Gram-negative bugs rising in resistance

MRSA gets headlines as KPC emerges

While methicillin-resistant Staphylococcus aureus (MRSA) has grabbed recent national media attention and alarmed the public, there is a quiet but troubling trend of emerging resistance in lesser-known gram-negative bacteria, a medical epidemiologist at the Centers for Disease Control and Prevention recently warned.

"MRSA is an important pathogen, but it's not the only pathogen causing health care-associated infections," said Arjun Srinivasan, MD, of the CDC's division of health care quality promotion. "The other pathogens are not to the scale that MRSA is, but certainly present challenges to us in health care. . . . There is the potential for shifting epidemiology of health care-associated infections."

Resistance is emerging in Klebsiella pneumoniae to carbapenems, a class of broad-spectrum beta-lactam antibiotics, he said recently in Atlanta at a meeting of the Association for Professionals in Infection Control and Epidemiology. Once so rare it was thought to be a reporting error when discovered, now 8% of all isolates of K. pneumoniae are resistant to carbapenems. Moreover, the antibiotic resistance appears to be emerging through a distinct mechanism that can be transferred to other bacteria. "This clearly is not a reporting [artifact]," Srinivasan said. "I think this is the emergence of a new phenotype of resistance that we are dealing with described as K. pneumoniae carbapenemase [KPC] resistance."

KPC found in many bugs

In addition to the carbapenems, the KPC enzyme confers resistance to all beta-lactams including penicillin as well as the extended-spectrum cephalosporins, he said. While primarily found in K. pneumoniae, the KPC enzyme has been reported in K. oxytoca, Citrobacter freundii, Escherichia coli, and species varieties of Enterobacter, Salmonella, and Serratia. It also has been reported in Pseudomonas aeruginosa in the country of Columbia.

Sporadic cases of KPC-producing organisms have been reported throughout the United States, but have primarily hit New Jersey and New York City. "This is an organism that they are struggling with significantly," he said. "It is an endemic problem there, but we have also had sporadic reports from states all over the country. Why is this a significant problem? Well, I think these KPC-producing organisms might present the next challenge that we are going to face in health care for a number of reasons. First of all, they occur in enterobacteriaceae, [which] are very common organisms."

Moreover, emerging KPC resistance could pose problems in the community as well by heightening drug resistance in pathogens such as E. coli that already pack plenty of virulence. "KPCs are appearing in more places, which I think is a cause for concern. When you look at the resistance profiles, these are really resistant organisms," Srinivasan said, emphasizing the point by showing a slide of a KPC-producing K. pneumoniae strain that was resistant to more than 20 drugs. "These are highly resistant and very difficult to treat," he said. "If you talk to experts in antimicrobial development they will tell you that there are not a lot of drugs on the horizon that are going to be effective against these highly resistant gram negatives."

That is not welcome news since the KPC enzyme is plasmid-based and can be transferred from one bacterial species to another. "The other problem with these plasmids is that many times they carry other resistance genes," Srinivasan explained. "[That] means if an organism receives this plasmid, it can have resistance to not only all the betalactams and carbapenems, but may also get resistance to other antimicrobials out of this single genetic event."

Proceeded by long LOS

Reviewing some limited clinical data, Srinivasan said the infections are generally appearing in patients after prolonged hospitalization in the range of 25 days. Though the data are limited, mortality figures were in the 25% to 38% range. "These are serious infections," he said. KPC-producing organisms may appear after patient treatment with carbapenems, a typical pattern of selective pressure creating resistance. However, in one data set, only about a quarter of the infected patients had prior antibiotic exposure to carbapenems, he noted. "It suggests there are other factors at play," he said. "One of the factors we think that is very strongly at play here is health care-associated transmission of the organisms."

That means infection control professionals — as has always been the case — will have something to worry about other than MRSA, which is increasingly the subject of legislation and media attention that is putting resource demands on ICPs scrambling to respond. Hospital Infection Control asked Srinivasan whether the intense focus on MRSA could allow these KPC-producers and other gram-negative pathogens an opportunity to proliferate. "The onus is on us to do exactly what you're suggesting and say MRSA is very important, but there are other pathogens that you need to control as well," he answered. "The onus is now on us — while we have all this attention — to educate them that [MRSA] is one of a number of problems."