October 360: Trending Infectious Disease News of the Month

October was a month full of infectious disease news and updates.

The month started off strong as the editorial team trekked to Washington DC to cover IDWeek 2019. Contagion® spoke with dozens of infectious diseases experts about the ever-changing landscape of the field and meeting highlights.

Some of the biggest news from the meeting included late-breaker oral abstracts on valacyclovir for prevention of fetal cytomegalovirus, all cause-mortality of cefiderocol versus meropenem in patients with nosocomial gram-negative pneumonia, and an oral abstract presentation that explained that antibiotic prophylaxis prior to dental procedures in largely unnecessary and tied to risks.

In a special IDWeek News Network, our staff sat down with George Sakoulas, MD; Joseph Reilly, BS, PharmD, BCGP; and Thomas Lodise, PharmD, PhD, to learn more about the treatment landscape for 2 major topics in infectious diseases, pneumonia and acute bacterial skin and skin structure infections.

In US Food and Drug Administration (FDA) news, F/TAF (Descovy) was approved for pre-exposure prophylaxis in men who have sex with men and transgender women. An extended approval was granted for flu drug baloxavir marboxil (Xofluza) for the treatment of patients at high risk for influenza complications. Just last week delafloxacin (Baxdela) was granted an extended approval for the treatment of community-acquired pneumonia.

An FDA Advisory Committee meeting was held on October 16^th to evaluate cefiderocol. The committee voted 14-2 that substantial evidence of efficacy and safety was provided for the treatment of cUTI in patients with limited or no alternative options. However, many members of the committee expressed concerns about the results of the CREDIBLE-CR study.

The latest issue of Contagion® print was debuted with a feature by Hermione Hurley, MD, MBCHB, and colleagues discussing the rise in infectious diseases that have accompanied the opioid epidemic. Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS, explored addressing misconceptions about antibiotic resistance with patients to provide education about the threat in his Editor-In-Chief letter.

As always, check out the Contagion® Outbreak Monitor to learn more about infectious diseases outbreaks in your area.

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

#5 Valacyclovir Cuts Rate of Fetal Cytomegalovirus Infection by 71%

Congenital cytomegalovirus (CMV) infection can result in brain, liver, spleen, lung, and growth problems and, more commonly, hearing loss in infants. To date, there are no treatments to prevent viral transmission, and the highest risk of fetal injury occurs following a maternal primary infection early in pregnancy.

In a late-breaking presentation at IDWeek 2019, investigators from Israel sought to evaluate the effect of the antiviral drug valacyclovir on the rate of vertical transmission of CMV. Pregnant women with serologic confirmation of primary CMV infection during the periconceptional period and first trimester were included in the randomized, double-blind, placebo-controlled trial.

Participants were randomly assigned to a treatment group of either 8 grams/day of valacyclovir initiated at the time of serological detection and continued until amniocentesis, or placebo. The primary end point—the rate of vertical CMV transmission—was determined by amniotic fluid CMV polymerase chain reaction, and secondary end points were evidence of symptomatic congenital CMV infection, either in utero or postnatally.

Read the full article.

#4 Did the 2016 Fluoroquinolone Boxed Warning Change Outpatient Treatment of Uncomplicated UTIs?

The treatment of urinary tract infections in the outpatient setting represents an area with an opportunity for antimicrobial stewardship efforts. According to the 2010 Infectious Diseases Society of America (IDSA) guidelines, nitrofurantoin, trimethoprim-sulfamethoxazole, and Fosfomycin are recommended first-line antibiotic treatment options for acute uncomplicated cystitis. Although fluoroquinolones are efficacious against common urinary pathogens, they are associated with a “propensity for collateral damage” and consequently should be reserved for patients who are unable to receive treatment with the first-line agents.¹

On May 12, 2016, the US Food and Drug Administration (FDA) issued a safety announcement reinforcing the recommendation to avoid fluoroquinolones in uncomplicated urinary tract infections (uUTI), as well as in acute sinusitis and acute bronchitis. Other treatment options are often available for these uncomplicated infections to avoid the “disabling and potentially permanent serious side effects” of fluoroquinolones on the tendons, muscles, joints, nerves, and central nervous system.² On July 26, 2016, this statement was formally added to the boxed warning on fluoroquinolone drug labelling.³

Read the full article.

#3: What Can the United States Learn from Australia's 2019 Flu Season?

Australia’s influenza season started 2 months earlier and peaked sooner compared to years past, leading health care experts to believe the United States could face an equally tough season.

As of August, 12.5 million flu vaccines were distributed throughout Australia. The death toll down under reached 430, but officials still believe it could rise. That’s more than usual, according to the New York Times. Their reporting concluded 662 individuals died this year from the flu, compared to 745 in 2017, though mortality rates are calculated differently in Australia.

In 2017, Australia had its worst-ever flu outbreak since monitoring and tracking techniques were put in place. Subsequently, one of the worst modern US flu seasons followed, during which an estimated 79,000 people died.

Read the full article.

#2: FDA Advisory Committee Backs Cefiderocol Efficacy for cUTI 14-2

The US Food and Drug Administration convened a meeting of the Antimicrobial Advisory Committee to discuss the new drug application of cefiderocol. The application, submitted by Shionogi Inc., proposes the agent for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis due to gram-negative bacteria in patients with limited or no other alternative treatments.

Cefiderocol is a siderophore cephalosporin. Its mechanism of entry and stability is active against all classes of β-lactamases, which enables it to overcome the primary mechanisms of gram-negative bacterial resistance to βlactam antibiotics.

Cefiderocol was evaluated in 3 studies: a randomized, active controlled noninferiority trial for cUTI which compared cefiderocol to imipenem-cilastatin; a descriptive study (CREDIBLE-CR) which compared cefiderocol to best available therapy in patients with infections due to carbapenem-resistant organisms; and top-line results from a recently completed active-controlled noninferiority trial in hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) (APEKS-NP) comparing cefiderocol to meropenem.

Read the full article.

#1: FDA Approves Descovy for HIV PrEP in MSM, Transgender Women

The US Food and Drug Administration (FDA) has approved emtricitabine 200 mg and tenofovir alafenamide 25 mg (F/TAF; Descovy) for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV infection through sex, excluding those who have receptive vaginal sex. The approval was granted to Gilead Sciences.

F/TAF is not indicated in individuals at risk of HIV infection from receptive vaginal sex because the effectiveness in this population has not been evaluated.

"PrEP drugs are highly effective when taken as indicated in the drug labeling and can prevent HIV infection," said Jeffrey Murray, MD, MPH, deputy director of the Division of Antiviral Products in the FDA's Center for Drug Evaluation and Research in the FDA’s statement. "This approval provides more prevention options for certain patients at-risk for acquiring HIV and helps further efforts by the FDA and the US Department of Health and Human Services to facilitate the development of HIV treatment and prevention options to reduce new HIV infections."

F/TAF was evaluated in a randomized, double-blind multinational trial that included 5387 HIV-negative men and transgender women who have sex with men and were at risk for HIV infection. This trial assessed the safety and efficacy of the product and compared once daily F/TAF to emtricitabine, tenofovir disoproxil fumarate, 200 mg/300 mg (F/TDF; Truvada).

The participants were followed for 48 to 96 weeks. The primary end point was the rate of HIV infection in each group and the trial concluded that F/TAF was similar to F/TDF in reducing the risk of acquiring HIV. The most common adverse reaction in individuals without HIV who were taking F/TAF in the trial was diarrhea.

“What we were able to determine from this study is that Descovy is non-inferior in its efficacy for PrEP compared to Truvada," Brad Hare, chief of infectious disease at Kaiser-Permanente, San Francisco, and lead presenter of the trial data at CROI 2019, told Contagion®. "We also had some pre-specified secondary end points looking at safety parameters, specifically bone and renal safety using these drugs, and we found a significant difference between the arms that favored the Descovy product over Truvada."

Read the full article.