trimethoprim--sulfamethoxazole-drug-combination and Graft-vs-Host-Disease

Nocardiosis occurs in up to 1.7% of hematopoietic stem cell transplantation (HSCT) recipients. Risk factors for its development and subsequent outcomes have been incompletely studied. The present study evaluated risk factors for nocardiosis in HSCT recipients and an association with 12-month mortality following Nocardia infection. We performed a nested case-control study of HSCT recipients at 3 transplantation centers between 2011 and 2021. Allogeneic HSCT recipients were matched 1:4 to controls based on age, sex, date of transplantation, and transplantation site. Because of theorized differences in the risk for nocardiosis between allogeneic HSCT recipients and autologous HSCT recipients and a low number of infected autologous HSCT recipients, only allogeneic HSCT recipients were matched to controls. Associations with nocardiosis in the allogeneic group were assessed by multivariable conditional logistic regression. Outcomes of all HSCT recipients with nocardiosis included 12-month mortality and post-treatment recurrence. Twenty-seven HSCT recipients were diagnosed with nocardiosis, including 20 allogeneic HSCT recipients and 7 autologous HSCT recipients. Twenty (74.1%) had localized pulmonary infection, 4 (14.8%) had disseminated infection, and 3 (11.1%) had localized skin infection. The allogeneic recipients were diagnosed at a median of 12.2 months after transplantation, compared with 41 months for the autologous recipients. All autologous HSCT recipients had alternative reasons for ongoing immunosuppression at diagnosis, most frequently therapy for relapsed hematologic disease. No infected patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In multivariable analysis of 20 allogeneic patients and 80 matched controls, graft-versus-host disease (GVHD) requiring current immunosuppression and lack of prophylaxis were associated with nocardiosis. Nocardiosis was significantly associated with subsequent mortality, with a 12-month mortality rate of 29.6%; however, no patients who completed treatment experienced Nocardia recurrence. OUR DATA INDICATE THAT: intensified immunosuppression following allogeneic HSCT, such as treatment for GVHD, is associated with the development of nocardiosis. Nocardiosis occurs more distantly from transplantation in autologous recipients, possibly driven by therapy for relapsed hematologic disease. No patients receiving TMP-SMX prophylaxis developed nocardiosis. Nocardia infection is associated with high

Topics: Case-Control Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Nocardia Infections; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis.. We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis.. The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine.. In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antilymphocyte Serum; Atovaquone; CD4 Lymphocyte Count; Dapsone; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppression Therapy; Incidence; Lymphopenia; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cerebral toxoplasmosis is a rare, potentially fatal, complication of hematopoietic cell transplantation. Early definitive diagnosis is very difficult and it may be associated with a poor prognosis. Herein, we describe a 60-year-old woman who developed cerebral toxoplasmosis after cord blood transplantation for myelodysplastic syndrome. During treatment with tacrolimus and methylprednisolone for relapsed grade 2 acute gut GVHD, fever and disturbance of consciousness occurred on day 210. Brain MRI showed multiple ring-enhancing nodular lesions in the thalamus, basal ganglia, brainstem, and subcortical white matter. Cerebrospinal fluid (CSF) assessment revealed elevations of both anti-to-xoplasma IgM and IgG, which were also elevated in serum, but no evidence of other infections or malignancies. Notably, the IgM level was higher in the CSF than in serum. Thus, cerebral toxoplasmosis was diagnosed. Soon after administration of oral sulfamethoxazole/trimethoprim and intravenous clindamycin in combination with short-term dexamethasone for the cerebral edema, her symptoms and signs began to improve. On day 229, both IgM and IgG titers in CSF had clearly decreased but remained essentially constant in serum. She was discharged without clinically significant neurological disorders. This case suggests that CSF specific anti-toxoplasma IgM titers might be useful for early diagnosis of cerebral toxoplasmosis after transplantation.

Topics: Antibodies, Protozoan; Biomarkers; Clindamycin; Cord Blood Stem Cell Transplantation; Early Diagnosis; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Immunoglobulin M; Methylprednisolone; Middle Aged; Myelodysplastic Syndromes; Tacrolimus; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome; 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 epididymo-orchitis and central nervous system nocardiosis in a 22-year-old man with T-cell acute lymphoblastic leukemia; he was an allogeneic marrow recipient with acute and chronic graft-versus-host disease.. He had microscopic hematuria and cytomegalovirus antigenemia. He deteriorated subsequently while on cyclosporine and steroids, requiring hospital admission owing to fever and swelling of the left testis and generalized tonic-clonic convulsions.. Brain magnetic resonance imaging showed abnormal signal area in right parietal and left parieto-occipital lobes. The lesions had mass effect, edema, and ring enhancement. Findings were indicative of a brain abscess. A testicular biopsy from the lower pole of the left testis was done. A white-to-yellowish discharge was seen and subsequently, Nocardia grew in culture.. Trimethoprim-sulfamethoxazole was prescribed, and significant improvement was seen after 2 weeks. The patient was discharged. He was subsequently referred after 3 weeks due to graft-versus-host disease and died of pancytopenia.

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

Topics: Anti-Infective Agents; Drug Design; Graft vs Host Disease; Hematopoietic Stem Cells; Humans; Organ Transplantation; Pneumonia, Pneumocystis; Stem Cell Transplantation; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of pulmonary nocardiosis in a female patient with graft-versus-host disease (GVHD) underwent therapy with imatinib mesylate for a relapse of chronic myeloid leukemia (CML) after allogeneic bone marrow transplantation (BMT). The patient developed chronic GVHD 8 months after the use of imatinib and was on corticosteroid therapy. Three months after the development of chronic GVHD, she acquired pulmonary nocardiosis and a computed tomography (CT) scan of the chest showed multiple nodular lesions with cavitations over both lungs. She was successfully treated with single-agent trimethoprim-sulfamethoxazole (TMP/SMX) and the infection did not recur. Our case indicated that pulmonary nocardiosis could occur in patients with GVHD undergoing imatinib and corticosteroid therapy and might be treated by single-agent TMP/SMX.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Benzamides; Bone Marrow Transplantation; Bronchiolitis Obliterans; Female; Graft vs Host Disease; Humans; Imatinib Mesylate; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung; Nocardia asteroides; Nocardia Infections; Piperazines; Pneumonia, Bacterial; Pyrimidines; Tomography, X-Ray Computed; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: 2-Aminopurine; Alemtuzumab; Antibiotic Prophylaxis; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antigens, CD; Antigens, Neoplasm; Antineoplastic Agents; Bone Marrow Transplantation; CD52 Antigen; Clinical Trials as Topic; Cytomegalovirus Infections; Disease Susceptibility; Famciclovir; Ganciclovir; Glycoproteins; Graft vs Host Disease; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Incidence; Infections; Lymphoproliferative Disorders; Opportunistic Infections; Pneumonia, Pneumocystis; Rituximab; Transplantation Conditioning; Trimethoprim, Sulfamethoxazole Drug Combination; Viremia; Virus Activation

We describe a case of disseminated nocardiosis in a 53-year-old male allogeneic marrow recipient with chronic GVHD, 15 years post BMT. Six months prior to admission he was treated for recurrent chronic GVHD with corticosteroids with a good response. He deteriorated subsequently while still on steroids requiring admission for fever, anorexia, weight loss, productive cough and progressive dyspnoea. On admission he had multiple nodular lesions on chest roentgenogram and subsequently grew Nocardia farcinica in blood culture. N. farcinica is rare post BMT, has a high mortality, is resistant to various antibiotics and needs prolonged antimicrobial therapy. We report the successful management of our patient with single agent trimethoprim-sulphamethoxazole.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Bone Marrow Transplantation; Chronic Disease; Graft vs Host Disease; Humans; Male; Middle Aged; Nocardia; Nocardia Infections; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) is routinely given after allogeneic blood or marrow transplantation. We evaluated the effectiveness of dapsone prophylaxis (50 mg orally twice daily, 3 times per week) compared with twice-weekly trimethoprim-sulfamethoxazole (TMP-SMZ) in preventing PCP after allogeneic blood or marrow transplantation. Patients included all (n=646) who received allogeneic blood or marrow transplants between 1 September 1993 and 31 December 1996 who survived at least 100 days after transplantation. A cohort of 111 dapsone recipients was compared with the remaining 535 who received TMP-SMZ. Ten patients developed PCP; 8 were taking dapsone. PCP incidence in the TMP-SMZ cohort was 0.37% versus 7.2% for dapsone. The relative risk for PCP associated with dapsone use was 18.8 (P<.001) and was not accounted for by age, clinical extensive chronic graft-versus-host disease, donor source, or malignant relapse. Dapsone prophylaxis at this dosage is associated with significantly higher rates of PCP than is TMP-SMZ after allogeneic marrow transplantation. We advise caution in prescribing alternatives to TMP-SMZ prophylaxis in this setting.

Topics: Adult; Anti-Infective Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Cohort Studies; Dapsone; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Protozoan; Autopsy; Bone Marrow Transplantation; Child; Child, Preschool; Female; Graft vs Host Disease; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination