Nosocomial Candida krusei fungemia in cancer patients: report of 10 cases and review.

The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed. Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy. Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole. However, attributable and crude mortality due to C. krusei fungemias was higher than for C. albicans fungemia. The authors review 172 C. krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C. krusei fungemia from our cancer institute.

Invasive infections due to Clavispora lusitaniae.

Three cases of Clavispora lusitaniae invasive fungal infections are reported. All three infections appeared in cancer patients presented with fungaemia, one additionally with meningitis. Two of them were breakthrough -- they developed during therapy with conventional amphotericin B with a dose of 0.5 mg kg(-1) day(-1) . All three were cured: two with intravenous fluconazol and one with an increasing dose (1 mg kg(-1) day(-1)) of amphotericin B. In one of two breakthrough cases the sensitivity of the strain to antifungals was tested against antifungal agents and showed in vitro resistance to amphotericin B (MIC 2 eta g ml(-1)).

Candida parapsilosis fungemia in cancer patients--incidence, risk factors and outcome.

The paper presents an analysis of fungemia cases which were caused by C. parapsilosis in a cancer center within 10 years, with the aim to compare risk factors and the outcome with fungemias caused by C. albicans and other non-albicans Candida spp. fungemias. Before 1990 (1988-1989) in our institutes C. parapsilosis fungemias were not observed at all. During 1990-1997, the proportion of C. parapsilosis among fungemias increased, in 1990-1993 from 0% to 7.1% in 1996-1997 to 14.2-15%. It represents 25% out of non-albicans Candida spp. fungemias and 7.9% out of all fungemias and is the third commonest pathogen after C. albicans (50.5%) and C. krusei (9.9%). Two from eight (25%) C. parapsilosis fungemias were breakthroughs, one appeared during prophylaxis with ketoconazol and one with fluconazol. Considering the proportion of C. parapsilosis among blood cultures, 13 of 170 blood cultures contained C. parapsilosis (6.6% among all yeasts from blood cultures). C. parapsilosis was the second commonest fungal organism isolated from blood cultures (after C. albicans) in our cancer center. Infected vascular catheters were surprisingly not the major risk factor: central venous catheters were documented as a source in two cases only. The commonest risk factors were similar to those occurring with other fungemias--such as preceding antimicrobial therapy (62.5%), neutropenia (50%) and prior prophylaxis with azoles.

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.

Analysis of 553 episodes of monomicrobial bacteraemia in cancer patients: any association between risk factors and outcome to particular pathogen?

Relationships between aetiology, various risk factors (such as neutropenia, catheter insertion, endoscopy, therapy with corticosteroids, therapeutic use of antimicrobials, antibiotic prophylaxis, source of infection), symptomatology and outcome were studied in 553 monomicrobial bacteraemic episodes in cancer patients observed within 7 years at the National Cancer Institute of the Slovak Republic. The ratio of gram-positive to gram-negative bacteraemia was 1:1 (43.5% vs 43.8%), and yeasts caused 7.2% of monomicrobial episodes. The highest mortality was associated with Pseudomonas aeruginosa (19.2%), non-albicans Candida yeasts (25%) and Bacteroides fragilis (22.6%). Independent risk factors for particular pathogens were investigated by a computerized logistic regression model. The only independent risk factor for staphylococcal and enterococcal bacteraemia was vascular catheter insertion (OR = 1.95 and 2.05, CI = 95%, P = 0.035 and 0.044, respectively). However, there were no independent specific risk significant factors for viridans streptococcal bacteraemia and bacteraemia due to Enterobacteriaceae or Ps. aeruginosa. Neutropenia was found to be an independent predictor for development of Acinetobacter spp. bacteraemia (OR = 3.84, CI = 95%, P = 0.044). Prior therapy with third-generation cephalosporines was a predictive, independent risk factor for the development of fungaemia (OR = 1.99, CI = 95%, P = 0.028) but not of enterococcal bacteraemia. We also did not observe any association between prior therapy with imipenem and Stenotrophomonas maltophilia bacteraemias. Multivariate analysis confirmed that fungaemia may be independently associated with higher mortality than bacteraemia caused by Enterobacteriaceae and staphylococci. However, the mortality of fungaemia was statistically no different from that of Ps. aeruginosa, Stenotrophomonas spp. and viridans streptococci bacteraemias.

Bacteremia in cancer patients with solid tumors undergoing chemotherapy versus surgery: risk factors, etiology and outcome in 276 patients.

Etiology, risk factors, outcome and complications of bacteremia in 276 patients with solid tumors were analyzed. A group of 78 patients with solid tumors and surgical therapy only was compared with 172 patients with solid tumors who were treated with chemotherapy only. The most frequently observed risk factors of bacteremia in patients after surgery was urinary catheter insertion, wound as source of bacteremia, age > 60, staphylococci, enterococci and Enterobacteriaceae as etiologic agents. In comparison, viridans streptococci and Pseudomonas aeruginosa as etiologic agents as well as vascular catheters were significantly more frequently found in those treated with chemotherapy only. Patients with bacteremia after surgery only had a lower incidence of septic shock (6.4 vs. 16.9%, P < 0.03) and also lower mortality (5.6 vs. 14.9%, P < 0.04) attributable to shock than patients being treated for solid tumors with chemotherapy only.

Bacteremia due to Enterobacter spp. in cancer patients--analysis of 51 episodes.

Fifty one episodes of bacteremia due to Enterobacter spp. appearing within 7 years among 12 301 admissions in a single cancer institution were studied for risk factors, clinical presentation and outcome. Fifteen episodes were due to Enterobacter aerogenes, 23 due to E. cloacae and 13 due to E. agglomerans. The proportion of bacteremia due to Enterobacter spp. among Gram-negative bacteremias was 10.1% and infection associated mortality was 13.8%. The incidence in 1989-1995 varied from 3.7 to 8.7% and was relatively stable. Most common risk factors were: solid tumors as underlying disease, central venous catheter insertion, prior surgery and prior chemotherapy within 48 h. Neutropenia and urinary catheters were not at high risk in either one of the patients subgroups. Comparing two subgroups of 51 bacteremias, monomicrobial and polymicrobial (when Enterobacter spp. was isolated from blood culture with other microorganism), previous chemotherapy, vascular catheter insertion and prior endoscopy were more frequently associated with polymicrobial Enterobacter spp. bacteremia. There was also differences in infection associated mortality: bacteremias due to Enterobacter spp. only had significantly lower mortality in comparison to polymicrobial Enterobacter spp. bacteremias (3.3 vs. 29.3%; P<0.02). Susceptibility of Enterobacter spp. strains isolated from 51 episodes was stable and showed only two episodes due to quinolone-resistant strains, both in 1992 despite of the use of ofloxacin in prophylaxis of neutropenic patients since 1990 in our institute. Ninety-two to 94% of all strains were susceptible to aminoglycosides, 96-98% to ofloxacin and ciprofloxacin, respectively and 94.9% to meropenem but only 75.5% to ceftazidime.

Resistance pattern of 2816 isolates isolated from 17631 blood cultures and etiology of bacteremia and fungemia in a single cancer institution.

The resistance pattern of 2816 isolates from 17631 blood cultures and the etiology of isolates causing bacteremia and fungemia among 14591 admissions were investigated in an 80-bed single cancer institute during seven years (1990-1996) under the same empiric therapeutic antibiotic policy but with different prophylactic strategies. No change was found in the proportion of Gram-positive versus Gram-negative bacteria isolated from bacteremias (70% vs. 30%) during the past seven years. Furthermore, the proportion of coagulase-negative staphylococci and enterococci was about the same before and after the introduction of ofloxacin in prophylaxis. However, the proportion of Pseudomonas aeruginosa and Stenotrophomonas maltophilia causing bacteremia increased. There was no increase in Candida krusei and Candida glabrata after the introduction of fluconazole into our prophylactic regimen in 1992. Penicillin-resistance in viridans streptococci increased after penicillin was introduced into prophylaxis in acute leukemia in 1993. Until 1995 no quinolone-resistant Enterobacteriaceae were observed. Susceptibility to quinolones did not significantly change within the past seven years in Enterobacteriaceae after their introduction to prophylaxis in 1991, but Pseudomonas aeruginosa decreased from 90 to 58.2%. Glycopeptide resistance in enterococci and staphylococci was minimal in the observed period (0.9-4.3%).

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.

Do vancomycin serum levels predict failures of vancomycin therapy or nephrotoxicity in cancer patients?

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B. Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15 microg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 microg/mL had peak levels exceeding 40 microg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity. A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of gram-positive bacteremia in cancer 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%).

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.).

Etiology of bacteraemia in patients with various malignancies: is there association between certain antineoplastic drugs and microorganism?

The authors studied a relationship between particular bacterial or fungal organisms isolated from blood cultures and type of malignancy and antineoplastic drugs in 237 cancer patients. Sixty four had acute myelogenous leukemia (AML), 43 non-Hodgkin's lymphoma (NHL) and 140 solid tumors (ST). All patients had at least one positive blood cultures for one or more microorganism drawn during 1-10 days after cytotoxic chemotherapy, viridans streptococcal bacteremia was more frequently observed in patients with AML (12.5%) and NHL (27.9%) than ST (43%, p < 0.01 and 0.03). The incidence of anaerobic bacteria was similar in patients with NHL and ST, and in both groups significantly higher (p < 0.05) than in AML. Enterobacteriaceae caused bacteremia less frequently in patients with AML than in those with ST (12.5 vs 27.8%, p < 0.05). However, the highest incidence of Stenotrophomonas maltophilia bacteremia was seen in patients with AML (6.3% vs 2.3%, p < 0.04 and 0.03). Concerning fungemia, Candida albicans occurred significantly more frequently in blood cultures in patients with NHL, and molds in patients with AML. Cytarabine and metothrexate seems to be more frequently associated with viridans streptococci, cytarabine and mitoxanthrone with Stenotrophomonas maltophilia, B. fragilis with cisplatin and 5-fluorouracil, Fusarium spp., Mucorales and Aspergillus spp. with acute leukaemia (AL) treated with cytarabine and mitoxantrone. The association of other pathogens with an underlying disease or chemotherapeutic regimen could not be documented. (Tab. 1, Ref. 19.).

Bacteremia in cancer patients with solid tumors undergoing chemotherapy versus surgery: risk factors, etiology and outcome in 276 patients.

Risk factors, etiology, symptomatology and outcome of bacteremia in 276 patients with solid tumors were evaluated. A group of 78 patients with solid tumors and surgical therapy was compared with 172 patients with solid tumors but treated solely by chemotherapy. The most frequently observed risk factors of bacteremia in patients after surgery were the vascular and urinary catheter insertions, wound as source of bacteremia, staphylococci, enterococci and Enterobacteriaceae as etiologic agents. Comparing the group of therapeutically treated patients with solid tumors, with the group of those treated only by chemotherapy, a statistically significant difference in risk factors between both groups was observed only in the incidence of catheter insertion (more frequently in surgically treated patients), neutropenia (more frequently in those treated by chemotherapy). Wound as source of bacteremia was more frequently observed in those after surgery. Enterobacteriaceae and enterococci were significantly more frequently observed in patients with solid tumors treated by surgery. Surprisingly, patients after surgery the mortality due to septic shock was lower in (6.4% vs 16.9%, p < 0.03) than in the control group of patients with solid tumors treated solely by chemotherapy. (Tab. 1, Ref. 5.).

Do low vancomycine serum levels predict failures of vancomycine therapy in neutropenic cancer patients?

Vancomycine serum levels were measured in 198 cancer patients with documented grampositive bacteremia and twenty two failed. Failures were analyzed for risk factors of therapy failure. Only 8 of 22 showed low serum peak or through vancomycin levels. One patient was treated less than 7 days, 9 had persisting and 4 catheter associated bacteremia. Bacteremias due to VAN resistant strains were excluded. In 14 out of 22 patients, multiple or one risk factor could be determined, but in 8 patients, no risk factor was found. Hence the, case control study was conducted to compare the group of failures in 22 patients with a group of patients with underlying disease and neutropenia treated successfully within the same period and same antibiotic policy at the same cancer center, by VAN for gram-positive bacteremia. Persisting, catheter associated and enterococcal bacteremias were the only statistical significant risk factors predicting a therapy failure in cancer patients. Neither Vancomycine serum peak nor through levels predicted the outcome: failure or cure of gram-positive bacteremia in cancer patients. (Tab. 1, Ref. 5.).