Predictors of mortality in bacteremic cancer patients: retrospective analysis of 64 deaths occurring among 262 bacteremic episodes.

A total of 262 bacteremic episodes were observed in cancer patients in a single cancer institution during the last 7 years, and the recorded outcome was death in 65. The 65 patients who died (24.8% overall mortality) were divided retrospectively into two subgroups: (a) those who died of underlying disease with bacteremia (45 cases, 16.9% crude mortality) and (b) those who died of bacteremia (20 patients, 7.7% attributable mortality). Comparison of several risk factors in subgroups of patients who achieved a cure (197 cases) and of those who died and whose deaths were attributable (20 cases) revealed six risk factors that were associated with attributable mortality: (1) chemotherapy-induced neutropenia (P < 0.03), (2) Acinetobacter/Stenotrophomonas spp. bacteremias (P < 0.001), (3) liver failure (P < 0.001), (4) inappropriate therapy (P < 0.0001), (5) organ complications (P < 0.003) and (6) multiresistant organisms (P < 0.001). Enterococci and Pseudomonas aeruginosa, surprisingly, were found more frequently in those who died of an underlying disease with bacteremia than among patients who were cured (17.6% vs 7.6%, P < 0.05 and 29.1% vs 13.8%, P < 0.02). Those who died of infection had higher numbers of positive blood cultures, with 2.05 per episode, than did those who died of underlying disease with bacteremia (1.82) or those who were cured (1.51). Other risk factors, such as underlying disease, type of chemotherapy, origin of bacteremia, age, and catheters did not predict either overall or attributable mortality within the study group.

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.

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.

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.

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%).

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.

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%).

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.).

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.).

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.

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.

Bloodstream infections due to anaerobic bacteria in cancer patients: epidemiology, etiology, risk factors, clinical presentation and outcome of anaerobic bacteremia.

Thirty one bacteremic episodes (BE) in 31 patients due to anaerobic bacteremia (AB) in 979 BE among 9986 admissions at a 360 beds National Cancer Institute within last 6 years were analyzed for time distribution, risk factors, clinical presentation and outcome. Overall incidence of AB was 3.6%, but the proportion to other groups of microorganisms is decreasing. 73% were Bacteroides fragilis, 10.8% Peptostreptococci and Propionibacteria and 5.4% Clostridia. The most common risk factor for AB was prior surgery, solid tumor as underlying disease, prophylaxis with quinolones and previous therapy with third generation cephalosporines. 48.4% of AB were polymicrobial. Infected wound was the most common source of infection in 38.7% of our cancer patients. Six patients (19.4%) presented septic shock, and 45.2% died, but only in 22.6% death was related to bacteremia. Comparing the groups of AB due to B. fragilis (BF) to non-Bacteroides spp. (NB)AB, infection-associated mortality was higher in BFAB in comparison to NBAB. Other risk factors such as hematologic malignancies, previous prophylaxis with quinolones, prior surgery and prior therapy with broad spectrum antimicrobials, were more frequently associated with BFAB.