« 嫌気性菌 | メイン | 2008/9/10 »

耐性菌UpDate

耐性菌UpDate

耐性菌 初めて問題になったのは??
  → ペニシリナーゼ産生黄色ブドウ球菌
  → ペニシリンを創部感染に使用できなくなった!!
   → だから今、第一世代セフェム を使う…

●βラクタム系

MSSA
 ペニシリンは効かない
 ペニシリナーゼを基本的にもっているから
  …βラクタマーゼ阻害薬を使うことで効くようになる

MRSA
 ABPC/SBT 効かない
 PBPの変異があるから

PRSP
 SBT 効かない
 MIC>8 はまだ日本には少ないが…
 新しい定義のPRSPには高容量でもダメ
  6種類のPBPsがある

BLNAR β-lactamase-non-puroducing Ampicillin resistant
 H. influenze
 急性喉頭蓋炎 で成人も死ぬ

…市中肺炎にABPC/SBTである意義はあるのか?
 H.influenze
 BLNARいなければいいけれど…

…第三世代にすれば、PBPにつく場所がまた違うからOK

腸球菌 enterococcus
 VCM しか使えなくなることもある
 faeciumは生まれつきにβラクタムにある程度の耐性もっている
  セフェムは効かない
  vitroでは3〜4世代はきくけれど、vivoでは一切効かない

enterococcusに一切効かない禁忌は?
 オキサシリンなどペニシリナーゼ耐性の薬剤は一切効かない!


・βラクタマーゼ 陰性桿菌の耐性の基本

●アミノグリコシド

取り込み低下(緑膿菌)
  …GMが基本
   耐性あればTOBも
   最後にAMK に耐性に (時々逆転するが、あくまで例外)
  …全部RでGMのみSなアシネトバクター はまあしょうがないけれど
   あくまで非常事態。原則信用しない
修飾酵素(そのほかさまざまな細菌)

●キノロン
DNAgyrase変異 S.aureus とGNR
effuluxポンプ S.aureus の一部
修飾酵素 (E.coliの一部)


◎ 野良猫
市中緑膿菌感染は緑膿菌用抗菌薬、全部Sに

●マクロライド、クリンダマイシン、ストレプトグラミン
リボゾームの変異

●マクロライドのみ耐性
Efflux

→ CLDMはグラム陽性(黄色ブドウ球菌含む)によく効く
  保険適用 のMax 2400 世界容量!!
   どうしても治したいとき便利

  MRSA
   CLDM S で、CLDMで治しきれることある
  MRSE
   一部はCLDMでたたける
  GES 連鎖球菌
   CLDMで治療できるときとできないときがある

  場合によっては切り札!

●テトラサイクリン
ドキシサイクリン
ミノサイクリン
 …STI 梅毒、PID(クラミジア)

MRSA でS と出るときあり
 基本的には信用しないけれど…
 6週間IEで叩けないとき、邪道に、これ使うときも

 チゲサイクリン
  MRSA〜緑膿菌まできく

●ST トリメトプリム
 
 腸球菌には生まれつき効かない

●リファンピシン

●サルフォナミド

●クロラムフェニコール

小児科ではケースによってよく使う
肺炎球菌とかに広く効く。髄膜移行性いい
 ブドウ球菌には使えないけれど

●グリコペプタイド

●リネゾリド

けっこうすぐに耐性でてくるらしい

■一部のGNRは 生まれつきAmpC過剰産生

class A ペニシリナーゼ
     進化したらESBL… 原則ペネム!!
     これのクラスのみ、βラクタマーゼ阻害薬効く

C セファロスポリナーゼ
     進化すると広範囲に効かなくなる

B メタロβラクタマーゼ ≒カルバペネマーゼ
     …緑膿菌 周りの菌から耐性機構を受け取る
      一部は生まれつきペネム耐性 
       ステノトロフォマス マルトフィリア
        …基本はSTでなおす  他、キノロン
         亀田はもともとCPFX耐性だったり
         MINO はevidence少ないが OK
       バーくふぉーてらうすくらしあ…なんとか 

   D オキサシリナーゼ


■ MRSA

小児科でハベカシン使うのは…
 ホスミシンも…

 etcは明治製菓が小児科をターゲットに
 小児科はアミノグリコシド 使い慣れているから …ターゲットに

 アミノグリコシドはそもそもGPCには無力だから
 日本でしか使われない


緑膿菌に…
セフォペラゾン
  髄液にいかない、vitroで信用できない から、捨てた
  それをファイザーが拾った
  しかも、海外よりこれが少ない
  SBT アメリカですら、Max 2gにしろと言われる
 セフタジシムに勝ち目ない


・市中MRSA
 妙にβラクタム以外にはSが多い
 CLDMも使用できることもある
   …耐性を獲得した末、ではないから
  …逆にMSSAはCLDM使えなかったり

 Dテスト陰性だったらCLDMも使用可能
  …マクロライドのみに耐性か、どっちにも耐性か見分ける
   Dな形になるのは、陽性
   Oな形になるのは、陰性


・βラクタム耐性がでてきている日本では
 ペネムも信用できないことある
 だから、VCM + ペネム とエンピリックに使う


・クレブシエラ
ABPC βラクタマーゼ、いずれでてくる


腸球菌
 どんなときにターゲットにすべき???
 無菌のところからでてきたら、ターゲット
  血液・髄液

 尿からでてる のは 当たり前
  バルーン入っている高齢者で、臨床症状でていたら気にする

3年間の急性胆管炎
 血液培養は3割陽性 
 fecium 血液からでたのは2例
   よくなっていても怖いからVCMいれたり


・ハベカシン
MRSA叩こうとしたのは世界で明治製菓だけ
だから、evidenceない


MSSAに
 GM
 cell wall をCEZで抑えているときにはいるから、シナジー
 3日くらいつかう
 だからそもそもアミノグリコシドは使わない

ハベカシンはVCMより腎にダメージ大きい

・MRSA
 腸炎おこさない、としているが
 MRSE・MRSA がでたら小児では壊死性腸炎怖いから AMKつかう
 …のは ?

 でも、 全身の培養から出てきてたら、菌血症になっている可能性高い

「クレブシエラ腸炎」
アンピシリンつかったら、出血性腸炎で、便培養からがんがんでてくると。
でも、あるんじゃないかと言われてきている。動物実験で証明されてきている

「MRSA腸炎」
動物実験、限定条件下ではおこる
小腸に偽膜ができる 剖検で見つかっている

基本はCD腸炎だけれども。

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