Department of General Internal Medicine and Clinical Infectious Diseases, Fukushima Medical University, Fukushima, Japan.
Department of General Internal Medicine and Infectious Diseases, Kita-Fukushima Medical Center, Fukushima, Japan.
J Antimicrob Chemother. 2024 Aug 1;79(8):1962-1968. doi: 10.1093/jac/dkae192.
Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment.
This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications.
A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted OR = 25.98, 95% CI = 1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30).
This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages.
四环素类药物是立克次体病（包括由恙虫病东方体引起的恙虫病）的标准治疗药物。虽然日本的一些专家主张将氟喹诺酮类药物与四环素类药物联合用于治疗恙虫病，但联合治疗的负面问题尚未得到全面评估。氟喹诺酮类药物是否应与四环素类药物联合用于治疗恙虫病存在争议。本研究旨在评估氟喹诺酮类药物联合四环素类药物治疗恙虫病的弊端。
这是一项使用日本数据库进行的回顾性队列研究，该数据库包含了 2008 年 4 月至 2020 年 12 月的索赔数据。比较了联合治疗组（四环素类药物和氟喹诺酮类药物）与单药治疗组（仅四环素类药物）的死亡率和并发症发生率。
共纳入 797 例患者：525 例接受联合治疗，272 例接受单药治疗。与单药治疗组相比，联合治疗组的死亡率调整比值比（OR）为 2.30（95%置信区间：0.28-18.77）。根据亚组分析，与接受单药治疗的患者相比，接受环丙沙星联合治疗的患者死亡率更高（调整 OR=25.98，95%CI=1.71-393.75）。此外，联合治疗组中有 27.7%的患者同时接受了非甾体抗炎药（NSAIDs）与氟喹诺酮类药物联合治疗。与未使用 NSAIDs 的单药治疗组相比，联合 NSAIDs 治疗组更易发生惊厥（调整 OR：5.44，95%CI：1.13-26.30）。
本研究未发现联合治疗可改善死亡率的证据，反而揭示了其有害影响。这些发现有助于对联合治疗进行公平评估，包括考虑其弊端。
