trimethoprim--sulfamethoxazole-drug-combination and Multiple-Myeloma

BACKGROUND Central nervous system infection by the Nocardia species is associated with high morbidity and mortality. Its occurrence in patients with multiple myeloma is rare and acquisition of the infection in such patients was associated with the use of novel therapeutic agents (eg, bortezomib and lenalidomide) or bone marrow transplantation. Here, we report the first case of Nocardia brain abscesses in a patient with multiple myeloma, without the above risk factors. CASE REPORT A 44-year-old woman with IgG-kappa type multiple myeloma presented with generalized tonic-clonic seizures. Magnetic resonance imaging of the brain revealed 3 space-occupying lesions in left frontal, left parietal, and right parietal regions. Craniotomy and enucleation of the left frontal lesion revealed an abscess. The culture result was Nocardia farcinica. The patient was treated with meropenem, amikacin, and trimethoprim-sulfamethoxazole for 6 weeks, followed by trimethoprim-sulfamethoxazole for 12 months, with good outcome. CONCLUSIONS Cerebral nocardiosis is a rare entity and its occurrence in our case may hint toward myeloma-associated humoral immune dysfunction as a pathogenesis and the importance of humoral immunity in the defense against this infection. However, chemotherapy-induced cell-mediated dysfunction cannot be ruled out as a risk factor for the infection. Despite its rarity, this case aims to raise awareness of the condition and reiterate the importance of considering the rare but life-threatening conditions in the differential diagnosis of brain lesions, especially when there is a misdiagnosis of the radiological findings, as occurred in this and previous cases; this avoids delays in appropriate surgical and medical treatment, which can affect outcomes.

Topics: Adult; Amikacin; Antineoplastic Agents; Bortezomib; Brain Abscess; Female; Humans; Immunoglobulin G; Lenalidomide; Meropenem; Multiple Myeloma; Nocardia; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Combinations; Humans; Hypoglycemia; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly streptococcal and staphylococcal infections. This study evaluated the impact of prophylactic antibiotics on the incidence of serious bacterial infections (SBIs) during the first 2 months of treatment in patients with newly diagnosed MM. Patients with MM receiving initial chemotherapy were randomized on a 1:1:1 basis to daily ciprofloxacin (C; 500 mg twice daily), trimethoprim-sulfamethoxazole (T; DS twice daily) or observation (O) and evaluated for SBI (Eastern Cooperative Oncology Group ≥grade 3) for the first 2 months of treatment. From July 1998 to January 2008, 212 MM patients were randomized to C (n=69), T (n=76) or O (n=67). The incidence of SBI was comparable among groups: C=12.5%, T=6.8% and O=15.9%; P=0.218. Further, any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, P=0.954). We demonstrate that prophylactic antibiotics did not decrease the incidence of SBI (≥grade 3) within the first 2 months of treatment. We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacteria; Bacterial Infections; Ciprofloxacin; Female; Humans; Incidence; Male; Middle Aged; Multiple Myeloma; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX).. Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy.. Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients.. Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.

Topics: Aged; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Female; Humans; Incidence; Male; Middle Aged; Multiple Myeloma; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The treatment landscape for multiple myeloma (MM) has progressed significantly, and over the past decade, bortezomib-based induction therapy has been a standard of care. However, the practice of antibacterial prophylaxis during induction therapy has been diverse. The aim of our study is to evaluate the proportion of patients with febrile episodes and bacteremia among patients with MM, during the first 12 weeks of bortezomib-based induction therapy, without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), in a region with high fluoroquinolone resistance rate. Of note, these patients have direct access to health care facilities and timely supportive care.. We evaluated newly diagnosed MM patients from 2014 to 2018 receiving bortezomib-based induction therapy for the proportion of patients who had febrile episodes and bacteremia in the first 12 weeks of bortezomib-based induction therapy. We also evaluated if there were factors associated with increased febrile episodes including age, absolute neutrophil count, creatinine clearance, M-band level at diagnosis, nadir platelet count, International Staging System, and Revised International Staging System.. Of the 108 evaluable patients, there were a total of 25 (23.1%) patients who had febrile episodes, and 1 (0.9%) patient who had bacteremia during the first 12 weeks of bortezomib-based induction therapy. All patients recovered well. No deaths were seen. Febrile episodes were associated with lower absolute neutrophil count (P = .036), renal impairment (P = .013), and ISS stage (P = .026).. The proportion of patients with significant bacterial infection during the first 12 weeks of bortezomib-based induction therapy without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), is low in a population with adequate access to health care facilities and timely supportive care.

Topics: Aged; Bacterial Infections; Bortezomib; Female; Fluoroquinolones; Humans; Induction Chemotherapy; Male; Middle Aged; Multiple Myeloma; Retrospective Studies; Singapore; Trimethoprim, Sulfamethoxazole Drug Combination

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Topics: Acute Kidney Injury; Aged, 80 and over; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Critical Care; Drug Interactions; Fatal Outcome; Female; Humans; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

We report a case of intractable hyperkalaemia in an elderly patient with myeloma, who received conventional dose of trimethoprim-sulfamethoxazole and hyperkalaemia resolved following therapy with fludrocortisone. We recommend monitoring of serum potassium in high-risk patients receiving conventional doses of trimethoprim-sulfamethoxazole for 5 or more days.

Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Fludrocortisone; Humans; Hyperkalemia; Male; Multiple Myeloma; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

To characterize clinical, diagnostic and course features of pneumonia caused by Pneumocystis carinii (PC) in hematologic inpatients.. 27 patients with blood diseases were studied. 22 of them had acute respiratory insufficiency and 5 had unclear lung affection. The data from bronchoalveolar lavage (BAL), lung biopsy, serum tests for IgG, IgM anti-PC-antibodies were used for diagnosis of PC-pneumonia.. PC-pneumonia was diagnosed in 8 of 27 patients. Clinical manifestations characteristic for PC-pneumonia were not found. In 5 patients the diagnosis was made on the evidence provided by BAL. Lymphocyte count in BAL was elevated to 27.7 +/- 8.7%. Open biopsy of the lung and transbronchial biopsy diagnosed PC-pneumonia in 2 and 1 patients, respectively. Previous BAL examinations failed to detect PC-pneumonia in 2 of them. In all the patients PC-pneumonia was associated with another infection (bacterial, cytomegaloviral). Histologically, the picture of the disease was determined by the severity of the lung affection or its complications. 5 of 8 patients failed treatment with trimethoprim-sulphamethoxazole and died. Marked respiratory insufficiency was registered at PC-pneumonia diagnosis in all the lethal cases.. Clinical and x-ray pictures of PC-pneumonia in hemoblastosis patients are not specific. All such patients with symptoms of lung infection resistant to antibacterial and antifungal therapy should be examined for PC-pneumonia.

Topics: Acute Disease; Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Refractory, with Excess of Blasts; Anti-Infective Agents; Biopsy; Bronchoalveolar Lavage Fluid; Female; Hematologic Diseases; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lung; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Radiography, Thoracic; Respiratory Insufficiency; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia complicated the course of two patients with multiple myeloma. The diagnosis was established in both cases by bronchoalveolar lavage, which demonstrated the typical pneumocysts. Clinical and roentgenographic improvement in both patients was observed following a course of trimethoprim-sulfamethoxazole. One patient had lymphocyte subsets performed with a CD4/CD8 ratio of 0.8; both patients were HIV antibody-negative by ELISA. Both patients tolerated prophylactic TMP-SMX given concurrently with the subsequent chemotherapy for myeloma. We suggest that the immune defect seen in multiple myeloma may have placed these patients at risk for opportunistic infections such as P carinii pneumonia; however, as opposed to patients with AIDS, our patients tolerated therapy with TMP-SMZ quite well.

Topics: Bronchoalveolar Lavage Fluid; Humans; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination