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ASP Scan (Weekly) for Apr 23, 2021

ASP Scan (Weekly) for Apr 23, 2021

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

Bacterial coinfection common in hospitalized flu patients, study finds

Analysis of a large sample of US inpatients hospitalized with influenza and community-acquired pneumonia (CAP) found that bacterial coinfection occurred in more than 10% of flu patients and that flu patients with bacterial coinfection had worse outcomes, researchers reported today in Infection Control & Hospital Epidemiology.

Because evidence from previous pandemic influenza seasons has shown that bacterial coinfections in hospitalized flu patients are common, guidelines from the Infectious Diseases Society and the American Thoracic Society recommend that inpatients diagnosed with influenza also receive empiric antibiotics. To help guide the choice of empiric antibiotic therapy, researchers from the Cleveland Clinic, Harvard Medical School, and the University of Massachusetts evaluated the frequency of bacterial coinfection and the distribution of bacterial pathogens over time in a national sample of inpatients during nonpandemic years. They also compared outcomes in patients with and without coinfection.

Among 38,665 patients hospitalized with CAP at 179 US hospitals from July 2010 through June 2015, 4,313 (11.2%) tested positive for influenza within 3 days of admission. In the first 3 hospital days, patients who tested positive for influenza were less likely than those who tested negative to have an identified bacterial infection (10.3% vs 16.2%), and the cultures of patients who tested positive for influenza were more likely to contain Staphylococcus aureus (34.2% vs 28.8%) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%). Of the S aureus isolates, the proportion that were methicillin resistant (MRSA) was lower among influenza-positive patients than among influenza-negative patients (42.8% vs 53.2%). After day 3, pathogens for both groups were similar.

Bacterial coinfection in influenza-positive patients was associated with increased odds of in-hospital mortality (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 2.17 to 4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98 to 4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59 to 1.96).

“In conclusion, during nonpandemic years, influenza infection resulting in hospitalization is frequently accompanied by bacterial coinfection,” the study authors wrote. “Treatment with empiric antibiotics, at least for the first 2 days while awaiting maturation of clinical cultures and assessing patient response, is appropriate.”

They add that since most S aureus strains in flu patients were not methicillin-resistant, antibiotic coverage for MRSA is not routinely warranted.
Apr 23 Infect Control Hosp Epidemiol abstract


Risk factors, mechanisms noted in colistin-resistant Enterobacterales

Originally published by CIDRAP News Apr 21

A study of colistin-resistant Enterobacterales (CORE) isolates from patients in southeast Michigan found that increased age and prior antibiotic receipt were associated with increased risk of CORE colonization or infection, researchers reported today in Open Forum Infectious Diseases.

In the study, one of the first to provide large-scale colistin resistance data on clinical Enterobacterales isolates in the United States, researchers with the University of Michigan and Case Western Reserve University examined routine clinical isolates obtained in single tertiary health system in Ann Arbor from January 2016 through March 2017.

Patients with CORE isolates were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) isolates and uninfected control patients, and multivariable logistics regression was used to compare clinical and microbiologic features. The researchers also conducted whole-genome sequencing (WGS) on a subset of CORE isolates.

Of 16,373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. CORE specimens included 45 Enterobacter isolates, 31 Escherichia coli isolates, and 27 Klebsiella pneumoniae isolates. Multivariable analysis of 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls found that antibiotic exposure in the prior 90 days (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.23 to 4.03) and being age 55 and older (OR, 4.06; 95% CI, 2.24 to 7.36) were predictors of CORE. But notably, none of the 103 patients with CORE were exposed to colistin before culture collection. The same factors were also predictors of COSE.

Among the 33 isolates that underwent WGS, several genetic mutations associated with colistin resistance were found; three MCR-1 genes, one MCR-1.1 gene, and four pmrA/B mutations were identified in E coli isolates, and 5 mgrB and pmrA mutations were detected on K pneumoniae isolates. Mechanisms of colistin resistance among Enterobacter isolates could not be determined.

“Further studies are needed to determine the drivers of and determinants of polymyxin resistance among Enterobacterales, including exposure to non-polymyxin antimicrobials,” the authors concluded.
Apr 21 Open Forum Infect Dis abstract


Rapid diagnostic for neonatal sepsis receives CARB-X funding

Originally published by CIDRAP News Apr 20

CARB-X announced today that it is awarding Durham, North Carolina, biotech company Baebies Inc. up to $3.9 million to develop a rapid, easy-to-use diagnostic test for sepsis in newborns.

The diagnostic platform the company is developing uses digital microfluidics technology to test a small blood sample for bacterial infection and return results within 15 minutes. The test will also be able to determine the pathogen causing the infection and its antibiotic susceptibility, and measure host response markers unique to neonatal populations.

The project is currently in the feasibility phase of development, and if it meets project milestones, Baebies will be eligible for an additional $7.7 million from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator).

Sepsis is the body’s overwhelming and often life-threatening response to an infection caused by bacteria. Neonatal sepsis kills up to 1.4 million infants worldwide each year, many in low- and middle-income nations with poor sanitation and limited healthcare resources.

“There is a critical need for a rapid and easy-to-use diagnostic platform for bacteremia—especially for the newborn population given the low circulating blood volume available for testing,” Baebies Inc. co-founder and President Vamsee Pamula, PhD, said in a CARB-X press release. “Through this CARB-X partnership, the development of blood culture and identification of bacteria on our FINDER platform not only enables clinicians to receive results fast, but also conserves the limited blood volume by maximizing the diagnostic yield.”
Apr 20 CARB-X press release


Studies show drop in fluoroquinolone use following FDA warning

Originally published by CIDRAP News Apr 20

Two new studies show that US use of oral fluoroquinolones dropped significantly after the Food and Drug Administration’s (FDA’s) 2016 safety warnings and label change.

Following a review of evidence linking fluoroquinolones to disabling and potentially permanent adverse effects involving tendons, muscles, joints, and the central nervous system, the FDA in May 2016 announced that it would remove indications for oral fluoroquinolones in acute, uncomplicate urinary tract infection (uUTI), acute sinusitis (AS), and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The impact to date of this label change on fluoroquinolone prescribing has been unclear.

To see whether the label change resulted in decreases in oral fluoroquinolone use, researchers from the University of Florida analyzed data from a nationally representative sample of privately insured patients before and after the label change.

In results published yesterday in JAMA Internal Medicine, the researchers found that, prior to the label change, fluoroquinolones were used in 41.6% of uUTI episodes, 31.9% of AE-COPD episodes, and 8.3% AS episodes, and trends in monthly fluoroquinolone prevalence were nearly flat. The month of the label changes (July 2016), they observed an immediate significant reduction for uUTI (-7.2%), and a smaller reduction for AS (-1.2%) and AE-COPD (-2.6%). Monthly declines continued thereafter.

At the end of the study period, fluoroquinolones were used in 19.2% of uUTI episodes, 14.6% of AE-COPD episodes, and 2.9% of AS episodes—pointing to some opportunities for improvement, the researchers concluded.
Apr 19 JAMA Internal Med abstract

In the other study, published yesterday in Antimicrobial Agents and Chemotherapy, researchers with the University of Pittsburgh School of Medicine and the VA Pittsburgh Healthcare System examined national prescription audit databases from August 2014 through February 2020 to explore the same issue.

They found that, from 2015 through 2019, fluoroquinolone fills decreased from 35,616,786 (111.1 per 1,000 persons) to 21,100,050 (64.3/1,000 persons) annually, with an annual decline of 10.8%. Ciprofloxacin, levofloxacin, and moxifloxacin fills fell annually by 10.4%, 11.2%, and 17.7%, respectively. Fills dropped significantly in May 2016 and continued to decrease significantly through June 2018. During the baseline period (August 2014 through April 2016), there was no significant change in monthly fluoroquinolone fills.

“Taken together, our data demonstrate national progress toward achieving stewardship goals for outpatient fluoroquinolones, and attest to the impact of FDA safety warnings in limiting use of these drugs,” the authors wrote.
Apr 19 Antimicrob Agents Chemother abstract


CARB-X to fund development of bacteriophage-based drug

Originally published by CIDRAP News Apr 19

CARB-X announced today that it is awarding Phico Therapeutics of Cambridge, United Kingdom, up to $5.3 million to develop an intravenous bacteriophage drug to treat ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

The award will support development of Phico’s SASPject PT 3.9 project, which combines engineered bacteriophages with antibacterial small acid-soluble spore proteins (SASPs) to target and inactivate P aeruginosa bacteria. Phico says SASPs are unaffected by the sequence of bacterial DNA, which makes it unlikely that bacteria could develop resistance.

The project will be eligible for an additional $12.86 million in funding from CARB-X if the project progresses successfully to phase 1 clinical trials.

“This approach has the potential to target the bacteria without damaging other cells or contributing to the rise of resistance,” CARB-X Research and Development Chief Erin Duffy, PhD, said in a CARB-X press release. “If successful, this new intravenous drug could transform the way patients with ventilator-associated pneumonia are treated in hospitals, and save lives.”

The Centers for Disease Control and Prevention estimates there were 32,600 multidrug-resistant P aeruginosa infections and 2,700 deaths in US hospitals in 2017.
Apr 19 CARB-X press release


Review finds increased MRSA risk from dog ownership

Originally published by CIDRAP News Apr 19

A review and meta-analysis of previously published studies has identified dog ownership as a risk factor for methicillin-resistant S aureus (MRSA) colonization, German researchers reported last week in the Journal of Antimicrobial Chemotherapy.

To get a better understanding of the risk for multidrug-resistant organism (MDROs) colonization posed by pet ownership, the researchers conducted three separate reviews and meta-analyses of literature on pet ownership and MRSA, third-generation cephalosporin-resistant Enterobacterales (3GCRE) and carbapenem-resistant Enterobacterales (CRE), and vancomycin-resistant Enterococcus (VRE). The primary outcome was the relative risk of carrying an MDRO in humans with pet contact (including dogs, cats, rodents, birds, and reptiles) compared with those without pet contact.

The researchers calculated an increased risk of MRSA carriage for dog owners, with a risk ratio (RR) of 2.28 (95% confidence interval [CI], 1.47 to 3.56), but not for other pet owners. The meta-analysis for 3GCRE/CRE did not show a significantly higher risk for colonization among pet owners compared with non-pet owners, with an RR of 1.18 (95% CI, 0.83 to 1.68) for pet owners in general. For VRE, there were insufficient data to perform a meta-analysis.

The study authors say the MRSA risk among dog owners is higher than found in literature reviews and, because of limitations concerning study populations and study designs, may be an overestimate. The data suggest that transmission occurs primarily from humans to dogs, who then may serve as a reservoir for reinfection and transmission to other household members. In addition, dogs may be a vector for livestock-associated strains of MRSA.

“If indeed pets play a role as a risk factor for MDRO acquisition in humans, our meta-analyses only suggested this relation for the transmission of MRSA via dogs,” they wrote.
Apr 17 J Antimicrob Chemother abstract

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