Aminoglycoside Of Choice Research Articles

Intravenous aminoglycoside usage and monitoring of patients with cystic fibrosis in Australia. What's new?

The aim of this study was to determine the current situation regarding aminoglycoside use and monitoring in patients with cystic fibrosis (CF) throughout Australia. A questionnaire was sent out to all CF units. Information gathered included patient characteristics, aminoglycoside use, dosing, therapeutic drug-monitoring methods, toxicity monitoring and incidence of occurrence. Responses were obtained from 27 of the 28 units identified. Tobramycin was the aminoglycoside of choice. All but three centres were using once-daily dosing for aminoglycoside administration. Initial dosing in tobramycin-naïve patients was based on bodyweight (range 7-12 mg/kg). Patients being readmitted were mainly prescribed the dose that they had received on their previous admission. All units gave i.v. doses by infusion with five units using bolus dosing as well. The method of therapeutic drug monitoring varied greatly. A computer programme was used by 15 units. Toxicity monitoring usually coincided with therapeutic drug monitoring. Nephrotoxicity was reported as having occurred in 13 units and ototoxicity in 15 units. The highest incidence of toxicity was ototoxicity in 20% of patients in one CF unit. Aminoglycoside dosing regimens have changed since the last survey was carried out in 1999. There has been an increase in the use of once-daily dosing from 54 to 88% of units. The reporting of both ototoxicity and renal toxicity has also increased (from 27 to 75% and from 19 to 65%, respectively). Standardization of management protocols for antibiotic use and patient monitoring may help reduce the risk of cumulative toxicity to aminoglycosides in CF patients.

AMINOGLYCOSIDE USE AND THE SUSCEPTIBILITY OF GRAM-NEGATIVE PATHOGENS IN A NEONATAL INTENSIVE CARE UNIT 1756

The extensive use of aminoglycosides is associated with selection for resistant bacteria. Therefore, aminoglycoside use and the susceptibility of gram-negative bacteria (GNB) are monitored in our neonatal intensive care unit(NICU). We previously reported on the exclusive use of amikacin (AMK) in our nursery from 11/80 through 12/85 (Ped Inf Dis J. 6:461,1987). From 1/86 - 9/91 AMK continued to be the aminoglycoside of choice (period I). During period I, there were 5,836 admissions and AMK was used for 24,025 of 24,111 total aminoglycoside patient days (99.6%). GNB were isolated from 189 of 14,961 clinical specimens cultured during period I. 1.1% of the gram-negative isolates were amikacin-resistant and 2.7% were gentamicin-resistant.

Aminoglycoside therapy

The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis and Pseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularemia and bubonic plague. Several experimental studies support a once-daily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice.

The Aminoglycosides: Streptomycin, Kanamycin, Gentamicin, Tobramycin, Amikacin, Netilmicin, and Sisomicin

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides remain useful in the treatment of serious, hospital-acquired, gram-negative bacillary infections, especially those caused by Pseudomonas aeruginosa. Formidable nephrotoxicity and ototoxicity have limited the use of neomycin to topical or oral administration. Widespread antimicrobial resistance among Enterobacteriaceae has restricted the use of streptomycin and kanamycin to a few specific clinical situations. Gentamicin, tobramycin, and amikacin are active against a wide range of Enterobacteriaceae and many P. aeruginosa organisms. In medical centers where gentamicin resistance is prevalent, amikacin is the aminoglycoside of choice. Fortunately, amikacin resistance has not seemed to increase substantially, even in institutions where usage has been extensive for a long period. No new aminoglycoside has proved to be superior to amikacin.

A one year survey on the epidemiology of aminoglycoside resistance in a general hospital: influence of amikacin.

SummaryIn a 15 month period we have studied the epidemiology of aminoglycoside resistance in ai general hospital. We determined the effect of preferential amikacin usage on the resistance levels of amikacin, gentamicin, tobramycin, netilmicin and dibekacin. The resistance levels’ to each of these antibiotics were monitored in a> 3 month baseline phase during which amikacin usage was less than 1 %. During the remainder 12 months, amikacin was the aminoglycoside of choice and in this period no significant change in aminoglycoside resistance was noted. Nevertheless some changes in the combined resistance were found. From the aminoglycoside resistant strains only 8.8 % showed resistance to amikacin. Isolated amikacin resistance was not found and amikacin resistant strains showed cross-resistance to nearly all the other aminoglycosides.

Netilmicin (Netromycin, Schering-Plough).

Netilmicin sulfate, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside recently released for use in Canada and not yet released in the U.S. Its place in therapeutics, compared with gentamicin (G), tobramycin (T), and amikacin (A), is not yet established. Preliminary work in animals has suggested a lower incidence of nephrotoxicity and ototoxicity than with other aminoglycosides, and in vitro work has suggested some activity against G/T-resistant organisms. However, netilmicin appears to be virtually identical to G,T, and A in antimicrobial spectrum (except for its poorer activity against P. aeruginosa), human toxicity, and clinical use. For G/T-resistant organisms, amikacin is still the aminoglycoside of choice. In summary, netilmicin has not been demonstrated to have significant advantages over other aminoglycosides (G,T,A), and it is more expensive; thus, its potential value is limited.

355 RECOMMENDED AMIKACIN DOSES IN NEWBORNS OFTEN PRODUCE EXCESSIVE SERUM LEVELS

Emergence of a multiply drug resistant Enterobacter cloacae during a 7 week period in 1980 resulted in serious systemic disease in 4 infants and a high colonization rate in other infants in a newborn intensive care unit. Amikacin was employed as the aminoglycoside of choice in the initial treatment of suspected sepsis until the organism disappeared from the unit. Peak and trough serum amikacin levels were available in 18 infants. Recommended doses (7.5-10mg/kg loading; 15mg/kg bid IV) were given to 5 infants 1000gm infants (p = NS). These data show that surprisingly excessive blood levels of amikacin are likely in infants < 1000gm and may also occur in larger infants using currently recommended dosage schedules (J. Pediatr. 91:358, 1977). These unexpected findings emphasize the need to monitor drug levels and individualize therapy in very low birthweight infants.

Animal model distinguishing in vitro from in vivo carbenicillin-aminoglycoside interactions.

Aminoglycosides and carbenicillin are frequently co-administered to patients with serious gram-negative infections. Aminoglycosides are inactivated by carbenicillin in vitro, and a loss of antibacterial activity of both antibiotics results. Although these interactions are presumed to occur in vivo, previous studies have not used assay methodology that can distinguish inactivation occurring prior to and during microbiological assay from inactivation in vivo. To address this problem, we gave seven bilaterally nephrectomized mongrel dogs doses designed to achieve simultaneous therapeutic serum concentrations of aminoglycosides and carbenicillin. Serum samples were tested by radioimmunoassay on three occasions: immediately, to determine in vivo interactions, and at 24 h and 1 week to assess the time course of in vitro inactivation. In comparison with immediate radioimmunoassay, gentamicin and tobramycin concentrations decreased by 39 and 53%, respectively, when assayed at 24 h (P < 0.05) and by 75 and 82% when assayed at 7 days (P < 0.001). In contrast, amikacin concentrations were reduced by only 9 and 30% at 24 h and 7 days. Tobramycin concentrations were also determined by immediate microbiological assay and were found to be similar to those in samples stored for 24 h before radioimmunoassay. Immediate radioimmunoassay demonstrated that carbenicillin reduced in vivo serum half-lives of gentamicin and tobramycin by 40% (P < 0.05). The half-life of amikacin in vivo was not significantly altered. In the presence of carbenicillin, amikacin was the most stable aminoglycoside both in vivo and in vitro, and it is the aminoglycoside of choice in patients with renal failure who require this combination.

Drug therapy reviews: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics, part 4: Aminoglycosides

The aminoglycoside antibiotics are reviewed with regard to mechanism of action, bacterial resistance, antimicrobial spectrum, combinations with other agents, pharmacology, dosages in patients with normal and impaired renal function, adverse reactions, therapeutic use, prophylatic use and selection. Streptomycin is suggested in the therapy of tuberculosis, brucellosis, tularemia and yersinia infections; several of these require the coadministration of another agent. The choice between streptomycin and gentamicin for combination therapy of enterococcal endocarditis may be simplified by knowledge of the prevalence of high-level streptomycin-resistant strains in the hospital or by use of an in vitro screening test. Neomycin is the agent used orally in the treatment of hepatic encephalopathy. Paromomycin is indicated only for the treatment of amebic infections. The major difference among gentamicin, tobramycin and amikacin lies in the low but increasing prevalence of gram-negative bacilli which are resistant to gentamicin and tobramycin and susceptible to amikacin. In those institutions in which gentamicin-resistant strains are of concern, amikacin is the aminoglycoside of choice in high-risk patients until the infecting bacterium has been determined.