1.Clinical Factors Associated with Acquisition of Resistance to Levofloxacin in Stenotrophomonas maltophilia.
Ji Hyeon BAEK ; Chang Oh KIM ; Su Jin JEONG ; Nam Soo KU ; Sang Hoon HAN ; Jun Yong CHOI ; Dongeun YONG ; Young Goo SONG ; Kyungwon LEE ; June Myung KIM
Yonsei Medical Journal 2014;55(4):987-993
PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in > or =3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.
Aged
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Anti-Bacterial Agents/*pharmacology/*therapeutic use
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Fluoroquinolones/pharmacology/therapeutic use
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Gram-Negative Bacterial Infections/drug therapy
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Humans
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Levofloxacin/*pharmacology/*therapeutic use
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Microbial Sensitivity Tests
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Middle Aged
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Retrospective Studies
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Stenotrophomonas maltophilia/drug effects/*pathogenicity
2.Extended-spectrum beta-Lactamases: Implications for the Clinical Laboratory and Therapy.
Sohei HARADA ; Yoshikazu ISHII ; Keizo YAMAGUCHI
The Korean Journal of Laboratory Medicine 2008;28(6):401-412
Production of extended-spectrum beta-lactamase (ESBL) is one of the most important resistance mechanisms that hamper the antimicrobial treatment of infections caused by Enterobacteriaceae. ESBLs are classified into several groups according to their amino-acid sequence homology. While TEM and SHV enzymes were the most common ESBLs in the 1990s, CTX-M enzymes have spread rapidly among Enterobacteriaceae in the past decade. In addition, some epidemiological studies showed that organisms producing CTX-M enzymes had become increasingly prevalent in the community setting in certain areas in the world. Several novel enzymes with hydrolyzing activity against oxyimino-cephalosporins, albeit with additional enzymatic characteristics different from those of original TEM and SHV ESBLs (e.g., inhibitor-resistance), have been discovered and pose a problem on the definition of ESBLs. Although several methods to detect the production of ESBL are available in clinical laboratories, existence of other factors contributing resistance against beta-lactams, e.g., inducible production of Amp-C beta-lactamase by some species of Enterobacteriaceae, or inhibitor-resistance in some ESBLs may hinder the detection of ESBLs with these methods. Carbapenems are stable against hydrolyzing activity of ESBLs and are regarded as the drug of choice for the treatment of infections caused by ESBL-producing Enterobacteriaceae. Although several other antimicrobial agents, such as fluoroquinolones and cephamycins, may have some role in the treatment of mild infections due to those organisms, clinical data that warrant the use of antimicrobial agents other than carbapenems in the treatment of serious infections due to those organisms are scarce for now.
Anti-Bacterial Agents/*pharmacology/therapeutic use
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Carbapenems/pharmacology/therapeutic use
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Disk Diffusion Antimicrobial Tests
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Enterobacteriaceae/drug effects/*enzymology/genetics
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Enterobacteriaceae Infections/*drug therapy/microbiology
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Fluoroquinolones/pharmacology/therapeutic use
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Humans
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Microbial Sensitivity Tests/methods
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beta-Lactamases/*biosynthesis/metabolism
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beta-Lactams/*pharmacology/therapeutic use
3.Bacteremia Caused by Corynebacterium amycolatum with a Novel Mutation in gyrA Gene that Confers High-Level Quinolone Resistance.
Seoyoung YOON ; Heejung KIM ; Yangsoon LEE ; Sinyoung KIM
The Korean Journal of Laboratory Medicine 2011;31(1):47-48
Although Corynebacterium amycolatum can cause opportunistic infections, it is commonly considered as contaminant. In this report, we present a case of bacteremia caused by C. amycolatum with a novel mutation in the gyrA gene that confers high-level quinolone resistance to the organism.
Aged, 80 and over
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Anti-Bacterial Agents/*pharmacology
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Bacteremia/*microbiology
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Corynebacterium/drug effects/*genetics/isolation & purification
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Corynebacterium Infections/*diagnosis/drug therapy
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DNA Gyrase/*genetics
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Drug Resistance, Bacterial/genetics
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Fluoroquinolones/*pharmacology
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Humans
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Male
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Microbial Sensitivity Tests
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Mutation
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Vancomycin/therapeutic use
4.Synthesis and antibacterial activity of 7-(7-aminomethyl-5-azaspiro 2,4 hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues.
Jian-jun QI ; Hui-yuan GUO ; Ming-liang LIU ; Lan-ying SUN
Acta Pharmaceutica Sinica 2004;39(3):184-189
AIMTo find new antibacterial agents of quinolone with high activity and low toxicity.
METHODSTo design and synthesize 7-(7-aminomethyl-5-azaspiro [2,4] hept-5-yl)-1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues, and to study their antibacterial activity in vitro and in vivo.
RESULTSTwenty new compounds (2 - 11, 17 - 26) were obtained including five targeted compounds (22 - 26). The structures of the compounds were confirmed by 1HNMR, MS and HRMS. Compounds 22 - 26 showed broad spectrum of antibacterial activity against Gram-positive and Gram-negative organisms. Especially for compound 24, the relevant MIC values for 13 strains of Gram-positive organisms were < 0.001 - 0.03 mg(-1), including 4 strains of S. pneumoniae, 2 strains of S. pyogenes, 3 strains of S. aureus and 2 strains of Enterococci which exhibited more potent activity than contrast agents (clinafloxacin and gatifloxacin). The MIC values of 24 for 6 strains Gram-positive organisms were 0.01 - 1 mg x L(-1), which exhibited equal or lower activity than contrast agents. They were more effective than ciprofloxacin and gatifloxacin against intraperitoneal infections caused by S. pneumoniae and S. aureus in mice.
CONCLUSIONCompounds (23, 24 and 26) showed excellent antibacterial activity in vitro and in vivo and should be worth further investigation.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; pharmacology ; Ciprofloxacin ; pharmacology ; Female ; Fluoroquinolones ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Molecular Conformation ; Molecular Structure ; Quinolines ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Spiro Compounds ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Staphylococcus aureus ; drug effects ; Streptococcus pneumoniae ; drug effects