ALBANY, NY–A next-generation tetracycline, omadacycline could improve care for veterans with community-acquired bacterial pneumonia (CABP) and acute skin and skin structure infections (ABSSSI).

The Food and Drug Administration recently approved the new drug, which has been modified to overcome mechanisms that enable pathogens to resist tetracycline. It also demonstrated efficacy against several common organisms that have developed resistance to other powerful antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae and the gram-negative bacteria Haemophilus influenzae and Escherichia coli.

It also has shown marked effectiveness against atypical pathogens such as Legionella and Mycoplasma, according to the New England Journal of Medicine Journal Watch.1

Omadacycline’s efficacy in resistant infections offers a number of advantages for veterans and other patients, said Thomas Lodise, PharmD, PhD, professor at the Albany College of Medicine and a clinical pharmacy specialist at the Albany Stratton VAMC.

“There are growing concerns about increased resistance with both MRSA and strep. Non-cellulitis ABSSSI and even some cellulitis is assumed to be MRSA until proven otherwise, and most strains of CABP are caused by strep,” Lodise told U.S. Medicine. Even “macrolides can’t be used alone because of high rates of resistance and concerns about quinolones grow by the year.”

In the last six months, both the FDA and the European Medicines Agency have issued new warnings about fluoroquinolone and quinolone antibiotics. The FDA required labeling changes that warn of mental health side effects including disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium as well as an increased risk of hypoglycemic coma. Existing U.S. boxed warnings alerted patients to increased risk of tendinitis and tendon rupture, worsening of myasthenia gravis and potential for irreversible peripheral neuropathy.

The European warnings also cite concerns about depression, sleep disturbance, muscle pain and weakness, impaired vision and hearing and altered sense of taste and smell.

Omadacycline and other tetracyclines are also associated with lower rates of Clostridium difficile infection (CDI). CDI lengthens hospital stays, leads to higher rates of readmission and significantly increases mortality.

C. difficile is a big concern within the VA,” Lodise said, but the “tetracycline class does not disrupt the gut microbiome,” giving omadacycline “one more potential advantage” in regard to these highly problematic infections. An analysis of the phase 3 Omadacycline for Pneumonia Treatment In the Community (OPTIC) study that Lodise co-authored found that no patients treated with omadacycline developed a C. difficile infection compared to 2% of those treated with moxifloxacin. Nearly 400 patients received each of the treatments.2

Reducing C. Difficile Cases

Reducing the number of patients who acquire CDI has a significant impact on costs. Lodise and his colleagues estimated that treating patients with omadacycline instead of moxifloxacin would save $52,000 to $132,884 per 100 patients, depending on the acquisition cost for omadacycline and the incidence of CDI.

The biggest advantage to the new drug, however, is its availability in bioequivalent intravenous (IV) and oral formulations, according to Lodise. An oral-only regimen could enable patients to receive intense outpatient treatment instead of hospitalization for acute skin infections or abscesses. Patients with CABP could start on the IV formulation of omadacycline in the hospital, then switch to the oral version, reducing the hospital length of stay, he said. An oral-only regimen is not approved for CABP.

“For acute skin infections and CABP, hospital stays account for 80% or more of all costs of treatment,” he noted. “If we develop a standard protocol to shift to outpatient setting or reduce the length of stay by one or two days, we can significantly drive down costs,” Lodise explained. “Even if a few patients are readmitted, it would still be cost-effective.”

In another study presented at the American Society of Health-System Pharmacists Midyear Conference in December, Lodise and colleagues found that if the drug’s average daily cost was below $350, it would be cost effective if its use reduced hospital stays by one day. A two-day reduction in length of stay would make omadacycline cost effective up to a price point of $836.3

Omadacycline has just come onto the market in the first quarter of 2019 with a price of $350 per day for commercial payers. As Lodise noted, the “VA always pays less.”

He cautioned that physicians should discuss the unique requirements for taking the novel antibiotic with patients up front. Omadacycline “has strict fasting rules. Taking food will reduce its bioavailability by half, so patients should have no food or multivitamins for four hours before and two hours after” taking the medication. As the four hour fasting before the daily dose is most easily accomplished first thing in the morning, “patients in the VA may have to move other medications until later,” he advised.

In addition, patients should be aware that vomiting and nausea are frequent side effects of the medication.

The CABP trial had a mortality imbalance, 2% among those receiving omadacycline versus 1% for those who received moxifloxacin, Lodise said. While the cause has not been established, he advised that any patient treated for CABP should be closely monitored, especially those with a high mortality risk. He also noted that the ABSSSI trial found the reverse, with more patients dying in the conventional treatment arm than in the omadacycline arm.

1. Sakoulas G. FDA Approves Omadacylcine for CABO and ABSSSI. NEJM Journal Watch. October 31, 2018.

2. LaPensee K, Lodise T, Mistry R, Young K. Cost-saving analysis with use of omadacycline among hospitalized community-acquired pneumonia patients at risk of Clostridium difficile infection being treated with Moxifloxacin: Budge Impact Model Findings, Poster #4-049, ASHP Midyear Conference, December 2-6, 2018; Anaheim, CA.

3. LaPensee K, Lodise T. Cost-saving opportunities among hospitalized community-acquired pneumonia patients treated with omadacycline, an aminomethylcycline antibiotic with IV and oral formulations, compared to ceftriaxone and macrolide therapy. Poster #4-048, ASHP Midyear Conference, December 2-6, 2018; Anaheim, CA.