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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/29038284/evaluation-of-the-microbiological-efficacy-of-a-single-2-g-dose-of-an-extended-release-azithromycin-by-population-pharmacokinetics-and-simulation-in-japanese-patients-with-gonococcal-urethritis
#1
Midori Soda, Shin Ito, Naoki Matsumaru, Sakiko Nakamura, Izumi Nagase, Hikari Takahashi, Yuta Ohno, Mitsuru Yasuda, Miho Yamamoto, Katsura Tsukamoto, Yoshinori Itoh, Takashi Deguchi, Kiyoyuki Kitaichi
The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2 g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy on gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, AZM minimum inhibitory concentration (MIC) values for Neisseria gonorrhoeae isolates were determined, and microbiological outcomes were assessed...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038283/ctx-m-15-producing-shewanella-sp-clinical-isolate-expressing-oxa-535-a-chromosome-encoded-oxa-48-variant-putative-progenitor-of-the-plasmid-encoded-oxa-436
#2
Agnès B Jousset, Laura Dabos, Rémy A Bonnin, Delphine Girlich, Anaïs Potron, Nicolas Cabanel, Laurent Dortet, Philippe Glaser, Thierry Naas
Shewanella spp. constitute a reservoir of antibiotic resistance determinants. In a bile sample, we have identified three Extended Spectrum β-lactamase (ESBL)-producing bacteria (Escherichia coli, Klebsiella pneumoniae and Shewanella sp. JAB-1) isolated from a child suffering from cholangitis. Our objectives were to characterize the genome and the resistome of the first ESBL-producing isolate of the genus Shewanella and determine whether plasmidic exchange occurred between the three-bacterial species. Bacterial isolates were characterized using MALDI-TOF, standard biochemical tools and antimicrobial susceptibility testing...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038282/intracellular-tenofovir-diphosphate-and-emtricitabine-triphosphate-in-dried-blood-spots-following-directly-observed-therapy-the-dot-dbs-study
#3
Peter L Anderson, Albert Y Liu, Jose R Castillo-Mancilla, Edward M Gardner, Sharon M Seifert, Cricket McHugh, Theresa Wagner, Kayla Campbell, Mary Morrow, Mustafa Ibrahim, Susan Buchbinder, Lane R Bushman, Jennifer J Kiser, Samantha MaWhinney
Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, cross-over pharmacokinetic study of TFV-DP in DBS during 33%, 67% or 100% of daily dosing, under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038281/putative-integrative-mobile-elements-that-exploit-the-xer-recombination-machinery-carrying-blaimi-type-carbapenemase-genes-in-the-enterobacter-cloacae-complex-in-singapore
#4
Tse H Koh, Nurdyana Binte Abdul Rahman, Jeanette W P Teo, My-Van La, Balamurugan Periaswamy, Swaine L Chen
Whole genome sequencing was performed on 16 isolates of carbapenemase-producing Enterobacter cloacae complex to determine the flanking regions of blaIMI-type genes. Phylogenetic analysis of MLST targets separated the isolates into 4 clusters. The blaIMI-type genes were all found on IMEX elements. The IMEX elements of 5 isolates were similar to those described in Canada, while the remainder were novel. Five isolates had IMEX elements lacking a resolvase and recombinase.
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038280/targeting-human-cytomegalovirus-infected-cells-by-redirecting-t-cells-using-an-anti-cd3-anti-gb-bispecific-antibody
#5
Weixu Meng, Aimin Tang, Xiaohua Ye, Xun Gui, Leike Li, Xuejun Fan, Robbie D Schultz, Daniel C Freed, Sha Ha, Dai Wang, Ningyan Zhang, Tong-Ming Fu, Zhiqiang An
Host immune response to human cytomegalovirus (HCMV) is effective against HCMV reactivation from latency although not sufficient to clear the virus. T cells are primarily responsible for control of the viral reactivation. When host immune system is compromised, as in transplant recipients with immunosuppression, HCMV reactivation and progressive infection can cause serious morbidity and mortality. Adoptive T cell therapy is effective for control of HCMV infection in transplant recipients. However, it is a highly personalized therapeutic regimen, and difficult to implement in routine clinical practice...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038279/a-ctg-clade-candida-yeast-genetically-engineered-for-the-genotype-phenotype-characterization-of-azole-antifungal-resistance-in-human-pathogenic-yeasts
#6
Isabelle Accoceberry, Amandine Rougeron, Nicolas Biteau, Pauline Chevrel, Valérie Fitton-Ouhabi, Thierry Noël
A strain of the opportunistic pathogenic yeast Candida lusitaniae was genetically modified for its use as a cellular model for assessing by allele replacement the impact of lanosterol C14α-demethylase ERG11 mutations on azole resistance. Candida lusitaniae was chosen because it is susceptible to azole antifungals, it belongs to the CTG clade of yeast which includes most of the Candida species pathogenic for humans, and it is haploid and easily amenable to genetic transformation and molecular modeling. In this work, allelic replacement is targeted at the ERG11 locus by the reconstitution of a functional auxotrophic marker in the 3' intergenic region of ERG11 Homologous and heterologous ERG11 alleles are expressed from the resident ERG11 promoter of C...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038278/fidaxomicin-and-op-1118-inhibit-c-difficile-toxin-a-and-b-mediated-inflammatory-responses-via-inhibition-of-nf-%C3%AE%C2%BAb-activity
#7
Hon Wai Koon, Jiani Wang, Caroline C Mussatto, Christina Ortiz, Elaine C Lee, Diana Hoang-Ngoc Tran, Xinhua Chen, Ciaran P Kelly, Charalabos Pothoulakis
Objective:Clostridium difficile causes diarrhea and colitis by releasing toxin A and toxin B. In the human colon, both toxins cause intestinal inflammation and stimulate TNFα expression via activation of NF-κB. It is well established that the macrolide antibiotic fidaxomicin is associated with reduced relapses of C. difficile infection. We showed that fidaxomicin and its primary metabolite, OP-1118, significantly inhibited toxin A-mediated intestinal inflammation in mice in vivo and toxin A-induced cell rounding in vitro We aim to determine whether fidaxomicin and OP-1118 possess anti-inflammatory effects against toxin A and toxin B in the human colon and examine the mechanism of this response...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038277/dilution-factor-of-quantitative-bacterial-cultures-obtained-by-bronchoalveolar-lavage-in-patients-with-ventilator-associated-bacterial-pneumonia-implications-for-optimal-antimicrobial-therapy-ventilator-associated-bacterial-pneumonia-study-group
#8
George L Drusano, Michael L Corrado, Gino Girardi, Evelyn J Ellis-Grosse, Richard G Wunderink, Helen Donnelly, Kenneth V Leeper, Mona Brown, Tasnova Malek, Robert Duncan Hite, Michelle Ferrari, Danijela Djureinovic, Marin H Kollef, Lisa Mayfield, Ann Doyle, Jean Chastre, Alain Combes, Thomas J Walsh, Krisztina Dorizas, Hassan Alnuaimat, Brooks Edward Morgan, Jordi Rello, Cristopher Alan Mazo Torre, Ronald N Jones, Robert K Flamm, Leah Woosley, Paul G Ambrose, Sujata Bhavnani, Christopher M Rubino, Catharine C Bulik, Arnold Louie, Michael Vicchiarelli, Colleen Berman
Ventilator-Associated Bacterial Pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent IDSA/ATS guidelines recommended a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence and fewer antibiotic days counterbalanced with a higher relapse rate for patients whose pathogen is a non-fermenter. The bacterial burden causing an infection will have a substantial impact on treatment outcome and resistance selection...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038276/reduced-chlorhexidine-and-daptomycin-susceptibility-in-vancomycin-resistant-enterococcus-faecium-after-serial-chlorhexidine-exposure
#9
Pooja Bhardwaj, Amrita Hans, Kinnari Ruikar, Ziqiang Guan, Kelli L Palmer
Vancomycin-resistant Enterococcus faecium (VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a bisbiguanide cationic antiseptic that is routinely used for patient bathing and other infection control practices. VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX exposure have not been studied in enterococci. In this study, we serially exposed VREfm to increasing concentrations of CHX for a period of 21 days in two independent experimental evolution trials...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038275/in-vivo-bioluminescent-monitoring-of-therapeutic-efficacy-and-pharmacodynamic-target-assessment-of-antofloxacin-against-escherichia-coli-in-a-neutropenic-murine-thigh-infection-model
#10
Yu-Feng Zhou, Meng-Ting Tao, Yu-Zhang He, Jian Sun, Ya-Hong Liu, Xiao-Ping Liao
Antimicrobial resistance among uropathogens has increased infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescence imaging and determined pharmacokinetic/pharmacodynamic (PK/PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were performed after subcutaneous antofloxacin administration of 2...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038274/thrombocytopenia-with-tedizolid-and-linezolid
#11
Erica Yookyung Lee, Aisling Caffrey
Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved 06/2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration Adverse Event Reporting System (07/2014-12/2016), we observed a significantly increased risk of thrombocytopenia of similar magnitude with both antibiotics: linezolid reporting odds ratio [ROR] 37.9 (95% confidence interval [CI] 20.78-69.17); tedizolid ROR 34...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038273/pharmacokinetic-modelling-of-voriconazole-to-develop-an-alternative-dosing-regimen-in-children
#12
Silke Gastine, Thomas Lehrnbecher, Carsten Müller, Fedja Farowski, Peter Bader, Judith Ullmann-Moskovits, Oliver A Cornely, Andreas H Groll, Georg Hempel
Background. The pharmacokinetic variability of voriconazole in immunocompromised children is high and adequate exposure, particularly in the first days of therapy, is uncertain.Methods A population pharmacokinetic model was developed to explore VCZ exposure in plasma after alternative dosing regimens. Concentration data were obtained from a pediatric phase II study. Non-linear mixed effects modelling was used to develop the model. Monte Carlo simulations were performed to test an array of three times daily (TID) intravenous dosing regimens in children 2 to 12 years of age...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038272/population-pharmacokinetic-analysis-of-cefiderocol-a-parenteral-siderophore-cephalosporin-in-healthy-subjects-subjects-with-varying-renal-function-and-patients-with-complicated-urinary-tract-infection-or-acute-uncomplicated-pyelonephritis
#13
Nao Kawaguchi, Takayuki Katsube, Roger Echols, Toshihiro Wajima
Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria including carbapenem-resistant strains. The aim of this study is to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with varying renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens, and to calculate the fraction of time during the dosing interval where the free drug concentration in plasma exceeds the minimum inhibitory concentration (MIC) (fT>MIC)...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038271/evaluation-of-antifungal-efficacy-of-three-new-cyclic-lipopeptides-of-the-class-bacillomycin-from-bacillus-subtilis-rlid-12-1
#14
Ramya R, Manjari Shrivastava, Namitha N N, Ram Lal Thakur, Arunaloke Chakrabarti, Utpal Roy
New lipopeptide homologues (AF3, AF4 and AF5) with antifungal activities against Candida and Cryptococcus spp. were purified from the cell free supernatant of Bacillus subtilis RLID 12.1. The lipopeptides AF3, AF4 and AF5 were identified with the same peptide sequence Asn-Pro-Tyr-Asn-Gln-Thr-Ser with variations in the fatty acid branching type and chain length (anteiso-C17, iso-C17 and iso-C18 respectively). Comparing the three homologues for minimum inhibitory concentrations (MIC) against 81 Candida (64 no...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038270/activity-of-meropenem-vaborbactam-against-carbapenem-resistant-enterobacteriaceae-in-a-murine-model-of-pyelonephritis
#15
William J Weiss, Mark E Pulse, Phung Nguyen, Kelly Peterson, Jessica Silva, Jerry W Simecka, David Valtierra, Mojgan Sabet, David C Griffith
The recently approved combination of meropenem-vaborbactam (Vabomere™) is highly active against Gram-negative pathogens, especially KPC-producing, carbapenem-resistant Enterobacteriaceae We evaluated the efficacy of meropenem-vaborbactam against three clinically relevant isolates in a murine polynephritis model. Data indicated that the combination of meropenem-vaborbactam significantly increased the bacterial killing compared to the untreated controls. These data suggest that this combination may have utility in the treatment of complicated urinary tract infections due to KPC-producing, carbapenem-resistant Enterobacteriaceae...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038269/clinical-epidemiology-of-carbapenem-resistant-enterobacteriaceae-a-systematic-review-and-meta-analyses
#16
Karlijn van Loon, Anne F Voor In 't Holt, Margreet C Vos
Carbapenem-resistant Enterobacteriaceae (CRE) are major healthcare-associated pathogens and responsible for hospital outbreaks worldwide. To prevent a further increase in CRE infections and to improve infection prevention strategies, it is important to summarize the current knowledge about CRE prevention in hospital settings. This systematic review aimed to identify risk factors for CRE acquisition among hospitalized patients. In addition, we summarized environmental sources/reservoirs and the most successful infection prevention strategies related to CRE...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038268/urinary-tract-conditions-affect-fosfomycin-activity-against-escherichia-coli-strains-harboring-chromosomal-mutations-involved-in-fosfomycin-uptake
#17
G Martín-Gutiérrez, F Docobo-Pérez, J Rodriguez-Beltrán, J M Rodríguez-Martínez, J Aznar, A Pascual, J Blázquez
The steps by which Escherichia coli strains harboring mutations related with fosfomycin (FOS) resistance arise and spread during urinary tract infections (UTI) is far to be understood. The aim of this study was to evaluate the effect of urine, pH and anaerobiosis on FOS activity against a set of isogenic strains carrying the most prevalent chromosomal mutations conferring FOS-resistance (ΔuhpT, ΔglpT, ΔcyaA and ΔptsI) and their combinations. Also, fosfomycin resistant E. coli clinical isolates from patients with UTI were studied...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038267/a-retrospective-analysis-of-treatment-and-clinical-outcomes-among-patients-with-methicillin-susceptible-staphylococcus-aureus-bloodstream-isolates-possessing-detectable-meca-by-a-commercial-pcr-assay-compared-to-patients-with-methicillin-resistant-staphylococcus
#18
Dylan Jones, Ramy H Elshaboury, Erik Munson, Thomas J Dilworth
mecA-positive Staphylococcus aureus isolates phenotypically susceptible to cefoxitin (mecA-MSSA) have been identified. We describe treatment and outcomes among patients with mecA-MSSA bloodstream infections (BSI) and MRSA BSI patients matched 1:1 on age, BSI origin and BSI type (n=17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often experienced clinical failure (58.8% and 11.8%, p=0.010), driven largely by persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher risk for poor clinical outcomes...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038266/potency-of-meropenem-vaborbactam-in-lung-surfactant
#19
Debora Rubio-Aparicio, Jeff Loutit, Michael Dudley, Olga Lomovskaya
This study investigated whether pulmonary surfactant has an effect on the in vitro antibacterial activity of either meropenem alone or meropenem in combination with vaborbactam at a fixed concentration of 8 μg/mL against several Klebsiella pneumoniae carbapenemase (KPC)-producing strains of gram-negative bacteria. Results showed that the potency of meropenem alone and meropenem-vaborbactam were not affected when tested with pulmonary surfactant.
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038265/verapamil-increases-the-bioavailability-and-efficacy-of-bedaquiline-but-not-clofazimine-in-a-murine-model-of-tuberculosis
#20
Jian Xu, Rokeya Tasneen, Charles A Peloquin, Deepak V Almeida, Si-Yang Li, Kala Barnes-Boyle, Yu Lu, Eric Nuermberger
Drug efflux pumps play an important role in intrinsic and acquired drug resistance. Verapamil, an efflux inhibitor that enhances the activity of bedaquiline, clofazimine and other drugs against Mycobacterium tuberculosis has been proposed as a potential adjunctive agent for treatment of tuberculosis (TB). However, the extent to which verapamil enhances in vivo efficacy by inhibiting bacterial efflux pumps versus inhibiting mammalian drug transporters to improve oral bioavailability has not been delineated. We found that verapamil potentiated the in vitro activity of bedaquiline and clofazimine against M...
October 16, 2017: Antimicrobial Agents and Chemotherapy
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