Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients.

OBJECTIVES: This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients. METHODS: An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model. RESULTS: A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01 (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication [OR=2.84 (0.76-10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)]. CONCLUSIONS: The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.

A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients.

BACKGROUND: Empirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients. METHODS: Ninety-five patients with febrile neutropenia were included in a prospective, controlled, randomized, non-blind, comparative study. Patients were randomly assigned to one of the treatment groups (63 to the ceftriaxone/ciprofloxacin group and 32 to the ceftazidime/amikacin group) and evaluated as successes or failures according to defined criteria. Daily assessments were made of all patients and all adverse events were recorded. RESULTS: The overall incidence of documented infections was 45.9%: 24/47 (51.1%) in the ceftriaxone/ciprofloxacin group and 10/27 (37%) in the ceftazidime/amikacin group. There was a significant difference in clinical efficacy between the groups (p=0.011) at the end of therapy. The ceftriaxone/ciprofloxacin group had an overall incidence of resolution and improvement of 95.7% in comparison to 75% in the ceftazidime/amikacin group. Thirty-nine organisms were isolated, 26 (66.67%) gram-negative and 13 (33.33%) gram-positive. There was a low incidence of adverse events in both groups. CONCLUSION: The combination of a single, high dose of ceftriaxone plus ciprofloxacin daily was more effective than the standard combination of thrice daily ceftazidime plus amikacin with no significant adverse events in either group.

Randomized trial comparing oral ciprofloxacin plus penicillin V with amikacin plus carbenicillin or ceftazidime for empirical treatment of febrile neutropenic cancer patients.

Aminoglycoside-containing combination therapy has been the standard empirical approach for febrile neutropenic cancer patients. With the advent of the broad-spectrum oral fluoroquinolones, it is now possible to evaluate an initial empirical alternative therapy. A prospective randomized study was conducted comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus carbenicillin or ceftazidime (group B). Main criteria for eligibility were febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions); 55 episodes were assigned to group A and 48 to group B. Most febrile episodes were of unknown origin. There were 10 microbiologically documented episodes with two cases of bacteremia. Both regimens were well tolerated. Oral regimen was substantially cheaper than parenteral regimen. Treatment success without regimen modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08-0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to standard parenteral therapy in this low-risk group of neutropenic patients, with unquestionable cost containment.