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2000
Volume 24, Issue 11
  • ISSN: 1566-5240
  • E-ISSN:

Abstract

Introduction

Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides.

Objective

In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs).

Methods

We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords “aminoglycosides”, “pharmacokinetics”, “ODD”, “MDD”, “once daily”, “multiple daily”, “dosing regimen”, “nephrotoxicity”, “ototoxicity”, “efficacy”, “safety”, and “toxicity”. As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD MDD of aminoglycosides. A total number of 20 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years. Results: The most common clinical condition in the included studies was cystic fibrosis.

Conclusion

In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.

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References

  1. ElshahawiSI ShaabanKA KharelMK ThorsonJSJCSR A comprehensive review of glycosylated bacterial natural products.Chem Soc Rev201544(21)759169710.1039/C4CS00426D
    [Google Scholar]
  2. DezanetC. KempfJ. Mingeot-LeclercqM.P. DécoutJ.L. Amphiphilic aminoglycosides as medicinal agents.Int. J. Mol. Sci.20202119741110.3390/ijms21197411 33049963
    [Google Scholar]
  3. BryskierA. Antibiotics and antibacterial agents: classifications and structure-activity relationship Antimicrobial Agents. American Society of MicrobiologyHoboken, New JerseyWiley Online20051338
    [Google Scholar]
  4. SerioA.W. MagalhãesM.L. BlanchardJ.S. ConnollyL.E. Aminoglycosides: Mechanisms of Action and Resistance Antimicrobial Drug Resistance.Antimicrob. Agents Chemother.200044123249325610.1007/978‑3‑319‑46718‑4_14
    [Google Scholar]
  5. BowersD.R. SchillingA.N. TamV.H. Aminoglycoside Pharmacodynamics. Antibiotic Pharmacodynamics.AmsterdamSpringer2016199220
    [Google Scholar]
  6. LeeS. HinzA. BauerleE. Targeting a bacterial stress response to enhance antibiotic action.Proc. Natl. Acad. Sci.200910634145701457510.1073/pnas.0903619106 19706543
    [Google Scholar]
  7. SandovalR.M. MolitorisB.A. Gentamicin traffics retrograde through the secretory pathway and is released in the cytosol via the endoplasmic reticulum.Am. J. Physiol. Renal Physiol.20042864F617F62410.1152/ajprenal.00130.2003 14625200
    [Google Scholar]
  8. AventM.L. RogersB.A. ChengA.C. PatersonD.L. Current use of aminoglycosides: Indications, pharmacokinetics and monitoring for toxicity.Intern. Med. J.201141644144910.1111/j.1445‑5994.2011.02452.x 21309997
    [Google Scholar]
  9. WarcholM.E. Cellular mechanisms of aminoglycoside ototoxicity.Curr. Opin. Otolaryngol. Head Neck Surg.201018545445810.1097/MOO.0b013e32833e05ec 20717031
    [Google Scholar]
  10. KarasawaT. SteygerP.S. Intracellular mechanisms of aminoglycoside-induced cytotoxicity.Integr. Biol.20113987988610.1039/c1ib00034a 21799993
    [Google Scholar]
  11. JanaS. Molecular understanding of aminoglycoside action and resistance.Appl. Microbiol. Biotechnol.2006702140150
    [Google Scholar]
  12. FossoM.Y. LiY. Garneau-TsodikovaS. New trends in the use of aminoglycosides.MedChemComm2014581075109110.1039/C4MD00163J 25071928
    [Google Scholar]
  13. Durante-MangoniE. GrammatikosA. UtiliR. FalagasM.E. Do we still need the aminoglycosides?Int. J. Antimicrob. Agents200933320120510.1016/j.ijantimicag.2008.09.001 18976888
    [Google Scholar]
  14. PrayleA. WatsonA. FortnumH. SmythA. Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis.Thorax201065765465810.1136/thx.2009.131532 20627927
    [Google Scholar]
  15. McDermottJ.H. MahaveerA. JamesR.A. Rapid point-of-care genotyping to avoid aminoglycoside-induced ototoxicity in neonatal intensive care.JAMA Pediatr.2022176548649210.1001/jamapediatrics.2022.0187 35311942
    [Google Scholar]
  16. LeT.A. HibaT. ChaudhariD. Aminoglycoside-related nephrotoxicity and ototoxicity in clinical practice: A review of pathophysiological mechanism and treatment options.Adv. Ther.20234041357136510.1007/s12325‑023‑02436‑x 36738370
    [Google Scholar]
  17. LeisJ.A. RutkaJ.A. GoldW.L. Aminoglycoside-induced ototoxicity.Curr. Pharm. Des.201513111912610.1503/cmaj.140339
    [Google Scholar]
  18. HuthM. RicciA. ChengA. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection.Int. J. Otolaryngol.2011201193786110.1155/2011/937861
    [Google Scholar]
  19. FuX. WanP. LiP. Mechanism and prevention of ototoxicity induced by aminoglycosides.Front. Cell. Neurosci.20211569276210.3389/fncel.2021.692762 34211374
    [Google Scholar]
  20. RicciAJ GreenhouseRJ ChengAG Aminoglycoside antibiotics with reduced ototoxicity.US2014274932A12016
  21. XieJ. TalaskaA.E. SchachtJ. New developments in aminoglycoside therapy and ototoxicity.Hear. Res.20112811-2283710.1016/j.heares.2011.05.008 21640178
    [Google Scholar]
  22. DillardL.K. MartinezR.X. PerezL.L. FullertonA.M. ChadhaS. McMahonC.M. Prevalence of aminoglycoside-induced hearing loss in drug-resistant tuberculosis patients: A systematic review.J. Infect.2021831273610.1016/j.jinf.2021.05.010 34015383
    [Google Scholar]
  23. KalmansonO.A. McLoughlinK.C. KiserT.H. GubbelsS.P. Debilitating gentamicin ototoxicity: Case report and recommendations against routine use in surgical prophylaxis.Ann. Otol. Rhinol. Laryngol.202234894231176333
    [Google Scholar]
  24. MantefardoB. SisayG. Case Report: Kanamycin ototoxicity and MDR-TB treatment regimen.Int. Med. Case Rep. J.20211481581710.2147/IMCRJ.S336259 34858067
    [Google Scholar]
  25. VinksA.A. DerendorfH. MoutonJ.W. Fundamentals of antimicrobial pharmacokinetics and pharmacodynamics.New YorkSpringer201410.1007/978‑0‑387‑75613‑4
    [Google Scholar]
  26. FligorB.J. Ed. Early Diagnosis and Management of Hearing Loss in Medically Fragile Children Seminars in Hearing.Leipzig, GermanyThieme Medical Publishers2013
    [Google Scholar]
  27. WargoK.A. EdwardsJ.D. Aminoglycoside-induced nephrotoxicity.J. Pharm. Pract.201427657357710.1177/0897190014546836 25199523
    [Google Scholar]
  28. NolinT.D. HimmelfarbJ. Mechanisms of drug-induced nephrotoxicity Adverse drug reactions.Springer2010111130
    [Google Scholar]
  29. Lopez-NovoaJ.M. QuirosY. VicenteL. MoralesA.I. Lopez-HernandezF.J. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view.Kidney Int.2011791334510.1038/ki.2010.337 20861826
    [Google Scholar]
  30. NaughtonC.A. Drug-induced nephrotoxicity.Am. Fam. Physician2008786743750 18819242
    [Google Scholar]
  31. DrusanoG.L. LouieA. Optimization of aminoglycoside therapy.Antimicrob. Agents Chemother.20115562528253110.1128/AAC.01314‑10 21402835
    [Google Scholar]
  32. OliveiraJ.F.P. SilvaC.A. BarbieriC.D. OliveiraG.M. ZanettaD.M.T. BurdmannE.A. Prevalence and risk factors for aminoglycoside nephrotoxicity in intensive care units.Antimicrob. Agents Chemother.20095372887289110.1128/AAC.01430‑08 19364846
    [Google Scholar]
  33. InkerL.A. SchmidC.H. TighiouartH. Estimating glomerular filtration rate from serum creatinine and cystatin C.N. Engl. J. Med.20123671202910.1056/NEJMoa1114248 22762315
    [Google Scholar]
  34. HatalaR. DinhT.T. CookD.J. Single daily dosing of aminoglycosides in immunocompromised adults: A systematic review.Clin. Infect. Dis.199724581081510.1093/clinids/24.5.810 9142773
    [Google Scholar]
  35. NicolauD.P. FreemanC.D. BelliveauP.P. NightingaleC.H. RossJ.W. QuintilianiR. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients.Antimicrob. Agents Chemother.199539365065510.1128/AAC.39.3.650 7793867
    [Google Scholar]
  36. ThomasJ. HardenA. Methods for the thematic synthesis of qualitative research in systematic reviews.BMC Med. Res. Methodol.2008814510.1186/1471‑2288‑8‑45 18616818
    [Google Scholar]
  37. TiwariS. RehanH.S. ChandraJ. MathurN.N. SinghV. Efficacy and safety of a single daily dose of gentamicin in hospitalized Indian children: A quasi-randomized trial.J. Antimicrob. Chemother.20096451096110110.1093/jac/dkp330 19759043
    [Google Scholar]
  38. PérezV. SaénzD. MadrizJ. A double-blind study of the efficacy and safety of multiple daily doses of amikacin versus one daily dose for children with perforated appendicitis in Costa Rica.Int. J. Infect. Dis.2011158e569e57510.1016/j.ijid.2011.04.012 21733727
    [Google Scholar]
  39. Abdel-HadyE. El HamamsyM. HedayaM. AwadH. The efficacy and toxicity of two dosing-regimens of amikacin in neonates with sepsis.J. Clin. Pharm. Ther.2011361455210.1111/j.1365‑2710.2009.01152.x 21198719
    [Google Scholar]
  40. BuchholtzK. LarsenC.T. SchaadtB. HassagerC. BruunN.E. Once versus twice daily gentamicin dosing for infective endocarditis: a randomized clinical trial.Cardiology20111192657110.1159/000329842 21846985
    [Google Scholar]
  41. Solorzano-SantosF. Miranda-NovalesM. Diaz-PenaR. Bernaldez-RíosR. Díaz-BensussenS. Rivera-MárquezH. Amikacin in single daily doses in children with fever.Clin. Nutr.19964811318
    [Google Scholar]
  42. OlsenK.M. RudisM.I. RebuckJ.A. Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity.Crit. Care Med.20043281678168210.1097/01.CCM.0000134832.11144.CB 15286543
    [Google Scholar]
  43. RiethmuellerJ. BallmannM. SchroeterT.W. Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients.Infection200937542443110.1007/s15010‑009‑8117‑4 19756418
    [Google Scholar]
  44. MulheranM. Hyman-TaylorP. TanK.H.V. Absence of cochleotoxicity measured by standard and high-frequency pure tone audiometry in a trial of once- versus three-times-daily tobramycin in cystic fibrosis patients.Antimicrob. Agents Chemother.20065072293229910.1128/AAC.00995‑05 16801404
    [Google Scholar]
  45. TorfossD. HøibyE.A. TangenJ.M. Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: A prospective, randomized, multicentre trial.J. Antimicrob. Chemother.200759471171710.1093/jac/dkm003 17327294
    [Google Scholar]
  46. Abdel-BariA. MokhtarM.S. SabryN.A. El-ShafiS.A. BazanN.S. Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients.Saudi Pharm. J.201119191710.1016/j.jsps.2010.11.001 23960738
    [Google Scholar]
  47. McDadeE.J. WagnerJ.L. MoffettB.S. PalazziD.L. Once-daily gentamicin dosing in pediatric patients without cystic fibrosis.Pharmacotherapy201030324825310.1592/phco.30.3.248 20180608
    [Google Scholar]
  48. BakriF.E. PallettA. SmithA.G. DuncombeA.S. Once-daily versus multiple-daily gentamicin in empirical antibiotic therapy of febrile neutropenia following intensive chemotherapy.J. Antimicrob. Chemother.200045338338610.1093/jac/45.3.383 10702563
    [Google Scholar]
  49. RozdzinskiE. KernW.V. ReichleA. Once-daily versus thrice-daily dosing of netilmicin in combination with β-lactam antibiotics as empirical therapy for febrile neutropenic patients.J. Antimicrob. Chemother.199331458558910.1093/jac/31.4.585 8514653
    [Google Scholar]
  50. UijtendaalE.V. RademakerC.M.A. SchobbenA.F.A.M. Once-daily versus multiple-daily gentamicin in infants and children.Ther. Drug Monit.200123550651310.1097/00007691‑200110000‑00002 11591895
    [Google Scholar]
  51. WhiteheadA. ConwayS.P. EtheringtonC. CaldwellN.A. SetchfieldN. BogleS. Once-daily tobramycin in the treatment of adult patients with cystic fibrosis.Eur. Respir. J.200219230330910.1183/09031936.02.00221602 11866010
    [Google Scholar]
  52. VicP. AtegboS. TurckD. Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis.Arch. Dis. Child.199878653653910.1136/adc.78.6.536 9713009
    [Google Scholar]
  53. CosciaA. MaiorcaD. MartanoC. Use of netilmicin once or twice daily in preterm newborns: evaluation of nephrotoxicity by urinary α1-microglobulin and retinol binding protein.J. Chemother.200820332432610.1179/joc.2008.20.3.324 18606587
    [Google Scholar]
  54. Al AnsariN.A. FowerakerJ. MackeownD. BiltonD. Evaluation of once daily tobramycin versus the traditional three time daily for the treatment of acute pulmonary exacerbations in adult cystic fibrosis patients.Qatar Med. J.2006200611310.5339/qmj.2006.1.13
    [Google Scholar]
  55. LeoniF. CiolliS. PascarellaA. FanciR. CaporaleR. Rossi FerriniP.L. Ceftriaxone plus conventional or single-daily dose amikacin versus ceftazidime/amikacin as empiric therapy in febrile neutropenic patients.Chemotherapy199339214715210.1159/000239118 8458248
    [Google Scholar]
  56. SmythA. TanK.H.V. Hyman-TaylorP. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis—the TOPIC study: A randomised controlled trial.Lancet2005365945957357810.1016/S0140‑6736(05)17906‑9 15708100
    [Google Scholar]
  57. SinghR. SripadaL. SinghR. Side effects of antibiotics during bacterial infection: Mitochondria, the main target in host cell.Mitochondrion201416505410.1016/j.mito.2013.10.005 24246912
    [Google Scholar]
  58. RadiganE.A. GilchristN.A. MillerM.A. Management of aminoglycosides in the intensive care unit.J. Intensive Care Med.201025632734210.1177/0885066610377968 20837630
    [Google Scholar]
  59. MooreR.D. LietmanP.S. SmithC.R. Clinical response to aminoglycoside therapy: Importance of the ratio of peak concentration to minimal inhibitory concentration.J. Infect. Dis.19871551939910.1093/infdis/155.1.93 3540140
    [Google Scholar]
  60. DewR.B.III SuslaG.M. Once-daily aminoglycoside treatment.Infect. Dis. Clin. Pract.199651122410.1097/00019048‑199601000‑00004
    [Google Scholar]
  61. MironD. Once daily dosing of gentamicin in infants and children.Pediatr. Infect. Dis. J.200120121169117310.1097/00006454‑200112000‑00016 11740327
    [Google Scholar]
  62. BarclayM.L. BeggE.J. ChambersS.T. Adaptive resistance following single doses of gentamicin in a dynamic in vitro model.Antimicrob. Agents Chemother.19923691951195710.1128/AAC.36.9.1951 1416886
    [Google Scholar]
  63. Al-HamadA. Improving gentamicin dosing: A suggested approach to a simplified once-daily dosing schedule.J. Infect. Public Health20147324724810.1016/j.jiph.2013.10.001 24613407
    [Google Scholar]
  64. BlaserJ. StoneB.B. GronerM.C. ZinnerS.H. Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance.Antimicrob. Agents Chemother.19873171054106010.1128/AAC.31.7.1054 3116917
    [Google Scholar]
  65. DrusanoG.L. Prevention of resistance: A goal for dose selection for antimicrobial agents.Clin. Infect. Dis.200336S1S42S5010.1086/344653 12516029
    [Google Scholar]
  66. GonzalezL.S.III SpencerJ.P. Aminoglycosides: A practical review.Am. Fam. Physician199858818111820 9835856
    [Google Scholar]
  67. PrayleA. SmythA.R. Aminoglycoside use in cystic fibrosis: Therapeutic strategies and toxicity.Curr. Opin. Pulm. Med.201016660461010.1097/MCP.0b013e32833eebfd 20814306
    [Google Scholar]
  68. StankowiczM.S. IbrahimJ. BrownD.L. Once-daily aminoglycoside dosing: An update on current literature.Am. J. Health Syst. Pharm.201572161357136410.2146/ajhp140564 26246292
    [Google Scholar]
  69. DrewR. Dosing and administration of parenteral aminoglycosides. In: UpToDate.Available from: https://medilib.ir/uptodate/show/475#:~:text=INTRODUCTION%20%E2%80%94%20The%20traditional%20approach%20to,patients%20with%20normal%20renal%20function.2014
  70. SextonD.J. TenenbaumM.J. WilsonW.R. SteckelbergJ.M. TiceA.D. GilbertD. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.Clin. Infect. Dis.19982761470147410.1086/515038
    [Google Scholar]
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  • Article Type:
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Keyword(s): Aminoglycosides; nephrotoxicity; ototoxicity; pharmacokinetics; safety; toxicity
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