trimethoprim--sulfamethoxazole-drug-combination and Leukemia--Myeloid--Acute

The case report describes a woman who has an acute psychosis episode during the second course of trimethoprim/sulfamethoxazole therapy, after having an allogeneic hematopoietic stem cell transplant that favored a dose-related effect of this adverse effect.

Topics: Acute Disease; Adult; Anti-Infective Agents; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Psychoses, Substance-Induced; Risk Factors; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; 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

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Combinations; Humans; Leukemia, Myeloid, Acute; Remission Induction; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; United States

High-dose cytosine arabinoside (HDAra-C) has been used for remission induction, and in conventional doses for maintenance in a trial of single-agent therapy in 43 previously untreated patients with acute myelogenous leukemia (AML). Rationale for the trial was provided by the observed decrease in leukemic blast cell self-renewal in culture following exposure to Ara-C. Compared with a previous trial of 57 patients treated with multidrug therapy, single-drug Ara-C was associated with a significantly improved complete remission rate (P = .010), although the survival time was not increased. All patients with low self-renewal responded to HDAra-C in contrast to the previous trial where some patients with this phenotype failed remission induction. The clinical observations are consistent with the view that the antileukemic effect of Ara-C has some specificity for cellular events required for self-renewal of blast cells. Exposure in vivo to Ara-C was associated with an increase in blast stem cell renewal at relapse, indicating that maintenance with other drugs should be tested. The study demonstrates the importance of biological attributes in design and analysis of clinical trials.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Cytarabine; Doxorubicin; Drug Combinations; Humans; Leukemia, Myeloid, Acute; Middle Aged; Neoplastic Stem Cells; Phenotype; Remission Induction; Statistics as Topic; Sulfamethoxazole; Thioguanine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Stem Cell Assay

We conducted a randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral trimethoprim/sulfamethoxazole (TMP/SMX) in the prevention of bacterial infections in children with cancer. Sixty-three patients with acute leukemia were studied during the induction phase of chemotherapy; 28 patients with solid tumors who were starting intensive chemotherapy were also enrolled and treated for 2 months. There was no significant difference in the frequency of febrile episodes between the 43 children receiving trimethoprim/sulfamethoxazole and the 48 receiving placebo. However, when the group of 74 children who experienced granulocytopenia (absolute granulocyte count less than 500/microL) was analyzed separately, significant reductions in the frequencies of confirmed bacteremia (2.6% v 20.0%, P = .02) and febrile episodes (35.9% v 65.7%, P = .01) were observed in the trimethoprim/sulfamethoxazole group. Furthermore, life table analysis showed that children with leukemia receiving trimethoprim/sulfamethoxazole had significantly more days without fever and without bacteremia. No benefits from prophylaxis were recognized in the subgroup with solid tumors. Although the frequency of oral thrush was greater (P = .02) in the trimethoprim/sulfamethoxazole group (25.6%) than in the placebo group (6.3%), invasive fungal infection did not occur. Although the mean duration of granulocytopenia was greater among those receiving trimethoprim/sulfamethoxazole (13.7 v 9.0 days, P = .05), this did not appear to increase the overall risk for bacterial infection. These data suggest that trimethoprim/sulfamethoxazole reduces the frequency of bacteremia and febrile episodes in granulocytopenic children undergoing induction chemotherapy for acute leukemia.

Topics: Adolescent; Anti-Infective Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Microbial Sensitivity Tests; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A 16-year-old boy received an unrelated bone marrow transplant while in second remission of acute myeloid leukemia. He suffered from severe oral mucosal complications and had difficulty taking oral drugs such as sulfamethoxazole/trimethoprim (ST). Engraftment was obtained on transplant day 35, and blurred vision and headache appeared around transplant day 60. Funduscopy revealed retinal hemorrhage and macular edema, and an MRI scan of the head revealed a nodular lesion in the left putamen. Toxoplasma gondii was detected by CSF PCR, and cerebral toxoplasmosis was diagnosed. Following therapy with ST and clindamycin, the patient was administered pyrimethamine, sulfadiazine, and leucovorin. Symptoms improved promptly, and CSF PCR was negative 45 days after the start of treatment. Since the prevalence of toxoplasma antibodies increases with age, it is crucial to avoid toxoplasma reactivation by ST after hematopoietic cell transplantation in postpubescent patients.

Topics: Adolescent; Bone Marrow Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Pediatric acute myeloid leukemia (AML) is a challenging disease to treat in low- and middle-income countries (LMICs). Literature suggests that survival in LMICs is poorer compared with survival in high-income countries (HICs).. This study evaluates the outcomes of Kenyan children with AML and the impact of sociodemographic and clinical characteristics on outcome.. A retrospective medical records study was performed at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, between January 2010 and December 2018. Sociodemographic and clinical characteristics, and treatment outcomes were evaluated. Chemotherapy included two "3 + 7" induction courses with doxorubicin and cytarabine and two "3 + 5" consolidation courses with etoposide and cytarabine. Supportive care included antimicrobial prophylaxis with cotrimoxazole and fluconazole, and blood products, if available. Seventy-three children with AML were included. The median duration of symptoms before admission at MTRH was 1 month. The median time from admission at MTRH to diagnosis was 6 days and to the start of AML treatment 16 days. Out of the 55 children who were started on chemotherapy, 18 (33%) achieved complete remission, of whom 10 (56%) relapsed. The abandonment rate was 22% and the early death rate was 46%. The 2-year probabilities of event-free survival and overall survival were 4% and 7%, respectively. None of the sociodemographic and clinical characteristics were significantly associated with outcome.. Survival of Kenyan children with AML is dismal and considerably lower compared with survival in HICs. Strategies to improve survival should be put in place including better supportive care, optimization of the treatment protocol, and reduction of the abandonment rate and time lag to diagnosis with sooner start of treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Doxorubicin; Etoposide; Fluconazole; Humans; Kenya; Leukemia, Myeloid, Acute; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PJP) is infrequently found in patients with acute myeloid leukemia (AML) whereas its more commonly found in lymphoid malignancies like acute lymphoblastic leukemia and various lymphomas. AML patients are conventionally treated with intensive chemotherapeutic regimen which includes Daunorubicin, Idarubicin, Cytarabine and various other drugs. Trimethoprim/Sulfamethoxazole prophylaxis is not routinely administered to such patients. In recent years, targeted therapies like Venetoclax which is a Bcl-2 inhibitor have been introduced for AML treatment which is given in combination with other chemotherapy and targeted molecules. There is tremendous use of Venetoclax for AML recently specially in unfit and elderly population. We are witnessing this uncommon infection more commonly in those patients treated with Venetoclax based therapy. We report the case series of five patients of AML who were treated with Venetoclax based therapy and had subsequently developed PJP leading to death in four of them. The incidence of PJP was 13.2% among the patients treated with Venetoclax based treatment at our institution in that timeframe. The low index of suspicion led to delay in diagnosis and thereby treatment. Such an association of Venetoclax and Pneumocystis jirovecii pneumonia has not been reported till date, so this prompts for early detection and treatment of this potentially life threatening but treatable infection. So the role of routine prophylaxis with Trimethoprim/Sulfamethoxazole in those receiving Venetoclax based therapy in AML patients merits a thought.

Topics: Aged; Bridged Bicyclo Compounds, Heterocyclic; Cytarabine; Humans; Idarubicin; Leukemia, Myeloid, Acute; Pneumocystis carinii; Pneumonia, Pneumocystis; Proto-Oncogene Proteins c-bcl-2; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Pediatric patients under treatment for acute myeloid leukemia (AML) are at high risk for invasive fungal infection (IFI). We evaluated the efficacy of prophylactic administration of voriconazole (VRCZ) with two different doses.. Between October 2005 and June 2011, 17 children and adolescents (aged 0-20 years) undergoing chemotherapy for AML were prophylactically administered with 5 mg/kg/d of oral VRCZ. Furthermore, 22 AML patients (aged 0-19 years) were administered 10 mg/kg/d of oral VRCZ between July 2011 and December 2014. The incidences of IFI with two different doses of VRCZ were compared.. Irrespective of the dosage of VRCZ, eight patients developed IFI. Of these eight patients, four belonged to the 5 mg/kg/d group and four to the 10 mg/kg/d group. Cumulative incidences of IFI at 180 days after the initiation of chemotherapy were not different between the 5 mg/kg/d and 10 mg/kg/d groups. The trough plasma VRCZ concentration in the 10 mg/kg/d group ranged from < 0.09 μg/mL to 2.17 μg/mL, with a median level of 0.27 μg/mL, and patients with the targeted trough concentration (1-4 μg/mL) comprised only 18.8% of the evaluable patients in this group, whereas the trough plasma VRCZ concentration of the evaluable patients in the 5 mg/kg/d group were all below the limit of sensitivity (< 0.09 μg/mL).. More dose escalation is required based on this study. As VRCZ concentration is considerably influenced by genetic polymorphisms and drug-drug interactions, VRCZ should be used under therapeutic drug monitoring to keep effective drug concentrations.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antifungal Agents; Child; Child, Preschool; Drug Monitoring; Female; Humans; Infant; Infant, Newborn; Invasive Fungal Infections; Japan; Leukemia, Myeloid, Acute; Male; Neutropenia; Pneumonia, Bacterial; Pre-Exposure Prophylaxis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Voriconazole; Young Adult

Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years.. Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire.. Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group.. The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Ciprofloxacin; Clostridioides difficile; Colistin; Diarrhea; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Female; Fever; Fluoroquinolones; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

A 36-year old female with acute myelogenous leukemia presented with a sudden decrease in vision one month following bone marrow transplantation (BMT). She had been taking multiple immunosuppressants to treat her recently-developed graft-versus-host-disease (GVHD). Visual acuity was 20/60 in her right eye and 20/25 in her left. Ophthalmic examination revealed mild inflammatory reaction in both the anterior chamber and the vitreous of both eyes, as well as densely opaque yellow-white infiltrates with well-demarcated borders in the posterior retina of both eyes. She was originally diagnosed as CMV retinitis, but treatment with ganciclovir failed to improve her ocular condition. Subsequent work-up, including serology and brain MRI, led to a diagnosis of combined ocular and cerebral toxoplasmosis. After 6 weeks of antiparasitic therapy, her retinal lesions became inactive and her cerebral lesions improved. Immunosuppressed patients with necrotizing retinochoroiditis should be suspected of having toxoplasmosis. Accurate differentiation between this condition and CMV, and early intervention with the appropriate treatment may be critical to preserve the best vision.

Topics: Adult; Anti-Bacterial Agents; Bone Marrow Transplantation; Chorioretinitis; Clindamycin; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; Functional Laterality; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Tomography, Optical Coherence; Toxoplasmosis, Cerebral; Toxoplasmosis, Ocular; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of breakthrough cerebral toxoplasmosis during atovaquone therapy in a child who was intolerant of conventional prophylactic regimens after hematopoietic stem cell transplantation. The available data on the efficacy of atovaquone prophylaxis in Toxoplasma sero-positive stem cell transplant recipients remain limited, and other strategies, such as preemptive strategy using toxoplasma PCR or TMP-SMX desensitization should be considered in this setting.

Topics: Anti-Infective Agents; Atovaquone; Child; Encephalitis; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Time Factors; Toxoplasmosis, Cerebral; Treatment Outcome; 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

Topics: Anti-Infective Agents; Female; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Middle Aged; Myoclonus; Nocardia asteroides; Nocardia Infections; 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 aetiology, clinical characteristics and outcome of bacteraemia in patients with acute myeloid leukaemia were studied. All positive blood cultures collected at a haematological ward during 2 7-y periods were evaluated. Altogether, 274 episodes of bacteraemia in 152 patients were recorded, 80 episodes during 1980-86 and 194 during 1990-96. During the 2 periods, trimethoprim-sulfamethoxazol in combination with amikacin was the first-line empirical therapy in patients with neutropaenia and fever. In 1990, antimicrobial prophylaxis with ciprofloxacin and fluconazole was introduced. The incidence of bacteraemia due to viridans streptococci or coagulase-negative staphylococci increased from the first period to the second, whereas the incidence of Enterobacteriaceae decreased. In granulocytopaenic patients during 1990-96, viridans streptococci accounted for 21% of the isolates and in patients treated prophylactically with fluoroquinolone, viridans streptococci accounted for 31%. All viridans streptococci were sensitive to penicillin. At the time of the positive blood cultures, the patients of the second period were granulocytopaenic in 83% of the episodes. The mortality related to septicaemia during the later period was 13% and only 1 of 33 (3%) of the patients with viridans streptococci died. Eight patients (9%) died in relation to septicaemia following curative antileukaemic therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Ciprofloxacin; Drug Resistance, Microbial; Female; Fluconazole; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Penicillins; Streptococcal Infections; Streptococcus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 46-year-old woman developed concurrent CMV and Pneumocystis carinii pneumonia (PCP) 140 days after autologous peripheral blood stem cell transplantation (APBSCT) for AML. She was seropositive for CMV before undergoing APBSCT and had required prednisone for immune thrombocytopenia and allergic dermatitis for 9 weeks prior to the onset of pneumonia. She had also been receiving PCP prophylaxis with pentamidine aerosol every month for 3 months before developing symptoms. The pneumonia was complicated by severe hypoxia, requiring ventilator support and pneumothorax requiring chest tube thoracostomy. She recovered following treatment with trimethoprim-sulfamethoxazole (TMP-SMX), prednisone, gancyclovir and intravenous immunoglobulin. Although the overall incidence of severe CMV disease is low after APBSCT, preventive measures such as surveillance culture and secondary prophylaxis with gancyclovir may be warranted in patients whose cellular immune response is further compromised by corticosteroid use or other factors.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Middle Aged; Pneumonia, Pneumocystis; Pneumonia, Viral; Prednisone; Transplantation, Autologous; 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

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

Mixed opportunistic infection with Pneumocystis carinii and Candida prior to cytotoxic therapy in a young male diagnosed as having acute non-lymphoblastic leukaemia resulted in early catastrophe. The role of awareness of this complication and its prompt management is discussed.

Topics: Adult; Bone Marrow; Humans; Leukemia, Myeloid, Acute; Lung; Male; Opportunistic Infections; Pneumonia, Pneumocystis; 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

Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria.

Topics: Ceftazidime; Colistin; Enterobacter; Feces; Gentamicins; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Neutropenia; Nystatin; Oropharynx; Risk Factors; Staphylococcus; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Continuous infusion of amikacin, cotrimoxazole and carbenicillin was the second empirically established combination of antibiotics used when fever occurred during the induction phase of chemotherapy in sixty-five patients (58 acute myeloid leukemias, 5 acute lymphoid leukemias, 2 non Hodgkin lymphomas). Clinical evidence of infection was available in 25 cases and the infection was bacteriologically documented in 19 cases. Therapy was successful in 57 patients (89%). When infection was clinically or bacteriologically documented tha success rates were 92 and 82% respectively. The average length of treatment was ten days. In 25 patients receiving 2 g of amikacin in continuous infusion, the mean serum concentration was 15,9 micrograms/ml; in 17 patients receiving 3 g, the mean serum concentration was 19,4 micrograms/ml.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The treatment of acute myelocytic leukemia in childhood and young adults has lagged behind that for acute lymphocytic leukemia. The studies described here were directed towards evaluating the role of intensive chemotherapy in the treatment of this illness. Intensive remission induction therapy combining cytosine arabinoside with an anthracycline antibiotic produced a complete remission rate comparable to that achieved in acute lymphocytic leukemia (45 of 49 patients or 92%). Intensive consolidation chemotherapy produced a median duration of complete remission of 160 weeks with 40% of patients projected to be in remission at 4 years. By contrast, the median duration of remission for patients treated with moderate consolidation/maintenance therapy was 23 weeks with only 10% of patients in remission at 4 years. These studies demonstrate that intensive chemotherapy can be administered to pediatric patients and young adults and that this approach to therapy produces a high remission rate with a 3 year median duration of remission.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Agents; Cytarabine; Daunorubicin; Doxorubicin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Sulfamethoxazole; Thioguanine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination