Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
GARDP, Bugworks to collaborate on phase 1 trial for new antibiotic
The Global Antibiotic Research and Development Partnership (GARDP) announced yesterday that it is collaborating with Indian biopharmaceutical company Bugworks on a phase 1 clinical trial to assess a new class of antibiotic compounds for multidrug-resistant bacteria.
The first-in-human trials will test the safety and tolerability of BWC0977, a novel antibiotic compound developed by Bugworks to treat patients with serious infections caused by critical-priority pathogens such as carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The compound belongs to a class of chemicals that have displayed evidence of broad-spectrum antibacterial activity, and it is being investigated because of its potential to treat multiple conditions, including bloodstream, urinary, and abdominal tract infections, as well as pneumonia.
"Our ultimate aim is to develop a highly differentiated drug which could be used in all regions of the world that urgently need innovative solutions to tackle drug-resistant superbugs," Bugworks co-founder and CEO Anand Anandkumar, PhD, said in a GARDP press release.
GARDP, which signed a memorandum of understanding with Bugworks in 2020 to accelerate the development and availability of antibiotics, will provide support for an embedded study that will assess the cardiovascular risk of the compound. The phase 1 study is also being supported by CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator).
Jun 9 GARDP press release
PAHO issues alert on extremely drug-resistant Shigella
Originally published by CIDRAP News Jun 9
The Pan American Health Organization (PAHO) this week issued an alert on the potential emergence and spread of extremely drug-resistant (XDR) Shigella sonnei in Latin America and the Caribbean.
Although to date cases of shigellosis caused by S sonnei have been reported only in countries with high surveillance capacity and high water, sanitation, and hygiene standards, the alert notes that cases of gastrointestinal infection caused by XDR S sonnei in men who have sex with men (MSM) have been rising in the United Kingdom and several other European countries. While shigellosis—one of the leading causes of severe infectious disease worldwide—is mainly caused by consumption of contaminated food and water, it can be transmitted through oral and anal sex and is considered a sexually transmitted disease.
Because millions of people in the Americas still lack access to clean drinking water and safe facilities for the disposal and elimination of feces, PAHO is concerned that if XDR S sonnei is introduced into the region in travelers returning from endemic areas, including MSM, there will be an increased risk of a major outbreak of diarrheal diseases that could be lethal in the main risk groups, including children under 5 years.
"Also of concern is the possible contribution of S. sonnei XDR to the spread of antibiotic resistance in the community through horizontal transfer of mobile genetic elements such as plasmids to other bacterial species," PAHO said.
Given this risk, PAHO is recommending that national authorities in the region strengthen surveillance and epidemiologic investigation of XDR S sonnei, strengthen the ability of clinical labs to identify and monitor resistance in S sonnei, continue efforts to provide access to safe water and adequate sanitation, boost infection prevention and control measures in healthcare settings, and work to prevent and minimize sexual transmission of the pathogen.
Jun 6 PAHO epidemiologic alert
Phage therapy shows promise in patients with non-TB Mycobacterium
Originally published by CIDRAP News Jun 9
Compassionate use of bacteriophage therapy in a small cohort of patients with antibiotic-resistant non-tuberculosis Mycobacterium (NTM) infections was well-tolerated and produced favorable responses in more than half, an international team of researchers reported today in Clinical Infectious Diseases.
For the study, a team led by researchers from the University of Pittsburgh and the University of California San Diego screened 200 isolates from patients with antibiotic-refractory NTM infections for susceptibility to bacteriophages. NTM infections, particularly those caused by Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases and have become challenging to treat because of intrinsic antibiotic resistance. Based on two previous case reports of successful compassionate use of bacteriophages in NTM patients, the researcher wanted to further explore the potential.
Screening identified lytic phages for 55 isolates, and 20 patients who met the eligibility criteria were selected to receive personalized adjunctive phage therapy intravenously or by aerosolization. In 11 cases, only a single phage candidate was identified; in others, two or more phages were combined into a cocktail. The patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.
No adverse reactions attributed to therapy were seen in any patient, and favorable clinical or microbiological responses were observed in 11 patients, with infections largely resolved in 5. Some patients, however, saw little clinical benefit. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4, but were not consistently associated with unfavorable responses in others. No phage resistance was observed in any of the 11 patients who received a single phage.
The study authors say further research into optimal routes of administration, dosage, pharmacodynamics, and tissue penetration is needed.
"This series of 20 patients treated with phages on a compassionate-use basis provides support for further evaluation of phages for treatment of mycobacterial infections," they wrote. "Although phage treatment of mycobacterial infections shows promise, this cohort illustrates some key limitations and lessons."
Jun 9 Clin Infect Dis abstract
Gender bias may affect acceptance of antibiotic stewardship efforts
Originally published by CIDRAP News Jun 8
A single-center study suggests gender bias may play a role in whether antibiotic stewardship recommendations by pharmacists are accepted by hospitalists, researchers reported yesterday in Infection Control & Hospital Epidemiology.
To examine the role of gender in acceptance of stewardship recommendations, researchers retrospectively evaluated the effectiveness of the ROAD (Reducing Overuse of Antibiotics at Discharge) Home intervention at an academic medical center in Michigan. The intervention consisted of an antibiotic timeout (a structured conversation to review appropriateness of discharge antibiotics) during pharmacist rounds with hospitalists. The primary outcome of the study was the percentage of recommendations made by pharmacists that were accepted by hospitalists.
During the intervention period (May to October 2019), pharmacists conducted 295 antibiotic timeouts: 158 were conducted by 12 women and 137 were conducted by 8 men. Pharmacists recommended an antibiotic change in 82 timeouts (27.8%), of which 51 (62.2%) were accepted. Compared with male pharmacists, female pharmacists were less likely to recommend a discharge antibiotic change (19.0% vs 38.0%). Female pharmacists were also far less likely to have a recommendation accepted (33.3% vs 78.8%). Thus, timeouts conducted by female versus male pharmacists were less likely to result in an antibiotic change (6.3% vs 29.9%).
After adjusting for patient characteristics, pharmacist gender remained significantly associated with whether recommended changes were accepted (adjusted odds ratio [aOR], 0.10; 95% confidence interval [CI], 0.03 to 0.36 for female versus male pharmacists) and whether the timeout resulted in an antibiotic change (aOR, 0.15; 95% CI, 0.07 to 0.33).
The study authors say that while the findings need to be confirmed in larger studies, the implication that gender bias may play a role in whether physicians accept antibiotic stewardship recommendations could have "profound effects" on whether antibiotic stewardship interventions reach patients and improve their outcomes, and could also affect other pharmacy-led interventions. They also note that women make up 56% of clinical pharmacists, and the number has been growing.
"Given this growth and the importance of pharmacists in areas beyond stewardship (eg, medication reconciliation, transitions of care, patient counselling), there is a critical need to study and mitigate any gender related biases that may exist," they conclude.
Jun 7 Infect Control Hosp Epidemiol study
Electronic algorithms show promise for identifying antibiotic overuse
Originally published by CIDRAP News Jun 7
Electronic algorithms developed by an antibiotic stewardship team at the University of Pennsylvania were highly accurate in detecting inappropriate antibiotic prescribing for bronchitis and pharyngitis, scientists reported yesterday in Open Forum Infectious Diseases.
Using ICD-10 diagnostic codes, the team of clinicians, pharmacists, and researchers identified adult patients in the University of Pennsylvania Health System who were treated for acute bronchitis and pharyngitis from Mar 15, 2017, to Mar 14, 2018. They then randomly selected 300 patients each with bronchitis and pharyngitis—two conditions for which antibiotic prescribing is common and often inappropriate—and compared assessment of antibiotic prescribing based on manual chart review (the gold standard) with the assessment of electronic algorithms constructed for each diagnosis using electronic health record data.
The criteria for appropriate prescribing, choice of antibiotic, and duration were based on established guidelines.
Of 300 subjects with bronchitis, 167 (55.7%) received an antibiotic inappropriately based on manual chart review. The electronic algorithm demonstrated 100% sensitivity and 95.3% specificity for detection of inappropriate prescribing. Of 300 subjects with pharyngitis, 94 (31.3%) had an incorrect prescribing decision. Among 29 subjects with a positive rapid streptococcal antigen test, 27 (93.1%) received an appropriate antibiotic and 29 (100%) received the correct duration. The electronic algorithm also demonstrated very high sensitivity and specificity for all outcomes.
The study authors say the findings highlight the potential for using electronic health records to reduce the workload of antibiotic stewardship programs (ASPs).
"The results suggest our electronic algorithms for these two common outpatient clinical conditions can be used to efficiently and accurately identify instances of inappropriate antibiotic prescribing," they wrote. "These algorithms could provide longitudinal data on patterns of inappropriate antibiotic use and be reported at the level of the health system, the practice, and/or the individual provider to better inform and support ASP targets and initiatives."
Jun 6 Open Forum Infect Dis abstract
Researchers identify colistin-resistant bacteria in Brazilian rivers
Originally published by CIDRAP News Jun 6
A study of samples from two Brazilian rivers found a high incidence of colistin-resistant bacteria and MCR-1 producers, Brazilian and Portuguese researchers reported today in the Journal of Global Antimicrobial Resistance.
The analysis of eight water samples taken along the course of the Sapucai and Sapucaizinho rivers in Sao Paulo found 11 strains of bacteria (8 Escherichia coli, 2 Klebsiella pneumoniae, and 1 K quasipneumoniae) that were resistant to colistin, a last-resort antibiotic for multidrug-resistant (MDR) infections. Whole-genome sequencing revealed that six of the strains were positive for the MCR-1 gene, with four carrying MCR-1.1 and two carrying MCR-1.26. All of the E coli strains and one of the K pneumoniae strains were MDR and carried numerous antimicrobial-resistance mechanisms.
The analysis also identified several E coli sequence types, including the high-risk clones ST10 and ST131-H22, which have been found to cause infections in humans and animals, and revealed that the MCR-1 genes were detected in highly similar IncX4 plasmids—the mobile pieces of DNA that have been associated with the global dissemination of MCR-1 genes in humans and food-producing animals.
The study authors say the findings likely reflect anthropogenic activities nearby and that the presence of high-risk MDR E coli clones at the human-animal-environment interface is of concern because of the risk of human exposure.
Jun 6 J Glob Antimicrob Resist study
