trimethoprim--sulfamethoxazole-drug-combination and Neutropenia

Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality.. This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention.. We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies.. Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients.. Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software.. One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection (53 trials, 6383 participants; RR 0.51, 95% CI 0.42 to 0.62) and other indicators of infection.There were no significant differences between quinolone prophylaxis and TMP-SMZ prophylaxis with regard to death from all causes or infection, however, quinolone prophylaxis was associated with fewer side effects leading to discontinuation (seven trials, 850 participants; RR 0.37, 95% CI 0.16 to 0.87) and less resistance to the drugs thereafter (six trials, 366 participants; RR 0.45, 95% CI 0.27 to 0.74).. Antibiotic prophylaxis in afebrile neutropenic patients significantly reduced all-cause mortality. In our review, the most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefits of antibiotic prophylaxis outweighed the harm such as adverse effects and the development of resistance since all-cause mortality was reduced. As most trials in our review were of patients with haematologic cancer, we strongly recommend antibiotic prophylaxis for these patients, preferably with a quinolone. Prophylaxis may also be considered for patients with solid tumours or lymphoma.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Cause of Death; Drug Resistance, Bacterial; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Quinolones; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Chemotherapy-induced neutropenia can cause fatal bacterial infections. Colony-stimulating factors (CSFs) are usually recommended as prophylaxis, while routine use of prophylactic antibiotics remains controversial. Based on our literature search in PubMed, quinolones and trimethoprim/sulfamethoxazole were the most frequently used prophylaxis, while CSFs were administered in 22.1% of patients. Lung cancer patients who received prophylactic antibiotics exhibited significantly fewer episodes of febrile neutropenia, fewer documented infections as well as shorter duration of related hospitalisations. Prophylactic use of wide spectrum antibiotics seems effective and should be considered as an alternative strategy in the prevention of chemotherapy-induced neutropenia in lung cancer patients.

Topics: Antibiotic Prophylaxis; Antineoplastic Agents; Colony-Stimulating Factors; Fever; Humans; Lung Neoplasms; Neutropenia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections, but not in reducing mortality rates.. This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention.. Electronic searches on The Cochrane Cancer Network Register of Trials (2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1980 to 2004) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted.. RCTs or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients.. Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated.. One hundred trials (10,274 patients) performed between the years 1973 to 2004 met inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR, 0.66 [95% CI 0.54 to 0.81]). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 60 (95% CI 34 to 268). Prophylaxis resulted in a significant decrease in the risk of infection-related death, RR 0.58 (95% CI 0.45 to 0.74) and in the occurrence of fever, RR 0.78 (95% CI 0.75 to 0.82). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all-cause mortality, RR 0.52 (95% CI, 0.37 to 0.84).. Our review demonstrated that prophylaxis significantly reduced all-cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all-cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Quinolones; Randomized Controlled Trials as Topic; 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

Bacterial infections remain an important cause of morbidity and mortality in neutropenic patients. A number of prophylactic strategies have been used in order to reduce the risk of infection during severe granulocytopenia. The measures that have been investigated include isolation of the patient, granulocyte transfusion, active or passive immunisation, acceleration of granulocyte recovery and prophylactic use of antibacterial agents. However, many of these approaches have fallen out of favour, mostly because of concerns about the long lasting efficacy. This paper focuses on the available prophylactic strategies, with emphasis on the use of antibacterial agents.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Bacterial Infections; Clinical Trials as Topic; Fluoroquinolones; Humans; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: 4-Quinolones; Animals; Anti-Infective Agents; Antibiotic Prophylaxis; Bacterial Infections; Humans; Mice; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

To perform a meta-analysis to estimate the efficacy of quinolone antibiotics in preventing infections, fevers, and deaths among cancer patients neutropenic following chemotherapy.. We searched MEDLINE to identify randomized trials of quinolone prophylaxis, controlled either with no prophylaxis or trimethoprim/sulfamethoxazole (TMS) prophylaxis. We pooled relative risks for outcomes using a random-effects model.. Eighteen trials with 1,408 subjects were included. Compared with no prophylaxis, quinolones significantly reduced the incidence of gram-negative bacterial infections (relative risk, 0.21; 95% confidence interval [CI], 0.12 to 0.37), microbiologically documented infections (0.65; 0.50 to 0.85), total infections (0.54; 0.31 to 0.95), and fevers (0.85; 0.73 to 0.99). Quinolone prophylaxis did not alter the incidence of gram-positive bacterial, fungal, or clinically documented infections, or infection-related deaths. Results were similar for trials that used TMS as the control regimen. Among those who received quinolones, the incidence of infections due to quinolone-resistant organisms was 3.0% (95% CI, 1.7% to 5.2%) for gram-negative species and 9.4% (95% CI, 5.3% to 16.3%) for gram-positive species. Based on limited data, the incidence of quinolone-resistant infections was not higher among quinolone recipients than controls. With fever as outcome, blinded trials found quinolones less efficacious than did unblinded trials.. Quinolone prophylaxis substantially reduces the incidence of various infection-related outcomes, but not deaths, in these patients. Although this reduction in infections may translate into a decrease in morbidity, the reduction in fevers (and by extension, use of empiric antibiotics) appears small, and blinded trials provided less evidence for benefit than unblinded trials. Quinolone-resistant infections are uncommon, but continued vigilance is warranted.

Topics: Anti-Infective Agents; Antineoplastic Agents; Fever; Humans; Neoplasms; Neutropenia; Opportunistic Infections; Quinolones; Randomized Controlled Trials as Topic; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Infection are part of the natural course of lung cancer but overall they are poorly understood. The clinical studies on which is based our knowledge often lack sufficient clinical and microbiological documentation of the infection. Nevertheless, infection is frequently caused by Gram+ pathogens, among which pneumococci remain common. When lung cancer patients are treated with chemotherapy, the resulting neutropenia predisposes further to infection; its spectrum is similar to what has been observed in other granulocytopenic patients. The frequency and severity of the infection depends mainly on the severity and duration of neutropenia. Cotrimoxazole prophylaxis in neutropenic patients with lung cancer has been found effective in several studies. As far as therapy of fever and/or infection in neutropenic lung cancer is concerned, it does not appear that it should be handled differently from febrile neutropenia in other chemotherapy treated neutropenic patients.

Topics: Anti-Infective Agents; Antineoplastic Agents; Gram-Positive Bacterial Infections; Humans; Lung Neoplasms; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

Prevention of infection from bowel-derived organisms in neutropenic patients requires both the appropriate use of chemoprophylaxis and close attention to the prevention of cross-colonization or cross-infection with resistant Enterobacteriaceae and pseudomonads. Control of common-source infection and control of Gram-positive infection are also important. The objectives of chemoprophylaxis should be considered and their efficacy regularly assessed. Non-absorbable antibiotics may have an important place in minimizing selection of resistant strains, but absorbed agents such as cotrimoxazole (trimethoprim/sulphamethoxazole) and 4-quinolones offer advantages over these and nalidixic acid as prophylactic agents. Ciprofloxacin prophylaxis is probably more effective at reducing Gram-negative bacteraemia than co-trimoxazole but overall mortality may be higher. Further confirmation and investigation of the reasons for this are needed. Protocols of rational antibiotic prophylaxis and treatment involving these agents can be modified to cover only the Gram-negative superinfections that are likely.

Topics: 4-Quinolones; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Cross Infection; Enterobacteriaceae Infections; Humans; Intestine, Large; Neutropenia; Pseudomonas Infections; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Gram-negative infections in neutropenic patients originate frequently from the gut flora. Attempts to decrease the incidence of these infections have utilized several regimens for gastrointestinal decontamination, of which some have proven to be clinically useful. Orally administered nonabsorbable antibiotics (aminoglycosides, polymyxins) can decrease the incidence of gram-negative sepsis during neutropenia, but, with the possible exception of netilmicin, tolerance to these agents is generally poor, and compliance is low. Trimethoprim-sulfamethoxazole has been used widely for the prophylaxis of infections in neutropenic patients. Clinical results with this agent have been conflicting, as its efficacy is clearly related to epidemiological patterns of resistance of the pathogens in the population under study. More recently, the quinolones, which are well tolerated by patients and are presently active on most strains of Enterobacteriaceae, have been associated with a virtual eradication of gram-negative infections in neutropenic patients. These results have been paralleled by an increase in the frequency of gram-positive infections, which, fortunately, cause an incidence of mortality that is much lower than that seen in gram-negative sepsis. The fact that the quinolones are absorbed systemically might help to explain their efficacy in chemoprophylaxis during neutropenia. This paper discusses the chemoprophylaxis of gram-negative infection during neutropenia in the light of theoretical concepts such as 'colonization resistance', 'selective decontamination', and 'bacterial translocation'.

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Neutropenia; Quinolones; Trimethoprim, Sulfamethoxazole Drug Combination

Ciprofloxacin with erythromycin, each at a dose of 250 mg 12-hourly, is effective prophylaxis against Gram-negative bacteraemia in neutropenic patients. The erythromycin component may contribute little to prophylaxis and does select for erythromycin-resistant viridans streptococci which then cause bacteraemia. Ciprofloxacin prophylaxis does not prevent coagulase-negative staphylococcal bacteraemia and resistant strains are selected. Initial use of vancomycin with a ureidopenicillin in pyrexial patients is currently justified by the exclusively Gram-positive nature of breakthrough bacteraemia. In patients failing to respond to this regimen, treatment modification to include full-dose amphotericin is frequently effective. Surveillance and containment isolation of patients carrying resistant Gram-negative species is prudent to prevent the spread of such resistant bacteria in oncology/haematology units.

Topics: Ciprofloxacin; Erythromycin; Feces; Gram-Negative Bacteria; Humans; Neutropenia; Sepsis; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear.. HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14-34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761.. From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference -0·2%, 95% CI -1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the co-trimoxazole group vs 17·4% in the placebo group, p=0·19) or grade 3-4 clinical adverse events (16·5% vs 18·4%, p=0·18). Grade 3-4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93), but grade 3-4 neutropenia was more frequent in the co-trimoxazole group than in the placebo group (8·1% vs 5·8%, p=0·03). More co-trimoxazole resistance in commensal Escherichia coli isolated from stool samples was seen in children aged 3 or 6 months in the co-trimoxazole group than in the placebo group (p=0·001 and p=0·01, respectively). 572 (20%) children were breastfed. HIV infection and mortality did not differ significantly by duration of breastfeeding (3·9% for 6 months vs 1·9% for 12 months, p=0·21).. Prophylactic co-trimoxazole seems to offer no survival benefit among HEU children in non-malarial, low-breastfeeding areas with a low risk of mother-to-child transmission of HIV.. US National Institutes of Health.

Topics: Adult; Anti-HIV Agents; Botswana; Breast Feeding; Double-Blind Method; Drug Resistance, Microbial; Escherichia coli; Female; HIV Infections; Hospitalization; Humans; Infant; Infant Death; Infant, Newborn; Infectious Disease Transmission, Vertical; Neutropenia; Perinatal Death; Pregnancy; Pregnancy Complications, Infectious; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia infection is of concern in patients with cancer. Antibiotics active against S. maltophilia are rarely used in the treatment of febrile neutropenia, making it important to identify the factors influencing mortality in cancer patients with S. maltophilia infection. The objective of this study was to analyze the clinical characteristics and outcomes of cancer and hemopathic patients with S. maltophilia infection and assess the factors influencing the mortality. The microbiology laboratory records of Erciyes University, Faculty of Medicine Hospital were reviewed to retrospectively identify patients with S. maltophilia infection between January 2007 and June 2011. A total of 38 patients (25 male, 13 female) were eligible for the study. The median age of the patients was 53 years. The underlying disease was hematological malignancy and disorders in 76.3 % (29 cases), solid tumors in 15.8 % (six cases), aplastic anemia in 7.9 % (three cases), while 18.4 % (seven cases) were hematopoietic stem cell transplantation (HSCT) recipients. An indwelling central venous catheter was used in 32 cases (84.2 %). Twenty-seven patients (71.1 %) were neutropenic at the onset of infection. Nine patients (23.7 %) were receiving corticosteroid therapy. The overall 14-day mortality rate was 50 %. Three of the patients received empirical antibacterial treatment, and three HSCT recipients received trimethoprim-sulfamethoxazole prophylaxis, which is active against S. maltophilia. Severe sepsis (OR 13.24, 95 % confidence interval (CI) 1.62-108.57) and the duration of the treatment (OR 0.73, 95 % CI 0.60-0.90) were related to death based on logistic regression analysis findings. In immunocompromised hematology-oncology patients with severe sepsis, S. maltophilia should be considered as a possible cause of infection, and should be given effective empirical antibiotic treatment immediately; the antimicrobial spectrum may be narrowed according to results of antibiotic susceptibility test.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Infective Agents; Female; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies; Sepsis; Severity of Illness Index; Stenotrophomonas maltophilia; Survival Rate; Time Factors; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed.. Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1.. Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole + nevirapine and the cotrimoxazole + placebo groups were compared using negative-binomial regression.. Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole + nevirapine and cotrimoxazole + placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole + nevirapine versus cotrimoxazole + placebo.. Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

Topics: Adult; Anemia; Anti-HIV Agents; Blotting, Western; Breast Feeding; Drug Administration Schedule; Drug Eruptions; Exanthema; Female; HIV Seropositivity; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Milk, Human; Neutropenia; Nevirapine; Pregnancy; Risk Factors; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)-infected populations.. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines.. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; p = .08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; p < .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, <750 cells/mm(3)). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; p < .001).. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.

Topics: Amodiaquine; Anti-HIV Agents; Antimalarials; Artemisinins; Artesunate; Chemoprevention; Child; Child, Preschool; Drug Therapy, Combination; HIV Infections; Humans; Infant; Malaria; Neutropenia; Sesquiterpenes; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda

Neutropenia is the most frequent side effect of cotrimoxazole in sub-Saharan Africa. We estimated the incidence of haematological disorders during the first 6 months of a zidovudine-containing highly active antiretroviral therapy (HAART) regimen in sub-Saharan African adults receiving cotrimoxazole.. Prospective cohort study in Abidjan, with blood cell count measurement at baseline (HAART initiation), month 1, month 3 and month 6.. A total of 498 adults [baseline: 80% currently on cotrimoxazole prophylaxis; median CD4 count 237/mm3 [interquartile range (IQR) 181;316]; median neutrophil count 1647/mm3 (IQR 1221;2256); median haemoglobin 113 g/l (IQR 102;122)] started zidovudine (AZT)/lamivudine/efavirenz. During follow-up, 118 patients had a grade 3-4 neutropenia [(56.3/100 person-years (PY)], 23 had a grade 3-4 anaemia (9.6/100 PY) and no cases of grade 3-4 thrombocytopenia. Of the 118 patients with grade 3-4 neutropenia, 86 (73%) had to stop cotrimoxazole because neutropenia persisted, and one (<1%) had to stop AZT because of persistent neutropenia after cotrimoxazole was stopped (neutropenia-related HAART modification: 0.4/100 PY). Of the 23 patients with grade 3-4 anaemia, 11 had to stop AZT (anaemia-related HAART modification: 4.4/100 PY). In patients who stopped cotrimoxazole but not AZT, the median gain in neutrophils at 1 month was +540/mm3 (IQR +150;+896).. At baseline, most patients had a normal neutrophil count and 80% of them were already receiving cotrimoxazole. An unexpectedly high rate of grade 3-4 neutropenia occurred shortly after introduction of AZT. Almost all of the persistent severe neutropenia disappeared after cotrimoxazole was stopped. This suggests an accentuated drug interaction between the two drugs in these sub-Saharan African individuals. Grade 3-4 anaemia was much less frequent, but remained the first cause of AZT discontinuation.

Topics: Adult; Anemia; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Blood Cell Count; Blood Platelets; Cohort Studies; Cote d'Ivoire; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Neutropenia; Prospective Studies; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

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

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

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacteremia; Child; Colistin; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Ofloxacin; Penicillin V; Penicillins; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In a prospective randomized comparison, 217 episodes of fever (oral temperature > 38.5 degrees C on 1, or 38.0 degrees C on 2 occasions with a minimum interval of 4 h between recordings) during neutropenia (neutrophil count < 0.5 x 10(9)/I), patients were empirically treated with trimethoprim-sulfamethoxazole plus amikacin (TMP/SMZ plus AMI) or ceftazidime. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiological evidence of infection on the primary therapy alone. The overall success rate did not differ between the 2 treatment groups: 31/102 (30%; 21-39%, 95% confidence interval, CI) for TMP/SMZ plus AMI and 41/115 (36%; 27-44%) for ceftazidime (difference 0.06 +/- 0.13, 95% CI). The corresponding numbers for documented infections were 12/50 (24%; 12-36%) and 14/60 (23%; 12-35%), respectively (difference 0.01 +/- 0.16). One patient in the TMP/SMZ plus AMI group and 2 patients in the ceftazidime group died from Gram-negative bacteraemias within 72 h. No other early deaths were observed. Antibiotics were changed due to adverse events in 2 episodes of each treatment group. In conclusion, this study demonstrates that TMP/SMZ plus AMI combination is comparable (i.e. a difference of < 20%) to ceftazidime monotherapy with regard to efficacy and safety in haematological patients with severe neutropenia. Both regimens require frequent modifications, particularly in bacteraemic fever episodes. However, in centres with a low frequency of isolation of Pseudomonas and especially of multi-resistent Pseudomonas strains, TMP/SMZ plus AMI offers an inexpensive alternative for the empirical treatment of febrile neutropenia.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Blood; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Middle Aged; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Female; Humans; Incidence; Leucovorin; Male; Middle Aged; Neutropenia; Placebos; Pneumonia, Pneumocystis; Probability; Risk Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

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

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

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

The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antineoplastic Agents; Bacterial Infections; Child; Female; Gram-Negative Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Ofloxacin; Trimethoprim, Sulfamethoxazole Drug Combination

Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic.. In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day).. The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone.. In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Chemical and Drug Induced Liver Injury; Dapsone; Double-Blind Method; Drug Combinations; Female; Humans; Male; Neutropenia; Pentamidine; Pneumonia, Pneumocystis; Random Allocation; Survival Rate; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

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

Eighty-four cancer patients at risk of infection because of neutropenia were randomized to receive nalidixic acid as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) for infection prophylaxis. Infections were documented significantly earlier and more often among patients who entered the trial with neutrophil counts of less than 0.1 X 10(9)/liter. TMP-SMX recipients experienced fewer microbiologically documented infections and bacteremias and were free of infection for a higher proportion of days with severe neutropenia (less than 0.1 X 10(9)/liter) than nalidixic acid recipients. Gram-negative bacillary and Staphylococcus aureus infections accounted for the major differences. Although the majority of aerobic gram-negative bacilli were eliminated from the feces after 1 week of prophylaxis with either agent, TMP-SMX was proved superior to nalidixic acid in this regard and was associated with acquired drug resistance by gram-negative bacilli less frequently. Both agents selected for colonization and subsequent infection by gram-positive cocci. Our data suggest that prophylaxis is most likely to be effective if administered to patients for at least 1 week before they become severely neutropenic. Nalidixic acid used as a single agent in doses of 4 g daily, however, cannot be recommended as an alternative to TMP-SMX for infection prophylaxis in neutropenic cancer patients.

Topics: Agranulocytosis; Antineoplastic Agents; Bacteria; Bacterial Infections; Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Humans; Intestines; Microbial Sensitivity Tests; Mycoses; Nalidixic Acid; Neoplasms; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In 103 patients with small-cell lung cancer, we compared four courses of standard doses of Adriamycin (A) (Adria Laboratories, Columbus, Ohio), vincristine (V), and cyclophosphamide (C) with a regimen of increased doses of cyclophosphamide and to a lesser extent, Adriamycin. We found no significant difference in rate (22% v 21%) or median duration (seven v nine months) of complete remission. Patients not in complete remission after the four cycles of AVC received two courses of VP-16 (etoposide) and cisplatin: the complete remission rate increased to 49% and 48% respectively. Patients on the high-dose arm received co-trimoxazole prophylaxis; those on the standard arm did not. Patients on the high-dose arm had a higher incidence of neutropenia (nadir less than 500 cells/microL) but a lower incidence of infection for similar degrees of neutropenia. However, they also suffered more severe side effects of a different kind. Cotrimoxazole thus allowed for the administration of higher doses of chemotherapy to outpatients by protecting them from infection. However, the higher doses of cyclophosphamide and Adriamycin, did not improve treatment results, produced more severe side effects, and is not recommended.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cats; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Combinations; Etoposide; Female; Humans; Infection Control; Lung Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine; Vomiting

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

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

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

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

Ketoconazole or miconazole was randomly administered to 42 and 46 neutropenic patients respectively. Of the total number of stool cultures 12% were positive for yeasts in both groups; 4% of the total number of cultures from other sites (nose, throat, skin) were positive in both groups. Candida albicans was the most common isolate, but other fungal species were also identified. No patient developed fungemia; 5/88 patients developed severe oropharyngeal candidiasis while receiving prophylaxis. Among the 21 autopsies performed, 5 cases of pulmonary aspergillosis and 2 local and 1 disseminated candidiasis were demonstrated in 7 patients. Although there was no placebo group of patients in this study, post-mortem data suggest that miconazole or ketoconazole might reduce the incidence of disseminated candidiases in neutropenic patients.

Topics: Agranulocytosis; Antifungal Agents; Candidiasis; Drug Combinations; Female; Humans; Imidazoles; Ketoconazole; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Neutropenia; Piperazines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

It is well known that patients with granulocytopenia due either to bone marrow failure, acute leukemia or its treatment, or as a result of other intensive chemotherapy are at enhanced risk of serious infection. Several approaches have been designed to minimize the risk of infection in these patients by means of suppression of gastrointestinal flora. A retrospective review of infection in febrile neutropenic patients revealed a significant decrease in bacteremia in patients who had received some oral antimicrobial regimen compared with those who did not. In one large series, infection due to the four most common infecting organisms in neutropenic patients (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella species) occurred in 28% of 380 patients receiving some oral antibiotic regimen compared with 44% of 426 receiving no oral prophylaxis. Aminoglycosides alone or in combination with vancomycin or polymyxin and bacitracin and other agents have been utilized in gut decontaminating regimens. More recently, selective decontamination with a variety of oral agents including nalidixic acid, cotrimoxazole, colistin, etc. have been shown to be effective in some trials. Although cotrimoxazole initially was thought to be beneficial in reducing infection and bacteremia in neutropenic patients, the recently completed EORTC trial did not show a significant difference in incidence of infection or bacteremia in acute leukemia patients attendant upon the use of oral trimethoprim-sulfamethoxazole. There was a significant reduction in infections and bacteremia in patients with malignancies other than acute non-lymphocytic leukemia. Thus, there is a need for infection prevention in neutropenic patients but the optimal method for achieving this goal remains to be determined.

Topics: Administration, Oral; Agranulocytosis; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Humans; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

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

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

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

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Feces; Gentamicins; Humans; Neoplasms; Neutropenia; Pilot Projects; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Biological Products; Child; Child, Preschool; Colistin; Drug Combinations; Framycetin; Humans; Lactobacillus; Neoplasms; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico.. A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval.. 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352).. The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Topics: Adult; Cohort Studies; HIV; HIV Infections; Humans; Mexico; Neutropenia; Pneumonia, Pneumocystis; Prospective Studies; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agammaglobulinemia; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Churg-Strauss Syndrome; Delphi Technique; Duration of Therapy; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Influenza Vaccines; Influenza, Human; Maintenance Chemotherapy; Microscopic Polyangiitis; Neutropenia; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Recurrence; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

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

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

To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies.. We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case.. CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior β-lactam/β-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08).. CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE-active agents and improve outcomes in this vulnerable population.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; New York City; Prevalence; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

With the increasing use of carbapenems, carbapenem-resistant Gram-negative bacteria have become a major concern in health care-associated infections. The present study was performed to evaluate the clinical and microbiological features of breakthrough Gram-negative bacteremia (GNB) during carbapenem therapy and to assess risk factors for development of breakthrough GNB. A case-control study was performed at a tertiary hospital from 2005 to 2014. Case patients were defined as individuals whose blood cultures grew Gram-negative bacteria while the patients were receiving carbapenems for at least 48 h before breakthrough GNB. Age-, sex-, and date-matched controls were selected from patients who received carbapenem for at least 48 h and did not develop breakthrough GNB during carbapenem treatment. A total of 101 cases of breakthrough GNB were identified and compared to 100 controls. The causative microorganisms for breakthrough GNB were Stenotrophomonas maltophilia (n = 33), Acinetobacter baumannii (n = 32), Pseudomonas aeruginosa (n = 21), and others (n = 15). Approximately 90% of S. maltophilia isolates were susceptible to levofloxacin and trimethoprim-sulfamethoxazole. The most common infection types were primary bacteremia (38.6%) and respiratory infections (35.6%). More than half of the patients died within a week after bacteremia, and the 30-day mortality rate was 70.3%. In a multivariate analysis, a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization by causative microorganisms were significantly associated with breakthrough GNB. Our data suggest that S. maltophilia, A. baumannii, and P. aeruginosa are the major pathogens of breakthrough GNB during carbapenem therapy, in association with a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization.

Topics: Acinetobacter baumannii; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Cross Infection; Female; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Intensive Care Units; Length of Stay; Levofloxacin; Male; Middle Aged; Neutropenia; Pseudomonas aeruginosa; Respiratory Tract Infections; Risk Factors; Stenotrophomonas maltophilia; Survival Analysis; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

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

Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.. We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana.. A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93).. Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

Topics: Anemia; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Infant; Neutropenia; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Recipients of hematopoietic stem-cell transplantation (HSCT) are at high risk for infections caused by Stenotrophomonas maltophilia.. We conducted a retrospective analysis of all infections caused by S. maltophilia in HSCT recipients in a single center in Israel during a 4 year period.. Of 570 patients undergoing HSCT, 19 patients with an invasive S. maltophilia infection were identified. Sixteen had allogeneic HSCT and 3 had autologous HSCT. Seventeen patients (90%) had an indwelling central venous catheter (CVC) at the time of infection. S. maltophilia infections were detected in three clinical settings: as a complication of prolonged neutropenia (n = 9), as a CVC-related non-neutropenic infection occurring after CVC manipulation (n = 8) and as a respiratory tract infection (n = 2). Eleven patients (58%) had a polymicrobial infection. Ten patients (52.6%) received carbapenems during the previous month. The treatment for all patients included broad spectrum antibiotics, which were switched according to susceptibilities upon identification of the isolates. All isolates were susceptible in vitro to TMP-SMX. CVCs were removed in 12 patients (70%). Six patients, all after allogeneic HSCT, died. The CVC was removed in only two of the five patients with CVCs who died.. Stenotrophomonas maltophilia is an emerging nosocomial pathogen in HSCT recipients, both in the early neutropenic phase and in the non-neutropenic phase. It is commonly associated with the presence and manipulation of an indwelling CVC. Removal of the CVC in addition to appropriate antibiotic therapy (TMP-SMX) is crucial for infection control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Communicable Diseases, Emerging; Cross Infection; Female; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neutropenia; Retrospective Studies; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Haematological anomalies are frequent during HIV infection, and can be the fact of virus and or bone marrow toxicity of antiretroviral drugs. In order to analyze the evolution of the haematological parameters during HAART this work was carried out in the internal medicine department of the national teaching hospital Yalgado-Ouédraogo in Ouagadougou. So 107 patients receiving for the first time HAART and followed regularly were retained. The immunological efficacy at the end of the first six months was 60, 75% with an average gain of 119 CD4/mm3. The haematological changes at the end of these first six months showed: --an anaemia in 51.4% of the cases at month 6 versus 80.3% at baseline (p=0.0001). The average rate of haemoglobin was 11.8 versus 11.2 g/dl at baseline in the AZT containing HAART regimen (p=0.014) and 12.2 versus 10.7 g/dl at baseline in the group without AZT (p=0.00006). --a neutropenia in 35.5% of the cases at month 6 versus 31.7% at baseline (p=0.6). The average rate of neutrophil was 1908/mm3 versus 2267.1/mm3 at baseline in the AZT containing HAART regimen and 2150.7/mm3 versus 2001.9/mm3 at baseline in the group without AZT These results show that the therapeutic efficacy measured on the immunological answer is accompanied by a reduction of haematological anomalies. They also suggest the necessity to evaluate the cotrimoxazole impact before deciding the interruption of AZT.

Topics: Adolescent; Adult; Anemia; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Burkina Faso; Female; Follow-Up Studies; Hematologic Diseases; Hemoglobins; HIV Infections; Humans; Lymphopenia; Male; Middle Aged; Neutropenia; Retrospective Studies; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination chemotherapeutic agent, a commonly used antibiotic. Adverse drug reactions occur in 6-8% of patients. Although, the most common adverse reactions include mild gastrointestinal distress and cutaneous events, also a wide range of hematological abnormalities have been ascribed to TMP-SMX. We report a 40-year-old male patient who developed an early onset neutropenia, thrombocytopenia, generalised rash and oral candidiasis after 5 days long TMP-SMX therapy. Although generalised rash may seen more and improves with discontinuation of the therapy; severe neutropenia, thrombocytopenia and oral candidiasis are seen very rare and rarely leads to fatality as it was in our case. Despite thrombocyte transfusions, whole blood transfusions, red cell concentrates and filgrastim therapy we lost our patient. We want to underline that although the TMP-SMX combination is usually well tolerated it can also lead to fatal complications.

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Candidiasis, Oral; Cefepime; Cephalosporins; Chlorhexidine; Drug Eruptions; Escherichia coli; Escherichia coli Infections; Exanthema; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Male; Meropenem; Neutropenia; Nystatin; Platelet Transfusion; Prednisolone; Recombinant Proteins; Thienamycins; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

In a placebo-controlled trial of co-trimoxazole prophylaxis in Côte d'Ivoire, neutropenia was the most frequent short-term side effect. The long-term incidence of neutropenia in sub-Saharan African adults receiving co-trimoxazole has never been reported. We followed a prospective cohort of HIV-infected adults receiving co-trimoxazole (sulphamethoxazole 800 mg/trimethoprim 160 mg daily) in Abidjan. Grades of neutropenia were successively defined as at least one absolute neutrophil count (ANC) of: <1500/mm(3) (severity grade >/=1), <1000/mm(3) (grade >/=2), <750/mm(3) (grade >/=3) or <500/mm(3) (grade 4). In total, 533 adults were followed-up during 1450 person-years, with a total of 3154 ANCs. The probability of remaining free of neutropenia at 48 months was 0.29 (95% CI 0.23-0.34) for grade >/=1, 0.64 (95% CI 0.60-0.71) for grade >/=2, 0.82 (95% CI 0.77-0.86) for grade >/=3 and 0.96 (95% CI 0.93-0.99) for grade 4. The only factor significantly associated with a higher rate of all grades of neutropenia was a low baseline CD4 count. There was no association between any grade of neutropenia and the global risk of serious morbidity during the study period. In adults receiving co-trimoxazole in Abidjan, mild neutropenia is a common observation with no evidence of negative clinical consequences. The consequences of associating co-trimoxazole with other haematotoxic drugs should be carefully assessed.

Topics: Adult; Anti-Infective Agents; Cote d'Ivoire; Female; HIV Infections; Humans; Incidence; Male; Neutropenia; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Fever; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Middle Aged; Neutropenia; Paclitaxel; Pneumonia, Pneumocystis; Polyethylene Glycols; Prednisone; Recombinant Proteins; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia is an aerobic gram-negative bacillus that is a frequent coloniser of fluids used in the hospital setting. It causes infection in immunosuppressed hosts, especially those who are neutropaenic, on chemotherapy and broad spectrum antibiotics. Skin and soft tissue manifestations of Stenotrophomonas maltophilia infection are becoming an increasingly recognised entity; the clinical spectrum ranges from mucocutaneous, skin to soft tissue infections.. We present a case of an 8-year-old girl with acute myeloid leukaemia who developed metastatic skin lesions secondary to Stenotrophomonas maltophilia bacteraemia. The authors reviewed a total of 24 reported cases of mucocutaneous, skin and soft tissue infections by Stenotrophomonas maltophilia. The presentations include metastatic cellulitis, primary cellulitis and infected mucocutaneous ulcers.. This is the first locally reported case of metastatic nodular skin lesions caused by Stenotrophomonas maltophilia bacteraemia. This is also the first reported paediatric case of embolic skin lesions caused by Stenotrophomonas maltophilia. Of the 6 cases of Stenotrophomonas maltophilia bacteraemia seen in the paediatric oncology patients from year 2000 to 2004 at our hospital, only 1 case developed metastatic skin lesions.. Stenotrophomonas maltophilia skin infection should be included into the list of differential diagnoses for metastatic skin lesions in neutropaenic patients, especially with an underlying haematologic malignancy who has received recent chemotherapy and broad spectrum antibiotics. Haematologic malignancy, transplantation, neutropaenic, immunosuppressive therapy and a high severity of illness score were important prognostic factors.

Topics: Acute Disease; Anti-Infective Agents; Bacteremia; Cellulitis; Child; Comorbidity; Female; Gram-Negative Bacterial Infections; Humans; Leukemia, Myeloid; Neutropenia; Prognosis; Skin Diseases, Bacterial; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Chlamydia pneumoniae is known to cause acute respiratory tract infections in the non-immunocompromised population. So far, no data about the incidence of chlamydial infections in neutropenic patients are available. Macrolide antibiotics are not considered to be first-line treatment options in neutropenic patients. We report the case of a patient with Hodgkin's disease who developed C. pneumoniae pneumonia during mild neutropenia. C. pneumoniae should be considered as a causative agent of pneumonia in neutropenic patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Aza Compounds; Bleomycin; Chlamydophila Infections; Chlamydophila pneumoniae; Dacarbazine; Doxorubicin; Drug Therapy, Combination; Female; Fluoroquinolones; Hodgkin Disease; Humans; Imipenem; Immunocompromised Host; Moxifloxacin; Neutropenia; Pneumonia, Bacterial; Quinolines; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Vincristine

Most children with autoimmune neutropenia (AIN) have a benign clinical course because of the spontaneous resolution of neutropenia. The authors observed the clinical course of AIN in infancy accompanied by the prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX) during neutropenia.. Eight infants with AIN were followed by serial tests for antineutrophil antibodies and management of infectious complications.. The spontaneous disappearance of antineutrophil antibodies that preceded the normalization of the neutrophil count was found in all patients. Until the resolution of neutropenia, TMP-SMX was administered in five patients, resulting in a reduction in the incidence of infection with no adverse effects.. These observations demonstrate the possibility of the safety and usefulness of TMP-SMX treatment in patients with AIN.

Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Autoimmune Diseases; Communicable Disease Control; Female; Follow-Up Studies; Humans; Infant; Infections; Male; Neutropenia; Neutrophils; Trimethoprim, Sulfamethoxazole Drug Combination

To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration.. Prospective study.. 7 healthy euthyroid dogs.. Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed.. Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued.. Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.

Topics: Animals; Anti-Infective Agents; Dog Diseases; Dogs; Female; Kinetics; Male; Neutropenia; Prospective Studies; Thyroid Gland; Thyrotropin; Thyroxine; Trimethoprim, Sulfamethoxazole Drug Combination

Autoimmune neutropenia in infancy (AIN) is caused by granulocyte-specific autoantibodies. Clinical presentation and diagnosis have not been well studied, resulting in cumbersome diagnostic investigations and unnecessary treatment such as granulocyte colony-stimulating factor (G-CSF) therapy.. Clinical, laboratory and immunological data of 18 infants with AIN were evaluated. Granulocyte-specific autoantibodies were detected by the direct granulocyte immunofluorescence test (D-GIFT), indirect granulocyte immunofluorescence test (I-GIFT) and immunoblotting.. The average age of onset and resolution of neutropenia in AIN was 7.4 +/- 3.4 mo (mean +/- SD) and 20.4 +/- 4.9 mo, respectively. Sixteen of the 18 patients presented with mild infectious symptoms; the other 2 patients were detected by chance and presented with no infectious symptoms. D-GIFT was positive in all patients, and I-GIFT was positive in 17 of these 18 patients. Most patients showed preferential binding to neutrophils from NA(1 + 2-)-phenotyped donors by 1-GIFT and immunoblotting. An antibiotic (sulfamethoxazole-trimethoprim) was given to 15 patients for prophylaxis. G-CSF was given to only one infectious patient.. A combination of diagnostic tests for the detection of granulocyte-specific autoantibodies was useful in diagnosing AIN, thus avoiding unnecessary investigations. Continuous treatment with G-CSF was not necessary for prophylaxis, even if neutrophil counts were extremely low.

Topics: Anti-Infective Agents; Autoimmune Diseases; Drug Therapy, Combination; Female; Fluorescent Antibody Technique, Direct; Fluorescent Antibody Technique, Indirect; Granulocytes; Humans; Immunoblotting; Infant; Infant, Newborn; Male; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

The frequency of isolation of viridans streptococci from the blood of neutropenic patients with cancer has significantly increased over the course of the last 10-15 years. Risk factors in this patient population include severe neutropenia, oral mucositis, administration of high-dose cytosine arabinoside, and antimicrobial prophylaxis with either trimethoprim-sulfamethoxazole or a fluoroquinolone. In some patients with cancer and neutropenia who develop viridans streptococcal bacteremia, a toxic shock-like syndrome has been described; Streptococcus mitis has been the causative species in most cases. Because resistance of viridans streptococci to a variety of antimicrobial agents is increasingly recognized, penicillin susceptibility cannot be assumed, and empirical vancomycin therapy should be used to treat neutropenic patients with cancer who have shock or are developing acute respiratory distress syndrome. Given the seriousness of septicemia caused by viridans streptococci and the potential for selection of other resistant microorganisms, the routine practice of antimicrobial prophylaxis for neutropenic patients with cancer should be reconsidered.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Fluoroquinolones; Humans; Neutropenia; Risk Factors; Streptococcal Infections; Streptococcus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Bipolar Disorder; Chronic Disease; Clozapine; Drug Synergism; Female; Humans; Middle Aged; Neutropenia; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

The extent and duration of neutropenia and the characteristics of the underlying disease are determinant factors for the prognosis of febrile syndromes. Despite the fact that traditionally the peripheral blood stem cell transplantation (PBSCT) were considered to cause high risk neutropenia, in all probability the neutropenia observed in the PBSCT in some solid tumours could be considered moderate risk. Febrile episodes in patients with these characteristics were evaluated.. We prospectively analysed 132 autologus PBSCT in patients with breast cancer (1994-1999). Conditioning regime: STAMP V. Antibacterial prophylaxis: ofloxacin (400 mg/12 hrs PO). Classification of the febrile syndrome: bacteremia, microbiologically documented infection withut bacteremia, clinical infection and a fever of unknown origin.. 122 patients had a fever (92%), mean age: 45 years (range: 27-61). There were 32 (26%) bacteremias, 13 (11%) microbiologically documented infections without bacteremia and 54 (44%) clinical infections. The mean number of days with a neutrophil count of <1x109/1 was 14 (range: 11-20). In the 74 patients (61%) that had a granulocyte colony stimulating factor (G-CSF), the mean number of days to reach a 0,5x109/I neutrophil count (7,6) and the average number of days in hospital (26) were significantly less. There was a main infectious point in 80 patients (65%): the most frequent being oropharynx in 33 cases (46%) and digestive in 29 cases (41%). 48 gram negative (GN) 29 gram positive (GP) bacteria were isolated (71% of the GN's were resistant to ofloxacin). Between 1997-1999 the GN/GP ratio was 2,3. There were no deaths related to the infection.. Given the excellent evolution of our patients we can consider their neutropenia to be moderate or low risk, and they are a long way from the death rates caused by infections published by other types of hemopoietic transplants. The predominance of GN over the last few years and their limited sensitivity to quinolones means that their prophylactic use in these patients should be reconsidered.

Topics: Acyclovir; Adult; Anti-Infective Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bacteremia; Bacterial Infections; Breast Neoplasms; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Drug Resistance; Female; Fever; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Infection Control; Middle Aged; Neutropenia; Ofloxacin; Premedication; Prospective Studies; Transplantation Conditioning; Trimethoprim, Sulfamethoxazole Drug Combination

Purine analogs and alkylating agents are the most active drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). Although fludarabine is the most widely tested purine analog in CLL, myelosuppression has limited its use in combination chemotherapy regimens. Because pentostatin (Nipent; SuperGen, San Ramon, CA), a related purine analog with proven activity in CLL, has less myelosuppression, we postulated that it would prove advantageous and could be more readily combined with alkylating agents. We are conducting a phase I/II trial of combination chemotherapy with pentostatin and cyclophosphamide for previously treated patients with CLL. Patients need to have Rai high-risk disease or "active" intermediate-risk disease. The treatment regimen consists of a fixed dose of pentostatin (4 mg/m2) combined with an increasing dose of cyclophosphamide. We plan to treat cohorts of three patients each at cyclophosphamide dose levels of 600, 900, 1,200, 1,500, and 2,000 mg/m2. Cycles will be repeated every 21 days. If unacceptable toxicity is encountered at one dose level, then three additional patients (total of six patients) will be accrued to that dose level before further dose escalations will be permitted. A second instance of unacceptable toxicity will close that dose level and identify the preceding level as the phase II dose. Additional patients will be accrued to the phase II dose level to better assess response. Supportive measures include the use of granulocyte colony-stimulating factor (5 microg/kg/d) to limit neutropenia. Sulfamethoxazole/trimethoprim will be given as prophylaxis against Pneumocystis carinii pneumonia and acyclovir will be administered as prophylaxis for herpes zoster. Response will be assessed according to standard criteria, and flow cytometry and fluorescent in situ hybridization will be used to assess for minimal residual disease in patients with trisomy 12.

Topics: Acyclovir; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemoprevention; Chromosomes, Human, Pair 12; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Herpes Zoster; Humans; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Neutropenia; Patient Selection; Pentostatin; Pneumonia, Pneumocystis; Remission Induction; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Trisomy

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

Topics: Anti-Infective Agents; Female; Fever; Humans; Infant, Newborn; Leukocyte Count; Maternal-Fetal Exchange; Neutropenia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Trimethoprim, Sulfamethoxazole Drug Combination

All cases of HIV-associated gingival ulceration seen at a dedicated dental clinic in a 5-year period were reviewed and compared against other patients attending the clinic. 94 (7.1%) of 1308 patients had 146 episodes of gingival ulceration. 89 patients had 140 episodes similar to acute necrotising ulcerative gingivitis (ANUG) and responded well to conventional treatment for ANUG. The cases were compared with 269 controls in logistic regression. Gingival ulceration was associated with oral candidiasis, lower age and lack of AIDS diagnosis possibly due to a protective effect of co-trimoxazole medication. 5 patients with neutropenia had extensive ulceration without the microflora of ANUG. Histopathology, viral and bacterial culture revealed non-specific changes. The ulcers did not respond to the treatment regimen for ANUG but responded to treatment of their neutropenia. Gingival ulceration is not common in HIV infection. Most cases resemble severe ANUG. It is more frequent in younger people, those with oral candidiasis and without AIDS. Co-trimoxazole may be protective. A minority of cases with ulceration and associated neutropenia resembled the non-specific oral ulceration associated with HIV.

Topics: Adult; Analysis of Variance; Anti-Infective Agents; Candidiasis, Oral; Case-Control Studies; Chi-Square Distribution; Female; Gingivitis, Necrotizing Ulcerative; HIV Infections; Humans; Male; Neutropenia; Oral Ulcer; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

A patient presented with severe bactrim-induced neutropenia with a reversed CD4+/CD8+ lymphocyte ratio. R-metHUG-CSF at 300 micrograms daily produced a dramatic neutrophil response and the therapy was discontinued after 2 weeks.

Topics: Bone Marrow; CD4-CD8 Ratio; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Immunologic Factors; Male; Neutropenia; Recombinant Proteins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The objective of this study was to quantify the risk of serious blood and skin disorders associated with co-trimoxazole.. We conducted a population-based cohort study of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole at Group Health Cooperative and Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

To quantify the risk of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole.. We conducted a population-based cohort study at Group Health Cooperative of Puget Sound (GHC).. During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis.. We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.

Topics: Adult; Aged; Anti-Infective Agents; Child, Preschool; Cohort Studies; Erythema Multiforme; Female; Hematologic Diseases; Hospitalization; Humans; Leukopenia; Longitudinal Studies; Male; Middle Aged; Neutropenia; Pancytopenia; Product Surveillance, Postmarketing; Risk Assessment; Skin Diseases; Stevens-Johnson Syndrome; Thrombocytopenia; 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: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anti-Infective Agents; Antiviral Agents; Ceftazidime; Cephalosporins; Granulocyte Colony-Stimulating Factor; Humans; Male; Neutropenia; Pyrimethamine; Sulfadiazine; Trimethoprim, Sulfamethoxazole Drug Combination

A recent Spanish study has shown that Bactrim, a treatment for PCP pneumonia, can be taken three times a week instead of once daily. Using Bactrim, also known as Septra, in this manner produces fewer side effects while still remaining effective. The study confirms the results of several previous small studies done in the U.S.

Topics: Humans; Immunocompromised Host; Neutropenia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: Bacterial Infections; Humans; Neutropenia; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

At the age of four months, a boy with a normal history and family history, suddenly fell ill with a life-threatening pneumocystis carinii-pneumonia. Surprisingly, this opportunistic infection was not brought about by a T-cell deficiency. However, the patient's diagnosis turned out to be the rare "Hyper-IgM-syndrome", confirmed by: serum levels of IgM always at least normal whereas IgG, IgA and IgE were markedly decreased or absent; the development of neutropenia and occasional diarrhea. Generally, infections with pneumocystis carinii are rare in isolated deficiencies of immunoglobulines, but relatively frequent in primary "Hyper-IgM-syndrome" (approx. 12% of the cases described). The boy finally recovered after receiving Cotrimoxacol (20 mg/kg bw/d) in an intensive care unit. Now, at the age of nearly two his condition is almost good under regular substitution of IgG. Cotrimoxacol (4 mg/kg bw/d) is recommended to prevent further pneumocystis carinii infections and most of the pathogenes which frequently appear in neutropenias.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Male; Neutropenia; 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

The results of therapy of febrile episodes during the pregraft phase in bone marrow transplant was retrospectively evaluated in 84 granulocytopenic patients. Most patients received co-trimoxazole and i.v. ticarcillin as antibacterial prophylaxis. 47 episodes were treated with a third generation cephalosporin plus an aminoglycoside, with a 55% favorable response rate. 37 episodes were treated with a wide spectrum penicillin plus an aminoglycoside, with a 41% response rate (p greater than 0.05). Among the 23 infections caused by gram-negative bacilli the response rate was 89% (8 of 9) with the first regimen, and 21% (3 of 14) with the second one (p = 0.003). The investigation of in vitro sensitivity suggested that prophylactic ticarcillin favors the infections due to bacilli with cross-resistance to wide spectrum penicillins. The antibiotic regimen did not influence the final resolution or the mortality rate of the febrile episode.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Bone Marrow Transplantation; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacteria; Humans; Male; Neutropenia; Premedication; Retrospective Studies; Sepsis; Ticarcillin; 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

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

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

The correlation of fecal gram-negative bacilli (GNB), neutropenia, and bacteremia was studied in 45 bone marrow transplant recipients. Weekly stool cultures were prospectively monitored for GNB resistant to routine prophylactic and empiric antimicrobial agents. Seven cases of GNB bacteremia occurred in 45 patients described as follows. Twenty-three patients had no fecal or blood GNB. Fifteen patients had fecal GNB and no blood GNB; three of these latter patients had less than or equal to 50/mm3 circulating white blood cells (WBC) at the time of isolation of fecal GNB but two of the three were concurrently receiving appropriate empiric antibiotics. Two patients had blood GNB but no fecal GNB: one patient had a trimethoprim/sulfamethoxazole (TMP-SMZ)-sensitive isolate that would not be detectable in the feces by our methodology and one patient had feces analyzed only after the bacteremic event. Five patients had fecal GNB and blood GNB: one of these patients did not have a fecal sample analyzed prior to bacteremia but the remaining four patients had the same species/antibiogram of GNB isolated from the feces two to three days prior to the detection of bacteremia. Thus, the fecal GNB could have been used to predict the antibiogram of the subsequent blood GNB. In addition, all four of these latter bacteremic patients had less than or equal to 50/mm3 circulating WBC at the time of documented fecal GNB. Thus, bone marrow transplant recipients with fecal GNB coupled with severe neutropenia (less than or equal to 50/mm3 circulating WBC) were more likely to develop bacteremia (P less than 0.02) than were those with fecal GNB and greater than 50/mm3 circulating WBC.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Bone Marrow Transplantation; Child; Drug Combinations; Drug Resistance, Microbial; Feces; Gram-Negative Bacteria; Humans; Immune Tolerance; Neutropenia; Prospective Studies; Sepsis; Sulfamethoxazole; Ticarcillin; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000.

Topics: Acute Disease; Adult; Agranulocytosis; Amodiaquine; Drug Combinations; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Malaria; Male; Middle Aged; Neutropenia; Proguanil; Retrospective Studies; Sulfaguanidine; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Chlorides; Drug Combinations; Drug Therapy, Combination; Female; Glycogen Storage Disease Type I; Hematopoiesis; Humans; Ketoconazole; Leukocyte Count; Lithium; Lithium Chloride; Neutropenia; Skin Diseases, Infectious; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Agranulocytosis; Anti-Infective Agents, Urinary; Drug Combinations; Female; Humans; Neutropenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The in vitro activity of coumermycin, fusidic acid, cotrimoxazole, and vancomycin was determined by broth microdilution assay against 33 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates from the Detroit Receiving Hospital, Detroit, Mich. Coumermycin was the most active drug tested, while fusidic acid, vancomycin, and cotrimoxazole also had good activity. The four antimicrobials were tested in vivo against 7 strains of MRSA employing the mouse protection model. Again, coumermycin was the most active, followed by vancomycin, cotrimoxazole, and fusidic acid. Coumermycin was very active, while vancomycin and fusidic acid were inactive in neutropenic mice infected with an MRSA strain. Coumermycin retained activity when given 18 h before an MRSA infection, while vancomycin activity was lost. Coumermycin was active in a local thigh infection while vancomycin was inactive. The results indicate that coumermycin is potent against MRSA with activity equal or superior to comparable agents in various experimental mouse infections.

Topics: Aminocoumarins; Animals; Anti-Bacterial Agents; Coumarins; Drug Combinations; Female; Fusidic Acid; Methicillin; Mice; Microbial Sensitivity Tests; Neutropenia; Penicillin Resistance; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Agranulocytosis; Drug Combinations; Drug Resistance, Microbial; Humans; Neutropenia; Risk; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Antimicrobial sensitivities, especially trimethoprim-sulfamethoxazole, were studied in all clinical isolates of Escherichia coli in an intensive care unit for over 18 months. Twenty-four per cent of strains were resistant to trimethoprim-sulfamethoxazole. Combined resistance to ampicillin +/- chloramphenicol (+/- tetracycline) and streptomycin (+/- kanamycin) with resistance to trimethoprim-sulfamethoxazole was demonstrated. These data confirm the previously reported increasing trimethoprim-sulfamethoxazole resistance which is probably plasmid-mediated and specify the resistances associated with trimethoprim-sulfamethoxazole resistance. These findings suggest that widespread prophylaxis in granulocytopenic patients with lower urinary tract infection by the trimethoprim-sulfamethoxazole association should be re-examined.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Combinations; Drug Resistance, Microbial; Escherichia coli; Humans; Neutropenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adult; Anemia, Aplastic; Anti-Bacterial Agents; Antifungal Agents; Antilymphocyte Serum; Bone Marrow; Bone Marrow Transplantation; Child; Child, Preschool; Drug Combinations; Fanconi Syndrome; Humans; Immunosuppression Therapy; Middle Aged; Neutropenia; Pancytopenia; Plateletpheresis; Prognosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of hematologic abnormalities was evaluated in 120 children with otitis media treated respectively with cotrimoxazole (trimethoprim-sulfamethoxazole) (group 1), cotrimoxazole plus folinic acid (group 2) and amoxicillin (group 3) in therapeutic doses for ten days. Only eosinophilia (an absolute count greater than or equal to 0.5 X 10(9)/l) (group 1 = 10%, 2 = 5%, 3 = 7.5%) and neutropenia (polymorphonuclear neutrophilic leucocyte count less than or equal to 1.5 X 10(9)/l) (group 1 = 35%, 2 = 17.5%, 3 = 13.3%) were noted. Early neutropenia (evident on the 5th day of therapy) occurred in all the treatment groups, thus it is not related to cotrimoxazole administration and in most cases neutrophil count reversed to normal in few days without drug discontinuation. Late neutropenia (evident after 10 days of treatment) appeared only in cotrimoxazole treated children (p less than 0.05). No superimposed bacterial infection was demonstrated in any case. Late neutropenia seems to be strictly related to the sequential blockage of folinic acid metabolism and can be prevented by the concomitant administration of folinic acid.

Topics: Agranulocytosis; Amoxicillin; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Eosinophilia; Female; Folic Acid; Humans; Infant; Male; Neutropenia; Otitis Media; Risk; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Over a five-day period, three neutropenic patients developed bacteremia with an identical strain of Klebsiella aerogenes (serotype K16) resistant to co-trimoxazole and gentamicin. All three patients had received prophylaxis with oral co-trimoxazole before the onset of bacteremia. This report outlines some of the problems associated with co-trimoxazole prophylaxis.

Topics: Aged; Drug Combinations; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Neutropenia; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Child; Drug Combinations; Humans; Leukemia, Lymphoid; Neutropenia; Pulmonary Fibrosis; Sulfamethoxazole; Thrombocytopenia; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; Adult; Bacteria; Child; Drug Combinations; Drug Interactions; Drug Resistance, Microbial; Dysentery, Bacillary; Humans; Infusions, Parenteral; Neutropenia; Nocardia Infections; Otitis Media; Pneumonia, Pneumocystis; Salmonella Infections; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections