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March 2013
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IDSA Journal Club
March 2013

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” in each issue of Clinical Infectious Diseases.


Rates of CRE on the Rise in U.S. Health Facilities, Raising Public Health Concerns
Reviewed by Rachel Simmons, MD

Two recent reports indicate that while carbapenemase-resistant Enterobacteriaceae (CRE) are relatively rare in the U.S., rates in health care facilities have increased significantly and alarmingly over the last 10 years.

In the March 8 Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention (CDC) reported new CRE data from the National Healthcare Safety Network (NHSN), the National Nosocomial Infectious Surveillance (NNIS) system, and the Surveillance Network-USA. During the first 6 months of 2012, 4.6 percent of all hospitals, 3.9 percent of short stay hospitals, and 17.8 percent of long-term acute care hospitals reported at least one or more infections with CRE according to NHSN surveillance data on catheter-associated urinary tract infections and central-line-associated blood stream infections from nearly 4,000 hospitals.

These infections were more common in larger hospitals, teaching hospitals, and in the Northeast. From 2001 to 2011, the rate of CRE increased from 1.2 percent (12 out of 2,631 isolates) to 4.2 percent (186 out of 4,388 isolates), according to NNIS and NHSN data. Klebsiella species had the highest rates of CRE in 2011, at 10.4 percent of isolates, compared to 1 percent (E. coli) and 3.6 percent (Enterobacter) for other species.

CDC also reported data collected from 64 patients with CRE infections from three sites (Atlanta, St. Paul-Minneapolis, and Portland, Ore.) as part of the Emerging Infections Program. Most were infected with Klebsiella species. The vast majority had some type of health-care exposure. Four percent of the patients died, 22 percent required intensive care unit (ICU) care within seven days of the positive culture, and 82 percent were hospitalized.

In the March 2013 issue of Infection Control and Hospital Epidemiology, investigators reported additional details on rates of Klebsiella pneumoniae isolates resistant to carbapenems (CRKP). The proportion of CRKP increased from less than 0.1 percent in 2002 to 4.5 percent in 2010. ICUs had the highest prevalence of CRKP compared to inpatient settings and nursing homes. By 2010 the percentage of Klebsiella species isolates that was resistant to carbapenems was 6.16 percent in the Northeast, 5.9 percent in the Midwest, 2.17 percent in the South Central, 2.49 percent in the South Atlantic, and less than 1 person in the West regions.

Given the very limited treatment options for these infections, they are a significant public health threat. A CDC-developed toolkit offers guidance for preventing their spread. The recommendations for all facilities include surveillance of culture data for CRE and CRE screening for patients linked to those with CRE infection or colonization. For facilities with CRE transmission, CDC recommends active surveillance for CRE by screening a pre-determined set of patients, such as all patients admitted to a facility, high-risk patients, or patients in high-risk settings like ICUs.

(Vital Signs: Carbapenem-Resistant EnterobacteriaceaeMMWR. March 8, 2013 /62(09);165-170 and Braykov et al. Infect Control Hosp Epidemiol 2013;34(3):259-268.)

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Influenza Virus Detected in Aerosols During Routine Patient Care
Reviewed by Sheila Mitsuma, MD

Traditionally, influenza virus transmission is believed to occur primarily through large-particle respiratory droplets. In the April 1 issue of the Journal of Infectious Diseases, investigators challenge this paradigm by demonstrating that influenza virus RNA can be detected in small-particle aerosols emitted from patients during routine care.

Sixty-one children and adults with symptomatic influenza A or B were included in this study. Air samples were taken at ≤1, 3 and 6 feet from each patient’s head and evaluated for the presence of influenza virus by real-time reverse transcriptase PCR. No aerosol generating procedures were undertaken during sampling.

Influenza virus was detected in the room air of 26 patients (43 percent), predominantly in smaller particles with diameters < 4.7um. Viral loads in air samples decreased in proportion to increasing distance from patient heads. At 6 feet, viral loads dropped considerably but still exceeded the 50 percent human infectious dose of virus in one patient (based on the authors’ calculations). Variables associated with the detection of aerosolized influenza virus included high nasopharyngeal viral load and patient-reported severity of illness.

These findings raise concern that airborne transmission may contribute to the spread of influenza, call into question current infection control practices, which focus on prevention of droplet and fomite transmission, and underscore the importance of influenza vaccination in healthcare workers. However, an important caveat to this study is that viral nucleic acid was detected in small-particle aerosols, not infectious virus. To what extent small-particle aerosols play a role in the transmission of infectious virus from person to person has yet to be determined and requires further study.

(Bischoff et al. J Infect Dis. (2013) 207 (7): 1037-1046.)

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Printed vs. Computerized Decision Support to Reduce Antibiotic Use in Acute Bronchitis: Implications for Antimicrobial Stewardship
Reviewed by Christopher J. Graber, MD, MPH

A cluster-randomized trial of printed versus computerized decision support interventions to reduce antibiotic use in acute bronchitis recently published in JAMA Internal Medicine (formerly Archives of Internal Medicine) showed modest reduction in antibiotic use with either approach.

Thirty-three primary care practices in the Geisinger Health System in central Pennsylvania were randomized from October 2009 to March 2010 to either receive:

  • Printed decision support: A poster outlining evidence-based management of acute respiratory tract infections was posted in each examination room and educational brochures were provided to patients presenting with cough;
  • Computerized decision support:  An electronic alert appeared for any patient with a chief complaint of “cough” that triggered delivery of an educational brochure to the patient and a structured electronic template to the provider; or
  • No intervention.

Education was delivered at the intervention sites by clinical champions who participated in a half-day training session and were provided data regarding their specific clinic’s antibiotic use. The primary outcome measurement was prescription of any antibiotic for acute uncomplicated bronchitis as compared to the three previous winter seasons. Patients with chronic heart or lung disease, HIV, malignancy, or other acute respiratory illnesses (i.e., sinusitis, pharyngitis, otitis media, and pneumonia) were excluded from analysis.

The overall percentage of patients with uncomplicated acute bronchitis who were prescribed antibiotics dropped from 80 percent to 68 percent in the printed decision support sites and from 74 percent to 61 percent in the computerized decision support sites. Both were statistically significant findings after accounting for patient-, clinician-, and site-specific factors, though there was no significant difference between the two approaches. Antibiotic use increased slightly at the control sites: 73 percent to 74 percent. Similar patterns of total visits, 30-day return visits, and proportion of acute bronchitis diagnoses were seen across all arms.

Although modest reductions in antibiotic use were seen in the intervention arms, antibiotic usage for uncomplicated acute bronchitis should ideally approach zero, the accompanying editorial notes. Clearly, we have a long way to go. Reinforcing to individual patients and to society that antibiotics are likely to do more harm than good for acute bronchitis and adapting principles of organizational change from business, cognitive psychology, and behavioral economics are suggested as potential ways forward.

(Gonzales et al. JAMA Int Med 2013;173:267-73 and Linder. JAMA Int Med 2013;173:273-5.)

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VRE Colonization of the Gut and Microbiota: Preliminary Findings Suggest Novel Approach
Reviewed by Paul Pottinger, MD

Vancomycin-resistant enterococci (VRE) colonization of the gastrointestinal tract is a major challenge for infection control and patient care, particularly among immunosuppressed individuals. Up to 20 percent of colonized stem cell transplant patients will subsequently develop VRE bacteremia, and concern for this possibility drives up the use of empiric daptomycin and linezolid use in these patients when they develop febrile neutropenia. And spontaneous clearance is rarely documented.

However, there is cause for hope in the March 2013 issue of Infection and Immunity. In a series of elegant experiments, investigators successfully drove down high-level VRE colonization (which they aptly call VRE “domination”) by a billion fold from mice by feeding them a suspension of fecal pellets from healthy mice. Using broad-range 16-S primers for PCR sequencing, they discovered that the stool offered a rich diversity of microbiota, in particular anaerobic bacteria, including the Barnesiella species. Feeding the mice a suspension of either placebo or feces heavy in oxygen-tolerant species was unsuccessful at eliminating VRE carriage.

The researchers then looked prospectively at the fecal flora of 94 human patients undergoing hematopoietic stem cell transplantation. Those who went on to develop VRE gut domination had an average of two logs less Barnesiella than those who did not. This statistically significant difference suggests—but does not prove—that this species may protect against VRE overgrowth, and by extension protect patients from VRE bacteremia.

It remains unknown whether administering Barnesiella to human patients would be an effective strategy. These findings are observational and preliminary, but they are cause for optimism. Fecal microbiota transfers are gaining a reputation for safety, tolerability, and efficacy in the management of human C. difficile infection. Hopefully, future research in people will demonstrate that VRE dominance in the gut is amenable to a similar approach.

(Ubeda et al. Infect Immun. 2013 Mar;81(3):965-73.)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, and Donald Kaye, MD, in each issue of Clinical Infectious Diseases:

March 15

  • U.S. National Park Employees and Zoonotic Infections
  • Trimethoprim-Sulfamethoxazole for Streptococcus pyogenes Infections?

March 1

  • Whole-Genome Sequencing and Outbreak Analysis: You Only Find Things if You Look
  • Fighting Fire With Fire: Immunosuppressive Treatment of an Immunodeficiency

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