Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Eastern Cambodia.

Abstract:

:In Cambodia, multidrug-resistant Plasmodium falciparum undermines the treatment of uncomplicated malaria, and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia. We conducted a single-arm, open-label, prospective study between July and December 2017 at the Koh Gnek (Mondulkiri) and Veun Sai (Rattanakiri) health centers in eastern Cambodia. Eligible patients were aged ≥7 years (females, ages 12 to 18 years, were excluded), weighing ≥20 kg, with microscopically confirmed P. falciparum monoinfection and fever. Oral pyronaridine-artesunate was administered once daily for 3 days, dosed according to body weight, plus a single dose of primaquine on day 0. Sixty patients were recruited to Koh Gnek, and 61 patients were recruited to Veun Sai. The primary outcomes, i.e., the day 42 PCR-adjusted adequate clinical and parasitological responses (ACPRs), were 98.3% (95% confidence interval [CI], 88.4 to 99.8) in Koh Gnek and 96.7% (95% CI, 87.3 to 99.2) in Veun Sai (Kaplan-Meier). In a per-protocol analysis, the proportions of patients with day 42 PCR-adjusted ACPRs were 98.3% (57/58; 95% CI, 90.8 to 100.0) at Koh Gnek and 96.7% (58/60; 95% CI, 88.5 to 99.6) at Veun Sai. The Kelch13 (C580Y) mutation was present in 70.0% (77/110) of isolates. The copy numbers were increased in 61.3% (73/119) of isolates for Pfpm2 and in 1.7% (2/119) for Pfmdr1 There was no relationship between outcome and the 50% inhibitory concentration of pyronaridine. Adverse events were consistent with malaria, and there were no serious adverse events. Pyronaridine-artesunate has high efficacy in eastern Cambodia and could be used to increase the diversity of antimalarial therapy in the region. (This study is registered in the Australian New Zealand Clinical Trials Registry [ANZCTR] under no. ACTRN12618001300268.).

authors

Leang R,Mairet-Khedim M,Chea H,Huy R,Khim N,Mey Bouth D,Dorina Bustos M,Ringwald P,Witkowski B

doi

10.1128/AAC.02242-18

subject

Has Abstract

pub_date

2019-02-26 00:00:00

issue

3

eissn

0066-4804

issn

1098-6596

pii

AAC.02242-18

journal_volume

63

pub_type

杂志文章
  • Do formulation differences between the reference listed drug and generic piperacillin-tazobactam impact reconstitution?

    abstract::Pharmaceutical differences between the reference listed drug (RLD) and generic formulations of piperacillin-tazobactam may impact the reconstitution process for intravenous administration. This study evaluated the RLD against three generic formulations and measured their reconstitution times using a standardized proce...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.04563-14

    authors: Zheng H,Truong J,Carroll F,Pai MP

    更新日期:2015-03-01 00:00:00

  • Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A.

    abstract::The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staph...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.18.5.766

    authors: Girolami RL,Stamm JM

    更新日期:1980-11-01 00:00:00

  • N-Acetyl-l-Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae.

    abstract::Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and nontypeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01992-16

    authors: Domenech M,García E

    更新日期:2017-01-24 00:00:00

  • Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application.

    abstract::Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) followi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05145-11

    authors: Berdugo M,Larsen IV,Abadie C,Deloche C,Kowalczuk L,Touchard E,Dubielzig R,Brandt CR,Behar-Cohen F,Combette JM

    更新日期:2012-03-01 00:00:00

  • Clinical isolate of herpes simplex virus type 2 that induces a thymidine kinase with altered substrate specificity.

    abstract::In vitro and in vivo studies were done on a herpes simplex virus type 2 strain recovered from a patient on acyclovir (ACV) which was ACV resistant but expressed thymidine (dThd) kinase (EC 2.7.1.21) activity. Plaque-purified clones derived from the original clinical sample were heterogeneous with respect to plaque siz...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.7.1117

    authors: Ellis MN,Keller PM,Fyfe JA,Martin JL,Rooney JF,Straus SE,Lehrman SN,Barry DW

    更新日期:1987-07-01 00:00:00

  • Enterococcus gallinarum N04-0414 harbors a VanD-type vancomycin resistance operon and does not contain a D-alanine:D-alanine 2 (ddl2) gene.

    abstract::Enterococcus gallinarum N04-0414 (MIC for vancomycin, 256 microg/ml) harbored a vanD-type vancomycin resistance operon as well as the intrinsic vanC1 operon. The D-Ala:D-Ala ligase 2 gene (ddl2) was not present in the strain, though it is found downstream of the vanS gene from the vanC operon in E. gallinarum ATCC 495...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.3.1067-1070.2006

    authors: Boyd DA,Miller MA,Mulvey MR

    更新日期:2006-03-01 00:00:00

  • Multicenter evaluation of a new DNA microarray for rapid detection of clinically relevant bla genes from beta-lactam-resistant gram-negative bacteria.

    abstract::A new commercial low-density microarray which identifies common extended-spectrum β-lactamase plasmid-mediated cephalosporinase genes, as well as carbapenemase (bla(KPC) and bla(NDM)) genes, was evaluated. We tested 207 clinical and reference/collection isolates of the Enterobacteriaceae possessing different bla genes...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00353-11

    authors: Bogaerts P,Hujer AM,Naas T,de Castro RR,Endimiani A,Nordmann P,Glupczynski Y,Bonomo RA

    更新日期:2011-09-01 00:00:00

  • CEM-101 activity against Gram-positive organisms.

    abstract::The in vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of the MICs and minimum bactericidal concentrations (MBCs), timed killing, single-step and multistep mutation rates, the erythromycin indu...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01662-09

    authors: Woosley LN,Castanheira M,Jones RN

    更新日期:2010-05-01 00:00:00

  • Toxicity of nalidixic acid on candida albicans, Saccharomyces cerevisiae, and Kluyveromyces lactis.

    abstract::The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temper...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.9.3.485

    authors: Sobieski RJ,Brewer AR

    更新日期:1976-03-01 00:00:00

  • Comparative evaluation of a new fluorescent carboxyfluorescein diacetate-modified microdilution method for antifungal susceptibility testing of Candida albicans isolates.

    abstract::This report presents a fluorescent carboxyfluorescein diacetate (CFDA)-modified microdilution method used for the susceptibility testing of Candida albicans to amphotericin B, fluconazole, ketoconazole, itraconazole, voriconazole, and flucytosine. Four different broth microdilution susceptibility testing methods were ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.10.3236-3242.2002

    authors: Liao RS,Rennie RP,Talbot JA

    更新日期:2002-10-01 00:00:00

  • Clinical and pharmacokinetic evaluation of parenteral moxalactam in infants and children.

    abstract::Thirty-four infants and children ranging in age from 2.5 to 180 months (mean, 40 months) were treated with parenteral moxalactam (150 mg/kg per day) for suspected or proved bacterial infections outside the central nervous system. Six patients infected with Haemophilus influenzae b, nine infected with Staphylococcus au...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.21.6.898

    authors: Keyserling H,Feldman WE,Moffitt S,Manning N,Hollins M

    更新日期:1982-06-01 00:00:00

  • CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus.

    abstract::We designed, synthesized, and characterized a novel nucleoside analog, (1S,3S,5S)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-5-hydroxy-1-(hydroxymethyl)-2-methylene-cyclopentanecarbonitrile, or 4'-cyano-methylenecarbocyclic-2'-deoxyguanosine (CMCdG), and evaluated its anti-hepatitis B virus (anti-HBV) activity, safet...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02143-18

    authors: Higashi-Kuwata N,Hayashi S,Das D,Kohgo S,Murakami S,Hattori SI,Imoto S,Venzon DJ,Singh K,Sarafianos SG,Tanaka Y,Mitsuya H

    更新日期:2019-03-27 00:00:00

  • Combinations of Respiratory Chain Inhibitors Have Enhanced Bactericidal Activity against Mycobacterium tuberculosis.

    abstract::As an obligate aerobe, Mycobacterium tuberculosis uses its electron transport chain (ETC) to produce energy via oxidative phosphorylation. This pathway has recently garnered a lot of attention and is a target for several new antimycobacterials. We tested the respiratory adaptation of M. tuberculosis to phenoxyalkylben...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01677-17

    authors: Berube BJ,Parish T

    更新日期:2017-12-21 00:00:00

  • Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.

    abstract::The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococca...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.10.1507

    authors: Cohen MS,Chai Y,Britigan BE,McKenna W,Adams J,Svendsen T,Bean K,Hassett DJ,Sparling PF

    更新日期:1987-10-01 00:00:00

  • Tn5253 family integrative and conjugative elements carrying mef(I) and catQ determinants in Streptococcus pneumoniae and Streptococcus pyogenes.

    abstract::The linkage between the macrolide efflux gene mef(I) and the chloramphenicol inactivation gene catQ was first described in Streptococcus pneumoniae (strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different defective IQ elements were detected in Streptococcus pyogen...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03638-14

    authors: Mingoia M,Morici E,Morroni G,Giovanetti E,Del Grosso M,Pantosti A,Varaldo PE

    更新日期:2014-10-01 00:00:00

  • Biogenesis of the mycobacterial cell wall and the site of action of ethambutol.

    abstract::The effect of ethambutol (EMB) is primarily on polymerization steps in the biosynthesis of the arabinan component of cell wall arabinogalactan (AG) of Mycobacterium smegmatis. Inhibition of the synthesis of the arabinan of lipoarabinomannan (LAM) occurred later, and thus in the cases of AG and LAM, the polymerization ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.11.2484

    authors: Mikusová K,Slayden RA,Besra GS,Brennan PJ

    更新日期:1995-11-01 00:00:00

  • Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B.

    abstract::We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.48.12.4808-4812.2004

    authors: Offner F,Krcmery V,Boogaerts M,Doyen C,Engelhard D,Ribaud P,Cordonnier C,de Pauw B,Durrant S,Marie JP,Moreau P,Guiot H,Samonis G,Sylvester R,Herbrecht R,EORTC Invasive Fungal Infections Group.

    更新日期:2004-12-01 00:00:00

  • Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration.

    abstract::Extended-infusion ceftolozane-tazobactam treatment at 1.5 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa in a critically ill patient on continuous venovenous hemofiltration. Serum drug concentrations were measured at 1, 4, 5, 6, and 8 h after the start of infusion. Prefilter levels of ceftolo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02608-15

    authors: Oliver WD,Heil EL,Gonzales JP,Mehrotra S,Robinett K,Saleeb P,Nicolau DP

    更新日期:2015-12-28 00:00:00

  • Comparative in vitro susceptibility of yeasts to amphotericin B and three methyl ester derivatives.

    abstract::The in vitro antifungal activities of two N-aminoacyl derivatives of amphotericin B methyl ester (AME) were compared by tube dilution with those of amphotericin B and AME, using 60 isolates representing 10 yeast species. A total of 70% of the strains were inhibited by concentrations of the N-aminoacyl AME derivatives ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.1.106

    authors: Oblack DL,Hewitt WL,Martin WJ

    更新日期:1981-01-01 00:00:00

  • Properties of penicillin-binding proteins in Neisseria gonorrhoeae.

    abstract::The properties of penicillin-binding proteins (PBPs) of Neisseria gonorrhoeae were studied by comparing PBPs of clinical isolates of different penicillin susceptibility and by putting various beta-lactam antibiotics in competition with radioactive penicillin for PBP binding. Apparent molecular weights of the three maj...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.19.2.316

    authors: Barbour AG

    更新日期:1981-02-01 00:00:00

  • Retrograde Trafficking Inhibitor of Shiga Toxins Reduces Morbidity and Mortality of Mice Infected with Enterohemorrhagic Escherichia coli.

    abstract::The most deadly outbreak of Escherichia coli O104:H4 occurred in Europe in 2011. Here, we evaluated the effects of the retrograde trafficking inhibitor Retro-2(cycl) in a murine model of E. coli O104:H4 infection. Systemic treatment with Retro-2(cycl) significantly reduced body weight loss and improved clinical scores...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00455-15

    authors: Secher T,Shima A,Hinsinger K,Cintrat JC,Johannes L,Barbier J,Gillet D,Oswald E

    更新日期:2015-08-01 00:00:00

  • Use of multivariate analysis to compare antimicrobial agents on the basis of in vitro activity data.

    abstract::Multivariate techniques such as principal component analysis or similar factor analysis help in analyses of the simultaneous interrelationships among several variables. A comparative multivariate analysis on the in vitro activities of eight antimicrobial agents, including the novel molecule daptomycin, is presented. M...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.2.184

    authors: Hernández JM,Conforti P

    更新日期:1994-02-01 00:00:00

  • Characterization of spontaneous, In vitro-selected, rifampin-resistant mutants of Mycobacterium tuberculosis strain H37Rv.

    abstract::Resistance to rifampin in Mycobacterium tuberculosis results from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.12.3298-3301.2000

    authors: Morlock GP,Plikaytis BB,Crawford JT

    更新日期:2000-12-01 00:00:00

  • Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function.

    abstract::The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.1.31

    authors: Ohkawa M,Hirano S,Tokunaga S,Motoi I,Shoda R,Ikeda A,Sugata T,Sawaki M,Shimamura M,Okasho A,Kuroda K

    更新日期:1983-01-01 00:00:00

  • 3-Deazauridine: inhibition of ribonucleic acid virus-induced cytopathogenic effects in vitro.

    abstract::3-Deazauridine, a synthetic analogue of uridine and a potential antitumor agent, was found to possess antiviral activity against a number of ribonucleic acid-containing animal viruses in mammalian cell culture. Inhibition of virus-induced cytopathogenic effects by 3-deazauridine was observed in cells infected with rhi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.2.3.159

    authors: Shannon WM,Arnett G,Schabel FM Jr

    更新日期:1972-09-01 00:00:00

  • The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice.

    abstract::The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contribution...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00372-15

    authors: Lin YT,Huang YW,Chen SJ,Chang CW,Yang TC

    更新日期:2015-07-01 00:00:00

  • Antimicrobial activities of mefloquine and a series of related compounds.

    abstract::Mefloquine was found to have bactericidal activity against methicillin- and fluoroquinolone-susceptible and -resistant strains of Staphylococcus aureus and Staphylococcus epidermidis and gentamicin- and vancomycin-resistant strains of Enterococcus faecalis and Enterococcus faecium. The MICs were 16 microg/ml, and the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.4.848-852.2000

    authors: Kunin CM,Ellis WY

    更新日期:2000-04-01 00:00:00

  • Efficacy of alcohol-based hand rinses under frequent-use conditions.

    abstract::Fifty volunteers randomly assigned to one of five hand washing agents (10 subjects per agent)--a nonantiseptic liquid soap (control), an antiseptic hand rinse containing 60% isopropyl alcohol (IPA) with emollients (Alc A), an antiseptic hand rinse containing 70% IPA and 0.5% chlorhexidine gluconate with emollients (Al...

    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.30.4.542

    authors: Larson EL,Eke PI,Laughon BE

    更新日期:1986-10-01 00:00:00

  • Defined anaerobic growth medium for studying Candida albicans basic biology and resistance to eight antifungal drugs.

    abstract::The polymorphic fungus Candida albicans is one of the most versatile opportunistic pathogens in humans. Many organs of the human body are potential targets for infection by this pathogen, but infection is commonly localized in the gastrointestinal tract, an environment providing anaerobic growth conditions. We describ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.7.2350-2354.2004

    authors: Dumitru R,Hornby JM,Nickerson KW

    更新日期:2004-07-01 00:00:00

  • Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections.

    abstract::9-R-[2-(Phosphonomethoxy)propyl]-adenine (tenofovir) is an acyclic nucleoside phosphonate with antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). Tenofovir is not orally bioavailable but becomes orally active against HIV-1 infection as the disoproxil ester (tenofovir di...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00460-07

    authors: Painter GR,Almond MR,Trost LC,Lampert BM,Neyts J,De Clercq E,Korba BE,Aldern KA,Beadle JR,Hostetler KY

    更新日期:2007-10-01 00:00:00