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Antimicrobial Agents and Chemotherapy

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https://www.readbyqxmd.com/read/29229643/cystatin-9-and-c-a-novel-immunotherapy-that-protects-against-multi-drug-resistant-new-delhi-metallo-beta-lactamase-1-producing-klebsiella-pneumoniae
#1
Alex J Holloway, JiehJuen Yu, Bernard P Arulanandam, Sarah M Hoskinson, Tonyia Eaves-Pyles
Multidrug-resistant (MDR) bacterial pneumonia can induce dysregulated pulmonary and systemic inflammation leading to morbidity and mortality. Antibiotics to treat MDR pathogens do not function to modulate the extent and intensity of inflammation and can have serious side effects. Herein, we evaluate the efficacy of two human cysteine proteinase inhibitors, cystatin 9 and cystatin C, as a novel immunotherapeutic treatment to combat MDR New Delhi metallo-beta-lactamase-1 (NDM-1) producing Klebsiella pneumoniae (Kp)...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229642/suppression-of-reactive-oxygen-species-accumulation-accounts-for-paradoxical-bacterial-survival-at-high-quinolone-concentration
#2
Gan Luan, Yuzhi Hong, Karl Drlica, Xilin Zhao
When bacterial cells are exposed to increasing concentrations of quinolone-class antibacterials, survival drops, reaches a minimum, and then recovers, sometimes to 100%. Despite decades of study, events underlying the paradoxical, high-concentration survival remain obscure. Since reactive oxygen species (ROS) have been implicated in antimicrobial lethality, conditions generating paradoxical survival were examined for diminished ROS accumulation. Escherichia coli cultures were treated with various concentrations of nalidixic acid, followed by measurement of survival, rate of protein synthesis, and ROS accumulation...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229641/hyperbaric-oxygen-reduces-aspergillus-fumigatus-proliferation-in-vitro-and-influences-in-vivo-disease-outcomes
#3
Sourabh Dhingra, Jay C Buckey, Robert A Cramer
Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, developing new clinical modalities as standalone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we test the in vitro and in vivo impact of hyperbaric oxygen (100% oxygen, >1 ATA) (HBO) on A...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229640/adverse-effects-of-intravenous-vancomycin-based-prophylaxis-during-therapy-for-pediatric-acute-myeloid-leukemia
#4
Yilun Sun, Rachael L Huskey, Li Tang, Hiroto Inaba, Aditya H Gaur, Raul Ribeiro, Jeffrey E Rubnitz, Joshua Wolf
Background Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infection, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk, but might increase risk of renal or liver toxicity, or Clostridium difficile infection (CDI).Methods A retrospective review was conducted of patients treated for newly diagnosed AML at St. Jude Children's Research Hospital from 2002 to 2008. Nephrotoxicity was classified according to pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE) criteria, and hepatotoxicity according to Common Terminology Criteria for Adverse Events criteria...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229639/whole-cell-screen-of-fragment-library-identifies-gut-microbiota-metabolite-indole-propionic-acid-as-antitubercular
#5
Dereje A Negatu, Joe J J Liu, Matthew Zimmerman, Firat Kaya, Véronique Dartois, Courtney C Aldrich, Martin Gengenbacher, Thomas Dick
Several key tuberculosis drugs including pyrazinamide, with a molecular weight of 123.1 g/mol, are smaller than the usual drug like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular weights centered around 400-500 g/mol. Fragment (molecular weight < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1000 fragments, present in the Maybridge Ro3 library, for whole cell activity against Mycobacterium tuberculosis Twenty-nine primary hits showed dose-dependent growth inhibition equal or better than pyrazinamide...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229638/sequencing-of-fks-hot-spot1-from-saprochaete-capitata-searching-for-a-relationship-with-reduced-echinocandin-susceptibility
#6
Inés Arrieta-Aguirre, Pilar Menéndez-Manjón, María Soledad Cuétara, Iñigo Fernández de Larrinoa, Juan Carlos García-Ruiz, María Dolores Moragues
Saprochaete capitata, formerly known as Geotrichum capitatum, is an emerging fungal pathogen with low susceptibility to echinocandins. Here, we report the nucleotide sequence of the S. capitata Hot Spot 1 region of the FKS gene (FKS HS1) which codifies for the catalytic subunit of β-1,3-D-glucan synthase, the target of echinocandins. For that purpose, we firstly designed degenerated oligonucleotide primers derived from conserved flanking regions of the FKS1 HS1 segment of 12 different fungal species. Interestingly, the analysis of the translated FKS HS1 sequences of 12 isolates of S...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229637/elucidating-the-pharmacokinetics-pharmacodynamics-of-aerosolized-colistin-against-multidrug-resistant-acinetobacter-baumannii-and-klebsiella-pneumoniae-in-a-mouse-lung-infection-model
#7
Yu-Wei Lin, Qi Tony Zhou, Mei-Ling Han, Ke Chen, Nikolas J Onufrak, Jiping Wang, John D Turnidge, Benjamin P Howden, Alan Forrest, Hak-Kim Chan, Jian Li
Pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. AUC/MIC in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229636/topical-antibiotic-use-co-selects-for-the-carriage-of-mobile-genetic-elements-conferring-resistance-to-unrelated-antimicrobials-in-staphylococcus-aureus
#8
Glen P Carter, Mark B Schultz, Sarah L Baines, Anders Goncalves da Silva, Helen Heffernan, Audrey Tiong, Peter H Pham, Ian R Monk, Timothy P Stinear, Benjamin P Howden, Deborah A Williamson
Topical antibiotics such as mupirocin and fusidic acid are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229635/plasmodium-falciparum-recrudescence-two-years-after-a-first-treated-uncomplicated-infection-without-return-in-a-malaria-endemic-area
#9
Denis Malvy, Marylin Torrentino-Madamet, Coralie L'Ollivier, Marie-Catherine Receveur, Fakhri Jeddi, Laurence Delhaes, Renaud Piarroux, Pascal Millet, Bruno Pradines
We report here evidence, confirmed by the lack of travel activity outside of France and genetic diversity analysis using polymorphic microsatellite markers, that Plasmodium falciparum malaria infection effectively treated with an artemisinin-based combination can remain dormant and relapse during pregnancy at least 2 years after treatment.
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29229634/genomic-insights-into-colistin-resistant-klebsiella-pneumoniae-from-a-tunisian-teaching-hospital
#10
Nadia Jaidane, Rémy A Bonnin, Wejdene Mansour, Delphine Girlich, Elodie Creton, Garance Colleton, Cherifa Chaouch, Noureddine Boujaafar, Olfa Bouallegue, Thierry Naas
The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a public health concern since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) gram-negatives. In this study, we have investigated the molecular basis of colistin-resistance in 13 MDR Kp isolated from 12 patients in a teaching hospital in Sousse, Tunisia. Whole-genome sequencing (WGS) was used to decipher the molecular mechanism of colistin-resistance and to identify the resistome of these CoRKp It revealed a genome of ca...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203495/pa5470-counteracts-antimicrobial-effect-of-azithromycin-by-releasing-stalled-ribosome-in-pseudomonas-aeruginosa
#11
Jing Shi, Yiwei Liu, Yueying Zhang, Yongxin Jin, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu
Pseudomonas aeruginosa causes various acute and chronic infections in human. Treatment with azithromycin (AZM) has been shown to benefit patients with chronic P. aeruginosa infections. By binding to the exit tunnel of 50S ribosome, AZM causes ribosome stalling and depletion of intracellular tRNA pool. It has been shown that AZM is able to kill stationary-phase P. aeruginosa cells and repress quorum sensing regulated virulence factors as well as swarming motility. In P. aeruginosa, PA5470 encodes a putative peptide chain release factor, whose expression is highly induced by macrolide antibiotics...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203494/polymyxin-b-and-zti-01-fosfomycin-for-injection-against-kpc-producing-klebsiella-pneumoniae-evaluation-of-activity-and-emergence-of-resistance
#12
John K Diep, Rajnikant Sharma, Evelyn J Ellis-Grosse, Cely S Abboud, Gauri G Rao
ZTI-01 (fosfomycin for injection) is a broad spectrum antibiotic with a novel mechanism of action and is currently under development in the USA for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multi-drug resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing K. pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203493/a-prospective-trial-on-the-use-of-trough-concentration-versus-area-under-the-curve-auc-to-determine-therapeutic-vancomycin-dosing
#13
Michael N Neely, Lauren Kato, Gilmer Youn, Lironn Kraler, David Bayard, Michael van Guilder, Alan Schumitzky, Walter Yamada, Brenda Jones, Emi Minejima
We hypothesized that dosing vancomycin to achieve trough concentrations >15 mg/L overdoses many adults compared to AUC-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, non-study clinicians targeted trough concentrations of 10-20 mg/L (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with the BestDose Bayesian software to achieve a daily, steady-state AUC:MIC≥400, with maximum AUC 800 mg*h/L, regardless of trough concentration...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203492/extreme-drug-tolerance-of-mycobacterium-tuberculosis-in-caseum
#14
Jansy P Sarathy, Laura E Via, Danielle Weiner, Landry Blanc, Helena Boshoff, Eliseo A Eugenin, Clifton E Barry, Véronique A Dartois
Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence and drug tolerance are among the factors driving the long therapy duration. Assays to measure in situ drug susceptibility of Mycobacterium tuberculosis (Mtb) bacteria in pulmonary lesions are needed if we are to discover new fast acting regimens and address the global TB threat. Here we take a first step towards this goal and describe an ex vivo assay developed to measure the cidal activity of anti-TB drugs against Mtb bacilli present in cavity caseum, obtained from rabbits with active TB...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203491/chemogenomic-profiling-of-the-fungal-pathogen-candida-albicans
#15
Yaolin Chen, Jaideep Mallick, Alaa Maqnas, Yuan Sun, Baharul I Choudhury, Pierre Cote, Lan Yan, Ting-Jun-Hong Ni, Yan Li, Dazhi Zhang, Roberto Rodríguez-Ortiz, Quan-Zhen Lv, Yuan-Ying Jiang, Malcolm Whiteway
There are currently a small number of classes of antifungal drugs, and these drugs are known to target a very limited set of cellular functions. We derived a set of approximately 900 non-essential, transactivator-defective disruption strains from the tetracycline regulated GRACE strain collection of the fungal pathogen Candida albicans This strain set was screened against classic antifungal drugs to identify gene inactivations that conferred either enhanced sensitivity or increased resistance to the compounds...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203490/mutations-in-genes-encoding-penicillin-binding-proteins-and-efflux-pumps-play-a-role-in-%C3%AE-lactam-resistance-in-helicobacter-cinaedi
#16
Emiko Rimbara, Shigetarou Mori, Hyun Kim, Masato Suzuki, Keigo Shibayama
β-Lactams are often used to treat Helicobacter cinaedi infections; however, the mechanism underlying β-lactam resistance is unknown. In this study, we investigated β-lactam resistance in a H. cinaedi strain, MRY12-0051 (MIC of AMX and CRO: 32 and 128 μg/ml; obtained from human feces). Based on a comparative whole genome analysis of MRY12-0051 and the CRO-susceptible H. cinaedi strain MRY08-1234 (MIC of AMX and CRO: 1 and 4 μg/ml; obtained from human blood), we identified five mutations in genes encoding penicillin-binding proteins (PBPs), including two in pbpA, one in pbp2, and two in ftsI Transformation and penicillin-binding assays indicated that CRO resistance was mainly associated with mutations in pbpA; mutations in ftsI also led to increased resistance to AMX...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203489/distribution-and-molecular-characterization-of-acinetobacter-baumannii-international-clone-ii-lineage-in-japan
#17
Mari Matsui, Masato Suzuki, Masahiro Suzuki, Jun Yatsuyanagi, Masanori Watahiki, Yoichi Hiraki, Fumio Kawano, Atsuko Tsutsui, Keigo Shibayama, Satowa Suzuki
Multidrug-resistant (MDR) Acinetobacter spp. have been globally disseminated in association with successful clonal lineage Acinetobacter baumannii international clone II (IC II). Because the prevalence of MDR Acinetobacter spp. in Japan remains very low, we characterized all Acinetobacter spp. (n=866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology of Acinetobacter spp. The most prevalent species was A. baumannii (n = 645; 74.5%), with A. baumannii IC II (n = 245) accounting for 28...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203488/epidemiology-of-carbapenem-resistant-enterobacteriaceae-infections-report-from-china-cre-network
#18
Yawei Zhang, Qi Wang, Yuyao Yin, Hongbin Chen, Longyang Jin, Bing Gu, Liangyi Xie, Chunxia Yang, Xiaobo Ma, Huayin Li, Wei Li, Xiaoqian Zhang, Kang Liao, Sijin Man, Shifu Wang, Hainan Wen, Binbin Li, Zhusheng Guo, Jinjing Tian, Fengyan Pei, Li Liu, Lijun Zhang, Cuimei Zou, Tongping Hu, Jun Cai, Hong Yang, Jiaming Huang, Xianghong Jia, Wenhui Huang, Bin Cao, Hui Wang
Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of infection burden are lacking. We established incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem non-susceptible C. freundii, E. coli, E. cloacae, or K. pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase genes identification were performed...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203487/role-of-smeu1vwu2x-operon-in-the-alleviation-of-oxidative-stresses-and-the-occurrence-of-sulfamethoxazole-trimethoprim-resistant-mutants-in-stenotrophomonas-maltophilia
#19
Chao-Jung Wu, Tsu-Ting Chiu, Yi-Tsung Lin, Yi-Wei Huang, Li-Hua Li, Tsuey-Ching Yang
Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an important mechanism for bacteria to combat antimicrobials. RND efflux pumps are also critical for bacterial physiology such as oxidative stress tolerance. Stenotrophomonas maltophilia, a multi-drug resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of them, smeU1VWU2X operon is unique for its possession of two additional genes, smeU1 and smeU2, which encode proteins of short-chain dehydrogenase/reductase (SDR) family...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203486/in-vitro-in-silico-and-in-vivo-analysis-of-novel-aromatic-amidines-against-trypanosoma-cruzi
#20
Camila C Santos, Jéssica R Lionel, Raiza B Peres, Marcos M Batista, Patrícia B da Silva, Gabriel M de Oliveira, Cristiane F da Silva, Denise G J Batista, Sandra Maria O Souza, Carolina H Andrade, Bruno J Neves, Rodolpho C Braga, Donald A Patrick, Svetlana M Bakunova, Richard R Tidwell, Maria de Nazaré C Soeiro
Five bis-arylimidamides were assayed as anti-T.cruzi agents using in vitro, in silico and in vivo approaches. All were considered no PAINS, have favorable pharmacokinetic landscape, were active against trypomastigotes and intracellular forms but combined with benznidazole gave no interaction. The most selective (28SMB032) moved to in vivo led to 40% parasitemia reduction (0.1mg/kg/5 days by ip) but without mortality protection. In silico target fishing suggested DNA as main target, but ultrastructural data did not match...
December 4, 2017: Antimicrobial Agents and Chemotherapy
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