Pharmacodynamic evaluation of the neutralization of endotoxin by PMX622 in mice.


:Polymyxin B (PMB) binds to and neutralizes endotoxin, but its systemic clinical utility is limited by neuro- and nephrotoxicity. PMX622 is a covalent conjugate of PMB and Dextran-70 designed to retain the ability of PMB to neutralize endotoxin and to retain the favorable colloidal, pharmacokinetic, and metabolic properties of Dextran-70. PMX622 has demonstrated efficacy in a number of animal models and effectively neutralized endotoxin in phase I clinical trials. Here, we systematically evaluated the pharmacodynamic properties of PMX622 in a murine model of endotoxin-induced lethality in galactosamine-sensitized mice. PMX622 completely and dose dependently inhibited lethality in this model. A stoichiometric relationship was found between the endotoxin challenge dose and the dose of PMX622 needed for protection. PMX622 neutralized endotoxin from four different genera of gram-negative bacteria but not Neisseria meningitidis. PMX622 was significantly less toxic than PMB in the mouse, suggesting that PMX622 has a better margin of safety than PMB. The timing of PMX622 administration relative to endotoxin was crucial. PMX622 was active for several hours prior to the endotoxin challenge; however, PMX622 did not protect mice if administered >/=15 min after endotoxin challenge. This suggests that PMX622 would best be clinically used prophylactically rather than therapeutically. These studies will be crucial in designing and interpreting human clinical trials assessing PMX622 efficacy.


Lake P,DeLeo J,Cerasoli F,Logdberg L,Weetall M,Handley D




Has Abstract


2004-08-01 00:00:00














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    abstract::The antileishmanial efficacies of four proprietary amphotericin B (AmB) formulations (Fungizone, AmBisome, Abelcet, and Amphocil) and an experimental nonionic surfactant vesicle (NIV) formulation were compared in a murine model of acute visceral leishmaniasis. By a multiple-dosing regimen, groups of Leishmania donovan...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Mullen AB,Carter KC,Baillie AJ

    更新日期:1997-10-01 00:00:00

  • Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors.

    abstract::Resistance to the recently approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) commonly involves substitutions at positions E138K and K101E in HIV-1 reverse transcriptase (RT), together with an M184I substitution that is associated with resistance to coutilized emtricitabine (FTC). Previou...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Xu HT,Colby-Germinario SP,Huang W,Oliveira M,Han Y,Quan Y,Petropoulos CJ,Wainberg MA

    更新日期:2013-11-01 00:00:00

  • Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in HCV GT2.

    abstract::Hepatitis C virus (HCV) genotype (GT) 2 represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to interferon-α, the presence of polymorphisms in NS5A can impact efficacy of NS5A inh...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Asante-Appiah E,Ingravallo P,McMonagle P,Bystol K,Xia E,Curry S,Qiu P,Black S,Chase R,Liu R,Lahser F

    更新日期:2019-09-16 00:00:00

  • Prolonged malaria prophylaxis with chloroquine and proguanil (chloroguanide) in a nonimmune resident population of an endemic area with a high prevalence of chloroquine resistance.

    abstract::One hundred thirty nonimmune subjects living in Yaoundé, Cameroon, completed an 18-month prospective study on the efficacy and safety of weekly chloroquine and daily proguanil (chloroguanide) (Ch-P) in malaria prevention. A total of 9 of 78 Ch-P-treated subjects and 26 of 52 subjects who received no prophylaxis contra...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章


    authors: Gozal D,Hengy C,Fadat G

    更新日期:1991-02-01 00:00:00

  • Selective interaction of the human immunodeficiency virus type 1 reverse transcriptase nonnucleoside inhibitor efavirenz and its thio-substituted analog with different enzyme-substrate complexes.

    abstract::Accumulating data have brought the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) into the forefront of antiretroviral therapy. Among the emerging compounds in this class, a particularly attractive one is efavirenz (Sustiva), recently approved for clinical use by the U.S. Food and Drug Administration. In...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Maga G,Ubiali D,Salvetti R,Pregnolato M,Spadari S

    更新日期:2000-05-01 00:00:00

  • Efficacy of tigecycline for secondary Acinetobacter bacteremia and factors associated with treatment failure.

    abstract::We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Liou BH,Lee YT,Kuo SC,Liu PY,Fung CP

    更新日期:2015-01-01 00:00:00

  • In vitro activity of OPC-17116.

    abstract::The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Neu HC,Fang W,Gu JW,Chin NX

    更新日期:1992-06-01 00:00:00

  • In vitro culture system to determine MICs and MBCs of antimicrobial agents against Treponema pallidum subsp. pallidum (Nichols strain).

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Norris SJ,Edmondson DG

    更新日期:1988-01-01 00:00:00

  • In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4.

    abstract::The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing mycobacteria at pHs 6.8 and 7.4, as determined radiometrically. The MICs at pH 7.4 were abo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rastogi N,Goh KS,Berchel M,Bryskier A

    更新日期:2000-10-01 00:00:00

  • Pharmacokinetics of a new parenteral oligosaccharide antibiotic, SCH27899 (Ziracin), in healthy subjects.

    abstract::The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章


    authors: Kozawa O,Uematsu T,Matsuno H,Niwa M,Kohno K,Kawato A,Takahashi K,Nagashima S,Kanamaru M

    更新日期:2001-03-01 00:00:00

  • Sustained delivery of commensal bacteria from pod-intravaginal rings.

    abstract::Topical administration of live commensal bacteria to the vaginal tract holds significant potential as a cost-effective strategy for the treatment of sexually transmitted infections and the delivery of mucosal vaccines. Probiotic-releasing intravaginal rings (IVRs) embody significant theoretical advantages over traditi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Gunawardana M,Mullen M,Yoo J,Webster P,Moss JA,Baum MM

    更新日期:2014-01-01 00:00:00

  • Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the β-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验


    authors: Griffith DC,Loutit JS,Morgan EE,Durso S,Dudley MN

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Walker DJ,Pitsch JL,Peng MM,Robinson BL,Peters W,Bhisutthibhan J,Meshnick SR

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Blango MG,Mulvey MA

    更新日期:2010-05-01 00:00:00

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    authors: Vincent IM,Ehmann DE,Mills SD,Perros M,Barrett MP

    更新日期:2016-03-25 00:00:00

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    journal_title:Antimicrobial agents and chemotherapy

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    authors: Bidell MR,Palchak M,Mohr J,Lodise TP

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: el Benna J,Pasquier C,Labro MT

    更新日期:1991-07-01 00:00:00

  • Pharmacokinetics and safety of caspofungin in neonates and infants less than 3 months of age.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Sáez-Llorens X,Macias M,Maiya P,Pineros J,Jafri HS,Chatterjee A,Ruiz G,Raghavan J,Bradshaw SK,Kartsonis NA,Sun P,Strohmaier KM,Fallon M,Bi S,Stone JA,Chow JW

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  • Susceptibility of Eikenella corrodens to newer beta-lactam antibiotics.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Goldstein EJ,Gombert ME,Agyare EO

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  • Establishment and Validation of Galleria mellonella as a Novel Model Organism To Study Mycobacterium abscessus Infection, Pathogenesis, and Treatment.

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    journal_title:Antimicrobial agents and chemotherapy

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  • Rapid, modified Kirby-Bauer susceptibility test with single, high-concentration antimicrobial disks.

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    journal_title:Antimicrobial agents and chemotherapy

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  • Impact of Antifungal Compounds on Viability and Anti-Aspergillus Activity of Human Natural Killer Cells.

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    journal_title:Antimicrobial agents and chemotherapy

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    authors: Schmidt S,Schubert R,Tramsen L,Lehrnbecher T

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    journal_title:Antimicrobial agents and chemotherapy

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    authors: Peltroche-Llacsahuanga H,Goyard S,d'Enfert C,Prill SK,Ernst JF

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Krief S,Martin MT,Grellier P,Kasenene J,Sévenet T

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  • Comparative effects of amoxycillin and ampicillin in the treatment of experimental mouse infections.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Comber KR,Osborne CD,Sutherland R

    更新日期:1975-02-01 00:00:00

  • Pharmacokinetic evaluation of single-dose intravenous daptomycin in patients with thermal burn injury.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章


    authors: Mohr JF 3rd,Ostrosky-Zeichner L,Wainright DJ,Parks DH,Hollenbeck TC,Ericsson CD

    更新日期:2008-05-01 00:00:00

  • Chemical genomic screening of a Saccharomyces cerevisiae genomewide mutant collection reveals genes required for defense against four antimicrobial peptides derived from proteins found in human saliva.

    abstract::To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Lis M,Bhatt S,Schoenly NE,Lee AY,Nislow C,Bobek LA

    更新日期:2013-02-01 00:00:00

  • Antimicrobial resistance and incompatibility groups of R plasmids in Salmonella typhimurium isolated from human sources in Bombay from 1978 to 1980.

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    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rangnekar VM,Banker DD,Jhala HI

    更新日期:1983-01-01 00:00:00

  • Integron-mediated rifampin resistance in Pseudomonas aeruginosa.

    abstract::A new rifampin resistance gene, arr-2, has been found in Pseudomonas aeruginosa. The ARR-2 protein shows 54% amino acid identity to the rifampin ADP-ribosylating transferase encoded by the arr gene from Mycobacterium smegmatis. This arr-2 gene is located on a gene cassette within a class I integron. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Tribuddharat C,Fennewald M

    更新日期:1999-04-01 00:00:00