Mycoses

Candida

Resistance of Candida spp. to fluconazole is the subject of an increasing number of reports in the literature. However, a nationwide study of Candida bloodstream isolates indicates that fluconazole susceptibility has not decreased in recent years. (Abstract J-112.) The situation at individual institutions may, of course, differ.

The predictive value of in vitro susceptibility testing of Candida spp. remains a matter for further examination. A retrospective survey of 90 patients with candidemia was unable to find a correlation between the results of in vitro susceptibility testing and outcome of therapy. (Abstract J-145a.)

A randomized trial found that fluconazole (100 mg qd for 10 days) was superior to itraconazole (200 mg capsules qd for 14 days) in the treatment of non-neutropenic cancer patients with oropharyngeal candidiasis. While the clinical response rates were similar (86.5% vs 80.1%; P = 0.18), the fluconazole recipients had a higher rate of microbiological cure (80.1% vs 68.2%; P = 0.03). (Abstract MN-21.)

A retrospective analysis found that, of 76 patients with candidemia who completed a course of antifungal therapy without complication, delayed manifestations of infection were uncommon, irrespective of duration of therapy (26% were treated for < 2 weeks), occurring in only two patients. One patient treated for three weeks subsequently presented with spondylodiscitis, and one treated for 22 weeks had persistent infection due to an infected kidney stone. (Abstract J-97.) This suggests that relatively brief courses of antifungal therapy may be adequate in many patients with candidemia.

G-CSF (and GM-CSF) increases PMN killing of intracellular Candida and enhances the activity of fluconazole. Fifty-one non-neutropenic patients with fever and candidemia or proven deep-seated candidiasis were randomized to receive, in addition to fluconazole, either G-CSF (filgrastim) or placebo daily. All-cause mortality at 28 days was similar in the two groups, but there was a trend toward more rapid resolution of infection in the G-CSF recipients. This difference did not reach statistical significance, perhaps because of the small sample size. There was a correlation between increasing WBC and shorter time to resolution. (Abstract J-100.)

Aspergillus

The keys to a favorable outcome in the patient with invasive aspergillosis are early diagnosis and institution of therapy. CT scans may be helpful in diagnosis. Thoracic CT demonstrated a "halo" surrounding a nodule in 21 of 21 histologically proven cases of invasive pulmonary aspergillosis in neutropenic patients, although its appearance was transient (usually less than 5 days) in some patients who had multiple CTs. (Abstract J-40.)

Sixty-three (1.2%) of 4968 ICU patients over approximately 2.5 years had Aspergillus recovered from their sputum. Infection was definitely (demonstrated by tissue examination) or probably present in 17, representing 27% of those with a positive culture. All but two of these 17 were severely immunocompromised; all 17 died. Only 38% of the patients believed to be simply colonized with Aspergillus were severely immunocompromised. (Abstract K-15.)

Terbinafine and itraconazole were found to be synergistic in vitro against Aspergillus fumigatus. (Abstract E-63b.)

Cryptococcus

Secondary resistance to fluconazole of C. neoformans from AIDS patients has been reported. Primary resistance in an immunocompetent host has not, to my knowledge, been previously identified, until now. An isolate of C. neoformans, clinically and microbiologically (MIC > 256 mcg/mL) resistant to fluconazole, was recently isolated from the CSF of an apparently immunocompetent patient with meningitis who had never previously received fluconazole. (Abstract J-24.)

Miscellaneous Mycoses

Ninety patients with paracoccidioidomycosis, 71 treated with trimethoprim-sulfamethoxazole and 19 with itraconazole, were retrospectively analyzed. The cure rates in the two cohorts were, 94% and 95%, respectively, despite the fact that those treated with itraconazole appeared to have more severe infection. However, the mean duration of itraconazole therapy was only seven months, while trimethoprim-sulfamethoxazole was administered for a mean of 24 months. (Abstract J-142.)

Terbinafine was found to be synergistic with either itraconazole or fluconazole against Pseudallescheria boydii in vitro. (Abstract J-115.) Terbinafine was effective in the treatment of 17 (89%) of 19 patients with cutaneous or lymphocutaneous sporotrichosis. (Abstract J-96.)

An outbreak involving 23 patients with fungemia due to the dematiaceous fungus, Exophiala janselmi, a "black yeast," which causes phaeohyphomycosis occurred in Brazil. Most were severely immunocompromised. Although eight patients died, death was potentially due to fungemia in only one. (Abstract J-141.)

Chromoblastomycosis is a form of phaeohyphomycosis with chronic infection of the skin and subcutaneous tissues caused by several fungi that form characteristic "sclerotic bodies" in tissue and which is often recalcitrant to chemotherapy. Thirty patients with chromoblastomycosis due to Fonsecaea spp. (8 due to F. pedrosi), half of whom had failed previous therapy, were treated with itraconazole in doses of 200-400 mg daily. Eight of nine with mild disease were cured after a mean of 10.9 months of therapy, with no relapses observed after a mean of 31.2 months. Similarly, 11 of 12 patients with moderately severe disease were cured after an average of 12.9 months of therapy; one patient relapsed after 6.3 months of follow-up. While five patients had significant improvement, only four of the nine with severe infection had apparent cure after a mean treatment duration of 30 months. One relapse occurred at 35 months; this patient responded to retreatment. (Abstract J-103.)

Antifungal Agents

Voriconazole, a monotriazole antifungal agent in clinical trials, was more active in vitro (MIC90, 0:12 mcg/mL) against isolates of Cryptococcus neoformans than either itraconazole (MIC90, 0.5 mcg/mL) or fluconazole (MIC90, 8.0-16 mcg/mL) and retained activity against isolates with fluconazole MICs of more than 16 mcg/mL. (Abstract J-1.) Voriconazole was more active in vitro against C. albicans and other Candida species, than fluconazole. Its MIC90 against C. glabrata was 0.12 mcg/mL and against C. krusei was 0.5 mcg/mL; the comparable results for fluconazole were 16 mcg/mL and 32 mcg/mL, respectively. (Abstract J-6.)

Coadministration of omeprazole significantly reduced the Cmax of itraconazole from 1.80 to 1.29 mcg/mL; P < 0.01). The Cmax of the active metabolite, hydroxyitraconazole, was not affected. (Abstract A-88a.)

Paclitaxel antagonized the in vitro activity of amphotericin B against an array of fungal pathogens. (Abstract J-153.)

Mycobacteria

Obtaining sputum specimens from children with suspected pulmonary tuberculosis is always difficult and sometimes impossible, leading to the use of gastric aspirates instead. However, in this study, the diagnostic yield of specimens obtained from children for acid fast smear and culture by nasopharyngeal aspiration was equivalent to that of specimens obtained by gastric aspiration. (Abstract D-1127.)

Neither rifampin nor ethambutol are significantly removed by hemodialysis, while isoniazid and pyrazinamide are removed. (Abstract A-96.)

A pseudoepidemic of Mycobacterium chelonae infection was associated with contamination of bronchoscopes and automated cleaning machines. After attempts to eradicate the contamination by increasing the glutaraldehyde concentration used during the cleaning cycle to 2% failed, it was determined that the M. chelonae was resistant to glutaraldehyde. Paracetic acid is suggested as a possible alternative agent. (Abstract K-146.)