Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
FDA approves combo antibiotic for hospital-acquired, ventilator-associated pneumonia
Pharmaceutical company Merck announced today that the Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the antibacterial combination drug Recarbrio to treat adult patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by gram-negative pathogens.
Recarbrio is a combination of the antibiotic imipenem-cilastatin and the beta-lactamase inhibitor relebactam. It was approved by the FDA in July 2019 to treat patients who have complicated urinary tract infections and intra-abdominal infections with no alternative treatment options.
The additional indication in HABP/VABP is based on the results of a phase 3 clinical trial—RESTORE-IMI—that compared outcomes in 535 HABP/VABP patients treated with either 1.25 grams of Recarbrio or 4.5 grams of piperacillin/tazobactam administered intravenously every 6 to 7 hours for 7 to 14 days. Recarbrio met the primary and key secondary endpoints in the trial, showing non-inferiority to piperacillin/tazobactam in 28-day all-cause mortality and clinical response at early follow-up.
"At a time of great public health concern about the need for new treatments to meet the evolving challenges posed by Gram-negative bacteria, we are proud to continue bringing new therapeutic options to health care practitioners in an effort to help them overcome the challenges in patient care,” Nicholas Kartsonis, MD, senior vice president of clinical research, infectious diseases and vaccines at Merck Research Laboratories, said in a company press release.
The company cautions that to reduce the development of antibiotic-resistant bacteria and maintain the effectiveness of the drug, Recarbrio should only be used to treat infections caused by susceptible bacteria.
Jun 5 Merck press release
New global antimicrobial resistance surveillance network launches
The International Society for Infectious Diseases and the Program for Monitoring Emerging Diseases (ProMED) yesterday announced a new global antimicrobial resistance (AMR) surveillance network, according to a ProMED-mail post.
The ProMED-AMR surveillance network will collect new information on antibiotic-resistant pathogens using digital disease detection methods and non-traditional sources, and a global team of AMR experts will vet, analyze, and comment on that information. The network will also produce and disseminate reports on trends, new cases, and clusters of AMR to an international audience in real time.
"The primary goal of ProMED-AMR is to build global public health capacity to rapidly detect and validate the occurrence of antimicrobial resistant pathogens in animals, humans, and the environment to help prevent further AMR expansion," ProMED-mail editor Larry Madoff, MD, said in the post. "ProMED-AMR will engage the international infectious diseases community in a forum for the exchange of ideas, information, and commentary relating to AMR and increase the knowledge base of effective and safe medicines to prevent and treat infectious diseases."
ProMED-AMR will be led by Matt Levison, MD, ProMED associate editor and an infectious disease specialist.
Jun 5 ProMed-mail post
WHO posts plan on drinking water, hygiene, wastewater to curb AMR
Originally published by CIDRAP News Jun 4
The World Health Organization (WHO) this week published a technical brief on water, sanitation, hygiene (WASH), and wastewater management to prevent infections and curb the spread of AMR.
The Global Action Plan to Combat AMR has identified WASH and wastewater management as crucial elements in the battle against AMR spread, but key participants and actions haven't been well represented in stakeholder platforms and national action plans, the WHO said.
The 32-page technical summary was compiled by the WHO, United National (UN) Food and Agriculture Organization (FAO), and World Organization for Animal Health (OIE), all UN agencies. It lays out the evidence and rationale within AMR national action plans and highlights sector-specific policies to fight AMR.
Evidence and suggested actions are grouped under six domains: coordination and leadership, households and communities, healthcare facilities, animal and plant production, manufacturing of antimicrobials, and surveillance and research.
Jun 1 WHO technical brief
US study finds small decline in inappropriate outpatient antibiotics
Originally published by CIDRAP News Jun 3
The proportion of unnecessary antibiotic prescriptions issued by US physicians' offices and emergency departments (EDs) decreased minimally from 2010 through 2015, driven mainly by a decrease in unnecessary prescriptions for children, researchers reported yesterday in Clinical Infectious Diseases.
For the study, researchers from the Centers for Disease Control and Prevention (CDC), the University of Utah, and Boston Children's Hospital used the National Ambulatory Medical Care and National Hospital Ambulatory Medical Care surveys to identify visits to physicians' offices and EDs and antibiotic prescriptions for 2010-11, 2012-13, and 2014-15.
They used a tiered diagnosis system from previous CDC studies to assign a single diagnosis based on the most likely indication for antibiotics, with diagnoses characterized as acute respiratory infections (ARIs) and other conditions. Antibiotic-inappropriate ARIs included asthma, allergy, bronchitis, bronchiolitis, influenza, non-suppurative otitis media, viral upper respiratory infection, and viral pneumonia.
For each period, the researchers calculated the mean annual number of visits and antibiotic prescriptions per 1,000 population. Rates and percentages were calculated overall, for ARIs, antibiotic-inappropriate ARIs, other conditions, and each condition for all ages and by age-group.
They used previous CDC methods to assess the percent of unnecessary antibiotic prescriptions and calculated the mean annual number of unnecessary prescriptions per 1,000 people as the difference between actual and necessary rates.
Overall, there was an 8% decline in antibiotic prescriptions from physicians' offices and EDs from 2010-11 through 2014-15, and a 26% decline in prescriptions for ARIs. The percent of antibiotic-inappropriate visits with antibiotic prescriptions was similar in 2010-11 and 2014-15 overall and in all age-groups.
Thirty percent of antibiotic prescriptions in 2010-11 were unnecessary, compared with 28% in 2014-15. Among children 0 to 19 years of age, unnecessary prescribing declined by 32%, but it did not change among adult age-groups.
"Increased stewardship efforts are needed, especially among clinicians who treat adults, to reach the National Action Plan goal of reducing inappropriate antibiotic prescribing by 50% by 2020," the authors of the study concluded.
Jun 2 Clin Infect Dis abstract
Regulatory period found similar for antimicrobials, non-antimicrobials
Originally published by CIDRAP News Jun 3
An examination of drugs approved by the FDA since 1984 found no evidence that the regulatory approval process for antimicrobials is more time consuming than it is for non-antimicrobials, researchers from Brigham and Women's Hospital and Harvard Medical School reported yesterday in The Lancet Infectious Diseases.
To better understand the array of regulatory pathways the FDA has adopted to expedite the regulatory process for drugs addressing serious unmet needs and how those pathways have impacted drug development and review times, the researchers examined all new drugs and biologics approved by the agency from 1984 through 2018.
They then broke those products down into antimicrobials and non-antimicrobials and recorded each drug's use of the Orphan Drug Act, fast-track, priority review, accelerated approval, and breakthrough therapy programs, as well as dates of investigational new drug application, new drug application, and new drug approval.
The results of the analysis showed that 1,065 new drug products were approved during the study period. Of those, 178 were antimicrobial products, which were more likely than non-antimicrobial products to benefit from priority review (103 [58%] of 178 vs 402 [45%] of 887, P = 0.0023), fast-track designation (58 [37%] of 157 vs 151 [19%] of 814], P < 0.001), and accelerated approval (23 [18%] of 129 vs 67 [9%] of 711, P = 0.0046) and less likely to have Orphan Drug Act designation (25 [14%] of 178 vs 267 [30%] of 887, P < 0.0001).
In addition, median time from investigational new drug application to approval was shorter for antimicrobial than for non-antimicrobial drugs (5.9 years vs 7·6 years, P < 0.001).
"We did not find evidence that antimicrobial development is more time-consuming than non-antimicrobial development or that regulators have been excessively rigid in their approach," the authors wrote.
Jun 2 Lancet Infect Dis abstract
Cefiderocol gets FDA approval for use in nosocomial pneumonia
Originally published by CIDRAP News Jun 2
Drug maker Shionogi & Co. of Osaka, Japan, announced yesterday that the FDA has accepted the company's sNDA and granted Priority Review designation for the use of cefiderocol to treat adults with nosocomial pneumonia.
Cefiderocol, sold under the brand name Fetroja, is a cephalosporin antibiotic with a novel mechanism of penetrating the tough outer membrane of gram-negative bacteria and the ability to overcome resistance mechanisms used by gram-negative pathogens to evade antibiotics. It was approved by the FDA for treatment of complicated urinary tract infections caused by gram-negative pathogens on Nov 12, 2019.
According to a company press release, the sNDA is based on results from a phase 3 study that showed cefiderocol met the primary endpoint of non-inferiority compared with high-dose extended-infusion meropenem in treatment of patients with healthcare-acquired and ventilator-associated pneumonia caused by gram-negative pathogens.
The results showed that 14 days after initiation of treatment, all-cause mortality in the modified intention-to-treat population was 12.4% for cefiderocol (18 of 145 patients) and 11.6% for meropenem (17/146).
The company said cefiderocol also met key secondary endpoints of clinical and microbiologic outcomes at test-of-cure and demonstrated no unexpected safety signals.
"We are committed to working with the FDA in order to bring Fetroja to more patients fighting these challenging and life-threatening Gram-negative infections as quickly as possible," said Akira Kato, PhD, president and CEO at Shionogi Inc., the company's US-based subsidiary.
Jun 1 Shionogi press release
Discharge stewardship linked to better antibiotic prescribing, study finds
Originally published by CIDRAP News Jun 2
Expanding an antimicrobial stewardship program (ASP) to ensure that hospital patients are discharged with appropriate therapy was associated with improvements in appropriate antibiotic prescribing and fewer days of antibiotic therapy at an Ohio hospital, researchers reported today in Infection Control & Hospital Epidemiology.
The study assessed the percentage of patients discharged on appropriate therapy before and after implementation of the discharge stewardship intervention, in which the discharge ASP pharmacist at Northeast Ohio Medical University reviewed patient medical records and anti-infective regimens and provided recommendations on antibiotic therapy to the medical team, if appropriate.
Other outcomes included antimicrobial days of therapy (DOT) and the percentage of readmissions of healthcare visits for treatment failure within 30 days. A total of 122 patients were included in the study, with 61 each in the pre-intervention and post-intervention groups.
Analysis of the two groups found that the percentage of appropriate therapy on discharge was 47.5% before the ASP expansion compared with 85.2% afterward (relative risk [RR], 0.28; 95% confidence interval [CI], 0.147 to 0.538; P < .001). In the post-intervention phase, 48 recommendations were made across 40 patients upon discharge, with an 81% acceptance rate. Recommendations included change in duration (44%), followed by discontinuation (17%), change in dose (14.5%), and change in drug (10%).
The average duration of therapy was 7.8 days in the post-intervention group, compared with 8.9 days in pre-intervention group (P = 0.079). Antimicrobial DOTs were also lower after the intervention than before (555 days vs 626.5 days, respectively). The total 30-day readmission rate was 19.7% in the pre-intervention group versus 11.5% in the post-intervention group (RR, 0.583; 95% CI, 0.246 to 1.38; P = 0.212), a difference not considered statistically significant.
"This project demonstrated that the expansion of an ASP significantly improved the rate of appropriate discharge anti-infective prescribing," the authors of the study write. "A larger patient population is necessary to fully describe the effect on readmissions, adverse events, and treatment failure. Time spent on ASP will also be useful to determine the real-world feasibility of expanding to a larger population."
Jun 2 Infect Control Hosp Epidemiol abstract
WHO touts growth of global antibiotic surveillance system
Originally published by CIDRAP News Jun 1
The WHO said today that a record number of countries are now monitoring and reporting data on antibiotic resistance but warned that the data reveal worrisome trends.
The WHO said its Global Antimicrobial Resistance and Use Surveillance System (GLASS), launched in 2015, now aggregates data from more than 64,000 surveillance sites in 66 countries. In 2018, the number of surveillance sites was 729 from 22 countries. In addition, more countries are reporting on the recently approved indicator on antimicrobial resistance as part of Sustainable Development monitoring.
GLASS data show that resistance to ciprofloxacin, an antibiotic commonly used to treat urinary tract infections, varied from 8.4% to 92.9% in 33 reporting countries.
"As we gather more evidence, we see more clearly and more worryingly how fast we are losing critically important antimicrobial medicines all over the world," Tedros Adhanom Ghebreyesus, PhD, director-general of the WHO, said in a press release. "These data underscore the importance both of protecting the antimicrobials we have and developing new ones, to effectively treat infections, preserve health gains made in the last century and ensure a secure future."
The WHO also expressed concern that antibiotic use in COVID-19 patients could exacerbate resistance trends. But the organization is hopeful that its recent guidance, which recommends against providing antibiotics to patients with mild COVID-19 or those with suspected or confirmed moderate COVID-19 unless there is clinical indication to do so, will help limit unnecessary use.
Jun 1 WHO press release
Data show antibiotic use in UK pigs leveling off after years of decline
Originally published by CIDRAP News Jun 1
New data from the United Kingdom's Agriculture and Horticulture Development Board (AHDB) show that total antibiotic use by UK pig farmers in 2019 was the same as it was in 2018.
The data, obtained from the electronic medicine book (eMB) and representing 95% of pigs slaughtered in the United Kingdom, show that 110 milligrams (mg) of antibiotics per population correction unit (PCU) were used in pigs in 2018 and 2019. From 2015 through 2018, antibiotic use in pigs fell from 278 mg/PCU to 110 mg/PCU, a drop of 60%.
But the use of highest-priority critically important antibiotics—those considered critical for treating bacterial infections in people—continued to fall, declining from 0.06 mg/PCU to 0.04 mg/PCU, and use of the last-resort antibiotic colistin fell from 0.004 mg/PCU to 0.002 mg/PCU.
AHDB officials say the levelling off is likely the result of a spike in swine dysentery cases in 2019. Swine dysentery is a bacterial disease frequently treated with antibiotics.
"It is disappointing that this may have prevented further reduction in our antibiotic use last year," AHDB Acting Head of Animal Health & Welfare, Mandy Nevel, PhD, said in a press release. "However, it is right that we put animal health and welfare first and, having discussed the results with the Pig Veterinary Society (PVS) and the wider industry, we can confirm that the consensus is the industry took the responsible approach and treated animals where necessary."
Jun 1 AHDB press release
