Systemic mycoses in the immunocompromised host: an update in antifungal therapy.

Despite significant advances in the management of immunosuppressed patients, invasive fungal infections remain an important life-threatening complication. In the last decade several new antifungal agents, including compounds in pre-existing classes (new generation of triazoles, polyenes in lipid formulations) and novel classes of antifungals with a unique mechanism of action (echinocandins), have been introduced in clinical practice. Ongoing and future studies will determine their exact role in the management of different mycoses. The acceleration of antifungal drug discovery offers promise for the management of these difficult to treat opportunistic infections.

Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial.

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: Thirty-one patients with MCC who had not received prior therapy for metastatic disease were enrolled. Their median age was 60 years; performance status (World Health Organization) was 0 in 12, 1 in 14, and 2 in five patients; 19 patients (61%) had prior surgery, and 14 (45%) had adjuvant chemotherapy. CPT-11 was administered on day 1 at 150 mg/m(2) as a 90-minute intravenous (IV) infusion; L-OHP was administered on day 2 at 65 mg/m(2) as a 2-hour IV infusion; and on days 2 and 3, LV 200 mg/m(2) preceded 5-FU administration of 400 mg/m(2)/d initial IV bolus dose followed by 600 mg/m(2)/d 22-hour IV continuous infusion. The regimen was repeated every 2 weeks. RESULTS: All patients were assessable for toxicity and 30 for response to treatment. Complete response was achieved in two patients (6.5%) and partial response in 16 (51.6%) (overall response rate, 58.1%; 95% confidence interval, 40.7% to 75.4%); eight patients (25.8%) had stable disease, and five (16.1%) had disease progression. The median duration of response was 9 months, and the median time to disease progression was 13 months. Neutropenia grade 3 to 4 occurred in 14 patients (45%) and febrile neutropenia in two (6%). Diarrhea grade 3 to 4 was observed in 10 patients (32%), neurotoxicity grade 3 to 4 in three (9%), and asthenia grade 3 in two (10%). No treatment-related death has occurred. CONCLUSION: The triplet combination of 5-FU/LV + CPT-11 + L-OHP is a highly active regimen with manageable toxicity as front-line treatment in MCC.

Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: Retrospective analysis of 245 episodes.

BACKGROUND: Pseudomonas aeruginosa bacteremia is a serious and possibly fatal condition in patients with cancer. OBJECTIVES: To ascertain the frequency, demographics, and predisposing factors for P. aeruginosa bacteremia in patients with cancer and to determine the efficacy of various therapeutic regimens. SUBJECTS AND METHODS: Patient records of the Clinical Microbiology Laboratory, The University of Texas, M. D. Anderson Cancer Center, Houston, were reviewed. From January 1, 1991, through December 31, 1995, 245 eligible cases of P. aeruginosa bacteremia were identified. We examined the patient records for the underlying malignant neoplasm and its management, symptoms and signs of infection, culture results of appropriate specimens, antibiotic therapy, and outcome. We also compared our present experience with a previous analysis from this institution covering the period from January 1, 1972, to December 31, 1981. RESULTS: The incidence of P. aeruginosa bacteremia has decreased compared with the previous study (2.8 vs 4.7 cases per 1000 admissions). It was most common in patients with acute leukemia (55 of 1000 registrations), and the frequency in this disease has not changed. Half of the patients were not in the hospital when they developed their infection. The overall cure rate was 80%, which was a significant (P<.001) increase compared with the 62% cure rate in the previous study. In this study, no significant difference in the cure rates was observed between monotherapy with a beta-lactam and combination therapy overall (P = .72), and in patients with shock (P = 1.0) and those with pneumonia (P = .60). The patients' initial neutrophil counts were not of prognostic value; however, the cure rate depended on subsequent changes in neutrophil count during therapy. CONCLUSIONS: The frequency rate of P. aeruginosa bacteremia has decreased in patients with solid tumors but has remained unchanged in patients with acute leukemia. Antibiotic regimens for empirical therapy of neutropenic patients and especially patients with acute leukemia should still provide coverage against P. aeruginosa.

Efficacy of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The efficacies of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin, each as monotherapy, were evaluated in a rabbit model of induced left-sided Pseudomonas aeruginosa endocarditis. Therapy started 48 h after infection and lasted 5 days. All agents were given intramuscularly; amikacin at 7 mg/kg/12 h, and each quinolone at 35 mg/kg/12 h. All animals survived except for 1 of the group that received amikacin, and 2 of the untreated control group. No sterile vegetations were found in the untreated group and the group of fleroxacin, while 3 animals from the amikacin, ofloxacin, and enoxacin groups, and 2 from the ciprofloxacin and pefloxacin groups had sterile vegetations. All agents used significantly reduced the number of CFU per gram of vegetation versus untreated controls. Enoxacin and ciprofloxacin were equipotent and more effective than pefloxacin, ofloxacin and amikacin. Fleroxacin had a weaker activity.