Abstract
Tigecycline is a broad-spectrum antibiotic usually used as a last resort for infections caused by multidrug-resistant and extensively drug-resistant Gram-negative bacteria, such as Enterobacterales and Acinetobacter spp. The evolvement of antimicrobial resistance has led to the increased demand for tigecycline. However, data comparing the efficacy and safety of high (HD) versus standard doses (SD) of tigecycline are limited. Therefore, this study aimed to compare the clinical and microbiological outcomes of these doses in hospitalized patients.
This was a retrospective cohort multicenter study. Adult patients admitted between January 2018 and October 2020 who received tigecycline as monotherapy or in combination with other antibiotics for at least 3 days with a microbiologically documented infection were included. Clinical cure was the primary endpoint. Secondary endpoints included microbiological cure, mortality and length of stay.
Of 292 patients, 77 were in the HD group while 215 were in the SD group. Baseline characteristics were similar, except for the duration of tigecycline therapy, which was 3 days longer in the HD group (P= 0.007), and source of infection (P<0.0001). Most patients in the HD group had either respiratory (54.5%), skin and soft tissue infections (SSTIs; 22.1%), or more than one site of infections (23.4%). On the other hand, most patients in the SD group had either respiratory (40.4%) or skin and soft tissue infections (40.8%), While microbiological cure was higher in the HD group (16.9% vs. 10.8%; P=0.005), clinical cure rates were lower in the HD group (24.7% vs. 39.1%; P= 0.02). Mortality rate was higher in the HD group at 63.6% compared with 39.1% in the SD group (P<0.0001). Notably, most isolates from patients in the HD group had intermediate susceptibility to tigecycline (51.3%), whereas isolates were mostly susceptible in the SD group (47.9%; P <0.0001).
HD regimen of tigecycline in this study was not superior to SD. The less favorable outcomes could be attributed to the lower susceptibility to tigecycline in the HD group. More studies are needed to assess the impact of HD in patients with susceptible isolates.