Evaluation of Amphotericin B Lipid Formulations for Treatment of Severe Coccidioidomycosis.

Abstract:

:Patients with severe coccidioidomycosis infections are often treated with either amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB). Outcome data with these agents in severe coccidioidomycosis cases are currently lacking. The purpose of this study is to evaluate the efficacy and toxicity of ABLC and L-AmB in treating severe coccidioidomycosis. A retrospective pre-post study design was employed. Chart reviews were completed from 1 January 2005 to 31 December 2014 for all patients who received lipid-based amphotericin B. Inclusion criteria included having a follow-up complement fixation (CF) titer or a treatment emergent adverse event (TEAE) prior to follow-up. Patients with meningeal involvement and pregnant patients were excluded. Treatment outcomes were assessed based on documented completion of therapy as well on symptoms, complement fixation titer, and changes to laboratory monitoring parameters. A total of 108 patients were identified, 69 of whom met the inclusion criteria. There were no statistical differences in demographics or disease burden in those that received ABLC and those that received L-AmB, except that those who received L-AmB were more likely to have previously diagnosed chronic kidney disease (nL-AmB = 4, 12.5% vs nABLC = 0, 0.0%; P = 0.042) and to have a lower creatinine clearance at the start of therapy (L-AmB = 79.6 mg/dl versus ABLC = 100.4 mg/dl; P = 0.008). Successful treatment was achieved in 27 (73.0%) of ABLC patients and 22 (68.8%) of L-AmB patients (P = 0.700). Amphotericin B was discontinued due to documented completion of therapy for 17 (45.9%) ABLC patients and 18 (56.3%) L-AmB patients (P = 0.553). Acute kidney injury (AKI) was the documented reason of treatment cessation for 10 (27.0%) ABLC and 1 (3.1%) L-AmB patient (P = 0.007). ABLC and L-AmB both appear to be equally efficacious in the treatment of severe coccidioidomycosis. L-AmB may have less renal toxicity than ABLC and may be the preferred agent in baseline renal impairment.

authors

Sidhu R,Lash DB,Heidari A,Natarajan P,Johnson RH

doi

10.1128/AAC.02293-17

subject

Has Abstract

pub_date

2018-06-26 00:00:00

issue

7

eissn

0066-4804

issn

1098-6596

pii

AAC.02293-17

journal_volume

62

pub_type

杂志文章
  • Efficacy of teicoplanin-gentamicin given once a day on the basis of pharmacokinetics in humans for treatment of enterococcal experimental endocarditis.

    abstract::With the aim of investigating home therapy for enterococcal endocarditis, we compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicillin plus gentamicin administered t.i.d., for treating experimental enterococcal endocarditis. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.5.1387-1393.2001

    authors: López P,Gavaldà J,Martin MT,Almirante B,Gomis X,Azuaje C,Borrell N,Pou L,Falcó V,Pigrau C,Pahissa A

    更新日期:2001-05-01 00:00:00

  • Experimental prediction of the evolution of ceftazidime resistance in the CTX-M-2 extended-spectrum beta-lactamase.

    abstract::We applied in vitro evolution to an Escherichia coli strain containing bla(CTX-M-2) and obtained 10 independent mutant bla(CTX-M-2) alleles that confer elevated resistance to ceftazidime (MIC > or = 32 microg/ml) but lost the ability to confer resistance to cefepime. All alleles had a Pro-to-Ser substitution at positi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.3.1242-1244.2005

    authors: Welsh KJ,Barlow M,Tenover FC,Biddle JW,Rasheed JK,Clark LA,McGowan JE Jr

    更新日期:2005-03-01 00:00:00

  • Sequence of pNL194, a 79.3-kilobase IncN plasmid carrying the blaVIM-1 metallo-beta-lactamase gene in Klebsiella pneumoniae.

    abstract::The nucleotide sequence of pNL194, a VIM-1-encoding plasmid, is described in this study. pNL194 (79,307 bp) comprised an IncN-characteristic segment (38,940 bp) and a mosaic structure (40,367 bp) including bla(VIM-1), aacA7, aadA1, aadA2, dfrA1, dfrA12, aphA1, strA, strB, and sul1. Tn1000 or Tn5501 insertion within fi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00665-10

    authors: Miriagou V,Papagiannitsis CC,Kotsakis SD,Loli A,Tzelepi E,Legakis NJ,Tzouvelekis LS

    更新日期:2010-10-01 00:00:00

  • Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model.

    abstract::A-837093 is a potent and specific nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase. It possesses nanomolar potencies in both enzymatic and replicon-based cell culture assays. In rats and dogs this compound demonstrated an oral plasma half-life of great...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00723-07

    authors: Chen CM,He Y,Lu L,Lim HB,Tripathi RL,Middleton T,Hernandez LE,Beno DW,Long MA,Kati WM,Bosse TD,Larson DP,Wagner R,Lanford RE,Kohlbrenner WE,Kempf DJ,Pilot-Matias TJ,Molla A

    更新日期:2007-12-01 00:00:00

  • First detection of metallo-beta-lactamase VIM-2 in Pseudomonas aeruginosa isolates from Colombia.

    abstract::Carbapenem resistance rates in Pseudomonas aeruginosa isolates in Colombia, as in many South American countries, are high for reasons that remain unclear. From our nationwide network, we describe the first detection of the metallo-beta-lactamase VIM-2 in clinical isolates of P. aeruginosa from multiple cities within C...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.1.226-229.2006

    authors: Villegas MV,Lolans K,del Rosario Olivera M,Suarez CJ,Correa A,Queenan AM,Quinn JP,Colombian Nosocomial Resistance Study Group.

    更新日期:2006-01-01 00:00:00

  • Mutations Reducing In Vitro Susceptibility to Novel LpxC Inhibitors in Pseudomonas aeruginosa and Interplay of Efflux and Nonefflux Mechanisms.

    abstract::Upregulated expression of efflux pumps, lpxC target mutations, LpxC protein overexpression, and mutations in fabG were previously shown to mediate single-step resistance to the LpxC inhibitor CHIR-090 in P. aeruginosa Single-step selection experiments using three recently described LpxC inhibitors (compounds 2, 3, and...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01490-19

    authors: Jones AK,Caughlan RE,Woods AL,Uehara K,Xie L,Barnes SW,Walker JR,Thompson KV,Ranjitkar S,Lee PS,Dean CR

    更新日期:2019-12-20 00:00:00

  • In vitro assessment of methylene blue on chloroquine-sensitive and -resistant Plasmodium falciparum strains reveals synergistic action with artemisinins.

    abstract::Methylene blue (MB) represents a promising antimalarial drug candidate for combination therapies against drug-resistant parasite strains. To support and facilitate the application of MB in future field trials, we studied its antiparasitic effects in vitro. MB is active against all blood stages of both chloroquine (CQ)...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.11.4592-4597.2005

    authors: Akoachere M,Buchholz K,Fischer E,Burhenne J,Haefeli WE,Schirmer RH,Becker K

    更新日期:2005-11-01 00:00:00

  • Human macrophage inflammatory protein 3alpha: protein and peptide nuclear magnetic resonance solution structures, dimerization, dynamics, and anti-infective properties.

    abstract::Human macrophage inflammatory protein 3alpha (MIP-3alpha), also known as CCL20, is a 70-amino-acid chemokine which exclusively binds to chemokine receptor 6. In addition, the protein also has direct antimicrobial, antifungal, and antiviral activities. The solution structure of MIP-3alpha was solved by the use of two-d...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00805-07

    authors: Chan DI,Hunter HN,Tack BF,Vogel HJ

    更新日期:2008-03-01 00:00:00

  • β-lactam combinations that exhibit synergy against Mycobacteroides abscessus clinical isolates.

    abstract::Mycobacteroides abscessus (Mab) is an opportunistic environmental pathogen that can cause chronic pulmonary disease in the setting of structural lung conditions such as bronchiectasis, COPD and cystic fibrosis. These infections are often incurable and associated with rapid lung function decline. Mab is naturally resis...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02545-20

    authors: Story-Roller E,Galanis C,Lamichhane G

    更新日期:2020-12-23 00:00:00

  • Preclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A Inhibitor, EDP-239.

    abstract::EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated in vitro and in vivo EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6. In the presence of human serum, the potency of EDP-2...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1128/AAC.00808-16

    authors: Owens CM,Brasher BB,Polemeropoulos A,Rhodin MH,McAllister N,Peng X,Wang C,Ying L,Cao H,Lawitz E,Poordad F,Rondon J,Box TD,Zeuzem S,Buggisch P,Lin K,Qiu YL,Jiang L,Colvin R,Or YS

    更新日期:2016-09-23 00:00:00

  • In vitro activity of tosufloxacin (A-61827; T-3262) against selected genital pathogens.

    abstract::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.6.971

    authors: Segreti J,Hirsch DJ,Harris AA,Kapell KS,Orbach H,Kessler HA

    更新日期:1990-06-01 00:00:00

  • Colostrum hexasaccharide, a novel Staphylococcus aureus quorum-sensing inhibitor.

    abstract::The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colost...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03722-14

    authors: Srivastava A,Singh BN,Deepak D,Rawat AK,Singh BR

    更新日期:2015-04-01 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

  • Association of composite IS26-sul3 elements with highly transmissible IncI1 plasmids in extended-spectrum-beta-lactamase-producing Escherichia coli clones from humans.

    abstract::The association of an IS440-sul3 platform with Tn21 class 1 integrons carried by IncI1 plasmids encoding extended-spectrum β-lactamases (ESBLs; mainly SHV-12 and CTX-M-14) among worldwide Escherichia coli clones of phylogroups A (ST10, ST23, and ST46), B1 (ST155, ST351, and ST359), and D/B2 (ST131) is reported. An in ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01448-10

    authors: Curiao T,Cantón R,Garcillán-Barcia MP,de la Cruz F,Baquero F,Coque TM

    更新日期:2011-05-01 00:00:00

  • A novel C5a-derived immunobiotic peptide reduces Streptococcus agalactiae colonization through targeted bacterial killing.

    abstract::Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Cu...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01590-13

    authors: Cavaco CK,Patras KA,Zlamal JE,Thoman ML,Morgan EL,Sanderson SD,Doran KS

    更新日期:2013-11-01 00:00:00

  • Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms.

    abstract::Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02157-15

    authors: Sanglard D,Coste AT

    更新日期:2015-10-19 00:00:00

  • Contribution of mutation at amino acid 45 of AcrR to acrB expression and ciprofloxacin resistance in clinical and veterinary Escherichia coli isolates.

    abstract::Fluoroquinolone-resistant Escherichia coli isolates which overexpressed acrB and had a substitution at amino acid 45 of AcrR were complemented with wild-type acrR. Complementation led to increased sensitivity to ciprofloxacin and to ethidium bromide, suggesting that mutation at amino acid 45 of AcrR contributes to cip...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.10.4390-4392.2005

    authors: Webber MA,Talukder A,Piddock LJ

    更新日期:2005-10-01 00:00:00

  • Pharmacokinetic/Pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors.

    abstract::This analysis was conducted to determine whether the hepatitis C virus (HCV) viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day monotherapy studies of patients infected with genotype 1 chronic HCV. This analysis in...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06283-11

    authors: Reddy MB,Morcos PN,Le Pogam S,Ou Y,Frank K,Lave T,Smith P

    更新日期:2012-06-01 00:00:00

  • Synergy between cilofungin and amphotericin B in a murine model of candidiasis.

    abstract::The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5) CFU of Candida albicans. At 4 days postinfection, intraperitoneal therapy was initiated and was continued for 14 days. The...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.35.7.1334

    authors: Hanson LH,Perlman AM,Clemons KV,Stevens DA

    更新日期:1991-07-01 00:00:00

  • Antibodies to nystatin demonstrate polyene sterol specificity and allow immunolabeling of sterols in Saccharomyces cerevisiae.

    abstract::Polyclonal antibodies elicited by injection into rabbits of a nystatin-bovine serum albumin conjugate were reactive with both nystatin and amphotericin B. Upon labeling of polyene-treated Saccharomyces cerevisiae sterol auxotrophs grown on various sterols, nystatin reacted specifically with ergosterol, while amphoteri...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.12.2092

    authors: Walker-Caprioglio HM,MacKenzie JM,Parks LW

    更新日期:1989-12-01 00:00:00

  • Natural occurrence of structures in oral streptococci and enterococci with DNA homology to Tn916.

    abstract::Seventeen oral streptococci and 18 enterococci were tested for the presence of DNA sequences homologous to the conjugative transposon Tn916 encoding tetracycline resistance. All the strains were resistant to tetracyclines, including minocycline, and most of them were resistant to other antibiotics. Tn916-like structur...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.1.59

    authors: Bentorcha F,Clermont D,de Cespédès G,Horaud T

    更新日期:1992-01-01 00:00:00

  • Efficacy and safety of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 milligrams twice daily for 5 days versus amoxicillin-clavulanate at 875/125 milligrams twice daily for 7 days in the treatment of acute exacerbations of chronic bronc

    abstract::This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment o...

    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.49.1.153-160.2005

    authors: Sethi S,Breton J,Wynne B

    更新日期:2005-01-01 00:00:00

  • Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis.

    abstract::Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01521-17

    authors: Denti P,Garcia-Prats AJ,Draper HR,Wiesner L,Winckler J,Thee S,Dooley KE,Savic RM,McIlleron HM,Schaaf HS,Hesseling AC

    更新日期:2018-01-25 00:00:00

  • Comparison of oral fluconazole and clotrimazole troches as treatment for oral candidiasis in patients infected with human immunodeficiency virus.

    abstract::Thirty-nine adult patients with human immunodeficiency virus infection and oral candidiasis were randomly assigned to receive either one fluconazole capsule (100 mg) or five clotrimazole troches (10 mg each) daily for 14 days. Among 36 evaluable patients, clinical resolution rates were 100 and 65%, respectively (P = 0...

    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.34.11.2267

    authors: Koletar SL,Russell JA,Fass RJ,Plouffe JF

    更新日期:1990-11-01 00:00:00

  • In vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis.

    abstract::We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This r...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.8.1711

    authors: Gollapudi SV,Chuah SK,Harvey T,Thadepalli HD,Thadepalli H

    更新日期:1993-08-01 00:00:00

  • An Exposure-Response Perspective on the Clinical Dose of Pretomanid.

    abstract::Pretomanid was approved by the U.S. FDA, via the limited population pathway for antibacterial and antifungal drugs, as part of a three-drug regimen with bedaquiline and linezolid for the treatment of extensively drug-resistant and treatment-intolerant or nonresponsive multidrug-resistant tuberculosis. The recommended ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01121-20

    authors: Nedelman JR,Salinger DH,Subramoney V,Woolson R,Wade K,Li M,Everitt D,Mendel CM,Spigelman M

    更新日期:2020-12-16 00:00:00

  • Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis.

    abstract::The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.2.225

    authors: Hughes WT,Gray VL,Gutteridge WE,Latter VS,Pudney M

    更新日期:1990-02-01 00:00:00

  • Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment.

    abstract::A case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also de...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00330-20

    authors: Avanzi C,Maia RC,Benjak A,Nery JA,Sales AM,Miranda A,Duppre NC,Nogueira Brum Fontes A,Pereira da Silva T,Olmo Pinheiro R,Neves-Manta F,Moreira SJM,Busso P,Sarno EN,Suffys PN,Cole ST,Moraes MO

    更新日期:2020-06-23 00:00:00

  • Genetic analysis of azole resistance in the Darlington strain of Candida albicans.

    abstract::High-level azole resistance in the Darlington strain of Candida albicans was investigated by gene replacement in C. albicans and expression in Saccharomyces cerevisiae. We sequenced the ERG11 gene, which encodes the sterol C(14)alpha-demethylase, from our copy of the Darlington strain. Both alleles contained the histi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.11.2985-2990.2000

    authors: Kakeya H,Miyazaki Y,Miyazaki H,Nyswaner K,Grimberg B,Bennett JE

    更新日期:2000-11-01 00:00:00

  • Purification and characterization of an antibacterial substance produced by a marine Alteromonas species.

    abstract::An extracellular inhibitory substance produced by the marine Alteromonas strain P-31 (NCMB 2144) was isolated and purified. The inhibitor was a macromolecule with a molecular weight of 90,000 estimated by Sephadex G-100 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The inhibitory activi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.10.1674

    authors: Barja JL,Lemos ML,Toranzo AE

    更新日期:1989-10-01 00:00:00