trimethoprim--sulfamethoxazole-drug-combination and Leukemia

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.

Topics: Acute Disease; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Infection Control; Infections; Leukemia; Multicenter Studies as Topic; Neutropenia; Norfloxacin; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

At present, there is strong concern about the efficacy of current antimicrobial prophylaxis for the management of neutropenic patients. The purpose of this study was to test the effectiveness of levofloxacin, a new quinolone with expanded activity against grampositive bacteria, versus cotrimoxazol as a prophylactic treatment for granulocytopenic patients.. In this prospective and controlled study, we included 249 consecutive episodes of neutropenia, such as those resulting from lymphoma and leukemia treatment, during 28 months (from November 1999 to February 2002). These episodes were divided into 3 cohorts: the first was treated with levofloxacin, the second with cotrimoxazol and the third was a subgroup without antibiotic prophylaxis (control group). The incidence of infection, rate of mortality, and reduction of hospitalization rate for treatment with parenteral antibiotics were tested.. There was a reduction in documented infections (clinically or microbiologically) when comparing the levofloxacin cohort with the control cohort (p < 0.0001) and the levofloxacin cohort with the cotrimoxazol group (p < 0.01). The reduction in the hospitalization rate for treatment with parenteral antibiotics reached statistical significance when comparing the levofloxacin group with the control cohort (p < 0.001) and levofloxacin group with the cotrimoxazol group (p < 0.05). Although the rate of global mortality was lower in the levofloxacin group than in the other two groups, no statistical significance was observed.. Our results show that levofloxacin effectively reduces the incidence of infection, the rate of hospitalization and the requirement for parenteral antibiotics. Although we found a reduction in the overall mortality and in the infection-related mortality, the corresponding data did not reach statistical significance.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Humans; Leukemia; Levofloxacin; Lymphoma; Middle Aged; Neutropenia; Ofloxacin; Opportunistic Infections; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (< 100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purported activity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.

Topics: Acute Disease; Adult; Agranulocytosis; Bacterial Infections; Double-Blind Method; Female; Humans; Leukemia; Male; Middle Aged; Prospective Studies; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Bacterial Infections; Bone Marrow Transplantation; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Imipenem; Leukemia; Lymphoma; Male; Middle Aged; Neutropenia; Pneumocystis Infections; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

In a controlled randomized study among 48 patients undergoing 75 courses of aggressive antileukemic therapy, it was shown that cotrimoxazole was less effective than penicillin G in preventing septicemia due to viridans streptococci. Both antibiotics were given intravenously. During 35 episodes of chemotherapy in the group of patients on penicillin G only, one patient developed a streptococcal bacteremia; this contrasted with bacteremia and septicemia in seven patients during 40 episodes in the group on cotrimoxazole. In three of these seven patients, septicemia was associated with respiratory failure and it was the cause of death in one. Both aerobic gram-negative rods and streptococci which caused infection despite cotrimoxazole prophylaxis were resistant to cotrimoxazole. Side effects such as hypersensitivity and favorable or unfavorable interaction with the oral selective decontamination regimen were similar for the two drugs, with the exception of colonization with Candida spp, which occurred more often in patients on cotrimoxazole than in patients on penicillin.

Topics: Agranulocytosis; Antineoplastic Agents; Bacteremia; Drug Hypersensitivity; Drug Interactions; Drug Resistance, Microbial; Humans; Length of Stay; Leukemia; Penicillin G; Streptococcal Infections; Streptococcus; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.

Topics: Acute Disease; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Infection Control; Infections; Leukemia; Multicenter Studies as Topic; Neutropenia; Norfloxacin; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

A total of 63 neutropenic patients receiving cytotoxic therapy for acute leukemia were randomly allocated to receive norfloxacin (400 mg every 12 hours) or cotrimoxazole (160/800 mg every 12 hours) to prevent bacterial infection. Compliance was more than 95 percent and no adverse effects attributable to the study drugs were observed. The overall incidence of febrile illness (67 percent) was similar between the groups; however, no gram-negative bacillary infections were observed in 31 norfloxacin recipients compared with four of 32 cotrimoxazole recipients. Furthermore, nine norfloxacin recipients had 17 gram-positive bacteremias compared with two in two cotrimoxazole recipients (p = 0.0034). Norfloxacin was more effective than cotrimoxazole for preventing acquisition of aerobic gram-negative bacilli in surveillance cultures. Neither study drug allocation nor the presence of an indwelling central venous catheter influenced outcome among the 42 patients who subsequently received empiric systemic antibiotics for suspected infection. Although gram-positive infection remains an unsolved problem, norfloxacin appears to be a safe, effective, well-tolerated alternative to cotrimoxazole for preventing gram-negative infection in neutropenic patients with acute leukemia.

Topics: Acute Disease; Adult; Antineoplastic Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Female; Gram-Negative Bacteria; Humans; Leukemia; Male; Neutropenia; Norfloxacin; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Adult; Anti-Infective Agents; Ciprofloxacin; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Humans; Infection Control; Leukemia; Neomycin; Neutropenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Ciprofloxacin, a new quinolone derivative, was given prophylactically (500 mg twice daily) to 15 patients with acute leukemia during remission induction treatment. The effect on the microbial flora of the alimentary tract was evaluated. A rapid elimination of Enterobacteriaceae was observed. Bacteriodes and Clostridium species were not affected. Few ciprofloxacin resistant strains were isolated but did not lead to colonization. In a randomized study 56 patients with acute leukemia received either ciprofloxacin or trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by Gram-negative bacilli were seen in the ciprofloxacin group compared to 17 in the other group (p less than 0.02). Ciprofloxacin prevented colonization with resistant Gram-negative bacilli while 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole (p less than 0.01). Ciprofloxacin was better tolerated than trimethoprim-sulfamethoxazole + colistin; fewer side effects occurred.

Topics: Adult; Bacterial Infections; Ciprofloxacin; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Humans; Leukemia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with acute nonlymphocytic leukemia were randomized to receive remission induction therapy consisting of seven days of cytosine arabinoside and three days of daunorubicin ("7 + 3") or to receive the same regimen intensified by either the addition of 6-thioguanine or by extension of the administration of cytosine arabinoside to ten days. Additionally, all patients were randomized to receive or not to receive cotrimoxazole antibacterial prophylaxis during the remission induction phase. Neither an increase in intensity of chemotherapy nor the antibacterial prophylaxis increased the remission rate above the 53% for patients treated with the standard "7 + 3" regimen. The second part of this study addressed the issue of the utility of long-term maintenance chemotherapy. To this end, patients were randomized to discontinue all treatment after 8 months of maintenance chemotherapy or to continue maintenance therapy for a total of 3 years. Although there was a transient increase in the relapse rate for patients who discontinued therapy, the proportion of long-term remitters was identical in the two patient groups. Additionally, there is a suggestion of a survival advantage for patients randomized to discontinue all therapy at 8 months.

Topics: Acute Disease; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Leukemia; Prognosis; Random Allocation; Remission Induction; Research Design; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In a comparative study of infection prophylaxis, patients with acute leukemia receiving remission induction therapy were assigned either no prophylaxis, sulfamethoxazole and trimethoprim, ketoconazole, or the combination of sulfamethoxazole and trimethoprim and ketoconazole. Both sulfamethoxazole and trimethoprim and the combination of sulfamethoxazole and trimethoprim and ketoconazole substantially reduced the overall incidence of infection consequent to a marked decrease in bacterial infection. However, sulfamethoxazole and trimethoprim were associated with an increased rate of fungal infection, while ketoconazole decreased this complication. No form of prophylaxis reduced infectious mortality or increased the complete remission rate. However, because of its effect in reducing infectious morbidity, we conclude that patients with acute leukemia receiving remission induction treatment should be given antibacterial and antifungal prophylaxis.

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Drug Combinations; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Humans; Ketoconazole; Leukemia; Middle Aged; Mycoses; Pneumonia; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Of 545 patients expected to develop prolonged neutropenia and randomized to received trimethoprim-sulfamethoxazole (TMP-SMZ) or placebo, 342 were evaluable for occurrence of infection or bacteremia. Some centers used oral nonabsorbable antibiotics in addition. Infection occurred in 64 (39%) of 165 placebo recipients and 46 (26%) of 177 TMP-SMZ recipients (P = .016), whereas bacteremia occurred in 32 (19%) and 22 (12%), respectively (P = .106, difference not significant [NS]). In the 139 patients with acute nonlymphocytic leukemia (ANLL), infection occurred in 35 (55%) of 64 placebo-treated patients and 31 (41%) of 75 TMP-SMZ-treated patients (P = .162, NS), whereas bacteremia occurred in 15 (23%) and 18 (24%; NS), respectively. Excluding patients with ANLL, infection occurred in 29 (29%) of 101 placebo-treated patients and 15 (15%) of 102 TMP-SMZ recipients (P = .038), whereas bacteremia occurred in 17 (17%) and four (4%; P = .005), respectively. Gram-positive cocci were isolated less frequently from TMP-SMZ-treated, bacteremic patients, but more of their isolates were resistant to TMP-SMZ than were those from placebo recipients.

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Enterobacteriaceae Infections; Granulocytes; Humans; Leukemia; Leukocyte Count; Neutropenia; Sepsis; Staphylococcal Infections; Streptococcal Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.

Topics: Acute Disease; Adolescent; Adult; Amidines; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Humans; Infant; Infant, Newborn; Leukemia; Male; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Antineoplastic Agents; Drug Combinations; Drug Evaluation; Female; Humans; Infection Control; Leukemia; Leukocyte Count; Male; Middle Aged; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In an attempt to reduce the incidence of fever and infection, we randomized patients with cancer to receive trimethoprim/sulfamethoxazole plus erythromycin (TMP/SMX + E) versus placebos after each cycle of chemotherapy (no crossover) and to continue until granulocytopenia (polymorphonuclear leukocytes less than 500/mm3) resolved or the patient became febrile. We evaluated 541 episodes (150 patients); 249 episodes (77 patients) with TMP/SMX + E and 292 episodes (73 patients) with placebos. The patients' median age was 17 years. Thirty percent of the patients had leukemia, 23% had lymphoma, and 47% had solid tumors. Compliance with prescribed medication was prospectively rated as excellent in 60.6%, good in 11.7%, poor in 11.1%, and unknown in 16.6%; compliance was better for the placebo group (P = 0.001). The overall incidence of fever or infection was 22.1% for the TMP/SMX + E group versus 26.9% for the placebo group. When only episodes with excellent compliance in which granulocytopenia was documented were compared, the incidence of fever or infection was 18.1% for the TMP/SMX + E group vs 32.2% for the placebo group (P = 0.009), with bacterial infection occurring in 3.8% of the TMP/SMX + E group vs 11.9% of the placebo group (P = 0.019), and unexplained fever in 10.5% of the TMP/SMX + E group vs 19.6% of the placebo group (P = 0.037). Patients with good or poor compliance showed no significant benefit from the TMP/SMX + E, and patients with excellent compliance did best, regardless of whether they were receiving antibiotics or placebos, suggesting that patient compliance is an important independent variable. The incidence of fever or infection was significantly lower for patients with leukemia with excellent compliance who received antibiotics (P = 0.037) than for patients with lymphomas or solid tumors. Oral antibiotic prophylaxis reduced the incidence of fever and infection in some granulocytopenic patients, but the benefit was limited and restricted to patients whose compliance was complete.

Topics: Adolescent; Adult; Agranulocytosis; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Erythromycin; Female; Fever; Humans; Infant; Leukemia; Lymphoma; Male; Neoplasms; Patient Compliance; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Female; Framycetin; Humans; Leukemia; Male; Middle Aged; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Agranulocytosis; Child; Clinical Trials as Topic; Drug Combinations; Fever; Humans; Infection Control; Infections; Leukemia; Lymphoma; Neutropenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

This study was conducted to determine the efficacy of dosing trimethoprim/sulfamethoxazole on 2 consecutive days per week for the prevention of Pneumocystis carinii (jiroveci) pneumonia in a pediatric leukemia and lymphoma population and to determine whether trimethoprim/sulfamethoxazole contributes to neutropenia during maintenance therapy.. Charts were reviewed for all pediatric patients with leukemia and lymphoma diagnosed between January 1, 1993, and December 31, 2002. Data were collected through April 1, 2004.. A total of 575 charts were reviewed; 529 patients were included in the analysis. A total of 482 (345 leukemia, 137 lymphoma) patients were evaluated on trimethoprim/sulfamethoxazole dosed 2 consecutive days per week for 268074 patient-days. No breakthrough cases were documented in compliant patients; 2 noncompliant patients developed P. carinii pneumonia. A total of 238 patients who were on trimethoprim/sulfamethoxazole prophylaxis and 13 patients who were receiving an alternative medication prophylaxis were evaluated for neutropenia during maintenance therapy. The median number of maintenance days on trimethoprim/sulfamethoxazole was 605.5 days and on alternative drug was 617 days. The median number of neutropenic maintenance days on trimethoprim/sulfamethoxazole was 15.5 days and on the alternative drug was 16 days. The median proportion of neutropenic days per patient was 0.029 on trimethoprim/sulfamethoxazole and 0.022 on the alternative drug.. Intermittent dosing of trimethoprim/sulfamethoxazole on 2 consecutive days per week is an effective alternative prophylactic regimen for P. carinii pneumonia in pediatric patients with leukemia and lymphoma. This analysis does not support a difference in neutropenia during maintenance therapy between patients who are treated with trimethoprim/sulfamethoxazole versus an alternative drug.

Topics: Anti-Infective Agents; Child; Drug Administration Schedule; Humans; Leukemia; Lymphoma; Neutropenia; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasmosis is a rare but life-threatening complication of allogeneic stem-cell transplantation. Polymerase chain reaction (PCR) offers the possibility to make the diagnosis earlier than conventional techniques, and is then expected to improve the prognosis. We undertook a prospective screening using a competitive PCR in blood in 32 stem-cell transplant recipients. The sampling covered the first 150 days post-transplant, at days 21, 30, 45, 60, 90, 120, and 150. Twenty-four patients had anti-toxoplasma antibodies before transplant. Three of them (12.5%) had transient PCR-positive samples at 21, 45, and 90 days post-transplant, respectively. The three PCR-positive patients were febrile but had no funduscopic examination or cerebral computerised tomography (CT) scan abnormalities. The PCR signal disappeared when the patients were given trimethoprim-sulfamethoxazole, and no full-blown toxoplasmosis was observed. Toxoplasma reactivation evidenced using PCR is frequent in seropositive patients not receiving trimethoprim-sulfamethoxazole during the 1-3 months post-transplant. Toxoplasma PCR should be included in the diagnostic strategy of fever of unexplained origin in allogeneic stem-cell transplant recipients. Then, prompt specific therapy can be initiated to avoid development of full-blown toxoplasmosis.

Topics: Adult; Anemia, Aplastic; Animals; Anti-Infective Agents; Antibodies, Protozoan; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Toxoplasma; Toxoplasmosis; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aclarubicin; Acute Disease; Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Finland; Humans; Immunocompromised Host; Incidence; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Pneumonia, Pneumocystis; Prednisone; Premedication; Retrospective Studies; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

We studied episodes of fever and neutropenia in children and adolescents without documented infections to determine the risk of recurrent fever after early discontinuation of empiric antibiotic therapy; 213 episodes occurred in 106 patients. All patients received empiric antibiotic therapy after cultures were obtained. Antibiotic therapy was discontinued if no infection was found, culture results were negative for 48 hours, and the patient was afebrile for 24 hours. In 83 episodes without documented infection, antibiotic therapy was stopped with absolute neutrophil counts < 0.5 x 10(9)/L (< 500/mm3); 50 episodes occurred in patients with solid tumors, leukemia in remission, and other hematologic conditions (group 1), and 33 in patients with active leukemia (group 2). Fever recurred before neutropenia resolved in 6% of group 1 and 45% of group 2 episodes; five patients in group 2 had documented infection. Recurrent fever risk correlated with absolute neutrophil count and monocyte count at the time antibiotic therapy was stopped, in both groups, as did increasing absolute neutrophil count and increasing leukocyte count in group 2. We conclude that discontinuing antibiotic therapy is safe in febrile episodes without documented infections before neutropenia resolves in patients with high potential for bone marrow recovery. The risk of recurrent fever and infection is significant for patients with neutropenia and poor marrow recovery potential.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever of Unknown Origin; Humans; Infant; Infusions, Intravenous; Leukemia; Male; Neoplasms; Neutropenia; Recurrence; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Infections are still a frequent cause of morbidity in patients with hematologic malignancies. Until 10 years ago the microorganisms most frequently encountered were aerobic gram-negative bacilli, which in many centers were responsible for, on average, one infection per neutropenic period. Many different approaches to the prevention of these infections have been designed. Patients have been kept in strict isolation and given broad-spectrum antibiotics prophylactically. This approach has led to a decrease in the incidence of infections in these patients, but compliance and emergence of resistance have been important limiting factors. The rationale of selective decontamination with trimethoprim-sulfamethoxazole or quinolones was that the elimination of potentially pathogenic aerobic gram-negative bacilli from the gastrointestinal tract would prevent colonization and subsequent infection. The use of these antibiotics has led to a shift in the spectrum of infections. Infections due to gram-negative bacilli have been virtually eliminated, but the number of infections caused by gram-positive bacteria is rapidly increasing; however, the latter infections are most often only minor. In some centers quinolones are now used together with agents active against these gram-positive bacteria. The approach of selective decontamination has not led to fewer febrile episodes or to a lower mortality in neutropenic patients. Future studies should be directed towards identifying the cause of febrile episodes and the epidemiology of gram-positive bacterial infections.

Topics: Acute Disease; Bacterial Infections; Communicable Diseases; Humans; Infection Control; Leukemia; Neutropenia; Quinolones; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a survey over a 21-year period of the incidence and risk of occurrence of episodes of pneumonia and pneumonitis in children treated for solid tumours and leukaemia. One hundred episodes occurred amongst 219 patients, seven of which were associated with death. Focal opacification on the chest radiograph was more common than diffuse opacification. Patients with leukaemia had a significantly higher rate of occurrence of pneumonia and pneumonitis during the periods of induction and maintenance compared with the off-treatment period, and during the relapse period compared with the period of maintenance. Patients with solid tumours had a significantly higher rate of occurrence during treatment compared to the off-treatment period. The rate of occurrence on treatment was the same in patients with solid tumours and acute leukaemia. Children with malignancy have a high incidence of pneumonia and pneumonitis and death is rare if the patient does not have terminal malignant disease.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Child; Clinical Protocols; Daunorubicin; Humans; Immunocompromised Host; Leukemia; Methotrexate; Neoplasms; Opportunistic Infections; Pneumonia; Pneumonia, Viral; Prednisolone; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Co-trimoxazole has been used in a hospital for over 10 years as a major antibacterial agent in the treatment of malignant haematological diseases. Routine selective gut decontamination with co-trimoxazole combined with colistine and an antifungal agent has led to a reduction in infections in neutropenic patients from 40% to 25% since the strategy was adopted, and this had been accompanied by a change in the most frequent pathogens, from Gram-negative to Gram-positive organisms. Co-trimoxazole has proved to be the drug of choice for Pneumocystis carinii infections. Finally, it is used as first-line therapy in febrile immunosuppressed patients who are not on selective decontamination, with an efficacy of over 90%. Apart from mild abdominal discomfort, an elevated allergy rate of 14% in patients with overt leukaemia is a major disadvantage. On the other hand, substantial prolongation of episodes of bone marrow aplasia has not been observed.

Topics: Anti-Infective Agents; Drug Combinations; Humans; Intestines; Leukemia; Neutropenia; Opportunistic Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

From 1982 to 1987, 22 patients with proven Pneumocystis carinii pneumonia were diagnosed at Wellington Hospital. Patients comprised 15 males and 7 females aged 15-76 years and included seven with AIDS, eight with haematological malignancy and seven with renal disease. Two distinct clinical prodromes occurred. In renal patients a classic fulminating pneumonitis developed over 24 to 72 hours. In patients with AIDS a more indolent illness occurred lasting 3 or more weeks and was characterised by fever, dry cough and breathlessness. Haematology patients showed no specific duration of prodrome. At the time of diagnosis all had an abnormal chest radiograph and the arterial PO2 was reduced in all but one case. An invasive diagnostic procedure was performed in all except one case where the diagnosis was made at post mortem. Two patients required a second procedure to establish the diagnosis. Procedures performed included bronchoalveolar lavage [14], open lung biopsy [7] and transbronchial lung biopsy [2]. All patients were treated with high dose cotrimoxazole and 18 survived to leave hospital. A review of the approach to the diagnosis and treatment of Pneumocystis carinii pneumonia is presented.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Drug Combinations; Female; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Kidney Diseases; Leukemia; Male; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of drug-induced skin rashes and related factors were analysed in a retrospective study of 151 patients with acute non-lymphocytic leukaemia (ANLL). 91 (60%) developed a drug-related toxicodermia to one or more drugs during remission, induction and maintenance therapy. The incidence of rashes was mainly confined to the blastic stage of leukaemia and occurred significantly less often during remission. Patients with acute myeloid leukaemia, FAB classification M1, M2 and M3 (M1-3) developed skin reactions more often than those of types M4 and M5 (M4-5). Women suffered more frequently from drug-induced skin lesions than men. The incidence of drug-associated rashes was significantly higher in patients with ANLL than in the general population for: Allopurinol (16%), co-trimoxazole (14%), miconazole (28%), and ketoconazole (18%). The incidence for the penicillins (12%) and cephalosporins (3%) conformed to the upper limit as reported for the general population. Additional toxic effects of combined therapy could not explain the differences observed and a dearrangement of the immunesystem during the blastic stage of leukaemia is suggested.

Topics: Acute Disease; Adult; Allopurinol; Cephalosporins; Drug Combinations; Drug Eruptions; Female; Humans; Ketoconazole; Leukemia; Male; Miconazole; Penicillins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Between 1976 and 1983, 53 cases of Pneumocystis carinii pneumonia were documented at the Mayo Clinic. Underlying diseases included leukemia in 15 patients, lymphoma in nine, nonhematologic malignancies in five, acquired immune deficiency syndrome in two, an various inflammatory diseases treated by corticosteroids in 16 patients. Cytotoxic drugs with corticosteroids were used in 68 percent of patients, whereas 23 percent received corticosteroids alone. Clinical features consisted of progressive dyspnea (74 percent), cough (55 percent), and fever (62 percent), with normal findings on examination (43 percent), or crackles (53 percent). Arterial oxygen tension and oxygen saturation were 48.6 +/- 12.8 mm Hg and 81.2 +/- 6.5 percent, respectively. Chest roentgenographs exhibited diffuse alveolar and interstitial infiltrates with predominantly perihilar distribution. The diagnostic rates for open lung biopsy and bronchoscopy were 97 percent and 62 percent, respectively. Clinical improvement and survival following appropriate therapy were noted in 22 patients (41.5 percent), whereas the remaining 31 patients died within four weeks of hospitalization. When survivors were compared with nonsurvivors, there was no difference in mean age, leukocyte counts, arterial oxygen tension, or duration of symptoms before treatment. A coexisting pulmonary infection was identified more frequently in nonsurvivors (51.6 percent) than in survivors (22.7 percent, p = 0.01). The mortality from P. carinii pneumonia alone was 47 percent, whereas 76 percent of those with coexisting infection died. Despite antibiotic therapy and potentially effective chemoprophylaxis, P. carinii pneumonia remains a significant and life-threatening complication of diseases or treatments associated with immune suppression.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Drug Combinations; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Digestive System; Drug Combinations; Humans; Leukemia; Leukocyte Count; Neomycin; Polymyxin B; Polymyxins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Sulfamethoxazole; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Rapidly progressive pulmonary distress occurs as a secondary complication in immunocompromised pediatric patients. These patients usually develop a pattern of diffuse alveolar and/or interstitial infiltrates on chest x-ray and pursue a rapidly downhill course despite intensive respiratory support with the use of multiple and varied antimicrobial regimens. These patients are subjected to diagnostic open lung biopsies to establish a diagnosis. The diagnostic value of open lung biopsy and its current impact on therapy is not clearly established. This retrospective study attempts to determine the impact of open lung biopsy on diagnosis and therapeutic outcome. Between November, 1974, and October, 1982, 40 diagnostic open lung biopsies were performed on immunocompromised patients with clinically progressive respiratory disease. Adequate follow-up for complete evaluation was possible in 34 of these patients. Most of these patients had hematologic malignancies and all were on chemotherapeutic drugs at time of open lung biopsy. Open lung biopsy was considered helpful, ie, resulted in a change in antimicrobial therapy or substantiated preoperative therapy, in 17 of our 34 patients (50%). A "treatable" condition, amenable to antimicrobial therapy, was diagnosed in 16 of our patients (47%). Pneumocystis carinii pneumonitis (PCP) was the most common diagnosis in 11 (69%) of our "treatable" patients. The remaining five "treatable" patients had sarcoidosis (1), histiocytosis X (1), bacterial pneumonitis (1) and fungal pneumonitis (2). No diagnosis was achieved by open lung biopsy in ten (30%) of our patients. There were two complications attributable to open lung biopsy (6%), including one death. All PCP patients treated with trimethoprim sulfamethoxazole (T/S) survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Biopsy; Child; Child, Preschool; Drug Combinations; Female; Humans; Immunosuppression Therapy; Infant; Leukemia; Lung; Male; Neoplasms; Pneumonia, Pneumocystis; Pneumonia, Viral; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The amikacin-carbenicillin-cotrimoxazole combination was used as an empiric treatment for febrile episodes in patients with acute leukemia and severe granulocytopenia. The choice of drugs was based on the finding in our institute that the majority of infections are caused by gram-negative rods, particularly Pseudomonas, with high percentage of strains resistant to gentamycin and tobramycin. Granulocyte transfusions were given to the patients who did not show satisfactory clinical improvement 48 h after start of antibiotic therapy. There were cures in 84.6% of the febrile episodes treated with this antibiotic combination, including five of eight episodes of microbiologically confirmed bacteremia. Survival after 21 days of antibiotic therapy amounted to 89.1%. Renal toxicity occurred in 10.9% of the episodes treated. The prompt use of this antibiotic combination seems to be a safe and efficacious therapeutic tool for treating these high-risk patients.

Topics: Acute Disease; Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Middle Aged; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Cephalothin; Child; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Male; Middle Aged; Sulfamethoxazole; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination