Several years after its FDA approval, this antibiotic continues to prove its efficacy in vitro across various pathogens related to these infections.
Complicated intra-abdominal infections (cIAI) are challenging to treat because of the potential for high morbidity and mortality in these patients.
In addition, there can often be more variability in the number of clinicians involved in care as well as the types of patients who are experiencing these infections. “[cIAI] They are probably a little more heterogenous because the clinical decision-making comes from multiple areas; there are surgeons and there are emergency room physicians [involved],” Tony Hodges, MD, FACP, FCCP, Chief Medical Officer, La Jolla Pharmaceutical Company. “The ages of the patients may range from pediatric to the aged. The comorbidities that align with those age groups are also there and the risk factors for antimicrobial resistance also vary within those cohorts.”
Fortunately, there are treatment options for these infections. One particular antibiotic, eravacylcine (Xerava), which is produced by La Jolla, was FDA approved in August of 2018 for the treatment of cIAI in adults 18 years and older. Eravacycline is a tetracycline-class antibacterial injection that has demonstrated potent activity against multidrug-resistant pathogens. In clinical trials, eravacycline was well tolerated and produced favorable results in curing patients with cIAI and demonstrated non-inferiority to ertapenem and meropenem.
The drug was assessed for cIAI in 2 Phase 3 studies called IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline.) In the first trial, IGNITE1, 541 patients with cIAI were randomized to receive intravenous (IV) treatment with either eravacycline 1.0 mg/kg every 12 hours (n = 270) or ertapenem, 1.0 g every 24 hours (n = 271) for at least 4, 24-hour cycles. The primary endpoint was cure rates after about 1 month. The clinical cure was 86.8% and 87.6% in the eravacycline and ertapenem groups, respectively.
In the second trial, IGNITE4, a total of 499 patients with cIAIs were randomized to IV treatment with eravacycline 1.0 mg/kg twice-daily (n = 250) or meropenem 1 g every 8 hours (n = 249). The clinical cure rates evaluated about 1 month after the start of the treatments were comparable for eravacycline and meropenem whether evaluated according to the criteria set out by the FDA (90.8% vs 91.2%) and EMA (92.4% vs 91.6%).
One of the novel aspects of this therapy is its ability to withstand resistance that other tetracycline-class medications have not, explained Hodges. “It has withstood resistance to primarily historically tetracycline-resistant mechanisms that have degraded or caused resistance with others within the class.”
This is also the biggest takeaway about the therapy in its latest studies.
La Jolla is presenting four posters on eravacycline at the ongoing European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) conference.
In 2 of the posters, In vitro Surveillance of Eravacycline Against Enterobacterales and Non-Fermentor Clinical Isolates, Including Resistant Isolates, Collected in Europe During 2021, and In vitro surveillance of eravacycline against Gram-positive pathogens, including resistant isolates, collected In Europe during 2021, Hodges explains these studies are primarily looking at minimal inhibitory concentration (MIC) with regards to in vitro data.
“What you’ll see is retention or lack of MIC drift over the last 5 to 6 years historically…across intra-abdominal pathogens,” Hodges stated.
Hodges talked with Contagion about these studies, an in-depth discussion on the treatment guidelines and breakpoints related to these infections, and the goal of reaching “target attainment” for better treatment for patients to reduce complications and obtain stewardship.