AOVV E, Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
Eur Respir J. 2013 Jun;41(6):1386-92. doi: 10.1183/09031936.00124312. Epub 2012 Sep 20.
Clinical experience on meropenem-clavulanate to treat tuberculosis (TB) is anecdotal (according to case reports on 10 patients). The aim of our case-control study was to evaluate the contribution of meropenem-clavulanate when added to linezolid-containing regimens in terms of efficacy and safety/tolerability in treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases after 3 months of second-line treatment. 37 cases with MDR-/XDR-TB were prescribed meropenem-clavulanate (3 g daily dose) in addition to a linezolid-containing regimen (dosage range 300-1200 mg·day(-1)), designed according to international guidelines, which was prescribed to 61 controls. The clinical severity of cases was worse than that of controls (drug susceptibility profile, proportion of sputum-smear positive and of re-treatment cases). The group of cases yielded a higher proportion of sputum-smear converters (28 (87.5%) out of 32 versus nine (56.3%) out of 16; p=0.02) and culture converters (31 (83.8%) out of 37 versus 15 (62.5%) out of 24; p=0.06). Excluding XDR-TB patients (11 (11.2%) out of 98), cases scored a significantly higher proportion of culture converters than controls (p=0.03). One case had to withdraw from meropenem-clavulanate due to increased transaminase levels. The results of our study provide: 1) preliminary evidence on effectiveness and safety/tolerability of meropenem-clavulanate; 2) reference to design further trials; and 3) a guide to clinicians for its rationale use within salvage/compassionate regimens.
临床使用美罗培南-克拉维酸治疗结核病（TB）的经验是零星的（根据 10 例患者的病例报告）。我们的病例对照研究的目的是评估在二线治疗 3 个月后，在包含利奈唑胺的方案中添加美罗培南-克拉维酸对治疗耐多药（MDR）和广泛耐药（XDR）TB 病例的疗效和安全性/耐受性的贡献。37 例 MDR-/XDR-TB 患者除了根据国际指南设计的包含利奈唑胺的方案（剂量范围 300-1200mg·天（-1））外，还每天服用美罗培南-克拉维酸（3g 剂量）。将该方案开给 61 名对照。病例的临床严重程度高于对照组（药敏谱、痰涂片阳性和复治病例的比例）。病例组痰涂片转化率更高（28（32 例中的 87.5%）比 9（16 例中的 56.3%）；p=0.02）和培养转化率更高（31（37 例中的 83.8%）比 15（24 例中的 62.5%）；p=0.06）。排除 XDR-TB 患者（98 例中的 11 例）后，病例组的培养转化率明显高于对照组（p=0.03）。1 例因转氨酶升高而不得不停止使用美罗培南-克拉维酸。我们的研究结果提供了：1）美罗培南-克拉维酸有效性和安全性/耐受性的初步证据；2）参考设计进一步的试验；3）为临床医生在挽救/同情性方案中合理使用提供指导。
