de Kantor Isabel N, Barrera Lucia
Panel de Consultores en Tuberculosis, OMS, Buenos Aires.
Medicina (B Aires). 2007;67(3):231-7.
The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistance to all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.
药敏试验在指导二线抗结核药物治疗中的价值仍存在争议。我们重新分析了三份报告，这些报告涉及20世纪60年代在布宜诺斯艾利斯的穆尼兹医院，结核分枝杆菌的体外药敏与使用这些药物治疗的住院患者临床结局之间的关系。这些患者接受了由异烟肼、链霉素和对氨基水杨酸组成的标准方案的不规则治疗；他们对至少前两种药物产生了耐药性，且培养持续呈阳性。采用比例法在罗-琴培养基上对乙硫异烟胺、环丝氨酸和卡那霉素进行药敏试验。在未接受过这些药物治疗的患者分离株中检测到一定程度的耐药性，这可能是由于与先前使用的一线结构类似物存在交叉耐药性。然而，研究表明对乙硫异烟胺和环丝氨酸的耐药性与先前使用这些药物治疗之间存在显著关联。在治疗的前三个月内检测到对所有三种药物的耐药性增加。对乙硫异烟胺的体外耐药性出现较早且最为常见，其次是对环丝氨酸和卡那霉素的耐药性。对卡那霉素耐药性频率较低可能与当时使用该药物的剂量较低有关。对三种药物同时耐药而非对两种或一种药物耐药似乎是治疗失败的标志。在近6%的患者中观察到耐药性明显逆转，对这些患者后续分离株重复进行药敏试验，表明该比例的试验结果再现性不一致。
