Amikacin toxicity

Kumar A, Dada T. Preretinal haemorrhages an unusual manifestation of intravitreal amikacin toxicity. Aust NZ J Ophthalmol 1999 27(6) 435-6. 

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

Ototoxicity with both auditory and vestibulatory effects is the most serious of the adverse reactions of aminogycosides as it is mostly irreversible. Vestibular involvement manifests itself by dizziness, nystagmus, vertigo and ataxia. Cochlear toxicity results initially in high-frequency hearing loss. Amikacin more often causes cochlear damage than vestibular problems, while gentamicin and tobramycin are associated more frequently with vestibular symptoms. 

Amikacin and kanamycin (see Chapter 46) have been used in the treatment of tuberculosis. Amikacin is very active against several mycobacterium species however, it is expensive and has significant toxicity. It is considered in the treatment of MDR tuberculosis after streptomycin and capreomycin. An additional use of amikacin is in the treatment of disseminated MAC in AIDS patients. There is no cross-resistance between streptomycin and other aminoglycosides most M. tuberculosis strains that are resistant to streptomycin are... 

It is used in the treatment of tuberculosis caused by streptomycin resistant strains but since agents with lesser toxicity e.g. capreomycin and amikacin are available, its use is obsolete. 

The aminoglycoside antibiotics are discussed in Chapter 45. Kanamycin has been used for treatment of tuberculosis caused by streptomycin-resistant strains, but the availability of less toxic alternatives (eg, capreomycin and amikacin) has rendered it obsolete. 

Aminoglycosides are a group of bactericidal antibiotics originally obtained from various streptomyces species and sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. The group includes streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. 

H. Schreier, K. J. McNicol, M. Ausborn, D. M. Soucy, H. Derendorf, A. A. Stec-enko, and R. J. Gonzalez-Rothi, Pulmonary delivery of amikacin liposomes and acute liposome toxicity in sheep, Int. J. Pharm. 87 183 (1992). 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

Chloramphenicol (9) is liable to breakdown by chloramphenicol acetyl-transferases [185]. Fluoro derivatives (57, 58) resist enzymatic attack but little has been heard of these, apparently because of their toxicity [319], Aminoglycoside antibiotics (AGACs) may be chemically modified by AMEs. Some derivatives (e.g. amikacin, 43) are more recalcitrant than others, e.g. kanamycin (42) (see Figure 4.2). Other enzyme-resistant AGACs of low toxicity are needed. 

The same spectrum of toxicity (ototoxicity and nephrotoxicity) is shared by all members of the group, The more important and frequent interactions are pharmacodynamic. Streptomycin and gentamicin produce predominantly vestibular effects, whereas amikacin, kanamycin and neomycin primarily affect auditory function. All are rapidly excreted by the kidney,... 

Retinal damage in the farm of macular inferction has occurred after intravitreal administration of gentamicin. Because amikacin is less toxic when injected intravitreally, the current recommendation far treatment of postoperative endophthalmitis is intravitreal amikacin (or ceftazidime) for gram-negative coverage. 

Macular toxicity followed the use of intravitreal amikacin 0.2 mg for postoperative endophthalmitis in a 69-year-old white woman (4). 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

The pharmacokinetics and toxicity of liposomal amikacin have been investigated in a patient treated for advanced pulmonary multidrug-resistant tuberculosis (14). The... 

Whitehead TC, Lovering AM, Cropley IM, Wade P, Davidson RN. Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis 1998 17(ll) 794-7. 

There are interesting differences in the toxicity patterns of aminoglycosides in animals. Gentamicin and tobramycin affect the cochlear and vestibular systems to a similar extent, while amikacin, kanamycin, and neomycin preferentially damage the cochlear and streptomycin the vestibular system. Netilmicin appears to be the least toxic (26,27). 

In a survey of aminoglycoside treatment in 2022 patients in Saudi Arabia, 8.8%, 18%, and 12% had trough concentrations considered toxic for amikacin, gentamicin, and tobramycin respectively, whereas there were peak serum drug concentrations in the subtherapeutic range in 53%, 50%, and 57% respectively (197). Toxic concentrations were noticed mainly in patients aged over 60 years and in patients in the intensive care unit, coronary care unit, and burn unit. 

Barza M, Lauermann MW, Tally FP, Gorbach SL. Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity. Antimicrob Agents Chemother 1980 17(4) 707-14. 

Lau WK, Young LS, Black RE, Winston DJ, Linne SR, Weinstein RJ, Hewitt WL. Comparative efficacy and toxicity of amikacin/carbenicillin versus gentamicin/carbenicil-lin in leukopenic patients a randomized prospective trial. Am J Med 1977 62(6) 959-66. 

Bock BV, Edelstein PH, Meyer RD. Prospective comparative study of efficacy and toxicity of netilmicin and amikacin. Antimicrob Agents Chemother 1980 17(2) 217-25. 

---