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 Gram-negative 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 mean creatinine clearance at onset of therapy was 59.4 +/- 28 ml/min. All bacterial isolates were sensitive to amikacin. Fixed doses of amikacin 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 ml/min., and < 50 ml/min, respectively. Forty-two causative gram-negative bacteria were isolated from 40 patients. The most common bacteria were Pseudomonas aeruginosa (18), and Escherichia coli (10). Overall clinical success and bacteriological eradication occurred in 85% and 87.5% of patients; 78.9% and 79% of patients with hospital-acquired infections; 90.5% and 95.2% of patients with community-acquired infections; and 62.5% and 81.3% of patients requiring mechanical ventilation, respectively. Therapeutic failure was documented in 15% of patients. Death 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. aeruginosa (2), Serratia spp. (1), and Acinetobacter spp. (1). Overall mortality occurred in 22.5% patients. Death unrelated to infection occurred in 7 patients. There was no clinical evidence of ototoxicity in any of our patients, however, nephrotoxicity was documented in 5%. In conclusion, once-daily amikacin combined with ceftazidime is practical, efficacious and probably safe in critically ill infected patients.