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).

Antibiotic use and development of resistance in blood culture isolates: 8 years of experience from a cancer referral center.

The consumption of antimicrobial agents in a Slovakian national cancer institute from 1989-1996 was compared with resistance rates in clinically significant blood culture isolates. We observed an increase in resistance of viridans streptococci to penicillin and of enterococci to ampicillin. Resistance to vancomycin and teicoplanin was stable over the entire period despite a 20-fold increase in vancomycin consumption. Nor did we observe increased resistance to ofloxacin despite a 10-fold increase in consumption. Consumption of aminoglycosides and resistance levels were both stable. A different situation was observed with third-generation cephalosporins, where resistance of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter spp. to ceftazidime and cefotaxime increased with increasing consumption. Resistance of Enterobacteriaceae to cefotaxime and ceftazidime was stable. Resistance to imipenem did not change significantly. However, the number of Stenotrophomonas maltophilia bacteremias increased significantly after imipenem was introduced in 1991. Because of improved outcome in bacteremia, an increased incidence of both gram-negative and gram-positive bacteremia led to only a slight increase in associated mortality.

Prospective study on fungemia in children with cancer: analysis of 35 cases and comparison with 130 fungemias in adults.

The aim of this prospective study on fungemia in children with cancer compared with adults with cancer appearing during the last 10 years in a pediatric hospital and in national cancer institutions was to investigate risk factors, etiology, therapy, complications and outcome. Univariate analysis showed significant differences in 35 children with cancer and fungemia in comparison with 130 cases of fungemias in adults with cancer. It was found that (1) therapy with corticosteroids (40 vs 18.5%, P<0.03), (2) breakthrough fungemia during ketoconazole prophylaxis (20 vs 7.7%, P<0.025), and (3) meningitis as a complication of fungemia (11.4 vs 0.8%, P< 0.001) occurred more frequently in the pediatric subgroup with fungemia. Candida albicans was more common as the causative agent of fungemia among adults (58.5 vs 37.1, P<0.02) than in children. However, mortality was similar in children with cancer and in adults with cancer and fungemia (31.4 vs 23.1%, NS). Comparison of risk factors revealed no differences between adults and children with cancer and fungemia except in etiology, breakthrough fungemia during prophylaxis with ketoconazole, prior therapy with corticosteroids and meningitis as a complication. The outcome was also similar in pediatric and adult cancer patients with fungal bloodstream infection.

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.

Documented fungal infections after prophylaxis or therapy with wide spectrum antibiotics: relationship between certain fungal pathogens and particular antimicrobials?

Antibiotics are known to be one of the major risk factors for fungal infection. We investigated whether there was a relationship between particular documented fungal infections and therapeutically or prophylactically administered antimicrobials in 105 patients with fungemia or histologically proven invasive aspergillosis or fusariosis. Out of 105 patients, 82.9% received antimicrobials affecting anaerobic microbial gut flora such as: imipenem, vancomycin, ceftazidime, metronidazole, clindamycin or ampicillin-sulbactam. In addition, 44.5% of patients had received prophylaxis with ofloxacin. 31.5% of Candida albicans fungemias occurred despite empiric therapy with amphotericin B and 21.1% during prophylaxis with azoles. The incidence of C. albicans infections (fungemias) was significantly higher (58.9% vs 33.7%, p<0.04) in patients receiving antibiotics not affecting anaerobic gut flora such as ofloxacin, an aminoglycoside or azithromycin. On the other hand, patients treated with third generation cephalosporins, carbapenems, glycopeptides, and broad spectrum penicillins were more likely to develop proven invasive Aspergillus spp. infection (27.9% vs 5.3%, p<0.001) in comparison to those treated with antimicrobials which preserve anaerobic gut flora.

Bacteremia due to multiresistant gram-negative bacilli in neutropenic cancer patients: a case-controlled study.

The aim of this study was to assess whether multiresistant gram-negative bacteremias (MRGNB) were associated with specific risk factors for higher mortality than sensitive gram-negative bacteremias. Two groups of subjects: (51 cases and 102 controls) were matched for sex, age, underlying disease, and neutropenia. There were no significant differences in the incidence of cytotoxic chemotherapy administered, vascular catheter insertion, catheter as source of bacteremia, and etiology of bacteremia. The proportion of Klebsiella-Enterobacter, Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia was similar in the two groups. Prior surgery (21.6% vs 7.9%, P < 0.05) was significantly associated with sensitive gram-negative bacteremia. Previous prophylaxis with ofloxacin (45.1% vs 24.5%; P < 0.05) and prior therapy with broad-spectrum antibiotics (41.2% vs 27.5%; P < 0.05), such as first and second generation cephalosporins (19.6% vs 7.8%; P < 0.05), third generation cephalosporins (41.2% vs 13.7%; P < 0.01), aminoglycosides (39.2% vs 9.8%; P < 0.01), ofloxacin (11.8% vs 2.0%; P < 0.005), and imipenem (19.6% vs 2.0%; P < 0.001) were significantly more frequently observed among cases than controls. Cases (patients with bacteremia due to multiresistant gram-negative bacteremias) were also significantly more frequently infected with bacteria resistant to ceftazidime (68.6% vs 17.6%; P < 0.001), amikacin (52.9% vs 7.8%; P < 0.001), imipenem (50.1% vs 23.5%; P < 0.05), ciprofloxacin (32.1% vs 5.9%; P < 0.001), and piperacillin (41.2% vs 7.8%; P < 0.01). With regard to outcome, attributable mortality was similar (15.7% vs 13.8%; not significant) in the two groups; however, cure rates were lower among cases (patients infected with MRGNB) because crude mortality was higher in cases (35.3% vs 13.8%; P < 0.01) than in controls.

Bacteremia due to multiresistant gram-negative bacilli in neutropenic cancer patients: a case controlled study.

The aim of this study was to see if multiresistant Gram-negative bacteremias (MRGNB) are associated with specific risk factors and/or higher mortality in comparison to sensitive GNB (SGNB). Both groups, 51 patients and 102 controls, were matched for sex, age, underlying disease and neutropenia. In addition there were no significant differences in the incidence of cytotoxic chemotherapy administered, vascular catheter insertion and catheter as source of bacteremia and etiology of bacteremia. The proportion of Klebsiella-Enterobacter, Pseudomonas aeruginosa, Acinetobacter spp. and Stenotrophomonas maltophilia was similar in both groups. Prior surgery (21.6% vs 7.6%, p<0.02) was significantly associated with SGNB. Previous prophylaxis with quinolones (45.1% vs 24.5%, p<0.045), and prior therapy with broad spectrum antibiotics (41.2% vs 27.5%, p<0.05) were significantly more frequently observed among patients than controls. Patients with bacteremia due to MRGNB were also significantly more frequently infected with resistant bacteria. Attributable mortality was similar (15.7% vs 13.75%, NS) in both groups, however cure rates were lower among MRGNB patients. Crude mortality was higher among patients (35.3% vs 13.75%, p<0.01) in comparison to controls. In conclusion, prior antimicrobial prophylaxis and therapy with several classes of antimicrobials represents a significant risk for development of resistance. Mortality due to multiresistant Gram-negative bacteremias was higher in comparison to bacteremias due to susceptible organisms.

Bacteremia due to methicillin-resistant staphylococci occurs more frequently in neutropenic patients who received antimicrobial prophylaxis and is associated with higher mortality in comparison to methicillin-sensitive bacteriemia.

Bacteriemia due to coagulase-negative staphylococci (CNS) resistant to methicillin and sensitive only to glycopeptides in 220 cancer patients was prospectively analyzed for risk factors and outcome. A group of 33 cases of bacteriemia with CNS-sensitive only to glycopeptides was compared with a group of 187 cases with CNS sensitive to methicillin. All cases appeared in two affiliated major cancer institutes in Bratislava with the same antibiotic policy. Univariate analysis showed differences in recorded risk factors: acute leukemia (48 vs. 33%, P < 0.05), neutropenia (57 vs. 32%, P < 0.045), previous prophylaxis with quinolones (30 vs. 11%, P < 0.01) and penicillin-V (15 vs. 3%, P < 0.02) and previous colonisation with CNS (27 vs. 3%, P < 0.01) were more frequently associated with bacteriemia resistant to methicillin and sensitive only to glycopeptides. Attributable mortality was also higher in this subgroup in comparison to bacteriemias with CNS sensitive to methicillin (12 vs. 3%, P < 0.05) however, overall mortality was similar. Bacteriemias due to CNS caused by sensitivity only to glycopeptides occurred more frequently in neutropenic patients (1), with acute leukemia (2), receiving quinolone and penicillin prophylaxis (3), and previously colonized (4), patients and had worse prognosis in comparison to those with methicillin-sensitive staphylococcal bacteriemias.