Amikacin Group Research Articles

Choilnergic mechanisms in epileptogenic seizures development

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded incomclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hosp[italized patients with severe infection.PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzyl-penicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations.RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p<0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxocity appeared to be significantly less with amikacin (4% versus 12%, p<0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin.CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Changes in the character of seizures induced by ehectrostimuiaticn of amygdaia in cats after treatment with choiinotropic drugs

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded incomclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hosp[italized patients with severe infection.PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzyl-penicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations.RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p<0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxocity appeared to be significantly less with amikacin (4% versus 12%, p<0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin.CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Empirical monotherapy with meropenem in serious bacterial infections

A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.

Effects of aminoglycoside antibiotics on the auditory brainstem response and post rotatory nystagmus in rats

Effects of three aminoglycoside antibiotics, amikacin (AMK), tobramycin (TOB), and gentamicin (GM), on the auditory and vestibular functions were assessed in rats, the most frequently used species in toxicity studies. Chronic electrodes for auditory brainstem response (ABR) recording were implanted on the epidural surface, and those for post rotatory nystagmus (PRN) were implanted at the nictitating membrane and the outer canthus. AMK, TOB, and GM were given intramuscularly twice daily for 3–4 weeks at a daily dose of 350, 150, and 100 mg/kg, respectively. The amplitude of each wave of the ABR was decreased or disappeared in the groups treated with AMK, TOB, and GM. In the PRN, the duration of the nystagmus was decreased in the TOB group and completely lost in the GM group. No abnormality was observed in the PRN in the AMK group. These results were similar to those reported in the ototoxicity studies of these drugs in guinea pigs and indicate that ototoxicity can be evaluated in rats as successfully as in guinea pigs by this procedure.

Prospective study of amikacin versus netilmicin in the treatment of severe infection in hospitalized patients

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded incomclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hosp[italized patients with severe infection. PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzyl-penicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations. RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p<0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxocity appeared to be significantly less with amikacin (4% versus 12%, p<0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin. CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Single-dose amikacin treatment of first childhood E. coli lower urinary tract infections

Urinary tract infection in children is usually treated with orally administered antibiotics for 10 to 14 days. Because of the unreliability of patient compliance with prescribed medications and because single-dose aminoglycoside therapy has been shown to be effective in women with cystitis, we assessed the efficacy of single-dose amikacin for treatment of first episodes of Escherichia coli lower urinary tract infection in girls. Upper and lower urinary tract infections were presumptively differentiated by simple criteria such as clinical symptoms, fever, and erythrocyte sedimentation rate. Fifty-four girls (ages 1 to 12 years) with two positive urine cultures (greater than 10(5) CFU/ml E. coli) were assigned by a table of random numbers to receive treatment with either sulfisoxazole 150 mg/kg/day orally for 10 days or a single dose of amikacin 7.5 mg/kg intramuscularly. Six of 23 patients (26%) in the amikacin group and four of 21 (19%) in the sulfisoxazole group had at least one positive urine culture within 40 days after completion of therapy. This difference was not statistically significant (P greater than 0.5). This suggests that a single dose of amikacin is as effective as a 10-day course of sulfisoxazole in the treatment of presumed first lower urinary tract infection in girls. Additional potential advantages of single-dose therapy are fewer side effects and less toxicity, excellent compliance, and reduced potential for selecting resistant organisms.

Short-course aminoglycoside therapy in patients with spinal cord injury Standard dose versus low dose

Twenty-nine patients with spinal cord injury and asymptomatic urinary tract infection were treated with standard or reduced doses of tobramycin and amikacin. The patients received five days of intramuscular antibiotics. Most of the patients in the tobramycin groups had Pseudomonas aeruginosa infection and most of those in the amikacin group had either Proteus rettgeri or Providencia stuartii infections. Only 1 patient had a positive urine antibody coating test. High antibiotic concentrations were demonstrated in the urine of all patients during therapy. Urine cultures were obtained two and seven days after completion of therapy. Forty-eight per cent of the patients were cured, while 31 per cent showed persistence or relapse, and 21 per cent had reinfection with other bacteria. No significant differences in results were observed between the standard-dose and low-dose regimens and between the amikacin and tobramycin groups. The low success rate of the regimens used may indicate the need to evaluate alternative therapeutic regimens to treat urinary tract infections in this special group of patients.

Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer

A randomized trial of ticarcillin plus gentamicin (group 1), ticarcillin plus amikacin (group 2) and ticarcillin plus netilmicin (group 3) as empiric antibiotic therapy in patients with granulocytopenia and cancer was carried out at the Baltimore Cancer Research Center. The response rate for all infections was 97 per cent in group 1, 91 per cent in group 2 and 95 per cent in group 3. Patients with bacteremias showed improvement in 93 per cent (group 1), 78 per cent (group 2) and 82 per cent (group 3) of cases. All failures were among patients with gram-negative bacteremias. Both antibiotic susceptibility of the bacteremic organism and granulocyte recovery correlated with patient improvement. Nephrotoxicity and ototoxicity were rare and were not significantly different in the three groups of patients. Therefore, ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin appear to be equally efficacious and minimally toxic in this patient population. Excellent over-all results can be expected with these combinations provided the etiologic agent is susceptible.

Comparison of amikacin and gentamicin in the treatment of urinary tract infections

The use of standard doses of gentamicin and small doses of amikacin was compared in the treatment of urinary tract infections in 30 adults. Patients were prospectively randomized to treatment with 3 to 4 mg/kg/day of gentamicin (group 1) or 9 mg/kg/day of amikacin (group 2). The age and sex of the patient, and the duration of the treatment were similar in the two groups. Eleven of the 15 patients in each group were diagnosed clinically as having pyelonephritis. The majority of patients in both groups either required a permanent Foley catheter or had associated diseases predisposing to urinary tract infections. In nine of 15 patients in each group, the bacterial etiology was Pseudomonas aeruginosa. Bacteriologic cures were achieved in nine of 15 patients treated with gentamicin (group 1) and in 10 of 15 patients treated with amikacin (group 2). The mean peak concentration of gentamicin was 5.4 μg/ml (range: 2 to 13 μg/ml), and the mean peak concentration of amikacin was 11.2 μg/ml (range: 8.2 to 19.6 μg/ml). In the patients treated with gentamicin, there was no correlation between the peak serum concentration of gentamicin, the in vitro minimum inhibitory concentration and the bacteriologic response to treatment. No direct evidence of antibiotic-induced toxicity was detected. These results suggest that a reduced amikacin dosage schedule gave results essentially equivalent to standard doses of gentamicin in adults with urinary tract infections.