trimethoprim--sulfamethoxazole-drug-combination and Hypoxia

The clinical features of three patients with a life-threatening reaction to trimethoprim-sulfamethoxazole (TMP-SMZ) are presented along with seven other cases from the literature. All patients developed sudden fever and hypotension immediately after the administration of TMP-SMZ; usually this reaction occurred within approximately 2 weeks of completion of a previous course of the drug. All but one patient had a rash. Most patients were hypoxemic and developed diffuse pulmonary infiltrates. All patients responded rapidly to supportive care, while bacterial cultures remained negative. The presence, absence, or character of previous adverse reactions to TMP-SMZ did not predict subsequent severe reactions. Although its mechanism remains unclear, this reaction has features of both IgE-mediated anaphylaxis and cytokine (tumor necrosis factor)-mediated effects. We advise extreme caution, with close observation, when this drug is first readministered to patients who have experienced any TMP-SMZ-associated toxicity within the previous 6-8 weeks.

Topics: Adult; Diarrhea; Dyspnea; Fever; HIV Infections; Humans; Hypotension; Hypoxia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Pulmonary alveolar proteinosis (PAP) is a rare disease with worldwide distribution and an estimated incidence of 0.36 cases per million. We report a case of a PAP coexisting with Pneumocystis jiroveci pneumonia and Mycobacterium tuberculosis infection. The patient was treated with serial lobar lung lavages, GM-CSF, cotrimoxazole, and antituberculosis drugs. His PaO2 on room air improved from 45.7 to 63.8 torr and pulmonary functions normalized (FVC 81.2%, FEV1 95.3%, FEV1/FVC 91.8). A high-resolution computed tomography scan of the thorax showed clearing of both lower lobes. Whole-lung lavage is used in the treatment of PAP, but it may worsen the hypoxemia and lead to hemodynamic instability during the procedure. To the best of our knowledge, there are no reports of bronchoscopic serial lobar lung lavages in cases of PAP performed in India. This method can be performed in bronchoscopic suites having general anesthesia facilities without the requirement of special gadgets.

Topics: Adult; Anti-Infective Agents; Bronchoalveolar Lavage; Bronchoscopy; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypoxia; India; Male; Oxygen; Periodic Acid-Schiff Reaction; Pneumonia, Pneumocystis; Pulmonary Alveolar Proteinosis; Respiration, Artificial; Respiratory Function Tests; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.

Topics: Adult; Altitude; Anti-Infective Agents; Area Under Curve; Asian People; China; Chromatography, High Pressure Liquid; Erythrocytes; Humans; Hypoxia; Male; Protein Binding; Sulfamethoxazole; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Bronchoscopy; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hypoxia; Middle Aged; Oxygen Inhalation Therapy; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Radiography, Thoracic; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a 58-year-old patient with relapsing high-grade non-Hodgkin's lymphoma who exhibited exacerbation of posthypoxic action myoclonus during high-dose intravenous trimethoprim-sulfamethoxazole (TMP-SMX) treatment for highly suspicious Pneumocystis jiroveci pneumonia (PCP). Three months previously the patient had experienced a hypoxic insult caused by respiratory arrest due to an anaphylactic reaction to antibiotic therapy. He had developed posthypoxic action myoclonus (Lance-Adams syndrome), which was well controlled by oral treatment with piracetam. However, after TMP-SMX therapy (115 mg/kg daily) was started for suspicion of newly developed PCP, posthypoxic action myoclonus worsened dramatically resulting in complete disability. Anti-myoclonic therapy with increased doses of piracetam and valproic acid did not significantly improve his clinical condition. Only when TMPSMX doses were reduced (38 mg/kg daily) on day 12 did action myoclonus cease within 2 to 3 days. We suggest that TMP-SMX can exacerbate posthypoxic action myoclonus.

Topics: Anti-Infective Agents; Humans; Hypoxia; Immunocompromised Host; Male; Middle Aged; Myoclonus; Pneumocystis; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination