さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

大腸菌キノロン耐性

当院の、大腸菌キノロン耐性は徐々に上昇

外部環境による影響が強く我々の力で抑えることが難しいのか?

マクロ環境として、PEST分析をさらさら

P : WHOから耐性菌驚異について、各国政府に対策を強化するように求めている。
日本政府は、耐性菌のサーベイランスを強化。
病院からかかりつけ医へ。
E : 耐性菌出現による利益確保困難のため抗菌薬創薬の意欲低下。
S : 超高齢化。患者の抗菌薬希望志向。製薬会社のプロモーション。飛行機などの容易なアクセス。
T : ASPの浸透。

以下、UpToDate より
キノロンについて

Fluoroquinolones are the only class of antimicrobial agents in clinical use that are direct inhibitors of bacterial DNA synthesis. They inhibit two bacterial enzymes, DNA gyrase and topoisomerase IV, which have essential and distinct roles in DNA replication. The fluoroquinolones are bactericidal. 

●Several mechanisms of resistance to fluoroquinolones have been described, including both chromosomal and plasmid-mediated mechanisms. Plasmid-mediated mechanisms are almost always associated with resistance to other antibiotics. 

●Encode the subunits of DNA gyrase and topoisomerase IV (altered target mechanism)
●Regulate the expression of cytoplasmic membrane efflux pumps or proteins that constitute outer membrane diffusion channels (altered permeation mechanism)

Plasmid-mediated resistance to the fluoroquinolones has been reported in some clinical strains of Klebsiella pneumoniae, Escherichia coli, Enterobacter, and other enteric bacteria due to expression of one of several plasmid-encoded Qnr proteins, which appear to protect DNA gyrase from quinolone action.Plasmids encoding Qnr proteins produce low-level quinolone resistance, but they also usually cause resistance to other classes of antibiotics and have been found in strains with additional chromosomal mutations, resulting in high-level quinolone resistance along with multidrug resistance. Accumulation of mutations can result in highly resistant strains.

●Fluoroquinolones, especially the newer agents, have a wide spectrum of activity that includes gram-negative bacilli, Streptococcus pneumoniae and other respiratory pathogens, other gram-positive cocci, and mycobacterial species. The specific antimicrobial spectrum varies with the different fluoroquinolones.

●The fluoroquinolones are well absorbed from the upper gastrointestinal tract, with bioavailability exceeding 50 percent for all compounds and approaching 100 percent for several .

●The principal routes of elimination differ among fluoroquinolones. Ofloxacin and levofloxacin are eliminated predominantly by the kidneys, whereas moxifloxacin is eliminated predominantly by nonrenal pathways. Most other fluoroquinolones (eg, ciprofloxacin) have mixed excretion by both renal and nonrenal routes. 

●Adverse effects most commonly associated with fluoroquinolones include gastrointestinal and central nervous system toxicities. Other adverse effects include rashes and other allergic reactions, tendinitis and tendon rupture, QT prolongation, hepatotoxicity, hypoglycemia and hyperglycemia, hematologic toxicity, and retinal detachment. 

●Fluoroquinolones can interact with a variety of other drugs. A common problem is that coadministration of fluoroquinolones with aluminum-, magnesium-, or, to a lesser extent, calcium-containing antacids leads to markedly reduced oral bioavailability of the quinolone, presumably because of the formation of cation-quinolone complexes, which are poorly absorbed. 

●The QT prolonging effects of fluoroquinolones may be augmented if fluoroquinolones are given together with any of the multiple other drugs that cause QT prolongation, such as amiodarone . These interactions may increase the risk of torsades de pointes and sudden death. Thus, fluoroquinolones should not be given together with other drugs known to prolong the QT interval.

●Specific interactions of fluoroquinolones with other medications may be determined using the drug interaction tool (Lexi-Interact Online). This tool can be accessed from the UpToDate online search page or through the individual drug information topics, section on Drug interactions.