S. Spanik

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.

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%.

Viridans Streptococcal Bacteraemia Due to Penicillin-Resistant and Penicillin-Sensitive Streptococci: Analysis of Risk Factors and Outcome in 60 Patients from a Single Cancer Centre Before and After Penicillin is Used for Prophylaxis

60 patients with 60 viridans streptococcal bacteraemic episodes (42 due to penicillin-sensitive and 18 due to penicillin-resistant viridans streptococci) were analysed in a population of 12,185 admissions and 1,380 bacteraemic episodes during a 7-year period in a National Cancer Institute. The incidence of viridans streptococci among bacteraemias decreased from 11.5% in 1989 to 2.5% in 1995 after penicillin was introduced for prophylaxis of febrile neutropenia in acute leukaemia in 1993. However, the proportion of penicillin-resistant viridans streptococcal bacteraemias increased from 0 in 1989 and 1990 before any prophylaxis was given, to 12.9-16.7% after quinolones were used for prophylaxis in 1991 and 1992, and to 44.4-81.8% in 1993-1995 after penicillin was added to the quinolones. Mortality rate was higher in the subgroup of penicillin-resistant viridans streptococcal bacteraemias (p < 0.05). Statistically significant risk factors in patients with penicillin-resistant (compared with penicillin-sensitive) viridans streptococcal bacteraemia were: acute leukaemia (p < 0.03), high doses of cytarabine (p < 0.05), mucocutaneous lesions (p < 0.004), breakthrough bacteraemia during prophylaxis with ofloxacine plus penicillin (p < 0.001). Multiple logistic regression analysis showed that only acute leukaemia (OR 2.05, CI 0.85-1.85, p < 0.00452) and penicillin-resistance (OR 0.71, CI 0.103-4.887, p < 0.0209) were significant independent predictors of inferior outcome. Breakthrough bacteraemia during empiric therapy with vancomycine occurred in 5 of 116 patients treated with vancomycine, and during therapy with ampicillin plus gentamicin in 6 patients of 18 treated.

Prospective study of nosocomial fungal meningitis in children--report of 10 cases.

Within an 8-year period, 10 cases of fungal nosocomial meningitis in children 0-13 y old were prospectively identified, 3 caused by yeasts other than Candida spp. (Rhodotorula rubra, Aureobasidium mansoni, Clavispora lusitaniae) and 7 by Candida albicans. Seven patients survived. whereas 3 neonates with fungal meningitis (all due to C. albicans) died. Risk factors for fungal nosocomial meningitis included cancer (2 children), previous neurosurgery (2 children), cranial trauma (1 case) and prematurity with low birthweight (5 cases). All patients except 1 had received broad-spectrum antibiotics before onset of meningitis. In addition to yeasts, bacteria were isolated from CSF of 4 children. One child had additional fungaemia. Univariate analysis was used to compare 10 cases of fungal to 91 cases of bacterial nosocomial meningitis. Except for concurrent bacteraemia, (60 vs 25.3%, P < 0.03), which was more frequently observed among fungal meningitis, there were no significant differences in risk factors, sequelae or outcome (mortality) between patients with fungal vs bacterial meningitis. A review of fungal meningitis reported within the last 20 y is included.

Invasive mold infections in cancer patients: 5 years' experience withAspergillus, Mucor, Fusarium andAcremonium infections

Twenty systemic mold infections due to hyphic fungi (molds) arising within the last 5 years in a 60-bed cancer department are analyzed. The most frequent risk factors were plants in ward (75%), prior therapy with broad spectrum antibiotics (70%), catheter insertion (70%), acute leukemia (65%) and neutropenia (60%). Before death, a definitive diagnosis was made in 40%, and a presumptive diagnosis in 60% of patients; post mortem the presumptive antemortem diagnosis was confirmed in all cases (100% of patients). Aspergillosis was the most common invasive fungal disease (55%), followed by mucormycosis (15%), fusariosis (15%), and acremoniosis (10%). Of 20 patients, 8 (40%) were cured or improved after antifungal therapy with amphotericin B, ambisome and/or itraconazole; 8/20 (40%) died of fungal infection and 4/20 (20%) of underlying disease with fungal infection. Even though the diagnosis was made and antifungal therapy started before death in 15/20 (75%), invasive mold infection had a 60% overall mortality in patients with malignant disease.

Candida glabrata, Candida krusei, non-albicans Candida spp., and other fungal organisms in a sixty-bed national cancer center in 1989-1993 : no association with the use of fluconazole

During the 5-year period 1989-1993, the incidence of Candida krusei, and other non-albicans Candida spp., was analyzed in a 60-bed cancer department. The frequency of C. krusei, before fluconazole was introduced into therapeutic protocols in 1990, was 16.5%, and after introduction of fluconazole into prophylaxis in acute leukemia in 1991, the incidence of C. krusei was 12.7%. After 3 years of using this drug in therapy and prophylaxis, the incidence of C. krusei in 1993 was 14.8%, what was lower than before this drug was introduced in our country. 97.6% of all isolated fungi were yeasts and only 2.4% were molds. Among yeasts, the most frequently isolated pathogen was Candida albicans with 64.3% in 1989 and 74.2% in 1993. The next was C. krusei with 21.2% in 1992 and 16.5% in 1989, but 14.8% in 1993, and Candida tropicalis and Candida glabrata with 9.03% in 1989 and 2.7% in 1993. Among the molds, Aspergillus spp. was the most frequently isolated genus. Analyzing the etiology of mycologically proven fungal infections confirmed by positive blood cultures or biopsies, C. albicans and Aspergillus spp. were the most common causative organisms.

Fungemia in cancer patients undergoing chemotherapy versus surgery: risk factors, etiology and outcome.

26 patients with fungemia and cancer treated with chemotherapy (group A) were compared to 25 patients with fungemia and cancer treated with surgery (group B), to assess differences in etiology, risk factors and outcome. Candida albicans was responsible for 42% of fungemias in group A, and for 92% of fungemias in group B (p < 0.005). Breakthrough fungemia occurring during antifungal prophylaxis appeared in 46.6% of group A vs 12% of group B (p < 0.02). There was significant difference in outcome between the groups: 20% of patients after surgery vs 7.7% of those after chemotherapy died from fungemia (p < 0.04). Most common risk factors recorded in both groups were catheter insertion and previous therapy with broad spectrum antibiotics.

Prospective Study of Fungaemia in a Single Cancer Institution over a 10-y Period: Aetiology, Risk Factors, Consumption of Antifungals and Outcome in 140 Patients

Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p = 0.025), > or = 3 positive blood cultures (p = 0.02), acute leukaemia (p = 0.00001), neutropenia (p = 0.0015), quinolone prophylaxis (p < 0.000005) and breakthrough fungaemia (p = 0.004) during prophylaxis with fluconazole (p = 0.03) and itraconazole (p = 0.005) were significantly more associated with non-Candida than C. albicans spp. Furthermore, attributable mortality was higher in the subgroup of non-Candida than C. albicans spp. (50.0 vs. 18.7%, p < 0.02). The only independent risk factor for inferior outcome was antifungal therapy of < 10 d duration (odds ratio 2.1, 95% confidence interval, p < 0.001). Aetiology, neutropenia and mucositis were not independent risk factors for higher mortality in multivariate analysis; however, they were risk factors for inferior outcome in univariate analysis (p < 0.05-0.005).Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p

Funguria in Cancer Patients: Analysis of Risk Factors, Clinical Presentation and Outcome in 50 Patients

SummaryFifty cancer patients with funguria of >105 CFU/ml, dysuria and leukocyturia were retrospectively analyzed for etiology, risk factors and outcome. In 72% of casesCandida albicans and in 28% non-albicansCandida spp. (Candida krusei, Candida tropicalis) and non-Candida spp. yeasts (Blastoschizomyces capitatus) were isolated.Torulopsis glabrata was not found among these patients. The most frequent risk factors were: antibiotic therapy with more than one antibiotic agent (96%), concomitant fungal infection in other localizations than the urinary tract (36%), colonization with the same species (48%), catheterization with urinary catheter or nephrostomy (46%), prophylaxis with quinolones (50%) and previous therapy with corticosteroids (72%). Structural or anatomic malformations of the urinary tract (26%), neutropenia (28%), antifungal prophylaxis with azoles (22%), and diabetes mellitus (12%) were less frequently seen. Thirty of 36 patients treated with systemic antifungals were cured and six were not.ZusammenfassungBei 50 Krebspatienten, die eine Fungiurie von >105 KBE/ml mit Dysurie und Leukozyturie aufwiesen, wurde eine retrospektive Analyse durchgeführt, in der die Ätiologie, die Risikofaktoren und die Verläufe berücksichtigt wurden. 72% der Fälle wurden durchCandida albicans und 28% durch nicht-albicansCandida spp. (Candida krusei, Candida tropicalis) und andere Hefen (Blastoschizomyces capitatus) verursacht.Torulopsis glabrata fand sich in dieser Patientengruppe nicht. Die häufigsten Risikofaktoren waren Antibiotikatherapie mit mehr als einem Antibiotikum (96%), gleichzeitige Pilzinfektion in einer anderen Lokalisation als dem Harntrakt (36%), Kolonisation mit derselben Spezies (48%), Harnableitung mit Harnblasenkatheter oder Nephrostomie (46%) Prophylaxe mit Chinolonen (50%) und Vortherapie mit Kortikosteroiden (72%). Seltenere Risiken waren strukturelle oder anatomische Anomalien des Harntraktes (26%), Neutropenie (28%), Pilzprophylaxe mit einem Azolderivat (22%), Diabetes mellitus (12%). 30 der 36 mit systemischen Antimykotika behandelten Patienten wurden geheilt, sechs sprachen auf die Therapie nicht an.

Risk Factors, Aetiology, Therapy and Outcome in 123 Episodes of Breakthrough Bacteraemia and Fungaemia during Antimicrobial Prophylaxis and Therapy in Cancer Patients

One hundred and twenty-three breakthrough bacteraemias (BB) were defined during a 5-year period in a National Cancer Centre, among 9986 admissions and a total of 979 bacteraemic episodes analysed. Of 123 bacteraemias in 103 patients, 77 were polymicrobial and 116 of the 323 organisms isolated were resistant to currently administered antimicrobial agents. Sixty-seven of the bacteraemic episodes were catheter-associated, as confirmed by the isolation of the same organisms from both blood and catheter tip. The strains isolated most frequently were coagulase-negative staphylococci (30.5%), corynebacteria (10%), Pseudomonas aeruginosa (10%), Enterococcus faecalis (9%) and viridans streptococci (8.5%). Gram-positive aerobes accounted for two-thirds of all micro-organisms isolated during breakthrough bacteraemic and fungaemic episodes. Polymicrobial episodes were associated more frequently with vascular catheters and neutropenia, and had a less favourable outcome than monomicrobial infections. Relapse was associated more frequently with catheter-related episodes, but the overall mortality rate was similar and independent of catheter insertion. Breakthrough bacteraemic and fungaemic episodes were associated more frequently with acute leukaemia. Catheter removal, as an independent variable, and modification of antimicrobial therapy were essential for better outcome.