V. Krcmery

Candidemia in Cancer Patients: A Prospective, Multicenter Surveillance Study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC)

In a surveillance study of candidemia in cancer patients that was conducted by the European Organization for Research and Treatment of Cancer, 249 episodes were noted; Candida albicans was isolated in 70% (63) of the 90 cases involving patients with solid tumors (tumor patients) and in 36% (58) of the 159 involving those with hematologic disease (hematology patients). Neutropenia in tumor patients and acute leukemia and antifungal prophylaxis in hematology patients were significantly associated with non-albicans candidemia in a multivariate analysis. Overall 30-day mortality was 39% (97 of 249). In a univariate analysis, Candida glabrata was associated with the highest mortality rate (odds ratio, 2.66). Two multivariate analyses showed that mortality was associated with older age and severity of the underlying disease. Among hematology patients, additional factors associated with mortality were allogeneic bone marrow transplantation, septic shock, and lack of antifungal prophylaxis.

An EORTC International Multicenter Randomized Trial (EORTC Number 19923) Comparing Two Dosages of Liposomal Amphotericin B for Treatment of Invasive Aspergillosis

This is the first completed prospective randomized clinical efficacy trial of antifungals in the treatment of invasive aspergillosis (IA) and the first to compare the clinical efficacy of two dosages of liposomal amphotericin B (L-AmB) for IA in neutropenic patients with cancer or those undergoing bone marrow transplantation. Eighty-seven of 120 patients were eligible and evaluable. Clinical responses were documented for 26 (64%) of 41 patients receiving 1 mg/(kg.d) (L-AmB-1) and 22 (48%) of 46 receiving 4 mg/(kg.d) (L-AmB-4). Radiologic response rates were similar: 24 (58%) of the L-AmB-1 recipients and 24(52%) of the L-AmB-4 recipients. The six-month survival rates were 43% (L-AmB-1) and 37% (L-AmB-4). These differences were not significant. The numbers of deaths directly due to IA at 6 months were similar: 9 (22%) of 41 L-AmB-1 recipients and 9 (20%) of 46 L-AmB-4 recipients. No other variable independently influenced survival, apart from central nervous system IA. L-AmB is effective in treating approximately 50%-60% of patients who have IA. A 1-mg/(kg.d) dosage is as effective as a 4-mg/(kg.d) dosage, and no advantages to use of the higher, more expensive, dosage has been observed.

Candida fungemia in neonates treated with fluconazole : report of forty cases, including eight with meningitis

PURPOSE OF THE STUDY To assess efficacy and safety of fluconazole in neonates with Candida fungemia. STUDY DESIGN Multicenter prospective protocol of all fungemias appearing between January 1, 1993, and December 31, 1997, in four major university hospitals. RESULTS Forty neonates, 28 of them with very low birth weight (<1500 g; 30.5 median gestation week), with documented Candida albicans fungemia were treated with intravenous fluconazole in a daily dosage of 6 mg/kg once daily for 6 to 48 days. Thirty-four received fluconazole as monotherapy and 6 received it in combination with amphotericin B. Thirty-two (80%) were cured; 4 of them relapsed despite at least 14 days of therapy, but they were ultimately cured without sequelae. Eight other neonates died, 4 because of fungal infection and 4 because of prematurity or hemorrhage or lung failure, with fungemia (20% overall and 10% attributable mortality). Two neonates had elevated liver enzymes during fluconazole therapy and 2 others had elevated serum creatinine during fluconazole monotherapy. In none of them did these abnormalities necessitate discontinuation of antifungal therapy. In 8 neonates fungal meningitis developed as a complication of fungemia. All but 3 fungemias were C. albicans; 3 were Candida parapsilosis. CONCLUSIONS Fluconazole was safe and effective antifungal therapy even in complicated or Candida fungemia in neonates and in infants with very low birth weight.

Hematogenous trichosporonosis in cancer patients: report of 12 cases including 5 during prophylaxis with itraconazol

Abstract Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988–1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993–1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs 15.8%, P<0.001) than that of hematogenous candidiasis.

Ciprofloxacin in treatment of nosocomial meningitis in neonates and in infants: report of 12 cases and review.

Twelve cases of neonatal and infant nosocomial meningitis treated with intravenous ciprofloxacin in doses of 10 to 60 mg/kg/day are described. Four neonates were 21 to 28 days old and eight infants were 2 to 6 months old. Six presented with Gram-negative meningitis: Escherichia coli (2), Salmonella enteritidis (1), Acinetobacter calcoaceticus (1), two with two organisms, and (H. influenzae plus Staphylococcus epidermidis, Acinetobacter spp. plus S. epidermidis), and six were attributable to Gram-positive cocci (four S. aureus and two Enterococcus faecalis). Ten cases were cured. In two cases, reversible hydrocephalus appeared that responded to intraventricular punctures. In seven children, no neurologic sequellae appeared after a 2- to 4-year follow-up. One neonate had relapse of meningitis 3 months later and was ultimately cured, but developed a sequellae of psychomotoric retardation. Follow-up varied from 27 months to 10 years. Current published case reports from Medline on quinolone use in meningitis in neonates and infants are reviewed.

Fungaemia due to Fusarium spp. in cancer patients

Five cases of fungaemia due to Fusarium spp. in cancer patients are described. Two were breakthrough cases, despite ongoing therapy with amphotericin B. Three were caused by Fusarium solani, one by F. oxysporum and one by F. dimerum. Four patients died, three of them despite therapy with amphotericin B for between 5-37 days. We describe only the second reported case of F. dimerum fungaemia. Since 1972, 93 cases of systemic infection with Fusarium spp. have been described: 43 had positive blood cultures and the overall mortality was 72%.

Longitudinal 10-year prospective survey of fungaemia in Slovak Republic: trends in etiology in 310 episodes☆

A 10-year prospective survey of fungaemia in the Slovak Republic, involving 31 microbiology laboratories and 71 hospitals, was conducted from 1989-1998 (10 years): 310 fungaemias were analyzed for etiology, clinical characteristics, therapy, and outcome. C. albicans was responsible for 191 (61.6%) fungaemias, non-albicans Candida spp. (NAC) for 97 (31.3%), non-Candida yeasts for 18 (5.8%) and moulds (Fulsarium spp.) for four fungaemias. The most frequent NAC isolated from blood cultures were C. parapsilosis--30 (9.7%), C. krusei--18 (5.8%), C. tropicalis--14 (4.5%), and C. glabrata--10 (3.2%). Secular trends in etiology showed a sustaining decrease of C. albicans (from 100% in 1989 to 50.7% in 1998) and increase of NAC (from 0% in 1989-1990 to 46.3% in 1998). Non-Candida yeasts and moulds showed a stable proportion during the investigated period. There were statistically significant differences in etiology of fungaemia various subgroups of patients: non-albicans Candida spp. was significantly more frequent observed among subgroups of patients with pancreatitis and coma (53.3% vs. 31.3%, p < or = 0.02) and less frequently in the subgroup of neonates (15.0% vs. 31.3%, p < or = 0.006). Vice versa, C. albicans appeared more frequently in neonates (85%).

Fungal urinary tract infections in patients at risk

Fungal urinary tract infection (UTI) represents a high-risk event in severely ill patients. Its increasing incidence in recent years is associated with extensive and prolonged use of broad-spectrum antimicrobial agents, corticosteroids, immunosuppressive and cytotoxic drugs. Other important risk factors comprise higher age, diabetes mellitus, chronic renal failure, hemodialysis, renal transplantation, structural or functional abnormalities of urinary tract with indwelling urinary catheter or nephrostomy. Fifty hospitalized symptomatic patients with funguria of > 10(5) CFU/ml and leucocyturia were analysed for etiology, risk factors and outcome. Candida albicans was isolated in 36 patients, non-albicans Candida species (Candida tropicalis, Candida krusei) and non-Candida yeasts (Blastoschizomyces capitatus) in 14 patients, respectively. All patients were treated with systemic antifungals. In total, 42 patients of 50 (84%) were cured (32/36 with C. albicans and 10/14 with non-C. albicans associated funguria). Systemic antifungal therapy should be considered in high-risk patients with fungal UTI.

Magnetic Resonance Imaging in Children Receiving Quinolones: No Evidence of Quinolone-lnduced Arthropathy

Twenty-nine children with cystic fibrosis (CF) were investigated for quinolone-induced arthropathy. Magnetic resonance imaging (MRI) was performed in 14/14 children treated with ofloxacin or ciprofloxacin and in 10/15 of those never treated with quinolones. The frequency of pathologic MRI findings, concerning cartilage thickness, careful analysis of the cartilage structure, presence of edema, cartilage-bone borderline and the presence of fluid in joints did not show any difference between both groups. Thus the presence of quinolone-induced arthrotoxicity cannot be confirmed in this study.

Antibiotic stewardship and consumption: findings from a pan-European hospital study

OBJECTIVES Much has been written about antibiotic stewardship although less is known about the structure and content of antibiotic policies at hospital level. As part of the European Commission Concerted Action Antibiotic Resistance Prevention And Control (ARPAC) Project, data on antibiotic stewardship were collated and relationships investigated by antibiotic consumption in European hospitals. METHODS A questionnaire survey on antibiotic stewardship factors was completed by 170 hospitals from 32 European countries. Data on committees, antibiotic formularies and policies addressing empirical therapy and prophylaxis were collated. Data on antibiotic use, expressed as defined daily doses per 100 occupied bed-days (DDD/100 BD), were provided by 139 hospitals from 30 countries, and 124 hospitals provided both data sets. Six key indicator stewardship variables were analysed by European region, case mix and antibiotic consumption. RESULTS Hospitals from Northern and Western Europe were more likely to convene antibiotic committees or drugs and therapeutic committees compared with those from Southern and South-Eastern Europe (P < 0.001). One-fifth of hospitals had neither an antibiotic committee nor a policy. Hospital antibiotic policies commonly included recommendations on individual drugs, drug choices, dosage, duration and route but were less likely to contain information on side effects and cost. There were no significant differences by median total (J01) antibiotic consumption, although other antibiotic subgroups differed by stewardship indicators. CONCLUSIONS Policies and practices relating to antibiotic stewardship varied considerably across European hospitals. These data provide a benchmark for newer European strategies tackling antibiotic resistance. More work is required to achieve harmonization of recommended practice, particularly in hospitals from Southern Europe.