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Mihailescu R.,University of Lausanne | Mihailescu R.,National Institute Of Infectious Diseases Prof Dr Matei Bals | Tafin U.F.,University of Lausanne | Corvec S.,University of Lausanne | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Increasing antimicrobial resistance reduces treatment options for implant-Associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 μg/ml; daptomycin, 0.125 μg/ml; vancomycin, 1 μg/ml; rifampin, 0.04 μg/ ml; and tigecycline, 0.125 μg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log10 CFU/ml at 128the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by>1 log10 CFU/ml with fosfomycin and tigecycline, 1.7 log10 with daptomycin, 2.2 log 10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log10 with fosfomycin-daptomycin, and>6.0 log10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-Associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cageassociated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 μg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cageassociated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-Associated infections, but it cannot replace rifampin as an antibiofilm agent.© 2014, American Society for Microbiology. Source

Revell A.D.,The HIV Resistance Response Database Initiative RDI | Wang D.,The HIV Resistance Response Database Initiative RDI | Wood R.,Desmond Tutu Center | Morrow C.,Desmond Tutu Center | And 11 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2013

Objectives: Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. Methods: Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases fromwell-resourced countries, plus 231 cases fromSouthern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. Results: Themodels achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achievedAUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania).Modelsweremore accurate for data fromthewell-resourced countries than for cases fromSouthern Africa and India (P<0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. Conclusions: We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available ©The Author 2013. Source

Ilie A.,National Institute Of Infectious Diseases Prof Dr Matei Bals
Therapeutics, Pharmacology and Clinical Toxicology | Year: 2011

The author presents case of an infected HIV patient, late presenter and antiretroviral treatment management using Raltegravir as first line therapy. The patient associated in 2008 chronic hepatitis C with sustained viral response. © reserved 2011. Source

Iacob S.A.,National Institute Of Infectious Diseases Prof Dr Matei Bals | Iacob D.G.,Carol Davila University of Medicine and Pharmacy
Protein and Peptide Letters | Year: 2014

The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice. © 2014 Bentham Science Publishers. Source

Gheorghita V.I.,Central Military Emergency Hospital Dr Carol Davila | Gheorghita V.I.,National Institute Of Infectious Diseases Prof Dr Matei Bals | Caruntu F.A.,National Institute Of Infectious Diseases Prof Dr Matei Bals | Caruntu F.A.,Carol Davila University of Medicine and Pharmacy | And 7 more authors.
Journal of Gastrointestinal and Liver Diseases | Year: 2013

Background & Aims: The aim of the study was to assess the clinical utility of serum HBsAg quantification as a surrogate biomarker for the prediction of sustained virological response (SVR) in chronic hepatitis B (CHB) patients treated with Pegylated Interferon alfa-2a (Peg-IFN α-2a). Methods: We performed a prospective cohort study which included 57 patients with CHB treated 48 weeks with Peg-IFN α-2a and followed for another 24 weeks. HBsAg was quantified at the baseline, during treatment and at the end of follow-up. SVR was defined as HBV-DNA below 2,000 IU/ml at 24 weeks after the end of therapy. Results: The majority of patients had HBeAg-negative CHB (68%, n=39). Positive predictive factors for SVR at baseline were low levels of HBsAg (3.72 log10 IU/ml, p=0.032) and HBV-DNA (3.96 log10 IU/ml, p=0.035). During treatment, patients who achieved SVR showed a marked decrease in serum HBsAg in comparison with nonresponders (at week 48 mean decrease of 1.06 ± 1.3 log10 IU/ml versus 0.04 ± 0.5 log10 UI/ml, p=0.005). On therapy, HBV-DNA reduction ≥ 2 log10 IU/ml with any decrease of HBsAg level at week 12 had a positive predictive value (PPV) of 80% (95% CI: 51.91-95.43%) for SVR, while HBV-DNA decline < 2 log10 IU/ml without any decline of HBsAg had a negative predictive value (NPV) of 85.71% (95% CI: 42.23-97.63%) for SVR. Conclusions: HBsAg quantification combined with HBV-DNA assessment could become an early useful tool to optimize the management of CHB patients treated with Peg-IFN α-2a, according to response guided therapy. Source

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