Comparison of the Superpolymyxin ™ and CHROMID® Colistin R screening media for the detection of colistin-resistant Enterobacteriaceae from spiked rectal swabs.
In this study we evaluated the performances of the Superpolymyxin™medium (ELITechGroup) and the CHROMID® Colistin R (bioMérieux) to screen for colistin-resistant Enterobacteriaceae from spiked rectal swabs. Stools were spiked with a total of 94 enterobacterial isolates (Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Enterobacter cloacae), including 53 colistin-resistant isolates. ESwabs™(Copan Diagnostics) were then inoculated with those spiked fecal suspensions and proceed as recommended by both manufacturers. The sensitivity of detection colistin-resistant Enterobacteriaceae were of ...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Girlich D, Naas T, Dortet L Tags: Antimicrob Agents Chemother Source Type: research

Genomic Characterization of Carbapenemase-producing Klebsiella pneumoniae with Chromosomally Encoded bla NDM-1.
We report here the K. pneumoniae strains carrying chromosomal bla NDM-1 in Thailand. The genomes of these two isolates include a 160-kbp insertion containing bla NDM-1, which is almost identical to that in the IncHI1B-like plasmid. Further analysis indicated that IS5-mediated intermolecular transposition and Tn3-transposase-mediated homologous recombination resulted in the integration of bla NDM-1 into the chromosome from an IncHI1B-like plasmid. The spread of this type of carbapenem-resistant Enterobacteriaceae may threaten public health and warrants further monitoring. PMID: 30323033 [PubMed - as supplied by publish...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Sakamoto N, Akeda Y, Sugawara Y, Takeuchi D, Motooka D, Yamamoto N, Laolerd W, Santanirand P, Hamada S Tags: Antimicrob Agents Chemother Source Type: research

Efficacy of antifungal monotherapies and combinations against Aspergillus calidoustus.
Abstract Invasive fungal infections due to Aspergillus calidoustus with decreased azole susceptibility are emerging in the setting of azole prophylaxis and are associated with poor outcomes. We assessed the in vitro activity of antifungal drugs used alone or in combinations against A. calidoustus and found a synergistic effect between voriconazole and terbinafine at concentrations within the therapeutic range. An invertebrate Galleria mellonella model of A. calidoustus infection tended to support the potential benefit of this combination. PMID: 30323034 [PubMed - as supplied by publisher] (Source: Antimicrobi...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Glampedakis E, Coste AT, Aruanno M, Bachmann D, Delarze E, Erard V, Lamoth F Tags: Antimicrob Agents Chemother Source Type: research

New Treatment Options Against Carbapenem-Resistant Acinetobacter baumannii Infections.
This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late stage pre-clinical studies for the treatment of CRAB and evaluates their expected benefits and potential shortcomings. PMID: 30323035 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Isler B, Doi Y, Bonomo RA, Paterson DL Tags: Antimicrob Agents Chemother Source Type: research

Pse-T2, an antimicrobial peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-resistant Pseudomonas aeruginosa infection.
Abstract Pseudin-2, isolated from the frog Pseudis paradoxa, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable AMPs, we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. In addition, truncated analogs of pseudin-2 and Lys-substituted peptides were synthesized to produce linear 18-residue amphipathic α-helices, which were further investigated for their mechanism and functions. These truncated analogs exhibited higher antimicrobial activity and lower cytotoxicity than pseudin-...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Kang HK, Seo CH, Luchian T, Park Y Tags: Antimicrob Agents Chemother Source Type: research

Daptomycin pore formation and stoichiometry depends on membrane potential of target membrane.
ásek I, Fišer R Abstract Daptomycin is a calcium-dependent lipodepsipeptide antibiotic clinically used to treat serious infections caused by Gram-positive pathogens. Its precise mode of action is somewhat controversial; the biggest issue is daptomycin pore formation, which we directly investigated here. We first performed a screening experiment using propidium iodide (PI) entry to Bacillus subtilis cells and chose the optimum and therapeutically relevant conditions (10 µg/mL daptomycin and 1.25 mM CaCl2) for the subsequent analyses. Using conductance measurements on planar lipid bilayers, we sh...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Seydlová G, Sokol A, Lišková P, Konopásek I, Fišer R Tags: Antimicrob Agents Chemother Source Type: research

Method-dependent epidemiological cutoff values (ECVs) for detection of triazole resistance in Candida and Aspergillus species for the SYO colorimetric broth and Etest agar diffusion methods.
oria L, Magobo R, Pelaez T, Quindós G, Rodriguez-Iglesia MA, Ruiz MA, Sánchez-Reus F, Sanguinetti M, Shields R, Szweda P, Tortorano A, Wengenack NL, Bramati S, Cavanna C, DeLuca C, Gelmi M, Grancini A, Lombardi G, Meletiadis J, Negri CE, Passera M, Peman J, Prigitano A, Sala E, Tejada M Abstract Although the Sensitrite Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole and voriconazole SYO and Etest MICs from 39 laboratories representi...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Espinel-Ingroff A, Turnidge J, Alastruey-Izquierdo A, Botterel F, Canton E, Castro C, Chen YC, Chen Y, Chryssanthou E, Dannaoui E, Garcia-Effron G, Gonzalez GM, Govender NP, Guinea J, Kidd S, Lackner M, Lass-Flörl C, Linares-Sicilia MJ, López-Soria L, M Tags: Antimicrob Agents Chemother Source Type: research

A pathway-directed screen for inhibitors of the bacterial cell elongation machinery.
Abstract New antibiotics are needed to combat the growing problem of resistant bacterial infections. An attractive avenue towards the discovery of such next generation therapies is to identify novel inhibitors of clinically validated targets like cell wall biogenesis. We have therefore developed a pathway-directed, whole-cell screen for small molecules that block the activity of the Rod system of Escherichia coli This conserved multi-protein complex is required for cell elongation and the morphogenesis of rod-shaped bacteria. It is composed of cell wall synthases and membrane proteins of unknown function that are ...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Buss JA, Baidin V, Welsh MA, Flores-Kim J, Cho H, Wood BM, Uehara T, Walker S, Kahne D, Bernhardt TG Tags: Antimicrob Agents Chemother Source Type: research

A Novel Actin Binding Drug with In Vivo Efficacy.
This study identified the primary cellular target of occidiofungin, which was determined to be actin. Occidiofungin modified with a functional alkyne group enabled affinity purification assays and localization studies in yeast. Occidiofungin has a subtle effect on actin dynamics that triggers an apoptotic cell death. We demonstrate highly specific localization of occidiofungin to cellular regions rich in actin in yeast and binding of occidiofungin to purified actin in vitro. Further, disruption of actin mediated cellular processes such as endocytosis, nuclear segregation, and hyphae formation were observed. All these proce...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Ravichandran A, Geng M, Hull KG, Li J, Romo D, Lu SE, Albee A, Nutter C, Gordon DM, Ghannoum MA, Lockless SW, Smith L Tags: Antimicrob Agents Chemother Source Type: research

No evidence for acquired mutations associated with cytochrome bc 1-inhibitor resistance in 13,559 clinical Mycobacterium tuberculosis complex isolates.
Abstract In 2016, tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) was responsible for an estimated 1.7 million deaths (1).…. PMID: 30323041 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Rybniker J, Andreas Kohl T, Barilar I, Niemann S Tags: Antimicrob Agents Chemother Source Type: research

Activation of 2,4-diaminoquinazoline in Mycobacterium tuberculosis by Rv3161c, a putative dioxygenase.
Abstract The diaminoquinazoline series has good potency against Mycobacterium tuberculosis Resistant isolates have mutations in Rv3161c, a putative dioxygenase. We carried out metabolite analysis on wild-type and an Rv3161c mutant strain after exposure to a diaminoquinazoline. The parental compound was found in intracellular extracts from the mutant, but not the wild-type. A metabolite consistent with a mono-hydroxylated form was identified in the wild-type. These data support the hypothesis that Rv3161c metabolizes diaminoquinazolines in M. tuberculosis. PMID: 30323042 [PubMed - as supplied by publisher] (So...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Melief E, Bonnett SA, Zuniga ES, Parish T Tags: Antimicrob Agents Chemother Source Type: research

Mutations in the MAB_2299c TetR regulator confer cross-resistance to clofazimine and bedaquiline in Mycobacterium abscessus.
mer L Abstract New therapeutic approaches are needed against Mycobacterium abscessus, a respiratory mycobacterial pathogen that evades efforts to successfully treat infected patients. Clofazimine and bedaquiline, two drugs used for the treatment of multi-drug resistant tuberculosis, are being considered as alternatives for the treatment in lung diseases caused by M. abscessus With the aim to understand the mechanism of action of these agents in M. abscessus, we sought herein to determine the means by which M. abscessus can develop resistance. Spontaneous resistant strains selected on clofazimine, followed by whole...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Richard M, Gutiérrez AV, Viljoen A, Rodriguez-Rincon D, Roquet-Baneres F, Blaise M, Everall I, Parkhill J, Floto RA, Kremer L Tags: Antimicrob Agents Chemother Source Type: research

Loss of C-5 sterol desaturase activity in Candida albicans - azole resistance or merely trailing growth?
In conclusion, the erg3 mutant phenotype is qualitatively and quantitatively distinct from both azole resistance and trailing growth. PMID: 30323044 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Luna-Tapia A, Butts A, Palmer GE Tags: Antimicrob Agents Chemother Source Type: research

Acquisition of extended-spectrum ß-lactamase GES-6 leading to resistance to ceftolozane-tazobactam combination in Pseudomonas aeruginosa.
Acquisition of extended-spectrum ß-lactamase GES-6 leading to resistance to ceftolozane-tazobactam combination in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 15;: Authors: Poirel L, Ortiz De La Rosa JM, Kieffer N, Dubois V, Jayol A, Nordmann P Abstract A clinical Pseudomonas aeruginosa isolate resistant to all β-lactams including ceftolozane-tazobactam and carbapenems was recovered. It belonged to the Sequence Type ST235 and produced the extended-spectrum β-lactamase (ESBL) GES-6 differing from GES-1 by two amino-acid substitutions (E104K and G170S). GES-6 possessed a...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Poirel L, Ortiz De La Rosa JM, Kieffer N, Dubois V, Jayol A, Nordmann P Tags: Antimicrob Agents Chemother Source Type: research

OXA-48-like-producing Klebsiella pneumoniae in southern Spain in 2014-2015.
Pascual Á Abstract The aim of this study was to characterize the population structure of 56 OXA-48-like-producing K. pneumoniae isolates, as well as ESBLs and carbapenemases genes, recovered in 2014 and 2015 from 16 hospitals in southern Spain. XbaI PFGE and MLST were performed to assess clonal relatedness. Representative isolates belonging to OXA-48-like-producing and CTX-M-15-co-producing pulsotypes were selected for characterization of bla OXA-48-like- and bla CTX-M-15-carrying plasmids by PCR-based replicon typing, IncF subtyping, WGS analysis and typing of Tn1999 structures. Forty-three (77%) OXA-48-p...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Machuca J, Lopez-Cerero L, Fernandez-Cuenca F, Mora-Navas L, Mediavilla-Gradolph C, LÓpez-RodrÍguez I, Pascual Á Tags: Antimicrob Agents Chemother Source Type: research

Effects of ivermectin and oxantel pamoate on tribendimidine: in vitro and in vivo drug-drug interaction study.
Abstract Soil-transmitted helminth (STH) infections still remain a major health problem in poor rural settings. The lack of efficacious drugs against all STH species raises the interest in drug combinations. Drug-drug interactions are, however, of major concern so that careful in vitro and in vivo characterization is needed. The combination of tribendimidine with either ivermectin or oxantel pamoate targets a broad range of STH and thus, represents a promising treatment alternative. Drug-drug interactions, however, have not yet been investigated. Therefore, the effect of combinations of ivermectin, oxantel pamoate...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Neodo A, Schulz JD, Huwyler J, Keiser J Tags: Antimicrob Agents Chemother Source Type: research

The Utility of Urine Cultures in Predicting Blood Culture Susceptibilities in Patients with Bacteremic Urinary Tract Infection.
Abstract In a review of 428 patients with bacteremic urinary tract infection, urine culture susceptibility results accurately predicted blood culture results when the same organism was isolated from both cultures. Early targeted therapy using urine culture results can potentially reduce broad-spectrum antibiotic exposure, its associated adverse effects, and length of hospitalization. PMID: 30323048 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Lam PW, Wiggers JB, Lo J, MacFadden DR, Daneman N Tags: Antimicrob Agents Chemother Source Type: research

Activity of Meropenem-Vaborbactam Against Pseudomonas aeruginosa and Acinetobacter baumannii in a Neutropenic Mouse Thigh Infection Model.
Abstract We have evaluated the activity of meropenem-vaborbactam against clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii in a neutropenic mouse thigh infection model. Data show that meropenem-vaborbactam regimens equivalent to 3-hour infusions every 8 hours with 2g meropenem-2g vaborbactam produced bacterial killing against strains with MICs of 2 - 16 mg/L and suggests that this combination may have utility in the treatment of infections caused by P. aeruginosa and A. baumannii. PMID: 30323049 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Sabet M, Tarazi Z, Griffith DC Tags: Antimicrob Agents Chemother Source Type: research

ARGONAUT-I: Activity of cefiderocol (S-649266), a siderophore cephalosporin, against Gram-negative bacteria including carbapenem resistant nonfermenters and Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases.
ARGONAUT-I: Activity of cefiderocol (S-649266), a siderophore cephalosporin, against Gram-negative bacteria including carbapenem resistant nonfermenters and Enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases. Antimicrob Agents Chemother. 2018 Oct 15;: Authors: Jacobs MR, Abdelhamed AM, Good CE, Rhoads DD, Hujer KM, Hujer AM, Domitrovic TN, Rudin SD, Richter SS, van Duin D, Kreiswirth BN, Greco C, Fouts DE, Bonomo RA, Antibacterial Resistance Leadership Group(ARLG) Abstract Activity of the siderophore cephalosporin cefiderocol, targeted for activity against carbapene...
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Jacobs MR, Abdelhamed AM, Good CE, Rhoads DD, Hujer KM, Hujer AM, Domitrovic TN, Rudin SD, Richter SS, van Duin D, Kreiswirth BN, Greco C, Fouts DE, Bonomo RA, Antibacterial Resistance Leadership Group(ARLG) Tags: Antimicrob Agents Chemother Source Type: research

Comparison of Pharmacist-Directed Management of Multiplex PCR Blood Culture Results with Conventional Microbiology Methods on Effective and Optimal Therapy within a Community Hospital.
Abstract Multiplex PCR combined with a pharmacist-driven reporting protocol was compared to standard-of-care within a community hospital to evaluate initial changes after notification of a positive blood culture. The intervention group demonstrated decreased time-to-change in antimicrobial therapy (p=0.0081), increased change to optimal antimicrobial therapy (p=0.013) and decreased vancomycin use for coagulase negative staphylococci contaminants (p
Source: Antimicrobial Agents and Chemotherapy - October 15, 2018 Category: Microbiology Authors: Porter AM, Bland CM, Young HN, Allen DR, Croft SR, Gayheart RE, Miller PW, Musgrove RJ, Robertson EM, Gibson GM Tags: Antimicrob Agents Chemother Source Type: research

Role of capsule in resistance to disinfectants, host antimicrobials and desiccation in Acinetobacter baumannii.
This study demonstrates that capsule is required for resistance to disinfectants, lysozyme and desiccation in Acinetobacter baumannii In addition, capsule is required for survival in a mouse lung model of infection. PMID: 30297362 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Tipton KA, Chin CY, Farokhyfar M, Weiss DS, Rather PN Tags: Antimicrob Agents Chemother Source Type: research

Polymorphism of polymeric amino acid regions in fungal proteins: correlation with altered echinocandin and azole susceptibility.
Abstract Polymorphism of polymeric amino acid (polyX) regions within fungal proteins represents a potential mechanism for rapid genotypic adaptation to environmental pressures including antifungal exposure. PolyQ was the most abundant repeat in the proteomes of 8 diverse fungal species, and was preferentially found in regulatory proteins. In Candida glabrata, polyX polymorphisms were characterized in 36 proteins implicated in azole or echinocandin susceptibility. General transcriptional repressor Tup1A exhibited Q44/Q45 polymorphism, and Hog1 signalling component Ssk2 exhibited N44/N45, in phylogenetically matched...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Challa K, Edlind T, Katiyar S Tags: Antimicrob Agents Chemother Source Type: research

Two regulators, PA3898 and PA2100, modulate the Pseudomonas aeruginosa multidrug resistance MexAB-OprM and EmrAB efflux-pumps and biofilm formation.
We present here a novel transcriptional regulator, PA3898, which controls biofilm formation and multidrug efflux-pumps in P. aeruginosa A mutant of this regulator significantly reduced the ability of P. aeruginosa to produce biofilm in vitro, and affected its in vivo fitness and pathogenesis in Drosophila melanogaster and BALB/c mouse lung infection models. Transcriptome analysis revealed that PA3898 modulates essential virulence genes/pathways, including multidrug efflux-pumps and phenazine biosynthesis. ChIP-seq identified its DNA binding sequences and confirmed PA3898 directly interacts with promoter regions of four gen...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Heacock-Kang Y, Sun Z, Zarzycki-Siek J, Poonsuk K, McMillan IA, Chuanchuen R, Hoang TT Tags: Antimicrob Agents Chemother Source Type: research

Breaking the vicious cycle of antibiotic killing and regrowth of biofilm-residing Pseudomonas aeruginosa.
ml;ussler S Abstract Biofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physico-chemical insults. In addition to the general recalcitrance of biofilm-bacteria, high bacterial loads in biofilm-associated infections significantly diminishes the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols, that have been established to serve the eradication of acute infections, fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy on Pseudomonas aerug...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Müsken M, Pawar V, Schwebs T, Bähre H, Felgner S, Weiss S, Häussler S Tags: Antimicrob Agents Chemother Source Type: research

Competitive fitness of essential gene knockdowns reveals a broad-spectrum antibacterial inhibitor of the cell division protein FtsZ.
Abstract To streamline elucidation of antibacterial compounds' mechanism of action, comprehensive high-throughput assays interrogating multiple putative targets are necessary. However, current chemogenomic approaches for antibiotic target identification have not fully utilized the multiplexing potential of next-generation sequencing. Here, we used Illumina sequencing of transposon insertions to track the competitive fitness of a Burkholderia cenocepacia library containing essential gene knockdowns. Using this method, we characterized a novel benzothiadiazole derivative, 10126109 (C109) with antibacterial activity ...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Hogan AM, Scoffone VC, Makarov V, Gislason AS, Tesfu H, Stietz MS, Brassinga AKC, Domaratzki M, Li X, Azzalin A, Biggiogera M, Riabova O, Monakhova N, Chiarelli LR, Riccardi G, Buroni S, Cardona ST Tags: Antimicrob Agents Chemother Source Type: research

Lipase precursor like protein promotes miltefosine tolerance in Leishmania donovani by enhancing parasite infectivity and eliciting anti-inflammatory responses in host macrophages.
Abstract Oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the year 2002 for the treatment of visceral leishmaniasis (VL). However, recent reports on its declining efficacy and increasing relapse rates pose a serious concern. An understanding of the factors contributing to MIL tolerance in Leishmania parasites is critical. In the present study, we assessed the role of lipase precursor like protein (Lip) in conferring tolerance towards miltefosine by episomally overexpressing Lip into L. donovani (LdLip++). We observed significant increase (∼3 fold) in MIL IC50 both at promastigote (3.90 ...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Deep DK, Singh R, Kulshrestha A, Wajid S, Salotra P Tags: Antimicrob Agents Chemother Source Type: research

Amixicile reduces severity of cryptosporidiosis, but does not have in vitro activity against Cryptosporidium.
Abstract Cryptosporidium causes significant morbidity in malnourished children. Nitazoxanide (NTZ) is the only approved treatment for cryptosporidiosis, but NTZ has diminished effectiveness during malnutrition. Here we show that amixicile, a highly selective water soluble derivative of NTZ diminishes Cryptosporidium severity in a malnourished mouse model despite a lack of direct anti-cryptosporidial activity. We suggest that amixicile; by tamping down anaerobes associated with intestinal inflammation, reverses weight loss and indirectly mitigates infection-associated pathology. PMID: 30297368 [PubMed - as sup...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Bartelt LA, Bolick DT, Kolling GL, Stebbins E, Huston CD, Guerrant RL, Hoffman PS Tags: Antimicrob Agents Chemother Source Type: research

Effects of Food and Omeprazole on Novel Formulation SUBA-Itraconazole in Healthy Subjects.
This study evaluated the pharmacokinetic profile of SUBA-itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. The effect of food was assessed in an open-label, randomized, cross-over bioavailability study of SUBA-itraconazole capsules 65 mg (2 x 65 mg BID) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Secondly, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n=28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA-itraconazole capsules ...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Lindsay J, Mudge S, Thompson GR Tags: Antimicrob Agents Chemother Source Type: research

Drug repurposing for Leishmania. Molecular basis of the leishmanicidal activity of the antidepressant sertraline.
López-Gonzálvez Á, Rivas L Abstract Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insig...
Source: Antimicrobial Agents and Chemotherapy - October 8, 2018 Category: Microbiology Authors: Lima ML, Abengózar MA, Nácher-Vázquez M, Martínez-Alcázar MP, Barbas C, Tempone AG, López-Gonzálvez Á, Rivas L Tags: Antimicrob Agents Chemother Source Type: research

A high rate of ceftobiprole resistance among clinical MRSA from a hospital in central Italy.
Abstract Ceftobiprole is a fifth-generation cephalosporin with activity against MRSA. One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates, MIC ≥4 mg/L). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. PBP analysis showed substitutions in all PBPs and a novel insertion in PBP2a. Genes mecB and mecC were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and spread of ceftobiprole-resistant strains. PMID: 30275082 [PubMed - as suppli...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Morroni G, Brenciani A, Brescini L, Fioriti S, Simoni S, Pocognoli A, Mingoia M, Giovanetti E, Barchiesi F, Giacometti A, Cirioni O Tags: Antimicrob Agents Chemother Source Type: research

Efficacious Analogs of the Lantibiotic Mutacin 1140 Against a Systemic MRSA Infection.
In this study, we evaluated the effect of charged and dehydrated residues on the pharmacokinetics of mutacin 1140. The dehydrated residues were determined to contribute to the stability of mutacin 1140, while alanine substitutions of the lysine or arginine residues improved the pharmacological properties of the antibiotic. Analogs K2A and R13A had a significantly lower clearance, leading to higher plasma concentrations over time. They also had improved bioactivities against several pathogenic bacteria. In a murine systemic MRSA infection model, a 10 mg/kg single intravenous bolus injection of the K2A and R13A analogs (1:1 ...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Geng M, Ravichandran A, Escano J, Smith L Tags: Antimicrob Agents Chemother Source Type: research

Selective inhibition of Neisseria gonorrhoeae by a dithiazoline in mixed infections with Lactobacillus gasseri.
Abstract The Gram-negative human pathogen Neisseria gonorrhoeae has progressively developed resistance to antibiotic monotherapies, and recent failures of dual-drug therapy have heightened concerns that strains resistant to all available antibiotics will begin circulating globally. Targeting bacterial cell wall assembly has historically been effective at treating infections with N. gonorrhoeae, but as the effectiveness of β-lactams (including cephalosporins) are challenged by increasing resistance, research has expanded into compounds that target the numerous other enzymes with roles in peptidoglycan metaboli...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Lenz JD, Shirk KA, Jolicoeur A, Dillard JP Tags: Antimicrob Agents Chemother Source Type: research

Nitazoxanide: A Therapeutic Option for Adenovirus Related Enteritis in Immunocompromised Adults.
Abstract Clinical efficacy of cidofovir for treatment of adenovirus-related disease is limited and toxicity is a major concern.…. PMID: 30275085 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Esquer Garrigos Z, Barth D, Hamdi AM, Abu Saleh OM, Sohail MR Tags: Antimicrob Agents Chemother Source Type: research

Emergence of Klebsiella pneumoniae harboring the aac(6')-Ian amikacin resistance gene.
Lázaro-Perona F Abstract Carbapenemase-producing Enterobacteriaceae (CPE) have become a major public health concern worldwide (1).…. PMID: 30275086 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Troyano-Hernáez P, Gutiérrez-Arroyo A, Gómez-Gil R, Mingorance J, Lázaro-Perona F Tags: Antimicrob Agents Chemother Source Type: research

Pentoxifylline alone or in combination with gentamicin or vancomycin inhibits live microbe-induced pro-inflammatory cytokine production in human cord blood and cord blood monocytes in vitro.
Conclusion: Our findings demonstrated that PTX inhibited microbe-induced pro-inflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro, thus supporting its utility as candidate adjunctive agent for newborn sepsis. PMID: 30275087 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Speer EM, Diago-Navarro E, Ozog LS, Dowling DJ, Hou W, Raheel M, Fries BC, Levy O Tags: Antimicrob Agents Chemother Source Type: research

Tri-chlorination of a teicoplanin type glycopeptide antibiotic by the halogenase StaI evades resistance.
In this study, we report that only one of the halogenase genes, staI, is necessary and essential for A47934 biosynthesis. Chlorination of the A47934 scaffold is important for antibiotic activity as assessed by binding affinity for the target N-acyl-D-Ala-D-Ala. Surprisingly, chlorination is also vital to avoid activation of enterococcal and Streptomyces VanB-type GPA resistance through induction of resistance genes. Phenotypic assays showed stronger induction of GPA resistance by the dechlorinated compared to the chlorinated GPA. Correspondingly, the relative expression of enterococcal vanA resistance gene was shown to be ...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Yim G, Wang W, Pawlowski AC, Wright GD Tags: Antimicrob Agents Chemother Source Type: research

Emergence and within-host genetic evolution of methicillin-resistant Staphylococcus aureus resistant to linezolid in a cystic fibrosis patient.
In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in MRSA colonizing strains belonging to the same lineage. PMID: 30275089 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Rouard C, Garnier F, Leraut J, Lepainteur M, Rahajamananav L, Languepin J, Ploy MC, Bourgeois-Nicolaos N, Doucet-Populaire F Tags: Antimicrob Agents Chemother Source Type: research

Correlation of invitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris.
This study investigated the clinico-mycological profile of 85 tinea corporis/cruris patients, and performed antifungal susceptibility testing by CLSI micro-broth dilution and SQLE mutation analysis of isolates obtained and correlated these with the response to TRB. Cases confirmed by KOH mount of skin scrapings were started on TRB 250 mg once a day (OD). If>50% clinical clearance was achieved by 3 weeks, the same dose was continued (Group 1). If response was
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Khurana A, Masih A, Chowdhary A, Sardana K, Borker S, Gupta A, Gautam RK, Sharma PK, Jain D Tags: Antimicrob Agents Chemother Source Type: research

Pharmacokinetics of Intravenous Isavuconazole in Solid Organ Transplant Recipients.
In conclusion, moderate inter-patient variability in isavuconazole exposure, identification of factors associated with lower exposure, recognition that Ctrough is a surrogate marker for AUC and availability of a simple analytical method, suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients' clinical outcomes, and to determine the clinical role of TDM. PMID: 30275091 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Wu X, Clancy CJ, Rivosecchi RM, Zhao W, Shields RK, Marini RV, Venkataramanan R, Nguyen MH Tags: Antimicrob Agents Chemother Source Type: research

A Phase 1 Study to Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal Function.
Abstract Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infection. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single dose of plazomicin 7.5 mg/kg as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin AUC0-∞ values in subjects with moderate and severe impairment, respectively, relative to normal renal function. PMID: 30275092 [PubMed - as supplied by publisher] (Source: Antimicrobial A...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Komirenko AS, Riddle V, Gibbons JA, Van Wart S, Seroogy JD Tags: Antimicrob Agents Chemother Source Type: research

Antimicrobial susceptibility of 260 Clostridium botulinum types A, B, Ba and Bf strains and a neurotoxigenic Clostridium baratii type F strain isolated from California infant botulism patients.
Abstract Infant botulism is an infectious intestinal toxemia that results from colonization of the infant large bowel by Clostridium botulinum (or rarely, by neurotoxigenic C. baratii or C. butyricum), with subsequent intraintestinal production and absorption of botulinum neurotoxin that then produces flaccid paralysis. The disease is often initially misdiagnosed as suspected sepsis or meningitis, diagnoses that require prompt empiric antimicrobial therapy. Antibiotics may also be needed to treat infectious complications of infant botulism, such as pneumonia or urinary tract infection. Clinical evidence suggests (...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Barash JR, Castles JB, Arnon SS Tags: Antimicrob Agents Chemother Source Type: research

Tenofovir exposure during pregnancy and postpartum in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission of hepatitis B virus.
iTAP study team Abstract We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected, HIV-uninfected, women receiving tenofovir disoproxil fumarate (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who received TDF within a randomized-controlled trial were included. Individual plasma tenofovir exposures (AUC0-24) were estimated using a population pharmacokinetic approach. Estimated geometric mean tenofovir AUC0-24 was 20% (95% CI: 19-21%) lower during pregnancy compared to postpartum; this modest reduction in the absence of HBV transmission suggests no...
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Cressey TR, Harrison L, Achalapong J, Kanjanavikai P, Patamasingh Na Ayudhaya O, Liampongsabuddhi P, Siriwachirachai T, Putiyanun C, Suriyachai P, Tierney C, Salvadori N, Chinwong D, Decker L, Tawon Y, Murphy TV, Ngo-Giang-Huong N, Siberry GK, Jourdain G, Tags: Antimicrob Agents Chemother Source Type: research

A simple alternative sampling method for benznidazole pharmacokinetic assessment: a dried blood spot technique-based LC-MS/MS method.
This article describes the first micro-sampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and paediatric patients in remote endemic areas and help to address existing knowledge gaps in the treatment in CD. PMID: 30275095 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - October 1, 2018 Category: Microbiology Authors: Galindo Bedor DC, Bedor NCTC, da Silva JWV, Sousa GD, Pereira de Santana D, Garcia-Bournissen F, Altcheh J, Blum B, Alves F, Ribeiro I Tags: Antimicrob Agents Chemother Source Type: research

Is Alternate-Day Therapeutic Drug Monitoring in the Intensive Care Unit Not Intensive Enough?
PMID: 30249715 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - September 27, 2018 Category: Microbiology Authors: Sorooshian P, Snow TAC Tags: Antimicrob Agents Chemother Source Type: research

Reply to Sorooshian and Snow, "Is Alternate-Day Therapeutic Drug Monitoring in the Intensive Care Unit Not Intensive Enough?"
Reply to Sorooshian and Snow, "Is Alternate-Day Therapeutic Drug Monitoring in the Intensive Care Unit Not Intensive Enough?" Antimicrob Agents Chemother. 2018 Oct;62(10): Authors: Fournier A, Eggimann P, Pantet O, Pagani JL, Dupuis-Lozeron E, Pannatier A, Sadeghipour F, Voirol P, Que YA PMID: 30249716 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - September 27, 2018 Category: Microbiology Authors: Fournier A, Eggimann P, Pantet O, Pagani JL, Dupuis-Lozeron E, Pannatier A, Sadeghipour F, Voirol P, Que YA Tags: Antimicrob Agents Chemother Source Type: research

Erratum for Yew et al., "Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity".
Erratum for Yew et al., "Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity". Antimicrob Agents Chemother. 2018 Oct;62(10): Authors: Yew WW, Chang KC, Chan DP PMID: 30249717 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - September 27, 2018 Category: Microbiology Authors: Yew WW, Chang KC, Chan DP Tags: Antimicrob Agents Chemother Source Type: research

A large, refractory nosocomial outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control.
RACE Investigators’ Group Abstract Carbapenem-resistant Enterobacteriaceae (CRE) are a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli (KPC-EC) outbreak and wider CRE incidence trends over eight years in the Central Manchester Foundation NHS Trust (CMFT), UK, to determine the impact of Infection Prevention and Control measures.Bacteriology and patient administration data (2009 to 2017) were linked; a subset of CMFT/reg...
Source: Antimicrobial Agents and Chemotherapy - September 24, 2018 Category: Microbiology Authors: Decraene V, Phan HTT, George R, Wyllie DH, Akinremi O, Aiken Z, Cleary P, Dodgson A, Pankhurst L, Crook DW, Lenney C, Walker AS, Woodford N, Sebra R, Fath-Ordoubadi F, Mathers AJ, Seale AC, Guiver M, McEwan A, Watts V, Welfare W, Stoesser N, Cawthorne J, Tags: Antimicrob Agents Chemother Source Type: research

Site-directed mutagenesis of the 1,3- β glucan synthase catalytic subunit of Pneumocystis jirovecii and susceptibility assays suggest its sensitivity to caspofungin.
Site-directed mutagenesis of the 1,3-β glucan synthase catalytic subunit of Pneumocystis jirovecii and susceptibility assays suggest its sensitivity to caspofungin. Antimicrob Agents Chemother. 2018 Sep 24;: Authors: Luraschi A, Richard S, Hauser PM Abstract The echinocandin caspofungin inhibits the catalytic subunit Gsc1 of the enzymatic complex synthetizing 1,3-β glucan, an essential compound of the fungal wall. Studies in rodents showed that caspofungin is effective against Pneumocystis asci. However, its efficacy against asci of Pneumocystis jirovecii, the species infecting exclusively h...
Source: Antimicrobial Agents and Chemotherapy - September 24, 2018 Category: Microbiology Authors: Luraschi A, Richard S, Hauser PM Tags: Antimicrob Agents Chemother Source Type: research

Investigating sulfoxide to sulfone conversion as a prodrug strategy for a PI4K inhibitor in a humanized mouse model of malaria.
Abstract The in vivo antimalarial efficacies of two PI4K inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2Rγnull (NSG) murine malaria disease model of Plasmodium falciparum infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure on oral dosing. Both compounds had similar efficacy (ED90 0.1 mg.kg-1) across a quadruple-dose regimen. Pharmacokinetic profiling revealed rapid sulfoxide clearance via conversion to the sulfone with the latter identifie...
Source: Antimicrobial Agents and Chemotherapy - September 24, 2018 Category: Microbiology Authors: Gibhard L, Njoroge M, Paquet T, Brunschwig C, Taylor D, Lawrence N, Abay E, Wittlin S, Wiesner L, Street LJ, Chibale K, Basarab GS Tags: Antimicrob Agents Chemother Source Type: research

A hyperactive form of the zinc cluster transcription factor Stb5 causes YOR1 overexpression and beauvericin resistance in Candida albicans.
In this study, we show that an activated form of another zinc cluster transcription factor, Stb5, confers resistance to the natural compound beauvericin by overexpression of YOR1, encoding an efflux pump of the ATP-binding cassette transporter superfamily. Beauvericin has recently been shown to potentiate the activity of azole drugs against C. albicans Although Yor1 did not contribute to fluconazole resistance when C. albicans cells were treated with the drug alone, Stb5-mediated YOR1 overexpression diminished the synergistic effect of the fluconazole/beauvericin combination, thereby enhancing fluconazole resistance in bea...
Source: Antimicrobial Agents and Chemotherapy - September 24, 2018 Category: Microbiology Authors: Ramírez-Zavala B, Manz H, Englert F, Rogers PD, Morschhäuser J Tags: Antimicrob Agents Chemother Source Type: research