William K. Lau

BACKGROUND: Radiofrequency ablation for atrial fibrillation is becoming widely practiced. METHODS AND RESULTS: Two patients undergoing circumferential pulmonary vein ablation for atrial fibrillation in different centers developed symptoms compatible with endocarditis 3 to 5 days after the procedure. Their clinical condition deteriorated rapidly, and both suffered multiple gaseous and/or septic embolic events causing cerebral and myocardial damage. One patient survived after emergency cardiac and esophageal surgery; the other died of extensive systemic embolization. An atrio-esophageal fistula was identified in both patients. CONCLUSIONS: Atrio-esophageal fistulas can occur after catheter ablation in the posterior wall of the left atrium. This diagnosis should be excluded in any patient with symptoms or signs of endocarditis after left atrial ablation, and expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower power and temperature settings for applications of radiofrequency energy along the posterior left atrial wall may prevent further cases of fistula formation.

BACKGROUND: Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains. METHODS: We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients > or = 18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily). RESULTS: For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (< or = 0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (approximately 5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9). CONCLUSION: Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

The purpose of this randomized, multicenter, open-label study was to compare the continuous infusion of piperacillin-tazobactam with the standard intermittent infusion in 262 hospitalized patients with complicated intra-abdominal infections. Within 1 day of surgical intervention, eligible patients were randomized (1:1) to piperacillin-tazobactam 12 g/1.5 g administered continuously over 24 h or 3 g/0.375 g administered over 30 min intermittently every 6 h for 4 to 14 days. The demographics of the patients in the groups were similar, with a median APACHE II score of 7 and a median length of hospitalization of 7 days. Among 167 clinically evaluable patients, 86.4% and 88.4% of the patients treated with the continuous infusion and the intermittent infusion, respectively, were clinically cured or improved at the test-of-cure visit (P = 0.817). Bacteriological success was observed in 83.9% and 87.9% of patients (P = 0.597) in the two groups, respectively, and no differences in bacteriological response by pathogen were noted. Defervesence and white blood cell count normalization occurred in the majority of patients within 3 days and were similar between patients receiving the continuous infusion and those receiving the intermittent infusion. Drug-related adverse events were generally mild and were reported in similar numbers of patients in each arm of the trial. The results of this study support continuous infusion as a safe and reasonable alternate mode of administration of piperacillin-tazobactam for the treatment of complicated intra-abdominal infection.

Amikacin was used in 77 treatment courses at a dosage of >/=7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a "peak" serum level exceeding 32 mug/ml and 55% of patients with "trough" levels exceeding 10 mug/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity.