rpx7009 and Pyelonephritis

Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis. Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Boronic Acids; Ceftazidime; Drug Combinations; Enterobacteriaceae; Humans; Klebsiella pneumoniae; Meropenem; Pyelonephritis; Thienamycins; Urinary Tract Infections

Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.. To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.. Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.. Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.. Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.. Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.. Among patients with complicated UTI, including acute pyelonephritis 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. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.. clinicaltrials.gov Identifier: NCT02166476.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Pyelonephritis; Thienamycins; Urinary Tract Infections; Urine

The recently approved combination of meropenem and vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Disease Models, Animal; Drug Combinations; Escherichia coli; Humans; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Pyelonephritis; Urinary Tract Infections