title: Efficacy and safety of once-daily amikacin in combination with ceftazidime in critically ill adults with severe gram-negative infections.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, King Khalid University Hospital (KKUH) and College of Medicine, Riyadh, Saudi Arabia.
authors.forename: D F
authors.initials: DF
authors.lastname: Fayed
authors.forename: N S
authors.initials: NS
authors.lastname: Dahmash
authors.forename: A H
authors.initials: AH
authors.lastname: al-Zeer
authors.forename: A M
authors.initials: AM
authors.lastname: Shibl
authors.forename: S O
authors.initials: SO
authors.lastname: Huraib
authors.forename: H
authors.initials: H
authors.lastname: Abu-Aisha
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000627:therapeutic use; D002442:Ceftazidime / Q000627:therapeutic use; D016638:Critical Illness; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000583:Amikacin; D002442:Ceftazidime