EFFICACY AND SAFETY OF ONCE-DAILY AMIKACIN IN COMBINATION WITH CEFTAZIDIME IN CRITICALLY ILL ADULTS WITH SEVERE GRAM-NEGATIVE INFECTIONS

Forty critically ill adult patients with severe Gramnegative infection were treated with once-daily amikacin combined with ceftazidime. The mean age was 56.6 +/- 19 years and mean APACHE II score was 22.7 +/- 6 .6. Forty percent of patients required mechanical ventilation. The mea n creatinine clearance at onset of therapy was 59.4 +/- 28 ml/min. All bacterial isolates were sensitive to amikacin. Fixed doses of amikaci n 15 mg/kg, 12 mg/kg, and 8 mg/kg body weight were given once daily to patients with estimated creatinine clearance of > 80 ml/min., 50-80 m l/min., and < 50 ml/min, respectively. Ferry-two causative gram-negati ve bacteria were isolated from 40 patients.:The most common bacteria w ere Pseudomonas aeruginosa (18), and Escherichia coli (10). Overall cl inical success and bacteriological eradication occurred in 85% and 87. 5% of patients; 78.9% and 79% of patients with hospital-acquired infec tions; 90.5% and 95.2% of patients with community-acquired infections; and 62.5% and 81.3% of patients requiring mechanical ventilation, res pectively. Therapeutic failure was documented in 15% of patients. Deat h due to infection was scored in two patients. The remaining were all due to persistence of the initial causative bacteria in patients with hospital-acquired infections. Persistence was documented with Ps. aeru ginosa (2), Serratia spp. (I), and Acinetobacter spp. (I). Overall mor tality occurred in 22.5% patients. Death unrelated to infection occurr ed in 7 patients. There was no clinical evidence of ototoxicity in any of our patients, however, nephrotoxicity was documented in 5%. In con clusion, once-daily amikacin combined with ceftazidime is practical, e fficacious and probably safe in critically ill infected patients.