The emergence and spread of resistance in Enterobacteriaceae are complicating the treatment of serious
nosocomial infections and threatening to create species resistant to all currently available agents. Approximately 20% of Klebsiella pneumoniae
infections and 31% of Enterobacter spp
infections in intensive care units in the United States now involve strains not susceptible to
third-generation cephalosporins. Such resistance in K pneumoniae to
third-generation cephalosporins is typically caused by the acquisition of plasmids containing genes that encode for extended-spectrum
beta-lactamases (ESBLs), and these plasmids often carry other resistance genes as well. ESBL-producing K pneumoniae and Escherichia coli are now relatively common in healthcare settings and often exhibit multidrug resistance. ESBL-producing Enterobacteriaceae have now emerged in the community as well. Salmonella and other Enterobacteriaceae that cause
gastroenteritis may also be ESBL producers, which is of relevance when children require treatment for invasive
infections. Resistance of Enterobacter spp to
third-generation cephalosporins is most typically caused by overproduction of
AmpC beta-lactamases, and treatment with
third-generation cephalosporins may select for AmpC-overproducing mutants. Some Enterobacter cloacae strains are now ESBL and AmpC producers, conferring resistance to both third- and fourth-generation
cephalosporins.
Quinolone resistance in Enterobacteriaceae is usually the result of chromosomal mutations leading to alterations in target
enzymes or
drug accumulation. More recently, however, plasmid-mediated
quinolone resistance has been reported in K pneumoniae and E coli, associated with acquisition of the qnr gene. The vast majority of Enterobacteriaceae, including ESBL producers, remain susceptible to
carbapenems, and these agents are considered preferred empiric
therapy for serious
Enterobacteriaceae infections.
Carbapenem resistance, although rare, appears to be increasing. Particularly troublesome is the emergence of KPC-type carbapenemases in New York City. Better antibiotic stewardship and infection control are needed to prevent further spread of ESBLs and other forms of resistance in Enterobacteriaceae throughout the world.