Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation.

Abstract:

:Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, phage dry-powder administration to the lungs has not yet been explored. Powder formulations provide potential advantages over a liquid formulation, including easy storage, transport, and administration. The purpose of this study was to assess the bactericidal activities of phage dry-powder formulations against multidrug-resistant (MDR) strain Pseudomonas aeruginosa FADDI-PA001 in a mouse lung infection model. Phage PEV20 spray dried with lactose and leucine produced an inhalable powder at a concentration of 2 × 107 PFU/mg. P. aeruginosa lung infection was established by intratracheal administration of the bacterial suspension to neutropenic mice. At 2 h after the bacterial challenge, the infected mice were treated with 2 mg of the phage powder using a dry-powder insufflator. At 24 h after the phage treatment, the bacterial load in the lungs was decreased by 5.3 log10 (P < 0.0005) in the phage-treated group compared with that in the nontreated group. Additionally, the phage concentration in the lungs was increased by 1 log10 at 24 h in the treated group. These results demonstrate the feasibility of a pulmonary delivery of phage PEV20 dry-powder formulation for the treatment of lung infection caused by antibiotic-resistant P. aeruginosa.

authors

Chang RYK,Chen K,Wang J,Wallin M,Britton W,Morales S,Kutter E,Li J,Chan HK

doi

10.1128/AAC.01714-17

subject

Has Abstract

pub_date

2018-01-25 00:00:00

issue

2

eissn

0066-4804

issn

1098-6596

pii

AAC.01714-17

journal_volume

62

pub_type

杂志文章
  • In vitro and in vivo activities of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae.

    abstract::The in vitro potency and in vivo efficacy of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae were investigated by pharmacokinetic studies with M. pneumoniae-infected hamsters. By using fluoroquinolones, macrolides, and tetracyclines as references, Q-35 was found to possess the greatest mycoplasmacidal activ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.9.1826

    authors: Gohara Y,Arai S,Akashi A,Kuwano K,Tseng CC,Matsubara S,Matumoto M,Furudera T

    更新日期:1993-09-01 00:00:00

  • Comparative Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Enterobacteriaceae Isolates Producing Extended-Spectrum β-Lactamases from U.S. Hospitals.

    abstract::The activities of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators were evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum β-lactamase (ESBL) genes detected by whole-genome sequencing analysis. Isolates were collected during 2017 in U.S. hospi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00160-19

    authors: Castanheira M,Doyle TB,Mendes RE,Sader HS

    更新日期:2019-06-24 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

  • Rapid microbiological assay for chlorhydroxyquinoline that uses a cryogenically stored inoculum.

    abstract::A rapid microbiological assay for chlorhydroxyquinoline is described. It is a turbidimetric procedure that uses Streptococcus faecalis as the test organism. Results are available within 5 h. Data are presented to show the advantages of using a cryogenically stored inoculum over an inoculum prepared on a daily basis. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.11.5.848

    authors: Cosgrove RF

    更新日期:1977-05-01 00:00:00

  • Phenotypic tolerance: antibiotic enrichment of noninherited resistance in bacterial populations.

    abstract::When growing bacteria are exposed to bactericidal concentrations of antibiotics, the sensitivity of the bacteria to the antibiotic commonly decreases with time, and substantial fractions of the bacteria survive. Using Escherichia coli CAB1 and antibiotics of five different classes (ampicillin, ciprofloxacin, rifampin,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.4.1483-1494.2005

    authors: Wiuff C,Zappala RM,Regoes RR,Garner KN,Baquero F,Levin BR

    更新日期:2005-04-01 00:00:00

  • Ultrastructural alterations induced by ICI 195,739, a bis-triazole derivative with strong antiproliferative action against Trypanosoma (Schizotrypanum) cruzi.

    abstract::The ultrastructural alterations induced in vitro by ICI 195,739, a recently developed bis-triazole derivative with potent antiproliferative effects on Trypanosoma (Schizotrypanum) cruzi, are reported. On epimastigotes, the triazole at its minimum growth-inhibitory concentration (0.1 microM) produced immediately (withi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.35.4.736

    authors: Lazardi K,Urbina JA,de Souza W

    更新日期:1991-04-01 00:00:00

  • 4,4'-isopropylidine-bis(2-isopropyl)phenol, a new inhibitor for cell wall formation of Bacillus subtilis.

    abstract::4,4'-Isopropylidine-bis[2-isopropyl]phenol was found to possess antimicrobial activity against gram-positive bacteria and some fungi, whereas it had no effect on gram-negative organisms. The drug has a potent inhibitory action on the synthesis of cell wall mucopeptides of Bacillus subtilis by inhibiting the enzyme d-g...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.9.4.580

    authors: Shimi IR,Shoukry S,Zaki Z

    更新日期:1976-04-01 00:00:00

  • ampG gene of Pseudomonas aeruginosa and its role in β-lactamase expression.

    abstract::In enterobacteria, the ampG gene encodes a transmembrane protein (permease) that transports 1,6-GlcNAc-anhydro-MurNAc and the 1,6-GlcNAc-anhydro-MurNAc peptide from the periplasm to the cytoplasm, which serve as signal molecules for the induction of ampC β-lactamase. The role of AmpG as a transporter is also essential...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00009-10

    authors: Zhang Y,Bao Q,Gagnon LA,Huletsky A,Oliver A,Jin S,Langaee T

    更新日期:2010-11-01 00:00:00

  • Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens.

    abstract::Despite the development of novel antibiotics active against Gram-positive bacteria, vancomycin generally remains the first treatment, although rapidly achieving concentrations associated with maximal efficacy provides an unresolved challenge. The objective of this study was to conduct a population pharmacokinetic anal...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01708-10

    authors: Roberts JA,Taccone FS,Udy AA,Vincent JL,Jacobs F,Lipman J

    更新日期:2011-06-01 00:00:00

  • Indirect mouse model for the evaluation of potential antiviral compounds: results with Venezuelan equine encephalomyelitis virus.

    abstract::An indirect mouse model was utilized to evaluate the antiviral activity of several compounds against Venezuelan equine encephalomyelitis (VEE) virus infection in mice. Mice were given various dosages of lysine-stabilized polyriboinosinic acid-polyribocytidylic acid, a tilorone analogue, kethoxal, or mepacrine before a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.11.4.683

    authors: Kuehne RW,Pannier WL,Stephen EL

    更新日期:1977-04-01 00:00:00

  • Novel dengue virus-specific NS2B/NS3 protease inhibitor, BP2109, discovered by a high-throughput screening assay.

    abstract::Dengue virus (DENV) causes disease globally, with an estimated 25 to 100 million new infections per year. At present, no effective vaccine is available, and treatment is supportive. In this study, we identified BP2109, a potent and selective small-molecule inhibitor of the DENV NS2B/NS3 protease, by a high-throughput ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00855-10

    authors: Yang CC,Hsieh YC,Lee SJ,Wu SH,Liao CL,Tsao CH,Chao YS,Chern JH,Wu CP,Yueh A

    更新日期:2011-01-01 00:00:00

  • In vitro studies of the combined effect of ampicillin and sulfonamides on Nocardia asteroides and results of therapy in four patients.

    abstract::The minimal inhibiting concentrations (MIC) of ampicillin, trisulfapyrimidines, and various combinations of these drugs were determined for four clinical isolates of Nocardia asteroides on Mueller-Hinton agar. The combination of ampicillin and sulfonamides was found to be synergistic for three of the four isolates whe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.1.3.215

    authors: Orfanakis MG,Wilcox HG,Smith CB

    更新日期:1972-03-01 00:00:00

  • The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase.

    abstract::We recently reported that HIV-1 resistant to 3'-azido-3'-deoxythymidine (AZT) is not cross-resistant to 3'-azido-2',3'-dideoxypurines. This finding suggested that the nucleoside base is a major determinant of HIV-1 resistance to nucleoside analogs. To further explore this hypothesis, we conducted in vitro selection ex...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00414-11

    authors: Meteer JD,Koontz D,Asif G,Zhang HW,Detorio M,Solomon S,Coats SJ,Sluis-Cremer N,Schinazi RF,Mellors JW

    更新日期:2011-08-01 00:00:00

  • Preliminary trial of recombinant fibroblast interferon in chronic hepatitis B virus infection.

    abstract::Five patients with chronic hepatitis B were treated with 8-day courses of leukocyte (alpha) interferon (5 X 10(6) U/day) and with 8-day courses of recombinant fibroblast (betaser) interferon at dosages of 5 X 10(6), 35 X 10(6), and 105 X 10(6) U/day. Inhibition of hepatitis B virus replication as evidenced by a decrea...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.29.1.122

    authors: Eisenberg M,Rosno S,Garcia G,Konrad MW,Gregory PB,Robinson WS,Merigan TC

    更新日期:1986-01-01 00:00:00

  • Hepatitis C virus (HCV) NS5B nonnucleoside inhibitors specifically block single-stranded viral RNA synthesis catalyzed by HCV replication complexes in vitro.

    abstract::Replication complexes of hepatitis C virus synthesized two major species of viral RNA in vitro, double stranded and single stranded. NS5B nonnucleoside inhibitors inhibited dose dependently the synthesis of single-stranded RNA but not double-stranded RNA. Moreover, replication complexes carrying a mutation resistant t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00498-06

    authors: Yang W,Sun Y,Phadke A,Deshpande M,Huang M

    更新日期:2007-01-01 00:00:00

  • Effect of ketoconazole on isolated mitochondria from Candida albicans.

    abstract::Ketoconazole, an oral antimycotic imidazole drug, blocked the transport of electrons in the respiratory chain of Candida albicans under aerobic conditions with different substrates, such as NADH and succinate. This effect was a nonspecific inhibition of NADH oxidases and succinate oxidases. The addition of ketoconazol...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.21.6.919

    authors: Shigematsu ML,Uno J,Arai T

    更新日期:1982-06-01 00:00:00

  • Ribosylation by mycobacterial strains as a new mechanism of rifampin inactivation.

    abstract::Several fast-growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were dete...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.4.1007

    authors: Dabbs ER,Yazawa K,Mikami Y,Miyaji M,Morisaki N,Iwasaki S,Furihata K

    更新日期:1995-04-01 00:00:00

  • Liquid chromatographic assay of ketoconazole.

    abstract::A reverse-phase, high-pressure liquid chromatographic method for the rapid and quantitative determination of ketoconazole has been developed. Drug levels from 0.5 to 10 microgram/ml can be determined in either yeast nitrogen base medium or human serum by using an octadecylsilane column. A retention time of 4.9 +/- 0.1...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.1.110

    authors: Andrews FA,Peterson LR,Beggs WH,Crankshaw D,Sarosi GA

    更新日期:1981-01-01 00:00:00

  • Clinical isolates of Aspergillus species remain fully susceptible to voriconazole in the post-voriconazole era.

    abstract::We studied the activity of voriconazole against 400 clinical strains of Aspergillus from the pre-voriconazole (1999 to 2002) and post-voriconazole (2003 to 2007) periods. Although the mean MICs of strains from the post-voriconazole period were slightly higher (0.39 versus 0.57 microg/ml; P < 0.001), all strains were s...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00629-08

    authors: Guinea J,Recio S,Peláez T,Torres-Narbona M,Bouza E

    更新日期:2008-09-01 00:00:00

  • Outcomes of moderate-to-severe Pneumocystis pneumonia treated with adjunctive steroid in non-HIV-infected patients.

    abstract::While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy wit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00669-11

    authors: Moon SM,Kim T,Sung H,Kim MN,Kim SH,Choi SH,Jeong JY,Woo JH,Kim YS,Lee SO

    更新日期:2011-10-01 00:00:00

  • Double-blind clinical trials of oral cyclacillin and ampicillin.

    abstract::A double-blind study was performed to compare the clinical response and the incidence of side effects in 2,581 patients administered ampicillin or cyclacillin for infections of the genitourinary or respiratory tract, infections of the skin and soft tissues, or for otitis media. There was no significant difference in c...

    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.15.1.55

    authors: Gold JA,Hegarty CP,Deitch MW,Walker BR

    更新日期:1979-01-01 00:00:00

  • Pharmacokinetic and pharmacodynamic approach for comparing two therapeutic regimens using amikacin.

    abstract::The efficiencies of two dosage schedules of amikacin (2 x 10 mg/kg of body weight per 24 h and 1 x 20 mg/kg/24 h intramuscularly for 5 days) against Pseudomonas aeruginosa sepsis in rabbits were compared. Blood samples were drawn at various times after the first application, and amikacin concentrations in serum were a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.5.981

    authors: Staneva M,Markova B,Atanasova I,Terziivanov D

    更新日期:1994-05-01 00:00:00

  • Selective inhibition of the accumulation of extracellular proteases of Pseudomonas aeruginosa by gentamicin and tobramycin.

    abstract::Gentamicin and tobramycin inhibited the accumulation of extracellular proteases secreted by Pseudomonas aeruginosa. The secretion of protease was inhibited at concentrations of these drugs that were below the level required to inhibit general protein synthesis. Neither magnesium ions nor high ionic strength antagonize...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.27.4.468

    authors: Warren RL,Baker NR,Johnson J,Stapleton MJ

    更新日期:1985-04-01 00:00:00

  • Prevalence of erm gene classes in erythromycin-resistant Staphylococcus aureus strains isolated between 1959 and 1988.

    abstract::The epidemiology of the two common erythromycin resistance methylase (erm) genes ermA and ermC was analyzed by Southern blotting in 428 erythromycin-resistant Staphylococcus aureus strains isolated from blood between 1959 and 1988 in Denmark. ermA and/or ermC was present in 98% of the erythromycin-resistant strains te...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.2.369

    authors: Westh H,Hougaard DM,Vuust J,Rosdahl VT

    更新日期:1995-02-01 00:00:00

  • Effects of moxalactam and cefuroxime on mitogen-stimulated human mononuclear leukocytes.

    abstract::The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied. Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells. Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted. Compared with control cell cultures...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.3.360

    authors: Manzella JP,Clark JK

    更新日期:1983-03-01 00:00:00

  • Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility.

    abstract::Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00261-20

    authors: Liston SD,Whitesell L,Kapoor M,Shaw KJ,Cowen LE

    更新日期:2020-04-21 00:00:00

  • In vitro antifungal susceptibilities of Trichosporon species.

    abstract::The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of Trichosporon spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.4.1144-1146.2002

    authors: Paphitou NI,Ostrosky-Zeichner L,Paetznick VL,Rodriguez JR,Chen E,Rex JH

    更新日期:2002-04-01 00:00:00

  • Determination of Pharmacodynamic Target Exposures for Rezafungin against Candida tropicalis and Candida dubliniensis in the Neutropenic Mouse Disseminated Candidiasis Model.

    abstract::Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4 Candida tropicalis and 4 Candida dubliniensis strains, using the neutropenic mouse invasive candidiasis model. The area under the concentration-time cur...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01556-19

    authors: Lepak AJ,Zhao M,Andes DR

    更新日期:2019-10-22 00:00:00

  • Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients.

    abstract::The pharmacokinetics of cidofovir (HPMPC; (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine) were examined at five dose levels in three phase I/II studies in a total of 42 human immunodeficiency virus-infected patients (with or without asymptomatic cytomegalovirus infection). Levels of cidofovir in serum following...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.6.1247

    authors: Cundy KC,Petty BG,Flaherty J,Fisher PE,Polis MA,Wachsman M,Lietman PS,Lalezari JP,Hitchcock MJ,Jaffe HS

    更新日期:1995-06-01 00:00:00

  • Mapping simocyclinone D8 interaction with DNA gyrase: evidence for a new binding site on GyrB.

    abstract::Simocyclinone D8, a coumarin derivative isolated from Streptomyces antibioticus Tü 6040, represents an interesting new antiproliferative agent. It was originally suggested that this drug recognizes the GyrA subunit and interferes with the gyrase catalytic cycle by preventing its binding to DNA. To further characterize...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00972-09

    authors: Sissi C,Vazquez E,Chemello A,Mitchenall LA,Maxwell A,Palumbo M

    更新日期:2010-01-01 00:00:00