Neonatal Medicine and Research. 2017;5(4):NS01-NS3.
28. Renna G, Siro-Brigiani G, Cuomo V. Comparative evaluation of the neuromuscular blocking activity of three new aminoglycoside antibiotics in rats. Toxicology letters. 1981;9(2):107-12.
29. Potter JM, Edeson R, Campbell R, Forbes A. Potentiation by gentamicin of non-depolarizing neuromuscular block in the cat. Anaesthesia and Intensive Care. 1980;8(1):20-5.
30. Regazzi M, Berardi A, Picone S, Tzialla C. Pharmacokinetic and pharmacodynamic considerations of antibiotic use in neonates. Antibiotics. 2023;12(12):1747.
31. Simeoli R, Cairoli S, Decembrino N, Campi F, Dionisi Vici C, Corona A, et al. Use of antibiotics in preterm newborns. Antibiotics. 2022;11(9):1142.
32. Butranova OI, Ushkalova EA, Zyryanov SK, Chenkurov MS. Developmental pharmacokinetics of antibiotics used in neonatal ICU: focus on preterm infants. Biomedicines. 2023;11(3):940.
33. Vella-Brincat JW, Begg EJ, Robertshawe BJ, Lynn AM, Borrie TL, Darlow BA. Are gentamicin and/or vancomycin associated with ototoxicity in the neonate? A retrospective audit. Neonatology. 2011;100(2):186-93.
34. Iosifidis E, Evdoridou I, Agakidou E, Chochliourou E, Protonotariou E, Karakoula K, et al. Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: epidemiology, molecular analysis and risk factors. American journal of infection control. 2013;41(10):857-61.
35. Clock SA, Ferng Y-H, Tabibi S, Alba L, Patel SJ, Jia H, et al. Colonization with antimicrobial-resistant gram-negative bacilli at neonatal intensive care unit discharge. Journal of the Pediatric Infectious Diseases Society. 2017;6(3):219-26.
36. Hasvold J, Bradford L, Nelson C, Harrison C, Attar M, Stillwell T. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis. Journal of neonatal-perinatal medicine. 2013;6(2):173-7.
37. Zhao R, Yu K, Zhang J, Zhang G, Huang J, Ma L, et al. Deciphering the mobility and bacterial hosts of antibiotic resistance genes under antibiotic selection pressure by metagenomic assembly and binning approaches. Water research. 2020;186:116318.
38. Friedland I, Funk E, Khoosal M, Klugman K. Increased resistance to amikacin in a neonatal unit following intensive amikacin usage. Antimicrobial agents and chemotherapy. 1992;36(8):1596-600.
39. Rodrigues D, Baldissera GS, Mathos D, Sartori A, Zavascki AP, Rigatto MH. Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity. Brazilian Journal of Microbiology. 2021;52(4):1913-9.
40. HU W, YANG Q, WANG X, TAN B, CHEN Y, SUN H. Amikacin therapy and management of premature infants infected with carbapenem-resistant Klebsiella pneumoniae. Chinese Journal of Clinical Pharmacology and Therapeutics. 2024;29(12):1401.
41. Bor M, Ilhan O. Carbapenem-resistant Klebsiella pneumoniae outbreak in a neonatal intensive care unit: risk factors for mortality. Journal of Tropical Pediatrics. 2021;67(3):fmaa057.
42. El Desoky E, Sheikh A, Al Hammadi A. Aminoglycoside and vancomycin serum concentration monitoring and mortality due to neonatal sepsis in Saudi Arabia. Journal of clinical pharmacy and therapeutics. 2003;28(6):479-83.
43. Hughes KM, Johnson PN, Anderson MP, Sekar KC, Welliver RC, Miller JL. Comparison of amikacin pharmacokinetics in neonates following implementation of a new dosage protocol. The Journal of Pediatric Pharmacology and Therapeutics. 2017;22(1):33-40.
44. Siddiqi A, Khan D, Khan F, Razzaq A. Therapeutic drug monitoring of amikacin in preterm and term infants. Singapore medical journal. 2009;50(5):486.
45. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics. 2006;117(1):67-74.
46. Millar M, MacKay P, Levene M, Langdale V, Martin C. Enterobacteriaceae and neonatal necrotising enterocolitis. Archives of disease in childhood. 1992;67(1 Spec No):53-6.
47. Furuno JP, Perencevich EN, Johnson JA, Wright M-O, McGregor JC, Morris Jr JG, et al. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization. Emerging infectious diseases. 2005;11(10):1539.
48. Weinstein RA, Fridkin SK. Vancomycin-intermediate and-resistant Staphylococcus aureus: what the infectious disease specialist needs to know. Clinical Infectious Diseases. 2001;32(1):108-15.
49. Dua’A A, Xu S, Luig M, Kim HY, Alffenaar J-W. Dosing of vancomycin and target attainment in neonates: a systematic review. International Journal of Antimicrobial Agents. 2022;59(2):106515.
50. Kato H, Hagihara M, Okudaira M, Asai N, Koizumi Y, Yamagishi Y, et al. Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk. International Journal of Antimicrobial Agents. 2021;58(2):106393.
51. Lignieres G, Rybak A, Levy C, Birgy A, Bechet S, Bonacorsi S, et al. Meningitis caused by extended-spectrum β-lactamase–producing Escherichia coli in infants in France: a case series. JAC-Antimicrobial Resistance. 2023;5(2):dlad042.
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Jan 9, 2026
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Morbidity and mortality rates in premature infants treated with aminoglycosides in neonatal intensive care units: A comparative study. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 25];23(4):1-12. Available from: https://www.pharmacypractice.org/index.php/pp/article/view/3342
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How to Cite
1.
Morbidity and mortality rates in premature infants treated with aminoglycosides in neonatal intensive care units: A comparative study. Pharm Pract (Granada) [Internet]. 2026 Jan. 9 [cited 2026 Jan. 25];23(4):1-12. Available from: https://www.pharmacypractice.org/index.php/pp/article/view/3342