Meropenem-vaborbactam combo may improve symptoms, eradicate causative agent in complicated UTI
Meropenem-vaborbactam may be effective in improving signs and symptoms and eradicating causative pathogens in patients with complicated urinary tract infections (UTIs), the phase III TANGO I* trial showed.
“Among patients with complicated UTI and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion,” said the researchers.
Participants in this multinational trial (60 sites in 17 countries) were 550 adults (mean age 52.8 years, 66.2 percent female) with complicated UTI or acute pyelonephritis, who were randomized to receive meropenem-vaborbactam (2 g/2 g over 3 hours; n=274) or piperacillin-tazobactam (4 g/0.5 g over 30 minutes; n=276) infusions every 8 hours for 10 days.
In patients who met specific improvement criteria following ≥15 doses of intravenous therapy, a switch to oral levofloxacin (500 mg every 24 hours) was allowed to complete the 10-day treatment period (93.6 and 95.1 percent of patients on meropenem-vaborbactam and piperacillin-tazobactam, respectively, switched to levofloxacin).
Of the patients who received study drugs (n=545), 68.6 percent (n=374) had bacterial pathogens of ≥105 colony-forming units (CFU)/mL in urine culture at baseline or the same pathogens in concurrent blood and urine cultures (microbiologic modified intention-to-treat [ITT] population). The most commonly detected pathogens were Escherichia coli (present in 65.1 and 64.3 percent of patients on meropenem-vaborbactam and piperacillin-tazobactam, respectively) and Klebsiella pneumoniae (15.6 and 15.4 percent, respectively).
Meropenem-vaborbactam fared better than piperacillin-tazobactam in terms of a composite of clinical cure or improvement and microbial eradication (98.4 percent vs 94.0 percent, difference, 4.5 percent, 95 percent confidence interval [CI], 0.7–9.1 percent; p<0.001 for noninferiority, p=0.01 for superiority). [JAMA 2018;319:788-799]
Meropenem-vaborbactam was also noninferior to piperacillin-tazobactam in microbial eradication in both the microbiologic modified ITT population (66.7 percent vs 57.7 percent, difference, 9.0 percent, 95 percent CI, -0.9 to 18.7 percent) and microbiologic evaluable population (patients with clinical and microbiologic outcome following intravenous therapy; 66.3 percent vs 60.4 percent, difference, 5.9 percent, 95 percent CI, -4.2 percent to 16.0 percent; p<0.001 for noninferiority for both comparisons).
Adverse event (AE) occurrence was similar between patients on meropenem-vaborbactam and piperacillin-tazobactam (39.0 percent vs 35.5 percent), including severe AEs (2.6 percent vs 4.8 percent), life-threatening AEs (1.1 percent vs 0 percent), and AEs leading to treatment discontinuation (2.6 percent vs 5.1 percent).
“Noninferiority was demonstrated [and superiority observed] for meropenem-vaborbactam compared with piperacillin-tazobactam for … overall success at the end of intravenous treatment in the microbiologic modified ITT population. This finding is notable, given the observed high efficacy of piperacillin-tazobactam,” said the researchers, who called for further studies to identify the population that would acquire the most clinical benefit from the meropenem-vaborbactam combination.