Omadacycline: A Modernized Tetracycline.

When tetracyclines were introduced in the 1940s, these antibiotics offered a broad spectrum of activity against multiple types of pathogens. However, their utility waned after the selection of tetracycline resistance in the pathogens against which they were effective. Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class of antibiotics that is unaffected by these resistance mechanisms. It has an appropriate spectrum of activity for community-acquired infections, including those caused by many resistant organisms. Omadacycline offers a well-tolerated treatment for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Omadacycline has minimal known drug-drug interactions, and should be administered in a fasting state, avoiding dairy and cation-containing products for at least 4 hours after dosing. It does not require dose adjustments for sex, age, or hepatic or renal impairment, and has a safety profile similar to that of other oral tetracyclines. Because omadacycline can be administered effectively orally, it can help reduce hospitalization costs associated with intravenous antibiotic administration. This special supplement to Clinical Infectious Diseases offers an in-depth examination of omadacycline development, including discussions of pharmacokinetic and pharmacodynamic trials, spectrum of activity and preclinical data, early clinical trials, phase III clinical trials, and an integrated safety summary.

Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

Moxifloxacin as an alternative or additive therapy for treatment of pulmonary tuberculosis.

OBJECTIVE: To evaluate clinical studies on the role of moxifloxacin in the treatment of pulmonary tuberculosis (TB). DATA SOURCES: A literature search was conducted using MEDLINE (1960-July 2011). Key search terms were moxifloxacin, BAY 12-8039, fluoroquinolones, and TB. References of review articles and of a Cochrane Review were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Prospective studies that evaluated the use of moxifloxacin in addition to or in substitution for first-line TB therapies were reviewed and included. Case series and retrospective studies were excluded. DATA SYNTHESIS: Four 8-week clinical trials were included. All had comparator regimens containing standard doses of rifampin, isoniazid, ethambutol, and pyrazinamide. Two evaluated the substitution of moxifloxacin for ethambutol, 1 evaluated the substitution of moxifloxacin for isoniazid, and 1 studied the addition of moxifloxacin to a standard regimen. The dose of moxifloxacin was 400 mg daily in all studies, but dosing frequency differed from 3 to 7 days per week. All used culture conversion at 8 weeks as the primary end point, although they collected cultures at different times. Only 1 study found a significant difference in time to culture conversion at 8 weeks. One study found no significant difference at any point during the study. The other 2 studies found a significant difference in time to culture conversion at 4 and 6 weeks. In all trials, moxifloxacin was well tolerated, with nausea being the only significant adverse effect reported compared to the other arms of the studies. CONCLUSIONS: Although it cannot be stated definitively, available evidence suggests that moxifloxacin appears to be as effective as ethambutol and is possibly as effective as isoniazid in the treatment of pulmonary TB. Given the generally poor second-line options for the treatment of TB, moxifloxacin is an attractive option as an alternative drug in TB treatment.

Tigecycline for the treatment of Acinetobacter infections: a case series.

BACKGROUND: Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections. OBJECTIVE: To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution. METHODS: A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients. RESULTS: Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8). CONCLUSIONS: In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.