Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Atypon full text link Atypon Free PMC article
Full text links

Actions

Share

.2011 Jun;55(6):2755-9.
doi: 10.1128/AAC.01807-10. Epub 2011 Mar 14.

In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator

Affiliations

In vitro and in vivo intracellular killing effects of tigecycline against clinical nontyphoid Salmonella isolates using ceftriaxone as a comparator

Hung-Jen Tang et al. Antimicrob Agents Chemother.2011 Jun.

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 MIC₅₀/MIC₉₀ values of tigecycline, ceftriaxone, and ciprofloxacin against 76 Salmonella isolates were 0.25/0.5, 1/8, and 0.125/0.5 μg/ml, respectively. The intracellular inhibitory activity of tigecycline at 0.5 μg/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 10⁷ CFU/ml and 10⁵ 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 × 10⁵ CFU was 80%, and that of mice exposed to ceftriaxone was 100%. When the inoculum was increased to 1.3 × 10⁶ 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.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Within peripheral blood mononuclear cells, the intracellular bacterial counts of two Salmonella isolates, S129-42 and S129-25, with an inoculum of 1 × 107 CFU/ml incubated with 0.5 μg/ml tigecycline, 1× MIC for both isolates. All experiments were performed in triplicate, and data are shown as mean values ± standard deviations.
Fig. 2.
Fig. 2.
Time-kill curves of Salmonella S129-42 isolates, with two inocula of 8 × 104 (A) and 8 × 106 (B) CFU/ml, incubated with 2 μg/ml tigecycline (TGC), 8 μg/ml ceftriaxone (CRO), or 1 μg/ml ciprofloxacin (CIP). These drug concentrations were the susceptible breakpoints recommended by the Clinical and Laboratory Standards Institute document, M100-S19. All experiments were performed in duplicate.
Fig. 3.
Fig. 3.
Intracellular (A) and extracellular (B) antibacterial activity of antibiotics in a mouse Salmonella peritonitis model. At 6 h after intraperitoneal inoculation of 1.3 × 106 CFU S129-42, tigecycline (6.25 mg/kg every 12 h), ceftriaxone (100 mg/kg every 12 h), or saline was injected subcutaneously. Intracellular and extracellular counts were evaluated over a period of 96 h. With tigecycline and ceftriaxone therapy, the intracellular and extracellular counts decreased with time. At 96 h, the levels were undetectable.
Fig. 4.
Fig. 4.
Survival rates of mice (n = 20 in each group) intraperitoneally infected with 2 × 105 CFU of ceftriaxone- and ciprofloxacin-resistant S9210131, followed by treatment with tigecycline (TGC; 6.25 mg/kg every 12 h), ceftriaxone (CRO; 100 mg/kg every 12 h), or normal saline (control) for 1 week. The 14-day survival rates were 75% in the TGC group, 30% in the CRO group, and 0% in the control group (P = 0.01, by log-rank test).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Azoulay-Dupuis E., et al. 2004. Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob. Agents Chemother. 48:1105–1111 - PMC - PubMed
    1. Biedenbach D. J., Toleman M., Walsh T. R., Jones R. N. 2006. Analysis of Salmonella spp. with resistance to extended-spectrum cephalosporins and fluoroquinolones isolated in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2004). Diagn. Microbiol. Infect. Dis. 54:13–21 - PubMed
    1. Chacon-Moreno B. E., et al. 2009. Efficacy of ciprofloxacin and moxifloxacin against Nocardia brasiliensis in vitro and in an experimental model of actinomycetoma in BALB/c mice. Antimicrob. Agents Chemother. 53:295–297 - PMC - PubMed
    1. Chang H. R., Vladoianu I. R., Pechere J. C. 1990. Effects of ampicillin, ceftriaxone, chloramphenicol, pefloxacin and trimethoprim-sulphamethoxazole on Salmonella typhi within human monocyte-derived macrophages. J. Antimicrob. Chemother. 26:689–694 - PubMed
    1. Chiu C. H., et al. 2002. The emergence in Taiwan of fluoroquinolone resistance in Salmonella enterica serotype choleraesuis. N. Engl. J. Med. 346:413–419 - PubMed

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full text links
Atypon full text link Atypon Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp