Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005 from children and adults.

The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy.

Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group.

BACKGROUND: As prophylaxis against influenza in families, amantadine and rimantadine have had inconsistent effectiveness, partly because of the transmission of drug-resistant variants from treated index patients. We performed a double-blind, placebo-controlled study of inhaled zanamivir for the treatment and prevention of influenza in families. METHODS: We enrolled families (with two to five members and at least one child who was five years of age or older) before the 1998-1999 influenza season. If an influenza-like illness developed in one member, the family was randomly assigned to receive either inhaled zanamivir or placebo. The family member with the index illness was treated with either 10 mg of inhaled zanamivir (163 subjects) or placebo (158) twice a day for 5 days, and the other family members received either 10 mg of zanamivir (414 subjects) or placebo (423) once a day as prophylaxis for 10 days. The primary end point was the proportion of families in which at least one household contact had symptomatic, laboratory-confirmed influenza. RESULTS: The proportion of families with at least one initially healthy household contact in whom influenza developed was smaller in the zanamivir group than in the placebo group (4 percent vs. 19 percent, P<0.001); the difference represented a 79 percent reduction in the proportion of families with at least one affected contact. Zanamivir provided protection against both influenza A and influenza B. A neuraminidase-inhibition assay and sequencing of the neuraminidase and hemagglutinin genes revealed no zanamivir-resistant variants. Among the subjects with index cases of laboratory-confirmed influenza, the median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivir was well tolerated. CONCLUSIONS: When combined with the treatment of index cases, prophylactic treatment of family members with once-daily inhaled zanamivir is well tolerated and prevents the development of influenza. In this study there was no evidence of the emergence of resistant influenza variants.

5-HT3 receptor antagonists in the control of cisplatin-induced delayed emesis.

Two large randomized, double-blind, placebo-controlled studies with an appropriate study design have been conducted to fully evaluate the efficacy of ondansetron in the control of cisplatin-induced delayed emesis. These studies show that ondansetron and particularly ondansetron plus dexamethasone have moderate efficacy in the control of cisplatin-induced delayed emesis and nausea. The benefit of ondansetron, with or without dexamethasone, may be greatest in patients with incomplete control of acute emesis. The efficacy of ondansetron in this setting compared to its greater efficacy during the acute phase of emesis induced by cisplatin and the more prolonged phases of acute emesis induced by cyclophosphamide and carboplatin indicates that non-5-HT3-mediated emetic mechanisms maybe are relatively more important in the delayed phase of emesis following cisplatin.

Comparison of cefuroxime axetil and amoxicillin-clavulanate suspensions in treatment of acute otitis media with effusion in children.

Two hundred sixty-three pediatric patients from the ages of 3 months to 11 years were enrolled in a randomized, investigator-blinded, multicenter study comparing the clinical and bacteriological efficacies and safety of cefuroxime axetil suspension (CAE) with those of amoxicillin-clavulanate suspension (AMX-CL) in the treatment of acute otitis media with effusion. Patients received CAE at 30 mg/kg of body weight per day (n = 165) in two divided doses or AMX-CL at 40 mg/kg/day (n = 98) in three divided doses for 10 days. The primary pathogens among 200 isolates from pretreatment cultures of middle ear fluid were identified as follows: Haemophilus influenzae (39%), over a third of which were beta-lactamase positive; Streptococcus pneumoniae (34%); and Moraxella catarrhalis (16%). Pathogens were eradicated or presumed to be eradicated from 81% (95 of 118) and 76% (50 of 66) of bacteriologically evaluable patients in the CAE and AMX-CL groups, respectively. A satisfactory clinical response (cure or improvement with or without resolution of effusion) occurred in 113 (77%) of 146 clinically evaluable patients in the CAE group and in 66 (74%) of 89 evaluable patients in the AMX-CL group. Clinical failure or recurrence (within 2 weeks following the completion of treatment) occurred in 22 and 26% of CAE- and AMX-CL-treated patients, respectively. Drug-related adverse events occurred in 18% of CAE-treated patients, whereas they occurred in 39% of AMX-CL-treated patients (P < 0.001); diarrhea or loose stools was the most commonly reported adverse event (CAE, 12%; AMX-CL, 31%; P < 0.001). These results indicate that CAE given twice daily is as effective as AMX-CL given three times daily in the treatment of acute otitis media with effusion in pediatric patients, but CAE was associated with significantly fewer drug-related adverse events.

Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis.

The bacteriological and clinical efficacies of cefuroxime axetil suspension (20 mg/kg of body weight per day in two divided doses) were compared with those of penicillin V suspension (50 mg/kg/day in three divided doses) in a multicenter, randomized, evaluator-blinded study. Children aged 2 to 13 years with clinical signs and symptoms of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. Patients were assessed and samples from the throat for culture were obtained at the time of diagnosis, 3 to 7 days after the initiation of treatment, and 4 to 8 days and 19 to 25 days after the completion of 10 days of therapy. Of the 385 evaluable patients, GABHS were eradicated from 244 of 259 (94.2%) cefuroxime-treated patients and 106 of 126 (84.1%) penicillin-treated patients (P = 0.001). Complete resolution of the signs and symptoms present at the time of diagnosis was achieved in 238 of 259 (91.9%) cefuroxime-treated patients and 102 of 126 (81.0%) penicillin-treated patients (P = 0.001). Potential drug-related adverse events were reported in 7.0 and 3.2% of the cefuroxime- and penicillin-treated patients, respectively (P = 0.078). In the present study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriological and clinical efficacies than those of penicillin V suspension given three times daily to pediatric patients with acute pharyngitis and a positive throat culture for GABHS.

Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections.

A randomized, single-blind, multicenter study was conducted to evaluate the safety and efficacy of cefuroxime axetil and cefadroxil suspensions for the treatment of skin or skin structure infections in 287 children. Each drug was given at a dosage of 30 mg/kg of body weight per day in two divided doses. Staphylococcus aureus and Streptococcus pyogenes, or a combination of the two, were the primary pathogens isolated from infected skin lesions. A satisfactory bacteriological response (cure or presumed cure) was obtained in 97.1 and 94.3% of children in the cefuroxime axetil and cefadroxil groups, respectively (P greater than 0.05). Satisfactory clinical responses (cure or improvement) were more likely to occur in cefuroxime axetil recipients than in cefadroxil recipients (97.8 versus 90.3%; P less than 0.05). Both regimens were equally well tolerated, with adverse events occurring in 7.9 and 6.1% of cefuroxime axetil and cefadroxil recipients, respectively. There were more patients who refused to take cefuroxime axetil (7 of 189) than there were who refused to take cefadroxil (0 of 98), but the difference was not statistically significant (P = 0.1). In this study, cefuroxime axetil was at least as effective as cefadroxil in resolving skin and skin structure infections in children.

The safety, efficacy, and tolerability of cefuroxime axetil suspension in infants and children receiving previous intravenous antibiotic therapy.

The tolerability, safety, and efficacy of cefuroxime axetil suspension was studied in 36 children (aged 3 mo to 12 y) who had been hospitalized for respiratory tract or soft-tissue infections. After receiving parenteral antibiotics for a mean of 3.7 days, children were discharged home to receive cefuroxime axetil suspension at doses of 10, 15, or 20 mg/kg every 8 or 12 hours for a mean of 8.2 days. One child was lost to follow-up. Three of 35 evaluated patients were withdrawn from therapy because of adverse events, one of which was a drug-related hypersensitivity reaction. Of the 32 children who completed therapy, 9 developed mild reactions including oral thrush, diarrhea, or diaper dermatitis; none were withdrawn from therapy. Complete clinical cure occurred in 28 children (80 percent); 4 (11.4 percent) were clinically improved but still required an additional antibiotic within one week of completing therapy with cefuroxime axetil suspension. This favorable tolerability and safety of cefuroxime axetil suspension warrants further efficacy trials in pediatric patients.

Pharmacokinetics of cefuroxime axetil suspension in infants and children.

The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 micrograms/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including beta-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10- or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-verus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose.

Inosiplex for localized herpes zoster in childhood cancer patients: preliminary controlled study.

By multiple criteria, inosiplex-a reputed stimulator of virus-sensitized lymphocytes-had no demonstrable therapeutic effects in a preliminary controlled study of patients with localized herpes zoster and cancer. Lymphocytes from the six drug-treated patients were no more responsive to varicella-zoster antigen and phytohemagglutinin than were lymphocytes from seven patients who received a placebo.

Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia.

Fifty patients with P. carinii pneumonitis were randomized to receive either pentamidine isethionate or trimethoprim-sulfamethoxazole therapy. Those not responding favorably to the first drug after three or more days of therapy were changed to the alternate drug. Of the 26 patients initially treated with TMP-SMZ, 20 recovered (0.77)-17 after TMP-SMZ alone and three of nine who were crossed over to pentamidine. Of the 24 patients initially treated with pentamidine, 18 recovered (0.75)-14 of 15 who received only pentamidine and four of nine who were crossed over to TMP-SMZ. Abnormal values for blood urea nitrogen, creatinine, or glucose; inflammation at injection sites; or combination of these effects occurred in 14 of the 15 patients treated with pentamidine alone. Only one of the 17 patients treated with TMP-SMZ alone developed any of these abnormalities. This study shows that TMP-SMZ is as effective as pentamidine in the treatment of PCP, and that it offers the advantages of minimal adverse effects, oral administration, and ready availability.

A viremic phase for herpes zoster in children with cancer.

Eight childhood cancer patients with herpes zoster were serially tested for the presence of varicella-zoster virus in blood. Cell cultures of leukocyte-rich plasma from four patients were positive for the virus. In this study viremia was clearly related to dissemination of dermal lesions-the spread of zoster lesions outside an infected dermatome. The child with the longest viremic phase, five days, had the longest and most severe course of skin dissemination, as well as biochemical evidence of hepatitis. One patient with viremia had advanced embryonal carcinoma and died of disseminated tumor before her clinical course could be evaluated. These observations, the first to document a viremic phase for herpes zoster in immunosuppressed children, furnish an added criterion for evaluation of antiviral drugs and live-virus vaccines in the treatment and prevention of varicella-zoster infections.

Percutaneous transthoracic needle aspiration of the lung. Diagnosing Pneumocystis carinii pneumonitis.

Percutaneous transthoracic needle aspiration was performed on 228 occasions to obtain lung specimens from 202 patients with suspected Pneumocystis carinii pneumonitis. In 121 patients the diagnosis was established by identifying P carinii organisms in lung aspirates. Six patients whose aspirates did not contain P carinii were found to have the organism at autopsy. Findings from toluidine blue O and Gomori methenamine silver nitrate stains were equally satisfactory for detecting P carinii, but the percentage of specific diagnosis was higher when specimens were stained with both. Pneumothorax that required a thoracotomy tube occurred in 39 patients. Other infectious agents, either bacteria or fungi, were found in only four patients. Percutaneous pulmonary needle aspiration--when performed under fluoroscopic guidance--is a rapid and effective method for the diagnosis of P carinii pneumonitis.