Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Systematic Review Article

Aminoglycosides: Single- or Multiple-daily Dosing? An Updated Qualitative Systematic Review of Randomized Trials on Toxicity and Efficacy

Author(s): Iman Karimzadeh, Meghdad Abdollahpour-Alitappeh, Shokouh Ghaffari, Motahareh Mahi-Birjand*, Amin Barkhordari and Effat Alemzadeh*

Volume 24, Issue 11, 2024

Published on: 07 November, 2023

Page: [1358 - 1373] Pages: 16

DOI: 10.2174/1566524023666230801160452

Price: $65

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 versus 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.

« Previous Next »
[1]
Elshahawi SI, Shaaban KA, Kharel MK, Thorson JSJCSR. A comprehensive review of glycosylated bacterial natural products. Chem Soc Rev 2015; 44((21)): 7591-697.
[http://dx.doi.org/10.1039/C4CS00426D]
[2]
Dezanet C, Kempf J, Mingeot-Leclercq MP, Décout JL. Amphiphilic aminoglycosides as medicinal agents. Int J Mol Sci 2020; 21(19): 7411.
[http://dx.doi.org/10.3390/ijms21197411] [PMID: 33049963]
[3]
Bryskier A. Antibiotics and antibacterial agents: classifications and structure-activity relationship Antimicrobial Agents. American Society of Microbiology. Hoboken, New Jersey: Wiley Online 2005; pp. 13-38.
[4]
Serio AW, Magalhães ML, Blanchard JS, Connolly LE. Aminoglycosides: Mechanisms of Action and Resistance Antimicrobial Drug Resistance. Antimicrob Agents Chemother 2000; 44(12): 3249-56.
[http://dx.doi.org/10.1007/978-3-319-46718-4_14]
[5]
Bowers DR, Schilling AN, Tam VH. Aminoglycoside Pharmacodynamics. Antibiotic Pharmacodynamics. Amsterdam: Springer 2016; pp. 199-220.
[6]
Lee S, Hinz A, Bauerle E, et al. Targeting a bacterial stress response to enhance antibiotic action. Proc Natl Acad Sci 2009; 106(34): 14570-5.
[http://dx.doi.org/10.1073/pnas.0903619106] [PMID: 19706543]
[7]
Sandoval RM, Molitoris BA. Gentamicin traffics retrograde through the secretory pathway and is released in the cytosol via the endoplasmic reticulum. Am J Physiol Renal Physiol 2004; 286(4): F617-24.
[http://dx.doi.org/10.1152/ajprenal.00130.2003] [PMID: 14625200]
[8]
Avent ML, Rogers BA, Cheng AC, Paterson DL. Current use of aminoglycosides: Indications, pharmacokinetics and monitoring for toxicity. Intern Med J 2011; 41(6): 441-9.
[http://dx.doi.org/10.1111/j.1445-5994.2011.02452.x] [PMID: 21309997]
[9]
Warchol ME. Cellular mechanisms of aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg 2010; 18(5): 454-8.
[http://dx.doi.org/10.1097/MOO.0b013e32833e05ec] [PMID: 20717031]
[10]
Karasawa T, Steyger PS. Intracellular mechanisms of aminoglycoside-induced cytotoxicity. Integr Biol 2011; 3(9): 879-86.
[http://dx.doi.org/10.1039/c1ib00034a] [PMID: 21799993]
[11]
Jana S. Molecular understanding of aminoglycoside action and resistance. Appl Microbiol Biotechnol 2006; 70(2): 140-50.
[12]
Fosso MY, Li Y, Garneau-Tsodikova S. New trends in the use of aminoglycosides. MedChemComm 2014; 5(8): 1075-91.
[http://dx.doi.org/10.1039/C4MD00163J] [PMID: 25071928]
[13]
Durante-Mangoni E, Grammatikos A, Utili R, Falagas ME. Do we still need the aminoglycosides? Int J Antimicrob Agents 2009; 33(3): 201-5.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.09.001] [PMID: 18976888]
[14]
Prayle A, Watson A, Fortnum H, Smyth A. Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis. Thorax 2010; 65(7): 654-8.
[http://dx.doi.org/10.1136/thx.2009.131532] [PMID: 20627927]
[15]
McDermott JH, Mahaveer A, James RA, et al. Rapid point-of-care genotyping to avoid aminoglycoside-induced ototoxicity in neonatal intensive care. JAMA Pediatr 2022; 176(5): 486-92.
[http://dx.doi.org/10.1001/jamapediatrics.2022.0187] [PMID: 35311942]
[16]
Le TA, Hiba T, Chaudhari D, et al. Aminoglycoside-related nephrotoxicity and ototoxicity in clinical practice: A review of pathophysiological mechanism and treatment options. Adv Ther 2023; 40(4): 1357-65.
[http://dx.doi.org/10.1007/s12325-023-02436-x] [PMID: 36738370]
[17]
Leis JA, Rutka JA, Gold WL. Aminoglycoside-induced ototoxicity. Curr Pharm Des 2015; 13(1): 119-26.
[http://dx.doi.org/10.1503/cmaj.140339]
[18]
Huth M, Ricci A, Cheng A. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Int J Otolaryngol 2011; 2011: 937861.
[http://dx.doi.org/10.1155/2011/937861]
[19]
Fu X, Wan P, Li P, et al. Mechanism and prevention of ototoxicity induced by aminoglycosides. Front Cell Neurosci 2021; 15: 692762.
[http://dx.doi.org/10.3389/fncel.2021.692762] [PMID: 34211374]
[20]
Ricci AJ, Greenhouse RJ, Cheng AG. Aminoglycoside antibiotics with reduced ototoxicity. US2014274932A1, 2016.
[21]
Xie J, Talaska AE, Schacht J. New developments in aminoglycoside therapy and ototoxicity. Hear Res 2011; 281(1-2): 28-37.
[http://dx.doi.org/10.1016/j.heares.2011.05.008] [PMID: 21640178]
[22]
Dillard LK, Martinez RX, Perez LL, Fullerton AM, Chadha S, McMahon CM. Prevalence of aminoglycoside-induced hearing loss in drug-resistant tuberculosis patients: A systematic review. J Infect 2021; 83(1): 27-36.
[http://dx.doi.org/10.1016/j.jinf.2021.05.010] [PMID: 34015383]
[23]
Kalmanson OA, McLoughlin KC, Kiser TH, Gubbels SP. Debilitating gentamicin ototoxicity: Case report and recommendations against routine use in surgical prophylaxis. Ann Otol Rhinol Laryngol 2022; 34894231176333.
[24]
Mantefardo B, Sisay G. Case Report: Kanamycin ototoxicity and MDR-TB treatment regimen. Int Med Case Rep J 2021; 14: 815-7.
[http://dx.doi.org/10.2147/IMCRJ.S336259] [PMID: 34858067]
[25]
Vinks AA, Derendorf H, Mouton JW. Fundamentals of antimicrobial pharmacokinetics and pharmacodynamics. New York: Springer 2014.
[http://dx.doi.org/10.1007/978-0-387-75613-4]
[26]
Fligor BJ. Ed Early Diagnosis and Management of Hearing Loss in Medically Fragile Children Seminars in Hearing. Leipzig, Germany: Thieme Medical Publishers 2013.
[27]
Wargo KA, Edwards JD. Aminoglycoside-induced nephrotoxicity. J Pharm Pract 2014; 27(6): 573-7.
[http://dx.doi.org/10.1177/0897190014546836] [PMID: 25199523]
[28]
Nolin TD, Himmelfarb J. Mechanisms of drug-induced nephrotoxicity Adverse drug reactions. Springer 2010; pp. 111-30.
[29]
Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 2011; 79(1): 33-45.
[http://dx.doi.org/10.1038/ki.2010.337] [PMID: 20861826]
[30]
Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician 2008; 78(6): 743-50.
[PMID: 18819242]
[31]
Drusano GL, Louie A. Optimization of aminoglycoside therapy. Antimicrob Agents Chemother 2011; 55(6): 2528-31.
[http://dx.doi.org/10.1128/AAC.01314-10] [PMID: 21402835]
[32]
Oliveira JFP, Silva CA, Barbieri CD, Oliveira GM, Zanetta DMT, Burdmann EA. Prevalence and risk factors for aminoglycoside nephrotoxicity in intensive care units. Antimicrob Agents Chemother 2009; 53(7): 2887-91.
[http://dx.doi.org/10.1128/AAC.01430-08] [PMID: 19364846]
[33]
Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367(1): 20-9.
[http://dx.doi.org/10.1056/NEJMoa1114248] [PMID: 22762315]
[34]
Hatala R, Dinh TT, Cook DJ. Single daily dosing of aminoglycosides in immunocompromised adults: A systematic review. Clin Infect Dis 1997; 24(5): 810-5.
[http://dx.doi.org/10.1093/clinids/24.5.810] [PMID: 9142773]
[35]
Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother 1995; 39(3): 650-5.
[http://dx.doi.org/10.1128/AAC.39.3.650] [PMID: 7793867]
[36]
Thomas J, Harden A. Methods for the thematic synthesis of qualitative research in systematic reviews. BMC Med Res Methodol 2008; 8(1): 45.
[http://dx.doi.org/10.1186/1471-2288-8-45] [PMID: 18616818]
[37]
Tiwari S, Rehan HS, Chandra J, Mathur NN, Singh V. Efficacy and safety of a single daily dose of gentamicin in hospitalized Indian children: A quasi-randomized trial. J Antimicrob Chemother 2009; 64(5): 1096-101.
[http://dx.doi.org/10.1093/jac/dkp330] [PMID: 19759043]
[38]
Pérez V, Saénz D, Madriz J, et al. 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 2011; 15(8): e569-75.
[http://dx.doi.org/10.1016/j.ijid.2011.04.012] [PMID: 21733727]
[39]
Abdel-Hady E, El Hamamsy M, Hedaya M, Awad H. The efficacy and toxicity of two dosing-regimens of amikacin in neonates with sepsis. J Clin Pharm Ther 2011; 36(1): 45-52.
[http://dx.doi.org/10.1111/j.1365-2710.2009.01152.x] [PMID: 21198719]
[40]
Buchholtz K, Larsen CT, Schaadt B, Hassager C, Bruun NE. Once versus twice daily gentamicin dosing for infective endocarditis: a randomized clinical trial. Cardiology 2011; 119(2): 65-71.
[http://dx.doi.org/10.1159/000329842] [PMID: 21846985]
[41]
Solorzano-Santos F, Miranda-Novales M, Diaz-Pena R, Bernaldez-Ríos R, Díaz-Bensussen S, Rivera-Márquez H. Amikacin in single daily doses in children with fever. Clin Nutr 1996; 48(1): 13-8.
[42]
Olsen KM, Rudis MI, Rebuck JA, et al. Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity. Crit Care Med 2004; 32(8): 1678-82.
[http://dx.doi.org/10.1097/01.CCM.0000134832.11144.CB] [PMID: 15286543]
[43]
Riethmueller J, Ballmann M, Schroeter TW, et al. Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients. Infection 2009; 37(5): 424-31.
[http://dx.doi.org/10.1007/s15010-009-8117-4] [PMID: 19756418]
[44]
Mulheran M, Hyman-Taylor P, Tan KHV, et al. 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 2006; 50(7): 2293-9.
[http://dx.doi.org/10.1128/AAC.00995-05] [PMID: 16801404]
[45]
Torfoss D, Høiby EA, Tangen JM, et al. 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 2007; 59(4): 711-7.
[http://dx.doi.org/10.1093/jac/dkm003] [PMID: 17327294]
[46]
Abdel-Bari A, Mokhtar MS, Sabry NA, El-Shafi SA, Bazan NS. Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients. Saudi Pharm J 2011; 19(1): 9-17.
[http://dx.doi.org/10.1016/j.jsps.2010.11.001] [PMID: 23960738]
[47]
McDade EJ, Wagner JL, Moffett BS, Palazzi DL. Once-daily gentamicin dosing in pediatric patients without cystic fibrosis. Pharmacotherapy 2010; 30(3): 248-53.
[http://dx.doi.org/10.1592/phco.30.3.248] [PMID: 20180608]
[48]
Bakri FE, Pallett A, Smith AG, Duncombe AS. Once-daily versus multiple-daily gentamicin in empirical antibiotic therapy of febrile neutropenia following intensive chemotherapy. J Antimicrob Chemother 2000; 45(3): 383-6.
[http://dx.doi.org/10.1093/jac/45.3.383] [PMID: 10702563]
[49]
Rozdzinski E, Kern WV, Reichle A, et al. Once-daily versus thrice-daily dosing of netilmicin in combination with β-lactam antibiotics as empirical therapy for febrile neutropenic patients. J Antimicrob Chemother 1993; 31(4): 585-9.
[http://dx.doi.org/10.1093/jac/31.4.585] [PMID: 8514653]
[50]
Uijtendaal EV, Rademaker CMA, Schobben AFAM, et al. Once-daily versus multiple-daily gentamicin in infants and children. Ther Drug Monit 2001; 23(5): 506-13.
[http://dx.doi.org/10.1097/00007691-200110000-00002] [PMID: 11591895]
[51]
Whitehead A, Conway SP, Etherington C, Caldwell NA, Setchfield N, Bogle S. Once-daily tobramycin in the treatment of adult patients with cystic fibrosis. Eur Respir J 2002; 19(2): 303-9.
[http://dx.doi.org/10.1183/09031936.02.00221602] [PMID: 11866010]
[52]
Vic P, Ategbo S, Turck D, et al. Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis. Arch Dis Child 1998; 78(6): 536-9.
[http://dx.doi.org/10.1136/adc.78.6.536] [PMID: 9713009]
[53]
Coscia A, Maiorca D, Martano C, et al. Use of netilmicin once or twice daily in preterm newborns: evaluation of nephrotoxicity by urinary α1-microglobulin and retinol binding protein. J Chemother 2008; 20(3): 324-6.
[http://dx.doi.org/10.1179/joc.2008.20.3.324] [PMID: 18606587]
[54]
Al Ansari NA, Foweraker J, Mackeown D, Bilton D. 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 2006; 2006(1): 13.
[http://dx.doi.org/10.5339/qmj.2006.1.13]
[55]
Leoni F, Ciolli S, Pascarella A, Fanci R, Caporale R, Rossi Ferrini PL. Ceftriaxone plus conventional or single-daily dose amikacin versus ceftazidime/amikacin as empiric therapy in febrile neutropenic patients. Chemotherapy 1993; 39(2): 147-52.
[http://dx.doi.org/10.1159/000239118] [PMID: 8458248]
[56]
Smyth A, Tan KHV, Hyman-Taylor P, et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis—the TOPIC study: A randomised controlled trial. Lancet 2005; 365(9459): 573-8.
[http://dx.doi.org/10.1016/S0140-6736(05)17906-9] [PMID: 15708100]
[57]
Singh R, Sripada L, Singh R. Side effects of antibiotics during bacterial infection: Mitochondria, the main target in host cell. Mitochondrion 2014; 16: 50-4.
[http://dx.doi.org/10.1016/j.mito.2013.10.005] [PMID: 24246912]
[58]
Radigan EA, Gilchrist NA, Miller MA. Management of aminoglycosides in the intensive care unit. J Intensive Care Med 2010; 25(6): 327-42.
[http://dx.doi.org/10.1177/0885066610377968] [PMID: 20837630]
[59]
Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: Importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987; 155(1): 93-9.
[http://dx.doi.org/10.1093/infdis/155.1.93] [PMID: 3540140]
[60]
Dew RB III, Susla GM. Once-daily aminoglycoside treatment. Infect Dis Clin Pract 1996; 5(1): 12-24.
[http://dx.doi.org/10.1097/00019048-199601000-00004]
[61]
Miron D. Once daily dosing of gentamicin in infants and children. Pediatr Infect Dis J 2001; 20(12): 1169-73.
[http://dx.doi.org/10.1097/00006454-200112000-00016] [PMID: 11740327]
[62]
Barclay ML, Begg EJ, Chambers ST. Adaptive resistance following single doses of gentamicin in a dynamic in vitro model. Antimicrob Agents Chemother 1992; 36(9): 1951-7.
[http://dx.doi.org/10.1128/AAC.36.9.1951] [PMID: 1416886]
[63]
Al-Hamad A. Improving gentamicin dosing: A suggested approach to a simplified once-daily dosing schedule. J Infect Public Health 2014; 7(3): 247-8.
[http://dx.doi.org/10.1016/j.jiph.2013.10.001] [PMID: 24613407]
[64]
Blaser J, Stone BB, Groner MC, Zinner SH. 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 1987; 31(7): 1054-60.
[http://dx.doi.org/10.1128/AAC.31.7.1054] [PMID: 3116917]
[65]
Drusano GL. Prevention of resistance: A goal for dose selection for antimicrobial agents. Clin Infect Dis 2003; 36(S1): S42-50.
[http://dx.doi.org/10.1086/344653] [PMID: 12516029]
[66]
Gonzalez LS III, Spencer JP. Aminoglycosides: A practical review. Am Fam Physician 1998; 58(8): 1811-20.
[PMID: 9835856]
[67]
Prayle A, Smyth AR. Aminoglycoside use in cystic fibrosis: Therapeutic strategies and toxicity. Curr Opin Pulm Med 2010; 16(6): 604-10.
[http://dx.doi.org/10.1097/MCP.0b013e32833eebfd] [PMID: 20814306]
[68]
Stankowicz MS, Ibrahim J, Brown DL. Once-daily aminoglycoside dosing: An update on current literature. Am J Health Syst Pharm 2015; 72(16): 1357-64.
[http://dx.doi.org/10.2146/ajhp140564] [PMID: 26246292]
[69]
Drew R. Dosing and administration of parenteral aminoglycosides. In: UpToDate. 2014. Available from: https://medilib.ir/uptodate/show/475#:~:text=INTRODUCTION%20%E2%80%94%20The%20traditional%20approach%20to,patients%20with%20normal%20renal%20function.
[70]
Sexton DJ, Tenenbaum MJ, Wilson WR, Steckelberg JM, Tice AD, Gilbert D. 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 1998; 27(6): 1470-4.
[http://dx.doi.org/10.1086/515038]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy