Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Mar 2020
Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening for Patients with a Diabetic Foot Infection.
Treatment of suspected methicillin-resistant Staphylococcus aureus (MRSA) is a cornerstone of severe diabetic foot infections; however, antibiotics can be associated with toxicity. The objective of this study was to determine the negative predictive value (NPV) of MRSA nares screening in the determination of subsequent MRSA in patients with a diabetic foot infection. This was a retrospective cohort study across Veterans Affairs (VA) medical centers from 1 January 2007 to 1 January 2018. ⋯ MRSA was isolated in 7.5% of cultures, and methicillin-susceptible S. aureus was isolated in 24.8%. Enterococcus was identified in 14.7% of cultures, Proteus in 7.3%, and Pseudomonas in 6.8% of cultures. Given the high NPVs, the use of MRSA nares screening may be appropriate as a stewardship tool for deescalation and avoidance of empirical anti-MRSA therapy in patients who are not nasal carries of MRSA.
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Antimicrob. Agents Chemother. · Feb 2020
Population Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from China.
The blood concentration of isoniazid (INH) is evidently affected by polymorphisms in N-acetyltransferase 2 (NAT2), an enzyme that is primarily responsible for the trimodal (i.e., fast, intermediate, and slow) INH elimination. The pharmacokinetic (PK) variability, driven largely by NAT2 activity, creates a challenge for the deployment of a uniform INH dosage in tuberculosis (TB) patients. Although acetylator-specific INH dosing has long been suggested, well-recognized dosages according to acetylator status remain elusive. ⋯ The dosage simulation targeting three indicators, including the well-recognized efficacy-safety indicator maximum concentration in serum (C max; 3 to 6 μg/ml), the reported area under the concentration-time curve from 0 h to infinity (AUC0-∞; ≥10.52 μg·h/ml), and the 2-h INH serum concentrations (≥2.19 μg/ml), was associated with the strongest early bactericidal activity. The optimal dosages targeting the different indicators varied from 700 to 900 mg/day, 500 to 600 mg/day, and 300 mg/day for the rapid, intermediate, and slow acetylators, respectively. Furthermore, a PPK model for isoniazid among Chinese tuberculosis patients was established for the first time and suggested doses of approximately 800 mg/day, 500 mg/day, and 300 mg/day for fast, intermediate, and slow acetylators, respectively, after a trade-off between efficacy and the occurrence of side effects.
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Antimicrob. Agents Chemother. · Feb 2020
Evaluation of the Activity of a Combination of Three Bacteriophages Alone or in Association with Antibiotics on Staphylococcus aureus Embedded in Biofilm or Internalized in Osteoblasts.
Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm and to be internalized and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections, but data on its activity against the specific bacterial lifestyles presented above remain scarce. ⋯ The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages as well as with vancomycin was significantly higher than in cells treated with lysostaphin, used as a control condition, owing to the absence of intracellular activity and the rapid killing of bacteria released after the death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalized in infected osteoblasts and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment, which avoids preventing them from infecting other osteoblasts. The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.
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Antimicrob. Agents Chemother. · Jan 2020
Randomized Controlled Trial Clinical TrialA Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein.
Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b. ⋯ There was no evidence of clinically significant viral resistance, and only three variants were detected. RV521 effectively reduced RSV viral load and disease severity in humans and was well tolerated. (This study has been registered at ClinicalTrials.gov under registration no. NCT03258502.).
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While resistance to antibacterial drugs is increasing globally, it is unevenly distributed. The number of cases that are truly difficult to treat remain below the number required to drive an adequate market for needed new therapies. ⋯ Here, I explore, at least briefly, the current situation and the financial risks to companies. I provide potential solutions to the failed market.