- Recombinant Herpes Zoster Vaccine in Autologous Stem Cell Transplant Recipients
- UTI Treatment in Men: Longer is Not Better
- Can the Government Improve Mortality in Sepsis?
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.
Reviewed by Razan El Ramahi, MBBS
Patients who undergo autologous hematopoietic stem cell transplantation (AHSCT) are at increased risk for herpes zoster (HZ) and are routinely prescribed antiviral prophylaxis following transplantation. HZ can occur despite prophylaxis and is associated with debilitating complications. The prospect of using the recombinant subunit herpes zoster vaccine (rHZV) in AHSCT recipients to protect against HZ is tempting.
The ZOE-HSCT trial, a multi-center, phase III, randomized, observer-blinded, placebo-controlled study reported in JAMA by Bastidas et al., aimed to study the safety and efficacy of rHZV in recipients of AHSCT. Patients were randomized to receive two doses of rHZV or two doses of placebo injections. The first dose was given 50-70 days post transplantation followed by a second dose in 1-2 months. The primary end point was the occurrence of confirmed HZ cases following the second dose. Among the 1,846 randomized participants, 94 percent and 92 percent received a second dose in the vaccine and placebo groups, respectively. Participants were followed for a median of 21 months during which there were 184 confirmed HZ occurrences: 49 in the vaccine and 135 in the placebo groups (incidence 30 and 94 per 1,000 person-years, respectively). Injection site reactions, most commonly pain, occurred at a higher frequency (86 percent) in the vaccine group compared to 10 percent in the placebo group. Serious adverse events and immune-mediated diseases were similar between the two cohorts.
This study concludes that two doses of rHZV shortly after AHSCT were successful in reducing the incidence of confirmed HZ disease and associated complications. The estimated vaccine efficacy was 68.2 percent, which is lower than the 90 percent reported in non-transplant adults aged 50 years or older. Since the median follow-up duration was 21 months, data regarding longer-term vaccine efficacy is unknown and warrants further study, but the results support the use of rHZV to lower HZ incidence in AHSCT patients.
Reviewed by Manie Beheshti, MD
Urinary tract infections (UTIs) in men have classically been considered complicated. With the increasing incidence of UTIs in an aging population during this era of antimicrobial stewardship, a clear understanding of the proper duration of therapy is lacking and has yet to be defined.
A recent study in Open Forum Infectious Diseases assessed the impact of UTI treatment duration in men on UTI recurrence. This cohort study retrospectively evaluated outpatient UTIs in adult men over an almost 5-year span at four outpatient clinics (two family medicine, one internal medicine, and one urology) in Texas. Exclusion criteria included anatomic abnormalities, concomitant non-UTI infections, compromised immune status, extended antibiotic duration over 14 days, and recent surgery within 30 days.
Of 573 unique patients studied, 32 (5.6 percent) had UTI recurrence, all of whom were symptomatic. After multivariate analysis, there was no significant association between treatment duration and UTI recurrence. However, an unexpected finding was that after excluding for complicating factors (such as prostatitis, benign prostatic hyperplasia, pyelonephritis, and nephrolithiasis), the recurrence rate was 2-fold higher in men treated with longer therapy, defined as greater than 7 days.
Although this study has limitations, it adds important data to support a shorter treatment duration (7 or less days) for UTIs in men without complicating factors. In addition to the lower likelihood of resistance, adverse effects, and cost, the increased rate of recurrence in this cohort treated longer than 7 days is a noteworthy signal. Of further interest, this study’s investigators have planned an upcoming randomized, controlled trial comparing 7 versus 14 days of antibiotic treatment for male UTI.
Reviewed by Nirav Patel, MD
Some physicians bristle at governmental intrusion in the delivery of care, especially when mandated and as a result, inflexible to address individual patient care concerns. New York state pioneered a series of regulations in 2013 mandating that all hospitals use protocols for sepsis care delivery, with reporting requirements for protocol adherence and outcomes. In a recent JAMA publication, Kahn and collaborators evaluated the impact of these mandates on 30-day hospital mortality, as well as intensive care unit (ICU) admission rate, hospital length of stay, central venous catheter use, and Clostridioides difficile infection rate.
The investigators compared the outcome measures in the 2 years before implementation of the New York regulations, as well as with four control states (Florida, Maryland, Massachusetts, and New Jersey). Over 1 million admissions for sepsis at over 500 hospitals were evaluated. Unadjusted 30-day mortality was 26.3 percent in New York and 22.0 percent in the control states before regulation and dropped to 22.0 percent in New York and 19.1 percent in the control states. After adjustment, the regulations were associated with a significant decrease in risk of mortality. For example, the last quarter demonstrated a 3.2 percent reduction in absolute mortality compared to expected mortality in New York, with similar decreases consistent across all time periods after regulation adoption. ICU admission rates were unchanged, while hospital length of stay showed a significant decrease as did C. difficile infection rate. On the other hand, there was a significant increase in central venous catheter use.
New York’s initial announcement of progress in 2017 was met with some trepidation in the literature. However, this study suggests a significant association between implementation of care regulations and an absolute reduction in mortality. Despite the retrospective nature of the study, the large number of patient encounters across hundreds of hospitals in multiple states suggests the findings are real and generalizable. Clearly, further analysis of these regulations is needed to understand the impact as well as potential unintended consequences, though ID physicians should be prepared to lead such sepsis management algorithms moving forward.