trimethoprim--sulfamethoxazole-drug-combination and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.

Topics: Administration, Oral; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Male; Mercaptopurine; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

The use of trimethoprim/sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia in patients with acute lymphoblastic leukemia (ALL) may cause undesirable adverse effects: fungal overgrowth, neutropenia, and drug resistance. A possible alternative is atovaquone, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity. However, it is not known if atovaquone alters the disposition or adverse effects of antileukemic drugs.. Using a crossover study design, we compared the pharmacokinetics of etoposide and its CYP3A4-formed catechol metabolite when given as a 300 mg/m2 i.v. infusion following daily atovaquone versus trimethoprim/sulfamethoxazole in nine patients.. The area under the concentration time curve (AUC) of etoposide, etoposide catechol and the catechol to etoposide AUC ratio were slightly higher (a median of 8.6%, 28.4%, and 25.9%) following atovaquone as compared to trimethoprim/sulfamethoxazole (P=0.055, P= 0.031 and P=0.023), respectively. In vitro analysis in human liver microsomes showed modest inhibition of etoposide catechol formation in the presence of atovaquone. Using uptake of 3H-vinblastine in L-MDR1 cells, atovaquone was shown to inhibit P-glycoprotein with an apparent Ki of 95.6 microM.. Although the effect of atovaquone on etoposide disposition was modest, in light of the fact that the risk of etoposide-related secondary acute myeloid leukemia has been linked to minor changes in schedule and concurrent therapy, we suggest caution with the simultaneous administration of atovaquone and etoposide, particularly if used with other CYP3A4/P-glycoprotein substrates.

Topics: Adolescent; Antifungal Agents; Antineoplastic Agents, Phytogenic; Area Under Curve; Atovaquone; Child; Child, Preschool; Cross-Over Studies; Drug Interactions; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Naphthoquinones; Pilot Projects; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

We report our experience replacing trimethoprim-sulfamethoxazole (TMP/SMX) with aerosolized pentamidine (AP) in 22 children with acute leukemia who could not tolerate TMP/SMX.. Children (age 1 to 15 years) with acute leukemia during maintenance chemotherapy or post-bone marrow transplantation (BMT) receiving prophylaxis for Pneumocystis carinii pneumonia (PCP) with TMP/SMX received AP following prolonged neutropenia or allergy to TMP/SMX. Patients received 300 mg of AP monthly (children < 4 years received 150 mg) dissolved in 5 mL of distilled water over 20 to 30 minutes.. Over a 3-year period, 358 courses of AP were administered over 10,124 observable days. AP was adequately tolerated on a monthly basis for prophylaxis against PCP in 22 children with acute leukemia. AP was demonstrated to be effective in preventing PCP. There were minimal side effects observed during this trial. The majority of children with acute lymphoblastic leukemia (ALL; 12 of 14 [86%]) undergoing maintenance chemotherapy were able to resume full-dose therapy.. AP in children is well tolerated and shows high efficacy for PCP prophylaxis in children with leukemia. We conclude that AP should be considered as second-line PCP prophylactic therapy for children with acute leukemia in instances in which TMP/SMX cannot be tolerated. Phase III trials are required to determine its effect on dose intensification and event-free survival.

Topics: Administration, Inhalation; Adolescent; Aerosols; Child; Child, Preschool; Humans; Immunosuppressive Agents; Infant; Leukemia, Myeloid, Acute; Pentamidine; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Ninety-five unselected patients with stage III and IV T cell lymphoblastic lymphoma were treated according to the United Kingdom Children's Cancer Study Group protocol 8503. This was a continuous, intensive leukaemia type regimen including cranial irradiation (18 Gy in 10 fractions) and continuing chemotherapy for 2 years identical to the concurrent Medical Research Council ALL protocol. Four-year event-free survival was 65% (95% CI 50-80%) with no significant difference between stage III and stage IV cases. 4.2% of patients died of infection or non-tumour related events. Following relapse salvage was unlikely without high dose chemotherapy and bone marrow rescue. These results show an improvement over previous U.K. studies but we need to continue to search for subsets of patients with resistant disease for whom even more intensive therapy possibly combined with bone marrow rescue is required.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Daunorubicin; Humans; Infant; Mercaptopurine; Methotrexate; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

230 leukaemic patients were entered into a randomised, prospective, multicentre trial of either ciprofloxacin (1 g/day) or co-trimoxazole (1920 mg/day) plus colistin (800 mg/day) for the prevention of infection during granulocytopenia. Bacteraemia due to resistant gram-negative rods occurred only in the co-trimoxazole-colistin group though both regimens were effective for selective gastrointestinal tract decontamination. However, there were fewer patients without any infective complications (31% vs. 18%: P = 0.02), fewer febrile days [mean (S.D.) 5.9 (1.1) vs. 8.2 (1.4): P = 0.0242], a lower proportion of infective events (0.9 (0.16) vs. 1.2 (0.18): P = 0.005) and fever occurred later (median 19 vs. 14 days: 0.025 less than P less than 0.05) in the co-trimoxazole-colistin group. The choice of prophylactic regimen therefore appears to depend upon whether or not protection against gram-negative infection is required or better systemic prophylaxis overall.

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Ciprofloxacin; Colistin; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Premedication; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Because trimethoprim-sulfamethoxazole (TMP-SMX) causes neutropenia in children with leukemia, we investigated the possibility that pharmacokinetic interaction between methotrexate (MTX) and TMP-SMX causes accumulation of the antileukemia agent. We studied the pharmacokinetics of MTX given intravenously or orally to nine children with acute lymphoblastic leukemia, once with and once without TMP-SMX. There was an increase in free MTX fraction during TMP-SMX therapy in all patients, from (mean +/- SD) 37.4 +/- 11% without TMP-SMX to 52.2 +/- 6.4% with TMP-SMX (p less than 0.01). Plasma clearance of total MTX did not change significantly, whereas clearance of free MTX decreased significantly (from 12.5 +/- 4 to 7.6 +/- 1.5 ml/kg/min; p less than 0.05). There was a consistent decrease in the renal clearance of free MTX (from 12.1 +/- 6.8 to 5.6 +/- 2.4 ml/kg/min; p less than 0.05). Elimination half-life of MTX was not affected significantly by TMP-SMX. There was a significant correlation between serum concentrations of TMP-SMX and the percentage of decrease in the renal clearance of free MTX (r = 0.91; p less than 0.05). These changes in protein binding and tubular clearance of MTX, caused by competition with TMP-SMX, result in a mean 66% increase in systemic exposure to MTX and may explain the myelotoxicity often observed with the coadministration of the two drugs.

Topics: Bone Marrow; Child; Child, Preschool; Drug Interactions; Female; Half-Life; Humans; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding; Trimethoprim, Sulfamethoxazole Drug Combination

Preliminary results are presented of an ongoing, prospective, randomized, study comparing ofloxacin, ciprofloxacin and co-trimoxazole/colistin for the prevention of infection in patients with acute leukaemia. The results for 59 patients (median age 47 years, range 21-72) included 88 episodes of neutropenia, each associated with a course of cytotoxic therapy. The main factor measured was the time elapsed from the beginning of neutropenia (neutrophils less than 500/microliter) until the first infectious febrile episode. The median time for the period was 12 days (range 1-56) for the cotrimoxazole/colistin group, 15 days (range 1-38) for the ofloxacin group and 20 days (range 1-36) for the ciprofloxacin group (differences not significant). Microbiologically proven major infections occurred in 10/27 treatment courses with co-trimoxazole/colistin 7/31 courses with ofloxacin and 7/30 courses with ciprofloxacin (P not significant). These were mostly due to Gram-positive cocci. There were no Gram-negative infections in the quinolone groups compared with one major Pseudomonas aeruginosa infection in the co-trimoxazole/colistin group. No Pneumocystis carinii infections were encountered. Adverse reactions associated with co-trimoxazole/colistin required discontinuation of medication in 11/27 treatment courses because of compliance problems, skin reactions or gastrointestinal intolerance. There were significantly fewer discontinuations in the ofloxacin (n = 2) and in the ciprofloxacin groups (n = 3). Major side effects of the quinolones included persistent icterus in one patient receiving ofloxacin and psychiatric symptoms in one patient receiving ciprofloxacin. It is concluded from these data that there were no statistically significant differences between the three treatment groups in respect of the prevention of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Ciprofloxacin; Colistin; Humans; Neutropenia; Ofloxacin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

229 children with acute lymphoblastic leukaemia (ALL) and with clinical and laboratory features associated with a high risk of treatment failure entered a randomised study of three treatment regimens. Before 1981, such patients had a 3-year event-free survival (EFS) of 47%. Two intensive therapies, the Berlin-Frankfurt-Munster (BFM) 76/79 regimen and the New York (NY) regimen were compared with a control regimen that had achieved the best outcome in previous Trials. Data on 214 cases (93.4%) were analysed. The 3-year EFS was 78% for the BFM and NY regimens and 49% for the control regimen, a significant difference. The differences persisted after stratification by age at onset, sex, white blood cell count at diagnosis, and marrow blast morphology. Control patients were 2.7 times more likely to fail induction, to die, or to relapse than were patients on the intensive regimens.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Drug Combinations; Female; Humans; Infant; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Radiotherapy Dosage; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Humans; Male; Methemoglobinemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Prospective collection of clinical information for all suspected and proven cases of PJP in children with cancer in the UK and Ireland.. A surveillance survey was undertaken using a key contact at each paediatric oncology Principle Treatment Centre (PTC).. To describe the mortality, outcomes and use of prophylaxis in this at-risk group.. The study confirms that PJP is rare, with only 32 cases detected in the UK over a 2-year period reported from all 20 PTCs. No deaths were directly attributed to PJP, in contrast to previously reported high mortality rates. Breakthrough infection may occur despite prescription of ostensibly adequate prophylaxis with co-trimoxazole; 11 such cases were identified. Six infections occurred in patients for whom prophylaxis was not thought to be indicated. Two infections occurred in patients for whom prophylaxis was specifically omitted due to concerns about potential bone marrow suppression or delayed engraftment.. PJP in children treated for malignant disease is rare. Breakthrough infection despite prophylaxis with co-trimoxazole may represent pathogen resistance or non-compliance. Further consideration of the use of PJP prophylaxis during acute myeloid leukaemia and non-Hodgkin's lymphoma treatment is warranted, alongside appraisal of the clinical implications of the possible marrow suppressive effects of co-trimoxazole and its interactions with methotrexate.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimetabolites, Antineoplastic; Child; Child, Preschool; Humans; Incidence; Infant; Ireland; Methotrexate; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

Although antibiotic prophylaxis with levofloxacin can reduce the risk of serious infection in immunocompromised patients, the potential contribution of prophylaxis to antibiotic resistance is a major drawback. We aimed to identify the effects of levofloxacin prophylaxis, given to paediatric patients with acute lymphoblastic leukaemia to prevent infections during induction chemotherapy, on antibiotic resistance in gastrointestinal microbiota after completion of induction and consolidation therapy.. This prospective, single-centre (St Jude Children's Research Hospital, Memphis, TN, USA) cohort study included children (≤18 years) receiving therapy for newly diagnosed acute lymphoblastic leukaemia and who received either primary levofloxacin prophylaxis or no antibacterial prophylaxis (aside from. Between Feb 1, 2012, and April 30, 2016, 118 stool samples (32 baseline, 49 after induction, and 37 after consolidation) were collected from 49 evaluable participants; of these participants, 31 (63%) received levofloxacin prophylaxis during induction therapy and 18 (37%) received no antibacterial prophylaxis. Over the course of induction therapy, there was an overall increase in the relative abundance of trimethoprim-sulfamethoxazole resistance genes (estimated mean fold change 5·9, 95% CI 3·6-9·6; p<0·0001), which was not modified by levofloxacin prophylaxis (p=0·46). By contrast, the prevalence of topoisomerase point mutations increased over the course of induction therapy in levofloxacin recipients (mean prevalence 10·4% [95% CI 3·2-25·4] after induction therapy. Analysing the gastrointestinal resistome can provide insights into the effects of antibiotics on the risk of antibiotic-resistant infections. In this study, antibiotic prophylaxis with trimethoprim-sulfamethoxazole or levofloxacin during induction therapy for acute lymphoblastic leukaemia appeared to increase the short-term and medium-term risk of colonisation with bacteria resistant to these antibiotics, but not to other drugs. More research is needed to determine the longer-term effects of antibacterial prophylaxis on colonisation with antibiotic-resistant bacteria.. Children's Infection Defense Center at St Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, and National Institutes of Health.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Child; Cohort Studies; Fluoroquinolones; Humans; Levofloxacin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Antibody Formation; Child; History, 20th Century; Humans; Pediatrics; Pneumonia, Pneumocystis; Poliovirus Vaccine, Oral; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment.. We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days.. Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Topics: Anti-Bacterial Agents; Colistin; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacterial Infections; Hemorrhage; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Bacterial; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Alveoli; Respiratory Distress Syndrome; Sputum; Stenotrophomonas maltophilia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To study dapsone in comparison with trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL).. A retrospective study with a prospective follow-up.. Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia.. TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to dapsone.. Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on dapsone. After shifting to dapsone, patients maintained significantly higher ANC (1.46±0.46 vs. 1.17±0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%±11.45 vs. 57.45±10.14, P=0.0081) and methotrexate (64.9%±14.29 vs. 56.5%±9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94±1.2 vs. 3.25±1.29 wk, P=0.0002).. Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Dapsone; Female; Humans; Infant; Male; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Members of the Fusarium solani species complex (FSSC) are causing the majority of the fusariosis in humans. Disseminated fusariosis has a high mortality and is predominantly observed in patients with leukemia. Here, we present the case of a fatal infection by a Fusarium strain with a degenerated phenotype, in a patient with acute lymphatic leukemia. Multiple nasal and skin biopsies as well as blood cultures yielded fungal growth, while in direct and histopathological examination of biopsy material septate hyphae were visible. Initial colonies were white with slimy masses with microconidia reminiscent of Fusarium/Acremonium, but with conidiospore production directly on the hyphae. Multi-locus sequence typing discerned a pionnotal-morphologically degenerated-colony of the recently recognized F. petroliphilum as etiological agent. The culture returned to a typical F. solani species complex morphology only after several weeks of growth in culture. Antifungal susceptibility tests indicate amphotericin B as best drug for this FSSC member rather than any of the azoles or echinocandins.

Topics: Amphotericin B; Antifungal Agents; Cefepime; Cephalosporins; Clarithromycin; Drug Resistance, Fungal; Female; Fusariosis; Fusarium; Humans; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Mycological Typing Techniques; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the frequency of using the potentially toxic combination of methotrexate and trimethoprim-sulfamethoxazole (TMP-SMX) in outpatient practice in the United States.. Data from the National Ambulatory Medical Care Survey for 1993-2010 were used to assess the frequency of using methotrexate with TMP-SMX and associated physician specialties and diagnoses.. TMP-SMX was coprescribed in 22,000 methotrexate visits per year (1.0% of methotrexate visits). Pediatricians prescribed the combination most frequently, and the most common diagnosis was acute lymphoblastic leukemia. There was no significant change over time in coprescription of TMP-SMX with methotrexate (P = 0.4).. Low-dose TMP-SMX with methotrexate chemotherapy appears to be standard for patients with acute lymphoblastic leukemia; however, other uses appear questionable, and clinicians should be cognizant of the risk for fatal interactions, especially when medications are prescribed by multiple providers.

Topics: Adult; Aged; Ambulatory Care; Anti-Infective Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Health Care Surveys; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Leukemia, Lymphoid; Male; Methotrexate; Middle Aged; Pancytopenia; Practice Patterns, Physicians'; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prescriptions; Risk Assessment; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; United States

A 4-year-old boy with acute lymphoblastic leukemia who was receiving 6-mercaptopurine during the maintenance chemotherapy experienced prolonged generalized tonic nocturnal seizures because of severe hypoglycemia after his evening dose by a 12-hour period of fasting. Investigations ruled out all causes of these seizures other than the 6-mercaptopurine-induced severe hypoglycemia.

Topics: Anti-Infective Agents; Antimetabolites, Antineoplastic; Child, Preschool; Humans; Hypoglycemia; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Child; Female; Hair Diseases; Humans; Immunosuppressive Agents; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission, Spontaneous; Trimethoprim, Sulfamethoxazole Drug Combination

Infectious complications remain a major problem after allogeneic hematopoietic stem cell transplant (HSCT). Specifically Toxoplasma gondii infection is a life-threatening condition in immunocompromised patients. In order to highlight the difficulties in obtaining an early and definitive diagnosis, we report three cases of toxoplasmosis after HSCT for hematologic malignancies: two cases of T. gondii retinochoroiditis, and one case of encephalitis. All patients had unrelated donors and received antithymocyte globulin; none had received trimethoprim/sulfamethoxazole prophylaxis. Toxoplasmosis occurred early post-transplant and diagnosis was obtained by real-time PCR. In one case, the correct diagnosis could only be established by PCR analysis of a retinal biopsy specimen. Rapid diagnosis--by invasive approaches--and an immediate onset of antiparasite treatment are crucial to avoid disseminated and often lethal Toxoplasma infections in the post-transplant period. Post-transplant prevention strategies and treatment to control advanced infection in this setting are discussed.

Topics: Anti-Infective Agents; DNA, Protozoan; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survival Rate; Toxoplasma; Toxoplasmosis; Transplantation, Homologous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Bacteremias are frequent during induction therapy for acute lymphoblastic leukemia (ALL) in children. Antibacterial prophylaxis therapy may thus be warranted. The purpose of this study was to analyze the rate of infections during induction therapy in two cohorts of children with ALL where one cohort received prophylactic sulfamethoxazole-trimethoprim (SMX-TMP).. All infections were registered through a retrospective non-randomized review of medical records of 171 consecutive children newly diagnosed with ALL below 15 years of age at diagnosis. A total of 85 children treated from 1992 to 2000 did not receive SMX-TMP, whereas 86 children treated from 2000 to 2008 received SMX-TMP 20 mg/kg in one daily oral dose during induction therapy.. A total of 26% of all children had no febrile episodes during induction. Infections were more frequent in children below 5 years of age. Significantly fewer children receiving SMX-TMP developed fever (17% vs. 34%, P = 0.02) and bacteremia (20% vs. 45%, P = 0.0003). Especially children with non-high risk criteria had fewer infections when receiving prophylaxis. When adjusting for age, type of catheter, and SMX-TMP prophylaxis on the risk of bacteremia by a multiple Cox regression analysis, we found that age and prophylaxis, but not the type of catheter, were associated with a significantly reduced risk of bacteremia.. Children with ALL receiving SMX-TMP prophylaxis during induction therapy experienced fewer febrile episodes, fewer days with fever demanding intravenous antibiotic treatment, and fewer episodes of bacteremia. Both SMX-TMP prophylaxis and age played significant independent roles for the occurrence of bacteremia.

Topics: Adolescent; Age Factors; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Child; Child, Preschool; Drug Evaluation; Female; Humans; Incidence; Infant; Male; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.

Topics: Anemia, Hemolytic; Anti-Infective Agents, Urinary; Child; Diagnosis, Differential; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transfusion Reaction; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of epididymo-orchitis and central nervous system nocardiosis in a 22-year-old man with T-cell acute lymphoblastic leukemia; he was an allogeneic marrow recipient with acute and chronic graft-versus-host disease.. He had microscopic hematuria and cytomegalovirus antigenemia. He deteriorated subsequently while on cyclosporine and steroids, requiring hospital admission owing to fever and swelling of the left testis and generalized tonic-clonic convulsions.. Brain magnetic resonance imaging showed abnormal signal area in right parietal and left parieto-occipital lobes. The lesions had mass effect, edema, and ring enhancement. Findings were indicative of a brain abscess. A testicular biopsy from the lower pole of the left testis was done. A white-to-yellowish discharge was seen and subsequently, Nocardia grew in culture.. Trimethoprim-sulfamethoxazole was prescribed, and significant improvement was seen after 2 weeks. The patient was discharged. He was subsequently referred after 3 weeks due to graft-versus-host disease and died of pancytopenia.

Topics: Acute Disease; Anti-Infective Agents; Bone Marrow Transplantation; Brain Abscess; Chronic Disease; Epididymitis; Epilepsy, Tonic-Clonic; Fatal Outcome; Graft vs Host Disease; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Nocardia Infections; Orchitis; Pancytopenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Infective Agents; Child, Preschool; Folic Acid Antagonists; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Linear IgA disease is characterized by the presence of linear IgA deposits in the basement membrane zone of the skin, and circulating basement membrane zone antibodies are detected in 80% of cases. The disease occurs in both adults and children, and is designated adult linear IgA disease in the former and chronic bullous disease of childhood (CBDC) in the latter. We describe a 5-year-old boy with acute lymphoblastic leukemia in remission, in whom CBDC developed after treatment with trimethoprim/sulfamethoxazole (cotrimoxazole). To our knowledge, this is the first reported case of possible drug-induced CBDC.

Topics: Anti-Infective Agents; Child, Preschool; Drug Eruptions; Humans; Immunoglobulin A; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Skin Diseases, Vesiculobullous; Trimethoprim, Sulfamethoxazole Drug Combination

(i) To compare the prevalence and levels of Capnocytophaga, a known systemic pathogen in immunocompromised patients, in the dental plaque of healthy children and children with cancer, and (ii) to determine the susceptibility of strains isolated from cancer patients to a range of antibiotics.. Thirty-one children with cancer undergoing a first course of immunosuppressive chemotherapy and 30 healthy control children were included in the study. Samples were collected on days 0, 7, 14, and 21 of the cure (and equivalent dates in controls). Susceptibility to antibiotics was tested using an agar dilution method and galleries with predefined concentrations of selected antibiotics.. There was a significant drop in the total anaerobic cultivable flora on day 14 and in the prevalence of Capnocytophaga on days 14 and 21 in the children with cancer. The proportion of Capnocytophaga in the anaerobic flora, however, was high in certain cancer patients. Beta-lactam/beta-lactamase inhibitor combinations, imipenem, clindamycin, and tetracycline were the most effective against Capnocytophaga.. This study showed that Capnocytophaga decreased in prevalence and proportion in the dental plaque of cancer patients during chemotherapy but became predominant in some cases. It is recommended that imipenem or beta-lactam/beta-lactamase inhibitor combinations be used to treat Capnocytophaga bacteraemia.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Capnocytophaga; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Colony Count, Microbial; Dental Plaque; Drug Resistance; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lymphoma; Male; Microbial Sensitivity Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Statistics, Nonparametric; Trimethoprim, Sulfamethoxazole Drug Combination

The occurrence of oral penicillin-resistant viridans group streptococci (VGS) was studied in 50 patients with either newly diagnosed acute leukaemia or autologous peripheral stem cell transplants. One patient was excluded because of Staphylococcus aureus growth in the stem cell harvest. VGS were isolated from the oral cavity of 48 of the remaining 49 patients. Of these 48 patients, 12 (25%) yielded VGS resistant (MIC > 2 mg/L) to penicillin. These 12 patients had a higher frequency of septicaemia (p 0.04) and more days of treatment with trimethoprim-sulphamethoxazole (p 0.04) than patients who harboured susceptible or intermediately resistant VGS (MIC 2 mg/L). There were no other statistically significant differences between the two groups. It is important to be aware of the high level of penicillin resistance in oral VGS in patients with haematological disease, and this parameter should be considered when selecting antibiotic therapy for cases of septicaemia caused by VGS in immunocompromised patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Mouth Mucosa; Penicillin Resistance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Stem Cell Transplantation; Streptococcal Infections; Sweden; Trimethoprim, Sulfamethoxazole Drug Combination; Viridans Streptococci

The authors report a fatal case of acute bacterial myocarditis in a nonneutropenic child with acute lymphoblastic leukemia. She was admitted to the hospital with a urinary tract infection resulting from and remained persistently febrile despite resolution of the infection. On hospital day 4 signs of acute cardiac failure developed. Despite aggressive resuscitation measures, she died. Pathologic examination revealed the cause of death to be bacterial myocarditis. In addition, she was found to have a generalized decrease in her serum immunoglobulin levels. Acute bacterial myocarditis in patients with malignancy has been rarely reported. The rapid clinical deterioration and death in the patient in this report is particularly interesting.

Topics: Acute Disease; Agammaglobulinemia; Antineoplastic Combined Chemotherapy Protocols; Cefotaxime; Child; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Myocarditis; Oxacillin; Pericarditis; Pleurisy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Shoulder Pain; Tobramycin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Children with acute lymphoblastic leukaemia (ALL) are treated with intensive chemotherapy, which results in profound immunosuppression. Treatment with trimethoprim/sulphamethoxazole (TMP-SMX) is therefore used in some departments as prophylaxis against infections with both bacteria and Pneumocystis carinii. The use of TMP/SMX for prophylaxis during the induction therapy is not uniform in the four departments of paediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy.. Between 1 January 1992 and 31 December 1997, 210 children were diagnosed with ALL in Denmark. From a retrospective review of the medical charts, the number of children with fever (> 38 degrees C), the number of febrile days, days of antibiotic treatment, and the number of positive blood cultures were registered for each febrile episode.. One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) vs. 60/76 (79%), p < 0.01) and significantly fewer children who received the prophylaxis had positive blood cultures before the start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p < 0.001)). Nineteen different species were isolated from the blood stream before the start of antibiotic treatment. In the non-prophylaxis group there were a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli, and P. aeruginosa. There was no difference in the mortality between the two groups (p = 0.44). There were no cases of P. carinii pneumonia in the period of induction therapy.. TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteraemias and febrile illness.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Child; Child, Preschool; Denmark; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Infant; Male; Opportunistic Infections; Pneumocystis Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Infective Agents; Bronchoalveolar Lavage Fluid; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lung; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Myelodysplastic Syndromes; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Primary Myelofibrosis; Radiography; Retrospective Studies; Thalassemia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii (P. carinii) is one of the major opportunistic pathogens responsible for hematopoietic stem cell transplantation (HSCT)-related pneumonias. Although trimethoprim-sulfamethoxazol (TMP/SMX) prophylaxis has been shown to prevent almost all P. carinii infections, 1%-2% of patients may still experience this complication. P. carinii pneumonia (PCP) is usually a late complication in patients receiving TMP/SMX prophylaxis, with most cases occurring later than 2 months post-transplant. We report a patient who developed early onset PCP after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling donor. On day 12, the patient complained of dyspnea and cough. A chest X ray showed infiltrates in right upper lobe with bilateral pleural effusion. By the findings of Grocott stain on bronchoalveolar lavage fluid obtained on day 14, he was diagnosed as having PCP. Intravenous TMP/SMX failed to improve the lesion. This is the earliest onset PCP in the literature after HSCT despite the prophylactic administration of TMP/SMX before transplant.

Topics: Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Combined Modality Therapy; Cytarabine; Daunorubicin; Etoposide; Fatal Outcome; Hematopoietic Stem Cell Transplantation; Humans; Immune System; Immunocompromised Host; Male; Methotrexate; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Respiratory Insufficiency; Transplantation Conditioning; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine; Whole-Body Irradiation

Pneumocystis carinii pneumonia (PCP) is a wellknown risk among patients with deficient T-cell function such as children treated for acute lymphoblastic leukemia (ALL). The purpose of this study was to estimate the risk for PCP during maintenance treatment (MT) to identify patients at risk who could benefit from prophylaxis.. We registered all episodes of PCP during MT in 71 children diagnosed between January 1992 and June 1997 with non-B-cell ALL at The Copenhagen University Hospital. Sulphametoxazole and trimetroprim (SMX/TMP) prophylaxis against PCP was given during induction and consolidation therapy but stopped prior to MT with oral methotrexate/6-mercaptopurine. Patients with standard (SR), intermediate (IR), and high risk (HR) ALL started MT at 3, 8, and 15 months from diagnosis, respectively.. The HR group had a cumulated risk of 70% for developing PCP, whereas the risk for PCP in children with IR and the SR was 11 and 8%, respectively (P < 0.0001). All but one of these 13 cases of PCP occurred within 8 months after cessation of SMX-TMP prophylaxis.. The higher incidence of PCP among HR compared to non-HR patients following cessation of SMX/TMP prophylaxis probably reflects the significantly longer T-cell suppressive consolidation therapy in this group. The very low incidence of PCP during the later part of MT emphasizes that methotrexate/6-mercaptopurine MT have more impact on B-cell than on T-cell function. TMP/SMX prophylaxis should be recommended for all children treated for ALL.

Topics: Adolescent; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Denmark; Female; Humans; Incidence; Infant; Lymphocyte Count; Male; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk; T-Lymphocytes; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Child; Female; Humans; Patient Compliance; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Children with acute lymphoblastic leukemia are treated with intensive chemotherapy resulting in profound immuno suppression. Therefore treatment with trimethoprim-sulfamethoxazole (TMP-SMX) may be used for prophylaxis against infections both with bacteria and Pneumocystis carinii in some departments. The use of TMP-SMX for prophylaxis during the induction therapy is not uniform in the four departments of pediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy.. Between January 1st 1992 and December 31st 1997, 210 children were diagnosed with ALL in Denmark. Based on a retrospective review of the medical charts the number of children with fever (>38 degrees C), the number of febrile days, days of antibiotic treatment and the number of positive blood cultures were registered for every febrile episode.. One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) v 60/76 (79%), p <0,01), and significantly fewer children who received TMP/SMX prophylaxis had positive blood cultures before start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p<0.001)). Nineteen different species were isolated from the blood stream before start of antibiotic treatment. In the non-prophylaxis group there was a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli and P. aeruginosa. There was no difference in the mortality between the two groups (p=0.44). There were no cases of P carinii pneumonia in the period of induction therapy.. TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteremias and febrile illness.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Child, Preschool; Female; Humans; Immunocompromised Host; Male; Opportunistic Infections; Pneumocystis Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Cough; Diagnosis, Differential; Female; Fever; Humans; Infant; Patient Compliance; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1), diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of consolidation (cytosine arabinosides, etoposide). After achieving remission, for further maintenance of remission, he was treated with 14 cycles of intensive chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and cyclophosphamide, 1200 mg/m2, vincristine, 1.5 mg/m2, epirubicin, 15 mg/m2, and cytosine arabinoside, 40 mg/m2, intravenously on days 4, 11, 39, and 40, respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX) infusion in a total dose of 150 mg/m2 plus oral leucovorin (30 mg/m2 ) rescue 36 h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was given regularly to prevent Pneumocystis carinii infection. The patient achieved remission during the first course of treatment, but 8 months later the disease relapsed. He then received four doses of MTX (800 mg intravenously) plus leucovorin rescue in the following 4 months. During the last MTX therapy, small hemorrhagic bullae were found on the lateral side of the right ankle, but subsided after a few days. Due to partial remission of the disease, he was admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on admission revealed hemoglobin 7.2 g/dL, white cell count 15,200/mm3, platelet count 153/mm3, blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m2 ) as a continuous intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion, leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to cover MTX toxicity included aggressive intravenous fluid replacement (4 L/m2 /day) and the addition of 25 meq/L sodium bicarbonate to the intravenous fluid to alkalinize the urine. Concurrent medication included 6-MP (50 mg) once daily and trimethoprim-sulfamethoxazole (120 mg, 600 mg) twice daily every other day. Plasma MTX levels were 52.36 micromol/L 24 h after MTX infusion, 1.87 micromol/L after 48 h, 0.57 micromol/L after 72 h, and 0.41 micromol/L after 96 h. These indicated delayed MTX plasma clearance. The blood creatinine level was mildly elevated from 0.5 mg/dL to 0.7 mg/dL. Thirty-six hours after the administration of MTX, the patient developed an erythematous

Topics: Adolescent; Anti-Infective Agents; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Humans; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Opportunistic Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Child; Humans; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate factors predisposing children with non-Hodgkin's lymphoma to toxicity from moderate dose methotrexate (MTX) (300 mg/m2 per 4 hours), we reviewed the medical records of 15 patients treated at our institution according to two similar protocols. Five patients experienced hyperemesis and/or severe mucositis. In two of these patients, pharmacokinetic analysis demonstrated delayed terminal excretion of methotrexate with a half-life of 3-3.5 days, compared to a previously reported t1/2 of 8-15 hours in subjects with normal clearance. All affected patients were large (body surface area 1.6-1.9 m2), and MTX toxicity was seen only during courses where intravenous MTX was given concurrently with intrathecal MTX. Four patients also received simultaneous prophylactic doses of oral trimethoprim-sulfamethoxazole (trimethoprim 5 mg/kg per day). We recommend that, in protocol design, consideration be given to avoiding concurrent use of intravenous and intrathecal MTX, and possibly trimethoprim-sulfamethoxazole. Where high doses of MTX are given based on large body surface area, urine alkalinization may be indicated.

Topics: Adolescent; Body Surface Area; Child; Child, Preschool; Female; Humans; Infusions, Intravenous; Injections, Spinal; Male; Metabolic Clearance Rate; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Thirty-four children with diagnosed cases of acute leukemias and being treated with cytotoxic chemotherapy at St James' Hospital, Leeds, were followed for between 6 months and 1 year to determine the changes in their oral microflora. They were examined before treatment commenced and then at monthly intervals. Swabs were taken from the oral cavity to test for the presence or absence of bacteria and Candida. Saliva samples were also used to assess the levels of Streptococcus mutans in the mouth. Sensitivity tests were carried out to assess the effect of the cytotoxic agents on the oral flora. All children received prophylactic nystatin and chlorhexidine gluconate mouthrinses four times daily for the whole period of the study. There was significant difference (p < 0.0001) for counts of S. mutans at different treatment stages. Sensitivity tests showed that S. mutans was sensitive to the cytotoxic drug daunorubicin, and this drug was probably responsible for the fall in S. mutans counts. A significant difference was also found in the types of bacteria isolated between the study and reference groups, but there was no change in the composition of the flora in the study group during treatment. These bacteria were also found to mirror those cultured from routine blood samples in children with acute leukemia.

Topics: Adolescent; Analysis of Variance; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Candida albicans; Candidiasis, Oral; Chi-Square Distribution; Child; Child, Preschool; Chlorhexidine; Colony Count, Microbial; Cytarabine; Daunorubicin; Etoposide; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mouth; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Streptococcus mutans; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), when used in combination, can cause metabolic acidosis, renal bicarbonate wasting, and growth failure. Retrospective review of repeated random serum chemistries from 10 children receiving TMP-SMZ and maintenance chemotherapy for acute lymphoid leukemia revealed low serum bicarbonate (P = .0002) and elevated serum chloride (P less than .0005) concentrations. These values normalized after all medications were discontinued. Prospective study of 8 children receiving TMP-SMZ and chemotherapy for acute lymphoid leukemia revealed lower serum bicarbonate concentrations and higher urine pH following a dose of TMP-SMZ than paired values obtained more than 3 days after a dose. Four children (50%) met serum bicarbonate and urinary pH criteria for the diagnosis of renal tubular acidosis soon after a dose of TMP-SMZ. The occurrence of TMP-SMZ-induced renal tubular acidosis has implications for the acid-base balance of children receiving TMP-SMZ on a long-term basis.

Topics: Acidosis, Renal Tubular; Adolescent; Bicarbonates; Child; Child, Preschool; Chlorides; Female; Humans; Hydrogen-Ion Concentration; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

In 42 patients with induction treatment of acute myeloblastic and lymphoblastic leukaemia the authors compared efficacy of selective decontamination of the gastrointestinal tract in prevention of infections during neutropenia less than 0.5.10(9)/l in two comparable groups. Twenty-two patients were treated with Ofloxacin (Tarivid, Hoechst Co.), 20 patients with Trimetroprim-Sulfamethoxazol (Biseptol, Polfa Co.). Both groups had concurrently also Ketoconazol in prevention of mycotic infection. The investigation revealed that Tarivid is a suitable alternative drug for selective decontamination, because it delays the onset of acquired infection, as compared with Biseptol, it reduced more efficiently the frequency of Gram-negative colonization and life-threatening Gram-negative sepsis, caused by resistent strains; its tolerance is significantly better. There was no significant difference in the occurrence of febrile days, febrile episodes, the duration of antibiotic treatment, the number of sepsis in two groups. The effect of Tarivid and Biseptol on the Gram-positive microbial flora is inadequate. Subclavian catheter increases in particularly the risk of Gram-positive sepsis in both groups.

Topics: Bacterial Infections; Female; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Ofloxacin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination