The Antimicrobial Stewardship Approach to Combating Clostridium Difficile

Clostridium difficile remains a major public health threat and continues to contribute to excess morbidity, mortality and healthcare costs. Antimicrobial stewardship programs have demonstrated success in combating C. difficile, primarily through antibiotic restrictive strategies. As the incidence and prevalence of C. difficile associate disease continues to increase both in the hospital and community setting, additional stewardship approaches are needed. This manuscript reviews stewardship interventions that have been successful against C. difficile associated disease and proposes future tactics that antimicrobial stewardship programs may employ to develop a more global approach to combat this difficult pathogen

An Update on the arsenal for multidrug-resistant Acinetobacter infections: Polymyxin antibiotics

Objective: To review recent clinical pharmacokinetic and pharmacodynamic data to optimize dosing regimens for polymyxin B and colistin for treatment of infections due to A. baumannii. Methods: A literature search was performed using the search terms Acinetobacter, polymyxin, colistin, polymyxin B on MEDLINE. Additional references were identified from the resulting citations. Results: Increasing the dose of polymyxin B or colistin and using either in combination with other antibiotic agents demonstrates improved antimicrobial activity against Acinetobacter spp. Polymyxin B, unlike colistin, is available as an active drug and appears to be relatively unaffected by renal function. This is advantageous both for patients with renal impairment and for those with intact renal function. Achieving therapeutic serum concentrations of colistin may be difficult for those with intact renal function due to rapid clearance of the prodrug, colistimethate sodium (CMS). Clinical data are still lacking for polymyxin B, and it remains to be seen whether advantages demonstrated in PK/PD analyses will persist in the larger scale of patient care and safety. Conclusions: The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii

Efficacy of inhaled ciprofloxacin in the management of non-cystic fibrosis bronchiectasis

Non-cystic fibrosis bronchiectasis (NCFBE), a historically under-recognized chronic respiratory condition, is a significant diagnosis currently experiencing a resurgence of interest in its clinical management. Ciprofloxacin is part of the current armamentarium used in the treatment of the recurrent respiratory tract infections seen in NCFBE. Inhaled ciprofloxacin, a novel method of drug delivery for the fluoroquinolone class, is being actively investigated. The inhaled formulation is designed to enhance drug delivery to the site of infection in the lung while minimizing the risk of systemic toxicity. This review summarizes the pharmacology and pharmacokinetics of ciprofloxacin and the rationale for the development of an inhaled formulation for NCFBE. Preclinical and clinical data regarding current development of inhaled ciprofloxacin formulations is also evaluated. Lastly, the anticipated role of inhaled ciprofloxacin in the management of NCFBE is discussed, including future considerations and potential limitations of therapy

Steady-State Plasma and Bronchopulmonary Concentrations of Intravenous Levofloxacin and Azithromycin in Healthy Adults

The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration. Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses. Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion. The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published. The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration. The respective mean (± standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 ± 4.52, 2.50 ± 0.97, and 1.24 ± 0.55 μg/ml; those for 750 mg of levofloxacin were 12.94 ± 1.21, 6.04 ± 0.39, and 1.73 ± 0.78 μg/ml; and those for azithromycin were 1.70 ± 0.74, 1.27 ± 0.47, and 2.86 ± 1.75 μg/ml. The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times. The respective concentrations in AM for 500 mg of levofloxacin were 83.9 ± 53.2, 18.3 ± 6.7, and 5.6 ± 3.2 μg/ml; those for 750 mg of levofloxacin were 81.7 ± 37.0, 78.2 ± 55.4, and 13.3 ± 6.5 μg/ml; and those for azithromycin were 650 ± 259, 669 ± 311, and 734 ± 770 μg/ml. Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times. The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma. Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections