In Vivo Pharmacodynamic Profile of Tigecycline against Phenotypically Diverse Escherichia coli and Klebsiella pneumoniae Isolates

被引:34
作者
Nicasio, Anthony M. [1 ]
Crandon, Jared L. [1 ]
Nicolau, David P. [1 ,2 ]
机构
[1] Hartford Hosp, Ctr Antiinfect Res & Dev, Hartford, CT 06102 USA
[2] Hartford Hosp, Div Infect Dis, Hartford, CT 06102 USA
关键词
MULTIDRUG-RESISTANT ENTEROBACTERIACEAE; EXPOSURE-RESPONSE ANALYSES; VITRO ACTIVITY; EFFICACY; PHARMACOKINETICS; ANTIMICROBIALS; CARBAPENEMASE; SKIN;
D O I
10.1128/AAC.01678-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Tigecycline is a glycylcycline with activity against Enterobacteriaceae, including multidrug-resistant isolates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum beta-lactamase (ESBL) and carbapenemases. Herein, we used an in vivo murine thigh model to characterize the pharmacodynamic profile of tigecycline against genotypically and phenotypically diverse K. pneumoniae and E. coli isolates. Doses of 3.125 to 300 mg/kg, divided 1 to 6 times daily, were administered subcutaneously against six (two nonresistant, one carbapenemase, and three ESBL producing) K. pneumoniae strains and five (two nonresistant and three ESBL producing) E. coli strains. The phenotypic profile (reported tigecycline MIC) for all isolates ranged from 0.125 to 2 mu g/ml. Mean correlation coefficients of free (f) drug exposures (percentage of the dosing interval that free drug concentration remained above the MIC [fT > MIC], the ratio of the free drug area under the concentration-time curve/MIC [fAUC/MIC], and the ratio of maximum concentration of free drug in serum/MIC) for all 11 isolates were 0.595, 0.969, and 0.897, respectively. The fAUC/MIC was the pharmacodynamic parameter that best described the efficacy of tigecycline against both E. coli and K. pneumoniae. Interestingly, reductions in the number of CFU were noted even though doses achieved an fT > MIC of 0%. With respect to fAUC/MIC in the neutropenic model, the cumulative 80% and 50% effective pharmacodynamic indexes (EI80 and EI50) for all 11 isolates were 8.4 and 4.7, respectively. An experiment in nonneutropenic mice infected with an ESBL-producing E. coli and K. pneumoniae isolate resulted in the lowest tigecycline fAUC/MIC EI80 and EI50 values at 1.8 and 1.0 for E. coli and 1.7 and 1.6 for K. pneumoniae. While the phenotypic profile of tigecycline appeared to drive efficacy irrespective of ESBL or carbapenemase production, the presence of a competent immune system markedly reduced this required exposure.
引用
收藏
页码:2756 / 2761
页数:6
相关论文
共 24 条
[1]  
[Anonymous], 2007, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, V6th
[2]   Tigecycline MIC testing by broth dilution requires use of fresh medium or addition of the biocatalytic oxygen-reducing reagent Oxyrase to standardize the test method [J].
Bradford, PA ;
Petersen, PJ ;
Young, M ;
Jones, CH ;
Tischler, M ;
O'Connell, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (09) :3903-3909
[3]   Effect of porin loss on the activity of tigecycline against Klebsiella pneumoniae producing extended-spectrum β-lactamases or plasmid-mediated AmpC-type β-lactamases [J].
Carmen Conejo, M. ;
Ramon Hernandez, J. ;
Pascual, Alvaro .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2008, 61 (03) :343-345
[4]   Antimicrobial activities of tigecycline and other broad-spectrum antimicrobials tested against serine carbapenemase- and metallo-β-lactamase-producing enterobactefiaceae:: Report from the SENTRY antimicrobial surveillance program [J].
Castanheira, Mariana ;
Sader, Helio S. ;
Deshpande, Lalitagauri M. ;
Fritsche, Thomas R. ;
Jones, Ronald N. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (02) :570-573
[5]   Pharmacodynamics of Tigecycline against Phenotypically Diverse Staphylococcus aureus Isolates in a Murine Thigh Model [J].
Crandon, Jared L. ;
Banevicius, Mary Anne ;
Nicolau, David P. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (03) :1165-1169
[6]   Indications of a new antibiotic in clinical practice:: Results of the Tigecycline Initial Use Registry [J].
Curcio, Daniel ;
Fernandez, Francisco ;
Cane, Alejandro ;
Barcelona, Laura ;
Stamboulian, Daniel .
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES, 2008, 12 (03) :198-201
[7]   Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline antimicrobial [J].
DiPersio, Joseph R. ;
Dowzicky, Michael J. .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2007, 29 (05) :518-527
[8]   Tigecycline activity tested against collected from 11,808 bacterial pathogens recently US medical centers [J].
Gales, Ana C. ;
Sader, Hello S. ;
Fritsche, Thomas R. .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2008, 60 (04) :421-427
[9]   Activity of tigecycline against ESBL-producing and AmpC-hyperproducing Enterobacteriaceae from South-East England [J].
Hope, R. ;
Warner, M. ;
Potz, N. A. C. ;
Fagan, E. J. ;
James, D. ;
Livermore, D. M. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 58 (06) :1312-1314
[10]   Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies [J].
Kelesidis, Theodoros ;
Karageorgopoulos, Drosos E. ;
Kelesidis, Iosif ;
Falagas, Matthew E. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2008, 62 (05) :895-904