August 360: Trending Infectious Disease News of the Month

As the summer season and months of vacation draw to a close, it is important to catch up on the news from August.

Each year August is commemorated as National Immunization Awareness Month. To mark the occasion, we organized a list of essential vaccines by age group, as recommended by the US Centers for Disease Control and Prevention (CDC).

The latest print edition of Contagion® was published earlier this month with an interesting feature written by Lindsay Courtney, PharmD, and Meghan Jeffres, PharmD, BCIDP, on the consequences of avoiding cefazolin. Additionally, in August’s Editor-in-Chief letter, Jason Gallagher, PharmD, tackled the topic of improving outpatient antimicrobial stewardship.

Back on the web, exciting new In the Literature articles addressed the effectiveness of agents for methicillin-sensitive Staphylococcus aureus and the role of gut bacteria in drug metabolism and exposure.

In US Food and Drug Administration news, lefamulin (Xenleta) was approved for community-acquired bacterial pneumonia. Additionally, a 3-drug regimen of pretomanid tablets in combination with bedaquline and linezolid was approved for the treatment of highly resistant tuberculosis. This approval marked only the third new anti-tuberculosis drug to be approved in the last 40 years and the first approved drug that was developed by a non-profit, the TB Alliance.

The editorial staff launched the Contagion® Connect podcast last week. The first episode tackles the topic of pandemic bonds and outbreak response financing, featuring a conversation with Alexandra L. Phelan, SJD, LLM, LLB. Stay tuned for new episodes on exciting infectious disease topics and be sure to subscribe.

A multistate outbreak of Listeria monocytogenes with an unknown cause was announced by the CDC and cases counts in measles and hepatitis A outbreaks continue to climb. August also marked 1 year of the Ebola outbreak in the Democratic Republic of the Congo with 2892 confirmed cases and 1893 confirmed deaths documented as of August 27, 2019. Visit the Contagion® Outbreak Monitor to keep up with the latest numbers.

Let’s take a look at the top 5 web articles from the month of August:

#5: Two Allergies or Cross-Reactive?

The first-generation intravenous cephalo­sporin, cefazolin, is a workhorse in most hospitals. It is the preferred choice for a majority of procedures in the surgical prophylaxis guidelines endorsed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Surgical Infection Society, and the Society for Healthcare Epidemiology of America.¹ Additionally, cefazolin has become a first-line choice for the treatment of methicillin-sensitive Staphylococcus aureus infections.

The results of several studies show that patients treated with cefazolin have lower mortality rates, fewer adverse events, and less allergic reactions compared with the antistaphylococcal penicillins, nafcillin and oxacillin.^2-4 Unfortunately, cefazolin is often avoided in patients with penicillin allergies due to the concern for cross-reactivity between penicillins and cephalosporins. It is our belief that avoidance of cefazolin due to concerns about cross-reactivity results in measurable patient harm and is not supported by published evidence.

Read the full article.

#4: Preclinical Trial of TDF Vaginal Ring for PrEP Ends Early

A preclinical trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring for HIV pre-exposure prophylaxis ended early after 8 of 12 women unexpectedly developed vaginal ulcers.

The National Institutes of Health-funded study, published in The Lancet, included 17 sexually active women, 12 of whom received intravaginal rings with TDF. None of the 5 women in the placebo group experienced vaginal ulcers.

The study came after preclinical macaque models and a small 2-week phase 1 clinical trial in which the vaginal ring was shown to be safe.

“The mechanisms by which the drug ring (and not the placebo ring) led to this unanticipated finding are not yet fully understood,” corresponding author Betsy Herold, MD, director of the Translational Prevention Research Center at Albert Einstein College of Medicine, told Contagion^®. “We did observe increases in inflammatory markers in women using the TDF compared [with] placebo ring by examining, for example, gene expression in biopsy tissue. The findings suggest that sustained levels of intracellular TFV-diphosphate (the active form of the drug in cells) and/or other metabolites released by the TDF but not placebo ring induce inflammation and may disrupt epithelial repair, which in the setting of microabrasions associated with ring use and/or sex, may predispose to ulceration. The ulcers were NOT predicted by the preclinical or earlier 2-week clinical study.”

Read the full article.

#3: FDA Approves Lefamulin for Community-Acquired Bacterial Pneumonia

The US Food and Drug Administration (FDA) has approved lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia (CABP) after results from 2 phase 3 studies showed the novel pleuromutilin antibiotic to be non-inferior to existing treatment options.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease,” said Ed Cox, MD, MPH, director of FDA’s Office of Antimicrobial Products in a statement issued by the FDA. “For managing this serious disease, it is important for physicians and patients to have treatment options. This approval reinforces our ongoing commitment to address treatment of infectious diseases by facilitating the development of new antibiotics.”

In total, the efficacy of lefamulin was evaluated in 1289 patients with CABP. In the LEAP 1 trial, IV to oral lefamulin was found to be non-inferior to IV to oral moxifloxacin with or without linezolid. In LEAP 2, lefamulin again successfully met the FDA primary endpoint of non-inferiority compared with moxifloxacin for early clinical response, which was evaluated in the intent-to-treat patient population 72 to 120 hours after treatment was initiated.

Read the full article.

#2: Florida Declares Public Health Emergency in Response to Hepatitis A Outbreak

Florida Surgeon General Scott Rivkees, MD, has declared a public health emergency in Florida in response to the statewide hepatitis A outbreak.

The Sunshine State has documented 2582 hepatitis A cases between January 1, 2018, and July 27, 2019. According to the Florida Department of Health, 98% of cases in this outbreak have been acquired within the state. Additionally, case counts in 2019 have already surpassed the total number of cases recorded in 2018.

"I am declaring this public health emergency as a proactive step to appropriately alert the public to this serious illness and prevent further spread of hepatitis A in our state," Rivkees said in a press release. "The best way to prevent hepatitis A is through vaccination. It is important that we vaccinate as many high-risk individuals as possible in order to achieve herd immunity.”

Read the full article.

#1: Prime and Pull: An Innovative Approach to HSV-2 Vaccine Development

Efforts to develop a vaccine to prevent herpes simplex virus (HSV) type 2 have had limited success. HSV-2, which causes genital herpes, affects about 400 million people worldwide.

Despite the challenges of vaccine research, a team of investigators from Yale University, the University of Pennsylvania, and University of Cincinnati Children’s Hospital Medical Center conducted a study in an animal model using a new approach—the prime and pull method.

“Prime and pull strategy is a new way of vaccination which relies on 2 steps,” Akiko Iwasaki, Waldermar Von Zedtwitz Professor of Immunobiology at Yale School of Medicine, and co-corresponding author of the study, told Contagion®.“The first step (prime) is to immunize with conventional vaccines through a needle in the arm. The second step (pull), is to apply a cream containing medication that helps attract immune cells, T cells, to the site of virus growth.”

The findings of the guinea pig model were published in the journal npj Vaccines.

After the guinea pigs were vaginally infected with HSV-2, they were subsequently vaccinated with various combinations of glycoproteins and adjuvant with or without subcutaneous or local applications of the cream imiquimod after infection. Throughout the study, the subjects were monitored daily for the presence of recurring lesions and vaginal swabs were collected to measure shedding.

Results indicate that both the vaccine and imiquimod alone reduced recurrent HSV disease, but the combination (prime and pull) was the most effective.

“Immunization with the trivalent vaccine alone or imiquimod alone decreased recurrent disease,” the authors write. “However, the largest decrease was with the combination of vaccine and local imiquimod (P<0.001 vs placebo or vaccine alone).”

Read the full article.