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March 2017
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, in each issue of Clinical Infectious Diseases.

Stool Transplant: No Better Than Vancomycin Taper for Acute, Recurrent C. difficile Infection?

Reviewed by A. Krishna Rao, MD, MS

Fecal microbiota transplantation (FMT), which transfers stool from a healthy donor into the patient's gut, has emerged as one of the most safe and effective treatments for recurrent Clostridium difficile infection (CDI). Prior randomized controlled trials (RCTs) have compared FMT to only two weeks of vancomycin and to placebo (the patient's own stool). Though effective in these studies, the performance of FMT in acute, recurrent CDI compared to standard therapy has been unknown.

A recent study in Clinical Infectious Diseases by Hota et al. compared 14 days of vancomycin followed by FMT to a six-week taper of vancomycin (a standard therapy) in patients experiencing an acute, recurrent episode of CDI. The design was an open label, RCT with 1:1 allocation between both treatment arms, and the primary endpoint was CDI recurrence within 120 days. The study was terminated due to futility after only 30 patients were randomized—58 percent of those in the vancomycin arm were recurrence free, compared to only 44 percent in the FMT arm. 

These findings may come as a surprise given the success of FMT in the literature to date. However, most RCTs did not test FMT in the acute recurrence setting and/or did not compare FMT to a vancomycin taper. Two of the recent RCTs included patients on suppressive vancomycin rather than acute therapy, and as Hota et al. point out, "it is not known what proportion of patients would have been symptom-free had their antibiotics been simply discontinued.” This study also comes on the heels of one that showed FMT using a fecal filtrate that did not contain any bacteria successfully cured five patients of their recurrent CDI, and another that found FMT to be no more effective than placebo at one of the sites.

This underscores the experimental nature and unanswered questions still plaguing FMT for CDI. Future studies will be needed to better define the scope and efficacy of FMT so that providers can optimally utilize it. 

( Hota et al.Clin Infect Dis..2017;64(3):265-271.)

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High-Dose Influenza Vaccination and Reduced Postinfluenza Mortality

Reviewed by Michael T. Melia, MD

Among adults aged ≥65 years, high-dose influenza vaccine has been shown to be more effective than standard-dose vaccine in preventing laboratory-confirmed influenza infections and influenza-related office visits. It has also been shown to reduce influenza hospitalizations, and it elicits higher hemagglutination-inhibition titers than standard-dose vaccine for influenza A(H1N1) and A(H3N2), and non-inferior titers for influenza B. 

A recent article in The Journal of Infectious Diseases describes a retrospective study of Medicare parts A and B beneficiaries aged ≥65 years who received inactivated influenza vaccines during the 2012-2013 and 2013-2014 seasons. The primary outcome was death in the 30 days following a Medicare claim for an inpatient hospitalization or an emergency department visit with a diagnosis of influenza. 

The authors studied nearly 5.8 million recipients of high- or standard-dose vaccine. High-dose vaccine was received by 38.2 percent of beneficiaries in 2012-2013 and 44.5 percent in 2013-2014. Aside from some differences by region of residence, there were no differences in baseline covariates between high- and standard-dose recipients. During 2012-2013, high-dose vaccine was 36.4 percent more effective than standard-dose vaccine in reducing postinfluenza death; there was no significant difference in death rates between the two groups during 2013-2014.

Although reasons for the different rates of high-dose vaccine efficacy in preventing postinfluenza deaths during the two seasons are uncertain, the lower rates of postinfluenza death among high-dose vaccine recipients during 2012-2013 may have been explained by greater circulation of influenza A(H3N2) as compared with 2013-2014, when 90 percent of detections were influenza A(H1N1)pdm09 viruses. Characteristics of recipients of high- or standard-dose vaccine did not differ between the two seasons. Given the burden of serious influenza-related complications shouldered by persons ≥65 years, this evidence of mortality benefit provides another data point in favor of high-dose vaccination for elderly persons.

( Shay et al.J Infect Dis. 2017 March 2.)

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Switch Outcomes for Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for HIV Infection

Reviewed by Lauren Richey, MD, MPH

Tenofovir alafenamide (TAF) is a new tenofovir prodrug associated with lower plasma levels of tenofovir compared with the widely used tenofovir disoproxil fumarate (TDF). A recent article published in the Journal of Acquired Immune Deficiency Syndromes (JAIDS) described long-term outcomes from a randomized, double-blind, multicenter switch study of these HIV medications. 

Over 600 virologically suppressed patients were randomized to switch to coformulated TAF with emtricitabine (FTC) or to continue TDF/FTC without any change to their third agent, which was a ritonavir-boosted protease inhibitor (PI) or a non-boosted agent. At 96 weeks, the TAF/FTC regimen was non-inferior to TDF/FTC for virological suppression, 88.6 percent versus 89.1 percent. Serious adverse events were similar for TAF/FTC (8 percent) versus TDF/FTC (9 percent), and adverse events leading to discontinuation were also similar, 2 percent versus 1 percent, respectively. Increases in estimated glomerular filtration rate (GFR) were found among participants who switched to TAF/FTC versus TDF/FTC (10 versus 4 mL/min). 

There were also significant changes in total proteinuria and albuminuria favoring the TAF/FTC group. The TAF/FTC group had statistically significant increases in bone mineral density compared with the TDF/FTC group. Lipids also increased from baseline in the TAF/FTC group compared with the TDF/FTC group (total cholesterol 14 versus 1 mg/dL).

Overall TAF/FTC was non-inferior and had a similar safety profile to the widely used TDF/FTC, but TAF/FTC was shown to have improved bone mineral density and renal parameters. These outcomes did not differ depending on the third agent. Of note, the participants with a boosted-PI received a coformulated regimen that included a 10 mg dose of TAF with FTC, while those on non-boosted third agents received a 25 mg dose of TAF with FTC. It is important to note that this 10 mg coformulation is not currently commercially available, but the 25 mg dose of TAF with 200 mg of FTC is currently available as Descovy. Whether this dosage change is clinically relevant or would affect the outcomes of patients on ritonavir-boosted PI regimens is unclear. 

( Raffi et al.J Acquir Immune Defic Syndr.. 2017 March 6.)

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Source Control and Outcomes in Patients With Severe Sepsis and Septic Shock

Reviewed by Kelly Cawcutt, MD

“Treat the underlying condition” is a dogma in medicine and is also true of sepsis. Early intervention is critical, and rapid mitigation of infection is a primary tenet of sepsis management. Source control is recommended within 12 hours for those with severe sepsis or septic shock. In a prospective, observational study recently published in Critical Care Medicine , researchers evaluated source control in these patients and hypothesized that delayed (>12 hours) source control would portend worse outcomes. 

The study was a secondary analysis and included 99 intensive care units (ICUs) in Spain. Adults admitted to an ICU during three four-month periods from 2011 to 2013 were included. Data collection included timing of sepsis onset, presence of shock, compliance with sepsis bundles, source control details, appropriateness and timing of antimicrobial therapy, and outcomes including mortality, days of mechanical ventilation, days of vasopressors, and length of stay. 

Among 3,663 patients included, 1,172 (32 percent) underwent source control. Of those requiring source control, abdominal infection was most common (67.2 percent); without source control, respiratory infection was most common (47.8 percent). Compliance with sepsis bundle components was worse in patients undergoing source control. 

Overall, via multivariate logistic regression, presence of source control was associated with a lower hospital mortality with an odds ratio of 0.809 (95 percent confidence interval [CI] 0.658 – 0.994). Regarding timing of source control (early versus late), 1,090 patients had time recorded and 825 (75.7 percent) of these had source control within 12 hours. Significant differences in demographics, clinical data, or mortality were not found. Time analysis of source control as a continuous variable failed to identify a relationship between timing and mortality, and no optimum time for source control was identified.

This study highlights the importance of source control in patients with severe sepsis and septic shock via an improvement in mortality despite the presence of increased severity of illness and worse bundle compliance. With one-third of patients requiring source control, providers must recognize this as a necessary evaluation and potential intervention in patients with severe sepsis and septic shock.

( Martinez et al.Crit Care Med.. 2017;45(1):11-19.)

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

March 15

  • Small Pulmonary Nodules During Febrile Neutropenia and the Overdiagnosis of Pulmonary Fungal Infections
  • Indoor Dust Resistome and Antimicrobial Chemicals 
  • Case Vignette: Paranasal Sinusitis and Melioidosis

March 1

  • Effective Treatment Options for Patients With Macrolide-Resistant Pulmonary MAC Infection 
  • Case Vignettes: Scabies and the Renaissance


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