Ibuprofen-mediated reversal of fluconazole resistance in clinical isolates of Candida.

INTRODUCTION: In view of the increasing prevalence of invasive Candidiasis in today's health-care scenario and the emergence of fluconazole resistance among clinical isolates of Candida, we sought to determine if Ibuprofen could elicit a reversal of fluconazole resistance and thereby offer a potential therapeutic breakthrough in fluconazole-resistant Candidiasis. MATERIALS AND METHODS: We selected 69 clinical isolates of Candida, which demonstrated an MIC of >32 µg/ml for fluconazole, and subjected them to broth microdilution in presence and absence of Ibuprofen. RESULTS: Forty two of the 69 isolates (60.9%) demonstrated reversal of Fluconazole resistance with concomitant use of Ibuprofen. This was characterized by significant species-wise variation (p=0.00008), with all the C. albicans isolates and none of the C. glabrata isolates demonstrating such reversal. Only 22.2% and 37.7% of C. krusei and C. tropicalis isolates respectively showed Ibuprofen-mediated reversal of Fluconazole resistance. CONCLUSION: Since Ibuprofen is a known efflux pump inhibitor, our findings hint at the possible mechanism of Fluconazole resistance in most of our Candida isolates and suggest a potential therapeutic alternative that could be useful in the majority of Fluconazole-resistant clinical isolates of Candida.

Antibiotic overuse as a risk factor for candidemia in an Indian pediatric ICU.

OBJECTIVE: To identify risk factors and mycological characteristics of candidemia in Pediatric ICU of a tertiary-care hospital. METHODS: Patients were screened for candidemia by blood culture. Recovered isolates were speciated and subjected to antifungal susceptibility testing. For every candidemic patient, three controls were matched for age, underlying diagnosis and period of hospitalization. Premature neonates were also matched for birth-weight. Proportion of cases and controls on specific antibiotics or indwelling devices was compared using Chi-square test, while unpaired t-test was used for comparing the number of antibiotics used and the number of days of antibiotic administration. Concordance between susceptibility testing methods was evaluated using Chi-square test. RESULTS: Significantly wider spectrum of antibiotic coverage was observed among the 28 candidemic patients. While every patient received antibiotic against enteric gram-negative bacilli, antibiotic usage for additional groups of microorganisms was significantly higher among cases. Association of candidemia with increasing use of indwelling devices was also observed. Endogenous colonization was higher in candidemic infants. Candida albicans was the commonest species (n = 18), followed by C. tropicalis (n = 7). Fluconazole and ketoconazole resistance was observed in 10.7 % cases. CONCLUSIONS: This information on pediatric candidemia could be used to devise locally-tailored strategies for identifying at-risk patients, underline the importance of routine antifungal susceptibility testing and formulate appropriate guidelines for management.

Diagnostic defaulters: an overlooked aspect in the Indian Revised National Tuberculosis Control Program.

INTRODUCTION: The Revised National Tuberculosis Control Program (RNTCP) aims to achieve detection of 70% of new smear-positive patients in a community and to cure 85% of such patients. Though an elaborate recording and reporting system is in place to monitor the success of the program, no record of patients who do not complete the diagnostic process is currently maintained. The present study, performed in a tertiary care hospital, attempted to estimate the proportion of this group of patients, who were labeled "diagnostic defaulters. METHODOLOGY: This prospective observational study was conducted over one year on consecutive patients presenting with cough of more than two weeks' duration. A total of two sputum samples were obtained from each patient, including a spot sample and a morning sample collected on the following day. Zeihl-Neelsen staining, reporting and external quality assessment of smear-microscopy was done per RNTCP guidelines. RESULTS: Of the 2,349 patients recruited, 175 defaulted on the second day. The positivity rates for the spot and morning samples were 18.3% and 18.9%, respectively (p > 0.001).  Of the 175 defaulters, 31 were found to be smear-positive, thereby implying that the proportion of diagnostic defaulters was 17.7%. All 21 diagnostic defaulters contacted by telephone were found to be unaware of their smear-positive status. CONCLUSION: The high proportion of diagnostic defaulters, the majority of whom were unaware of their sputum-positive status, emphasizes the need to recognize the importance of this group of patients to better control tuberculosis.