Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
DOD awards $16 million to fund development of novel antibiotic
The Defense Threat Reduction Agency, a division of the US Department of Defense, has awarded up to $16 million to VenatoRx Pharmaceuticals for discovery and development of a novel, first-in-class antibiotic for biodefense applications.
According to a VenatoRx press release, the project derives from the company's proprietary platform of non-beta-lactam penicillin binding protein inhibitors. Like beta-lactam antibiotics, the molecules block cell wall synthesis by binding to the bacterial penicillin binding proteins, but are designed to be impervious to the beta-lactamase enzymes that prevent beta-lactams from working.
"A non-beta-lactam class of antibiotics would circumvent more than 70 years of clinical bacterial resistance and represents a powerful countermeasure for first line treatment of infections caused by potential drug-resistant bacterial bioweapons, including Burkholderia spp., Yersinia pestis, and Francisella tularensis," Daniel Pevear, PhD, co-founder and senior VP of biology at VenatoRx, said in the press release.
In July 2017, VenatoRx received $3.4 million for development of the platform from CARB-X, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator.
Jan 4 VenatoRx Pharmaceuticals press release
Study provides insight into MRSA transmission in the operating room
Methicillin-resistant Staphylococcus aureus (MRSA) is more transmissible in the operating room than methicillin-sensitive S aureus (MSSA), University of Iowa researchers reported yesterday in the American Journal of Infection Control.
For the study, which aimed to provide further insight into intraoperative MRSA transmission dynamics by examining the association of MRSA with clonal transmission, the researchers collected 173 S aureus isolates from 274 randomly selected operating room environments at three hospitals over a 1-year period (March 2009-February 2010). They then conducted systematic-phenotypic and multilocus sequence typing analysis to identify clonally related transmission events. Confirmed transmission events were defined as at least two S aureus isolates obtained from more than 2 distinct intraoperative reservoirs sampled within or between cases in a study unit that were epidemiologically and clonally related.
The researchers identified 58 clonal transmission events, and approximately 38% of transmitted isolates were methicillin-resistant compared with 18% of non-transmitted isolates. MRSA isolates were associated with increased risk of clonal transmission compared with MSSA isolates (adjusted incidence risk ration [IRR] 1.68; unadjusted IRR 1.85). A typical pathway of intraoperative MRSA transmission involved transmission from patient reservoir skin sites to provider hand and environmental surfaces within and between cases.
The authors say the study suggests that a multimodal infection control program including improvements in hand hygiene, patient decolonization, and environmental cleaning is indicated for maximal reservoir control.
Jan 4 Am J Infect Control study
Real-time C diff notification reduces time to effective therapy, study finds
Originally published by CIDRAP News Jan 4
Implementation of a real-time notification system to alert a pharmacist-led antimicrobial stewardship program (ASP) of Clostridium difficile infection (CDI) in patients reduced the time to effective antimicrobial therapy, a team of pharmacists reported yesterday in the American Journal of Infection Control.
The single-center, retrospective cohort study was conducted at a 433-bed tertiary medical center in Lexington, Kentucky, and consisted of two arms: patients treated for CDI prior to implementation of a real-time notification system for CDI, and those treated post-implementation. The system notified the pharmacist-led ASP team via a secure listserv when toxigenic strains of C difficile were detected in the microbiologic laboratory. The pharmacists then notified the patient's healthcare provider to ensure that effective antimicrobial therapy and contact precautions were initiated.
The primary outcome of the study was time to initiation of effective antimicrobial therapy. Secondary outcomes included time to enter an order of effective antimicrobial therapy in the electronic medical record and time to initiate contact precautions.
The total number of patients in the study was 66: 44 in the pre-implementation cohort and 22 in the post-implementation cohort. Comparison of the two study arms showed that the median time from CDI detection to initiation of effective antimicrobial therapy fell from 5.75 hours in the pre-implementation patients to 2.05 hours post-implementation. The notification system also resulted in a shorter time from CDI detection to order entry of effective antimicrobial therapy—0.6 hours compared with 3 hours. In addition, median time to contact precautions dropped from 4.8 hours to 9 minutes.
The authors of the study say further research is needed to investigate the clinical impact of these outcomes on hospital length-of-stay, mortality, incidence of CDI, and total costs.
Jan 3 Am J Infect Control abstract
Concerns raised about fluoroquinolone use in New Zealand
Originally published by CIDRAP News Jan 3
Scientists in New Zealand are calling for tighter restrictions on the use of fluoroquinolones, according to reporting by the New Zealand Herald.
New Zealand's Pharmaceutical Management Agency, known as Pharmac, has a list of approved conditions that fluoroquinolones should be used for, but the paper reports that documents obtained from each of the country's 20 District Health Boards reveal that in several hospitals, the drugs have been given to patients with conditions other than those specified by Pharmac. In addition, prescriptions for fluoroquinolone eye drops, which are recommended for cornea infections and sometimes used to treat middle ear infections, have increased by more than 300%.
In May 2017, according to the paper, an infectious disease physician and a pharmacist wrote a letter to Pharmac asking the agency for a change in classification that would require physicians to get approval from an infectious disease specialist or microbiologist before using ciprofloxacin. In their letter, they cited the fact that ciprofloxacin use had increased significantly in New Zealand from 2006 to 2014, and during that time resistance to the drug had likewise increased. Pharmac has not yet announced any plans to restrict use of the drug.
Microbiologists are also concerned about potential side effects, such as nerve damage and tendon ruptures. The Herald reports that the New Zealand Centre for Adverse Reaction Monitoring has received 445 reports of suspected negative reactions to fluoroquinolones since 2007, including 64 cases of tendonitis and 24 tendon ruptures.
According to the Best Practice Advocacy Centre for New Zealand, a non-profit that advocates for best practices in healthcare treatments, ciprofloxacin should be reserved for use in acute pyelonephritis, traveler's diarrhea, gonorrhea, severe foodborne disease caused by Campylobacter or Salmonella, bone and joint infections, and invasive Pseudomonas infections—but only when no other options are available.
Jan 3 New Zealand Herald story
FDA to fast-track new drug application for plazomicin
Originally published by CIDRAP News Jan 3
Biopharmaceutical company Achaogen yesterday announced that the US Food and Drug Administration (FDA) will review the company's New Drug Application (NDA) for plazomicin, an antibiotic for the treatment of complicated urinary tract infections (cUTIs) and bloodstream infections caused by multidrug-resistant (MDR) gram-negative pathogens.
According to a company press release, the FDA has given the drug Priority Review designation, a fast-tract review awarded to drugs that would be a significant improvement over current therapy or provide a treatment where none currently exists. The FDA has set a target action date of Jun 25.
Plazomicin was developed to treat serious bacterial infections caused by MDR pathogens, including extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE) and has been evaluated in two phase 3 clinical trials, EPIC and CARE. In the EPIC trial, plazomicin met the objective of non-inferiority compared with meropenem in patients with cUTI and acute pyelonephritis. In the CARE trial, patients with serious CRE infections receiving plazomicin had a lower rate of mortality and serious disease-related complications compared with those given colistin. The drug was well-tolerated in both trials.
"The number of confirmed cases of CRE annually in the U.S. is at least 70,000, and is projected to double by 2022," Blake Wise, Achaogen's Chief Executive Officer, said in the press release. "We are excited about plazomicin's potential to address certain multi-drug resistant gram-negative infections and feel that plazomicin would be a valuable new treatment option for patients with serious bacterial infections, including those due to CRE and ESBL-producing Enterobacteriaceae."
Jan 2 Achaogen press release
Dec 12, 2016, Achaogen press release on phase 3 results
Experts issue call for action on antimicrobial resistance in ICU patients
Originally published by CIDRAP News Jan 2
Intensive care and infectious disease experts from the Antimicrobial Resistance in Critical Care (ANTARCTICA) coalition have released a statement in Intensive Care Medicine calling for increased awareness and action to reduce antimicrobial resistance (AMR) in intensive care units (ICUs).
The statement comes out of discussions held at a 2016 meeting in Milan on AMR in the ICU organized by the European Society of Intensive Care Medicine, the European Society of Clinical Microbiology and Infectious Diseases, and the World Alliance Against Antimicrobial Resistance. Recognizing that ICU patients are particularly at risk of acquiring AMR infections, that action is urgently required, and that multiple aspects of the problem need to be covered, the members of the coalition released a set of recommendations for investigating AMR in critically ill patients and developing guidance for treating these patients, along with priorities for improved management of MDR infections in different domains.
Recommendations from the coalition include committing to making AMR a priority in guideline development and research activities, documenting the global prevalence of gram-negative AMR infection and colonization, developing clinical guidance on specific topics such as antibiotic dosing and duration in the ICU and optimization of empiric treatment, collecting data on treatment and outcomes for extensively- and pan-drug-resistant infections, and assembling a consortium for collaborative research on AMR in the ICU.
Priorities were categorized into four domains (risk stratification, diagnosis, therapy, and prevention) and include identifying MDR pathogen-specific risk factors, developing tools for early diagnosis of sepsis and rapid identification of pathogens and resistance patterns, elucidating the role of combination therapy in MDR infections, and defining optimal use of barrier precautions.
The coalition also proposed a number of immediate interventions that can be taken to reduce AMR in the ICU, including enforcing infection control practices, developing an antimicrobial stewardship team, applying smart antibiotic dosing, and reviewing antibiotics daily.
Dec 29 Intensive Care Med paper
New candidate for multidrug-resistant UTIs shows promise in human trial
Originally published by CIDRAP News Jan 2
Biopharmaceutical company Achaogen today announced positive top-line results from a phase 1 clinical trial of C-Scape, an oral antibacterial candidate being developed for treatment of MDR gram-negative infections.
C-Scape is a combination of two previously approved drugs, the third-generation cephalosporin ceftibuten and the beta-lactamase inhibitor clavulanate. Achaogen is developing the combination therapy as a potential oral treatment for patients who have cUTIs caused by ESBL-producing Enterobacteriaceae, which are often resistant to currently available oral antibiotics and require intravenous carbapenem therapy. In preliminary non-clinical studies, C-Scape showed potent in vitro activity against ESBL-producing Enterobacteriaceae and rapid bactericidal activity.
The phase 1 trial was a double-blind, randomized, placebo-controlled, parallel group study to assess the safety, tolerability, and clinical pharmacology of C-Scape in 41 healthy subjects. According to a company press release, the results showed that the combination of ceftibuten and clavulanate was well tolerated when administered for 14 days and did not demonstrate any drug-drug interactions or serious side effects. The most commonly reported adverse events included vascular access site bruising, headache, diarrhea, gastroenteritis, and nausea.
"The positive top-line results from this first-in-human clinical trial for C-Scape are supportive of further evaluation and we continue to plan for Phase 3 in 2018," Kenneth Hillan, MBChB, Achaogen's president of research and development, said in the press release.
In January 2017 the FDA awarded C-Scape Qualified Infectious Disease Product (QIDP) status for the treatment of cUTI. The QIDP designation, created to provide incentives for new antibiotic treatments, includes priority review and an additional 5 years of marketing exclusivity.
Jan 2 Achaogen press release