The combo of Cefepime/Enmetazobactam is more effective than Piperacillin/Tazobactam at treating complicated urinary tract infection and acute pyelonephritis
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on October 7th, 2022
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To counter the high rate of resistance against β-lactam class antibiotics, β-lactamase inhibitors are usually used as a complement agent. The piperacillin/tazobactam combination is frequently used to treat serious bacterial infections such as complicated urinary tract infection and pyelonephritis. However, due to possible antibiotic resistance against these medications, new agents should be assessed for their efficacy. A recent study published in the Journal of the American Medical Association had made the comparison between the current standard therapy to the Cefepime/Enmetazobactam combo.
The phase 3 clinical trial included 1,034 adults that had been diagnosed with either complicated urinary tract infection or acute pyelonephritis. Their conditions were caused by gram-negative bacteria, and these patients had ≥105 colony-forming units [CFU]/mL of uropathogens in their urine. The patients were randomly assigned to receive infusions of either an experimental combination of 2.0 g of cefepime and 0.5 g of enmetazobactam or a reference combination of 4.0 g of piperacillin and 0.5 g of tazobactam. The therapy was administered for a minimum of 7 days and a maximum of 14 days.
The study found that both combinations were equally effective at curing the clinical disease. However, the cefepime/enmetazobactam therapy is 21.2% more effective at reducing the uropathogen load to lower than 103 CFU/mL, and 19.0% more effective at eradicating the bacteria by day 14. This indicates that the experimental combination is clinically superior to the piperacillin/tazobactam combination. In terms of safety, the frequency of reported adverse events is similar between the two groups, and most of the side effects are mild: elevated level of liver enzyme (alanine aminotransferase & aspartate aminotransferase) and blood bilirubin. The rate of treatment discontinuation due to adverse events is similar between the two groups.
The phase 3 clinical trial included 1,034 adults that had been diagnosed with either complicated urinary tract infection or acute pyelonephritis. Their conditions were caused by gram-negative bacteria, and these patients had ≥105 colony-forming units [CFU]/mL of uropathogens in their urine. The patients were randomly assigned to receive infusions of either an experimental combination of 2.0 g of cefepime and 0.5 g of enmetazobactam or a reference combination of 4.0 g of piperacillin and 0.5 g of tazobactam. The therapy was administered for a minimum of 7 days and a maximum of 14 days.
The study found that both combinations were equally effective at curing the clinical disease. However, the cefepime/enmetazobactam therapy is 21.2% more effective at reducing the uropathogen load to lower than 103 CFU/mL, and 19.0% more effective at eradicating the bacteria by day 14. This indicates that the experimental combination is clinically superior to the piperacillin/tazobactam combination. In terms of safety, the frequency of reported adverse events is similar between the two groups, and most of the side effects are mild: elevated level of liver enzyme (alanine aminotransferase & aspartate aminotransferase) and blood bilirubin. The rate of treatment discontinuation due to adverse events is similar between the two groups.