Enterobacteriaceae are the most common causes of complicated urinary tract infections, and multi-resistance among them is increasing. Therefore new antibiotic substances are being tested. One is the aminoglycoside plazomicin. In the EPIC study, prospective randomized phase 3 study, plazomicin and meropenem were compared with the aim of proving the non-inferiority of plazomicin. Evidence was deemed to have been provided if the difference in effectiveness over the width of the 95% confidence interval was not greater than 15%. The primary endpoints consisted of clinical healing and microbiological eradication on days 5 and 15-19 after the start of therapy (test-of-cure visit).
609 patients with complicated urinary tract infections including acute pyelonephritis participated. 388 were included in the effectiveness analysis. In the plazomicine group, healing on day 5 was achieved in 168 of 191 patients (88.0%) and in the meropenem group in 180 of 197 patients (91.4%). The difference of 3.4 percentage points remained with 95% confidence interval of –3.1 to +10.0% within the margin for the non-inferiority.
In the plazomic group, 81.7% had Cure found compared to 70.1% in the meropenem group. In this primary endpoint, the effect of the aminoglycoside was significantly better than that of the penem. Plazomicin therapy also achieved microbiological eradication more frequently, including that of enterobacteria, which were not sensitive to aminoglycosides (78.8% vs. 68.6%), and of enterobacteria that produced beta-lactamases with broad spectrum (ESBL; 82.4%) vs. 75.0%).
The rate of microbiological recurrences was 3.7% vs. 8.1% in the period 24–32 days after the start of therapy and the rate of clinical relapses 1.6% vs. 7.1%. The only disadvantage was more frequent increase in serum creatinine.
Conclusion: The newly developed aminoglycoside plazomicin is not inferior to meropenem treatment in patients with complicated urinary tract infections and acute pyelonephritis. Rüdiger Meyer
Wagenlehner FME, Cloutier DJ, Komirenko AS, et al .: Once-daily plazomicin for complicated urinary tract infections. .