トリメトプリム/スルファジアジン および トリメトプリム/スルファメトキサゾール
強化サルファ剤（TMS、SMZ-TMP、またはコトリモキサゾールとよく呼ばれる）は、獣医療で広く使用されている広域スペクトルの殺菌性抗菌薬の配合剤です。 **重要な臨床的ポイント：** - **優れた組織移行性：** 脂溶性が高く、**前立腺**、**血液脳関門（CNS）**、**眼**などの到達しにくい組織でも治療濃度に達します。 - **広域スペクトル：** メチシリン耐性ブドウ球菌（MRSA/MRSP）の多くの株、*ノカルジア*、および特定の原虫（*トキソプラズマ*、*コクシジウム*、*ニューモシスチス*）を含む、多くのグラム陽性および陰性菌に有効です。 - **膿による不活化：** 薬効は化膿性デブリや壊死組織（PABAとチミジンが豊富）によって著しく阻害されます。効果を得るためには膿瘍の排膿が必要です。 - **犬種の感受性：** ドーベルマン・ピンシャーは、サルファ剤誘発性の多系統免疫複合体疾患（過敏症）に対する犬種特異的な感受性があることが知られています。 - **剤形：** 獣医承認のトリメトプリム/スルファジアジン製品が存在しますが、多くの獣医師はヒト用承認のトリメトプリム/スルファメトキサゾール（Bactrim®、Septra®）を適応外使用し、同様の有効性を得ています。
作用機序: Potentiated sulfas exhibit **synergistic, bactericidal** activity by sequentially blocking the bacterial folic acid synthesis pathway. Mammalian cells are largely unaffected because they utilize preformed dietary folate rather than synthesizing it. - **Sulfonamides (Bacteriostatic alone):** Act as structural analogues of para-aminobenzoic acid (PABA). They competitively inhibit the bacterial enzyme **dihydropteroate synthase** → blocks the conversion of PABA to dihydrofolic acid (DFA). - **Trimethoprim (Bactericidal alone):** Reversibly inhibits the bacterial enzyme **dihydrofolate reductase** → blocks the conversion of DFA to tetrahydrofolic acid (THFA). - **Synergy:** The sequential blockade completely depletes THFA, an essential cofactor for bacterial DNA and RNA synthesis, leading to rapid bacterial cell death. > *Pharmacologic Note:* The optimal *in vitro* ratio for most susceptible bacteria is 1:20 (trimethoprim:sulfa), but synergistic activity occurs across a wide range (1:1 to 1:40). The serum concentration of the trimethoprim component is generally considered the primary driver of efficacy.
動物種別の用量
- UTI · 30 mg/kg PO q24h · PO · q24h · 7-14 days
- UTI, soft tissue infections · 15 mg/kg PO q12h · PO · q12h · 7-14 days
- Susceptible infections · 30 mg/kg q12h · PO · q12h · If treating Nocardia, double dose
- Toxoplasmosis · 15 mg/kg PO q12h · PO · q12h · 28 days
- Bacterial UTI · 30 mg/kg q12h PO · PO · q12h
- Susceptible infections · 30 mg/kg PO twice daily · PO · q12h
- Coccidiosis · 30 mg/kg PO once daily · PO · q24h · 14 days
- Susceptible infections · 44 mg/kg once daily IM or IV using 48% suspension · IM/IV · q24h
- Susceptible infections · 25 mg/kg, IV or IM q24h · IV/IM · q24h
- Susceptible infections (Calves) · 48 mg/kg IV or IM q24h · IV/IM · q24h
- Respiratory tract infections · 15-30 mg/kg PO q12h · PO · q12h · Give 30 minutes prior to feeding hay
投与経路
禁忌
- Hypersensitivity to sulfonamides, thiazides, or sulfonylurea agents
- Severe renal or hepatic impairment
- Doberman pinschers (highly susceptible to immune complex disease)
- Marked blood dyscrasias
- Animals intended for food (in the USA/certain jurisdictions)
有害事象
- Dogs: Keratoconjunctivitis sicca (KCS/dry eye - potentially irreversible)
- Dogs: Hypersensitivity reactions (Type 1 anaphylaxis or Type 3 serum sickness, polyarthritis, urticaria, facial swelling)
- Dogs: Acute neutrophilic hepatitis with icterus, idiosyncratic hepatic necrosis
- Dogs: Vomiting, anorexia, diarrhea
- Dogs: Hemolytic anemia, agranulocytosis
- Dogs: Hypothyroidism (with extended therapy)
- Dogs: Crystalluria, hematuria, polyuria, polydipsia
- Cats: Anorexia, crystalluria, hematuria, leukopenias, anemias
- Horses: Transient pruritus (after IV injection), diarrhea, hypersensitivity, hematologic effects
- Injection site reactions: Swelling, pain, tissue damage (IM, SC, or extravasation)
薬物相互作用
- Amantadine · May cause toxic delirium (reported in humans)
- Antacids · May decrease the bioavailability of sulfonamides if administered concurrently
- Cyclosporine · May increase the risk of nephrotoxicity
- Digoxin · May increase digoxin levels
- Diuretics, Thiazide · May increase risk for thrombocytopenia
- Hypoglycemic agents, oral · May potentiate hypoglycemic effects
- Methotrexate · May displace from plasma proteins and increase risk for toxic effects; can also interfere with MTX assays
- Phenytoin · May increase half-life of phenytoin
- Tricyclic antidepressants · May decrease efficacy of the antidepressant
- Warfarin · May prolong INR/PT and increase bleeding risk
モニタリング
- Clinical efficacy
- Adverse effects (GI, hypersensitivity)
- Complete blood counts (CBC) periodically with chronic therapy
- Schirmer Tear Test (STT) in dogs to monitor tear production (e.g., at 5 days, then every 2-3 weeks)
- Thyroid function tests (baseline and ongoing) for dogs on long-term treatment
過量投与
Manifestations of acute overdosage include GI distress (nausea, vomiting, diarrhea), CNS toxicity (depression, headache, confusion), facial swelling, bone marrow depression, and elevated serum aminotransferases. **Treatment:** - **Oral Overdose:** Empty the stomach following usual protocols and initiate symptomatic/supportive therapy. - **Fluid Therapy:** Maintain hydration. Acidification of urine may increase renal elimination of trimethoprim but increases the risk of sulfonamide crystalluria (especially with sulfadiazine). - **Monitoring:** Monitor complete blood counts and liver parameters. - **Bone Marrow Suppression:** If severe and associated with chronic overdose, may be treated with folinic acid (leucovorin). - *Note:* Peritoneal dialysis is not effective in removing TMP or sulfas from circulation.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。