Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice
Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice
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新合成的苯并嗪诺福霉素 KRM-1648 对小鼠诱导的鸟分枝杆菌复合感染的化疗效果
DOI：
10.1128/aac.36.2.387
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发表时间：
1992
影响因子：
4.9
通讯作者：
T. Hidaka
中科院分区：
文献类型：
--
作者：
H. Tomioka;H. Saito;K. Sato;T. Yamane;K. Yamashita;K. Hosoe;K. Fujii;T. Hidaka
研究了新合成的苯并恶嗪诺霉素（KRM-1648）的体内抗鸟分枝杆菌复合体（MAC）活性。当用Middlebrook 7H11琼脂培养基琼脂稀释法测定mic时，KRM-1648对艾滋病和非艾滋病患者分离的MAC具有相似的体外抗菌活性，这表明KRM-1648可能对艾滋病相关的MAC感染有用。KRM-1648对毒力较弱的胞内分枝杆菌N-260和N-478诱导的实验小鼠感染表现出较强的治疗作用。同样，KRM-1648对nk细胞缺陷小鼠（作为艾滋病相关MAC感染的合理模型）诱导的胞内支原体感染表现出出色的治疗效果，其中观察到感染部位的大体病变进展状态和细菌负荷。在第4周和第8周将感染的米色小鼠杀死，通过降低细胞内M. N-241、N-256和N-260感染的肺部病变发生率和程度以及肺和脾脏细菌负荷，可以看到明显的治疗效果。结果表明，N-260侵染的效果最高，N-241次之。观察小鼠感染至死亡，发现KRM治疗可延长感染小鼠的存活时间。然而，在感染后期，KRM-1648在抑制肺部病变的进展和感染部位（包括肺和脾脏）细菌负荷的增加方面没有效果。这可能意味着治疗艾滋病相关MAC感染的化疗有一些困难，即使使用KRM-1648治疗，也有一些困难，因为KRM-1648在体外和体内都有出色的抗MAC活性，正如本研究所示。
Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N-256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.
DOI：
10.1164/ajrccm/141.3.626
发表时间：
1990-03-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
HEIFETS, LB;LINDHOLMLEVY, PJ;FLORY, MA
通讯作者：
FLORY, MA