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May 2015
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IDSA Journal Club
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,” by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.

Effects of C. difficile Infections on Hospital Readmissions
Reviewed by Zeina Kanafani, MD, MS

Clostridium difficile infections (CDI) have been associated with increased morbidity and increased utilization of health services. The impact of recurrent CDI on hospital readmissions was recently highlighted in two articles published in the American Journal of Infection Control.

The first is a review of data from the Detroit Medical Center health system. The authors categorized hospital discharges in 2012 into all-cause discharges (no CDI; n=51,353) and CDI discharges (n=651), which were further subdivided into community-onset (CO) CDI (n=318) and hospital-onset (HO) CDI (n=297). They then categorized readmissions into four groups: all-cause readmissions (no CDI during index admission; n=7,379), CO and HO readmissions (patients from CO and HO CDI groups, readmitted for any reason; n=99 and 86, respectively), and CDI readmissions for CDI (patients with CDI in index admission readmitted for CDI; n=48).

CDI discharges were more likely to be ≥60 years of age compared to all-cause discharges (59 percent vs. 43 percent; p<0.001), and CDI cases were more likely to be discharged to a health care facility than to home (OR=3.65; p=0.001). Whereas 30 percent of CDI discharges were readmitted during the study period, only 14 percent of all-cause discharges were readmitted. In addition, the average length of stay among CO and HO CDI readmissions was longer than that for all-cause readmissions. Finally, the cost of a CDI discharge and readmission was around $9,000.

In the second article, Olsen et al. analyzed data from 3,950 CDI cases. The CDI recurrence rate within 42 days was 11 percent, and the readmission rate was 45 percent within 180 days. Compared with those without a recurrence, patients who experienced a recurrence were more likely to be readmitted (85 percent vs. 41 percent; p<0.001). They also had a greater mean number of readmissions within 180 days (1.72 vs. 0.81; p<0.001) and a greater mean number of hospital readmission days (18.6 vs. 17.6 days; p<0.001). On multivariable analysis, recurrent CDI was independently associated with a significant increase in both the total number of readmission hospital days (rate ratio 3.97; 95 percent CI 3.11-5.08) and the number of hospital readmissions (rate ratio 2.54; 95 percent CI 2.21-2.91).

These two retrospective studies confirm that patients who experience a recurrence of CDI are at higher risk of being readmitted than patients without a recurrence. Increased length of hospital stay, number of hospital admissions, and hence cost of care are all consequences of recurrences. Emphasis on prevention strategies is therefore essential in decreasing such morbidity among hospitalized patients with CDI.

(Chopra et al. Am J Infect Control. 2015;43(4): 314–317. and Olsen et al. Am J Infect Control. 2015;43(4):318–322.)

Ensuring Proper Antimicrobial Use at Hospital Discharge: The Next Frontier of Antimicrobial Stewardship? 
Reviewed by Christopher J. Graber, MD, MPH, FIDSA

Most antimicrobial stewardship programs in the inpatient setting focus on de-escalating unnecessary broad-spectrum intravenous antibiotic use and, in the outpatient setting, focus on reducing antibiotic use in situations where an antibiotic may not be indicated (i.e., uncomplicated upper respiratory infections). But the transition from inpatient to outpatient may be particularly fertile ground for reducing inappropriate antimicrobial usage.

A recent study published in Infection Control & Hospital Epidemiology examined the appropriateness of antimicrobial therapy prescribed at discharge at a large academic public safety-net hospital. The authors reviewed—for appropriateness of antibiotic prescription—a random sample of 150 charts of patients discharged on an oral antibiotic over a one-year time frame from July 2012 through June 2013. Urinary tract infection (UTI) (23 percent), skin and soft tissue infection (22 percent), community-acquired pneumonia (CAP) (17 percent), and gastrointestinal infection (15 percent) were the most common indications for antibiotics. Fluoroquinolones (37 percent) were the most frequently prescribed antibiotic class, despite local treatment algorithms discouraging fluoroquinolones as oral step-down therapy for UTI and CAP.

Fifty-three percent of antibiotic courses were deemed inappropriate, most commonly due to excessive treatment duration (33 percent of inappropriate courses), suboptimal antibiotic selection (17 percent), incorrect dose (9 percent), and conditions not requiring antibiotics (5 percent). CAP was associated with inappropriateness (even though the institution had a CAP treatment algorithm), and infectious diseases consultation and azithromycin use were associated with appropriateness.

The authors noted that almost two thirds of the total antibiotic duration was completed in the outpatient setting, further underscoring the need to ensure guideline-concordant therapy at hospital discharge, especially with regard to length of therapy.

(Yogo et al. Infect Control Hosp Epidemiology. 2015;36(4):474-8.)

Your Neighbor’s Antibiotics: A Novel Risk Factor for C. difficile Infection
Reviewed by Manie Beheshti, MD

Widely accepted risk factors for Clostridium difficile infection (CDI) include advanced age, antibiotic exposure, chemotherapy, hospitalization, use of proton pump inhibitors, and gastrointestinal surgery. Although exposure to patients with CDI is a more recognized risk factor, the role of the more prevalent asymptomatic carriers is less well understood.

In the April 2015 issue of the Journal of the American Medical Association (JAMA) Internal Medicine, researchers in Canada assessed the risk of CDI in hospitalized patients with respect to their hospital ward’s antimicrobial usage. This single-center study was conducted at a teaching hospital. Sixteen wards were included (five intensive care units, eight medical-surgical wards, and one oncology ward). Over the course of the nearly two-year study, over 34,000 patients were evaluated with a total of 255 CDIs. Using multivariable and multilevel models, the researchers found that regardless of recent antimicrobial exposure, there was a 34 percent increase in CDI for every 10 percent increase in days of antimicrobial therapy at the ward level.

The unique perspective of this study helps highlight CDI risks beyond just a single patient’s risk factors. Use of antibiotics at the ward level impacts CDI risk regardless of a patient’s antimicrobial use. This novel risk factor could have far greater implications in understanding CDI transmission and risk. Further, it adds to the growing list of benefits in the new era of antimicrobial stewardship. As stated in the accompanying editorial, “the main finding of this study reveals how antibiotics, by affecting a subset of patients … put the entire population, including those who do not receive antibiotics, at increased risk via increased transmission.”

(Brown et al. JAMA Intern Med. 2015;175(4):626-633.)

The QuantiFERON Quandary: Limitations in Steroid Treated Patients
Reviewed by Nirav Patel, MD

Interferon-gamma release assays (IGRAs) offer an alternative screening tool for latent tuberculosis infection (LTBI), with some added advantages over tuberculin skin testing, such as positive and negative controls built into the test itself. However, there have been concerns regarding the validity of IGRAs in the setting of preexistent anti-tuberculous drugs or in the presence of immunomodulators such as steroids, which a recent article in Tuberculosis attempts to address.

In the study, blood from 10 adult patients with LTBI was inoculated into the standard QuantiFERON-TB Gold In-Tube (QFT) as well as tubes containing therapeutic concentrations of isoniazid, rifampin, isoniazid+rifampin, ciprofloxacin, or dexamethasone. Analysis of cytokines, including TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, and MIP-1β, was performed, along with routine QFT.

No significant effects were noted in cytokine production in the presence of anti-tuberculous drugs; however, four of 10 patients converted the QFT result from positive to negative in the presence of dexamethasone. There was no corresponding change in the mitogen (positive) control.

Perhaps the results are not surprising, as tuberculosis specific T-cells represent only a very small fraction of peripherally circulating T-cells. Thus, responses in these specific T-cells may be blunted by steroid exposure, while mitogen stimulates all circulating T-cells, and would still meet criteria for a positive response.

Nonetheless, there is significant clinical concern regarding these findings, as many patients undergo LTBI screening using IGRAs prior to starting aggressive immunosuppressive regiments. A large number of these patients are already on steroid therapy at baseline and thus could have false-negative results. A detailed clinical evaluation for tuberculosis exposure risk and a consideration for treatment of LTBI remain essential.

(Special thanks to Daniel Hoft, MD, PhD, FIDSA, for his suggestions and comments.)

(Clifford et al. Tuberculosis. published online: February 13, 2015.)

Estimating HIV Transmission Rates at Each Step of the Care Continuum
Reviewed by Brian R. Wood, MD

The HIV care continuum or “treatment cascade” describes the number of individuals who are 1) infected but undiagnosed, 2) diagnosed but not retained in care, 3) retained in care but not prescribed antiretroviral therapy (ART), 4) prescribed ART but not virally suppressed, or 5) virally suppressed. Now, a new spin on this model may help guide HIV prevention efforts.

Researchers incorporated data from three large databases to estimate the number of HIV transmissions and rate (annual per-person transmissions) at each step of the care continuum, stratified by sex, risk category, and age group. The analysis, reported in Annals of Internal Medicine, demonstrates that of the approximately 1.2 million people living with HIV in the United States, 18.1 percent remain undiagnosed, 45.2 percent are diagnosed but not retained in care, 4.1 percent are retained in care but not prescribed ART, 7.2 percent are prescribed ART but not virally suppressed, and 25.3 percent are virally suppressed. The highest rate of transmission is attributable to undiagnosed individuals (6.6 transmissions per 100 person-years), followed by those diagnosed but not retained in care (5.3 transmissions per 100 person-years). These two groups account for 91.5 percent of HIV transmissions.

Successful advancement along the care continuum is associated with a reduction in transmission rate; viral suppression, the ultimate step in the cascade, leads to a 94 percent reduction. Men account for the majority of HIV transmissions, with the most frequent risk factor being male-to-male sex. Younger people (ages 25 to 34) and men who have sex with men (MSM) who use injection drugs account for the highest transmission rates overall.

The most notable finding is the staggering impact of undiagnosed individuals and those not retained in care on new HIV infections. However, the data also confirm the striking effect of viral suppression on transmission rate. This data can help us understand the impact of efforts to improve each step of the care continuum as we continue to strengthen screening, linkage, and retention in care programs and strive toward early, effective ART for all HIV-infected persons.

(Skarbinski et al. JAMA Intern Med. 2015;175(4):588-596.)

Back to Top

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

May 15
  • Vaccination Against Japanese Encephalitis: How Safe Is It?
  • Delayed Hemolysis After Artesunate Treatment of Severe Malaria
  • Case Vignette: Asymptomatic Bartonella Bacteremia in a Blood Donor
May 1
  • Sepsis in Hematopoietic Stem Cell Transplant and Solid Organ Transplant Recipients: Very Different Outcomes
  • Varicella Zoster Infection and Central Nervous System Complications in Children Since the Introduction of Vaccination
  • Case Vignette: Transplanting a Malarious Heart
April 15
  • Influenza and Pregnancy: Too Much of an Immune Response?
  • The Mechanism of Plasmodium falciparum Resistance to Artemisinin
  • Fat Cells—Enemies of Staphylococcus aureus
April 1
  • Decision Fatigue—When Prescribing an Antibiotic Is the Easy Way Out
  • Toscana Virus

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