Marcia Frellick

May 07, 2015

COPENHAGEN, Denmark — Two new antibiotics — the first broad-spectrum fluoroketolide antibiotic and a novel fluorocycline — could provide much-needed alternatives for the treatment of drug-resistant bacteria, according to studies presented here at the 25th European Congress of Clinical Microbiology and Infectious Diseases.

The fluoroketolide and fourth-generation macrolide, solithromycin, is under development by Cempra Pharmaceuticals for the treatment of community-acquired bacterial pneumonia.

And the fluorocycline antibiotic eravacycline, which is a tetracycline derivative, is under development by Tetraphase for the treatment of complicated intra-abdominal infections.

In the phase 3 SOLITAIRE study, solithromycin was as effective as moxifloxacin for the treatment of community-acquired bacterial pneumonia, but the treatment period was shorter (5 vs 7 days).

"We selected moxifloxacin because we wanted to test solithromycin against a very potent antibiotic," said David Oldach, MD, senior vice president of clinical research at Cempra.

SOLITAIRE Study

In the intention-to-treat population of 860 patients from 16 countries, solithromycin was noninferior to moxifloxacin on early clinical response (78.2% vs 77.9%). And in patients 75 years and older, solithromycin was more effective than moxifloxacin (84.0% vs 70.0%).

Adverse effects were comparable in the two groups.

The results mean that for bacterial pneumonia, macrolides alone might be enough in the future. This is good news, said Jorge Vidal, PhD, from Emory University in Atlanta.

"With the current global spread of pneumococcal strains resistant to multiple antibiotics, having a new alternative for patients infected with strains encoding resistance will give them an opportunity to clear the infection before it becomes lethal," he told Medscape Medical News.

In the phase 3 IGNITE1 study, eravacycline was shown to be highly active in vitro against the multidrug-resistant Gram-positive and Gram-negative pathogens that are being encountered at higher rates in intra-abdominal infections.

IGNITE Study

The 541 patients with documented complicated intra-abdominal infections were randomized in a 1:1 ratio to either intravenous eravacycline 1 mg/kg every 12 hours or intravenous ertapenem 1 g daily. Baseline cultures were obtained and treatment lasted no more than 14 days.

The test of cure visit came 1 month after randomization.

Test of cure rates were similar with eravacycline and ertapenem in the microbiologic intent-to-treat analysis of patients with at least one baseline pathogen (86.8% vs 87.6%; 95% confidence interval [CI], –7.1 to 5.5). A 10% noninferiority margin was used in this primary analysis, in accordance with US Food and Drug Administration guidance.

Test of cure rates were also similar with eravacycline and ertapenem in the microbiologic intent-to-treat analysis of patients who received the study drug (87.0% vs 88.8%; 99% CI, –9.2 to 5.6) and in patients with no major protocol deviations (92.9% vs 94.5%; 99% CI, –7.9 to 4.4).

The data support the use of eravacycline for the treatment of intra-abdominal infections, including infections caused by pathogens that are resistant to other antibiotics.

Eravacycline has an advantage in the fight against certain organisms, said Joseph Solomkin, MD, from the University of Cincinnati College of Medicine.

"The problem is with the carbapenem-resistant organisms, primarily Klebsiella and Pseudomonas. The current treatment — colistin or polymyxin B, typically given with high-dose meropenem or tigecycline — is very toxic. Tigecycline is dose-limited because of toxicity," he told Medscape Medical News.

However, "because eravacycline can be dosed at a higher level, it is probable that it would be effective against these organisms. This will require clinical observation," he explained.

Dr Oldach is an employee of Cempra. Dr Vidal reports receiving research funds from Cempra to study the nasopharyngeal pneumobiome. Dr Solomkin has been a consultant for AstraZeneca, Cubist, Tetraphase, Merck, Pfizer, Rempex Medicines Company, and Amicrobe.

25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) Presented April 28, 2015.

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