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.

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.

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.).

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.).

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).

Multicenter randomized study of two once daily regimens in the initial management of community-acquired respiratory tract infections in 163 children: azithromycin versus ceftibuten.

In a randomized trial, we compared the efficacy and toxicity of azithromycin and ceftibuten once daily in the initial (empiric) therapy of proven or suspected community-acquired respiratory tract infections (CARTI) in 163 pediatric patients: 95.5% of those treated with azithromycin and 83.6% of those treated with ceftibuten were cured or improved. Streptococcus pneumoniae was more frequently eradicated in the azithromycin than in the ceftibuten group, whereas gram-negative bacilli were more susceptible to ceftibuten. Elimination rates for Staphylococcus aureus and Haemophilus influenzae were similar; adverse reactions did not differ in both arms. Thus, azithromycin was more effective but equally safe than ceftibuten in the initial therapy of pediatric CARTI.

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.

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.