Alan M. Stamm

Treatment of Systemic Mycoses with Ketoconazole: Emphasis on Toxicity and Clinical Response in 52 Patients: National Institute of Allergy and Infectious Diseases Collaborative Antifungal Study

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Cryptococcosis associated with low-dose methotrexate for arthritis

One patient with psoriatic arthritis and a second with rheumatoid arthritis were each treated with low-dose methotrexate (10 to 15 mg per week, orally) for more than a year before pulmonary cryptococcosis developed. These are the first case reports of opportunistic fungal disease during this treatment. Low-dose methotrexate may be more immunosuppressive than has been appreciated. Patients demonstrating pneumonitis while receiving this therapy should be carefully evaluated to rule out an infectious cause.

Ventilator-associated pneumonia and frequency of circuit changes

BACKGROUND The purpose of this research was to determine whether changing tubing circuits for mechanical ventilation less often than every 48 hours would allow maintenance of acceptably low rates for ventilator-associated pneumonia. METHODS A computer search of the MEDLINE database from 1986 through 1996 was performed, and abstracts for 1992 through 1996 from the annual meetings of the Association for Professionals in Infection Control and Epidemiology and the Society for Healthcare Epidemiology of America were examined. RESULTS Eight studies indicate that the interval between ventilator tubing circuit changes can be extended to 7 days without increasing the rate of ventilator-associated pneumonia. Furthermore, the rate can be maintained at or below 10 pneumonias per 1000 ventilator-days, the approximate median of the National Nosocomial Infections Surveillance System. There is very little evidence to suggest that these circuits can safely be changed at longer intervals. CONCLUSIONS The weight of the evidence indicates that breathing circuits should be changed every 7 days. This practice of routine changes should be abandoned only if additional studies demonstrate that prolonged use of the same breathing circuit is associated with low rates of ventilator-associated pneumonia.

A comparison of 3 metrics to identify health care-associated infections

BACKGROUND The best approach to measurement of health care-associated infection rates is controversial. METHODS We compared 3 metrics to identify catheter-associated bloodstream infection (CA-BSI), catheter-associated urinary tract infection (CA-UTI), and ventilator-associated pneumonia (VAP) in 8 intensive care units during 2009. We evaluated traditional surveillance using National Healthcare Safety Network methodology, data mining with MedMined Data Mining Surveillance (CareFusion Corporation, San Diego, CA), and administrative coding with ICD-9-CM. RESULTS A total of 65 CA-BSI, 28 CA-UTI, and 48 VAP was identified. Traditional surveillance detected 58 CA-BSI and no false positives; data mining identified 51 cases but 51 false positives; administrative coding documented 6 cases and 6 false positives. Traditional surveillance detected 27 CA-UTI and no false positives; data mining identified 17 cases but 19 false positives; administrative coding documented 3 cases and 1 false-positive. Traditional surveillance detected 41 VAP and no false positives; data mining identified 26 cases but also 79 false positives; administrative coding found 17 cases and 13 false positives. Overall sensitivities were as follows: traditional surveillance, 0.84; data mining, 0.67; administrative coding, 0.18. Positive predictive values were as follows: traditional surveillance, 1.0; data mining, 0.39; administrative coding, 0.57. CONCLUSION Traditional surveillance proved superior in terms of sensitivity, positive predictive value, and rate estimation.

Infections Caused by Fungi and Higher Bacteria

Deeply invasive and disseminated infections caused by fungi and higher bacteria are very uncommon complications of pregnancy. Candidiasis, aspergillosis, and zygomycosis usually occur only in severely immunocompromised patients; such women are often less than normally fertile. Pregnancy requires a degree of health that is protective against disease caused by these microorganisms. Blastomycosis, cryptococcosis, histoplasmosis, and sporotrichosis are endemic diseases of low incidence. Their rarity decreases the likelihood of coincidental occurrence during pregnancy. Coccidioidomycosis is the only exception to these generalities; it poses a special threat to pregnant women living in endemic areas of the desert Southwest.1 Pregnancy increases 50- to 100-fold the rate of dissemination of previously contracted pneumonia. Similarly, infection acquired during pregnancy is 50–100 times more likely to hematogenously disseminate than is infection acquired by nongravid women. Coccidioidomycosis is also unique in terms of the frequency with which it involves the placenta; this occurs in about one-fourth of the cases of disseminated disease, but fetal involvement is rare. The only mycosis to cause fetal disease with any regularity is candidiasis, which may also involve the cord and membranes.