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November 2015
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.

The Relevance of C. difficile Molecular Assays: Do They Overdiagnose Clinical Disease?
Reviewed by Christopher J. Graber, MD, MPH, FIDSA

Currently, many clinical laboratories in the United States rely on polymerase chain reaction (PCR)-based molecular methods for diagnosing Clostridium difficile infection (CDI), having transitioned from immunoassay-based tests for toxins produced by C. difficile. This switch was prompted in part over concerns that the toxin immunoassay tests were not sufficiently sensitive. However, a new study in JAMA Internal Medicine suggests that PCR-based testing may overestimate actual clinical disease caused by C. difficile.

During a period (December 2010 through October 2012) at the University of California Davis Medical Center, where the clinical laboratory was transitioning from using a C. difficile toxin immunoassay to PCR-based testing, the clinical laboratory continued to report the toxin immunoassay results but not the PCR-based test results. This allowed the authors to determine the clinical outcomes of patients who had toxin-negative but PCR-positive results in the absence of the clinical providers acting on the PCR positivity.

More patients (n=162) were toxin-negative/PCR-positive than toxin-positive/PCR-positive (n=131), with lower fecal C. difficile bacterial loads, toxin concentrations, and fecal lactoferrin. Despite most toxin-positive/PCR-negative patients not receiving treatment, duration of diarrhea was shorter (2 vs. 3 days) with a lower overall risk of diarrhea during 15-day follow-up than the toxin-positive/PCR-positive patients. Clinical outcomes and CDI-related complications among the toxin-negative/PCR-positive group were similar to toxin-negative/PCR-negative patients, with only one toxin-negative/PCR-positive patient developing an uncomplicated, recurrent CDI that resolved before care was withdrawn for severe underlying illness. Forty-eight patients were toxin-negative/PCR-positive but had positive cell cytotoxin assays; this subgroup had low fecal toxin concentrations and clinical outcomes similar to PCR-positive patients that were cell cytotoxin-negative.

This study suggests that patients who are toxin-negative/PCR-positive may simply be colonized with C. difficile and not necessarily require treatment. Using a PCR-based assay as a stand-alone test to diagnose C. difficile-associated clinical disease may be problematic.

(Polage et al. JAMA Intern Med. 2015;175(11):1792-1801.)

 Maternal and Neonatal Consequences of Treated and Untreated Asymptomatic Bacteriuria in Pregnancy
Reviewed by Zeina Kanafani, MD, MS

Current approaches for screening and treatment of asymptomatic bacteriuria in pregnancy are based on trials done more than 30 years ago, note the authors of a recent paper in The Lancet Infectious Diseases that revisits the topic. The authors initially present the results of a 2007 Cochrane review, which showed that treatment with antibiotics compared to placebo was associated with a reduced incidence of pyelonephritis, low birth weight, and preterm delivery.

The current study used a prospective cohort design with an embedded randomized controlled trial. Women with singleton pregnancy, aged 18 and older, were recruited. A single dipslide was used for screening between 16 and 22 weeks of pregnancy, and cultures were done on two different media. Asymptomatic bacteriuria was defined as a concentration of at least 105 CFU per ml for a single organism. In the randomized trial, 40 pregnant women with asymptomatic bacteriuria self-administered 100 mg of nitrofurantoin, and 45 women were given placebo, both for five days, with a follow-up dipslide one week later. In addition, 163 pregnant women with asymptomatic bacteriuria were not given any treatment. The comparison groups included women receiving active treatment and 4,035 women who did not have asymptomatic bacteriuria on one hand, and placebo-treated and untreated women on the other hand.

The primary endpoint was a composite of pyelonephritis, preterm birth, or both. In the cohort study, the composite outcome was not different between placebo-treated or untreated asymptomatic bacteriuria-positive women, and women who did not have asymptomatic bacteriuria (2.9 percent vs. 1.9 percent). Although the absolute risk was low in both groups, the incidence of pyelonephritis was statistically higher among placebo-treated or untreated women than among asymptomatic bacteriuria-negative women (2.4 percent vs. 0.6 percent). In addition, in the randomized trial, actively treated women had a similar outcome compared with placebo-treated or untreated women (2.5 percent vs. 2.9 percent). All women who developed pyelonephritis had a mild and uncomplicated disease course.

As the authors conclude, the results suggest that the screen-treat strategy may need to be reevaluated.

(Kazemier et al. Lancet Infect Dis. 2015;15(11):1324–1333.)

Champions of HIV Prevention: An Important Role for ID-Trained Specialists
Reviewed by Brian R. Wood, MD

The tremendous efficacy of antiretroviral therapy (ART) treatment-as-prevention (TasP) and preexposure prophylaxis (PrEP) has led to paradigm shifts in HIV prevention and strategies to avert HIV transmission. National guidelines recommend early ART for all HIV-infected individuals and endorse PrEP for HIV-uninfected persons at high risk of transmission. What is the role for infectious disease (ID)-trained specialists in this evolving landscape?

A recent analysis published in Clinical Infectious Diseases demonstrates that ID-trained HIV practitioners consider TasP and PrEP as important parts of their clinical role and are prepared to champion HIV prevention strategies, though barriers to implementation persist. Investigators present results from 415 responses to a 2014 survey of adult HIV providers through the Emerging Infections Network. Notably, 87 percent of respondents reported they recommend initiation of ART regardless of CD4 count. This figure may be biased by those who returned the survey or other factors but suggests significant uptake of recent guidelines and movement towards early ART for all. Lingering “late adopters” would benefit from education regarding the value of early ART. The survey results also underscore that patient readiness, psychiatric issues, substance use, and cost continue to impede early ART.

High percentages of respondents reported willingness to counsel, offer visits, and prescribe PrEP to at-risk individuals. However, only 35 percent reported having prescribed PrEP in practice; rates for certain risk groups, such as people who inject drugs (PWID), were much lower. A striking theme is the frequent obstacles to implementing prevention methods for PWID, such as offering clean syringes or opiate substitution therapy.  

This survey did not include non-ID trained primary care physicians, who may be well-positioned to identify and counsel at-risk HIV-seronegative individuals and are a key link in the HIV prevention chain. However, the take-home message is that ID-trained HIV specialists can act as champions of HIV prevention and serve as a source of education and support to peers. As the authors suggest, “early adopters” should be visible and available to colleagues for support, and clearly there is significant work to be done to support prevention for certain at-risk groups like PWID.

(Krakower et al. Clin Infect Dis. 2015 Sept. 18.)

HIV PrEP in the Real World: More Promising Results
Reviewed by Manie Beheshti, MD

The approval of HIV preexposure prophylaxis (PrEP) in July 2012 by the Food and Drug Administration was met with more questions than answers. Since that time, many studies have aimed to address the question of applicability in various practical clinical settings. Two recent such studies provide further promising results.

In the Sept. 10 issue of The Lancet, researchers in the U.K. report on their findings (the PROUD study). Men who have sex with men (MSM) were enrolled in this randomized trial across 13 sexual health clinics in England. Over 500 participants were randomly assigned to receive PrEP at the onset of the study period versus deferral for one year. After 243 person-years of follow-up, the authors’ findings suggest that no breakthrough HIV infections occurred in those taking PrEP. Further, the proportion of sexually transmitted infections (STIs), including rectal gonorrhea and chlamydia, did not differ between those taking or not taking PrEP. During an interim analysis, the steering committee found the high efficacy reason enough to recommend that PrEP be offered to all study participants.

In the Nov. 15 issue of Clinical Infectious Diseases, researchers at a large integrated health care system evaluated patients on PrEP from July 2012 through February 2015. The study population was 99 percent MSM. Among 657 PrEP initiators who took a mean duration of 7.2 months of PrEP, no HIV acquisition was noted in the 388 person-years of follow-up. Three hundred and forty-four STIs were diagnosed with a notable 50 percent of PrEP users acquiring at least one STI within 12 months (a comparative control group was not studied).

These two studies demonstrate the high efficacy of PrEP in some real world settings, further adding to prior research that PrEP in the right setting is an effective means of HIV prevention. While incidence of STIs are higher in these study populations, it remains unclear if use of PrEP has an impact on STI incidence. Taken together with general sex education, reinforced condom use, and proper STI screening, including but not limited to HIV, use of PrEP in the right setting is yet another effective tool for patients at high risk of HIV acquisition.

(McCormack et al. Lancet. 2015 Sept. 10.)

(Volk et al. Clin Infect Dis. 2015;61(10):1601-3.) 

Choose Wisely: Balancing Central Venous Catheter Complications in the Era of No Patient Harm
Reviewed by Nirav Patel, MD

Any complication of medical care is deeply scrutinized in the current era of patient safety. Infection rates of central venous catheters are a prime target for intervention, as they are critical determinants of quality in published hospital rankings and part of the Value-Based Purchasing program from the Centers for Medicare and Medicaid Services.

In a study published in the New England Journal of Medicine, Parienti and collaborators compare complication rates for central venous catheters in various insertion locations. The multicentered trial randomized patients on a 1:1:1 basis for the subclavian, jugular, or femoral vein; or 1:1 basis if one of the sites was deemed not suitable.  Catheters were not antiseptic or antibiotic impregnated, and dressings were not chlorhexidine-impregnated; otherwise insertions were carried out by experienced clinicians using wide-sterile barriers and full sterile garb. The primary endpoint was a composite of catheter-related bloodstream infection and symptomatic deep vein thrombosis.

The study evaluated 3,471 catheters. Fifty total primary outcome events occurred: eight in the subclavian group, 20 in the jugular group, and 22 in the femoral group; with the subclavian group at a lower hazard ratio compared to either the jugular site (2.1, P=0.04) or the femoral site (3.5, P=0.003). Mechanical complications were noted to a greater extent in the subclavian arm, 18 vs. 12 in the jugular arm, and six in the femoral arm.

The authors note that mechanical complications related to catheter insertion are typically recognized immediately and can be quickly addressed, while later complications, such as deep vein thrombosis and bloodstream infection, incur cumulative risk with continual catheter use and are more difficult to mitigate. Thus a simplistic conclusion may be to recommend the exclusive use of the subclavian vein for all catheter insertions. However, clinicians must weigh the different risks in different patients, and most fundamentally, the choice of insertion site should still be made on a case-by-case basis.

(Parienti et al. N Engl J Med. 2015;373:1220-1229.)

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:

November 15
  • Propionibacterium acnes: Infection or Contamination?
  • Narcolepsy After Influenza Vaccination: A Possible Mechanism
  • Case Vignette: Algae in the Blood, With an Important Lesson in Clinical Microbiology and in Believing Your Infectious Diseases Consultant
November 1
  • Anaplasmosis in the United States
  • Measles, Immunological Amnesia, and the Extended Benefits of Vaccination
  • Norovirus GII.17: Get Ready for the Next Wave
October 15
  • Albumin Infusion: Not a Good Idea for All Causes of Sepsis in Cirrhotic Patients
  • Urinary Tract Infection or Sexually Transmitted Infection?
  • Case Vignette: A Rarely Identified Site of Coccidioides Species Dissemination
October 1
  • Waterborne Tularemia: Whole-Genome Sequencing Nails It
  • NK Cells and Susceptibility to Viral Infection
  • Case Vignette: HHV-8 Working Overtime: Hemophagocytic Syndrome, Multicentric Castleman Disease, and Kaposi Sarcoma in a Single Patient

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