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September 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, FIDSA, in each issue of Clinical Infectious Diseases.

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Using Patient Financial Incentives to Improve Linkage to HIV Care and Viral Suppression

Reviewed by Lauren Richey, MD, MPH, FIDSA

The HIV continuum of care includes diagnosis, linkage to care, retention in care, receipt of antiretroviral therapy, and viral suppression. Each of these is needed to improve clinical outcomes and to decrease transmission. The HPTN 065 study, the results of which were recently published in JAMA Internal Medicine, evaluated the use of patient financial incentives to improve linkage and viral suppression.

Thirty-nine clinic sites in the Bronx, N.Y., and Washington, D.C., were randomized to either financial incentives or standard of care. Financial incentives of up to $125 were given for labs and a clinical visit to patients newly diagnosed with HIV or to patients out of care for more than a year. The primary outcome was linkage to care within three months. For patients already engaged in care, a financial incentive of $70 a quarter was offered for viral suppression (400 copies/mL). The primary outcome for this group was the proportion of virally suppressed patients each quarter.

For linkage to care, the standard of care group increased linkage at three months from 73 percent to 83 percent, and the financial incentive group increased from 75 percent to 89 percent, which was not significantly different. For viral suppression, the baseline viral suppression was 62 percent, and the financial incentive group had a 3.8 percent higher proportion of viral suppression than the standard of care group (P = 0.01). This increase was slightly higher among patients not consistently virally suppressed at baseline (4.9 percent).

This study represents the largest to date using financial incentives in HIV care and demonstrates their feasibility in a large scale project that included more than 30 clinics in two different communities. The results were modest but significant for viral suppression. This lack of a robust improvement highlights the complex interplay of patient, community, and system factors that impact linkage and retention in care. Some of these factors are financial, but others are varied. A mixture of additional support services and interventions may be necessary to achieve ideal linkage and viral suppression.

(El-Sadr et al. JAMA Intern Med. 2017;177(8):1083-1092.)

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Is Antibiotic Therapy Really Needed for Acute, Uncomplicated Diverticulitis?

Reviewed by Michael T. Melia, MD

Several studies have suggested that antibiotic therapy does not improve outcomes among patients with acute, uncomplicated diverticulitis. Despite these data, many guidelines recommend antibiotic treatment, and practice remains heterogeneous. Now, a randomized, controlled trial from 22 Dutch centers further argues against routine antibiotic use for this entity.

A recent article in the British Journal of Surgery describes 570 patients enrolled between June 2010 and October 2012 with a first episode of mild, uncomplicated, left-sided, CT-confirmed acute diverticulitis. Patients were randomized to observation or antibiotic therapy with amoxicillin-clavulanic acid (1,200 mg IV every six hours for at least two days, then 625 mg orally three times daily to complete 10 days of treatment). Allergic patients were given ciprofloxacin + metronidazole. The primary outcome was time to recovery during six months of follow-up.

The median time to recovery was 14 days in the observation group and 12 days in the antibiotic group (hazard ratio for full recovery 0.91; P = 0.151). Recovery rates at six months did not differ between groups (89.3 percent in observation group, 93.2 percent in antibiotic group; P = 0.183), and readmission rates were comparable (17.6 percent in observation group, 12.0 percent in antibiotic group; P = 0.148). Among the observation group, more patients were treated on an outpatient basis, and the duration of initial hospitalization was shorter (two versus three days; P = 0.006). Rates of complicated, persistent, or recurrent diverticulitis were comparable between groups, and median abdominal pain scores declined at comparable rates.

This study should cause providers to pause before reflexively prescribing antibiotics for patients with acute, uncomplicated diverticulitis; patients managed with observation did not have more morbid courses, and they spent fewer days in the hospital. Given a lack of inferior outcomes, this study lends further support to supportive care—without broad-spectrum antibiotic therapy—for management of patients with acute, uncomplicated diverticulitis.

(Daniels et al. Br J Surg. 2017;104(1):52-61.)

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MRSA Decolonization in Neonates: Is It Safe?

Reviewed by Terri Stillwell, MD

With the changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) infections, hospitals are turning to different preventative strategies, such as decolonization with mupirocin and/or chlorhexidine, as a means to decrease health care-associated MRSA infections. The use of these agents has raised concerns that this may create a niche for more virulent pathogens. In a recent article in Infection Control and Hospital Epidemiology, the authors assessed whether MRSA decolonization with mupirocin changed the risk of subsequent infections in neonatal intensive care unit (NICU) patients, our most vulnerable population.

In a retrospective, multicenter cohort study, patients from three NICUs with established MRSA decolonization protocols (weekly surveillance screening followed by decolonization with mupirocin) were studied to see if risk of Gram-positive cocci (GPC) and Gram-negative bacilli (GNB) infections varied by exposure to mupirocin. From January 2007 to December 2014, 16,144 neonates were admitted to the study NICUs, 522 (3.2 percent) of which were found to be MRSA-colonized. Of those MRSA-colonized patients, 74 percent underwent decolonization with mupirocin.

During the study period, a total of 37 GPC infections occurred, an incidence rate (IR) of 2.0 per 1,000 patient days. Mupirocin-decolonized patients’ rate of GPC infections was 64 percent lower than those that did not receive mupirocin (1.4 vs. 3.9 infections per 1,000 patient days; P = 0.001). A total of 29 GNB infections occurred, an IR of 1.6 per 1,000 patient days. There was no statistically significant difference in GNB infections between those who had been decolonized with mupirocin and those who had not. Results remained true across various specimen types and pathogens, with Staphylococcus aureus bloodstream infections also lower in those who had received mupirocin decolonization (incidence rate ratio = 0.10, 95 percent confidence interval [CI]: 0.01-0.51).

While additional studies on long term effects of decolonization are still warranted, this study shows that mupirocin-based decolonization decreased risk of GPC infections, without increasing the risk of GNB infections.

(Pierce et al. Infect Control Hosp Epidemiol. 2017;38:930–936.)

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Targeting Travel Clinics to Improve MMR Vaccination Rates: We Must Do Better

Reviewed by Kelly Cawcutt, MD

Measles outbreaks continue to occur in the U.S. with over half of imported measles cases being secondary to unvaccinated U.S. travelers acquiring measles while abroad. Given the high infectivity of measles and high likelihood of transmission to other unvaccinated individuals, assessment of measles, mumps, and rubella (MMR) vaccination during pretravel consultation is prudent.

In a recent observational study of 24 pretravel clinics in the U.S. published in Annals of Internal Medicine, researchers assessed missed opportunities for MMR immunization among departing adult travelers. This study utilized travel clinic sites associated with the Global TravEpiNet consortium which uses structured questionnaires for travelers and providers including measles immunity and immunization history.

Nearly 41,000 adults were included, with 6,612 (16 percent) considered eligible for MMR immunization during their pretravel visit. Fifty-three percent of these were not ultimately vaccinated, due either to traveler refusal (48 percent; the most common reason for refusal was lack of concern for illness), provider decision (28 percent), or health system barrier (24 percent; predominantly the need to travel to a secondary site to receive the vaccine). When reviewed by site type and location, fewer travelers received vaccination if they presented in the South or to a non-academic center.

Based on this study, approximately 1 in 6 adult travelers from the U.S. would be eligible for MMR immunization during their pretravel consultation for both individual and public health benefit. The implications are significant. According to the authors, there are 30 million air travelers from U.S. to international locations per year. If this study is in fact generalizable, nearly 5 million of these travelers may be at risk for measles infection.

There is a clear opportunity to improve assessment and MMR immunization during pretravel consultations through improved awareness, increased provider and patient education regarding risk of measles, and by appropriate stock of the MMR vaccine at travel clinics.

(Hyle et al. Ann Intern Med. 2017;167:77–84.)

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Treating Sepsis with Continuous Beta-Lactam Infusions: Can We Reduce Mortality?

Reviewed by A. Krishna Rao, MD, MS

Sepsis affects 1 million people each year in the U.S. and is associated with significant morbidity and mortality. Advances in therapy have cut the overall mortality risk from 46.9 percent in the early 1990s to 29 percent by 2009. This still high risk for death has prompted exploration of other avenues where incremental improvements can be realized. Beta-lactam antibiotics are frequently used given their wide spectrum of activity. However, the optimal method of drug dosing and administration has not yet been elucidated. Their efficacy is time-dependent, with killing of bacteria occurring when serum/tissue concentrations are greater than the minimum inhibitory concentration. Thus, continuous infusions of beta-lactams have been studied but to-date have not shown a clear benefit.

A meta-analysis published in the American Journal of Respiratory and Critical Care Medicine included three randomized controlled trials that compared continuous infusions of beta-lactam antibiotics to intermittent therapy for severe sepsis. The investigators focused on severe sepsis as they hypothesized a greater benefit in that scenario. The primary endpoints were 30-day in-hospital mortality and clinical cure, as assessed by a blinded clinician. In an unadjusted analysis of continuous infusions, the relative risk (RR) was 0.73 for hospital mortality, which remained significant after adjusting for confounders. There was an improvement in clinical cure (RR 1.32) but this was not significant in the multivariable analysis. However, the high heterogeneity (I2 = 64 percent) for this endpoint and outlier status of one of the included studies likely influenced the results.

While the case is far from closed, this meta-analysis focusing on severe sepsis suggests that continuous beta-lactam infusions deserve further study. Fortunately, it appears that a large, multicenter effort is underway: the BLING III trial. It is anticipated to start by September 2017 and enroll 7,000 patients from 70 intensive care units worldwide. Such knowledge may help further improve outcomes from sepsis.

(Roberts et al. Am J Respir Crit Care Med. 2016;194:681-91.)

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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:

September 1

  • Proton Pump Therapy and Acute Gastroenteritis
  • The Intimate and 2-Way Relationship Between Patient and Hospital Microbiomes
  • Case Vignette: Pseudo-Delusional Parasitosis? Gongylonema Infection

August 15

  • Surviving Sepsis: Early Antibiotics Are the Overwhelmingly Important Key
  • Tenofovir Gel, HIV Prevention, and Pharmacomicrobiomics
  • Case Vignette: Rituximab and Seronegative Encephalitis Due to West Nile Virus

August 1

  • STOP-CHAGAS: Treatment of Indeterminate Chagas Disease
  • Substitution for Vancomycin and Nephrotoxicity

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