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Deadly Klebsiella Pneumoniae Strain Resistant to Carbapenems

Shaw, Gina

doi: 10.1097/01.EEM.0000428246.09846.60
    Klebsiella pneumoniae
    Klebsiella pneumoniae:
    antimicrobial drug resistance, United States, 1998-2010. ATM, aztreonam; SXT, trimethoprim/sulfamethoxazole; CAZ, ceftazidime; CIP, ciprofloxacin; TET, tetracycline; TOB, tobramycin; TZP, piperacillin/tazobactam; CPM, cefepime; AMK, amikacin; IPM, imipenem. Ceftriaxone and gentamicin not included for better data presentation.

    Forget MRSA. There's a deadly new bug in town.

    A lethal form of Klebsiella pneumoniae is now resistant even to carbapenems, an antibiotic class that has been the treatment of last resort, and it is now spreading across the country. Worse, it makes treating MRSA look like a day at the beach, say leading infectious disease specialists.

    “This bug is worse than MRSA,” said James R. Roberts, MD, the chair of emergency medicine and the director of toxicology at Mercy Catholic Medical Center and a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. “At least with MRSA, there are many antimicrobial options. But we don't have an effective treatment for multidrug-resistant Klebsiella.” Dr. Roberts first sounded the alarm about superbugs in an EMN article last year on extended-spectrum beta-lactamase-producing bacteria such as Klebsiella, which was followed by a special report on the hypervirulent Klebsiella. (See FastLinks.)

    Carbapenem-resistant Klebsiella pneumonia, or CRKP, first emerged in New York in the mid-2000s, but two new articles in leading infectious disease publications indicate that it is extending its reach across the country. The percentage of Klebsiella isolates that were resistant to imipenem increased from less than one percent to 4.3 percent between 2000 and 2010, according to researchers from the George Washington University and Providence Hospital in Washington, D.C., writing in the January edition of Emerging Infectious Diseases. (See FastLinks.)

    That disturbing trend closely mirrors data reported by scientists with the DC-based Center for Disease Dynamics, Economics & Policy in the March edition of Infection Control and Hospital Epidemiology. (Infect Control Hosp Epidemiol 2013;34[3]:259.) That group found CRKP throughout the country, though it is most prevalent in the Northeast, and that it is even making inroads into the outpatient setting.

    The deadly impact of CRKP left its mark at no less august an institution than the NIH Clinical Center in the summer of 2011 when it hitched a ride with a woman who had been transferred there from a New York hospital. She was only colonized with the resistant form of the bacteria, not actually infected with Klebsiella pneumoniae, and staff at the center implemented isolation protocols when that was discovered.

    Despite this and truly extraordinary detective work and infection control interventions by deputy hospital epidemiologist Tara Palmore, MD, and her staff at the clinical center (they ripped out the plumbing when the bacteria were found in a sink), the six-month outbreak ultimately led to 18 cases and 11 deaths at the NIH Clinical Center itself.

    Carbapenem-resistant Klebsiella poses a number of challenges for emergency physicians, not the least of which is its devastating mortality rate that ranges from 35 percent to 50 percent, depending on the study. It is also difficult to screen for the bug, unlike MRSA which only requires a simple nasal swab that yields results within hours. “There's no equivalent to that for CRKP: nothing cheap, nothing effective, nothing that's useful on a large scale,” said Guillermo Sanchez, a graduate student in the Physician Assistant program at the George Washington University and an author of the EID paper.

    As if that weren't enough, the available drugs for treating CRKP are sometimes worse than the disease itself. Because of its resistance to the carbapenems, infectious disease specialists are left with only a few bad options to try to treat it. “More often than not, the drugs we do go to are an aminoglycoside like amikacin, or colistin, a polymyxin that was used in the 1960s and is so nephrotoxic that it is rarely used anymore,” said Mr. Sanchez. “The nephrotoxicity of our only go-to drugs may contribute to the high mortality rate of this infection.” To make matters worse, reports of polymyxin-resistant strains of Klebsiella have emerged.

    “This is a huge public health concern,” says Grace Lee, PharmD, of the Pharmacotherapy Education & Research Center at the University of Texas Health Science Center at San Antonio, who published a review of case reports and case series on treating Klebsiella pneumoniae carbapenemase infections (not necessarily CRKP) in Annals of Clinical Microbiology and Antimicrobials in December. (2012;11:32; see FastLinks.)

    Emergency physicians should work with their hospital's microbiology lab and infection control team to identify whether carbapenem-resistant strains of Enterobacteriaceae have appeared in their institution. “Oftentimes in larger academic facilities, this has already happened, but I'm finding that many local community hospitals haven't done this yet,” Dr. Lee said. “Look back into your microbiological data to see if it has happened in your hospital.”

    Also be aware of the risk factors for CRKP, which mirror those for other multidrug-resistant organisms: recent exposure to a health care setting, admission from a long-term care facility, immunocompromised status, recent catheterization or mechanical ventilation, dialysis, ICU stay, and previous antibiotic use.

    It's important to differentiate between infection and colonization if a culture is positive for carbapenem-resistant Klebsiella. “When a culture comes up positive, it may be a clinician's inclination to treat,” Dr. Lee acknowledged. “But if you have someone who is colonized with CRKP but who is showing no signs and symptoms of infection, treating it might make it a worst-case scenario for when that patient does develop an infection. Now you've potentially made it more resistant and exposed the patient to unnecessary antibiotics and their associated toxicities.”

    If a patient has an infection from KPC-producing bacteria, Dr. Lee's research showed that monotherapy failed twice as often as combination therapy. “If you're treating patients who come to the ED with Klebsiella and you don't yet know its resistance, the most consistent finding is that combination therapy is associated with much better treatment outcomes. Which combination is better is still unclear.”

    The best course of action may be a very old-fashioned one once a carbapenem-resistant Klebsiella has been identified. “We recommend that the tetracyclines, in particular doxycycline, should be considered in the treatment of a mild CRKP infection like a UTI,” said Jose Bordon, MD, PhD, an infectious disease specialist at Providence Hospital and the principal investigator on the EID paper. “Our finding is that this very, very old antibiotic remains active against this infection.”

    Dr. Bordon recommended treatment with oral formulation doxycycline by mouth if the patient is stable and can be characterized as having a mild to moderate infection. “This is particularly convenient in the emergency room as well,” he noted.

    He made a more controversial recommendation for patients with more severe infections: tigecycline, or Tygacil, which received a label change in September 2010 from the FDA that warned of increased mortality risk. Dr. Bordon acknowledged that no clinical trial data support this approach. “But when you have very sick patients dying in front of you, if you wait for a clinical trial, it will be too late for them,” he said.

    That may sound just a bit too House M.D. for many people, but Dr. Roberts said it's difficult to overstate the impact of CRKP. “This is very similar to the early days of AIDS when an infection was a death sentence. Hopefully people smarter than I am will figure out what to do with it,” he said.

    Click and Connect!Access the links in EMN by reading this issue on our website or in our iPad app, both available


    • Read the Emerging Infectious Diseases article, “Klebsiella pneumoniae Antimicrobial Drug Resistance, United States, 1998-2010,” at
    • Dr. Roberts' article, “Extended Spectrum Beta-Lactamases: Far Worse than MRSA?” is available at
    • Read the EMN Special Report, “The Black-Box Bug,” at
    • Dr. Lee's article, “Treatment of Klebsiella Pneumoniae Carbapenemase (KPC) Infections: A Review of Published Case Series and Case Reports,” is available at
    • Review the CDC's Guidance for Control of Carbapenem-Resistant Enterobacteriaceae at
    • Comments about this article? Write to EMN at [email protected].
    © 2013 Lippincott Williams & Wilkins, Inc.