Impact of stewardship pharmacist driven MRSA nasal surveillance and de-escalation of anti-MRSA therapy (STEW PHARM MRSA NASAL SURVEILLANCE).

Objective: To determine if implementing stewardship pharmacist-driven methicillin-resistant (MRSA) nasal surveillance increases use of the test and reduces the inappropriate use of vancomycin for MRSA coverage in patients with pneumonia.

Design: Retrospective pre-/post-intervention study.

Setting: Large teaching acute care hospital.

Inpatient antibiotic resistance: Everyone's problem.

Greater efforts aimed at using antimicrobials sparingly and appropriately, as well as developing new antimicrobials with activity against multidrug-resistant pathogens, are ultimately needed to address the threat of antimicrobial resistance. This article describes the evidence-based management of inpatient infections caused by resistant bacteria and the role family physicians can play in reducing further development of resistance through antimicrobial stewardship practices.

Antibiotic stewardship: The FP's role.

Drug resistance is an expanding problem in outpatient settings. The text and tables that follow can help you fight it by adhering to optimal prescribing guidelines.

Antibiotic Tissue Penetration in Diabetic Foot Infections A Review of the Microdialysis Literature and Needs for Future Research.

Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile.

Efficacy of humanized carbapenem and ceftazidime regimens against Enterobacteriaceae producing OXA-48 carbapenemase in a murine infection model.

Enterobacteriaceae producing the OXA-48 carbapenemase are emerging worldwide, leaving few treatment options. Efficacy has been demonstrated in vivo with ceftazidime against a ceftazidime-susceptible OXA-48 isolate but not with imipenem despite maintaining susceptibility. The relationship between phenotype and in vivo efficacy was assessed for OXA-48 producers using humanized regimens of 2 g doripenem every 8 h (q8h; 4 h infusion), 1 g ertapenem q24h, 2 g ceftazidime q8h (2 h inf), and 500 mg levofloxacin q24h.

In vivo efficacy of human simulated regimens of carbapenems and comparator agents against NDM-1-producing Enterobacteriaceae.

Doripenem and ertapenem have demonstrated efficacy against several NDM-1-producing isolates in vivo, despite having high MICs. In this study, we sought to further characterize the efficacy profiles of humanized regimens of standard (500 mg given every 8 h) and high-dose, prolonged infusion of doripenem (2 g given every 8 h, 4-h infusion) and 1 g of ertapenem given intravenously every 24 h and the comparator regimens of ceftazidime at 2 g given every 8 h (2-h infusion), levofloxacin at 500 mg every 24 h, and aztreonam at 2 g every 6 h (1-h infusion) against a wider range of isolates in a murine thigh infection model. An isogenic wild-type strain and NDM-1-producing Klebsiella pneumoniae and eight clinical NDM-1-producing members of the family Enterobacteriaceae were tested in immunocompetent- and neutropenic-mouse models.

Efficacy of humanized carbapenem exposures against New Delhi metallo-β-lactamase (NDM-1)-producing enterobacteriaceae in a murine infection model.

Enterobacteriaceae producing the novel carbapenemase New Delhi metallo-β-lactamase (NDM-1) are emerging worldwide. While these organisms often display high levels of in vitro resistance to multiple antibiotics, in vivo efficacy data are lacking. Here, the activities of humanized ertapenem and doripenem exposures were characterized against a wild-type K.

Impact of various conditions on the efficacy of dual carbapenem therapy against KPC-producing Klebsiella pneumoniae.

The efficacy of dual carbapenem therapy under various conditions, including increased MIC, different immune status and treatment duration and use of a higher ertapenem dose, was evaluated in a murine thigh model. Three KPC-producing Klebsiella pneumoniae isolates with different phenotypic profiles were used. Human-simulated doripenem and ertapenem doses were given alone or in combination.

Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers.

Study Objective: To compare ertapenem pharmacokinetics, pharmacodynamics, and tolerability when administered as a rapid 5-minute infusion to the standard 30-minute infusion.

Design: Prospective, randomized, crossover pharmacokinetic study.

Setting: Clinical research center.

In vitro pharmacodynamics of vancomycin and cefazolin alone and in combination against methicillin-resistant Staphylococcus aureus.

Previous studies employing time-kill methods have observed synergistic effects against methicillin-resistant Staphylococcus aureus (MRSA) when a β-lactam is combined with vancomycin. However, these time-kill studies have neglected the importance of human-simulated exposures. We evaluated the effect of human simulated exposures of vancomycin at 1 g every 8 h (q8h) in combination with cefazolin at 1 g q8h against various MRSA isolates.

Acute physiology and chronic health evaluation II score is a better predictor of mortality than IBMP-10 in patients with ventilator-associated pneumonia.

Background: The (Immunodeficiency, Blood pressure [<90 mm Hg], Multilobular intiltrates [chest x-ray], Platelets [<100×10⁹/L], hospitalization [<10 days] before the onset of ventilator-associated pneumonia [VAP]) IBMP-10 is a new scoring system proposed as an easy-to-use alternative to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score for predicting mortality in patients with ventilator-associated pneumonia (VAP). The objective of this study was to determine the validity of the IBMP-10 score compared with APACHE II in predicting mortality for an independent population consisting predominantly of surgical and neurotrauma patients.

Methods: The IBMP-10 and APACHE II scores on the day of VAP diagnosis were calculated, and areas under the receiver-operating characteristic curves (AUROCs) were compared to determine the tests' abilities to predict 14- and 28-day mortality.

Determination of tissue penetration and pharmacokinetics of linezolid in patients with diabetic foot infections using in vivo microdialysis.

Staphylococcus aureus and other Gram-positive organisms, including methicillin-resistant S. aureus, continue to be the predominant pathogens associated with diabetic foot infections. Consequently, linezolid is often used to treat these infections.

In vivo efficacy of a human-simulated regimen of ceftaroline combined with NXL104 against extended-spectrum-beta-lactamase (ESBL)-producing and non-ESBL-producing Enterobacteriaceae.

Ceftaroline exhibits in vitro activity against extended-spectrum β-lactamase (ESBL)-, AmpC-, and KPC-producing Enterobacteriaceae when combined with the novel β-lactamase inhibitor NXL104. The purpose of this study was to evaluate the efficacy of a human-simulated regimen of ceftaroline plus NXL104 against Enterobacteriaceae in a murine thigh infection model. Twelve Enterobacteriaceae isolates were tested with neutropenic ICR mice.

In vitro pharmacodynamics of simulated pulmonary exposures of tigecycline alone and in combination against Klebsiella pneumoniae isolates producing a KPC carbapenemase.

Multidrug-resistant Klebsiella pneumoniae strains that produce a serine carbapenemase (KPC) are emerging worldwide, with few therapeutic options that retain consistent susceptibility. The objective of this study was to determine the effect of combination therapy with tigecycline versus tigecycline alone against KPC-producing isolates (KPC isolates). An in vitro pharmacodynamic model was used to simulate adult steady-state epithelial lining fluid concentrations of tigecycline (50 mg every 12 h) given alone and in combination with either meropenem (2 g by 3-hour infusion every 8 h) or rifampin (600 mg every 12 h).

Tissue penetration and pharmacokinetics of tigecycline in diabetic patients with chronic wound infections described by using in vivo microdialysis.

Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity.

Iontophoretic drug delivery across human nail.

Topical trans-nail delivery of antifungal drugs is limited by several physicochemical and physiological factors. Use of chemical permeation enhancers has been a common approach for enhancing trans-nail delivery of drugs. The potential of physical permeation enhancement techniques has been found to be higher than the potential of chemical permeation enhancers in transdermal delivery of hydrophilic drugs and macromolecular therapeutic agents.