Top Infectious Disease News of the Week—Week of April 7, 2019

#5 Future of Fluoroquinolones: Risks, Benefits of Antibiotic Workhorse

In the past decade, fluoroquinolones (FQs) have significantly fallen out of favor as empiric usage for many gram-negative (GN) infections. The US Food and Drug Administration (FDA) has issued statements regarding preferential use of alternative therapy for many common disease states because the risks of adverse effects (AEs) of FQs outweigh the potential benefits. A 21-member FDA advisory panel convened in November 2015 to discuss FQ use for common infectious indications. The overall consensus was to avoid FQs for acute bacterial sinusitis, acute chronic obstructive pulmonary disease exacerbations, and uncomplicated urinary tract infections unless no alternative treatments exist.¹ For these diseases, there are other effective options that are considered safer and to have less propensity for collateral damage.²

Current FDA boxed warnings for the FQ class include myasthenia gravis (MG) exacerbation as well as serious adverse reactions, including effects on the central nervous system (CNS), tendinitis, tendon rupture, and peripheral neuropathy.^1,3

Read about the future of fluoroquinolones.

#4 Four Fungal Horsemen: Emerging Trends in Fungal Disease Epidemiology

According to conventional wisdom, invasive fungal infections affect limited populations. These diseases tend to be cast as medical zebras even among people at greatest risk, including immunosuppressed patients and those residing in specific geographic areas of the United States. However, fungal disease epidemiology is changing. New risk groups have been identified, zoonotic epidemics with human spillover have taken hold, antifungal resistance has emerged, and previously defined endemic zones are expanding. Here we describe 4 of the most clinically consequential examples of emerging fungal infections. This overview does not cover the multidrug-resistant Candida auris because it has been covered extensively elsewhere.¹ Infectious disease specialists have and will continue to act on the front lines as fungal diseases continue to appear in new and curious places.

1. AZOLE-RESISTANT ASPERGILLUS FUMIGATUS

Aspergillus fumigatus is a mold common in the environment, and most people breathe in Aspergillus spores every day without getting sick. It is the most common cause of invasive mold infections in people who are immunocompromised and have lung diseases,^2-4 and mortality from invasive aspergillosis is high (>25%).^2,4-6

Read about emerging trends in fungal disease epidemiology.

#3 NIAID Announces Start of Human Trials for Universal Influenza Vaccine

A phase 1 human clinical trial has begun on an experimental universal flu vaccine developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The new announcement made by NIAID is the latest step toward an influenza vaccine capable of offering broad protection from flu viruses over multiple seasons. A study published in 2018 showed that a universal influenza vaccine candidate elicited strong antibody responses to the hemagglutinin (HA) stalk in mice, and more recently a team of investigators received a NIAID grant to continue developing a microneedle patch capable of delivering a universal flu vaccine candidate.

Current seasonal flu vaccines contain components selected to match circulating influenza viruses A and B and are designed to elicit a response to the head of the HA influenza protein, which is a constantly moving target due to antigenic drift. The new vaccine candidate—known as H1ssF_3928—represents a big step forward in years of research on developing a vaccine that targets a conserved region of the more constant stem of the protein.

Read about the launch a universal flu vaccine trial.

#2 FDA Approves Dolutegravir/Lamivudine for Treatment-Naive Patients With HIV

The US Food and Drug Administration (FDA) has issued an approval for dolutegravir and lamivudine (Dovato), as a complete regimen for treatment-naïve adults with HIV-1.

This marks the first FDA-approved 2-drug, fixed-dose, complete regimen for treatment-naïve adults with HIV, according to the press release.

"Currently, the standard of care for patients who have never been treated is a three-drug regimen. With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug," Debra Birnkrant, MD, director of the Division of Antiviral Products, said in the statement. "Having a drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time."

Read about the approval of dolutegravir/lamivudine.

#1 Receipt of PrEP at Study Enrollment Linked With Increased Incidence of STIs

As pre-exposure prophylaxis (PrEP) is recommended to populations at a higher risk for acquiring HIV, some clinicians have grown concerned that use of PrEP could be associated with an increased incidence of bacterial sexually transmitted infections (STIs).

Now, a new study by a team of Australian investigators published in the Journal of the American Medical Association reports that, among gay and bisexual men, receipt of PrEP during the study was associated with an increased incidence of STIs when compared with before the study period.

The team set out to describe STI incidence as well as behavioral risk factors among gay and bisexual men using PrEP, in addition to exploring changes in STI incidence following initiation of a PrEP regimen.

The research was conducted as part of the Pre-exposure Prophylaxis Expanded (PrEPX) study, which was a multisite, open-label intervention study within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. The study enrolled a total of 4275 participants between July 26, 2017, and April 1, 2018, in Victoria, Australia.

Of the 4275 total participants in PrEPX, 2981 were enrolled into this study across 5 clinics—3 of which were primary care, 1 sexual health, and 1 community-based HIV rapid testing service. Upon enrollment, the participants received daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP, along with quarterly HIV and STI testing and clinical monitoring. Each participant and had at least 1 follow-up visit and was monitored until April 30, 2018.

The median age of the participants was 34 years (interquartile range 28-42) and 98.5% of the study population identified as gay or bisexual males. Additionally, 29% of participants reported used PrEP prior to enrollment and 89 (3%) withdrew and were censored at date of withdrawal; therefore, 2892 (97%) were included at final follow-up.

The primary outcome of the study was incidence of chlamydia, gonorrhea, or syphilis. The investigators note that incidence rates and hazard ratios describing behavior risk factors of STI diagnosis were calculated and that incidence rate ratios (IRRs) were adjusted for change in testing frequency, and described changes in STI incidence from 1-year prior to study enrollment to study follow-up among 1378 participants with pre-enrollment testing data.

Read about STI incidence among gay and bisexual men using PrEP.