A Hypothesis-Generating Study of the Combination of Aspirin plus Macrolides in Patients with Severe Community-Acquired Pneumonia.

Abstract:

:While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of conventional antibiotic therapy. An observational study was conducted with patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, the United States, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to Infectious Diseases Society of America/American Thoracic Society criteria. Patients were divided into 4 groups, i.e., (i) the aspirin-only group (ASG), (ii) the macrolide-only group (MG), (iii) the aspirin plus macrolide group (ASMG), or (iv) the neither aspirin nor macrolide group (NASMG). Survival rates for the 4 groups were evaluated after adjustment for confounders and after weighting by propensity score. A total of 1,295 patients were included in the analysis. There were 237 patients (18.3%) in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. The mortality rate at 30 days was 15.5% in the ASMG, compared to 28.2% in the NASMG, 23.8% in the MG, and 21.1% in the ASG. After propensity score analysis, receipt of aspirin plus macrolide (hazard ratio, 0.71 [95% confidence interval, 0.58 to 0.88]; P = 0.002) was associated with a higher 30-day survival rate. This is a hypothesis-generating study in which data suggest that the combination of aspirin plus a macrolide improves 30-day survival rates for patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.

authors

Falcone M,Russo A,Shindo Y,Farcomeni A,Pieralli F,Cangemi R,Liu J,Xia J,Okumura J,Sano M,Jones C,Vannucchi V,Mancone M,Micek S,Xu F,Violi F,Kollef M

doi

10.1128/AAC.01556-18

subject

Has Abstract

pub_date

2019-01-29 00:00:00

issue

2

eissn

0066-4804

issn

1098-6596

pii

AAC.01556-18

journal_volume

63

pub_type

杂志文章,多中心研究
  • EfrEF and the Transcription Regulator ChlR Are Required for Chlorhexidine Stress Response in Enterococcus faecalis V583.

    abstract::Enterococcus faecalis is an opportunistic pathogen and leading cause of health care-associated infections. Daily chlorhexidine gluconate (CHG) bathing of patients is generally regarded as an effective strategy to reduce the occurrence of health care-associated infections. It is likely that E. faecalis is frequently ex...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00267-18

    authors: Li FJ,Palmer KL

    更新日期:2018-05-25 00:00:00

  • Comparative efficacies of amphotericin B lipid complex and amphotericin B deoxycholate suspension against murine blastomycosis.

    abstract::Amphotericin B as a lipid complex and as a deoxycholate suspension (Fungizone) was tested against murine blastomycosis. All doses of each form prolonged survival (P less than 0.05 to 0.001). Fungizone was more effective than lipid complex at doses of 0.8 mg/kg of body weight. However, lipid complex at 12.8 mg/kg was n...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.35.10.2144

    authors: Clemons KV,Stevens DA

    更新日期:1991-10-01 00:00:00

  • In vitro and in vivo inhibition of erythrocytic development of malarial parasites by docetaxel.

    abstract::The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stag...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.2.358

    authors: Sinou V,Grellier P,Schrevel J

    更新日期:1996-02-01 00:00:00

  • Molecular correlates of high-level antifolate resistance in Rwandan children with Plasmodium falciparum malaria.

    abstract::Antifolate drugs have an important role in the treatment of malaria. Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs, respectively. Rwanda has the highest levels of antimalarial drug resistance in Africa. We correlat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.00498-09

    authors: Karema C,Imwong M,Fanello CI,Stepniewska K,Uwimana A,Nakeesathit S,Dondorp A,Day NP,White NJ

    更新日期:2010-01-01 00:00:00

  • Antibiotic resistance in the ECOR collection: integrons and identification of a novel aad gene.

    abstract::The 72 Escherichia coli strains of the ECOR collection were examined for resistance to 10 different antimicrobial agents including ampicillin, tetracycline, mercury, trimethoprim, and sulfonamides. Eighteen strains were resistant to at least one of the antibiotics tested, and nearly 20% (14 of 72) were resistant to tw...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.6.1568-1574.2000

    authors: Mazel D,Dychinco B,Webb VA,Davies J

    更新日期:2000-06-01 00:00:00

  • Pharmacokinetics of ampicillin and sulbactam in pediatric patients.

    abstract::Intravenous ampicillin-sulbactam is effective in the treatment of various infections in adults, but little is known about the pharmacokinetics (PK) of ampicillin-sulbactam in children. The objective of this study was to determine the PK of ampicillin and sulbactam in pediatric patients with intra-abdominal infection, ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.43.5.1225

    authors: Nahata MC,Vashi VI,Swanson RN,Messig MA,Chung M

    更新日期:1999-05-01 00:00:00

  • Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae.

    abstract::Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01446-17

    authors: Sabet M,Tarazi Z,Nolan T,Parkinson J,Rubio-Aparicio D,Lomovskaya O,Dudley MN,Griffith DC

    更新日期:2017-12-21 00:00:00

  • Novel Zinc-Attenuating Compounds as Potent Broad-Spectrum Antifungal Agents with In Vitro and In Vivo Efficacy.

    abstract::An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, Z...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02024-17

    authors: Cohrt KAO,Marín L,Kjellerup L,Clausen JD,Dalby-Brown W,Calera JA,Winther AL

    更新日期:2018-04-26 00:00:00

  • Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

    abstract::There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) inf...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/AAC.01845-16

    authors: Song KH,Kim M,Kim CJ,Cho JE,Choi YJ,Park JS,Ahn S,Jang HC,Park KH,Jung SI,Yoon N,Kim DM,Hwang JH,Lee CS,Lee JH,Kwak YG,Kim ES,Park SY,Park Y,Lee KS,Lee YS,Kim HB

    更新日期:2017-02-23 00:00:00

  • Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of HIV Regulatory Complexes.

    abstract::Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many prote...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02366-16

    authors: Nakamura RL,Burlingame MA,Yang S,Crosby DC,Talbot DJ,Chui K,Frankel AD,Renslo AR

    更新日期:2017-06-27 00:00:00

  • Mercury resistance determinants related to Tn21, Tn1696, and Tn5053 in enterobacteria from the preantibiotic era.

    abstract::Three mer transposons from the Murray collection of preantibiotic enterobacteria show >99% sequence identity to current isolates. Tn5073 is most closely related to Tn5036 and Tn1696, and Tn5074 is most closely related to Tn5053. Tn5075 is most closely related to Tn21 but lacks integron In2 and is flanked by insertion ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 历史文章,杂志文章

    doi:10.1128/aac.47.3.1115-1119.2003

    authors: Essa AM,Julian DJ,Kidd SP,Brown NL,Hobman JL

    更新日期:2003-03-01 00:00:00

  • Radioimmunoassay for metabolites of 9,3"-diacetylmidecamycin, a macrolide antibiotic.

    abstract::A radioimmunoassay system has been developed for the measurement of two major metabolites of 9,3"-diacetylmidecamycin, Mb-6 and Mb-12. A radioimmunoassay for Mb-6 was performed by using anti-Mb-6 serum and a [125I]tyramined Mb-6 derivative as a radiolabeled antigen. The labeled antigen was prepared by the chloramine T...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.22.6.976

    authors: Shimada N,Ueda T,Yokoshima T,Umemura K,Shomura T

    更新日期:1982-12-01 00:00:00

  • Susceptibility of recent clinical isolates of herpes simplex virus to 5-ethyl-2'-deoxyuridine: preferential inhibition of herpes simplex virus type 2.

    abstract::We examined the in vitro susceptibilities of three reference strains and 41 recent clinical isolates of herpes simplex virus types 1 and 2 to 5-ethyl-2'-deoxyuridine. This thymidine analog exerts a type 2-preferential but not a type 2-specific antiviral effect. Utilizing a microtiter assay with BHK-21 cells, we found ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.5.637

    authors: Teh CZ,Sacks SL

    更新日期:1983-05-01 00:00:00

  • Antibiotic susceptibility profile of bifidobacteria as affected by oxgall, acid, and hydrogen peroxide stress.

    abstract::The effects of acid, oxgall, and H(2)O(2) on susceptibilities to antibiotics and nisin were examined for 13 strains of bifidobacteria. Susceptibilities to ampicillin, cloxacillin, penicillin, vancomycin, kanamycin, neomycin, paramomycin, streptomycin, chloramphenicol, erythromycin, tetracycline, and nisin A were assay...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00261-06

    authors: Kheadr E,Dabour N,Le Lay C,Lacroix C,Fliss I

    更新日期:2007-01-01 00:00:00

  • Untargeted Metabolomics To Ascertain Antibiotic Modes of Action.

    abstract::Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also co...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02109-15

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

    更新日期:2016-03-25 00:00:00

  • Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens.

    abstract::Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations in vitro and in v...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00516-19

    authors: Pericàs JM,Nathavitharana R,Garcia-de-la-Mària C,Falces C,Ambrosioni J,Almela M,García-González J,Quintana E,Marco F,Moreno A,Bayer AS,Miró JM,Karchmer AW,Hospital Clínic Endocarditis Study Group.

    更新日期:2019-07-25 00:00:00

  • Quinolones potentiate cefazolin-induced seizures in DBA/2 mice.

    abstract::The behavioral and convulsant effects of cefazolin, a beta-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvu...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.7.1497

    authors: De Sarro A,Zappalá M,Chimirri A,Grasso S,De Sarro GB

    更新日期:1993-07-01 00:00:00

  • Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis.

    abstract::Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isola...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00009-13

    authors: Mallo N,Lamas J,Leiro JM

    更新日期:2013-06-01 00:00:00

  • Novispirin G10-induced lung toxicity in a Klebsiella pneumoniae infection model.

    abstract::Mammalian cathelicidins are a class of innate antimicrobial peptides isolated from leukocytes and epithelial cells that aid host defense against bacterial infections. Synthetic analogs of cathelicidins offer the promise of potent broad-spectrum antimicrobial efficacy. We developed a combined lung infection and ex vivo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.12.3901-3906.2003

    authors: Bartlett KH,McCray PB Jr,Thorne PS

    更新日期:2003-12-01 00:00:00

  • DNA gyrase gyrA mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa.

    abstract::The mutations in the quinolone resistance-determining region of the gyrA gene from clinical isolates of Pseudomonas aeruginosa were determined by DNA sequencing. The strains were isolated in 1989 and 1993. No mutations were detected in the clinical isolates in 1989, while five types of mutations were identified in the...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.9.1970

    authors: Yonezawa M,Takahata M,Matsubara N,Watanabe Y,Narita H

    更新日期:1995-09-01 00:00:00

  • Molecular characterization of ISCR1-mediated blaPER-1 in a non-O1, non-O139 Vibrio cholerae strain from China.

    abstract::We report the detection of PER-1 extended-spectrum β-lactamase (ESBL) in a clinical non-O1, non-O139 Vibrio cholerae strain from China. ISCR1-mediated bla(PER-1) was embedded in a complex In4 family class 1 integron belonging to the lineage of Tn1696 on a conjugative IncA/C plasmid. A free 8.98-kb circular molecule pr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00166-15

    authors: Wu J,Xie L,Zhang F,Ni Y,Sun J

    更新日期:2015-07-01 00:00:00

  • Cinoxacin: effectiveness against experimental pyelonephritis in rats.

    abstract::The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mir...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.6.4.432

    authors: Holmes DH,Ensminger PW,Gordee RS

    更新日期:1974-10-01 00:00:00

  • Safe and sustained vaginal delivery of pyrimidinedione HIV-1 inhibitors from polyurethane intravaginal rings.

    abstract::The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the I...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05721-11

    authors: Johnson TJ,Srinivasan P,Albright TH,Watson-Buckheit K,Rabe L,Martin A,Pau CP,Hendry RM,Otten R,McNicholl J,Buckheit R Jr,Smith J,Kiser PF

    更新日期:2012-03-01 00:00:00

  • In Vitro Resistance Selection in Shigella flexneri by Azithromycin, Ceftriaxone, Ciprofloxacin, Levofloxacin, and Moxifloxacin.

    abstract::Shigella flexneri continues to be a major cause of diarrhea-associated illness, and increasing resistance to first-line antimicrobials complicates the treatment of infections caused by this pathogen. We investigated the pharmacodynamics of current antimicrobial treatments for shigellosis to determine the likelihood of...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00086-17

    authors: Allen GP,Harris KA

    更新日期:2017-06-27 00:00:00

  • Effect of an antacid containing magnesium and aluminum on absorption, metabolism, and mechanism of renal elimination of pefloxacin in humans.

    abstract::The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations 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.38.5.1129

    authors: Jaehde U,Sörgel F,Stephan U,Schunack W

    更新日期:1994-05-01 00:00:00

  • Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins.

    abstract::(1,3)Beta-D-glucan synthase (EC 2.4.1.34. UDP-glucose: 1,3-beta-D-glucan 3-beta-glucosyltransferase) uses UDP-glucose as substrate and catalyzes the polymerization of glucose ([1,3]-beta-linkages) to form the major carbohydrate component of the fungal cell wall. We have optimized in vitro assay conditions for (1,3)bet...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.7.2851-2856.2005

    authors: Maligie MA,Selitrennikoff CP

    更新日期:2005-07-01 00:00:00

  • 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

  • 23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22.

    abstract::Resistance to macrolides and ketolides occurs mainly via alterations in RNA moieties of the drug-binding site. Using an A2058G mutant of Mycobacterium smegmatis, additional telithromycin resistance was acquired via deletion of 15 residues from protein L22. Molecular modeling, based on the crystal structure of the larg...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00767-06

    authors: Berisio R,Corti N,Pfister P,Yonath A,Böttger EC

    更新日期:2006-11-01 00:00:00

  • In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem.

    abstract::The continued evolution of bacterial resistance to the β-lactam class of antibiotics has necessitated countermeasures to ensure continued effectiveness in the treatment of infections caused by bacterial pathogens. One relatively successful approach has been the development of new β-lactam analogs with advantages over ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02240-19

    authors: Cotroneo N,Rubio A,Critchley IA,Pillar C,Pucci MJ

    更新日期:2020-07-22 00:00:00

  • Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-beta-lactamase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program.

    abstract::A total of 104 carbapenemase (serine- and metallo-beta-lactamase [MbetaL])-producing strains of the Enterobacteriaceae family collected from 2000 to 2005 in medical centers distributed worldwide were tested against tigecycline and 25 comparators by reference broth microdilution methods. The most frequent carbapenemase...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01114-07

    authors: Castanheira M,Sader HS,Deshpande LM,Fritsche TR,Jones RN

    更新日期:2008-02-01 00:00:00