Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Clin Infect Dis. 2021 Nov 2;73(9):e3511-e3517. doi: 10.1093/cid/ciaa1509.
Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB.
Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992-2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses.
Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73-1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome.
In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.
耐多药结核病（MDR-TB）中吡嗪酰胺（PZA）耐药很常见；然而，其如何影响中期和治疗结局尚不清楚。虽然很少进行，但表型药敏试验（pDST）用于定义 PZA 耐药性，但基因型 DST（gDST）和最小抑菌浓度（MIC）可能会有所帮助。我们旨在评估 MDR-TB 患者中 PZA gDST 和 MIC 对痰培养转换（SCC）时间和治疗结局的影响。
本队列研究收集了 1992-2014 年在瑞典诊断为 MDR-TB 的所有患者的临床、微生物学和治疗数据。使用 MIC、pDST 和 pncA、rpsA 和 panD 基因的全基因组测序来定义 PZA 耐药性。使用 Cox 回归模型进行统计分析。
在 157 例 MDR-TB 患者中，56.1%（n=88）的菌株对 PZA 耐药，49.7%（n=78）接受 PZA 治疗。在未校正和校正分析中（危险比 [HR]，0.49；95%置信区间 [CI]，.29-.82；P=0.007），PZA gDST 耐药与 SCC 时间延长 29 天相关。PZA 敏感株的 PZA MIC 稀释度降低 2 倍与 SCC 无关，无论在未校正还是校正分析中（HR，0.98；95%CI，.73-1.31；P=0.89）。PZA 的 MIC 和 gDST 与治疗结局无关。
在 MDR-TB 患者中，gDST PZA 耐药与 SCC 时间延长相关。快速进行 PZA gDST 对于确定可能从 PZA 治疗中受益的患者很重要。
