Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Oct 2017
Transfersomal Phage Cocktail Is an Effective Treatment against Methicillin-Resistant Staphylococcus aureus-Mediated Skin and Soft Tissue Infections.
The emergence of drug resistance has rekindled interest in phage therapy as an alternative treatment option; its potency, safety, and proven efficacy are worth noting. However, phage therapy still suffers from issues of poor stability, narrow spectra, and poor pharmacokinetic profiles. Therefore, it is essential to look into the use of drug delivery systems for efficient delivery of lytic phages in vivo The present study evaluated the use of nanostructured lipid-based carriers, i.e., transfersomes, as transdermal delivery systems for encapsulating a methicillin-resistant Staphylococcus aureus (MRSA) phage cocktail. ⋯ The findings of the present study support the use of transfersomes as delivery agents to enhance the stability and in vivo persistence of the encapsulated phages. In addition, this study highlights the advantages offered by transfersome-encapsulated phages in providing better therapeutic options than free phages for treating skin and soft tissue infections. The transfersome-entrapped phage cocktail was able to protect all test animals (with no deaths) even when administered with a delay of 12 h postinfection, unlike free phages, thus making this treatment option more suitable for clinical settings.
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Antimicrob. Agents Chemother. · Sep 2017
Bactericidal and Sterilizing Activity of a Novel Regimen with Bedaquiline, Pretomanid, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis.
New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. ⋯ BDQ+PMD+MXF+PZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.
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Antimicrob. Agents Chemother. · Sep 2017
Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations.
Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly.
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Antimicrob. Agents Chemother. · Sep 2017
In Vitro Susceptibility of the Relapsing-Fever Spirochete Borrelia miyamotoi to Antimicrobial Agents.
Hard-tick-borne relapsing fever (HTBRF) is an emerging infectious disease throughout the temperate zone caused by the relapsing-fever spirochete Borrelia miyamotoi Antibiotic treatment of HTBRF is empirically based on the treatment of Lyme borreliosis; however, the antibiotic susceptibility of B. miyamotoi has not been studied to date. Thus, we set out to determine the in vitro antimicrobial susceptibility of B.miyamotoi A microdilution method with 96-well microtiter plates was used to determine the antibiotic susceptibilities of two B.miyamotoi strains isolated on two different continents (Asia and North America), two Borrelia burgdorferisensu lato strains, and one Borrelia hermsii isolate for purposes of comparison. ⋯ Since B. miyamotoi is susceptible to doxycycline, azithromycin, and ceftriaxone in vitro, our data suggest that these antibiotics can be used for the treatment of HTBRF. Oral amoxicillin is currently used as an alternative for the treatment of HTBRF; however, since we found that the B. miyamotoi strains tested were resistant to amoxicillin in vitro, this issue warrants further study.
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Antimicrob. Agents Chemother. · Sep 2017
Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation.
The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. ⋯ For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).