Abstracts
Molecular Epidemiology of Carbapenem Resistant Enterobacteriaceae
Barry N. Kreiswirth, PhD, Public Health Research Institute, UMDNJ–NJMS
In 1969, Surgeon General William H. Stewart declared an end to the era of infectious diseases, as antibiotic pipelines were overflowing and the threat of drug resistant strains limited. What Stewart could not predict was the large increase in immunosuppressed patients, both the result of HIV disease and active suppression for transplantation surgery and other heroic medical efforts. As such, advancements in medicine enabled patients with otherwise life threatening diseases to live longer, commonly with the aid of anti-infectives. After 70 years of unabated use, the effectiveness of our most potent antimicrobials are being compromised evidenced in the remarkable and rapid evolution of drug resistance mechanisms, many on mobile genetic elements that are able to spread within and between species. The recent emergence of community acquired methicillin resistant S. aureus (MRSA), extensively drug resistant (XDR)
M. tuberculosis and carbapenem-resistant
Enterobacteriaceae are highly drug resistant strains that have limited treatment options. Compounding this problem is the hollow antibiotic pipeline, the absence of antibiotic discovery programs in most pharmaceutical companies, and the limited success in developing novel compounds. Advancements in diagnostics, including real-time nucleic amplification platforms at the bedside, can enhance prudent use of antibiotics however has yet to be integrated in our healthcare setting. The gravity of antibiotic resistance has consequently led to alternative strategies, including phage therapy, antibody treatment, inhibitory peptides, and immunomodulators; but similar to our dependence on oil, we remain hooked on antibiotics, even though they too may go the route of the dinosaur.
MDR Pa, Ab, and Kp: The Big Three
Robert Bonomo, MD, Case Western Reserve University
Multidrug resistant (MDR) Gram negative bacteria are a major threat to patients in the community and in the hospital. Among pathogens that exhibit resistance to all antibiotics,
Pseudomonas aeruginosa,
Acinetobacter baumannii, and
Klebsiella pneumoniae are among the most notorious. Each of these MDR bacteria ("the big three") exhibit different mechanisms of resistance. A. baumannii has managed to collect a variety of genes from different origins and has assembled them in genetic constructs that defy comprehension. Interestingly, the virulence of
A. baumannii has also seemed to increase in parallel with resistance phenotypes. This combination of "malicious" traits has made
A. baumannii one of the most feared Gram negative bacteria on the planet.
P. aeruginosa has also acquired a large variety of resistance genes that defy all antibiotics, but has assembled them in a different manner. For unknown reasons, we have become complacent with MDR
P. aeruginosa. Lastly,
K. pneumoniae, a pathogen that was among the minority of hospital acquired infections, has become a formidable hazard by its acquisition of resistance to all cephalosporins and carbapenems. This "perfect storm" has left us with few if any treatment options.
Clinical Manifestations and Consequences of Carbapenem-Resistant Enterobacteriaceae: Therapeutic Implications of Emerging Multidrug Resistant Pathogens
Thomas J. Walsh, MD, NY Presbyterian Hospital/Weill Cornell
Since the original descriptions of pneumonia caused Klebsiella pneumoniae in the nineteenth century, this organism has been recognized as a pathogen causing devastating infections that become increasingly lethal in more immunocompromised patients. With relentless emergence of resistance to the most potent of agents of the antimicrobial armamentarium, carbapenemase-producing
K. pneumoniae (KPC) now have extended their host range into our profoundly immunocompromised patients. This expansion of host population also has been accompanied by the emergence of other members of the Enterobacteriaciae, including
Escherichia coli and
Enterboacter spp. Such patients present with critical illness, few therapeutic options, and consequently highly lethal infections.
Recent work in our Program by Dr. Michael Satlin in collaboration with Dr. Barry Kreiswirth of the Public Health Research Institute, International Center for Public Health, University of Medicine and Dentistry of New Jersey, Newark, NJ describes for the first time in the United States the emergence of carbapenem-resistant Enterobacteriaciae (CRE) as lethal causes of bloodstream infections (BSIs) in patients with hematologic malignancies [1]. CRE BSIs occurred in patients with newly diagnosed malignancies as well as in those with refractory or relapsed malignancies. Patients most frequently were exposed to numerous healthcare settings and received prior antibacterial therapy before developing CRE BSI. However, there were no consistent clinical manifestations among cases to indicate a CRE BSI. Although all patients received an antimicrobial regimen recommended for management of fever in immunocompromised hosts with cancer, these patients seldom received initial empirical therapy that was active
in vitro against their bloodstream isolates, leading to significant delays in effective treatment. Mortality rates were high and all deaths were related to CRE BSI. The consequences of these infections are a clarion call for rapid diagnostic assays and new antimicrobial agents to provide life-saving interventions for our critically ill patients.
Reference
[1] Satlin MJ, Calfee DP, Fauntleroy KA, Jenkins SG, Kreiswirth BN, Walsh TJ: Carbapenem-resistant Enterobacteriaceae bloodstream infections in patients with hematologic malignancies. 49th Annual Meeting of the Infectious Diseases Society of America. 2011