Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Investigational drug for resistant TB gets favorable FDA committee vote
An investigational drug to treat highly resistant strains of tuberculosis (TB) took another step in the regulatory approval process yesterday.
According to a news release from TB Alliance, the US Food and Drug Administration (FDA) Antimicrobial Drugs Advisory Committee voted yesterday that there is substantial evidence of the effectiveness and sufficient evidence of the safety of pretomanid as part of a combination treatment for adults with extensively drug-resistant (XDR), multidrug-resistant (MDR), or treatment-intolerant or nonresponsive TB. The oral regimen, known as BPaL, also includes bedaquiline and linezolid.
TB Alliance, which developed pretomanid, submitted a new drug application to the FDA in March and was granted priority review, a designation that speeds up the review process.
The committee's 14-4 vote, which is non-binding but will be taken into consideration by the FDA in its evaluation of the drug, was based on a review of safety and efficacy data from 19 clinical studies. Among those was the phase 3 Nix-TB trial, which tested the regimen in patients with XDR-TB and treatment-intolerant or non-responsive MDR-TB. An interim analysis found a favorable outcome in 90% of patients after 6 months of treatment and 6 months of follow-up.
"We are encouraged by the advisory committee's vote in favor of pretomanid for use in combination with bedaquiline and linezolid for the treatment of highly-resistant forms of TB and we look forward to the FDA's final action," Mel Spigelman, MD, president and CEO of TB Alliance, said in the release.
The FDA is expected to make a final decision on regulatory approval in August.
Jun 6 TB Alliance press release
Scoring system identifies infants at risk of invasive bacterial infections
Originally published by CIDRAP News Jun 6.
A nationwide team of pediatric infectious disease and emergency medicine specialists has developed a new scoring system to identify febrile infants with a low probability of invasive bacterial infection (IBI), according to a paper yesterday in Pediatrics.
The team conducted a case-control study of febrile infants less than 60 days old who presented to 11 US emergency departments (EDs) from July 2011 through June 2016. Infants with IBI, which is defined by growth of a pathogen in blood or cerebrospinal fluid, were matched to two patients at the same hospital who did not have IBI. For each case and control patient, the researchers extracted medical record data on variables that could be associated with the presence of IBI. Using multiple logistics regression, they then identified predictors of IBI and developed a scoring system based on those predictors.
Of the 394 infants with IBI who presented to the 11 EDs over the 5-year study period, 181 met the inclusion criteria and were matched to 362 control patients. Among the 181 infants with IBI, 155 had bacteremia without meningitis and 26 had bacterial meningitis.
Four predictors were associated with the presence of IBI and incorporated into the scoring system: age of less than 21 days (1 point), maximum temperature recorded in the ED 100.4°F to 101.1°F (2 points) or higher than 101.3°F (4 points), abnormal urinalysis results (3 points), and absolute neutrophil count (ANC) of more than 5,185 cells per microliter. Infants with a score of less than 2—fever by history only, normal urinalysis, and an ANC of fewer than 5,185 cells per microliter—were considered a low risk for IBI.
Assessment of the scoring system in the 492 infants with available data found that an IBI score of 2 or higher had a sensitivity of 98.8% (95% confidence interval [CI], 95.7% to 99.9%) and a specificity of 31.3% (95% CI, 26.3% to 36.6%). Moderate-risk score of 3 or higher or 4 or higher had higher specificity (52.0% and 53.7%, respectively) but lower sensitivity (92.9% and 88.2%, respectively). All 26 infants with meningitis had scores of 2 or higher.
The authors of the study say the IBI score could be used to potentially avoid lumbar punctures, some antibiotics, and hospitalization in low-risk infants. But because of the limitations of the case-control design, they say external validation of the scoring system is needed.
Jun 5 Pediatrics abstract
Stewardship survey finds prescribers prefer education over restriction
Originally published by CIDRAP News Jun 6.
A survey of French hospitals indicates French prescribers prefer antibiotic stewardship interventions that aim to improve their ability to make appropriate decisions about antibiotic prescribing over those that challenge their clinical authority, according to a study yesterday in the Journal of Antimicrobial Chemotherapy.
The cross-sectional survey was sent to all prescribers in 27 French hospitals from September 2016 through July 2017. All 27 hospitals had an antibiotic stewardship program (ASP) and an appointed antibiotic advisor (AA). Of the 1,963 questionnaires distributed, 920 (46.9%) were completed; the respondents were mainly attending physicians (71.7%) and medical specialists (61.3%).
The respondents identified two main objectives of their hospital's ASP: to limit the spread of antibiotic resistance in the hospital (77.8%) and to improve the care and prognosis of infected patients (76.1%). But only 36% thought the ASP aimed to prevent resistance in their patients. Most respondents acknowledged an AA's usefulness on therapeutic issues, such as choosing the appropriate antibiotic for a patient (84.7%) and adapting the antibiotic treatment to specific clinical situations (89.6%), but far fewer saw the AA as useful during the diagnostic process (31.4%).
When asked about the usefulness of different ASP interventions, 74% of respondents approved of information sessions for senior physicians, 73% approved of training sessions for residents, and 70% approved of staff meetings to discuss clinical cases. But far fewer approved of automatic stop orders (26.8%), removal of antibiotics from ward stocks (23.4%), or pre-approval from the AA (28.8%).
The authors of the paper conclude that for French ASPs to have a bigger impact on prescribing, they need to move beyond the current approach, where clinicians seek advice when they think they need it and confrontation with non-compliant prescribers is rare. They describe a need for restrictive measures alongside audits and individualized feedback and more educational outreach.
Jun 5 J Antimicrob Chemother abstract
ECDC spotlights NDM-producing CRE outbreak in Tuscany region, Italy
Originally published by CIDRAP News Jun 5.
Since November 2018, hospitals in the Tuscany region of Italy have reported 350 cases of New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE), the European Centre for Disease Prevention and Control (ECDC) reported yesterday in a rapid risk assessment.
"Due to its size and the resulting change in the epidemiology of CRE, the reported outbreak is a significant event, despite previous endemicity of Klebsiella pneumoniae carbapenamase (KPC)-producing CRE in this geographic area," the ECDC said. "The change in the type of carbapenemase further reduces treatment options because NDM-producing CRE are not susceptible to some of the new beta-lactam/beta-lactamase inhibitor combinations such as ceftazidime-avibactam and meropenem-vaborbactam."
The 350 cases were reported by seven Tuscan hospitals from November 2018 through May 2019. Of the infections, 242 are gastrointestinal, 50 bloodstream, 43 urinary tract, and 15 respiratory tract. The isolates are resistant to aminoglycosides but susceptible to fosfomycin and colistin.
The ECDC said that sporadic cases of NDM-producing CRE acquired outside of hospitals have been reported in other European countries, but cases have mostly been tied to healthcare settings. "Therefore, the risk of acquisition of NDM-producing CRE related to this outbreak is likely restricted to persons with recent healthcare," the agency said.
Response steps include further epidemiologic analysis of the cases, assessment of active surveillance for CRE carriage at the hospitals, and a meeting with hospital directors in Tuscany to relay information and reinforce infection control measures.
Jun 4 ECDC rapid risk assessment
Groups urge Wendy's to cut antibiotics from beef supply chain
Originally published by CIDRAP News Jun 4.
A coalition of food safety, health, and consumer groups today urged fast-food giant Wendy's to phase out the use of medically important antibiotics in its beef supply chain.
In a letter delivered at the annual meeting of Wendy's shareholders, the Antibiotics Off the Menu coalition called on the company to adopt a time-bound, verifiable policy for all its US beef suppliers that prohibits routine use of medically important antibiotics in cattle. This kind of commitment, the group writes, "will send a clear signal to meat producers and consumers that preserving the efficacy of these precious medicines is a top priority for Wendy's."
Last year, Wendy's said it would source 20% of its hamburger meat from a group of US producers who've committed to a 20% reduction in the use of the antibiotic tylosin, and would increase that amount over time. But the coalition wants the company to follow the lead of McDonald's, which in December 2018 announced it will work with its beef suppliers in the United States and nine other countries to cut the use of all medically important antibiotics. The policy requires McDonald's to set reduction targets by 2020 and to report progress on meeting those targets by 2022.
According to the most recent report from the FDA, 42% of the medically important antibiotics sold for use in food-producing animals in 2017 were intended for use in cattle.
"We know change is possible—we've seen it happen before when the fast-food restaurant industry took a stand on chicken," Lena Brook, director of food campaigns at the Natural Resources Defense Council (NRDC), said in a press release. "Wendy's has a responsibility to its customers to use its market influence for good, before these lifesaving drugs stop working when sick people and animals need them."
The coalition, which also includes US PIRG, the Center for Food Safety, Food Animal Concerns Trust, Consumer Reports, and the Antibiotic Resistance Action Center, is asking the six largest fast-food companies in the world to reduce medically important antibiotic use in all the meat they serve.
Jun 4 Antibiotics Off the Menu letter to Wendy's
Jun 4 NRDC press release
Tennessee study links infant antibiotic exposure to childhood asthma
Originally published by CIDRAP News Jun 3.
Researchers from Vanderbilt University Medical Center have found a dose-dependent association between infant antibiotic exposure and subsequent development of childhood asthma, according to a new study in Clinical Infectious Diseases.
In a population-based cohort study of 152,622 singleton, term birth, and non–low-birth-weight children born from 1995 through 2003 and enrolled in Tennessee's Medicaid program, 79% had at least one antibiotic prescription filled during their first year of life. Among the children who had at least one antibiotic fill, the median number of fills was four. The prevalence of asthma by age 6 was 14%.
Using multivariable logistic regression models, the researchers found that, compared with children who did not have an antibiotic fill during infancy, children who had at least one fill had nearly double the odds of developing asthma by age 6 (adjusted odds ratio [aOR], 1.88; 95% confidence interval [CI], 1.80 to 1.95). With each additional fill, the odds of having asthma by age 6 increased by 20% (aOR, 1.20; 95% CI, 1.19 to 1.20), and the dose-dependent relationship persisted after additionally controlling for timing and type of antibiotics.
While the study also showed that infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with those who received only narrow-spectrum antibiotics (aOR, 1.10; 95% CI, 1.05 to 1.19), no association was observed between the timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma.
The authors of the study note that they can neither confirm nor refute the causative role of antibiotics in the development of childhood asthma, and that they could not include in their analysis several factors known to be associated with asthma risk, including breastfeeding, exposure to mold or pets, daycare attendance, and other environmental exposures.
They conclude, "In light of the mounting evidence supporting the detrimental effect of infant antibiotic use on childhood asthma, patients and healthcare providers should critically weigh the risks and benefits of antibiotic use in infants before administration, considering possible alternative treatment strategies when available, and the research community should focus on how the adverse effects of antibiotics could be prevented when their use is required."
May 31 Clin Infect Dis abstract
FDA approves combination drug for healthcare-acquired pneumonia
Originally published by CIDRAP News Jun 3.
The FDA today announced the approval of Zerbaxa (ceftolozane and tazobactam) for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).
The approval of the supplemental New Drug Application (NDA) for Zerbaxa, which combines an anti-pseudomonal cephalosporin (ceftolozane) with an extended-spectrum beta-lactamase inhibitor (tazobactam), was based on the results of the phase 3 ASPECT-NP trial. The study found that Zerbaxa was safe and non-inferior to meropenem in 726 adult patients with HABP/VABP, showing similar 28-day mortality rates and cure rates in the intention-to-treat population. The approval was granted to Merck & Co.
Zerbaxa was already approved in the United States for treating complicated urinary tract infections and complicated intra-abdominal infections. The FDA agreed to a priority review of the supplemental NDA in April, citing an unmet need for new treatment options for healthcare-acquired pneumonia.
"Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients," FDA Principal Deputy Commissioner Amy Abernathy, MD, PhD, said in an FDA press release. "New therapies to treat these infections are important to meet patient needs because of increasing antimicrobial resistance."
According to the Centers for Disease Control and Prevention, HABP and VABP are the second most common type of hospital-acquired infection in the United States.
Jun 3 FDA press release
Groups urge passage of NY bill to restrict antibiotic use in farm animals
Originally published by CIDRAP News Jun 3.
A coalition of environmental, health, and consumer groups today called on New York's governor and state legislative leaders to support passage of a bill that would ban the use of antibiotics for disease prevention in food-producing animals.
In a letter to Governor Andrew Cuomo and legislative leaders, the groups cite overuse and misuse of antibiotics in food-animal production as a significant contributor to antibiotic resistance and the emergence of multidrug-resistant organisms that can infect people via food, water, airborne dust, and worker exposure. They argue that, with the lack of action from the federal government, states like New York need to address the issue by limiting antibiotic use in food animals to only when it is medically necessary.
The legislation, introduced by Senator Brian Kavanagh and Assemblywoman Jamie Romeo, would restrict veterinarians to using antibiotics only to treat animals that are sick, in relation to certain medical procedures, or to control outbreaks of disease from contagious animals. Similar legislation has been passed in Maryland and California.
"The overuse and misuse of antibiotics in agriculture is a big contributing factor in a growing public health crisis that needs to be addressed if we are to avoid widespread catastrophic illnesses that people routinely experienced before the development of effective antibiotics," Kavanagh said in press release from New York Public Interest Research Group (NYPIRG), one of the organizations that signed the letter. "We have an opportunity take action now."
Jun 3 NYPIRG press release