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.

• Viral Suppression and Cancer Incidence among HIV-Infected U.S. Veterans
• Can MRSA Nares Screening Results Be Used to Rule Out MRSA Pneumonia?
• Fidaxomicin Provides Effective Prophylaxis Against CDI in Hematopoietic Stem Cell Transplant Recipients

Viral Suppression and Cancer Incidence among HIV-Infected U.S. Veterans

Reviewed by Michael T. Melia, MD

The impact of HIV suppression on incident malignancy is not known for many cancers; prior studies have been limited by relatively few cancer outcomes. A recent analysis in Annals of Internal Medicine sheds further light on this issue.

The authors matched 42,441 HIV-positive persons with 104,712 HIV-uninfected persons from the Veterans Aging Cohort Study (VACS). They cross-referenced this cohort with two Veterans Affairs national cancer databases queried for all cancer types, AIDS-defining cancers (ADC), non-ADC caused by oncogenic viruses (virus NADC), and NADC not caused by oncogenic viruses (nonvirus NADC). They stratified infected patients into those with unsuppressed viral loads, those suppressed for up to two years (early suppression), and those who had been suppressed for more than two years (long-term suppression). They stratified their primary analysis by a number of variables, but not time-updated CD4 count.

When comparing unsuppressed patients to those with early and long-term suppression, there were significant and substantial trends towards lower cancer incidence rates for all cancer types and ADC. A decreasing trend was also seen for virus NADC, although the trend was just barely significant (P = 0.048). While there was no overall trend for nonvirus NADC, there were trends of lower incidence rates for some malignancies, including laryngeal, lung, melanoma skin, and leukemia. Importantly, cancer rate ratios were higher across all four cancer groups for patients with long-term suppression compared with HIV uninfected persons. When stratifying by time-updated CD4 count, there remained a significant trend for decreasing cancer incident ratios for all cancers and ADC; for virus NADC, such a trend was only seen for patients with a CD4 count less than 200 cells/mL.

While further study of the impact of CD4 count on cancer incidence is needed, this impressively large cohort study shows that viral suppression lowers cancer risk for HIV-infected patients, particularly for ADC, to a lesser extent for virus NADC, and perhaps for some nonvirus NADC. Even long-term suppression, however, does not lower cancer risk to that of an HIV-uninfected person.

(Park et al. Ann Intern Med. 2018;169(2):87-96.)

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Can MRSA Nares Screening Results Be Used to Rule Out MRSA Pneumonia?

Reviewed by Jennifer Brown, MD

Current IDSA guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA) coverage for patients with pneumonia who have risk factors for MRSA infection. Yet, timely de-escalation of anti-MRSA antimicrobials is ideal for antimicrobial stewardship. Determining which patients are candidates for de-escalation is challenging.

In the July 1 issue of Clinical Infectious Diseases, researchers described their meta-analysis that evaluated the diagnostic value of MRSA nasal screening in ruling out MRSA pneumonia. Studies that reported both positive rates of MRSA nasal screening (either culture or polymerase chain reaction) and rates of culture-confirmed MRSA pneumonia were included. Those that used only MRSA surveillance cultures from non-nares body sites were excluded.

Twenty-two studies, comprising 5,163 patients, were included in the final analysis. Most (81.8 percent) were retrospective studies and the criteria used to diagnose pneumonia varied. Only 11 (50 percent) studies reported the pneumonia type (e.g., ventilator-associated pneumonia [VAP], healthcare-associated pneumonia [HCAP], community-acquired pneumonia [CAP]). The pooled overall prevalence of MRSA pneumonia was 10 percent and the pooled prevalence of VAP was 8 percent. The sensitivity, specificity, positive predictive value, and negative predictive value of MRSA nares screens to predict MRSA pneumonia were 70.9 percent, 90.3 percent, 44.8 percent, and 96.5 percent, respectively; for CAP/HCAP they were 85.0 percent, 92.1 percent, 56.8 percent, and 98.1 percent, respectively; for VAP they were 40.3 percent, 93.7 percent, 35.7 percent, and 94.8 percent, respectively. The negative likelihood ratio and diagnostic odds ratio were most favorable for patients with CAP/HCAP.

The authors concluded that these high negative predictive values support the use of MRSA nasal screens as a tool to rule out MRSA pneumonia. However, the low prevalence of MRSA pneumonia, the low sensitivity of MRSA screening to predict MRSA pneumonia, and the heterogenicity of included studies are factors that merit consideration for institutions considering this approach.

(Parente et al. Clin Infect Dis. 2018;67(1):1-7.)

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Fidaxomicin Provides Effective Prophylaxis Against CDI in Hematopoietic Stem Cell Transplant Recipients

Reviewed by A. Krishna Rao, MD, MS

Clostridium difficile infection (CDI) is a major burden for the inpatient hematopoietic stem cell transplant (HSCT) population, where incidence is five- to nine-fold higher than in other inpatients. Since CDI has been associated with graft versus host disease and mortality, measures to prevent CDI in this population have been sought. As a narrow-spectrum, non-absorbable antibiotic with bactericidal activity against C. difficile, minimal disruption of the gut microbiome, and inhibition of spore formation, fidaxomicin is a potentially useful agent in CDI prophylaxis.

Mullane et al. conducted a multicenter clinical trial, recently described in Clinical Infectious Diseases, of the efficacy of fidaxomicin for CDI prophylaxis in adults undergoing HSCT. The study design incorporated double-masking, a placebo arm, and randomization stratified by transplant type (autologous/allogeneic). The treatment arm received fidaxomicin 200 mg once daily starting within two days of conditioning or the start of fluoroquinolone prophylaxis (or another treatment antibiotic), whichever came first, and continued fidaxomicin until seven days after engraftment or completion of antibiotics, but no longer than 40 days total. The primary composite endpoint was “prophylaxis failure”: laboratory-confirmed CDI, receipt of CDI treatment, and/or missing assessment of CDI.

The study included 600 patients in the modified intention to treat population. There was no difference in the primary endpoint, but laboratory-confirmed CDI, the pre-specified secondary endpoint, was lower in the treatment arm (4.3 percent versus 10.7 percent, difference of 6.4 percent [2.2 percent, 10.6 percent], P =0.001). Many subjects (75 percent) received antibiotics for treatment beyond routine fluoroquinolone prophylaxis, including ones that predispose to CDI such as carbapenems.

Research on CDI prophylaxis has included infection prevention and antimicrobial stewardship, but efficacy is limited, especially in high-risk groups. Effective pharmaceutical approaches include probiotics, but past clinical trials were not based on pre-clinical data and were thus plagued by significant heterogeneity along with safety concerns over use in the immunosuppressed. Other pharmaceuticals with a potential role in prophylaxis are still years away from approval. Thus, this study’s encouraging findings suggest fidaxomicin is currently the most promising pharmaceutical approach for CDI prophylaxis in HSCT patients. However, the overall cost remains high, likely precluding its cost-effective deployment, even in the high-risk HSCT population. CDI prophylaxis with fidaxomicin may be more practical in markets outside the U.S. or if prices are reduced.

(Mullane et al. Clin Infect Dis. Published online: 9 June 2018.)

Disclosures: Dr. Rao receives grant support from Merck & Company, Inc.

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