Randomized controlled trial of pyrimethamine plus sulfadiazine versus trimethoprim plus sulfamethoxazole for treatment of toxoplasmic encephalitis in AIDS patients.

BACKGROUND: Toxoplasmic encephalitis (TE), caused by Toxoplasma gondii, is common in AIDS patients. TE can result in tissue destruction via massive inflammation and brain abscess formation. METHODS: Randomized controlled trials were performed in AIDS patients to assess which drug regimen was optimally effective for the treatment of TE. AIDS patients with TE were randomly divided into 3 groups that received a 6-week course of either pyrimethamine (50 mg/day or 100 mg/day) plus sulfadiazine (4 g/day) and folinic acid (25 mg/day) or trimethoprim (10 mg/kg/day) plus sulfamethoxazole (50 mg/kg/day) (TMP-SMX), and results were evaluated with respect to clinical response, mortality, morbidity, and serious adverse events. The primary outcome was defined as death in the first 6-week period. The secondary outcome was successful treatment within 6 weeks without severe adverse events, bone marrow suppression, drug-induced rash, or any other event that caused a change in the treatment regimen. RESULTS: The results from this study showed that in AIDS patients, TE was most successfully treated with the combination of pyrimethamine (50 mg/day) plus sulfadiazidine (4 g/day) and folinic acid (25 mg/day); failure rates were not significantly different among the 3 treatment groups. CONCLUSIONS: Available data suggest that of the currently available options, treatment of TE with pyrimethamine at 50 mg/day plus sulfadiazidine at 4 g/day provides the best primary outcome for AIDS patients with TE; however, because this study was terminated prematurely, we suggest that treatment with intravenous TMP-SMX be further evaluated to determine its efficacy.

An outbreak of botulism in Thailand: clinical manifestations and management of severe respiratory failure.

BACKGROUND: Northern Thailand's biggest botulism outbreak to date occurred on 14 March 2006 and affected 209 people. Of these, 42 developed respiratory failure, and 25 of those who developed respiratory failure were referred to 9 high facility hospitals for treatment of severe respiratory failure and autonomic nervous system involvement. Among these patients, we aimed to assess the relationship between the rate of ventilator dependence and the occurrence of treatment by day 4 versus day 6 after exposure to bamboo shoots (the source of the botulism outbreak), as well as the relationship between ventilator dependence and negative inspiratory pressure. METHODS: We reviewed the circumstances and timing of symptoms following exposure. Mobile teams treated patients with botulinum antitoxin on day 4 or day 6 after exposure in Nan Hospital (Nan, Thailand). Eighteen patients (in 7 high facility hospitals) with severe respiratory failure received a low- and high-rate repetitive nerve stimulation test, and negative inspiratory pressure was measured. RESULTS: Within 1-65 h after exposure, 18 of the patients with severe respiratory failure had become ill. The typical clinical sequence was abdominal pain, nausea and/or vomiting, diarrhea, dysphagia and/or dysarthria, ptosis, diplopia, generalized weakness, urinary retention, and respiratory failure. Most patients exhibited fluctuating pulse and blood pressure. Repetitive nerve stimulation test showed no response in the most severe stage. In the moderately severe stage, there was a low-amplitude compound muscle action potential with a low-rate incremented/high-rate decremented response. In the early recovery phase, there was a low-amplitude compound muscle action potential with low- and high-rate incremented response. In the ventilator-weaning stage, there was a normal-amplitude compound muscle action potential. Negative inspiratory pressure variation among 14 patients undergoing weaning from mechanical ventilation was observed. Kaplan-Meier survival analysis identified a shorter period of ventilator dependency among patients receiving botulinum antitoxin on day 4 (P=.02). CONCLUSIONS: Patients receiving botulinum antitoxin on day 4 had decreased ventilator dependency. In addition, for patients with foodborne botulism, an effective referral system and team of specialists are needed.

Electrophysiological diagnosis and patterns of response to treatment of botulism with neuromuscular respiratory failure.

In this study we describe the electrophysiological findings in botulism patients with neuromuscular respiratory failure from major botulism outbreaks in Thailand. High-rate repetitive nerve stimulation testing (RNST) of the abductor digiti minimi (ADM) muscle of 17 botulism patients with neuromuscular respiratory failure showed mostly incremental responses, especially in response to >20-HZ stimulation. In the most severe stage of neuromuscular respiratory failure, RNST failed to elicit a compound muscle action potential (CMAP) of the ADM muscle. In the moderately severe stage, the initial CMAPs were of very low amplitude, and a 3-HZ RNST elicited incremental or decremental responses. A 10-HZ RNST elicited mainly decremental responses. In the early recovery stage, the initial CMAP amplitudes of the ADM muscle improved, with initially low amplitudes and an incremental response to 3- and 10-HZ RNSTs. Improved electrophysiological patterns of the ADM muscle correlated with improved respiratory muscle function. Incremental responses to 20-HZ RNST were most useful for diagnosis. The initial electrodiagnostic sign of recovery following treatment of neuromuscular respiratory failure was an increased CMAP amplitude and an incremental response to 10-20-HZ RNST. Muscle Nerve 40: 271-278, 2009.