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May 9, 2018

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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.

Erica Kaufman West, MD

Mortality Benefit in Treating HCV-Infected Patients Without Advanced Liver Disease

Reviewed by Erica Kaufman West, MD

The Department of Veterans Affairs (VA) has been a leader in treating all patients with chronic hepatitis C virus (HCV) infection regardless of patients’ fibrosis scores. Over 90,000 veterans have received direct-acting antiviral (DAA) therapy.  Unfortunately, some insurers have used fibrosis scores as a way to limit coverage to those only with advanced disease, despite national guidelines recommending all patients be treated.  

In a recent study published in Hepatology, researchers used a VA database to find HCV-monoinfected patients treated with non-interferon DAA regimens. They defined patients without advanced liver disease as those with a fibrosis-4 (FIB-4) score ≤ 3.25, no diagnosis of cirrhosis or of decompensated liver disease by ICD 9/10 codes, no hepatocellular carcinoma, and no history of liver transplantation. The researchers evaluated 40,664 HCV-monoinfected patients without clinically apparent advanced liver disease from 129 VA facilities. Of these, 39,374 (96.8 percent) developed sustained virologic response (SVR) and 1,290 (3.2 percent) did not (No SVR). The study authors compared these patients to 62,682 monoinfected patients without advanced disease who were not treated with DAAs. Mortality rates for those achieving SVR, No SVR, and never treated were 1.6 percent, 3.6 percent, and 5.0 percent, respectively. They also looked at mortality rates using several other methods and found a significant reduction associated with SVR no matter what variables were used. 

This is the largest study to date looking at mortality benefits with DAAs in patients without advanced liver disease. It shows unequivocally that there is no medical reason to withhold treatment from chronic HCV-infected patients at any fibrosis score. These findings will be especially relevant and useful for providers who continue to fight for their patients’ unlimited access to HCV treatment.

(Backus et al. Hepatology. 2018 Jan 29.)

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Zeina Kanafani, MD, MSAerosolized and Oral Ribavirin for Respiratory Syncytial Virus Infection

Reviewed by Zeina Kanafani, MD, MS

Ribavirin is a nucleoside analog that is approved by the Food and Drug Administration for the treatment of respiratory syncytial virus (RSV) infection. Although inhaled ribavirin has been shown to improve the outcome of adult hematopoietic cell transplant recipients with RSV infection, it is a costly treatment, and there is wide variability in dosing and administration practices. Recently, there has been interest in the use of oral ribavirin as an alternative treatment for RSV.

In a recent Transplant Infectious Disease article, researchers conducted a retrospective cohort study to evaluate the effectiveness and safety of oral compared to aerosolized ribavirin in the treatment of RSV infections, using 30-day mortality as a primary outcome. In addition, a composite outcome was used consisting of 30-day mortality, serious adverse events, and escalation of care. A total of 46 patients were included in the study, 20 in the oral ribavirin arm (43 percent) and 26 in the aerosolized ribavirin arm (57 percent). The most common underlying comorbidity was lung transplantation (n = 9 with oral ribavirin and n = 13 with aerosolized ribavirin), followed by hematopoietic stem cell transplantation (n = 7 and 9, respectively). Ribavirin was used for a median of 10 days in the oral therapy arm and 9 days in the aerosolized therapy arm. The two treatment groups were similar in the proportion of patients who required mechanical ventilation or admission to the intensive care unit. 

Mortality at 30 days was statistically similar in both groups (15 percent with oral ribavirin and 4 percent with aerosolized ribavirin; P = 0.33). All deaths occurred within 7 days of initiation of ribavirin therapy. The composite outcome was identified in 25 percent and 35 percent of patients, respectively; P = 0.48. Using bivariable and multivariable analysis, the investigators were not able to identify any factors that were independently associated with the composite outcome. It was estimated that the use of oral instead of aerosolized ribavirin would reduce direct treatment cost by $1.2 million for 2017. Compared to aerosolized ribavirin, oral ribavirin appears to be an effective, safe, and cost-saving treatment alternative in immunocompromised adult patients with RSV infection.

(Trang et al. Transpl Infect Dis. 2018;20:e12844)

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Nirav Patel, MDBack to the Basics: Hospital-Acquired Infections and Exposure to Other Sick Patients

Reviewed by Nirav Patel, MD

Horizontal infection control practices (those that target many organisms capable of causing disease) remain a critical, but occasionally underappreciated aspect of infection prevention, especially in the era of emphasizing individual multidrug-resistant organisms. Nonetheless, the importance of aggressive environmental conditioning to reduce the risk of infection is an essential strategy that hospitals must deploy as part of a multi-pronged approach to improving patient safety. A recent study in Infection Control and Hospital Epidemiology highlighted the underlying rationale.

The case-control study, the largest of its kind to date, evaluated over 750,000 inpatient discharges from 2006-2012 to compare individuals who acquired one of several hospital-acquired pathogens to those who did not. Further analysis of the cases assessed the microbiology results of the roommate and the prior patient who occupied the bed of the cases. Controls were matched by hospital (a community hospital, a pediatric hospital, and two tertiary/quaternary-care hospitals were included in the analysis), length of stay, and fiscal quarter of the hospitalization.

Over 10,000 hospital-acquired infections were evaluated in the final, multivariable analysis. Compared to controls, cases were 5.83 times more likely to have been exposed to a prior occupant with the same pathogen, and 4.82 times more likely to have a roommate with the same organism.

The authors should be commended for highlighting challenges at their institutions that are likely present at hospitals throughout the country. Their exceptionally large dataset and standardized interpretation of infection are clear strengths of this study.  Given the study design, unmeasured confounders not included in the analysis remain a limitation, as does a lack of molecular typing to determine the true source of the pathogen. This latter concern may not be relevant from a patient perspective: Patients do not want a hospital-acquired infection from any source, prior occupant, roommate, or other. Hopefully this study will help health care organizations reinforce the importance of good environmental hygiene.

(Cohen at al. Infect Control Hosp Epidemiol. 2018;39(5):541-546.)

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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 1

  • Chimeric Antigen Receptor-Modified T-Cell Therapy and Infection
  • Endocarditis Due to Gram-Negative Bacilli Other Than HACEK

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