Trimethoprim/sulfamethoxazole prophylaxis in neutropenic patients: Reduction of infections and effect on bacterial and fungal flora

A prospective, randomized study was undertaken in neutropenic patients to evaluate the efficacy of prophylactic trimethoprim/sulfamethoxazole in reducing infections and to assess the effect of prophylaxis on bacterial and fungal flora. Fifty-five patients with leukemia, lymphoma, or solid tumors randomly received either one single-strength trimethoprim/sulfamethoxazole tablet twice daily or no drug for the period of expected neutropenia. Trimethoprim/ sulfamethoxazole prophylaxis did not significantly reduce the mean number of febrile days per patient, but did decrease the number of documented infections. The control group experienced 28 infections, including 11 bacteremias and seven infection-associated deaths; the group that received trimethoprim/sulfamethoxazole had seven infections, including two bacteremias and no infection-related deaths. Patients treated with trimethoprim/sulfamethoxazole had no enteric gram-negative bacillary infections compared with 12 infections in the control group. Fungal infections occurred in four control patients but only in one patient who received trimethoprim/sulfamethoxazole. Surveillance cultures revealed that trimethoprim/sulfamethoxazole prophylaxis did not lead to colonization with trimethoprim/sulfamethoxazole-resistant Enterobacteriaceae, Pseudomonas, or fungi. Colonization with filamentous fungi was common in both groups and was related to season of the year rather than prophylactic antibiotic therapy. In conclusion, trimethoprim/ sulfamethoxazole prophylaxis reduced infectious episodes in neutropenic patients without increasing the risk of fungal and trimethoprim/sulfamethoxazole-resistant gram-negative bacillary infections.     

Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients

The clinical and microbiologic efficacy of trimethoprim alone and trimethoprim/sulfamethoxazole for infection prevention was evaluated in 75 patients during 92 episodes of granulocytopenia. Ultimately, 60 patients were evaluable during 77 episodes of granulocytopenia, 36 episodes in the trimethoprim group and 41 episodes in the trimethoprim/sulfamethoxazole group. The incidence of infection was higher in the trimethoprim group (50 percent) than in the trimethoprim/sulfamethoxazole group (39 percent), but this did not reach statistical significance. Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm³. In patients receiving trimethoprim/sulfamethoxazole, aerobic gram-negative bacilli cleared from fecal surveillance cultures more often and new aerobic gram-negative bacilli were acquired less often than in those receiving trimethoprim alone (p < 0.05). More myelosuppression was observed among patients receiving trimethoprim/sulfamethoxazole (p < 0.001). These observations suggest that trimethoprim alone may not be optimal for preventing colonization and infection in granulocytopenic patients and that combination with other agents may be necessary to increase the spectrum of activity. Trimethoprim/sulfamethoxazole itself may predispose toward an increased risk of infection by prolonging myelosuppression.     

A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Ciprofloxacin Urinary Tract Infection Group

PURPOSE: Bladder infections are very common in otherwise healthy women, and short-course antimicrobial treatment appears effective for many episodes of cystitis. This study reports the results of short-course ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole therapy. PATIENTS AND METHODS: We performed a randomized, double-blind study of the efficacy and safety of a 3-day course of oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute, uncomplicated, symptomatic lower urinary tract infection. RESULTS: A total of 866 patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of treatment (229 treated with ciprofloxacin, 228 treated with trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent reason for exclusion was the failure to identify a pretreatment pathogen. The most commonly isolated pathogen was Escherichia coli (81%). Eradication of the pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93% of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection) were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13% in the ofloxacin treatment group. Clinical success at the end of therapy was 93% in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the ofloxacin treatment groups. The frequency of all adverse events was 31% for ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin-treated patients (P = 0.03). Premature discontinuation of study drug due to an adverse event was more common in trimethoprim/sulfamethoxazole-treated patients (n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P = 0.02). CONCLUSION: Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole had similar efficacy when given for 3 days to treat acute, symptomatic, uncomplicated lower urinary tract infection in women.     

Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia

The efficacy of orally administered trimethoprim/sulfamethoxazole for infection prevention following induction chemotherapy was evaluated in 43 patients with acute leukemia. Twenty patients were randomly assigned to treatment with trimethoprim/sulfamethoxazole during 20 episodes of profound granulocytopenia; 23 patients in the control group were followed through 25 granulocytopenic episodes. The incidences of superficial skin and overall infections were significantly lower in those patients with multiple relapses who received trimethoprim/sulfamethoxazole (p = 0.008); however, there was no difference between the groups in regard to days of fever, days of antibiotic administration, days of hospitalization, or gram-negative rod bacteremia. As a result of this study, this regimen cannot be unequivocally recommended for infection prevention in neutropenic patients with acute leukemia undergoing induction or reinduction chemotherapy.     

A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients.

Oral trimethoprim/sulfamethoxazole (TMP/SMZ) therapy was investigated in the prophylaxis of infections in granulocytopenia. Hospitalized granulocytopenic patients were allocated at random to receive TMP/SMZ (group 1) or to a control group (group 2). The percentage of febrile granulocytopenic days was significantly reduced in group 1, 19 per cent compared to 39 per cent in group 2 (P less than 0.01). In group 1, there were no bacteremias in 59 episodes of granulocytopenia (909 days). In group 2, there were nine bacteremias in 52 episodes of granulocytopenia (796 days)(P = 0.001). Disseminated candidiasis developed in two patients in each group. Candida occurred in similar numbers in surveillance cultures in both groups; Staphylococcus aureus and Pseudomonas aeruginosa were slightly decreased, and Enterobacteriaceae resistant to TMP slightly increased in group 1. This study suggest that oral prophylactic TMP/SMZ therapy is an effective, well tolerated, easily administered alternative to "gut sterilization" with nonabsorbable antibiotics.     

Infectious complications during remission induction therapy in 577 patients with acute myeloid leukemia in the Japan Adult Leukemia Study Group studies between 1987 and 1991

The Japan Adult Leukemia Study Group analyzed infectious episodes in 577 patients with acute myeloid leukemia during remission induction therapy between 1987 and 1991. 542 patients (93.9%) experienced at least one infectious episode, 121 (21.0%) had microbiologically documented infection; there was clinically documented infection in 184 (31.9%) and unexplained fever in 237 (41.1%). Among 121 microbiologically documented infections, bacteremia/fungemia was observed in 68, pneumonia in 33, and other types of infections in 20. Among the bacteremia/fungemia, gram-negative bacteria accounted for 41.2% (Pseudomonas aeruginosa was the most common), gram-positive bacteria for 39.7%, fungi for 16.2% (Candida spp. being most frequent), and polymicrobial for 2.9%. The most frequent isolates among pneumonia were Pseudomonas aeruginosa and Aspergillus. A total of 70 patients (12.1%) died during remission induction. Mortality of 68 patients with bacteremia/fungemia was 26.5%; in these patients, mortality with concomitant pneumonia increased to 41.4%; without pneumonia, mortality was 15.4% (P < 0.05). Mortality according to the isolated microbes was 17.2% for gram-negative bacteria, 25% for gram-positive bacteria, and 54.5% for fungi. Mortality of 113 patients with pneumonia (33 microbiologically documented and 80 clinically documented), 20 with other microbiologically documented infections, 104 with other clinically documented infections, and 237 with unexplained fever was 25.7%, 5.0%, 5.8%, and 5.1%, respectively.     

Ofloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients

INTRODUCTION: The efficacy and safety of oral ofloxacin were compared with those of vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients undergoing chemotherapy for hematologic malignancy. PATIENTS AND METHODS: Antimicrobial prophylaxis was begun at the time of initiation of chemotherapy. Thirty patients received ofloxacin tablets (300 mg orally every 12 hours) plus a nystatin suspension. Thirty-two patients received vancomycin capsules (500 mg orally every eight hours) and polymyxin capsules (100 mg orally every eight hours) plus a nystatin suspension. RESULTS: In the group of patients receiving ofloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.13 versus 1.37, p less than 0.00005), fewer patients with documented infection (11 of 30 versus 21 of 32, p = 0.04), and fewer cases of gram-negative septicemia (zero of 30 versus five of 32, p = 0.05). Ofloxacin was also better tolerated (24 of 30 versus 10 of 32 patients highly compliant, p = 0.01) and associated with fewer gastrointestinal side effects (one of 30 versus nine of 32 patients with gastrointestinal side effects, p = 0.01) than vancomycin/polymyxin. However, except for a reduction of Staphylococcus aureus colonization and infection by ofloxacin, neither ofloxacin nor vancomycin/polymyxin was effective in eliminating colonization or infection with viridans group streptococci, coagulase-negative staphylococci, or other gram-positive organisms. Only three isolates of ofloxacin-resistant gram-negative bacteria (Pseudomonas fluorescens, Pseudomonas putida, and Enterobacter aerogenes) were isolated from surveillance cultures, but none caused infection. CONCLUSION: These results suggest that oral ofloxacin is a more tolerable and efficacious alternative to vancomycin/polymyxin for prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive infections, however, is still needed.     

Management of recurrent urinary tract infections with patient-administered single-dose therapy

In a randomized crossover trial, 38 women with recurrent urinary tract infections were assigned to use either continuous prophylaxis with trimethoprim-sulfamethoxazole or intermittent self-administered therapy (single-dose trimethoprim-sulfamethoxazole taken for acute urinary symptoms). The infection rate for patients on prophylaxis was 0.2 episodes/patient-year compared with 2.2 infections/patient-year for patients on self-administered therapy (p less than 0.001). Thirty-five of thirty-eight symptomatic episodes diagnosed by patients as infection were confirmed microbiologically, and 30 of the 35 infections responded clinically and microbiologically to patient-administered therapy with single-dose trimethoprim-sulfamethoxazole. No complications were seen in the 5 patients in whom therapy failed. The annual costs of prophylaxis and self-therapy were similar ($256 and $239, respectively) and both were less expensive than conventional therapy in women having 2 or more infections per year. In selected women, self-therapy is efficacious and economical compared with conventional therapy or prophylaxis.     

Norfloxacin versus cotrimoxazole for infection prophylaxis in granulocytopenic patients with acute leukemia. A prospective randomized study

Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections. Nineteen NOR patients (65%) and 22 TMP/SMX patients (73%) complained of febrile or infectious episodes during the study. The mean incidence of febrile complications per patient was higher in the TMP/SMX group: 1.05 vs 0.68 (p less than 0.05). Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli (GNB). NOR recipients had fewer days of fever, fewer days on parenteral antibiotics and a lower proportion of time spent febrile. Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group (resistant strains: 93%) and in 8/75 specimens in the NOR group (1 resistant strain). Overall, NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients.     

Norfloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients

Selective antimicrobial decontamination with norfloxacin was compared with vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients. In the group of patients receiving norfloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.88 versus 1.86, p = 0.002), fewer patients with documented infection (16 of 36 versus 20 of 30, p = 0.12), and fewer cases of gram-negative septicemia (0 of 36 versus five of 30, p = 0.02). Norfloxacin was better tolerated (30 of 36 versus 16 of 30 patients highly compliant, p = 0.02), and associated with fewer gastrointestinal side effects (eight of 36 versus 14 of 36 patients, p = 0.07). These results suggest that norfloxacin is a more tolerable and efficacious oral antimicrobial agent than vancomycin/polymyxin for the prevention of serious gram-negative bacillary infections in granulocytopenic patients.     

Empiric antibiotic therapy for suspected infection in granulocytopenic cancer patients: a comparison between the combination of moxalactam plus amikacin and ticarcillin plus amikacin

Moxalactam is a new cephalosporin with a broad spectrum of activity which includes Pseudomonas aeruginosa in addition to Klebsiella species Escherichia coli, and Staphylococcus aureus. Moxalactam was combined with amikacin (M + A) compared to ticarcillin plus amikacin (T + A) in a prospective, randomized double-blind trial of empiric therapy for febrile episodes among granulocytopenic cancer patients. One hundred and ninety-one epidoses were evaluated; T + A, 93 episodes and M + A, 98 episodes. Median granulocyte count of initiation of therapy was less than 100/microliters. Overall response rates were good. In the T + A group, 21 of 29 (72 percent) microbiologically documented infections, including seven of 14 (50 percent) bacteremias, and 24 of 27 (89 percent) clinically documented infections improved. In the M + A group, 20 of 28 (71 percent) microbiologically documented infections, including 11 of 18 (61 percent) bacteremias, and 25 of 25 (96 percent) clinically documented infections resolved. Adverse effects were minimal and equivalent in both groups. Hypokalemia (decrease in serum potassium of greater than 11 mEq/liter from baseline) occurred in 14 of the 93 episodes in the T + A group and in 10 of the 98 episodes in the M + A group with decline in mean serum potassium level of 0.5 and 0.4 mEq/liter respectively. Nephrotoxicity (increase in serum creatinine greater than 0.04 mg/dl) occurred in only one patient in the T + A group and in two patients in the M + A group. Moxalactam plus amikacin has a broader in vitro spectrum, is as effective, and is no more toxic than ticarcillin plus amikacin as empiric therapy for febrile granulocytopenic cancer patients.     

Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic patients in Saudi Arabia.

Sixty-four consecutive febrile episodes in 50 consecutive patients with malignancy and neutropenia were empirically treated with a combination of ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6% overall and 26.3% of episodes with microbiologically documented infections with septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes). The response rates were similar in patients with acute leukaemia or other malignancies. Poor response is attributed to increased frequency of infections with Gram-positive and fungal organisms. A modified empiric regimen including cover for Gram-positive and fungal organisms is suggested in similar patient populations.     

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence

We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P < 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.     

Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus

This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lethal infections in patients with hematological malignancies

Abstract: The hospital files of 410 patients with hematological malignancy treated at our clinic between 1977 and 1990 were reviewed to determine the importance of infections as a cause of death. The total number of infections was 203 (49.5%). A microbiologically documented infection was detected in 27.3%, a clinically documented infection in 9.5% and a possible infection in 12.7% of the patients. Gram-positive bacteria were responsible for 25.9%, gram-negative bacteria for 31.3%, anaerobic baeteria for 2.7%, viruses for 4.5% and fungi for 25.9% of the microbiologically documented infections. Of 29 systemic fungal infections only 2 were diagnosed before the patients died. The remaining diagnoses rested on autopsy findings. Empiric antifungal therapy was introduced in 1983; still, 74.2% of systemic fungal infections in 1977–1990 were detected after 1982. Patients with a verified infection had statistically significantly higher CRP concentrations than patients who died of other causes (152 mg/l vs. 117.5 mg/l, p = 0.018). We conclude that infection is a significant cause of death in patients with these diseases. The number of systemic fungal infections is increasing, despite the widespread use of antifungal medication and thus better diagnostic methods and more effective treatment are needed. –     

A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients.

Patients were randomly assigned to receive carbenicillin plus tobramycin by continuous infusion (C+T), carbenicillin plus cefamandole by continuous infusion (C+CC) or carbenicillin plus cefamandole by intermittent infusion (C+IC) during 490 febrile episodes. Carbenicillin was administered over 2 hours every 4 hours. The per cent of cures achieved during the 235 documented infections was 65 per cent for C+CC, 57 per cent for C+IC and 54 per cent for C+T. Among those infections caused by single gram-negative bacilli, C+CC produced a higher cure rate than C+IC or C+T(74 per cent versus 59 per cent versus 50 per cent). C+CC was significantly more effective than C+IC among patients with persistent severe neutropenia of less than 100 neutrophils/mm3 (65 per cent versus 21 per cent, p = 0.03). If the infecting organism was sensitive to both antibiotics, the cure rate which occurred during 12 per cent to 13 per cent of the febrile episodes, regardless of antibiotic regimen. However, it occurred significantly more often during documented infections than during fevers of unknown etiology (20 per cent versus 6 per cent, p less than 0.001). C+CC appears to be the most effective of the three regimens for the treatment of infections in patients with persistent severe neutropenia.     

A multicenter comparative trial of three-day norfloxacin vs ten-day sulfamethoxazole and trimethoprim for the treatment of uncomplicated urinary tract infections

Two-hundred nine patients with symptoms of acute urinary tract infection and pyuria were randomized to 400 mg of administered norfloxacin twice daily for three days, or 800 mg of sulfamethoxazole and 160 mg of trimethoprim administered twice daily for ten days. Therapeutic outcome was assessed five to nine days and four to six weeks after treatment. The cure rates were 71/74 (96%) with norfloxacin and 81/81 (100%) with sulfamethoxazole and trimethoprim five to nine days after treatment. Only seven patients had a recurrence at the second follow-up visit; four in the norfloxacin group and three in the sulfamethoxazole and trimethoprim group. No isolates were resistant to norfloxacin, but three Escherichia coli were resistant to sulfamethoxazole and trimethoprim. Fifteen patients in each group reported a side effect during treatment. Two patients in the norfloxacin group and four patients in the sulfamethoxazole and trimethoprim group discontinued therapy due to an adverse effect. In this multicenter study, a three-day course of norfloxacin was as effective and safe as a ten-day regimen of sulfamethoxazole and trimethoprim in the treatment of acute uncomplicated urinary tract infections.     

Ceftriaxone versus aztreonam plus cefazolin for infections in cancer patients with adequate neutrophil counts

Summary In a prospective randomized trial, 154 febrile episodes in cancer patients with adequate neutrophil counts (>1,000 cells/mm³) were treated with either ceftriaxone (72 episodes) or aztreonam plus cefazolin (82 episodes). Documented infections represented almost half of the febrile episodes. The overall response rates among the 144 evaluable episodes were similar for the two regimens: 76% (51/67) with ceftriaxone versus 82% (63/77) with aztreonam plus cefazolin (p=0.41, not significant). Although not statistically significant, the response rate of the microbiologically documented infections was slightly better in patients treated with the double -lactam combination (85% vs. 65%, p=0.16) and clinically documented infections showed a better response in the group of patients receiving monotherapy (87% vs. 59%, p=0.12). No serious adverse effects were observed during this study and both regimens were well tolerated. Ceftriaxone or the combination of aztreonam plus cefazolin showed a similar efficacy as empirical therapy for infections in cancer patients with adequate neutrophil counts.

---

Ceftriaxon im Vergleich zu Aztreonam plus Cefazolin zur Behandlung von Infektionen bei Krebspatienten mit adäquaten Neutrophilenzahlen

Zusammenfassung 154 Fieberschübe bei Krebspatienten mit adäquaten Neutrophilenzahlen (>1.000 Zellen/mm³) wurden in einer prospektiven randomisierten Studie entweder mit Ceftriaxon (72 Episoden) oder Aztreonam plus Cefazolin (82 Episoden) behandelt. Nahezu die Hälfte der fieberhaften Episoden waren dokumentierte Infektionen. Die Gesamtansprechrate bei den 144 auswertbaren Episoden war für beide Therapien ähnlich: 76% für Ceftriaxon (51/67) und 82% für Aztreonam plus Cefazolin (63/77) (p=0,41; nicht signifikant). Bei mikrobiologisch dokumentierten Infektionen war die Ansprechrate unter der Doppel-Betalaktam-Kombination etwas besser (85 % im Vergleich zu 65%; p=0,16), doch war dieser Unterschied nicht signifikant. Bei den klinisch dokumentierten Infektionen zeigten die mit der Monotherapie behandelten Patienten bessere Ansprechraten (87% gegenüber 59%; p=0,12). Während der Studie wurden keine ernsthaften Nebenwirkungen beobachtet, beide Therapien wurden gut vertragen. In der empirischen Therapie von Infektionen bei Krebspatienten mit adäquaten Neutrophilenzahlen erwiesen sich Ceftriaxon und die Kombination von Aztreonam plus Cefazolin als vergleichbar wirksam.

     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

The outcome of Pneumocystis carinii pneumonia in Danish patients with AIDS

A total of 100 consecutive patients with AIDS were evaluated for efficacy and safety of treatment and secondary prophylaxis directed against Pneumocystis carinii pneumonia (PCP). 89 episodes of PCP were recorded in 75 patients. 63 of the 75 patients (84%) with a first episode of PCP were discharged. Of 72 patients with a first episode of PCP who were initially treated with trimethoprim-sulfamethoxazole. 76% completed therapy successfully. Side effects were common, but generally mild and tolerated during continued treatment. 7/11 patients (64%) with a first episode of PCP who required mechanical ventilation were discharged. Long term prognosis for these patients was not worse than for patients who did not require mechanical ventilation. Relapse of PCP occurred in 3/50 patients (6%) during secondary prophylaxis, 160 mg trimethoprim and 800 mg sulfamethoxazole (TMP-SMZ) every 24 h, compared to 11/16 (69%) patients who were not receiving prophylaxis (p less than 0.00001). No patients discontinued prophylaxis because of side effects. It is concluded that for most patients with AIDS and PCP, treatment and secondary prophylaxis with TMP-SMZ is safe and effective.