trimethoprim--sulfamethoxazole-drug-combination and Transfusion-Reaction

AIDS is a disorder that the pediatrician must consider when evaluating children with a variety of clinical conditions, including overwhelming infection with a number of parasites. This article discusses these opportunistic parasitic infections, focusing on their link with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Child; Child, Preschool; Cryptosporidiosis; Drug Combinations; Female; gamma-Globulins; Homosexuality; Humans; Infant; Male; Parasitic Diseases; Pentamidine; Pneumonia, Pneumocystis; Sulfamethoxazole; Transfusion Reaction; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Zoonoses

In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted.. TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness.. If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented.. Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.

Topics: Age Factors; Anemia; Anthelmintics; Biomarkers; Blood Transfusion; Child; Child Mortality; Child, Preschool; Clinical Protocols; Dietary Supplements; Drug Administration Schedule; Health Status; Hemoglobins; Hospital Mortality; Humans; Infant; Infant Mortality; Malawi; Nutritional Status; Patient Admission; Recurrence; Research Design; Risk Factors; Severity of Illness Index; Time Factors; Transfusion Reaction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Uganda; Vitamins

Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes.. A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine. She was found to be anemic, thrombocytopenic, and in acute renal failure. On admission, the direct antiglobulin test was positive for complement (C3) only. After careful review of her medication list, the possibility of DIIHA was raised. She had started taking trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jiroveci pneumonia prophylaxis 24 days prior on a weekend dose schedule. Serologic tests on peripheral blood samples were performed using standard methods. Drug studies were performed at an immunohematology reference laboratory.. The patient's serum showed hemolysis of donor red blood cells in the presence of TMP-SMX and also TMP-SMX-induced platelet antibodies. The patient was treated with transfusions, hemodialysis, and immunosuppressive agents. Her clinical condition improved and she was discharged after 8 days in stable condition.. This case describes the first reported concurrent DIIHA and DIIT due to TMP-SMX-induced antibodies in an HSCT patient. DIIHA and DIIT can present a diagnostic challenge in the setting of intermittent medication dosing.

Topics: Anemia, Hemolytic; Blood Transfusion; Female; Humans; Immunosuppressive Agents; Middle Aged; Renal Dialysis; Thrombocytopenia; Transfusion Reaction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced immune thrombocytopenia (DITP) is a rare clinical disorder characterized by accelerated platelet (PLT) clearance in the presence of drug-dependent antibodies. Distinguishing DITP from other immune-mediated disorders such as posttransfusion purpura (PTP) and autoimmune thrombocytopenia can represent a clinical challenge.. A 68-year-old male with no prior transfusion history presented to the emergency department (ED) with dyspnea, epistaxis, and severe thrombocytopenia (<10 × 10(9)/L) 12 days after discharge from a hospital admission for a coronary artery bypass graft. Evaluation of the degree of thrombocytopenia and the temporal association between the peri- and postoperative receipt of multiple transfusions and the acute decrease in PLT count indicated PTP as a possible cause of the severe thrombocytopenia. Treatment with 1 g/kg intravenous immunoglobulin (IVIG) was initiated and followed by a rapid 48-hour increase in the PLT count. PLT antibodies lacking serologic specificity were subsequently identified in a sample collected upon presentation. Two weeks later he again presented to the ED with epistaxis and severe thrombocytopenia (<10 × 10(9)/L). Clinical history now revealed that the patient had been treated with trimethoprim-sulfamethoxazole by his primary care physician after his first hospitalization for a "cellulitic-appearing" leg and again before his final presentation for surgical site erythema and edema. IVIG was administered again with a rapid return of PLT count to baseline. Sulfamethoxazole-dependent PLT antibodies were subsequently identified in the original patient sample.. This case report documents a case of IVIG-responsive DITP initially misdiagnosed as PTP, highlighting the clinical overlap of these immunologic-mediated phenomena.

Topics: Aged; Humans; Male; Platelet Transfusion; Purpura, Thrombocytopenic; Sulfamethoxazole; Thrombocytopenia; Transfusion Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: Acquired Immunodeficiency Syndrome; Adult; Biopsy; Bronchoscopy; Diagnosis, Differential; HIV Antibodies; Humans; Lung; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Transfusion Reaction; Trimethoprim, Sulfamethoxazole Drug Combination

Therapy of opportunistic infection in patients with the acquired immunodeficiency syndrome is frustrating, and there is no convincing evidence that aggressive treatment and/or prophylaxis other than for Pneumocystis infection can significantly prolong life. While much clinical effort is expended on treating sequential life-threatening infections, the overall course is usually progressively downhill. Thus, any real impact on the disease should be aimed at the causative viral agent, because it is destruction of a critical component of the immune system that predisposes to opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Adult; Candidiasis; Cryptococcosis; Drug Combinations; Humans; Intestinal Diseases, Parasitic; Male; Mycobacterium Infections; Mycoses; Pneumonia, Pneumocystis; Sulfamethoxazole; Toxoplasmosis; Transfusion Reaction; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases