Pharmacokinetic/pharmacodynamic profile for tigecycline—a new glycylcycline antimicrobial agent

Meagher, Alison; Ambrose, Paul G.; Grasela, Thaddeus H.; Ellis-Grosse, Evelyn J.

doi:10.1016/j.diagmicrobio.2005.05.006

Cited by 111 publications

(76 citation statements)

References 24 publications

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“…According to previous in vitro and in vivo studies, tigecycline has been shown to achieve high intracellular concentrations and exhibits a promising survival outcome in infected mice compared with traditional ceftriaxone therapy (20,32). However, the low serum levels of tigecycline reached by currently recommended dosages might pose a clinical concern for treating Salmonella bacteremia in humans (23).…”

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confidence: 99%

Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from In Vitro and In Vivo Animal Studies

Tang

Chen

Zhang

et al. 2012

Antimicrob Agents Chemother

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fThe emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC 50 and MIC 90 for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 g/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10 2 -to 10 4 -fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 ؋ 10 5 and 10 6 CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 ؋ 10 4 and 10 5 CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P < 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

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confidence: 99%

Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from In Vitro and In Vivo Animal Studies

Tang

Chen

Zhang

et al. 2012

Antimicrob Agents Chemother

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“…81 The pharmacokinetic properties of tigecycline include a large Vd (7-9 L/kg), high protein binding (73-79%), long half-life (t 1 = 2 ) of approximately 40 hours, minimal metabolism, and low total clearance (0.2-0.3 L/h/kg). 82 The maximum serum concentration after multiple doses of 50 mg every 12 hours was only 0.63 mg/ml, notably below both EUCAST and CLSI breakpoints for Enterobacteriaceae. Tigecycline penetrates well into blister fluid and abdominal tissue but low epithelial lining fluid to plasma ratios were observed in patients with pneumonia.…”

Section: Tigecyclinementioning

confidence: 99%

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

Neuner

Gallagher

2016

Virulence

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Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging healthcare crisis. Infections due to CRE are associated with high morbidity and mortality, especially in critically ill patients. Due to the multi-drug resistant nature of these infections only limited treatment options are available. Antimicrobials that have been described for the treatment of CRE infections include carbapenems, polymyxins, fosfomycin, tigecycline, aminoglycosides, and ceftazidime-avibactam. Given the limited treatment options it is imperative the pharmacokinetic and pharmacodynamics (PK-PD) characteristics of these agents are considered to optimize treatment regimens. This review will focus on the PK-PD challenges of the current treatment options for CRE infections.

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“…To determine serum concentrations of tigecycline, ceftriaxone, and ciprofloxacin in mice, each drug was subcutaneously given to healthy mice at a single dose (6.25, 100, and 25 mg of tigecycline, ceftriaxone, and ciprofloxacin/kg body weight, respectively). The dose of tigecycline was selected based on published pharmacokinetic data, which indicated that the dose of 6.25 mg/kg in mice can achieve a maximum concentration of drug in serum (C max ) of 1.17 g/ml, similar to the C max of 0.93 g/ml at a dose of 100 mg every 12 h in humans (13,18). For ceftriaxone, the dose of 100 mg/kg in mice can achieve a C max of 91 g/ml, and 0.5 g every 12 h in healthy volunteers can achieve a C max of 69 to 102 g/ml (1,21,26).…”

Section: Methodsmentioning

confidence: 99%

“…Tetracycline is usually less susceptible to Salmonella than tigecycline, even though it has good intracellular concentration (14). Tigecycline has been reported to be active in vitro against Salmonella species and has exhibited excellent intracellular concentrations in vivo (15,18,20).…”

mentioning

confidence: 99%

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

Tang¹,

Ko²,

Chen³

et al. 2011

Antimicrob Agents Chemother

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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.

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Pharmacokinetic/pharmacodynamic profile for tigecycline—a new glycylcycline antimicrobial agent

Cited by 111 publications

References 24 publications

Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from In Vitro and In Vivo Animal Studies

Use of Carbapenems against Clinical, Nontyphoid Salmonella Isolates: Results from In Vitro and In Vivo Animal Studies

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

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

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