Shiloh
Editor, Senior Moderator
Source: http://www.cidrap.umn.edu/news-perspective/2017/03/stewardship-resistance-scan-mar-03-2017
Stewardship / Resistance Scan for Mar 03, 2017
Antibiotic development incentives; De-escalation to ertapenem; NDM-1 in Ethiopia
Filed Under:
Antimicrobial Stewardship; NDM-1
[h=3]GAO urges more FDA guidance on new antibiotic development[/h] A new report from the US Government Accountability Office (GAO) says the Food and Drug Administration (FDA) needs to provide more guidance to drug companies on how to use incentives to develop new antibiotics.
The incentives are part of the 2012 Generating Antibiotic Incentives Now (GAIN) Act, which made new antibiotics eligible for fast-track and priority review status and gave drug companies an extra 5 years of market exclusivity for those antibiotics if they were eligible under the qualified infectious disease products (QIDP) designation. The hope was that these incentives would spur antibiotic development.
So far, the FDA has taken steps to implement the GAIN Act. According to the GAO, the FDA granted 101 of 109 requests for QIDP designation from 2012 through 2015 and approved six drugs with QIDP designation for market in the United States. The agency has also released 14 updated or new guidance documents on antibiotic development and QIDP designation.
But in reviewing the FDA's efforts and in speaking with drug sponsors that have applied for QIDP designation, the GAO also found that half of the agency's updated or new guidance documents are in draft form and may not necessarily reflect scientific developments and the agency's current thinking. Several of the drug sponsors expressed concern over whether they could rely on these documents for guidance and suggested written guidance was needed for the QIDP designation.
"The lack of clarity on the role of draft guidance for and the lack of written guidance on the QIDP designation create uncertainty for drug sponsors about how much reliance they should place on these draft documents and could diminish the likelihood that drug sponsors apply for the designation because they do not fully understand its requirements and benefits," the report states.
The GAO recommends that the FDA clarify how drug sponsors should use draft guidance documents and develop written guidance on the QIDP designation and its incentives.
Mar 2 GAO report
[h=3]Study: De-escalation to ertapenem is safe, effective in ESBL pathogens[/h] A new study indicates ertapenem can be used as a de-escalation therapy for extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, particularly urinary tract and bloodstream infections.
In the randomized controlled trial published in BMC Infectious Diseases, 66 patients being treated at a hospital in Thailand for documented ESBL-producing Enterobacteriaceae infections from 2011 to 2014 were assigned to two groups: A control group of 34 patients who continued receiving standard group 2 carbapenems (imipenem, meropenem, doripenem, and biapenem) as empirical therapy, and an intervention group of 32 patients who were de-escalated to ertapenem, a narrower-spectrum group 1 carbapenem. The patients primarily had urinary tract infections and bacteremia.
The primary outcome was clinical cure rate at end of therapy. Secondary outcomes included microbiological eradication rate, superimposed infection rate during study treatment, 28-day mortality rate, and adverse drug reactions.
By using a 15% predefined margin, ertapenem was considered non-inferior to the control group regarding the clinical cure rate (% change = 14.0) the microbiological eradication rate (% change = 4.1), and the superimposed infection rate (% change = −16.5). Patients in the de-escalation group also had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days vs. 20.0 days P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ? 8.9 vs. 18.4 ? 12.6; P = .05).
"These findings confirm the efficacy of ertapenem and are consistent with the findings previously documented in many observational cohort studies," the authors write, adding that a study in the cost-effectiveness of de-escalation to ertapenem would also be useful.
Mar 1 BMC Infect Dis study
[h=3]NDM-1-producing A baumanni identified in Ethiopia[/h] A new study in BMC Infectious Diseases describes the identification of three Acinetobacter baumanni isolates carrying the carbapenem-resistance gene NDM-1 in Ethiopia. It's the first time organisms carrying the gene have been found in the country.
According to the study, the three A baumanni isolates were among 224 gram-negative isolates obtained from clinical infections and routine clinical specimens at a hospital in Jimma City, Oromiya regional state, between January 2014 and June 2015. Antimicrobial susceptibility testing and molecular characterization revealed that the isolates, which came from three different patients, were meropenem-resistant and NDM-1 positive. Two of the patients survived their infections, and the third died.
Genetic sequencing identified the three isolates' sequence type as ST957, suggesting a different origin from an NDM-1-positive A baumanni strain that had caused an outbreak in Kenya and was, to this point, the only other documented NDM-1-positive A baumanni in East Africa. The authors note that this finding argues against the regional spread of NDM-1-positive organisms and potentially indicates independent import of strains from other regions.
None of the other bacterial isolates analyzed in the study have been found to harbor the NDM-1 gene so far, and attempts to see if the A baumanni isolates could transfer the gene to strains of Escherichia coli were not successful under laboratory conditions. But the authors warn that natural transmission to other bacteria is likely, "given the evident lack of hygienic precautions due to limited resource settings."
"It is further likely, that the detected isolates are solely the tip of the iceberg regarding the presence of NDM-1 producing organisms in the region, as only a limited number of bacterial isolates could be evaluated," the authors write.
Mar 1 BMC Infect Dis study
Stewardship / Resistance Scan for Mar 03, 2017
Antibiotic development incentives; De-escalation to ertapenem; NDM-1 in Ethiopia
Filed Under:
Antimicrobial Stewardship; NDM-1
[h=3]GAO urges more FDA guidance on new antibiotic development[/h] A new report from the US Government Accountability Office (GAO) says the Food and Drug Administration (FDA) needs to provide more guidance to drug companies on how to use incentives to develop new antibiotics.
The incentives are part of the 2012 Generating Antibiotic Incentives Now (GAIN) Act, which made new antibiotics eligible for fast-track and priority review status and gave drug companies an extra 5 years of market exclusivity for those antibiotics if they were eligible under the qualified infectious disease products (QIDP) designation. The hope was that these incentives would spur antibiotic development.
So far, the FDA has taken steps to implement the GAIN Act. According to the GAO, the FDA granted 101 of 109 requests for QIDP designation from 2012 through 2015 and approved six drugs with QIDP designation for market in the United States. The agency has also released 14 updated or new guidance documents on antibiotic development and QIDP designation.
But in reviewing the FDA's efforts and in speaking with drug sponsors that have applied for QIDP designation, the GAO also found that half of the agency's updated or new guidance documents are in draft form and may not necessarily reflect scientific developments and the agency's current thinking. Several of the drug sponsors expressed concern over whether they could rely on these documents for guidance and suggested written guidance was needed for the QIDP designation.
"The lack of clarity on the role of draft guidance for and the lack of written guidance on the QIDP designation create uncertainty for drug sponsors about how much reliance they should place on these draft documents and could diminish the likelihood that drug sponsors apply for the designation because they do not fully understand its requirements and benefits," the report states.
The GAO recommends that the FDA clarify how drug sponsors should use draft guidance documents and develop written guidance on the QIDP designation and its incentives.
Mar 2 GAO report
[h=3]Study: De-escalation to ertapenem is safe, effective in ESBL pathogens[/h] A new study indicates ertapenem can be used as a de-escalation therapy for extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, particularly urinary tract and bloodstream infections.
In the randomized controlled trial published in BMC Infectious Diseases, 66 patients being treated at a hospital in Thailand for documented ESBL-producing Enterobacteriaceae infections from 2011 to 2014 were assigned to two groups: A control group of 34 patients who continued receiving standard group 2 carbapenems (imipenem, meropenem, doripenem, and biapenem) as empirical therapy, and an intervention group of 32 patients who were de-escalated to ertapenem, a narrower-spectrum group 1 carbapenem. The patients primarily had urinary tract infections and bacteremia.
The primary outcome was clinical cure rate at end of therapy. Secondary outcomes included microbiological eradication rate, superimposed infection rate during study treatment, 28-day mortality rate, and adverse drug reactions.
By using a 15% predefined margin, ertapenem was considered non-inferior to the control group regarding the clinical cure rate (% change = 14.0) the microbiological eradication rate (% change = 4.1), and the superimposed infection rate (% change = −16.5). Patients in the de-escalation group also had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days vs. 20.0 days P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ? 8.9 vs. 18.4 ? 12.6; P = .05).
"These findings confirm the efficacy of ertapenem and are consistent with the findings previously documented in many observational cohort studies," the authors write, adding that a study in the cost-effectiveness of de-escalation to ertapenem would also be useful.
Mar 1 BMC Infect Dis study
[h=3]NDM-1-producing A baumanni identified in Ethiopia[/h] A new study in BMC Infectious Diseases describes the identification of three Acinetobacter baumanni isolates carrying the carbapenem-resistance gene NDM-1 in Ethiopia. It's the first time organisms carrying the gene have been found in the country.
According to the study, the three A baumanni isolates were among 224 gram-negative isolates obtained from clinical infections and routine clinical specimens at a hospital in Jimma City, Oromiya regional state, between January 2014 and June 2015. Antimicrobial susceptibility testing and molecular characterization revealed that the isolates, which came from three different patients, were meropenem-resistant and NDM-1 positive. Two of the patients survived their infections, and the third died.
Genetic sequencing identified the three isolates' sequence type as ST957, suggesting a different origin from an NDM-1-positive A baumanni strain that had caused an outbreak in Kenya and was, to this point, the only other documented NDM-1-positive A baumanni in East Africa. The authors note that this finding argues against the regional spread of NDM-1-positive organisms and potentially indicates independent import of strains from other regions.
None of the other bacterial isolates analyzed in the study have been found to harbor the NDM-1 gene so far, and attempts to see if the A baumanni isolates could transfer the gene to strains of Escherichia coli were not successful under laboratory conditions. But the authors warn that natural transmission to other bacteria is likely, "given the evident lack of hygienic precautions due to limited resource settings."
"It is further likely, that the detected isolates are solely the tip of the iceberg regarding the presence of NDM-1 producing organisms in the region, as only a limited number of bacterial isolates could be evaluated," the authors write.
Mar 1 BMC Infect Dis study