Abstract:
:The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Klopman G,Li JY,Wang S,Pearson AJ,Chang K,Jacobs MR,Bajaksouzian S,Ellner JJdoi
10.1128/aac.38.8.1794subject
Has Abstractpub_date
1994-08-01 00:00:00pages
1794-802issue
8eissn
0066-4804issn
1098-6596journal_volume
38pub_type
杂志文章abstract::Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment of serious infections caused by multiresistant Gram-positive bacteria. This study investigated the renal protective activity of rutin in a rat model of VCM-induced kidney injury in male Wistar rats. VCM administered intr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01545-18
更新日期:2018-12-21 00:00:00
abstract::The in vitro interactions between bismuth subcitrate and a variety of antimicrobial agents against 12 Campylobacter pyloridis (C. pylori) isolates were studied by the agar dilution checkerboard technique. The combination of bismuth subcitrate with the older quinolone, oxolinic acid, produced synergistic activity again...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.9.1429
更新日期:1987-09-01 00:00:00
abstract::In the course of surveying for the carbapenem-hydrolyzing metallo-beta-lactamase gene bla(IMP) in pathogenic bacteria by the PCR method, we detected a gene encoding a variant metallo-beta-lactamase, designated IMP-3, which differed from IMP-1 by having low hydrolyzing activity for penicillins and carbapenems. PCR prod...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.8.2023-2027.2000
更新日期:2000-08-01 00:00:00
abstract::Genome studies suggest that DNA gyrase is the sole type II topoisomerase and likely the unique target of quinolones in Mycobacterium tuberculosis. Despite the emerging importance of quinolones in the treatment of mycobacterial disease, the slow growth and high pathogenicity of M. tuberculosis have precluded direct pur...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.4.1281-1288.2004
更新日期:2004-04-01 00:00:00
abstract::The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected po...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.3.383
更新日期:1986-03-01 00:00:00
abstract::BMY-28864, a water-soluble pradimicin derivative, had potent in vitro activity against a wide variety of fungi, including those associated with deep-seated mycosis; it inhibited the growth of standard strains and clinical isolates at concentrations of 12.5 micrograms/ml or less. At the MIC or higher concentrations, BM...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.11.2185
更新日期:1991-11-01 00:00:00
abstract::Doravirine (DOR, formerly known as MK-1439) is a human immunodeficiency type 1 virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is currently in phase 2b clinical trials. In vitro resistance selection of subtype B virus (MT4-green fluorescent protein [GFP] cells), as well as subtype A and C viru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04201-14
更新日期:2015-01-01 00:00:00
abstract::Quadruple mutations in the Plasmodium falciparum dihydrofolate reductase (PFDHFR) enzyme give rise to the highest level of pyrimethamine resistance leading to treatment failures. We describe here the presence of these quadruple mutations in a majority of P. falciparum isolates from Car Nicobar (Andaman and Nicobar) Is...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1546-1549.2006
更新日期:2006-04-01 00:00:00
abstract::We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subj...
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.44.11.3155-3157.2000
更新日期:2000-11-01 00:00:00
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
更新日期:2016-09-23 00:00:00
abstract::The multiple-dose pharmacokinetics of amoxicillin (AM [administered twice daily in a 25-mg/kg of body weight intravenous dose]) in 17 preterm infants (11 males; gestational age, 29 +/- 1.9 weeks; birth weight, 1,175 +/- 278 g) were evaluated on day 3 of life. Blood samples were collected from an arterial catheter at 0...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.431
更新日期:1995-02-01 00:00:00
abstract::Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.7
更新日期:1979-01-01 00:00:00
abstract::Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute Plasmodium vivax malaria, which is the first new treatment in almost 60 years. A population pharmacokinetic (POP PK) analysis was conducted with tafenoquine exposure ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00711-18
更新日期:2018-10-24 00:00:00
abstract::Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00320-12
更新日期:2012-08-01 00:00:00
abstract::A major clinical challenge for treating infectious diseases is the duration of antimicrobial therapy required to eradicate the pathogen. We hypothesized that modulation of the bacterial replication rate in the context of an antimicrobial exposure is coupled with the rate and extent of bactericidal effects. Herein we d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01605-16
更新日期:2016-12-27 00:00:00
abstract::Plasmodium falciparum, the deadliest species of malaria parasites, is dependent on glycolysis for the generation of ATP during the pathogenic red blood cell stage. Hexokinase (HK) catalyzes the first step in glycolysis, transferring the γ-phosphoryl group of ATP to glucose to yield glucose-6-phosphate. Here, we descri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00914-16
更新日期:2016-09-23 00:00:00
abstract::Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulaf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02326-17
更新日期:2018-03-27 00:00:00
abstract::The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic memb...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00321-09
更新日期:2009-09-01 00:00:00
abstract::Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry in...
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.00523-15
更新日期:2015-08-01 00:00:00
abstract::Treatment of Mycobacterium abscessus infections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practical in vivo model of infection. The objective of this study was to establish a simple in vivo model for M. abscessus infection, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02539-17
更新日期:2018-03-27 00:00:00
abstract::Actinobacillus actinomycetemcomitans and Capnocytophaga spp. are gram-negative bacteria implicated in the etiology of periodontal disease (particularly in individuals with neutrophil defects) and life-threatening systemic infections. They are resistant to many antibiotics of microbial origin but are sensitive to the n...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.12.2710
更新日期:1993-12-01 00:00:00
abstract::Ciprofloxacin is active in vitro against most bacteria that cause peritonitis associated with peritoneal dialysis. We compared the effects of pH (5.5 and 7.4) and medium (dialysis fluid) on the bactericidal activity of ciprofloxacin, tobramycin, vancomycin plus rifampin, and rifampin against Pseudomonas aeruginosa, Es...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.4.657
更新日期:1987-04-01 00:00:00
abstract::In 24 patients with hepatitic C virus (HCV) infection who participated in a randomized trial with alpha 2B interferon, HCV RNA analysis by the polymerase chain reaction with two separate primer sets was performed at weeks 0, 4, and 24 and during a follow-up period of 6 to 9 months. Prior to therapy all patients were H...
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.37.3.595
更新日期:1993-03-01 00:00:00
abstract::The majority of clinical isolates of Moraxella catarrhalis produce beta-lactamase. The role of this enzyme in the phenomenon of indirect pathogenicity, in which a true pathogen such as Streptococcus pneumoniae is protected from the action of certain beta-lactam antibiotics, is well recognized. By using a simple contin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.10.2521
更新日期:1998-10-01 00:00:00
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
更新日期:2007-01-01 00:00:00
abstract::The pharmacokinetics and distribution in tissue of several novel triazole antifungal agents were studied in different animal species in order to select an appropriate lead compound. The purpose of the study was also to determine species differences in pharmacokinetics for SYN azoles to select the most appropriate spec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.4.910-915.2000
更新日期:2000-04-01 00:00:00
abstract::Leukocyte chemotaxis was inhibited 9.6% compared with control in the presence of 10 mug of gentamicin per ml and 10.5% when exposed to 20 mug of amikacin per ml. However, cells incubated with an injectable form of gentamicin, containing preservatives, were inhibited an additional 25.8% relative to cells incubated with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.4.540
更新日期:1977-10-01 00:00:00
abstract::Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 μg/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techn...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00022-10
更新日期:2010-12-01 00:00:00
abstract::Candida biofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. In Candida albicans, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02378-12
更新日期:2013-04-01 00:00:00
abstract::Here, we report twoEnterobacter cloacaesequence type 231 isolates coproducing KPC-3 and NDM-1 that have caused lethal infections in a tertiary hospital in China. TheblaNDM-1-harboring plasmids carry IncA/C2and IncR replicons, showing a mosaic plasmid structure, and theblaNDM-1is harbored on a novel class I integron-li...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03053-15
更新日期:2016-03-25 00:00:00