The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporinebased HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNApositive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporinebased immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P ‫؍‬ .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P ‫؍‬ .001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P ‫؍‬ .008 and .18, respectively). Cirrhosis related to chronic infection with the hepatitis C virus (HCV) has emerged as one of the leading indications for orthotopic liver transplantation (OLT) worldwide, accounting for 50% of transplantation in Spain.

The demographic, clinical and microbiological data of patients with candidemia at the "Hopital Universitario La Fe", a tertiary-care hospital in Valencia, Spain, from 1995 to 1997 was analyzed retrospectively. Candida spp. were isolated in blood cultures from 145 patients, 32% of whom were children (25% of these were neonates). The most common species isolated was Candida albicans, followed by Candida parapsilosis, Candida krusei and Candida tropicalis. Risk factors for candidemia included underlying disease, therapy with broad-spectrum antibiotics and the presence of a central venous catheter. The majority of children were treated with amphotericin B, whereas 52% of adults received fluconazole. Overall mortality was 44% (30% in children and 50% in adults), and attributable mortality was 30% (24% in children and 33% in adults). Multivariate analysis indicated that neutropenia, corticosteroid therapy, lack of antifungal treatment, and failure to replace the central venous catheter were factors associated with candidemia-related death. Among the adult population, an APACHE II score greater than 15 predicted candidemia-related death.

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Pulmonary nocardiosis (PN) is an infrequent and severe infection due to Nocardia spp., microorganisms that may behave both as opportunists and as primary pathogens. The aim of this study and review was to evaluate the clinical features, evolution and prognostic factors of PN.The study group comprised 10 consecutive patients with pulmonary nocardiosis acquired in a community setting, diagnosed and followed in a tertiary teaching hospital.Chronic obstructive pulmonary disease (COPD), neoplastic disease and human immunodeficiency virus (HIV) infection were the most frequent predisposing factors. Four patients were receiving corticosteroid treatment. Clinical course was chronic and diagnosis was delayed 3 weeks or more in seven of the patients. Lobar or multilobar condensation was the most frequent radiographic pattern. Antimicrobial susceptibility testing showed: 100% sensitivity for amikacin; 83% for imipenem; 71% for cefotaxime; and 71% for trimethoprim-sulphamethoxazole. The disease remained localized in the lung in five cases, with a trend toward chronicity in one with bronchiectasis. In the other five, the disease disseminated, affecting subcutaneous tissue, the central nervous system and the kidney. Three patients died, one with disseminated disease and two who were receiving corticosteroid therapy.The following conclusions were reached: 1) pulmonary nocardiosis is difficult to diagnose, diagnosis is frequently delayed and a high level of suspicion is, thus, required in patients with underlying diseases or chronic corticosteroid therapy; 2) there is frequent dissemination and high mortality; and 3) antimicrobial combinations with proven synergy, such as imipenem and amikacin, are recommended for initial therapy. Eur Respir J 1997; 10: 1542-1546

Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC 2 ) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode ؎ one dilution range across all 17 laboratories. MIC 2 at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.