肠杆菌科的beta-内酰胺类抗生素耐药

Common -Lactamases in GNRs
NEJM 352:4. 2005
How are -lactamases transferred?
Transfer of Plasmids.
Extrachromosomal DNA Usually carry antibiotic resistance genes These genes can be encoded on transposons, which are also mobile.
Cefotaxime Ceftriaxone Ceftazidime
Fourth generation cephalosporins
Cefepime
Monobactams
Aztreonam
-lactam antibiotics
Carbapenems
Imipenem Meropenem Ertapenem Doripenem
TEM-1 has been transferred between the Enterobacteriaceae and H. influenzae and the Neisseriaceae
-lactam antibiotics
Penicillins
Ampicillin Piperacillin
Piperacillin R
Cephalothin R
Cefoxitin
S
Cefepime Pip/Tazo Imipenem
SR I S
Cefotaxime R
Ceftazidime IR
Ceftriaxone R
Aztreonam IR
Enterobacter cloacae susceptibility report
Beta-lactam/beta-lactamase inhibitors
Ampicillin/sulbactam Amoxicillin/clavulanate Ticarcillin/clavulanate Piperacillin/Tazobactam
-lactam antibiotics
First Generation cephalosporins
S
Laboratory detection of ESBLs
Resistance or intermediate to third-generation cephalosporins. Cefoxitin and cefotetan susceptible. ESBL disk diffusion test (clavulanate inhibition)
E-test ESBL strip Confirmatory ESBL MIC test (Microscan)
K. pneumoniae, K. oxytoca, E. coli, P. mirabilis
E. coli ESBL susceptibility
report
Ampicillin R
肠杆菌科的beta-内酰胺类抗生 素耐药
Mechanisms of GNR Resistance to lactams
Porin-mediated resistance
Antibiotic does not reach target.
-lactamase
Majority of resistance to -lactam antibiotics mediated through -lactamases. Many different types of -lactamases with different substrate (antibiotic) specificities.
Ampicillin R
Piperacillin R
Cephalothin R
Cefoxitin
R
Cefotaxime R
Ceftazidime I
Ceftriaxone R
Aztreonam I
Cefepime
S
Pip/Tazo
R
Imipenem
S
AmpC -lactamases
Chromosomally encoded-cell wall turnover Enterobacter sp., Citrobacter sp., Serratia sp., Morganella sp. Even E. coli. Third-generation cephalosporins are not good inducers of AmpC -lactamase Third-generation cephalosporin resistant strains are derepressed—meaning that the AmpC lactamase is not inducible anymore. AmpC mutants are cephamycin resistant
E. coli susceptibility Report
Ampicillin R
Piperacillin R
Cephalothin R
Cefoxitin
S
Cefotaxime R
Ceftazidime I
Ceftriaxone R
Aztreonam I
Cefepime
S
Pip/Tazo
I
Imipenem
ESBLs
Enzymes capable of hydrolyzing third-generation cephalosporins. Plasmid-mediated Derivatives (mutants) of original TEM-1 and SHV-1 lactamases. Susceptible in-vitro to clavulanate and cefoxitin.
Cefazolin Cephalothin
Second Generation oral antibiotics
Cefuroxime Βιβλιοθήκη Baidumany others)
Second Generation cephamycins
Cefoxitin Cefotetan
-lactam antibiotics
Third generation cephalosporins