Stopping the Hospital Spread of Gram-Negative Bacilli

John G. Bartlett, MD; Alexander J. Kallen, MD, MPH


November 15, 2011

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An Epidemiologist's Perspective

John G. Bartlett, MD: Hi. I am John Bartlett from Johns Hopkins University School of Medicine and I am here at the annual Infectious Diseases Society of America (IDSA) meeting for 2011. We are in Boston and I am joined by Dr. Alex Kallen from the Centers for Disease Control and Prevention (CDC). Dr. Kallen works in the hospital infection control section of the CDC. Obviously, his work is very important in terms of what we are discussing today with respect to resistant gram-negative bacilli and the infections they cause. Thank you for joining me here today, Alex.

I have a number of questions for you. Some of this has been presented at the meeting, and we need to get updated information. Let me ask you this question. Every doctor in the United States who works in a hospital, and many who work in outpatient settings, are encountering more and more resistance among gram-negative bacilli, as well as Staphylococcus aureus.

Let's talk about gram-negative bacilli. Why is there a great surge of this problem in the United States, Europe, and around much of the world that we have not really encountered since penicillin was discovered? We have always had something with which to treat these pathogens. Now we don't have much. Why?

A Surge of Highly Resistant Enterobacteriaceae

Alexander J. Kallen, MD, MPH: That's a great question, John. The main issue today, in the United States at least, is the emergence of very highly resistant Enterobacteriaceae -- such as Escherichia coli and Klebsiella -- that are resistant to our last-stage antibiotics, the carbapenems. These carbapenem-resistant Enterobacteriaceae were very uncommon in the United States before about 2000.

Since that time we have seen the emergence of a specific enzyme of carbapenamases called Klebsiella pneumoniae carbapenemase (KPC) that has spread widely throughout the United States. This enzyme basically renders all beta-lactams, penicillins, and cephalosporins ineffective but also is associated with other mutations that render it resistant to many other antibiotics as well. This has driven an epidemic of highly resistant gram-negative organisms throughout much of the United States.

Dr. Bartlett: Some have said prophetically that we may be witnessing the end of the beta-lactam class of antibiotics. That is really scary to a lot of us. It might be a bit histrionic but, nevertheless, what you are saying is really scary. What's driving that?

Dr. Kallen: There are a number of reasons. One that comes to the forefront is the fact that the resistance (KPC as well as some other carbapenemases such as the New Delhi metallo-beta-lactamase) is contained on plasmids, which are very highly mobile and are very easily spread from one bacteria to the next.

The second reason is something that has been going on for a long time. This is the movement of patients from acute care (where we have very active infection control practices) to long-term care -- frequently very early in their stays. This has led to a situation where we see transmission of these organisms to settings such as long-term care and long-term acute care, where infection control practices potentially aren't as strict. These patients are highly mobile and actually go back and forth between the hospital and long-term care frequently and present the opportunity for transmission of these organisms between patients.

New Bugs, Old Drugs

Dr. Bartlett: Let me ask you this question. Pretend I am a primary care physician and I am taking care of a patient who has been transferred from a long-term care facility to my hospital. I discover that the patient has a Klebsiella urinary tract infection that is resistant to the entire class of carbapenems. What is the rest of the sensitivity profile likely to be on that organism?

Dr. Kallen: These are generally very highly resistant, especially the KPC-producing species. Frequently they will be susceptible to the polymyxin antibiotics, which are now coming back into favor. These drugs, such as colistin and polymyxin, haven't been used for quite some time. The other antibiotic to which it might be susceptible is tigecycline, which is a newer antibiotic. Of course, sometimes aminoglycosides will be effective as well depending on the organism and the setting.

Dr. Bartlett: You would be guided by the sensitivity profile, and you may be forced to use drugs that many doctors have never actually used. Colistin is a drug that was approved by the US Food and Drug Administration around 1965. It dropped out of practice because it was neurotoxic and nephrotoxic. We don't have very much information about it and yet now, we are more and more likely to use it. When I last looked at [Johns] Hopkins hospital data, we had given it to more than 100 patients in the last year. That is becoming sort of a staple now for these resistant pathogens. How do we prevent these infections?

Dr. Kallen: That is a huge issue. The timeline for new antibiotics to treat these resistant organisms is a long one, in the range of 5-10 years before we have effective antibiotics. It's critical to try to prevent the transmission of these organisms. The lesson that we have learned at CDC is that people really need to recognize this as an important pathogen.

Time and again we are asked to conduct investigations in settings where the opportunity to intervene early on was missed due to a lack of recognition. Once these infections are recognized, the institution of contact precautions and hand hygiene are critically important, along with precautions such as minimizing device use. These organisms are very difficult to treat in the urinary tract when a catheter is present. Antibiotic stewardship must be practiced to prevent additional resistance down the road.

Lessons From Israel

Some recent and interesting data from Israel[1] suggest that cohorting patients, and particularly staff to take care of them, may be of some use as well.

Dr. Bartlett: I was really interested in that report from Israel. Could you elaborate on that a little bit? As I understand it, there was an outbreak of KPC-producing bacteria in multiple hospitals. They took all of the patients and put them in a facility managed by a consistent healthcare provider and had enormous success. That would not be easily done in this country.

Dr. Kallen: Right. They undertook a very aggressive national effort to control carbapenem-resistant Enterobacteriaceae. The first part of the study has been published[1] (which involved aggressively identifying and reporting these cases and putting them in contact precautions, and cohorting patients and staff) and they saw dramatic reductions in their cases. Their efforts continue and we anxiously await more information on their efforts and results.

Dr. Bartlett: It seemed to be, more or less, a sort of "poster child" for what you do. In other words, the curve went way up, hit a peak, and then it came right down as soon as they implemented cohorting and tight, tight infection control by people who were well trained in it.

Dr. Kallen: We have also seen that in investigations that we have done. When you cohort the patients and the staff, you reduce the likelihood of transmitting the organism because we know that people aren't 100% compliant with contact precautions and hand hygiene. You reduce the risk of transmitting infection to the patients who aren't colonized or infected.

Monitor Those Transferred Patients

Dr. Bartlett: For those who are taking care of patients who are transferred from other institutions, when should they specifically worry about this? You said time is important.

Dr. Kallen: The spread of these organisms seems to be relatively heterogeneous across the United States. It is common in some places and less common in others. It is important that people look back and recognize how often they have seen these organisms over the last 6-12 months. If they haven't identified these cases, then when they are admitted, clinicians and staff should be very aggressive about contact precautions and even consider surveillance cultures of epidemiologic link contacts, as you would for the outbreak of any multidrug-resistant organism (MDRO).

Dr. Bartlett: The epidemiologic pattern of your institution or the referring institution may be critical in knowing when to jump on it early.

Dr. Kallen: That is a great point. MDROs are rarely a single-institution problem and understanding the regional pattern of these organisms is critically important.

Dr. Bartlett: The other thing that probably needs to be emphasized is any foreign body that is infected needs to come out. You mentioned urinary catheters, but it also applies to central lines and a whole range of devices because we are prone to putting a lot of metal and plastic into these patients. By and large, those infections become incredibly refractory; in fact, they are almost impossible to eradicate unless you get rid of the foreign bodies. You can pour all the antibiotics you want into the patient and still have the problem.

Get the Right Cultures

If you have an epidemic in your intensive care unit or hospital ward with a lot of KPC-producing organisms, for example, I know you call infection control, but what are the key facets of that infection control program?

Dr. Kallen: In an outbreak setting, the focus is mainly identifying cases and limiting transmission. Identifying cases can be accomplished through screening of contacts, usually with rectal, perirectal, or stool cultures. Once those people are identified, try to contain them through contact precautions and cohorting staff and patients. Hand hygiene and device minimization are also important parts of the approach. It is very important to follow up to make sure that the first round of interventions is successful.

Dr. Bartlett: You mentioned something interesting. Most clinicians are aware of hand hygiene and contact precautions and so forth. They are not necessarily good at it, but nevertheless they are aware of it. What you said that may not be quite so obvious is the rectal culture. When should you do rectal cultures and what specifically should you ask the lab to tell you?

Dr. Kallen: Enterobacteriaceae are common in stool cultures. For surveillance, we usually recommend stool, potentially wound, and maybe even cultures of sites that have a device. When these are sent down to the laboratory -- a protocol is available at the CDC Website -- the lab should look specifically for carbapenem-resistant strains of these Enterobacteriaceae, which will be common on most rectal cultures of patients in the hospital.

Dr. Bartlett: Alex, I want to thank you very much for sharing your experience with us, and I want to thank the audience for their attention to this great problem.


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