Shiloh
Editor, Senior Moderator
Source: http://www.cidrap.umn.edu/news-perspective/2019/12/stewardship-resistance-scan-dec-12-2019
Stewardship / Resistance Scan for Dec 12, 2019
XDR Klebsiella in Germany; New antibiotic phase 3 failure
Filed Under:
Antimicrobial Stewardship
[h=3]Report details 19-case XDR Klebsiella pneumoniae outbreak in Germany[/h] Additional surveillance following a 17-case outbreak in northeastern Germany of extensively drug-resistant (XDR) Klebsiella pneumoniae has revealed 2 additional cases and details on the XDR strain, according to a study today in Eurosurveillance.
The outbreak was first detailed by the European Centre for Disease Prevention and Control (ECDC) on Oct 28. From June through the end of October, investigators reported 6 infected and 11 colonized patients in four Western Pomerania medical facilities, including a university hospital. The XDR K pneumoniae strain (ST307) produced carbapenemases NDM-1 and OXA-48, and was susceptible only to chloramphenicol, tigecycline, and cefiderocol, according to today's report. The authors also note synergistic activity against the strain for aztreonam combined with ceftazidime-avibactam.
As noted by the ECDC in October, the outbreak strain was similar to a previously reported patient from Finland who was hospitalized in St. Petersburg, Russia, but no epidemiologic links were found to the German outbreak.
The authors write in today's study, "The first case (index patient) presented no typical risk factors for K. pneumoniae infection such as a recent hospital stay or recent travel, and is therefore unlikely to be the primary case that brought the outbreak strain into the university hospital."
The investigators said the outbreak seemed controlled until the last week of October, when a new case was detected through admission screening at the university hospital. The patient had been hospitalized in July and September. A second new case was detected through rectal screening the following week.
The authors conclude, "Clinical and laboratory staff need to increase vigilance in order to improve early detection of XDR outbreaks. Early extensive screening and a high level of isolation precautions are needed to avoid further spread of these pathogens."
Dec 12 Eurosurveillance report
Oct 28 CIDRAP News scan on ECDC report
[h=3]New antibiotic narrowly misses the mark in phase 3 clinical[/h] Drug maker Iterum Therapautics announced this week that its lead antibiotic candidate, sulopenem, narrowly failed to demonstrate non-inferiority to ertapenem in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAIs).
According to a press release from Iterum, of Dublin, Ireland, the primary US Food and Drug Administration (FDA) endpoint in the Sulopenem for Resistant Enterobacteriaceae (SURE) trial was clinical response on day 28 in the microbiologic-modified intent to treat (micro-MITT) population. The trial randomized patients to receive either intravenous (IV) sulopenem followed by oral sulopenem or IV ertapenem followed by oral ciprofloxacin and oral metronidazole (patients with ciprofloxacin-resistant organisms at baseline received amoxicillin-clavulanate).
The difference in outcomes on this population was 4.7% (85.5% for sulopenem vs 90.2% for ertapenem), with a 95% confidence interval of -10.3% to 1.0%. To achieve non-inferiority, however, the lower limit of the difference in the outcome rates had to be greater than -10.0%. The company said the difference in outcomes was one patient shy of the target.
Company officials say that despite the results, they remain hopeful that the drug, which is also being evaluated for treating complicated and uncomplicated urinary tract infections, will ultimately receive FDA approval.
“We believe that these topline results, while narrowly missing the primary endpoint, provide data that emphasize the potential for sulopenem to help address the growing challenge of antibiotic resistance,” said Corey Fishman, CEO of Iterum Therapeutics. “If we obtain positive results in Q1 2020 from our Phase 3 complicated and uncomplicated urinary tract trials, we believe that the overall safety and efficacy results from this cIAI trial would be supportive in an FDA filing for oral and IV sulopenem and that sulopenem’s market potential remains robust.”
Dec 10 Iterum Therapeutics press release
Stewardship / Resistance Scan for Dec 12, 2019
XDR Klebsiella in Germany; New antibiotic phase 3 failure
Filed Under:
Antimicrobial Stewardship
[h=3]Report details 19-case XDR Klebsiella pneumoniae outbreak in Germany[/h] Additional surveillance following a 17-case outbreak in northeastern Germany of extensively drug-resistant (XDR) Klebsiella pneumoniae has revealed 2 additional cases and details on the XDR strain, according to a study today in Eurosurveillance.
The outbreak was first detailed by the European Centre for Disease Prevention and Control (ECDC) on Oct 28. From June through the end of October, investigators reported 6 infected and 11 colonized patients in four Western Pomerania medical facilities, including a university hospital. The XDR K pneumoniae strain (ST307) produced carbapenemases NDM-1 and OXA-48, and was susceptible only to chloramphenicol, tigecycline, and cefiderocol, according to today's report. The authors also note synergistic activity against the strain for aztreonam combined with ceftazidime-avibactam.
As noted by the ECDC in October, the outbreak strain was similar to a previously reported patient from Finland who was hospitalized in St. Petersburg, Russia, but no epidemiologic links were found to the German outbreak.
The authors write in today's study, "The first case (index patient) presented no typical risk factors for K. pneumoniae infection such as a recent hospital stay or recent travel, and is therefore unlikely to be the primary case that brought the outbreak strain into the university hospital."
The investigators said the outbreak seemed controlled until the last week of October, when a new case was detected through admission screening at the university hospital. The patient had been hospitalized in July and September. A second new case was detected through rectal screening the following week.
The authors conclude, "Clinical and laboratory staff need to increase vigilance in order to improve early detection of XDR outbreaks. Early extensive screening and a high level of isolation precautions are needed to avoid further spread of these pathogens."
Dec 12 Eurosurveillance report
Oct 28 CIDRAP News scan on ECDC report
[h=3]New antibiotic narrowly misses the mark in phase 3 clinical[/h] Drug maker Iterum Therapautics announced this week that its lead antibiotic candidate, sulopenem, narrowly failed to demonstrate non-inferiority to ertapenem in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAIs).
According to a press release from Iterum, of Dublin, Ireland, the primary US Food and Drug Administration (FDA) endpoint in the Sulopenem for Resistant Enterobacteriaceae (SURE) trial was clinical response on day 28 in the microbiologic-modified intent to treat (micro-MITT) population. The trial randomized patients to receive either intravenous (IV) sulopenem followed by oral sulopenem or IV ertapenem followed by oral ciprofloxacin and oral metronidazole (patients with ciprofloxacin-resistant organisms at baseline received amoxicillin-clavulanate).
The difference in outcomes on this population was 4.7% (85.5% for sulopenem vs 90.2% for ertapenem), with a 95% confidence interval of -10.3% to 1.0%. To achieve non-inferiority, however, the lower limit of the difference in the outcome rates had to be greater than -10.0%. The company said the difference in outcomes was one patient shy of the target.
Company officials say that despite the results, they remain hopeful that the drug, which is also being evaluated for treating complicated and uncomplicated urinary tract infections, will ultimately receive FDA approval.
“We believe that these topline results, while narrowly missing the primary endpoint, provide data that emphasize the potential for sulopenem to help address the growing challenge of antibiotic resistance,” said Corey Fishman, CEO of Iterum Therapeutics. “If we obtain positive results in Q1 2020 from our Phase 3 complicated and uncomplicated urinary tract trials, we believe that the overall safety and efficacy results from this cIAI trial would be supportive in an FDA filing for oral and IV sulopenem and that sulopenem’s market potential remains robust.”
Dec 10 Iterum Therapeutics press release