trimethoprim--sulfamethoxazole-drug-combination and Connective-Tissue-Diseases

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; beta-Glucans; Connective Tissue Diseases; Drug Therapy, Combination; Early Diagnosis; HIV Seronegativity; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Postoperative Complications; Prognosis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Although drug-induced Sweet syndrome is rare, granulocyte colony-stimulating factor, all-trans-retinoic acid, and miscellaneous drugs have been implicated in causing this disorder in adults. In pediatric patients, granulocyte colony-stimulating factor, all-trans-retinoic acid, trimethoprim-sulfamethoxazole, and azathioprine have been implicated as potential causes of drug-induced Sweet syndrome. To date, six cases, including the patient reported here, have been reported in children.

Topics: Adult; Azathioprine; Child; Connective Tissue Diseases; Erythema; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infections; Sweet Syndrome; Tretinoin; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug Therapy, Combination; Humans; Molecular Diagnostic Techniques; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.

Topics: Adrenal Cortex Hormones; Azathioprine; Behcet Syndrome; Chlorambucil; Connective Tissue Diseases; Cyclophosphamide; Cyclosporins; Drug Combinations; Granuloma; Granulomatosis with Polyangiitis; Hemorrhage; Humans; Lung Diseases; Lymphomatoid Granulomatosis; Respiratory Tract Infections; Sulfamethoxazole; Syndrome; Takayasu Arteritis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

The efficacy and adverse effects of prophylactic administration of Sulfamethoxazole-Trimethoprim (ST) for Pneumocystis carinii Pneumonia (PCP) were assessed in patients with connective tissue diseases (CTD). Eighty-four patients who were receiving more than 40 mg/day of prednisolone were entried in the present study. Patients with at least one of the two PCP risk factors (interstitial pulmonary fibrosis and lymphopenia), were administered either one (11 patients) or two (26 patients) ST tablets/day. The remaining 47 patients who did not receive ST served as the controls. Although PCP was detected in 4.3% of the patients in the no-ST group, none of the patients who received ST developed PCP. Five of these 26 patients who received two tablets of ST/day, experienced adverse reactions. However, no adverse reactions were detected in the patients who received one tablet of ST/day (p < 0.05). Abnormal laboratory data were obtained for 10 (38.5%) of the patients who received two tablets of ST/day and for 4 (36.4%) of the 11 patients who received one tablet of ST/day. The results of the present study suggest that the prophylactic administration of one tablets of ST in patients with CTD that have at least one of the two PCP risk factors is effective in preventing PCP.

Topics: Adult; Anti-Infective Agents; Connective Tissue Diseases; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18 years who were treated with a prolonged course (≥ 4 weeks) of glucocorticoids (≥ 20 mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4 weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

Topics: Atovaquone; Connective Tissue Diseases; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate short-term prognosis and prognostic factors for connective tissue disease-associated pneumocystis pneumonia (CTD-PCP) using the Japanese nationwide diagnosis procedure combination (DPC) inpatient database.. The present retrospective cohort study from April 2014 to March 2016 included data of patients with CTD-PCP extracted from the DPC database using the 10. In 15 901 766 cases registered from 1329 hospitals, 333 of 67 890 patients who were admitted with PCP were diagnosed with CTD-PCP and included in the study. The median age was 71.0 years, and 214 (64.3%), 80 (24.0%), and 29 (8.7%) patients received sulfamethoxazole/trimethoprim (ST) monotherapy and pentamidine-containing and atovaquone-containing therapy, respectively. There were 114 (34.2%) in-hospital deaths, and the 30-day and 60-day in-hospital survival rates after PCP treatment initiation were 66.0% and 53.7%, respectively. Older age (HR 1.06, 95% CI 1.03 to 1.08) and concomitant interstitial lung disease (ILD) (HR 1.65, 95% CI 1.12 to 2.42) were poor prognostic factors. Patients who completed PCP treatment with ST monotherapy had a significantly higher survival rate than those treated with those not treated with ST monotherapy (p=0.015; log-rank test). Pentamidine versus atovaquone as second-line therapy was significantly higher with atovaquone (p=0.012; log-rank test).. Older age and concomitant ILD were poor prognostic factors for CTD-PCP. ST was a reasonable first-line therapy in patients with CTD-PCP, and patients with inadequate response to ST treated with atovaquone tended to have a better prognosis than those treated with pentamidine.

Topics: Aged; Connective Tissue Diseases; Humans; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX), a prophylactic agent against pneumocystis pneumonia (PCP), can cause adverse drug reactions (ADRs), particularly in patients with systemic lupus erythematosus (SLE). However, the risk factors for ADRs remain unclear. Thus, we sought to examine the prevalence of TMP-SMX-related ADRs in patients with SLE and identify specific risk factors for ADR development in these patients.. We retrospectively reviewed data from patients with connective tissue disease (CTD) who were administered TMP-SMX as a PCP prophylactic. The prevalence of ADRs was compared between patients with SLE and those with other CTDs. Univariate and multivariate analyses were conducted to identify risk factors for ADRs in patients with SLE.. Of the 424 patients with CTD included in our study (SLE, n = 162; other CTDs, n = 262), 22 with SLE (13.6%) developed ADRs, and this rate was significantly higher than that observed in patients with non-SLE CTDs (n = 18 [6.9%], p = 0.033). In patients with SLE, univariate analyses revealed direct associations of ADRs with anti-Sm (p < 0.001), anti-RNP (p = 0.02), and anti-Ro/SS-A antibodies (p = 0.042). Multivariate analysis identified a significant association between anti-Sm antibody levels and the development of ADRs (adjusted odds ratio 5.27, 95% confidence interval 1.80-15.40, p = 0.002).. Patients with SLE who are prophylactically administered TMP-SMX are at high risk of ADRs. Among these patients, those who display a positive anti-Sm antibody should be carefully monitored for ADRs.

Topics: Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Lupus Erythematosus, Systemic; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared.. Hospitalized patients with connective tissue diseases who started steroid therapy and PCP prophylaxis were enrolled. PCP prophylaxis regimens were oral TMP-SMX, aerosolized pentamidine, or oral atovaquone. Information was retrospectively collected from medical records about laboratory findings, duration of PCP prophylaxis, and reasons for terminating PCP prophylaxis.. Ninety-six patients received PCP prophylaxis. All of them were initially treated with TMP-SMX, but this was replaced during the study period with pentamidine in 33 patients and with atovaquone in 7. Forty-one (43%) patients discontinued TMP-SMX because of adverse events, and 5 (15%) also discontinued pentamidine. None of the patients discontinued atovaquone. The most frequent causes of TMP-SMX and pentamidine cessation were cytopenia (N = 15) and asthma (N = 2). The rates of continuing treatment with TMP-SMX, pentamidine, and atovaquone at one year after starting PCP prophylaxis were 55.3%, 68.6%, and 100%, respectively (P = 0.01). None of the patients developed PCP.. Although TMP-SMX for PCP prophylaxis had to be discontinued in 43% of patients with connective tissue diseases, pentamidine and atovaquone were well tolerated.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Asthma; Atovaquone; Connective Tissue Diseases; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Male; Middle Aged; Opportunistic Infections; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Trimethoprim-sulphamethoxazole (TMP-STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP-STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs.. The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP-STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors.. Adverse events caused by TMP-STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody.. Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP-STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody.

Topics: Aged; Anti-Infective Agents; Antibiotic Prophylaxis; Antibodies, Antinuclear; Connective Tissue Diseases; Female; Humans; Lung Diseases; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Ribonucleoproteins; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of our study was to examine the primary prophylactic effect of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune dysfunction induced by the long-term use of prednisolone. Prevalence of adverse drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome.. This was a retrospective cohort study. Medical records of CTD patients who were treated with prednisolone ≥20 mg per day or equivalent doses of corticosteroid for more than 2 weeks and were followed for at least 12 weeks after receiving this dosage of corticosteroids at the Rheumatology clinic of Ramathibodi Hospital between October 2006 and September 2007 were reviewed. Information regarding clinical status, laboratory features, and clinical course of the enrolled subjects was recorded.. There were 138 episodes of PCP risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did not. All 6 PCP cases developed in patients without prophylaxis with an overall incidence of 4.3%. The incidence of PCP between the 2 groups was significantly different (P = 0.038). Absolute risk reduction and relative risk reduction were 7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare.. Sulfamethoxazole/trimethoprim single strength can be used effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only mild ADR developed at this dosage. Further evaluations in larger groups of CTD patients are warranted.

Topics: Adult; Anti-Infective Agents; Antibiotic Prophylaxis; Connective Tissue Diseases; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the efficacy of primary prophylaxis for Pneumocystis jiroveci pneumonia (PCP) in patients with connective tissue disease (CTD) and immunosuppression, we compared trimethoprim-sulfamethoxazole (TMP-SMZ) with aerosolized pentamidine. Forty-eight CTD patients of Kitasato University Hospital whose CD4+ lymphocyte count in the peripheral blood was less than 300 microl(-1) were reviewed from 2002 to 2004. Twenty-seven patients received TMP-SMZ and none of them developed PCP. Among 18 patients receiving aerosolized pentamidine, three patients developed PCP. These data indicate that TMP-SMZ is better for prophylaxis than aerosolized pentamidine.

Topics: Adult; Aerosols; Aged; CD4 Lymphocyte Count; Connective Tissue Diseases; Female; Humans; Immunocompromised Host; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Although the association of Pneumocystis carinii pneumonia (PCP) with connective tissue disease (CTD) has been noted for a long time, there are few series reported.. The objective of this study was to describe clinical features and prognosis of PCP infections in patients with CTD in China.. We retrospectively reviewed the characteristics, clinical features, and prognosis of PCP in patients with CTD in a single hospital.. A total of 7 cases were reviewed (systemic lupus erythematosus n = 2, microscopic polyangiitis n = 2, dermatomyositis n = 2, polymyositis n = 1). Eighty-six percent of patients developed PCP within 3 months of the diagnosis of CTD. All patients were receiving daily glucocorticoid therapy and cytotoxic drugs before the diagnosis of PCP. Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. The CD4 lymphocyte counts of all patients were 87 +/- 78/microL. One patient was diagnosed by induced sputum; 6 patients were diagnosed by bronchoalveolar lavage fluid. Complicating fungal infection was found in 4 of 7 patients at the time of diagnosis of PCP. All patients were treated by trimethoprim-sulfamethoxazole and corticosteroids. Six (86%) patients died. The mean duration of the time from diagnosis to death was 14 +/- 4 days.. Our results suggest that PCP is an uncommon and fatal opportunistic infection in patients with CTD. When patients with CTD who are receiving immunosuppressive therapy have low lymphocyte counts and/or CD4 lymphocyte counts less than 250/microL develop fever, dry cough, dyspnea, and chest radiography shows diffuse interstitial infiltrate, the diagnosis of PCP should be highly suspected. Induced sputum or BAL must be quickly performed to confirm diagnosis. Further study is needed as to whether earlier treatment will improve prognoses or whether patients with CTD with low CD4 counts should receive PCP prophylaxis.

Topics: Adult; Aged; Connective Tissue Diseases; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lymphocyte Count; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the circumstances, the clinical features and the outcome of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-free patients with connective tissue diseases (CTD).. Retrospective analysis of all cases referred 10 medical units in the last 10 years.. A total of 34 cases of PCP in patients with CTD were studied (Wegener's granulomatosis, n = 12; systemic lupus erythematosus, n = 6; polyarteritis nodosa, n = 4; poly/dermatomyositis, n = 5; others, n = 7). The majority of patients (25/34 patients; 74%) presented PCP during the first 8 months following the diagnosis of CTD. At the time of diagnosis of PCP, most patients (32/34; 94%) were receiving corticosteroids (mean prednisone equivalent dose: 1.2 mg/kg/day) associated in 24 cases with cytotoxic agents (cyclophosphamide, n = 19; methotrexate, n = 5). Most patients were lymphocytopenic at the onset of PCP: 91% (31/34) of patients had fewer than 1.5 x 10(9)/l circulating lymphocytes and 76% (26/34) had fewer than 0.8 x 10(9)/l. The mean duration of prodromal symptoms was 6 days: this is much shorter than for AIDS associated PCP. Half the patients required intensive care for respiratory failure. Mortality was high (11/34 patients; 32%) although deaths were partly due to infections acquired in intensive care units. Among the 23 survivors, 10 (43%) received secondary prophylaxis for PCP and 13 (57%), received the usual therapeutic regimen. No relapse has been observed in either group with a mean followup of 22 months.. Although rare, PCP must be considered in patients with any type of CTD and receiving cytotoxic agents and corticosteroids, particularly if they are lymphocytopenic. Thus, bronchoalveolar lavage must be rapidly performed in patients with CTD presenting with fever, pulmonary infiltrates, hypoxemia and lymphopenia.

Topics: Adult; Aged; Aged, 80 and over; Connective Tissue Diseases; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination