Aminoglycosides incidence

Resistance to drug toxic effects has also been observed in children. The incidence of aminoglycoside toxicity has been reported to be much lower in infants and children than in adults [39,48]. Diminished tissue sensitivity has been suggested as an explanation. 

Dosing interval Preliminary evidence indicates that aminoglycosides may be administered on a once-daily basis without compromising efficacy and without increasing the potential for nephrotoxicity and ototoxicity. It is possible that the incidence of nephrotoxicity may even be decreased. Elderly Elderly patients may have reduced renal function that is not evident in the results of routine screening tests, such as BUN or serum creatinine. A Ccr determination may be more useful. 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

There is a discrepancy between clinical observations, in which very few patients receiving aminoglycosides actually complain of hearing loss, and the reported incidences of ototoxicity in studies of audiometric thresholds. A major reason for this discrepancy relates to the fact that aminoglycosides cause high-frequency hearing loss well before they affect the speech frequency range in which they can be detected by the patient (21). 

In man, differences in the ototoxic risks of the currently used aminoglycosides are difficult to evaluate (20). There have been no prospective comparisons of more than two drugs using the same criteria in similar patient populations. However, several controlled comparisons of two aminoglycosides are available and provide some information. A survey of 24 such trials showed the following mean frequencies of ototoxicity gentamicin 7.7%, tobramycin 9.7%, amikacin 13.8%, netilmicin 2.3% (28). There was also a lower incidence of netilmicin-induced inner ear damage compared with tobramycin in two studies (29,30). 

Hearing loss was attributed to repeated exposure to aminoglycosides in 12 of 70 patients with cystic fibrosis (one child) (25). There was a non-linear relation between the number of courses of therapy and the incidence of hearing loss. The severity of loss was not related to the number of courses. Assuming that the risk of hearing loss was independent of each course, the preliminary estimate of the risk was less than 2 per 100 courses. 

Isepamicin is similar to amikacin but has better activity against strains that produce type I 6 -acetyltransferase. It can cause nephrotoxicity, vestibular toxicity, and ototoxicity. However, it is one of the less toxic of the aminoglycosides (1). The antibacterial spectrum of isepamicin includes Enterobacteriaceae and staphylococci anaerobes, Neisseriae, and streptococci are resistant (1). Isepamicin was as effective and safe as amikacin in the treatment of acute pyelonephritis in children and might prove an advantageous alternative in areas with a high incidence of resistance to other aminoglycosides (2). 

In a similar vein, Leehey et al. [201] have reported on the frequency of aminoglycoside-induced nephrotoxicity using three different dosing schemes, including two that were based on pharmacokinetic principles. It is noteworthy that despite careful calculation of the dosing scheme, this did not alter the incidence of nephrotoxicity. However, the duration of dosing correlated positively with nephrotoxicity incidence, as did treatment with furosemide, old age, and liver disease. 

Bertino JS Jr, Booker LA, Franck PA, Jenkins PL, Franck KR, and Nafziger A. 1993. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J/nfecfD/s 167 173-179. 

Sepsis is the most frequent cause of AKI in intensive care units [78,79]. Moreover, when sepsis is associated with AKI the mortality increases dramatically [78]. The incidence of AKI increases even further in patients with septic shock. Also, the use of nephrotoxins e.g. aminoglycosides,, amphotericin B in septic patients may precipitate or worsen the AKI. 

Recently, Perez Gutthann et al. [32] evaluated the incidence of NSAID-induced AKI from a population-based, case control study using data from Canada. Over 200, 000 health plan members were included because they had filled at least 1 prescription for NSAIDs during the 5-year interval. The crude incidence for AKI requiring hospitalization was 1.7/100, 000 persons. Current NSAID use increased risk of AKI 4 fold, a risk that equaled the risk associated with other known nephrotoxins, e.g. aminoglycosides, contrast media. The risk of AKI was especially high... 

Infections are a frequent cause of morbidity in the immunocompromised cancer patients and often necessitate antibiotic therapy. The use of certain bread-spectrum antibiotics, which are potentially nephrotoxic by themselves, may add to the renal toxicity of the anticancer agents. Clinically, the incidence of nephrotoxicity has heen recognized to be greater in patients receiving cisplatin in combination with aminoglycosides than in patients receiving cisplatin alone [46]. 

Approximately 10-26% of human patients reportedly develop nephrotoxicosis associated with aminoglycoside therapy. Individual cases of aminoglycoside nephrotoxicity have been reported in horses but the incidence is not known. 

Some drugs may be less toxic in pediatric patients than in adults. Aminoglycosides appear to be less toxic in infants than in adults. In adults, aminoglycoside toxicity is related to both peripheral compartment accumulation and the individual patient s inherent sensitivity to these tissue concentrationsAlthough neonatal peripheral tissue compartments for gentamicin have been reported to closely resemble those of adults with similar renal function, gentamicin is rarely nephrotoxic in infants. This dissimilarity in the incidence of nephrotoxicity implies that newborn infants may have less inherent tissue sensitivity for toxicity than adults. 

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