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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/27895022/inhibition-of-plasmodium-liver-infection-by-ivermectin
#1
António M Mendes, Inês S Albuquerque, Marta Machado, Joana Pissarra, Patrícia Meireles, Miguel Prudêncio
Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro Notably, ivermectin potently inhibits liver infection in vivo, by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission due to its effects on the mosquito vector...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895021/1-in-vitro-and-in-vivo-activity-of-sulfur-containing-linear-bisphosphonates-against-apicomplexan-parasites
#2
Sergio H Szajnman, Tamila Galaka, Zhu-Hong Li, Catherine Li, Nathan M Howell, María N Chao, Boris Striepen, Vasant Muralidharan, Silvia N J Moreno, Juan B Rodriguez
We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma gondii, the etiologic agent of toxoplasmosis. The most potent compound ( 22: , 1-[(n-decylsulfonyl)ethyl]-1,1-biphosphonic acid) is a sulfone-containing compound, which had an EC50 of 0.11 ± 0.02 μM against intracellular tachyzoites. The compound showed low toxicity when tested in tissue culture with a selectivity index of >2,000. 22: also showed high activity in vivo in a toxoplasmosis mouse model. The compound inhibited the Toxoplasma farnesyl diphosphate synthase (TgFPPS) but the concentration needed to inhibit 50% of the enzymatic activity (IC50) was higher than the concentration that inhibited 50% of growth...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895020/a-naturally-occurring-snp-in-plasmid-pb1000-produces-a-reversible-increase-in-antibiotic-resistance
#3
Alfonso Santos-Lopez, Cristina Bernabe-Balas, Manuel Ares-Arroyo, Rafael Ortega-Huedo, Andreas Hoefer, Alvaro San Millan, Bruno Gonzalez-Zorn
ColE1 plasmids are small mobilizable replicons that play an important role in the spread of antibiotic resistance in Pasteurellaceae. In this study we describe how a natural single nucleotide polymorphism (SNP) near the origin of replication of the ColE1-type plasmid pB1000 found in a Pasteurella multocida clinical isolate, generates two independent plasmid variants able to coexist in the same cell simultaneously. Using Haemophilus influenzae Rd strain as a model system, we combined antibiotic susceptibility tests, quantitative PCRs, competition assays and experimental evolution to characterize the consequences of the coexistence of the pB1000 plasmid variants...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895019/nephrotoxicity-during-vancomycin-therapy-in-combination-with-piperacillin-tazobactam-or-cefepime
#4
W Cliff Rutter, Jessica N Cox, Craig A Martin, Donna R Burgess, David S Burgess
BACKGROUND: Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in acute kidney injury (AKI) when combined with anti-pseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). METHODS: This was a retrospective, matched cohort study at an academic medical center between September 2010 and September 2014 including adult patients receiving TZP-VAN or FEP-VAN for at least 48 hours and without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or hospital transfer...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895018/the-occurrence-of-diverse-abgri1-type-genomic-islands-in-acinetobacter-baumannii-global-clone-2-gc2-isolates-from-korea
#5
Dae Hun Kim, Sook-In Jung, Ki Tae Kwon, Kwan Soo Ko
In this study, we analyzed the frequency of the AbGRI1-type genomic island (GI) and its association with genotypes. We obtained 130 A. baumannii isolates causing bloodstream infections from patients in Korea. Antimicrobial susceptibility testing and multilocus sequence typing were performed. The presence of AbGRI1-type GIs and their structure were determined by sequential PCR and sequencing. Ninety-eight isolates (75.3%) representing 14 sequence types (STs) belonged to CC208, corresponding to global clone 2 (GC2)...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895017/molecular-investigation-of-resistance-to-second-line-injectable-drugs-in-multidrug-resistant-clinical-isolates-of-mycobacterium-tuberculosis-in-france
#6
Florence Brossier, Anne Pham, Christine Bernard, Alexandra Aubry, Vincent Jarlier, Nicolas Veziris, Wladimir Sougakoff
The second line injectable drugs (SLID, i.e. amikacin, kanamycin, capreomycin) are key drugs for the treatment of multidrug-resistant tuberculosis. Mutations in rrs region 1400, tlyA and eis promoter are associated with resistance to SLID, to capreomycin and to kanamycin respectively. In this study, the sequencing data of SLID resistance-associated genes were compared to the results of phenotypic drug susceptibility testing by the proportion method for the SLID in 206 multidrug-resistant clinical isolates of Mycobacterium tuberculosis collected in France...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895016/are-prophylactic-and-therapeutic-target-concentrations-different-the-case-of-lopinavir-ritonavir-or-lamivudine-administered-to-infants-for-the-prevention-of-mother-to-child-hiv-1-transmission-during-breastfeeding
#7
Frantz Foissac, Jörn Blume, Jean-Marc Tréluyer, Thorkild Tylleskär, Chipepo Kankasa, Nicolas Meda, James K Tumwine, Mandisa Singata-Madliki, Kim Harper, Silvia M Illamola, Naïm Bouazza, Nicolas Nagot, Philippe Van de Perre, Stéphane Blanche, Déborah Hirt
The ANRS 12174 trial assessed the efficacy and tolerance of LPV/r versus 3TC prophylaxis administered to breastfed infants, whose HIV-infected mothers were not on ART. In this sub-study, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at week 6, 26 and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters based on previously published pharmacokinetic models for HIV-infected children...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895015/protective-effects-of-human-and-mouse-soluble-scavenger-like-cd6-lymphocyte-receptor-in-a-lethal-model-of-polymicrobial-sepsis
#8
Mario Martínez-Florensa, Marta Consuegra-Fernández, Fernando Aranda, Noelia Armiger-Borràs, Marianna Di Scala, Esther Carrasco, Jerónimo Pachón, Jordi Vila, Gloria González-Aseguinolaza, Francisco Lozano
Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria, and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold-standard antibiotics, in a lethal model of polymicrobial sepsis...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895014/ceftazidime-avibactam-as-salvage-therapy-for-infections-caused-by-carbapenem-resistant-organisms-a-case-series-from-the-compassionate-use-program
#9
Elizabeth Temkin, Julian Torre-Cisneros, Bojana Beovic, Natividad Benito, Maddalena Giannella, Raúl Gilarranz, Cameron Jeremiah, Belén Loeches, Isabel Machuca, María José Jiménez-Martín, José Antonio Martínez, Marta Mora-Rillo, Enrique Navas, Michael Osthoff, Juan Carlos Pozo, Juan Carlos Ramos Ramos, Marina Rodriguez, Miguel Sánchez García, Pierluigi Viale, Michel Wolff, Yehuda Carmeli
Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895013/frequent-cross-resistance-to-dapivirine-in-hiv-1-subtype-c-infected-individuals-on-failing-first-line-antiretroviral-therapy-in-south-africa
#10
Kerri J Penrose, Carole L Wallis, Chanson J Brumme, Kristen A Hamanishi, Kelley C Gordon, Raquel V Viana, P Richard Harrigan, John W Mellors, Urvi M Parikh
BACKGROUND: A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well-defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa (SA). METHODS: Plasma samples were obtained from individuals with >10,000 copies/mL HIV RNA and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895012/a-multicenter-observational-study-of-ceftaroline-fosamil-for-methicillin-resistant-staphylococcus-aureus-bloodstream-infections
#11
Evan J Zasowski, Trang D Trinh, Kimberly C Claeys, Anthony M Casapao, Noor Sabagha, Abdalhamid M Lagnf, Kenneth P Klinker, Susan L Davis, Michael J Rybak
Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is an advanced generation cephalosporin with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed description of its use in this setting remains limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 hours of ceftaroline from 2011 to 2015...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895011/evaluation-of-fluoroquinolone-activity-against-emergence-of-resistant-salmonella-enterica-serovar-typhimurium-using-in-vitro-dynamic-models
#12
Seung-Jin Lee, Elias Gebru Awji, Na-Hye Park, Seung-Chun Park
The objectives of this study were to determine pharmacokinetic/pharmacodynamic (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) using in vitro dynamic models, and to establish mechanisms of resistance. Three fluoroquinolones, difloxacin (DIF), enrofloxacin (ENR) and marbofloxacin (MAR), at five dose levels and 3 days of treatment were simulated. Bacterial killing-regrowth kinetics and emergence of resistant bacteria after antibacterial drug- exposure were quantified...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895010/mutations-associated-with-decreased-susceptibility-to-seven-antimicrobial-families-in-field-and-laboratory-derived-mycoplasma-bovis-strains
#13
Kinga M Sulyok, Zsuzsa Kreizinger, Enikő Wehmann, Inna Lysnyansky, Krisztián Bányai, Szilvia Marton, Ákos Jerzsele, Zsuzsanna Rónai, Ibolya Turcsányi, László Makrai, Szilárd Jánosi, Sára Ágnes Nagy, Miklós Gyuranecz
The molecular mechanisms of resistance to fluoroquinolones, tetracyclines, an aminocyclitol, macrolides, a lincosamide, a phenicol and pleuromutilins were investigated in Mycoplasma bovis For the identification of mutations responsible for the high minimal inhibitory concentrations (MICs) to certain antibiotics, whole genome sequencing of 35 M. bovis field isolates and 36 laboratory-derived antibiotic resistant mutants was performed. In vitro resistant mutants were selected by serial passages of M. bovis in broth medium containing subinhibitory concentrations of the antibiotics...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895009/an-incp-plasmid-carrying-the-colistin-resistance-gene-mcr-1-in-klebsiella-pneumoniae-from-hospital-sewage
#14
Feifei Zhao, Yu Feng, Xiaoju Lü, Alan McNally, Zhiyong Zong
A Klebsiella pneumoniae strain of ST313 recovered from hospital sewage was found to carry the plasmid-borne colistin resistance gene mcr-1, which was bracketed by two copies of the insertion sequence ISApl1 on a 57-kb self-transmissible IncP type plasmid of a new IncP-1 clade. The carriage of mcr-1 on a self-transmissible broad-host-range plasmid highlights that mcr-1 has the potential to be spread beyond the Enterobacteriaceae.
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27895008/de-novo-emergence-of-genetically-resistant-mutants-of-mycobacterium-tuberculosis-from-the-persistence-phase-cells-formed-against-antituberculosis-drugs-in-vitro
#15
Jees Sebastian, Sharmada Swaminath, Rashmi Ravindran Nair, Kishor Jakkala, Atul Pradhan, Parthasarathi Ajitkumar
Bacterial persisters are a subpopulation of cells that can tolerate lethal concentrations of antibiotics. However, the possibility of the emergence of genetically resistant mutants from antibiotic persister cell population, upon continued exposure to lethal concentrations of antibiotics, remained unexplored. In the present study, we found that Mycobacterium tuberculosis (Mtb) cells exposed continuously to lethal concentrations of rifampicin (RIF) or moxifloxacin (MXF) for prolonged durations showed killing, RIF/MXF persistence, and regrowth phases...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872081/novel-effects-of-lapatinib-revealed-in-the-african-trypanosome-using-hypothesis-generating-proteomics-and-chemical-biology-strategies
#16
Paul J Guyett, Ranjan Behera, Yuko Ogata, Michael Pollastri, Kojo Mensa-Wilmot
Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei Lapatinib, a human epidermal growth factor receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases associate with lapatinib, suggesting the drug may be a multi-targeted inhibitor of phosphoprotein signaling in the bloodstream trypanosome. Phosphoprotein signaling pathways in T. brucei have diverged significantly from those in humans...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872080/classical-%C3%AE-lactamase-inhibitors-potentiate-the-activity-of-daptomycin-against-methicillin-resistant-staphylococcus-aureus-and-colistin-against-acinetobacter-baumannii
#17
George Sakoulas, Warren Rose, Andrew Berti, Joshua Olson, Jason Mungia, Poochit Nonejuie, Eleanna Sakoulas, Michael J Rybak, Joseph Pogliano, Victor Nizet
We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), peptide antibiotic colistin (COL) against emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA) and heterogeneous-VISA (hVISA). COL and LL37 kill curves were performed against A...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872079/the-paradoxical-effect-of-echinocandins-in-aspergillus-fumigatus-relies-on-recovery-of-the-%C3%AE-1-3-glucan-synthase-fks1
#18
Veronika Loiko, Johannes Wagener
Echinocandins target the fungal cell wall by inhibiting biosynthesis of the cell wall carbohydrate β-1,3-glucan. This antifungal drug class exhibits a paradoxical effect which is characterized by the resume of growth of otherwise susceptible strains at higher drug concentrations (approx.4-32 μg/ml). The nature of this phenomenon is still unknown. In this study, we analyzed the paradoxical effect of the echinocandin caspofungin on the pathogenic mold Aspergillus fumigatus Using a conditional fks1 mutant, we show that very high caspofungin concentrations exert an additional antifungal activity beside inhibition of the β-1,3-glucan synthase...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872078/polymyxin-b-in-combination-with-rifampin-and-meropenem-against-polymyxin-b-resistant-kpc-producing-klebsiella-pneumoniae
#19
John Diep, David M Jacobs, Rajnikant Sharma, Jenna Covelli, Dana R Bowers, Thomas A Russo, Gauri G Rao
Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing K. pneumoniae and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae The rate and extent of killing with polymyxin B (1-128mg/L), rifampin (2-16mg/L), and meropenem (10-120mg/L) were evaluated against polymyxin B-susceptible (PB(S)) and -resistant (PB(R)) clinical isolates using 48h static time-kills...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872077/identification-of-inca-c-plasmid-replication-and-maintenance-genes-and-development-of-a-plasmid-multi-locus-sequence-typing-scheme
#20
Steven J Hancock, Minh-Duy Phan, Kate M Peters, Brian M Forde, Teik Min Chong, Wai-Fong Yin, Kok-Gan Chan, David L Paterson, Timothy R Walsh, Scott A Beatson, Mark A Schembri
Plasmids of incompatibility group IncA/C are becoming increasingly prevalent within pathogenic Enterobacteriaceae. They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multi-drug resistant uropathogenic Escherichia coli strain. Hyper-saturated transposon mutagenesis, coupled with transposon directed insertion site sequencing (TraDIS) was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A...
November 21, 2016: Antimicrobial Agents and Chemotherapy
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