Nosocomial breakthrough fungaemia during antifungal prophylaxis or empirical antifungal therapy in 41 cancer patients receiving antineoplastic chemotherapy: analysis of aetiology risk factors and outcome.

Forty-one episodes of breakthrough fungaemia occurring over a 7.5 year period in the National and St Elizabeth's Cancer Institutes in Bratislava, Slovakia, were analysed. Five of them occurred during prophylaxis with fluconazole (one Torulopsis glabrata, one Hansenula anomala, two Candida krusei and one Candida parapsilosis), ten with itraconazole (three Trichosporon pullulans, one Trichosporon beigelii, one Cryptococcus laurentii, three Candida albicans and two T. glabrata), 11 during prophylaxis with ketoconazole (one Candida norvegenesis, one C. parapsilosis, one C. krusei, one Candida tropicalis, five C. albicans, one Candida stellatoidea and one C. laurentii and 15 during empirical therapy with amphotericin B (ten C. albicans, two T. beigelii and three Candida lusitaniae). The most frequent risk factors for breakthrough fungaemia were neutropenia, previous therapy with multiple antibiotics and recent catheter insertion. Comparing these episodes with 38 non-breakthrough fungaemias (appearing at the same institute in the same period) differences in certain risk factors were noted: breakthrough fungaemias were more frequently observed in patients with acute leukaemia (39.0% vs 5.2%, P < 0.001), mucositis (34.2% vs 13.1%, P < 0.05), prophylaxis with quinolones (58.5% vs 15.8%, P < 0.0001) and catheter-associated infections (29.3% vs 2.6%, P < 0.003). In this subgroup overall mortality (36.6% vs 28.8%) or early attributable mortality (22.0% vs 23.6%) were not significantly different.

Eight-year surveillance of non-albicans Candida spp. in an oncology department prior to and after fluconazole had been introduced into antifungal prophylaxis.

From 1989 until 1996, during the last 8 years, the proportion of Candida (C.) krusei, and other non-albicans Candida spp. isolated from surveillance cultures and from sterile body sites, was analyzed among 13,758 admissions in a National Cancer Institute. During these admissions a total of 9,042 isolates were prospectively collected from surveillance cultures, and 126 from blood cultures. The proportion of C. krusei among all organisms was 12.7% to 16.5% in 1989 through 1991, i.e., before fluconazole was introduced into prophylactic protocols. After the introduction of fluconazole into prophylaxis in acute leukemia in 1992 the incidence of C. krusei was 7.9% to 8.6% during 1994 to 1996. After 5 years of using this drug for prophylaxis, the incidence of C. krusei was lower than before this drug was introduced in our institute. Among yeasts, the most frequently isolated pathogen was still Candida albicans (72.2% of all isolated fungal organisms). Among molds, Aspergillus spp. was the most frequently isolated agent. Analyzing the etiology of proven fungal infections (fungemias) confirmed by positive blood cultures, C. albicans was the most common causative organism in 53.8% of cases. The incidence of fungemia due to Torulopsis (C.) glabrata and C. krusei before and after fluconazole introduction did not change. Of 126 organisms isolated from blood cultures, there was no increase in T. (C.) glabrata or C. krusei after introduction of fluconazole for prophylaxis and therapy, and the quoted 6.4% of fungemic episodes remained stable with an incidence of 1 fungemia/year since 1991. The proportion of C. krusei and C. glabrata among Candida spp. was decreasing in our center between 1989 and 1996. Also, the proportion of non-albicans Candida spp. among isolates decreased from 25.7% in 1990 to 11.9% in 1996.

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%.

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.

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.

Bacteremia in neutropenic versus nonneutropenic cancer patients: etiology and outcome in 401 episodes.

Etiology, risk factors, symptomatology and outcome of 401 bacteremic episodes during the period of 6 years in a National Cancer Institute occurring among 9987 admissions were analyzed. Neutropenia as an independent risk factor was observed in 198 episodes, while 203 bacteremic episodes appeared in nonneutropenic patients. Both groups were compared in risk factors, etiology, clinical symptomatology and outcome. Proportion of particular pathogens did not show significant differences in both groups, except for E. faecalis occurring more frequently in the group of nonneutropenic patients in contrast to Enterobacteriaceae, occurring more frequently in neutropenic patients. There was significant by higher proportion of anaerobic bacteremia and fungemia in neutropenic than in nonneutropenic patients. Prior prophylaxis with quinolones with breakthrough bacteremia were also seen more frequently in the group of neutropenic patients. Septic shock and death due to bacteremia occurred more frequently in the group of neutropenic patients.

Staphylococcal bacteremia in cancer patients: risk factors and outcome in 134 episodes prior to and after introduction of quinolones into infection prevention in neutropenia.

A total of 134 episodes of staphylococcal bacteremia (SBE) appearing among 9987 admissions, and 979 episodes of bacteremia in cancer patients within 5 years, were analyzed for risk factors, clinical course and outcome; 64 were monomicrobial and 70 polymicrobial. The most frequent risk factors were acute leukemia, catheter insertion, long-lasting neutropenia, and prior prophylaxis with quinolones. There was no significant difference between polymicrobial and monomicrobial SBE in risk factors. The two groups differed only in the source of bacteremia (gastrointestinal and respiratory-tract infections were more common in monomicrobial SBE) and etiology-Staphylococcus aureus appeared more frequently in monomicrobial than in polymicrobial bacteremia (20.3% compared to 4.3%, P < 0.05). More complications (14.3%) such as abscesses, endocarditis, etc. appeared in the group of polymicrobial SBE (P < 0.05). No difference was observed in clinical course and outcome between monomicrobial and polymicrobial SBE. The incidence of SBE has increased since 1991, when quinolones were first used in prophylaxis in afebrile neutropenia at our center; however, the infection-associated mortality in monomicrobial SBE was low (4.3%).

Breakthrough bacteraemic and fungaemic episodes during antimicrobial prophylaxis and therapy in cancer patients: analysis of risk factors, etiology, therapy and outcome in 123 episodes.

One hundred twenty three breakthrough bacteraemias (BB) during 5 years in a National Cancer Institute, among 9986 admissions and 979 bacteraemic episodes were analysed. 123 BB were caused by 323 microbes, only 116 were resistant (31.5%) to currently administered antimicrobials. Sixty seven of 123 bacteraemic episodes were catheter associated confirmed by isolation of the same organisms from the blood and catheter tip. 77/123 BE were polymicrobial. The most frequently isolated strains were coagulase negative staphylococci (30.5%), Corynebacteria (10%), Ps. aeruginosa (10%), Str. faecalis (9%) and Viridans streptococci (8.5%). Gram-positive aerobes accounted for two-thirds of all organisms isolated during breakthrough bacteraemic and fungaemic episodes. Mixed polymicrobial breakthrough bacteraemic and fungaemic episodes were more frequently associated with vascular catheter insertion and neutropenia, and had a less favourable outcome in comparison to monomicrobial infections. The relapse was associated more frequently with catheter related bacteraemic and fungaemic episodes, but the overall mortality rate was similar independently from catheter insertion. Breakthrough bacteraemic and fungaemic episodes were associated more frequently with acute leukaemia. Polymicrobial breakthrough bacteraemic and fungaemic episodes were associated more frequently in neutropenic episodes and in venous catheters. Regarding the outcome, an extraction of the catheter with no dependence on variable and modification of antimicrobial therapy were essential for the improvement in the prognosis. (Tab. 5, Ref. 20.).

Imipenem-resistant Ps. aeruginosa bacteraemia in cancer patients: risk factors, clinical features and outcome.

Ninety nine patients with 101 bacteraemic episodes due to Ps. aeruginosa (PA) within 6 years were divided into two groups according to their resistance to imipenem-91 due to imipenem sensitive (ISPA) and 10 due to resistant (IRPA). Risk factors, the clinical course and the outcome were evaluated and compared. Acute leukaemia, prolonged neutropenia, previous therapy with amikacin, third generation of cephalosporins, imipenem and prophylaxis by quinolones were significantly more frequently associated with IRPA. Imipenem resistant PA bacteraemia were associated with higher incidence of septic shock (40% vs 19.8%, p < 0.02) and death (33.3%) than ISPA bacteraemias. Since 1992, when first IRPA appeared, the incidence of imipenem resistance increased tenfold, and in 1994, up to 10% of PA causing bloodstream infections in cancer patients in our center were imipenem resistant. (Tab. 3, Ref. 8.).

Bacteremia and fungemia occurring during antimicrobial prophylaxis with ofloxacin in cancer patients: risk factors, etiology and outcome.

The authors analyzed 27 breakthrough bacteremias occurring during ofloxacin prophylaxis in afebrile neutropenia over 7 years in 9989 admissions and 979 bacteremic and fungemic episodes in a National Cancer Center in Bratislava, Slovak Republic. The most frequently isolated organisms in breakthrough bacteremias were gram-positive (71.3%), mainly coagulase-negative staphylococci (41.3%), enterococci (9.2%) and Corynebacteria (9.2%), followed by gram-negative rods-Pseudomonas aeruginosa (13.2%) and Stenotrophomonas maltophilia (9.2%). The outcome of breakthrough bacteremias during ofloxacin prophylaxis was not associated with the underlying disease, neutropenia, catheter insertion or resistance, but only with multiple risk factors. A higher failure rate was observed in those patients having a catheter infected with a resistant organism and during neutropenia. No patients with Hickman catheter were included in the study. Patients with mixed breakthrough bacteremia due to gram-negative and gram-positive organisms had higher failure rates than those with monomicrobial bacteremia. Catheter extraction and rapid institution of intravenous antibiotics in combination should be administered in breakthrough bacteremia.

Funguria in cancer patients: analysis of risk factors, clinical presentation and outcome in 50 patients.

Fifty cancer patients with funguria of > 10(5) CFU/ml, dysuria and leukocyturia were retrospectively analyzed for etiology, risk factors and outcome. In 72% of cases Candida albicans and in 28% non-albicans Candida 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.

Polymicrobial bacteremia in cancer patients: analysis of risk factors, etiology and outcome in 214 episodes.

Two hundred and fourteen episodes of polymicrobial bacteremia in 182 cancer patients in a period of 6 years in a 360-bed National Cancer Institute were analyzed for etiology, risk factors and outcome. Variables were compared with 187 episodes of monomicrobial bacteremias in 147 cancer patients to find statistical significance among risk factors, etiology and outcome. Urinary catheters and breakthrough bacteremia were the only risk factors associated with polymicrobial in comparison to monomicrobial bacteremia (P < 0.05). Concerning etiology, Enterococcus faecalis, Candida spp., Acinetobacter calcoaceticus and Stenotrophomonas maltophilia were more commonly isolated in polymicrobial than in monomicrobial bacteremic episodes. Polymicrobial bacteremia presented more frequently with septic shock (22.9% vs. 9.0%, P < 0.05) and/or organ complications (25.2% vs. 11.8%, P < 0.05). However, mortality due to bacteremia did not significantly differ between polymicrobial and monomicrobial, but when polymicrobial bacteremia with and without coagulase negative staphylococci were compared, mortality in polymicrobial bacteremia without staphylococci was higher (10% vs. 4.7%, P < 0.04).

Vancomycin plus imipenem ceftazidime or ciprofloxacin in second line therapy in patients with febrile neutropenia not responding to first line therapy.

137 patients with febrile neutropenia after cytotoxic therapy not responding to ceftazidime plus or ceftriaxone plus netilmicin in received additionally to the previous combination either vancomycin alone or combined with another anti-gram-negative compound: imipenem in those treated prophylactically with ofloxacin and ciprofloxacin in those without prophylaxis. The addition of vancomycin to the previously ineffective combination of a third generation cephalosporin plus aminoglycoside, and replacement of ceftriaxone plus netilmicin with ceftazidime plus amikacin plus vancomycin or with ceftazidime plus vancomycin seems to be less effective (71.8-75 vs. 87.5-90.9%, p < 0.02) and more toxic (20.5-7.2 vs. 0-5%, p < 0.0005) than vancomycin in combination with a different anti-gram-negative compound as previously used: imipenem or ciprofloxacin.

Invasive mold infections in cancer patients: 5 years' experience with Aspergillus, Mucor, Fusarium and Acremonium 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.

Imipenen-resistant Ps. aeruginosa bacteraemia in cancer patients: risk factors, clinical features and outcome.

Ninety-nine patients with 101 bacteraemic episodes due to Pseudomonas aeruginosa (PA) within 6 years were divided into two groups according to their resistance to imipenem; of these 91 episodes were due to imipenem-sensitive (ISPA) and 10 due to imipenem-resistant (IRPA) strains. Risk factors, clinical course and outcome were evaluated and compared in the two groups. Acute leukaemia, long-lasting neutropenia, previous therapy with amikacin, third-generation cephalosporins, imipenem and prophylaxis with quinolones were significantly more frequently associated with IRPA than with ISPA. Imipenem-resistant PA bactereamias were associated with a higher incidence of septic shock (40% vs 19.8%) p. 161 0.02) and death 33.3%) than were ISPA bacteraemias. Since 1992, when first IRPA appeared, the incidence of imipenem-resistance increased tenfold, and in 1994, up to 10% of the PA populations causing bloodstream infections in cancer patients in our centre were imipenem-resistant.

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.