Daniel M. Keller, PhD

September 26, 2011

September 26, 2011 (Chicago, Illinois) — In patients in the community with urinary tract infections caused by Klebsiella pneumoniae, increasing resistance to multiple antibiotics presents a challenge to clinicians choosing empiric therapy.

Many of the organisms harbor carbapenemase (KPC) or CTX-M β-lactamase (CTX) enzymes, which confer resistance to various classes of antibiotics. A substantial proportion of isolates produce both enzymes or have other resistance mechanisms, Joanna Kopacz, MD, attending physician at New York Hospital Queens in Flushing, reported in a poster session here at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy.

Gram-negative organisms containing extended-spectrum β-lactamases (ESBLs) were initially associated with long-term care facilities and hospital settings, but they are on the rise in the community, and few oral antibiotics are still effective against them. Among the infections that primary care physicians diagnose, urinary tract infections rank second only to upper respiratory infections.

The investigators selected 47 K pneumoniae isolates reported as producing ESBLs between January and December 2009. Patients had not received any antibiotics, nor had they been hospitalized in the 30 days before the specimens were obtained. KPC and CTX were identified with polymerase chain reactions, and the minimum inhibitory concentrations of 12 antibiotics were determined.

The researchers found a wide distribution of resistance mechanisms. "Twenty-one percent had KPC enzymes, almost 30% had a CTX, close to 28% had both of the enzymes.... [Only] about 20% didn't harbor any of the enzymes," Dr. Kopacz told Medscape Medical News. "That means there's probably some other method of resistance."

"It is challenging because 90% of all the isolates showed resistance to the standard [oral] antibiotics that are used — trimethoprim/sulfa[methoxazole] and levofloxacin. The other point that's interesting is that [for] all the patients labeled as ESBL producers, the standard drug to use would be a carbapenem, and 50% of those patients showed resistance to carbapenem. So even though the lab might report the bacteria as an ESBL, the drug that you would normally choose might not be as effective as you would like it to be," Dr. Kopacz explained.

Most of the isolates were sensitive to other antibiotics (90% to polymyxin B, 87% to tigecycline, and 79 % to fosfomycin). Of the 47 patients, 10 received no antibiotics, 10 received a quinolone, 3 received aminoglycosides, and 1 received trimethoprim/sulfamethoxazole as single active agents. The rest received combination regimens.

The investigators reported that most of the patients had favorable outcomes. Dr. Kopacz noted that many times the outcomes were good, even if patients were treated with antibiotics to which the organism had been shown to be resistant.

Dr. Kopacz and colleagues concluded that the treatment of community urinary tract infections caused by K pneumoniae is a challenge. "There's no optimal guide to treat. Probably, if you're not sure which enzymes the patients are harboring, a combination therapy with different antibiotics might be the best to begin with," she advised. "Once you have all the susceptibilities, then you'll be able to tailor the treatment better."

She said that standard methods of susceptibility testing might not be as helpful as one would hope, so molecular testing of isolates will be needed to better understand the resistance mechanisms. Unfortunately, these methods are not routinely used in clinical microbiology laboratories. Unless patients are treated appropriately and the organisms are eradicated, asymptomatic carriers in the community will remain at risk for invasive disease and can serve as reservoirs for spreading resistant organisms.

David Hooper, MD, chief of the infection control unit and associate chief of the infectious disease division at Massachusetts General Hospital in Boston, and president of the American Society of Microbiology, told Medscape Medical News that multiple resistance mechanisms are troubling, and detection methods are a challenge. "I think 'vigilance' is the word of the day, for many days, in order to keep track of these," he said.

Many clinical laboratories do not have tests to distinguish between types of carbapenemases or resistance mechanisms. "But they all have mechanisms in place.... If there's carbapenem resistance as a property or phenotype of the organism, they can detect that and then act on that," Dr. Hooper said, adding that it is important to know the cause of resistance for epidemiologic investigations.

"The organisms have spread outside the initial areas where they were first causing problems, in New York City [and] New Jersey, so everyone is concerned about their spreading to their hospital or their environment," he noted.

The study received no commercial funding. Dr. Kopacz and Dr. Hooper have disclosed no relevant financial relationships.

51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract  C2-654. Presented September 18, 2011.

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