Gas gangrene

Japanese: ガス壊疽

(5) Gas gangrene
DefinitionGas gangrene is a fatal necrotizing infection caused by Clostridium bacteria (clostridia), a group of bacteria collectively known as gas gangrene bacteria that are highly cytotoxic and tissue damaging, that usually produces large amounts of gas and invades subcutaneous tissue, fascia, and even muscles. It is a synonym of myonecrosis, which refers to a state of muscle necrosis. Gas gangrene bacteria include Clostridium perfringens, C. septicum, C. novyi, C. sordellii, C. histolyticum, C. chauvoei, C. bifermentans, and C. limosum. There are traumatic (exogenous) and idiopathic (endogenous) types.
Spores of the pathogenic gas gangrene bacteria are widely distributed in nature and are present in soil and the intestines of humans and animals. C. perfringens and C. septicum are present in soil and the human intestinal tract and frequently cause traumatic or endogenous gas gangrene. The prevalence of these two species among healthy individuals is several tens of percent and a few percent, respectively.
C. perfringens produces α-toxin (43 kDa) and θ-toxin. C. perfringens α-toxin (phospholipase C) is a platelet agonist that aggregates with platelets to form thrombi in capillaries, small veins, and small arteries. Blockage of blood flow by a thrombus reduces the local redox potential and promotes the growth of anaerobic bacteria. The θ-toxin of C. perfringens, perfringolysin, is a pore-forming toxin that forms pores in the cell membrane. In addition, θ-toxin contributes to the progression of gas gangrene by modifying the inflammatory response at low concentrations. Other species of the gas gangrene group are known to produce pore-forming toxins, but characterization of the toxins and analysis of their role in disease have not progressed.
Classification
1) C. perfringens gas gangrene (traumatic):
It occurs when injuries reach the muscles, such as crush injuries or fractures, or when injuries reach the intestinal tract, such as stab wounds or gunshot wounds. The former is caused by C. perfringens spores in the soil, while the latter is caused by C. perfringens in the intestinal tract.
When the bacteria grow and produce toxins, the toxins cause embolism in small blood vessels, causing sudden, severe pain. As the bacteria grow, gas is produced and tissue destruction and swelling progress. Furthermore, if the toxins enter the bloodstream, they can cause intravascular hemolysis, shock, and multiple organ failure.
2) C. septicum and C. perfringens gas gangrene (idiopathic/endogenous):
It begins with sudden, severe pain and sometimes confusion or other impaired consciousness. It is seen in patients with colon cancer, diverticulitis, after gastrointestinal surgery, leukemia, cancer chemotherapy or radiation therapy, and AIDS patients. It is caused by a group of gas gangrene bacteria in the intestine. The bacteria enter the bloodstream from the intestine, multiply in the tissues, and cause gas gangrene.
3) Clostridium-associated anaerobic cellulitis:
In diabetic patients, the subcutaneous tissue and retroperitoneum are affected first, then the disease progresses explosively to a systemic stage. In some cases, the only manifestation is edema, as seen in C. novyi gas gangrene in drug addicts with repeated intramuscular injections.
4) Other acute infections involving the gastrocnemic bacteria:
These include C. sordellii infections associated with abortion, C. perfringens gas gangrene associated with biliary cholecystitis, and severe C. perfringens infections following trauma or surgery in the ophthalmologic field.
Diagnosis The key to diagnosing traumatic gas gangrene caused by C. perfringens is the sudden onset of severe pain at the site of injury and rapid expansion of the wound accompanied by bloody secretions containing foul-smelling gas. Gram staining of direct smears of secretions or biopsy specimens is characterized by the presence of Gram-positive bacilli, but no inflammatory cells. This finding is related to the action of toxins (thrombus formation and cell lysis) of the gas gangrene bacteria group. Blood cultures are positive. Idiopathic gas gangrene caused by C. perfringens or C. septicum occurs unrelated to trauma, so early diagnosis can be difficult. The initial symptom may be sudden loss of consciousness.
Prevention and Treatment
1) Prevention of gas gangrene:
The wound should be thoroughly debridement and disinfected. It is also important not to create or sustain an anaerobic environment at the wound by revascularization or other measures.
2) Treatment of gas gangrene:
Surgical treatment is important. In some cases, amputation of the limbs is chosen to save the patient's life. Antitoxin serum therapy and antibacterial chemotherapy are performed in conjunction with surgical treatment. Chloramphenicol, clindamycin, piperacillin, imipenem, and other drugs have antibacterial activity against the gas gangrene group. With the exception of clindamycin, there has been no resistance to antibacterial drugs. Experiments using an animal model of C. perfringens gas gangrene have shown that clindamycin, a protein synthesis inhibitor, is more effective than penicillin, a cell wall synthesis inhibitor that is the standard drug of choice for gas gangrene. Hyperbaric oxygen therapy is also performed, although it is currently only a supportive treatment. [Watanabe Kunitomo]
■ References
Stevens DL, et al: Life-threatening clostridial infections. Anaerobe, 18: 254-259, 2012.

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（5）ガス壊疽（gas gangrene）
定義
　ガス壊疽は，細胞・組織障害性が強い数種のガス壊疽菌群と総称されるクロストリジウム属細菌（clostridia）が原因となる皮下組織，筋膜，そして筋肉までが侵された通常大量のガス産生を伴う致死的壊死性感染症である．筋肉壊死に陥った状態をいうmyonecrosisと同意語である．Clostridium perfringens，C. septicum，C. novyi，C. sordellii，C. histolyticum，C. chauvoei，C. bifermentans，C. limosumなどがガス壊疽菌群である．外傷性（外因性）と特発性（内因性）がある．
病因
　ガス壊疽菌群の芽胞は自然界に広く分布し，土壌や人・動物の腸管内にも存在する．C. perfringensとC. septicumは土壌，ヒトの腸管に存在し，外傷性または内因性のガス壊疽の原因となる頻度が高い．健康人の両菌種の保有率はそれぞれ数十％，数％である．
　C. perfringensはα毒素（43 kDa），θ毒素を産生する．C. perfringens α毒素（ホスホリパーゼ C）は，血小板アゴニストであり，毛細血管・小静脈・小動脈の血管内で血小板と凝集による血栓を形成する．血栓による血流遮断は局所の酸化還元電位を低下させ，嫌気性菌の増殖を促進させる．C. perfringensのθ毒素パーフリンゴリジン（perfringolysin）は細胞膜にポアを形成する孔形成毒素である．また，θ毒素は低濃度で炎症性反応を修飾することにより，ガス壊疽の進展に貢献する．その他のガス壊疽菌群の菌種も孔形成毒素などを産生することがわかっているが，毒素の特徴付けや疾病における役割の解析は進んでいない．
分類
1）C. perfringensガス壊疽（外傷性）：
挫滅，骨折などで筋肉に達するような損傷を受けた場合，刺傷，銃創など腸管に達する損傷を受けた場合に起こる．前者では土壌中のC. perfringensの芽胞が，後者では腸管内のC. perfringensが原因である．C. perfringens
が増殖・毒素を産生すると，その毒素により小血管に塞栓をきたし，突然の激痛が現れる．菌の増殖に伴いガス産生，組織の破壊や腫脹が進行する．また，毒素が血流に入ると血管内溶血，ショック，多臓器不全などを起こす．
2）C. septicumおよびC. perfringensガス壊疽（特発性・内因性）：
突然の激痛，ときに錯乱などの意識障害で発症する．大腸癌，憩室炎，消化器外科手術後，白血病の患者，癌化学療法・放射線療法中の患者，AIDS患者などでみられる．腸管内のガス壊疽菌群が原因である．腸管から血流に侵入し，組織内で増殖し，ガス壊疽を起こす．
3）クロストリジウムが関与する嫌気性蜂巣炎：
糖尿病患者ではまず皮下組織や後腹膜が侵され，その後電撃的に全身疾患に移行する．筋肉内注射を繰り返している薬物常用者でみられるC. novyiガス壊疽のように浮腫のみが前面に出る場合もある．
4）ガス壊疽菌群が関与するその他の急性感染症：
妊娠中絶と関連したC. sordellii感染症，胆管胆囊炎と関連したC. perfringensガス壊疽，そして眼科領域でみられる外傷後・術後の重症C. perfringens感染症などがある．
診断
　C. perfringensによる外傷性ガス壊疽の診断のポイントは受傷部位の突然の激痛と悪臭のあるガスを含む血性分泌物を伴う急激な創部の拡大である．分泌物や生検によって得た検体の直接塗抹標本のGram染色所見の特徴はGram陽性桿菌を認めるが，炎症細胞を認めない点である．この所見はガス壊疽菌群の毒素の作用（血栓形成・細胞溶解）と関連している．血液培養が陽性となる．C. perfringensやC. septicumによる特発性ガス壊疽は外傷と無関係に起こるため，早期の診断が難しい場合がある．突然の意識障害が初発症状となる場合がある．
予防・治療
1）ガス壊疽の予防：
創部のデブリドマンと消毒を十分に行う．血行再建などにより創部に嫌気環境をつくらない，持続させないことも重要である．
2）ガス壊疽の治療：
外科的処置が重要である．救命のため四肢の切断が選択されることがある．抗毒素血清療法と抗菌化学療法が外科的処置とともに行われる．クロラムフェニコール，クリンダマイシン，ピペラシリン，イミペネムなどはガス壊疽菌群に抗菌力を有する．クリンダマイシンを除き抗菌薬に対する耐性化もない．C. perfringensガス壊疽動物モデルを用いた実験で，蛋白合成阻害薬であるクリンダマイシンが，ガス壊疽の標準的選択薬である細胞壁合成阻害薬のペニシリンより効果的であったことが示されている．また，現時点では補助的治療の域を出ないが，高圧酸素療法も行われる．［渡邉邦友］
■文献
Stevens DL, et al: Life-threatening clostridial infections. Anaerobe, 18: 254-259, 2012.

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