Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial.

CONTEXT: Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci. OBJECTIVE: To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections. DESIGN AND SETTING: Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000. PARTICIPANTS: Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795). INTERVENTIONS: Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397). MAIN OUTCOME MEASURES: Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups. RESULTS: At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P =.03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P =.08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P =.02). CONCLUSION: Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci.

Principles of appropriate antibiotic use for acute rhinosinusitis in adults: background.

The following principles of appropriate antibiotic use for adults with acute rhinosinusitis apply to the diagnosis and treatment of acute maxillary and ethmoid rhinosinusitis in adults who are not immunocompromised. Most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections. Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds. The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for patients with rhinosinusitis symptoms lasting 7 days or more who have maxillary pain or tenderness in the face or teeth (especially when unilateral) and purulent nasal secretions. Patients with rhinosinusitis symptoms that last less than 7 days are unlikely to have bacterial infection, although rarely some patients with acute bacterial rhinosinusitis present with dramatic symptoms of severe unilateral maxillary pain, swelling, and fever. Sinus radiography is not recommended for diagnosis in routine cases. Acute rhinosinusitis resolves without antibiotic treatment in most cases. Symptomatic treatment and reassurance is the preferred initial management strategy for patients with mild symptoms. Antibiotic therapy should be reserved for patients with moderately severe symptoms who meet the criteria for the clinical diagnosis of acute bacterial rhinosinusitis and for those with severe rhinosinusitis symptoms-especially those with unilateral facial pain-regardless of duration of illness. For initial treatment, the most narrow-spectrum agent active against the likely pathogens, Streptococcus pneumoniae and Haemophilus influenzae, should be used.

A quantitative study of the pancuronium antagonism at the motor endplate in human organophosphorus intoxication.

Nine patients with organophosphorus (OP) intoxication developing neuromuscular transmission defects were given pancuronium 1, 2, or 4 mg intravenously (IV). Thirteen patient controls with hypoxic encephalopathy received similar dosages. The responses were monitored electrophysiologically using single and repetitive nerve stimulation (20 and 50 Hz). In OP patients, pancuronium did not alter the amplitude of the single CMAP, whereas its repetitive discharges were reduced. Severe neuromuscular blocks were reversed only partially by pancuronium 4 mg. In less severe blocks, 1 and 2 mg resulted in marked improvement. In the patient controls, pancuronium 4 mg induced a severe neuromuscular block but not with 1 and 2 mg. Pancuronium dosages necessary to reverse severe OP-induced neuromuscular blockade produce a neuromuscular block when AChE activity is normal. Low dosages have little effect on normal neuromuscular transmission, but improve the block to a mild degree and may be useful as part of treatment in OP intoxications.

High pancuronium sensitivity of axonal nicotinic-acetylcholine receptors in humans during organophosphate intoxication.

The effect of low-dose pancuronium on neuromuscular transmission was studied in 2 patients during the early and late stages of severe organophosphate intoxication. Single evoked compound muscle action potentials (CMAP) were followed by repetitive discharges and a decrement-increment (D-I) phenomenon with 10-, 20-, and 50-Hz supramaximal nerve stimulation. Intravenous pancuronium, 1 mg, abolished the D-I phenomenon, while the repetitive discharges of the CMAP were only partially reduced. It is postulated, that the disappearance of the D-I phenomenon with persistence of the CMAP repetitive discharges results from blockade of nicotinic-acetylcholine receptors located on the terminal axon responsible for stimulus-induced antidromic backfiring. This response to a very low dose of pancuronium indicates a high sensitivity of the axonal nicotinic-acetylcholine receptor to pancuronium in humans, as had been previously postulated from animal experiments.

Pancuronium improves the neuromuscular transmission defect of human organophosphate intoxication.

Two patients with acute severe organophosphate intoxication showed (1) single evoked compound muscle action potentials (CMAP) with repetitive discharges and (2) prominent decremental responses of CMAP with 20 and 50 Hz supramaximal nerve stimulation. Following the intravenous injection of single small doses of pancuronium, marked improvement in these abnormalities occurred and persisted for several hours. We postulate that the physiologic improvement following low-dose pancuronium results from blockade of acetylcholine receptors, especially those located on the terminal axon responsible for antidromic backfiring.