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090417青木先生

●090417青木先生

(余裕あれば)
移行性
腎・肝代謝などのpk


●βラクタム
・ペニシリン
・セフェム
・カルバペネム
・monobactams
ペプチドグリカン層をattack

cf アムホテリシンB 細胞膜をアタックする(だから副作用強い)

・ベータラクタムリング
 ペニシリンにアレルギーあるのにセフェムにアレルギー起こさないひとがいる
 side-chaneにアレルギーあったりする

・新しいcephemは、ペニシリンからさらに遠ざかっている

・O=C-NにあるPBPがターゲット

●ペニシリン ... グラム陽性菌(球菌、桿菌)が得意
         グラム陰性球菌、横隔膜上の嫌気性菌に
・ペニシリンG(天然ペニシリン)
・黄色ブドウ球菌たたくペニシリン
・GNRをたたくペニシリン …無理なことやっているから多く使え
 ・Second generation
  Ampicilin, Amoxicilin, etc
・Third generation
Varbenicillin, Ticarcillin
・Fourth generation
Piperacillin 

●Benzylpenicillin
PCN G K
Procaine PCN G (筋肉注射用、日本にない) …梅毒の標準薬
Benzathine PCN G (筋肉注射用、日本にない)

Benzathine PCN G(経口 …ただ酸にあうと非常に不安定)
 → ちょっといじった Phenethicillin 昨年なくなった…

細菌代表:
・Group A β Streptococcus
  咽頭炎
  丹毒(境界はっきりしてる)
  蜂窩織炎・リンパ管炎
   …黄色ブドウ球菌は、ペニシリナーゼだすから効かない
    黄色ブドウ球菌の蜂窩織炎は、ギザギザで汚い。 …褥瘡や術後傷がある
   ぜんぜん傷なければ連鎖球菌っぽい

  また、連鎖球菌は時間単位で進行
     ブドウ球菌は、日単位で進行

白癬菌から連鎖球菌はいることがある

・肺炎球菌
ペニシリンでたたける。PRSPも効く

1000万Uを12時間ごとに投与すると、血中濃度12mdg/ml
 なのに、PRSP は、8mcg/ml
chest 1997 ;112;1657-1664

持続投与だと、
うまくいきうる
血中濃度 16-20mcg/ml

ただし!!! 髄液には1/100しかいかない!
   壊死性菌膜炎には、CLDMも加える!(毒合成を抑える)・抗体も

・緑色連鎖球菌
  ときどき、がんセンターとかでは耐性α連鎖球菌でたりするけれど

「手のひら、足の平に皮疹があったら、そうでないとわかるまでは梅毒」

・レプトスピラ、ライム病、ボレリア など梅毒以外も様々なスピロヘータに効果あり

・髄膜炎菌
  咽頭痛で来て… 耳に壊死

「膿胸 ペニシリンを使っちゃいけないが、PSGもけっこうきく」

「歯がない人の膿胸は、そうでないとわかるまで癌」
 (歯が必要)

・actinomycosis 障害物無視して貫いていく
 嫌気性菌だけれどPCGよく効く

●細菌の耐性メカニズム
・抗菌薬を破壊する飛び道具
 βラクタマーゼ、アミノグリコシド修飾不活性化酵素
・抗菌薬の攻撃目標の変化
 ペニシリン結合蛋白の変化
 トポイソメラーゼ、リボソームの変化
   …もともと攻撃目標(例:細胞壁)がなかったり
・抗菌薬を近づけさせない
  陣地に入れない(透過性の変化)
  陣地から出す(ポンプ)
  もともと菌が存在する場所に抗菌薬が移行できない(例:細胞内のリケッチア)

壊されない、
 メチシリン (MSSA)
→ターゲットを変えたのが
 メチシリン耐性ブドウ球菌 MRSA
さらに、VRSAも

●黄色ブドウ球菌専用のペニシリン
・Parenteral use
Cloxacillin (メチシリンr) これは販売中止
Nafcilli, Oxacillin
? Ampcollin + Cloxacillin

・oral use
Flucloxacillinなども販売中止

… 心内膜炎
 無実の大腸菌やバクテロイデスつぶしていたら、VRE、etcくる!
 nallow is butifle

point! 嫌気性菌には効かない
  嫌気性菌をたたきすぎると、VREだらけになったりする…
嫌気性菌は大事にするべし
 すさまじい数存在するがゆえに、緑膿菌やカンジダがのさばることができない


●Broad spectrum PCN
・Ampicillin
・Piperacillin
このふたつはほとんどそっくりなのだが、大ヒット!

●Aminopenicillin
Ampixillin
Amoxicillin

PCGの無い病院では代わりに

梅毒をAmocillin 3g で治したりする.。。

・インフルエンザ菌
・大腸菌
  半分以上に効く
  in vitro の S はvivoでも必ず効く!
 COPDの急性増悪、といった待てるものはいい
  常に皆殺しを選ぶより、観察でいいのではないか

・リステリア
・腸球菌は、ABPC+アミノグリコシド

●Piperacillin
昔は毎回20g使っていた

・緑膿菌


●セフェム

Cephalosporin
 は嫌気性菌が苦手
Enterococcus, MRSA, Listeria には効かない!!

Cephamycin
 嫌気性菌こそが売り
・セフメタゾール

1st
P.mirabilis, Ecoli, Klebsiera spp

2nd
HENPEK (or HEMPEK)
H.flu(臨床的にはここがポイント!), Enterobacter, Moraxella(インフルエンザ菌と行動がともに)
→ 耳鼻科、呼吸器に愛される (中耳炎、副鼻腔炎、COPD急性増悪)
  大人よりも小児に問題になりやすい
ただし、Enterobacterは第三世代以降で (消化器は…)

(Cephamycin)

3rd これ以降は髄液に入れる
HENPEK + SPICE
セラチア、シュード、indole positive mirabillis, シトロバクター、エンテロバクター

4th, 5th
beyond 3rd + Staph./Strept

●1st
黄色ブドウ球菌用

E.coli
ペニシリナーゼなし: 市中肺炎
    1st GC, ABPC
 ペニシリナーゼあり+ESBLあなし : 市中感染
1st GC
 ESBLあり: 院内感染
セファロスポリン全滅
... ESBLでなければ第一世代でいける

・おなかの中に事件が無い腸腰菌筋膿瘍は第一世代で


●2nd
インフルエンザ菌
・ペニシリナーゼなし(半分)
  2nd GC, ST, ABPC
・       あり(少ない) BLPAR
2nd GC, ST
・BLNAR (半分)・・・鍵穴変化
  2nd GCだめ → 3rd以降を
beta lactamaze negative

  …グラム染色で、ごみに見えやすい
   形がまちまち… 球菌や桿菌がまざっていたり… 染色性もまちまち

moraxella


●Cephamycin

E.coli, Klebsiella, B.fragilis
(横隔膜の下の三大横綱)
   腸穿孔や虫垂炎穿孔、PID
 院内誤嚥性肺炎 …寝たきりの口の中にはE.coliとかいる

腸球菌・MRSA・リステリア
ESBLはよくわからない


● 3rd
外膜透過性アップ、ベータラクタマーゼ安定、

PRSP をカバー :CTRX
 or
緑膿菌 をカバー :Ceftazidime(モダシン), Cefoperazon ...GPCも嫌気性菌も捨てた

●4th
Cefepime
 髄液移行性はちょっと悪い…

「常識が通用しないもの」
●ESBL : extended spectrum beta luctamaze

PEKに 凶暴性をもたせた上で、耐性をもたせた!!!!!!
   ペネムや
→ すぐに隔離や手洗いを!


ESBL は うそつきが多い 効かないくせにvitro でSを!
 セフェム が感受性あるのに…
 PIPC, AZT, 3rd のどれかひとつにRがあれば、ESBLの可能性あり!!!


●SPICE
突然、効かなくなる! 2週間後に…
おなじセラチア、シトロバクターなのに…
途中で遺伝子が変わる AmpC
→ベータラクタマーゼを大量につくり、3rdすら壊す!

SBT・TAZ無効!

・染色体型
・プラスミド型


ESBLは結婚詐欺 (最初から違う)
AmpC 心変わり (最初も最後もホント)

●緑膿菌は
もともと耐性を潜在的にもっている

・PRSP 3rd!
・淋菌 CTRX
・スピロヘータ 3rd

●カルバペネム
もっともスペクトラムが広い
 いろいろな鍵穴にはいれ、
 壊されにくく
 いろいろなチャネルを通れる

アシネトバクター とか予想されるなら…


●モノバクタム
結合できる鍵穴PBPがひとつだけ
→好気性グラム陰性桿菌
  …腎毒性の少ないアミノグリコシド
ただ、またたくまに耐性をつくる

  ・逆にアミノグリコシドは耐性作りにくい

・交差アレルギー少ない

モダシン、アズトレオナムはわりと交差する

●GNRをわける
1)PEC E.col, Kleb, Proteus
2)セラチア、シトロバクター、エンテロバクター
3)(非発酵) アシネトバクター、シュードモナス

 上ほど凶暴、下ほど耐性
  ばい菌は、毒性 or 耐性のどちらかをとる

●メータラクタマーゼインヒビター
ベータラクタマーゼを代わりに引き受ける

・AMPC/SBT
  歯が立たなかったブドウ球菌にも、
  嫌気性菌にも、 かなり広く効く  poor man's penem

×「最初はユナシンくらいから」 つかってれば、カンジダこいよ、になる


◆質問: カルバペネム
積極的に使うときは?
 周囲の感受性を知らないと…難しい
紹介元のコミュニケーション、そこのGNRと、感受性のスペクトラムを


コンビネーションアンチバイオグラム
 →抗生剤がだめなとき、次の抗生剤は?というコンボが見えてくる

◆質問: 切迫早産、ウテメリン
 突然の敗血症、培養がセラチア
  最初は4thが効いたが…再度発熱  栄養がよくて乗り切れたが…

…ライン感染があっても、局所所見の感度は2〜3割


●質問

CPFX, LVFX,


・SBT/CPZ
スルバクタムナトリウム・セフォペラゾンナトリウム


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