FDA Approves New Antibiotic to Treat Three Different Bacterial Infections

On April 3, 2024 FDA approved Zevtera (ceftobiprole medocaril sodium for injection) as a treatment for three types of bacterial infections: adults with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), adults with acute bacterial skin and skin structure infections (ABSSSI), and adult and pediatric patients three months or older with community-acquired bacterial pneumonia (CABP). In addition to the approval, FDA also granted Priority Review and Fast Track and Qualified Infectious Disease Product designations to Zevtera. All trials for Zevtera were randomized, controlled, double-blind, and multinational; the SAB and CABP trials were also multicenter.

In the SAB trial, the measure of efficacy was overall success, defined as survival, symptom improvement, Staphylococcus aureus bloodstream clearance, no new Staphylococcus aureus bacteremia complications, and no use of other antibiotics, at a post-treatment visit 70 days after the patient was given an antibiotic. The study saw that 69.8% of patients who were given Zevtera achieved overall success, as compared to 68.7% of patients who were given the comparator. In the ABSSSI trial, efficacy was measured by early clinical response 48–72 hours after beginning treatment, which required the primary skin lesion to reduce by at least 20% with no other antibacterial treatments or surgery. Of the patients who received Zevtera, 91.3% achieved an early clinical response as compared to 88.1% of those who received the comparator.

The CABP trial measured efficacy with clinical cure rates at a test-of-cure visit, which took place 7–14 days after end of treatment, which lasted three days. Of the patients who received Zevtera, 76.4% achieved clinical cure as compared to 79.3% of patients who received the comparator. Another analysis allowed for an earlier timepoint of clinical success at Day 3 of treatment, which was 71% of patients receiving Zevtera and 71.1% of patients receiving the comparator.

SAB, characterized by the Staphylococcus aureus pathogen, can lead to life-threatening bloodstream infections, such as sepsis and endocarditis. The pathogen is opportunistic and colonizes human anterior nares. This pathogen is also present in ABSSSI, in addition to Streptococcus pyogenes. ABSSSI are common and have symptoms that encompass a wide range of severities; infections are categorized as either complicated or uncomplicated skin and structure infections. In uncomplicated infections, patients can suffer from impetiginous lesions, furuncles, simple abscesses, and cellulitis. Complicated infections can cause infected ulcers, burns, and major abscesses, and often require surgical intervention alongside therapies.

CABP is a series infection and a prevailing cause of hospitalization and mortality. Mild cases can be managed as outpatients, but more severe cases require intensive care unit intervention (1). Staphylococcus aureus is one of the bacterial pathogens that can cause CABP, which can also be contracted via viruses and fungi (2). According to the National Library of Medicine, pneumonia is the eighth leading cause of death, with a mortality rate up to 23% for those with severe pneumonia admitted to the intensive care unit (3).

“The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Zevtera will provide an additional treatment option for a number of serious bacterial infections,” said Peter Kim, M.D., M.S., director of the Division of Anti-Infectives in FDA’s Center for Drug Evaluation and Research, in an FDA press release. “The FDA will continue our important work in this area as part of our efforts to protect the public health.”

Adults with SAB can experience a range of side effects from Zevtera, the most common being fever, vomiting, nausea, diarrhea, increased blood creatinine, high blood pressure, fever, fungal infection, abdominal pain, headache, shortness of breath (dyspnea), low levels of potassium in the blood (hypokalemia), increased levels of some liver tests (hepatic enzymes and bilirubin), and low white blood cell count (leukopenia). The most common side effects for adults with ABSSI include nausea, diarrhea, headache, increased levels of hepatic enzymes, rash, injection side reaction, vomiting, and altered taste (dysgeusia).

For adults with CABP, the most common side effects of Zevtera are increased levels of hepatic enzymes, vomiting, headache, rash, insomnia, nausea, abdominal pain, vein inflammation (phlebitis), high blood pressure, and dizziness. For pediatric patients, the most common side effects are headache, vomiting, diarrhea, infusion site reaction, increased levels of hepatic enzymes, vein inflammation (phlebitis), and fever.

The approval of Zevtera was granted to Basilea Pharmaceutica International Ltd.

References

1. Kwiecinski, J.M.; Horswill, A.R. Staphylococcus Aureus Bloodstream Infections: Pathogenesis and Regulatory Mechanisms. Curr Opin Microbiol. 2020, 53 Feb 51-60. 10.1016/j.mib.2020.02.005.
2. Shah, M.; Shah, H.D. Acute Bacterial Skin and Skin Structure Infections: Current Perspective. Indian J Dermatol. 2011, 56 (5). 10.4103/0019-5154.87134.
3. Regunath, H.; Oba, Y. Community-Acquired Pneumonia. StatPearls online. Jan. 26, 2024.

Source: FDA