Medical and Dental Consultantsí Association of Nigeria
Home - About us - Editorial board - Search - Ahead of print - Current issue - Archives - Submit article - Instructions - Subscribe - Advertise - Contacts - Login 
  Users Online: 847   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
 

  Table of Contents 
CASE REPORT
Year : 2016  |  Volume : 19  |  Issue : 4  |  Page : 563-566

Concomitant gentamicin-induced nephrotoxicity and bilateral ototoxicity


1 Department of Medicine, Kidney Care Centre, University of Medical Sciences, Ondo, Ondo State, Nigeria
2 Department of Renal Unit, Obafemi Awolowo University Teaching Hospital, Ile Ife, Osun State, Nigeria

Date of Acceptance20-Nov-2015
Date of Web Publication1-Jun-2016

Correspondence Address:
Dr. A A Akinbodewa
PMB 542, Medical Village, 23434 Ondo, Ondo State
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1119-3077.183312

Rights and Permissions
   Abstract 

Co-occurrence of aminoglycoside-induced ototoxicity and nephrotoxicity is rare, possibly as a result of divergent mechanisms of tissue damage despite similarities in the anatomy of the inner ear and the proximal renal tubular epithelium. We present the case of a 63-year-old hypertensive woman who developed nonoliguric acute exacerbation of chronic renal failure and sudden onset of sensorineural deafness after receiving daily injections of gentamicin. Coexisting ototoxicity and nephrotoxicity from aminoglycosides can occur, though rare. Adverse effects of aminoglycosides are better prevented by a careful exercise of discretion by prescribers.

Keywords: Acute kidney injury, aminoglycosides, co-occurrence, gentamicin, nephrotoxicity, ototoxicity


How to cite this article:
Akinbodewa A A, Okunola O. Concomitant gentamicin-induced nephrotoxicity and bilateral ototoxicity. Niger J Clin Pract 2016;19:563-6

How to cite this URL:
Akinbodewa A A, Okunola O. Concomitant gentamicin-induced nephrotoxicity and bilateral ototoxicity. Niger J Clin Pract [serial online] 2016 [cited 2020 Sep 24];19:563-6. Available from: http://www.njcponline.com/text.asp?2016/19/4/563/183312


   Introduction Top


Aminoglycosides are known to cause nephrotoxicity, ototoxicity, and, more rarely, neuromuscular blockade. Gentamicin-induced nephrotoxicity ranges between 8% and 26%, while by audiometry about 25% of patients on aminoglycoside therapy develop ototoxicity.[1],[2] However, concomitant renal toxicity and ototoxicity from aminoglycosides are rare. Gentamicin remains a first-line antibiotic for many severe infections due to its clinical effectiveness, low rates of resistance, affordability, and low risk of Clostridium difficile. This has made it one of the most frequently used aminoglycosides. Monitoring of plasma concentrations is effective in avoiding gentamicin-induced nephrotoxicity and ototoxicity, but this is not readily affordable in our environment.[3]


   Case Report Top


The patient is a 63-year-old poorly compliant hypertensive of 6 years duration who presented with hiccups; vomiting of 3 weeks duration; a abnormally elevated serum urea and creatinine (urea 47 mmol/L and creatinine 308 μmol/L); and sudden loss of hearing in both ears following administration of multiple injectables (gentamicin-included) on account of a febrile illness for about 2 weeks at a private hospital. The total daily dose of the gentamicin administered was, however, not specified. About the same time, she developed sudden onset of inability to hear in both ears. There was no associated earache, tinnitus, ear discharge, or vertigo. There was no significant change in her urine volume [Table 1].
Table 1: The fluid input and urine output chart of index patient showing predominantly nonoliguric level of urine output

Click here to view


At presentation, she was dehydrated and restless with blood pressure of 100/40 mHg. Urine culture yielded growth of  Escherichia More Details coli sensitive to imipenem, ceftriaxone, and chloramphenicol. Renal scan showed loss of corticomedullary differentiation bilaterally. There was no hydroureter or hydrocalyx. She had hypokalemia (2.5 mmol/L) and hyponatremia (129 mmol/L). Her corrected serum calcium was 2.39 mmol/L. Urinalysis showed 1 + glycosuria and 3 + proteinuria. Pure tone audiometry and tympanometry confirmed bilateral sensorineural deafness [Figure 1].
Figure 1: Audiogram of index patient showing bilateral profound sensorineural hearing loss

Click here to view


She was managed on intravenous ceftriaxone 1 g daily and rehydrated with normal saline. Hypokalemia was corrected with oral potassium chloride. She received a total of 4 sessions of hemodialysis with significant improvement in renal function. She was discharged home after the 3rd week of admission for follow-up in the renal and otorhinolaryngology clinics.

Three months after discharge, her renal function stabilized; with serum urea 4.2 mmol/L, creatinine 124 μmol/L, potassium 3.5 mmol/L, sodium 132 mmol/L, and bicarbonate of 24 mmol/L. However, the sensorineural deafness persisted.


   Discussion Top


Our index patient had coexisting nephrotoxicity and ototoxicity. A direct and dose-dependent relationship between nephrotoxicity and ototoxicity in the same patient has not yet been established despite earlier suggestions.[4] Studies showed that ototoxicity results mainly from apoptosis unlike dose-dependent necrosis in nephrotoxicity.[5]

Several factors have been reported as increasing the risk of gentamicin nephrotoxicity and ototoxicity, viz.: Elevated trough gentamicin levels, plasma concentration-time area under the curve, duration of treatment on aminoglycoside, concomitant vancomycin, frusemide use, volume depletion, elevated baseline serum creatinine, increasing age, presence of co-morbidities, liver dysfunction, sepsis, hypokalemia, hypomagnesaemia, the type of aminoglycoside, the frequency of aminoglycoside dosing, and the timing of aminoglycoside administration.[6],[7] In our index patient, identified risk factors include old age, volume depletion (dehydration and suboptimal blood pressure), background chronic kidney disease, and multiple dosing of gentamicin.

Gentamicin nephrotoxicity presents commonly as non-oliguric acute kidney injury as seen in our index patient [Table 1]. This usually occurs in association with the appearance of enzymuria.

The onset of renal failure from aminoglycoside toxicity is usually slower, and the daily rise of serum creatinine tends to be lower than other causes of acute kidney injury characteristically taking 7–10 days to increase after initiation of aminoglycoside therapy with associated aminoaciduria, glycosuria, hypomagnesemia, hypocalcemia, and hypokalemia.[8],[9]

Our index patient developed acute kidney injury about the 7th day of treatment with gentamicin. Hypokalemia (2.5 mmol/L) and glycosuria were also demonstrated in her blood and urine, respectively.

Recovery from aminoglycoside nephrotoxicity is usually slow, often taking 4–6 weeks, particularly in elderly individuals. In patients with underlying chronic kidney disease, recovery of renal function may be incomplete.[10] Recovery of renal function was quite prolonged in our index patient resulting in a prolonged hospital stay, of a total of 22 days. It might even have been longer without dialytic intervention. Gentamicin causes predominantly irreversible cochlear damage but when reversible, recovery may start from 24 h after stopping the aminoglycoside.[11]

The treatment of aminoglycoside nephrotoxicity is supportive; discontinue the aminoglycoside and other nephrotoxic agents, maintain fluid and electrolyte balance, and control sepsis. Parenteral vitamin B complex and a combination of Vitamin E and selenium have been suggested.[12]

While it is natural to favor outright avoidance of aminoglycosides where culture sensitivity results are indicative (especially in resource-poor settings), it may just be safer to use the lowest possible dose, shortest course of therapy, and administer once daily doses, particularly in high-risk individuals such as patients in the extremes of age, presence of diabetes mellitus, and electrolyte imbalance (hypokalemia and hypomagnesemia).[6],[7] Other important safety measures include serial monitoring of renal function, avoidance of combination of aminoglycosides with other nephrotoxins, adequate hydration, modification of the dose according to the glomerular filtration rate, and avoidance of use in patients with liver disease.[13]

Where economic conditions are more favorable or the use of aminoglycoside becomes imperative, serum drug levels may be monitored for safety. A recent review by Wargo and Edwards dealt with newer strategies to prevent patients from developing aminoglycoside-induced nephrotoxicity.[14] One of such strategies is individualized pharmacokinetic monitoring (IPM) in patients who are receiving aminoglycosides. Streetman et al. showed that patients who received IPM were significantly less likely to develop aminoglycoside-associated nephropathy.[15] IPM allows tailoring of aminoglycoside dosage to each patient to achieve optimal therapeutic goals while avoiding (or minimizing) toxicity; this is best achieved when the patients' peculiar clinical characteristics and drug serum trough and peak levels are carefully taken into consideration. For instance, a patient could indeed receive intravenous gentamicin once every 3–5 days with trough level monitoring to achieve excellent therapeutic outcomes.

Pharmacokinetic monitoring protocol for serum levels of aminoglycosides varies from center to center. The more popular protocols include the standard initial dose protocol and the extended interval dose protocol [Table 2].[16],[17] However, their practicability in our environment would require an upgrade of our microbiology facilities, establishment of a standard drug toxicology unit, continuous medical education, and skill acquisition programs for our medical doctors, pharmacists, and laboratory personnel.
Table 2: Pharmacokinetics of gentamicin recommended initial dosages for specific clinical indications

Click here to view



   Conclusion Top


Aminoglycoside-induced nephrotoxicity is avoidable. The indications for the use of aminoglycosides must be strongly established, and the predisposing factors for renal failure and ototoxicity must be vigorously sought out and eliminated, where possible. The use of aminoglycosides in the elderly should best be discouraged because of the likelihood of underlying age-related reduced renal reserve and impaired hearing ability.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Raveh D, Kopyt M, Hite Y, Rudensky B, Sonnenblick M, Yinnon AM. Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides. QJM 2002;95:291-7.  Back to cited text no. 1
    
2.
Goodman LS, Gilman A, Brunton LL, Lazo JS, Parker KL. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th eb. New York: McGraw Hill, 2006.  Back to cited text no. 2
    
3.
Gunnar K, Dahlager JI. Aminoglycoside toxicity: A review of clinical studies published between 1975 and 1982. J Antimicrob Chemother 1984;13 Suppl A: 23-8.  Back to cited text no. 3
    
4.
Lei L, Wang J, Huang X. Correlation between expression of Fas protein and hair cell apoptosis in basilar papilla of chicken. Lin Chuang Er Bi Yan Hou Ke Za Zhi 2002;16:297-9.  Back to cited text no. 4
    
5.
Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother 1999;43:1549-55.  Back to cited text no. 5
    
6.
Barza M, Ioannidis JP, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: A meta-analysis. BMJ 1996;312:338-45.  Back to cited text no. 6
    
7.
Govaerts PJ, Claes J, van de Heyning PH, Jorens PG, Marquet J, De Broe ME. Aminoglycoside-induced ototoxicity. Toxicol Lett 1990;52:227-51.  Back to cited text no. 7
    
8.
Oliveira JF, Cipullo JP, Burdmann EA. Aminoglycoside nephrotoxicity. Braz J Cardiovasc Surg 2006;21:444-52.  Back to cited text no. 8
    
9.
Appel GB. Aminoglycoside nephrotoxicity. Am J Med 1990;88:16S-20S.  Back to cited text no. 9
    
10.
Schentag JJ, Cerra FB, Plaut ME. Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients. Antimicrob Agents Chemother 1982;21:721-6.  Back to cited text no. 10
[PUBMED]    
11.
Moore RD, Smith CR, Lietman PS. Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis 1984;149:23-30.  Back to cited text no. 11
[PUBMED]    
12.
Shaibu O, Aminu C. Dose-dependent amelioration of gentamicin-induced nephrotoxicity in adult Swiss albino rats by Vitamin B-complex – A preliminary study. Trop J Pharm Res 2009;8:111-6.  Back to cited text no. 12
    
13.
Mingeot-Leclercq MP, Tulkens PM. Aminoglycosides: Nephrotoxicity. Antimicrob Agents Chemother 1999;43:1003-12.  Back to cited text no. 13
    
14.
Wargo KA, Edwards JD. Aminoglycoside-induced nephrotoxicity. J Pharm Pract 2014;27:573-7.  Back to cited text no. 14
    
15.
Streetman DS, Nafziger AN, Destache CJ, Bertino AS Jr. Individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity and fewer associated costs. Pharmacotherapy 2001;21:443-51.  Back to cited text no. 15
    
16.
Murphy JE. Clinical Pharmacokinetics. Bethesda, MD: American Society of Health-System Pharmacists; 1993.  Back to cited text no. 16
    
17.
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;39:650-5.  Back to cited text no. 17
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Ototoxicity: The Radical Drum Beat and Rhythm of Cochlear Hair Cell Life and Death
David V. Gauvin,Joshua Yoder,Zachary J. Zimmermann,Rachel Tapp
International Journal of Toxicology. 2018; 37(3): 195
[Pubmed] | [DOI]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed2634    
    Printed28    
    Emailed0    
    PDF Downloaded411    
    Comments [Add]    
    Cited by others 1    

Recommend this journal