ASP Scan (Weekly) for Feb 07, 2020

Sewage-based AMR surveillance
Resistance genes in Chicago waterways
Antibiotic combo for pneumonia
CARB-X funding for rapid diagnostic test
Antibiotic resistomes in the mouth
FDA bacitracin withdrawal request
CRE outbreak in Lithuania
ID consult stewardship

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Paper touts benefits of global sewage-based AMR surveillance

Implementation of a global sewage-based antimicrobial resistance (AMR) surveillance system based on metagenomics sequencing could yield substantial and rapid benefits and be implemented quickly and at minimal expense, according to a paper today in Science.

The paper, written by AMR experts at the Technical University of Denmark and the University of Edinburgh, argues that because current international AMR surveillance systems such as GLASS (the Global Antimicrobial Surveillance System) focus on surveillance of clinical isolates from hospitalized patients and resistance to last-resort antibiotics, they capture only one slice of the global AMR picture. Furthermore, this type of surveillance is based on small samples and is hard to implement in resource-poor settings. 

"This emphasis on clinical settings makes it difficult to determine the global spread of resistance to first-line drugs in the wider community, a large part of the global AMR burden," the authors write.

But global sewage-based surveillance using metagenomics sequencing, which can detect all known resistance genes, could complement clinical surveillance by generating pooled data from a large, non-hospital population that is not routinely assessed by conventional surveillance, the authors suggest. In addition, sewage-based surveillance is easy to implement, can be conducted in low-income settings using inexpensive equipment, and is not restricted to a limited set of bug-drug combinations.

"We therefore consider sewage-based surveillance to be a potentially valuable addition to current options for global AMR surveillance and monitoring," they write. "Though not a substitute for other surveillance methods, it can provide data that is otherwise hard to obtain and may sometimes be the easiest route to providing any information at all, especially in resource-poor settings."

The authors suggest an immediate working model could involve annual collection of sewage samples from across the globe and shipment to a central facility responsible for sequencing, bioinformatics, and reporting.
Feb 7 Science abstract


Study finds Chicago waterways harboring multidrug-resistance genes

Originally published by CIDRAP News Feb 6

A pilot study conducted in Chicago has identified waterways as a potential source of community-acquired multidrug-resistant Enterobacteriaceae (MDR-Ent), researchers reported this week in Antimicrobial Agents and Chemotherapy.

Motivated by research showing a greater risk of community-acquired MDR-Ent infections in children in certain Chicago neighborhoods, mainly those in zip codes in close proximity to area waterways, a team that included researchers from Rush University Medical Center and Virginia Tech evaluated four Chicago waterways for MDR-Ent and associated antibiotic resistance genes (ARGs) using culture-based and cultivation-independent shotgun metagenomic sequencing approaches. Three of the waterways (A1 – A3) are labelled safe for "incidental contact recreation" (fishing and boating) and one (A4) is a non-recreational waterway that carries non-disinfected water.

Analysis of the shotgun metagenomic sequence data revealed the presence of 37 different ARGs derived from Enterobacteriaceae, including those conferring resistance to quinolones, beta-lactamases, polymyxins, and aminoglycosides. The greatest number and highest relative abundances of Ent-associated ARGs was found in samples from A4, and A3—which was in the same area but not hydraulically connected—had a similar ARG profile. Escherichia coli concentrations were also highest in A4 and A3, and the ARGs of clinical concern were most abundant in A4 and A3. Among the ARGs of clinical concern were MCR-1 (which confers resistance to colistin), Qnr and OqxA/B (quinolones), CTX-M and OXA (beta-lactams), and AAC (aminoglycosides).

Fifteen E coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates cultured from A2-A4 samples were found to harbor transmissible ARGs that were also found in clinical isolates from children in the region, and 60% of those isolates were resistant to three or more antibiotic classes.

"These results suggest the potential for mobility of ARGs of clinical concern in waterways located in a high-risk region for MDR-Ent infections in Chicago," the authors of the paper write. "Ent and ARG profiles were consistent with the hypothesized concerns that waterways are a source of community-acquired MDR-Ent."
Feb 3 Antimicrob Agents Chemother abstract


FDA to review drug for hospital-acquired, ventilator-associated pneumonia

Originally published by CIDRAP News Feb 5

The Food and Drug Administration (FDA) has accepted for priority review a supplemental New Drug Application (sNDA) for the antibacterial combination drug Recarbrio to treat adult patients with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by gram-negative pathogens.

Recarbrio, developed and marketed by Merck, is a combination of the antibiotic imipenem-cilastatin and the novel beta-lactamase inhibitor relebactam. It was approved by the FDA in July 2019 to treat patients who have complicated urinary tract infections and complicated intra-abdominal infections and no alternative treatment options. The sNDA is based on the results of a phase 3 clinical trial in adult patients with HABP/VABP.

"This submission reinforces Merck's continued dedication to researching and developing potential antibiotic treatment options which address unmet medical needs," Nicholas Kartsonis, MD, Merck Research Laboratories senior vice president of clinical research in infectious diseases and vaccines, said in a company press release.

The FDA is expected to make a decision on the sNDA by early June.
Feb 3 Merck press release


CARB-X to fund development of rapid diagnostic test

Originally published by CIDRAP News Feb 4

CARB-X today announced an award of up to $6.8 million to Pattern Bioscience of Austin, Texas, to develop a rapid identification and antimicrobial susceptibility test (ID/AST) for drug-resistant pathogens.

According to a press release from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), Pattern's diagnostic test combines single cell analysis with deep learning and aims to provide pathogen identification and susceptibility results within 4 hours.

"Currently, it can take days of laboratory testing to diagnose a lethal bacterial infection," said Erin Duffy, chief of research and development at CARB-X. "Faster ID/AST results, like Pattern's diagnostic, if successful and eventually approved for use in patients, would enable medical staff to treat infections quickly with appropriate antibiotics."

If the project successfully achieves certain development milestones, Pattern will be eligible for up to an additional $15.1 million in funding from CARB-X.
Feb 4 CARB-X press release


Researchers say antibiotic resistance microbiomes of mouth, gut differ

Originally published by CIDRAP News Feb 4

The antimicrobial resistance microbiome (the resistome) in a person's mouth appears to differ from that person's gut resistome, a study today in Nature Communications found.

A resistome is a community of antimicrobial-resistant microbes, including their various resistance genes.

Researchers from King's College London analyzed data on saliva, dental plaque, and other oral microbiomes from 788 people using the Comprehensive Antibiotic Resistance Database (CARD) and compared them with resistomes found in the stomach and intestines. The patients were from Asia, Pacific, European, and US sites.

The investigators found that the mouth harbored unique resistome profiles compared with the gut. And although the antimicrobial resistance genes in the mouth were less diverse, they were more pervasive across the populations studied.

In a King's College news release, study co-author David Moyes asks, "If body sites have different resistomes, can a gut resistome represent the entirety of the human resistome? We must continue analysis of the microbiomes at other body sites to realise the huge potential for unlocking insights from open-source datasets of previously sampled cohorts."
Feb 4 Nat Commun study
Feb 4 King's College London news release 


FDA asks manufacturers to withdraw bacitracin from the market

Originally published by CIDRAP News Feb 3

The FDA has requested that manufacturers of bacitracin for injection voluntarily withdraw their products from the market.

In a statement issued late last week, the FDA said that while bacitracin for injection is approved to treat infants who have pneumonia or empyema caused by Staphylococci bacteria, healthcare providers no longer use it for these conditions because there are other effective, FDA-approved treatments that don't have the same serious risks, which include kidney toxicity and anaphylactic reactions. The move follows an April 2019 meeting of the FDA's Antimicrobial Drugs Advisory Committee that ended with an almost unanimous vote that the drug's risks outweigh its benefits.

"Based on FDA's review of currently available data, FDA believes that the potential problems associated with bacitracin for injection are sufficiently serious to remove the drug from the market," the agency said.

Topical or ophthalmic drugs containing bacitracin are not affected by the voluntary withdrawal request.
Jan 31 FDA statement


CRE outbreak continues in Lithuanian hospitals

Originally published by CIDRAP News Feb 3

The European Centre for Disease Prevention and Control (ECDC) today issued a rapid risk assessment on an ongoing hospital outbreak of K pneumoniae carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (KPC-CRE) in Lithuania.

The ECDC reports that 223 KPC-CRE cases were detected from Feb 1, 2019, to Jan 7, with 208 cases (93.3%) occurring in a single hospital (hospital 1) and five other hospitals affected. The vast majority of the isolates collected from cases were K pneumoniae (199 cases, 89%), followed by E coli (21 cases, 9%). Whole-genome sequencing (WGS) revealed that one major K pneumoniae strain—sequence type (ST) 392—was responsible for the outbreak in hospital 1 and was detected in the other five hospitals.

WGS also revealed that the ST392 outbreak strain carried a plasmid containing the blaKPC-2 carbapenemase gene, which was also found in different K pneumoniae sequence types and in E coli and Citrobacter spp isolates, "thus indicating plasmid-mediated spread of carbapenem resistance in addition to clonal expansion of one single CRE strain," the ECDC said.

Additional resistance to the last-resort antibiotic colistin was detected in half of the 52 KPC-CRE isolates for which colistin susceptibility was performed.

The number of CRE cases reported in the outbreak represents a significant increase for Lithuania, which reported only 5 and 12 cases in 2017 and 2018, respectively. The ECDC warns that the risk of continued spread in the Lithuanian healthcare system is likely to be high, since several patients with the outbreak strain have been transferred from hospital 1 to other hospitals. The risk of transmission for people outside the healthcare system is considered low.
Feb 3 ECDC rapid risk assessment


Stewardship program tied to drop in MRSA rates

Originally published by CIDRAP News Feb 3

After implementation of an antibiotic stewardship program involving an infectious disease consultant at four Japanese hospitals, a new study found that decreasing trends for methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Pseudomonas aeruginosa (DRPA) accelerated after the program was established, with the drop in MRSA rates increasing by 50% to 150%.

The study appeared Jan 31 in the International Journal of Infectious Diseases.

The stewardship program was implemented at one hospital from 2010 through 2013, and the other three from 2014 through 2017. They collected susceptibility data several years before and during the intervention and compared MRSA and DRPA rates with other hospitals throughout Japan.

Both MRSA and DRPA exhibited decreasing trends (P < 0.01 for all four hospitals and all bacterial cultures) throughout the study period, but the decrease was heightened after the intervention was initiated. The sharper decrease occurred for all DRPA regardless of the antibiotic class assessed (eg, carbapenems), and for MRSA the decline was 50% to 150% steeper among the four hospitals.
Jan 31 Int J Infect Dis study

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