In Vitro and In Vivo Intracellular Killing Effects of Tigecycline against Clinical Nontyphoid Salmonella Isolates Using Ceftriaxone as a Comparator

Abstract

Salmonella is an important, worldwide food-borne pathogen. Resistance to fluoroquinolones and cephalosporins has been increasingly reported, and new therapeutic agents are desperately needed. In this study, we evaluated the in vitro antimicrobial susceptibility of clinical nontyphoidal Salmonella isolates to tigecycline. Antibacterial activity of tigecycline, ceftriaxone, and ciprofloxacin were investigated by time-kill studies and the murine peritonitis model. The MIC 50 /MIC 90 values of tigecycline, ceftriaxone, and ciprofloxacin against 76 Salmonella isolates were 0.25/0.5, 1/8, and 0.125/0.5 g/ml, respectively. The intracellular inhibitory activity of tigecycline at 0.5 g/ml (1؋ MIC) against Salmonella isolates in human peripheral blood mononuclear cells was sustained for 24 h. In a mouse peritonitis model, tigecycline reduced the extracellular and intracellular bacterial counts from 10 7 CFU/ml and 10 5 CFU/ml, respectively, to an undetectable level within 96 h. The results were similar to those obtained with ceftriaxone. The survival rate of mice exposed to tigecycline after being infected by an inoculum of 1 ؋ 10 5 CFU was 80%, and that of mice exposed to ceftriaxone was 100%. When the inoculum was increased to 1.3 ؋ 10 6 CFU, the survival rate of mice treated by tigecycline was 20%, and that of mice exposed to ceftriaxone was 0% (P ‫؍‬ 0.2). When a ceftriaxone-and ciprofloxacin-resistant but tigecycline-susceptible isolate was tested, mice treated by tigecycline had a higher survival rate than those treated by ceftriaxone (15/20 [75%] versus 6/20 [30%]; P ‫؍‬ 0.011). Our results suggest that tigecycline is at least as effective as ceftriaxone for murine Salmonella infections and warrants further clinical investigations to delineate its potential against human Salmonella infections.

Non‐typhoidal Salmonella infections in children: Review of literature and recommendations for management

“…Broad‐spectrum antimicrobial agents with activity against multi‐drug‐resistant NTS include tigecycline and carbapenems . Carbapenems have been shown to be active against Salmonella species in vitro , and meropenem has been reported to achieve high intracellular concentrations in human macrophages .…”

Alteration of the Murine Gastrointestinal Microbiota by Tigecycline Leads to Increased Susceptibility to Clostridium difficile Infection

“…Wild-type C57BL/6 mice (males or females) were given either tigecycline (6.25 mg/kg of body weight) (n ϭ 20) or saline (n ϭ 8) by subcutaneous injection twice a day for a total of 10 days. This dose of tigecycline was selected for the mice because it reaches the maximum concentration of drug in serum (C max ) of 1.17 g/ml, which is similar to a C max of 0.93 g/ml, which correlates to a dose of 100 mg every 12 hours in humans (16). The mice were approximately 5 weeks old at the beginning of the study.…”

“…It was subsequently approved for the treatment of community-acquired pneumonia (11). Tigecycline is a broad-spectrum glycylcycline antibiotic that is potent against both Gram-positive and Gram-negative facultative and obligate anaerobes, including C. difficile (12)(13)(14)(15)(16). Tigecycline has a low MIC against C. difficile in vitro (17).…”

Targeting the hard to reach: challenges and novel strategies in the treatment of intracellular bacterial infections

“…This antibiotic has potent activities against a range of Gram‐positive and Gram‐ negative bacteria (Peterson, ). Tang et al () demonstrated bactericidal activities of tigecycline at 0.5 mgL −1 against intracellular S . Typhimurium in peripheral blood mononuclear cells.…”