We have correlated the in vitro results of testing the susceptibility of Cryptococcus neoformans to fluconazole with the clinical outcome after fluconazole maintenance therapy in patients with AIDS-associated cryptococcal disease. A total of 28 isolates of C. neoformans from 25 patients (24 AIDS patients) were tested. The MICs were determined by the broth microdilution technique by following the modified guidelines described in National Committee for Clinical Standards (NCCLS) document M27-A, e.g., use of yeast nitrogen base medium and a final inoculum of 10 4 CFU/ml. The fluconazole MIC at which 50% of isolates are inhibited (MIC 50 ) and MIC 90 , obtained spectrophotometrically after 48 h of incubation, were 4 and 16 g/ml, respectively. Of the 25 patients studied, 4 died of active cryptococcal disease and 2 died of other causes. Therapeutic failure was observed in five patients who were infected with isolates for which fluconazole MICs were >16 g/ml. Four of these patients had previously had oropharyngeal candidiasis (OPC); three had previously had episodes of cryptococcal infection, and all five treatment failure patients had high cryptococcal antigen titers in either serum or cerebrospinal fluid (titers, >1:4,000). Although 14 of the 18 patients who responded to fluconazole therapy had previously had OPC infections, they each had only a single episode of cryptococcal infection. It appears that the clinical outcome after fluconazole maintenance therapy may be better when the infecting C. neoformans strain is inhibited by lower concentrations of fluconazole for eradication (MICs, <16 g/ml) than when the patients are infected with strains that require higher fluconazole concentrations (MICs, >16 g/ml). These findings also suggest that the MICs determined by the modified NCCLS microdilution method can be potential predictors of the clinical response to fluconazole therapy and may aid in the identification of patients who will not respond to fluconazole therapy.Cryptococcosis is an infection caused by the ubiquitous fungus Cryptococcus neoformans, an encapsulated yeast-like fungus. The most frequent clinical presentation of the disease is meningoencephalitis (5, 6, 12, 18, 19; M. S. Saag, Editorial Response, Clin. Infect. Dis. 21:35-36, 1995); 75 to 90% of AIDS patients infected with C. neoformans will develop meningitis (5). Cryptococcosis in AIDS patients is seldom cured, and fluconazole is the drug of choice for the necessary lifelong suppressive (maintenance) therapy (17). Use of fluconazole for long-term suppressive therapy may be associated with the development of azole resistance in cryptococcal infections in AIDS patients (21).Methods for testing the antifungal susceptibility of C. neoformans could become important tools in the selection and monitoring of an appropriate antifungal drug for the treatment and prophylaxis of cryptococcal infections. Ghannoum et al. (9) developed a broth microdilution method for measuring the susceptibility of cryptococci to fluconazole, which is described as an alternative a...

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ABSTRACT:Reference intervals of hematologic and biochemical blood profiles were obtained from 56 male and 58 female Mediterranean pond turtles (Mauremys leprosa) captured from the wild in different periods of their annual cycle. Mean (or median in nonnormal distributions) values of leukocyte differential were 53.8% and 58.5% heterophils, 35.3% and 32.6% eosinophils, 6.3% and 5.8% lymphocytes, 4.3% and 2% monocytes, and 0% and 0% basophils in males and females, respectively. Biochemical values did not differ from other chelonians, but values were generally higher in females than in males.

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.