Delamanid Kills Dormant Mycobacteria In Vitro and in a Guinea Pig Model of Tuberculosis.

Abstract:

:Tuberculosis (TB) treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug susceptibilities. Drugs with broad activity are urgently needed. This study aimed to evaluate delamanid's activity against growing or dormant bacilli in vitro as well as in vivo Cultures of Mycobacterium bovis BCG Tokyo under aerobic and anaerobic conditions were used to study the activity of delamanid against growing and dormant bacilli, respectively. Delamanid exhibited significant bactericidal activity against replicating and dormant bacilli at or above concentrations of 0.016 and 0.4 mg/liter, respectively. To evaluate delamanid's antituberculosis activity in vivo, we used a guinea pig model of chronic TB infection in which the lung lesions were similar to those in human TB disease. In the guinea pig TB model, a daily dose of 100 mg delamanid/kg of body weight for 4 or 8 weeks demonstrated strong bactericidal activity against Mycobacterium tuberculosis Importantly, histological examination revealed that delamanid killed TB bacilli within hypoxic lesions of the lung. The combination regimens containing delamanid with rifampin and pyrazinamide or delamanid with levofloxacin, ethionamide, pyrazinamide, and amikacin were more effective than the standard regimen (rifampin, isoniazid, and pyrazinamide). Our data show that delamanid is effective in killing both growing and dormant bacilli in vitro and in the guinea pig TB model. Adding delamanid to current TB regimens may improve treatment outcomes, as demonstrated in recent clinical trials with pulmonary multidrug-resistant (MDR) TB patients. Delamanid may be an important drug for consideration in the construction of new regimens to shorten TB treatment duration.

authors

Chen X,Hashizume H,Tomishige T,Nakamura I,Matsuba M,Fujiwara M,Kitamoto R,Hanaki E,Ohba Y,Matsumoto M

doi

10.1128/AAC.02402-16

subject

Has Abstract

pub_date

2017-05-24 00:00:00

issue

6

eissn

0066-4804

issn

1098-6596

pii

AAC.02402-16

journal_volume

61

pub_type

杂志文章
  • WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015.

    abstract::WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00072-17

    authors: Sader HS,Castanheira M,Huband M,Jones RN,Flamm RK

    更新日期:2017-04-24 00:00:00

  • Local treatment of experimental Pseudomonas aeruginosa osteomyelitis with a biodegradable dilactide polymer releasing ciprofloxacin.

    abstract::A biodegradable system of poly-D,L-dilactide releasing ciprofloxacin was assessed in a Pseudomonas aeruginosa osteomyelitis model after inoculation of the test pathogen into the left tibia of 76 New Zealand White rabbits; 31 were controls (group A), and 45 were implanted with the polymer at the infection site (group B...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01360-07

    authors: Kanellakopoulou K,Thivaios GC,Kolia M,Dontas I,Nakopoulou L,Dounis E,Giamarellos-Bourboulis EJ,Andreopoulos A,Karagiannakos P,Giamarellou H

    更新日期:2008-07-01 00:00:00

  • Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus.

    abstract::Resistance to antifungal drugs, specifically azoles such as fluconazole, in the opportunistic yeast Candida albicans has become an increasing problem in human immunodeficiency virus (HIV)-infected individuals. The molecular mechanisms responsible for this resistance have only recently become apparent and can include a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.7.1482

    authors: White TC

    更新日期:1997-07-01 00:00:00

  • Use of a new mouse model of Acinetobacter baumannii pneumonia to evaluate the postantibiotic effect of imipenem.

    abstract::Acinetobacter baumannii is responsible for severe nosocomial pneumonia. To evaluate new therapeutic regimens for infections due to multiresistant strains and to study the pharmacodynamic properties of various antibiotics, we developed an experimental mouse model of acute A. baumannii pneumonia. C3H/HeN mice rendered t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.2.345

    authors: Joly-Guillou ML,Wolff M,Pocidalo JJ,Walker F,Carbon C

    更新日期:1997-02-01 00:00:00

  • The antibiotic monensin causes cell cycle disruption of Toxoplasma gondii mediated through the DNA repair enzyme TgMSH-1.

    abstract::Monensin is a polyether ionophore antibiotic that is widely used in the control of coccidia in animals. Despite its significance in veterinary medicine, little is known about its mode of action and potential mechanisms of resistance in coccidian parasites. Here we show that monensin causes accumulation of the coccidia...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01092-10

    authors: Lavine MD,Arrizabalaga G

    更新日期:2011-02-01 00:00:00

  • Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile.

    abstract::Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.3.582

    authors: Mahony DE,Lim-Morrison S,Bryden L,Faulkner G,Hoffman PS,Agocs L,Briand GG,Burford N,Maguire H

    更新日期:1999-03-01 00:00:00

  • In vitro activities of DX-619 and four comparator agents against 376 anaerobic bacterial isolates.

    abstract::The activity of DX-619 was evaluated against 376 anaerobic isolates using the reference CLSI agar dilution method. Overall, 90% of the strains were susceptible to DX-619 at < or =1 microg/ml. It was more active than the other four compounds tested except for meropenem, which showed virtually identical overall activity...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.5.1887-1889.2006

    authors: Molitoris D,Väisänen ML,Bolaños M,Finegold SM

    更新日期:2006-05-01 00:00:00

  • Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]-beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound infection.

    abstract::The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infecti...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.42.3.545

    authors: Kernodle DS,Gates H,Kaiser AB

    更新日期:1998-03-01 00:00:00

  • Pleiotropic antibiotic resistance mutations associated with ribosomes and ribosomal subunits in Mycobacterium smegmatis.

    abstract::Viomycin-resistant strains isolated from Mycobacterium smegmatis demonstrated pleiotropic resistance to tuberactinomycin-N, capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.6.1.46

    authors: Yamada T,Masuda K,Shoji K,Hori M

    更新日期:1974-07-01 00:00:00

  • Inducement and reversal of tetracycline resistance in Escherichia coli K-12 and expression of proton gradient-dependent multidrug efflux pump genes.

    abstract::Expression of eight transporter genes of Escherichia coli K-12 and its DeltaacrAB mutant prior to and after induction of both strains to tetracycline resistance and after reversal of induced resistance were analyzed by quantitative reverse transcriptase PCR. All transporter genes were overexpressed after induced resis...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.8.3578-3582.2005

    authors: Viveiros M,Jesus A,Brito M,Leandro C,Martins M,Ordway D,Molnar AM,Molnar J,Amaral L

    更新日期:2005-08-01 00:00:00

  • Purification and characterization of inducible beta-lactamases in Aeromonas spp.

    abstract::beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.1.44

    authors: Iaconis JP,Sanders CC

    更新日期:1990-01-01 00:00:00

  • Serum aminoglycoside assay by enzyme-mediated immunoassay (EMIT): correlation with radioimmunoassay, microbiological assays.

    abstract::Enzyme-mediated immunoassay (EMIT) serum aminoglycoside assay results were accurate and precise and correlated well with radioimmunoassay, fluoroimmunoassay, and acetyltransferase and microbiological assay determinations. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.6.1064

    authors: White LO,Scammell LM,Reeves DS

    更新日期:1981-06-01 00:00:00

  • In vitro and in vivo evaluations of A-80556, a new fluoroquinolone.

    abstract::A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC f...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.5.1071

    authors: Clement JJ,Tanaka SK,Alder J,Vojtko C,Beyer J,Hensey D,Ramer N,McDaniel D,Chu DT

    更新日期:1994-05-01 00:00:00

  • Once-daily aminoglycoside therapy: potential ototoxicity.

    abstract::Current data indicate that once-daily aminoglycoside therapy is as efficacious as traditional multiple daily dosing and equally or less toxic. Our experience with once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients) occurrence of documented ototoxicity after prolonged aminoglycoside exposure. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.9.2209

    authors: Singer C,Smith C,Krieff D

    更新日期:1996-09-01 00:00:00

  • Inhibition of mouse LM cell replication by trifluorothymidine: role of cytosolic deoxythymidine kinase.

    abstract::The effects of trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine, F3dThd) on the replication of three mouse cell lines, LM929, Ltk- (and LM929 derivative devoid of cytosolic deoxythymidine [dThd] kinase activity), and Ltk- c139 (a Ltk- derivative which expresses herpes simplex virus type 1-specified dThd kinase su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.5.881

    authors: Wigdahl BL,Parkhurst JR

    更新日期:1981-05-01 00:00:00

  • Updated functional classification of beta-lactamases.

    abstract::Two classification schemes for beta-lactamases are currently in use. The molecular classification is based on the amino acid sequence and divides beta-lactamases into class A, C, and D enzymes which utilize serine for beta-lactam hydrolysis and class B metalloenzymes which require divalent zinc ions for substrate hydr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.01009-09

    authors: Bush K,Jacoby GA

    更新日期:2010-03-01 00:00:00

  • bla(IMP-9) and its association with large plasmids carried by Pseudomonas aeruginosa isolates from the People's Republic of China.

    abstract::A novel plasmid-mediated metallo-beta-lactamase (IMP-9) is described in seven isolates of Pseudomonas aeruginosa from Guangzhou, China, isolated in 2000. The gene was carried on a large (approximately 450-kb) IncP-2 conjugative plasmid. This is the first report of carriage of bla(IMP) genes on such large plasmids. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.1.355-358.2006

    authors: Xiong J,Hynes MF,Ye H,Chen H,Yang Y,M'zali F,Hawkey PM

    更新日期:2006-01-01 00:00:00

  • Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.

    abstract::Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatme...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1128/aac.35.10.2078

    authors: Kearns GL,Reed MD,Jacobs RF,Ardite M,Yogev RD,Blumer JL

    更新日期:1991-10-01 00:00:00

  • In vitro reversion of amphotericin B resistance in Leishmania donovani by poloxamer 188.

    abstract::A micellar formulation of amphotericin B (AmB) solubilized with poloxamer 188 was evaluated against an AmB Leishmania donovani-resistant line. A concave isobologram showed a synergistic effect of this association against promastigotes. This result was confirmed with amastigotes since the 50% effective concentration of...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.8.2190-2192.2000

    authors: Espuelas S,Legrand P,Loiseau PM,Bories C,Barratt G,Irache JM

    更新日期:2000-08-01 00:00:00

  • Influence of reduced susceptibility to glycopeptides on activities of vancomycin and teicoplanin against Staphylococcus aureus in experimental endocarditis.

    abstract::The influence of reduced susceptibilities to glycopeptides on the activities of vancomycin and teicoplanin against an isogenic pair of clinical Staphylococcus aureus strains in experimental endocarditis was investigated. While vancomycin was similarly active against both strains, teicoplanin was approximately 100-fold...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.6.2018-2021.2003

    authors: Pavie J,Lefort A,Ploy MC,Massias L,Chau F,Garry L,Denis F,Fantin B

    更新日期:2003-06-01 00:00:00

  • Inducible high resistance to colistin in Proteus strains.

    abstract::Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.12.1.1

    authors: Shimizu S,Iyobe S,Mitsuhashi S

    更新日期:1977-07-01 00:00:00

  • Survey of Bacteroides fragilis group susceptibility patterns in Canada.

    abstract::The in vitro activities of penicillin, clindamycin, chloramphenicol, metronidazole, piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin-sulbactam, cefoxitin, ceftizoxime, cefotetan, moxalactam, and imipenem against 348 Bacteroides fragilis group isolates collected from six Canadian ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.2.343

    authors: Bourgault AM,Lamothe F,Hoban DJ,Dalton MT,Kibsey PC,Harding G,Smith JA,Low DE,Gilbert H

    更新日期:1992-02-01 00:00:00

  • Risk factors for emergence of resistance to broad-spectrum cephalosporins among Enterobacter spp.

    abstract::Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.45.9.2628-2630.2001

    authors: Kaye KS,Cosgrove S,Harris A,Eliopoulos GM,Carmeli Y

    更新日期:2001-09-01 00:00:00

  • Mathematical modeling to characterize the inoculum effect.

    abstract::Killing by beta-lactams is well known to be reduced against a dense bacterial population, commonly known as the inoculum effect. However, the underlying mechanism of this phenomenon is not well understood. We proposed a semi-mechanistic mathematical model to account for the reduced in vitro killing observed. Time-kill...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01831-09

    authors: Bhagunde P,Chang KT,Singh R,Singh V,Garey KW,Nikolaou M,Tam VH

    更新日期:2010-11-01 00:00:00

  • Impact of meropenem in combination with tobramycin in a murine model of Pseudomonas aeruginosa pneumonia.

    abstract::Pseudomonas aeruginosa pneumonia remains a difficult therapeutic problem. Optimal doses and modes of administration of single agents often do not result in acceptable outcomes. Further, emergence of resistance occurs frequently in this setting with single-agent chemotherapy. The purpose of these experiments was to eva...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02624-12

    authors: Louie A,Liu W,Fikes S,Brown D,Drusano GL

    更新日期:2013-06-01 00:00:00

  • Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection.

    abstract::Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in ch...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.01701-16

    authors: Antwi S,Yang H,Enimil A,Sarfo AM,Gillani FS,Ansong D,Dompreh A,Orstin A,Opoku T,Bosomtwe D,Wiesner L,Norman J,Peloquin CA,Kwara A

    更新日期:2017-01-24 00:00:00

  • Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole.

    abstract::We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01046-12

    authors: Avery LM,Steed ME,Woodruff AE,Hasan M,Rybak MJ

    更新日期:2012-11-01 00:00:00

  • Sequential therapy with caspofungin and fluconazole for Candida albicans infection.

    abstract::A sequential therapy of caspofungin (CAS) and fluconazole (FLC) administration for treatment of Candida albicans infection was investigated. Treatment with CAS followed by FLC was as effective as CAS treatment given alone for the same duration. Our data suggest that switching from CAS to FLC is a potentially explorabl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.10.4056-4058.2004

    authors: Barchiesi F,Spreghini E,Baldassarri I,Marigliano A,Arzeni D,Giannini D,Scalise G

    更新日期:2004-10-01 00:00:00

  • Comparative in vitro activity of norfloxacin (MK-0366) and ten other oral antimicrobial agents against urinary bacterial isolates.

    abstract::The in vitro activity of a new oral antimicrobial agent, norfloxacin (MK-0366), was compared with those of nalidixic acid, nitrofurantoin, co-trimoxazole, trimethoprim, sulfamethoxazole, cinoxacin, tetracycline, ampicillin, carbenicillin, and cephalexin against 628 urinary bacterial isolates. Norfloxacin was the most ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.21.5.848

    authors: Khan MY,Gruninger RP,Nelson SM,Klicker RE

    更新日期:1982-05-01 00:00:00

  • Percentages and distributions of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci.

    abstract::The activities of teicoplanin and vancomycin against 362 coagulase-negative staphylococci were determined by an agar dilution method. At the 4- and 32-micrograms/ml breakpoint levels of the National Committee for Clinical Laboratory Standards, 23.2% of the strains were intermediate and 1.7% were resistant to teicoplan...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.5.899

    authors: Goldstein FW,Coutrot A,Sieffer A,Acar JF

    更新日期:1990-05-01 00:00:00