Five Things I Learned at IDWeek This Year

John G. Bartlett, MD

Disclosures

November 24, 2015

Ebola Survivor: Dr Ian Crozier

The highlight of IDWeek 2015 was the talk given by Dr Ian Crozier (Figure 1).[1]

Figure 1. Dr Ian Crozier
(Source: Susan Urmy/Vanderbilt University).

Dr Crozier is 44-year-old Vanderbilt-trained infectious diseases physician who had a near-fatal encounter with Ebola just 3 weeks after his arrival in Kenema, West Africa, working on a ward with 60-80 Ebola patients. Dr Crozier was the third patient admitted to Emory Hospital with Ebola, and his condition was dire. He had multiorgan failure including encephalitis, severe diarrhea, renal failure, and respiratory failure. He also had a very high viral load, which has been associated with poor outcomes. He received supportive care, including intubation and dialysis. Quite miraculously, he survived and now is convalescing in his parents' home in Arizona with the hope of returning to West Africa.

Dr Crozier's course following discharge has been complicated by unexpected late complications, including mentation changes, postinfection arthritis, and ocular involvement with uveitis attributed to intra-ocular infection by Ebola virus and the well-publicized eye color change from blue to green (Figure 2). He described this eye as being "mushy" to palpation.

Figure 2. Dr Ian Crozier
(Source: Emory Eye Center).

This was accompanied by near blindness in the affected eye, allowing only perception of gross movement. His ophthalmology care was confounded by the lack of any precedent and the dilemma posed by the use of steroid injections to control inflammation but which risked promoting the infection. His subsequent course was equally dramatic. He attained 20/20 vision, and the virus is no longer recoverable from ocular fluid, although his ophthalmologist is uncertain whether the virus is really gone from this reservoir, which he referred to as "a sanctuary site" and others call an "immune privileged site." At present, he appears well but has neurologic sequelae including mentation and memory lapses with MRI-demonstrated central nervous system sequelae.

The presentation was beautifully delivered, the visuals were impressive, and the audience was clearly moved by a stunning combination of scholarship and humanitarianism. At the end, he received a prolonged standing ovation, something I have not seen in 39 consecutive annual Infectious Diseases Society of America (IDSA) meetings.

The postscript is also of interest in showing several other examples of persistence of viable Ebola virus in other "sanctuary sites" including semen from 46/90 men at 2-9 months after recovery, breast milk at 15 days, vaginal fluid at 33 days, and aqueous humor (presumably this patient) at 98 days.[2,3,4] The observation of viral persistence sends a new alarming message about Ebola survivors who have already survived an awful, largely untreatable, life-threatening infectious disease.

This bad news is further compounded by the recent observation of a British nurse who apparently "recovered" and was prepared to return to work but unexpectedly deteriorated and had to be readmitted to the hospital. She is now declared to be once again Ebola-free. The finding of Ebola virus in genital secretions is especially important because it indicates the need for an arbitrary period of sexual abstinence or use of a protective barrier.[5] This concern is no longer theoretical based on a molecularly proven postrecovery sexual transmission. Another concern is the possibility that these "sanctuary" sites of microbial pathogens might represent sites of persistent antigenic stimulation to explain some enigmatic inflammatory complications of Ebola, such as arthritis and inflammatory bowel disease.

Antibiotic Stewardship

The surge in importance of antibiotic stewardship gave a substantial boost to those trained in the field of infectious diseases because it clearly implies recognition of the importance of this skill, especially in the face of the antibiotic resistance crisis. The initiative[6] was discussed in many sessions, and the following is a preliminary synthesis of the current status. No plan has yet been clearly defined by Centers for Medicare & Medicaid Services (CMS), but following are some of the anticipated features of the initiative.

Antibiotic stewardship may be added to the Conditions of Participation, which has substantial potential financial consequences. The Centers for Disease Control and Prevention (CDC) is largely responsible for defining this program and has identified seven core components that include a designated leader, financial support for the program provided by the facility, and development of a stewardship plan based on antibiotic utilization and patient diagnostic data. Reporting of Clostridium difficile infection, a key target for stewardship programs, is already required under the CMS Inpatient Quality Reporting Program.

CDC has proposed a measure for antibiotic use that could be used for benchmarking, the standardized antibiotic administration ratio (SAAR). This measure builds on the work of Ron Polk and colleagues[7] and has been submitted to the National Quality Forum. The measure will be part of the antibiotic use option of the National Healthcare Safety Network that allows hospitals to electronically report antibiotic use data to the CDC. An antibiotic use benchmarking measure will help hospitals understand where their antibiotic use differs from that of facilities serving similar patient populations. It was emphasized that the CDC has a great desire for a "playbook" to provide guidance on how to best implement the core elements of stewardship programs to achieve the program goals.

Clostridium difficile Infection

Clostridium difficile infection (CDI) and its management received great attention at the meeting, especially the review from OpenBiome on stool transplants for relapsing CDI.[8] This is a nonprofit organization in Boston that provides commercially available stool for relapsing CDI. It represents a collaborative effort involving Massachusetts General Hospital (Harvard Medical School), Massachusetts Institute of Technology, and the University of Minnesota Microbiome Project.

Stool donors undergo extensive screening with a 45-minute interview and laboratory tests to exclude those with obesity, metabolic syndrome, autoimmune disease, and other disease connected with the colonic microbiome. The acceptance rate for donors is 2.8%. The donors provide three specimens weekly that are stored in frozen state and shipped on dry ice to requesting sites in 49 states and six countries. The cost per specimen is $250, which is far lower than the cost of the screening tests required for locally selected donors, and the recipient is not reimbursed by third parties.

The experience with 7144 treatments shows a definitive cure rate of about 86%, similar to the rate that is currently reported from sites using local specimen sources.[9,10,11] Of particular interest are the long-term outcomes of stool transplant based on multiple studies suggesting that the colonic microbiome has potentially important health consequences, such as the recent report of the thin patient with relapsing CDI who became fat after a transplant from a fat donor.[12] Studies in mice have shown that transfer of stool from a mouse with the metabolic syndrome to a germ-free mouse produces the metabolic syndrome in the recipient.[13]

Follow-up data will now be available in some of the recipients. The donors are healthy and stereotyped, but the recipients are diverse. Thus, the long-term outcomes of a recipient who is obese or has the metabolic syndrome and receives stool from a healthy, thin donor will be of great interest. This raises the question of potential for a broader application of stool transplants for other medical conditions based on phenotype of the recipient. It also raises questions about donor selection for the centers that are doing stool transplants with other specimen sources.

Medical Management of Appendicitis

The IDSA meeting included great interest in the medical treatment of appendicitis based on a recent report.[14] The trial included 530 patients with appendicitis who were randomly assigned to standard surgery or medical treatment (ertapenem for 3 days followed by oral levofloxacin/metronidazole for 7 days). Results showed more complications in the surgery group, including surgical site infections in 24% and a median "sick leave" time of 19 days vs 7 days in the medically treated group. Recurrent appendicitis occurred in 21% of those who received medical treatment. The main downside to medical treatment is that the patient still has an appendix and, thus, a risk for recurrence; but, overall, this looks like a medical management option to consider.

Middle East Respiratory Syndrome

The flu types that we worry about received substantial attention at the IDWeek meeting, not only because the flu season is close but because of the multitude of other very concerning respiratory viruses that we keep hearing about. Possibly the greatest current concern is Middle East Respiratory Syndrome (MERS), which is similar to SARS, which was so infamous in much of the world.[15] Similarities between MERS and SARS are:

  • Both are coronaviruses;

  • Both have many silent carriers, making infection control very difficult;

  • Both have "super-spreaders"—for SARS this was the Metropole Hotel in Hong Kong and a patient who became the source of spread to three countries (Canada, Singapore, and Vietnam), and for MERS it was the large, open ward where a Korean businessman was placed and subsequently became the source of 29 MERS cases; and

  • The number of cases was much greater for SARS (8311 vs 1311 cases), but SARS is gone and MERS is still going strong; MERS is also proving far more lethal at 38% mortality vs 10% for SARS.

The main message is that we must be astute to avoid missing these respiratory viruses that can have substantial consequences, as we have learned many times historically. Also, the label of "super-spreader" should not be applied to the patient because it is not the patient but the environment that is to blame.[16]

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