trimethoprim--sulfamethoxazole-drug-combination and Pulmonary-Fibrosis

From June/82 through November/85 bone marrow transplant recipients in our Institution were given only trimethoprim-sulfamethoxazole as prophylaxis against interstitial pneumonia. In December/85 we began a program of administration of passive immunoprophylaxis with hyperimmune plasma or cytomegalovirus-specific gamma globulin and transfusion of seronegative blood products to all bone marrow transplant recipients whether they were seropositive or seronegative prior to transplant. Nine of 36 patients in the historical control group and 9 of 32 patients in the study group developed an interstitial pneumonia. Interstitial pneumonia, once established, was treated empirically. The 9 patients in the control group received trimethoprim-sulfamethoxazole +/- adenine arabinoside, acyclovir, amphotericin B and anti-bacterial antibiotics; all died. Post-mortem study was performed in 7 (4 CMV, 3 idiopathic). The 9 patients in the study group received high dose cytomegalovirus-specific gamma globulin + acyclovir or ganciclovir in addition to the above measures. Four were cured, one relapsed and responded to treatment again. Five died (1 CMV, 1 candida, 3 idiopathic). We conclude that the prophylactic measures, as applied at our Institution, were inefficient. By contrast, therapy with specific immunoglobulin + acyclovir or ganciclovir can control a high percentage of patients. We compare this experience with reports from other centers.

Topics: Acyclovir; Adolescent; Adult; Bone Marrow Transplantation; Child; Female; gamma-Globulins; Ganciclovir; Humans; Infant; Male; Middle Aged; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination

In 1996, clinical improvement with oral co-trimoxazole was noted in a patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung transplant. Subsequently, 14 patients with end stage fibrotic lung disease also responded to oral co-trimoxazole. This prompted a double blind randomised placebo controlled pilot study in patients with advanced stages of idiopathic interstitial pneumonias (IIP) to objectively measure benefit.. Twenty patients (aged 49-84 years; 11 males) with progressive fibrotic lung disease who had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and showed oxygen desaturation on exertion were selected.. A detailed assessment of arterial gases, lung function, and progressive shuttle-walking tests combined with oxygen saturation monitoring. Quality of life data was recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients received active treatment upon decoding with continued follow up of all patients.. Primary 1. Shuttle walking test. Secondary 2. FVC and quality of life.. Active treatment showed a significant improvement in shuttle walking test from 255 to 355 m (p=0.002) (95% CI 200-450) with reduced oxygen desaturations during exercise (p=0.003). FVC improved on treatment (+21%) from median 1.9 to 2.3 L (p=0.05) (95% CI 1.3-3.0) but TLC and DLCO were not significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea Score showed improvement (p=0.05) at 3 months for the active group which was maintained at 12 months. The SGHRQ showed a significant reduction in symptom scores at 12 months (p=0.05). The placebo group showed no significant change in any parameters, but demonstrated identical improvement following oral co-trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in the active group at 3 months, but just failed to reach statistical significance. 'Out of study' HRCT scans in 12 patients showed significant reduction in ground glass changes (p=0.05) after 12 months of continuous co-trimoxazole treatment.. The findings of the pilot study show significant improvements in objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of 'a favourable response to treatment'.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Blood Cell Count; Blood Gas Analysis; Double-Blind Method; Female; Humans; Male; Middle Aged; Pilot Projects; Pulmonary Fibrosis; Quality of Life; Respiratory Function Tests; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Walking

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.

Topics: Adult; Agranulocytosis; Biopsy; Diagnosis, Differential; Drug Therapy, Combination; Erythromycin; Female; Humans; Male; Middle Aged; Neoplasms; Pneumonia, Pneumocystis; Prospective Studies; Pulmonary Fibrosis; Random Allocation; Trimethoprim, Sulfamethoxazole Drug Combination

Clinicians should be aware of the risk of opportunistic infections in patients who are immunocompromised. Opportunistic infections such as Pneumocystis jirovecii commonly are associated with HIV/AIDS, but less commonly considered in patients receiving immunosuppressive and/or immunomodulating therapies. This case report focuses on the management of an opportunistic infection in an HIV-negative patient on immunosuppressive medications for lymphoma and exacerbation of pulmonary fibrosis.

Topics: Aged; Anti-Bacterial Agents; Bendamustine Hydrochloride; HIV Seronegativity; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Lymphoma, Mantle-Cell; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition.

Topics: Animals; Antifungal Agents; Azithromycin; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Immunosuppressive Agents; Intercellular Signaling Peptides and Proteins; Itraconazole; Male; Mice; Mice, Inbred BALB C; Paracoccidioides; Paracoccidioidomycosis; Pentoxifylline; Pulmonary Fibrosis; Random Allocation; Thalidomide; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We report the case of an 84-year-old man with refractory immune thrombocytopenia purpura (ITP) who was treated with rituximab and subsequently developed severe interstitial lung disease. There has been increasing use of rituximab in the treatment of ITP with success rates of up to 62% in adult patients with recurrent ITP. Interstitial lung disease is a rare but recognised complication of rituximab but has been rarely reported in the setting of ITP.

Topics: Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Combined Modality Therapy; Disease Progression; Hemorrhage; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Pneumonia, Pneumocystis; Prednisone; Pulmonary Fibrosis; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Biopsy; Diagnosis, Differential; Gentamicins; Horse Diseases; Horses; Lung; Lung Diseases, Interstitial; Male; Penicillins; Prednisone; Pulmonary Fibrosis; Radiography, Thoracic; Radionuclide Imaging; Thorax; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a disorder with a very poor prognosis for patients who do not respond to therapy with corticosteroids alone or in combination with immunosuppressive drugs, e.g. cyclophosphamide or azathioprine. For patients with end-stage disease, lung transplantation remains the only possibility for long-term survival. We describe a patient who received a left single lung transplant for end-stage desquamative interstitial pneumonitis. One year later, the patient again began complaining of exertional dyspnoea and a gradual decline in the transfer factor of the lung for carbon monoxide (TL,CO) was apparent. A recurrence of the primary disease in the transplanted lung was suspected on transbronchial biopsies. During treatment with high doses of steroids, a Pneumocystis carinii pneumonia developed, which was treated with co-trimoxazole. The patient completely recovered and, after a period of over 2 yrs, remained in an excellent condition, after which time he was lost from follow-up.

Topics: Adult; Anti-Infective Agents; Glucocorticoids; Humans; Lung Transplantation; Male; Methylprednisolone; Pneumonia, Pneumocystis; Postoperative Complications; Pulmonary Fibrosis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

A newly synthesized biguanide inhibitor of dihydrofolate reductase in Plasmodium species was evaluated for its anti-Pneumocystis carinii activity. The compound N-3-(2,4,5-trichlorophenoxypropyloxy)-N'-(1-methylethyl)imidoca rbonimidic diamide hydrochloride, designated PS-15, was administered prophylactically and therapeutically to immunosuppressed rats latently infected with P. carinii. Doses of 5 and 25 mg of PS-15 per kg of body weight per day given orally during 7 weeks of dexamethasone immunosuppression prevented P. carinii infection in all (100%) 19 rats given the drug, while 6 of 9 (67%) untreated control rats developed P. carinii pneumonitis. A single weekly dose of 50 mg of PS-15 per kg also prevented the infection in all 10 rats. P. carinii pneumonitis was established after 4 weeks of immunosuppression and was then treated orally for 3 weeks with 25, 5, and 1 mg of PS-15 per kg/day. Complete resolution of the infection occurred in all (100%) 10 rats given 25 mg of PS-15, 6 of 9 (67%) rats given 5 mg of PS-15, and 6 of 8 (75%) rats given 1.0 mg of PS-15 per kg per day and in all (100%) 9 rats treated with trimethoprim-sulfamethoxazole. PS-15 was well tolerated at all doses. Because drug studies in the P. carinii rat model have been highly predictable of the effects of drugs on the disease in humans, these experiments suggest that PS-15 may have promise as a drug for the treatment of P. carinii pneumonitis in humans.

Topics: AIDS-Related Opportunistic Infections; Animals; Antimalarials; Dose-Response Relationship, Drug; Folic Acid Antagonists; Imides; Immunosuppressive Agents; Lung; Male; Phenyl Ethers; Pneumocystis Infections; Pneumonia, Pneumocystis; Proguanil; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

We present here three AIDS patients with disseminated cryptococcal infection and lung involvement. Two patients presented with respiratory symptoms and in the third one, pulmonary disease was only a radiologic finding. Chest X-ray films showed an interstitial pattern in two cases and pulmonary cavitation in one case. One patient has also simultaneous infection by P. carinii. Diagnosis was established by culture from bronchoalveolar lavage in all cases and also by non-induced sputum exam in two cases. All patients were treated with amphotericin B, with good clinical outcome, and without relapses under maintenance therapy with fluconazole. Cryptococcosis must be included in differential diagnosis of AIDS patients with diffuse interstitial lung infiltrates. The presence of C. neoformans in respiratory samples does not rule out the existence of other opportunistic infections, and therefore bronchoalveolar lavage is advisable.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Cryptococcosis; Diagnosis, Differential; Fluconazole; Humans; Incidence; Lung Diseases, Fungal; Male; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination

We report a four-year-old boy with HIV encephalopathy after vertical HIV infection. On the first admission to our hospital he showed ataxia, loose of expressive language and interstitial pneumonia. After treatment of the pneumonia the patient was started on oral zidovudine with 6 x 6 mg/kg bw/day, because of persisting neurologic symptoms and deep white matter lesions in the MR tomogram of the brain. Two months later he showed an improvement of the gait and the reappearance of the expressive language. Seven months after the start with zidovudine the MR tomogram of the brain revealed the disappearance of white matter lesions with exception of little areas of demyelinisation. No side effects of treatment were observed. The only persisting pathological clinical signs were developmental delay of about a half year and moderately hyperactive tendon reflexes of the lower extremities. Our case suggests that even oral treatment with zidovudine can have a beneficial effect on the HIV encephalopathy in infants.

Topics: Administration, Oral; AIDS Dementia Complex; Brain; Child, Preschool; Electroencephalography; HIV Antibodies; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Child; Child, Preschool; HIV Infections; Humans; Infant; Infant, Newborn; Lung Diseases; Lung Neoplasms; Mycoplasma Infections; Mycoses; Opportunistic Infections; Pneumonia, Pneumocystis; Pulmonary Fibrosis; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

Anaerobic bacterial pneumonia with septicemia was diagnosed in 2 Thoroughbred racehorses referred with respiratory tract disease that had failed to respond to initial treatment with various antibiotics including penicillin and trimethoprim-sulfamethoxazole. Multiple anaerobic organisms, including Bacteroides spp and Fusobacterium spp, were isolated from blood and transtracheal aspirates obtained from both horses and from aspirates of cutaneous nodules obtained from 1 horse. The latter horse responded to metronidazole treatment followed by procaine penicillin G administration and regained its health over the following 6 months. The other horse did not respond as favorably to a similar antibiotic regimen and died following an acute episode of pulmonary hemorrhage after remaining intermittently febrile for 7 weeks. Although in vitro antimicrobial susceptibility tests indicated that all anaerobic organisms isolated from both horses were susceptible to penicillin, the infection in these horses responded poorly to initial treatments with this drug. We speculated that adequate penicillin concentration was not attained in the deep foci of infection in the lungs. Animals with anaerobic bacterial infections that fail to respond to penicillin or from which penicillin-resistant anaerobes are isolated may benefit from treatment with metronidazole.

Topics: Animals; Bacteria, Anaerobic; Bacteroides; Female; Fusobacterium necrophorum; Horse Diseases; Horses; Male; Metronidazole; Pulmonary Fibrosis; Sepsis; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Humans; Immunosuppression Therapy; Kidney Transplantation; Norway; Pneumonia, Pneumocystis; Postoperative Complications; Pulmonary Fibrosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole may cause life-threatening reactions and even death, but such reactions are rare and do not detract from its usefulness. As with any therapy, however, caution should be observed in its use in children, and especially in the elderly.

Topics: Anti-Infective Agents; Child; Dermatitis, Exfoliative; Drug Combinations; Humans; Male; Nephritis, Interstitial; Pulmonary Fibrosis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

An acute pneumonic process in an immunosuppressed child poses a diagnostic and therapeutic challenge. These patients tolerate infection poorly. An open lung biopsy may provide prompt diagnosis. Nevertheless, a beneficial change in therapy that results in survival does not necessarily follow. Fifty-six immunosuppressed children with acute respiratory symptoms and interstitial pulmonary infiltrates underwent lung biopsy from 1974 to 1985. The most common underlying diagnosis was acute lymphocytic leukemia (60%). A specific etiology was determined in 46 (82%). Operative morbidity in 52% included prolonged intubation, recurrent pneumothorax, and hemorrhage. Overall, mortality was 34%. Those patients with solid tumor and those who required postoperative ventilation had a statistically significant higher mortality than all others. We defined biopsy "patient benefit" as follows: (1) the biopsy yielded an etiology for which a change of treatment was required; and (2) the child survived this acute illness. Despite the successful diagnostic results of this procedure, only 13 (23%) of the patients derived clinical benefit. Even though a specific infectious etiology was diagnosed in 39 (69%) patients only ten (18%) of these improved and survived after an appropriate change in therapy. Eight of these had Pneumocystis carinii. One survivor benefited from the treatment of documented radiation pneumonitis. Another was successfully treated for graft v host reaction but this diagnosis also was made by skin biopsy. One half of the biopsies were performed very early in the course of the illness, specifically to exclude Pneumocystis carinii of which we saw a peak incidence in 1978 to 1979.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Adult; Biopsy; Child; Child, Preschool; Diagnosis, Differential; Drug Combinations; Emergencies; Humans; Immune Tolerance; Infant; Leukemia, Lymphoid; Lung; Lung Diseases, Fungal; Pneumonia, Pneumocystis; Prognosis; Pulmonary Fibrosis; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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