Efficacy of high-dose tigecycline-containing regimens for the combination treatment of carbapenem-resistant Enterobacterales bacteraemia

Abstract

Background Carbapenem-resistant Enterobacterales (CRE) are critical priority pathogens due to limited therapeutic options. Standard-dose tigecycline (100 mg/day) may not achieve adequate plasma levels for treating CRE bacteraemia. High-dose tigecycline (HD-TGC; 200 mg/day) may improve drug exposure and clinical outcomes, though supporting evidence remains limited. This study aimed to evaluate the efficacy of an HD-TGC-containing regimen compared with other treatments for CRE bacteraemia. Methods We conducted a retrospective propensity-score matched study at Phramongkutklao Hospital in Bangkok, Thailand, including adults with monomicrobial CRE bacteraemia (2017-2021). The primary outcome was 30-day all-cause mortality. Secondary outcomes were clinical and microbiological responses on Day 7. Results Of 161 eligible patients, 37 (23.0%) received HD-TGC and 124 received other regimens. Klebsiella pneumoniae accounted for 90.6% of cases. Genotypic resistance testing in 28 isolates revealed blaOXA-48 (53.6%), blaNDM (21.4%), and blaNDM + OXA-48 (21.4%) genes. The median age was 71 years (IQR 49-81). Patients in the HD-TGC group had more severe illness, including higher Pitt bacteraemia scores and vasopressor use. After 1:1 matching, 37 pairs were analysed. A non-significant trend towards lower 30-day mortality was observed in the HD-TGC group (HR 0.59; 95% CI: 0.30-1.14; P = 0.118). Microbiological response on Day 7 was significantly higher in the HD-TGC group (75.9% versus 46.2%; P = 0.027), while clinical response rates were not significantly different (48.6% versus 37.8%; P = 0.479). Conclusions HD-TGC was associated with improved microbiological clearance and showed a trend towards reduced mortality in patients with CRE bacteraemia.