ASP Scan (Weekly) for Mar 16, 2018

MCR-4, MCR-5 in China
Award for blood infection test
Antibiotics and Staph biofilms
VRE bacteremia treatment
Drug-resistant bacteria in urine
Infection risk tool and stewardship
Multidrug resistance in Ghana

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

Study: MCR-4 and MCR-5 genes prevalent in China's pigs, poultry

Originally published by CIDRAP News Mar 15

A research team based in China yesterday reported that the newly identified colistin-resistance genes MCR-4 and MCR-5 occur widely in the country's pigs and poultry, according to a study in PLoS One.

They used a polymerase chain reaction (PCR) test to directly detect the genes in anal and nasal swabs from 1,454 apparently healthy pigs in nine of China's provinces and cloacal and oropharyngeal samples from 1,836 poultry from live-bird markets in 24 provinces.

For both of the genes, prevalence was significantly higher in swine than in poultry swabs. MCR-4 was found in 41.4% of pigs and 11.5% of poultry, and MCR-5 was present in 31.1% of pigs and 5.6% of poultry.  Poultry species that harbored the gene included geese, chickens, pigeons, and ducks. In both animal types, MCR-4 and MCR-5 prevalence was higher in the nasal and oropharyngeal swabs than in anal and cloacal swabs.

Researchers found both of the genes in swabs from 2.6% of poultry and 18.3% of pigs.

The authors noted that the levels of genes detected using PCR of swabs is considerably higher than those obtained with studies on bacterial isolates and may more accurately reflect the true prevalence of the genes. "However, the data did not enable us to determine the bacterial species that carried the resistance genes, or the location of the mcr in plasmids or in the bacterial chromosomes," they wrote.

The high levels of MCR-4 and MCR-5 in pigs and poultry from a large part of China is probably linked to prolonged and widespread use of colistin—a last-resort antibiotic—as a growth promoter, but the two genes might also be prevalent in other countries, as well, the team wrote. They also said the higher levels of the genes in nasal and oropharyngeal swabs suggests that bacteria in saliva or respiratory secretions might play key roles in maintaining and transmitting colistin-resistance genes in pigs and poultry.
Mar 14 PLoS One report


CARB-X funds new test to diagnose whole-blood infections

Originally published by CIDRAP News Mar 15

CARB-X, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, announced an award of $1 million to HelixBind, a Massachusetts-based company producing a new diagnostic test for whole-blood samples. The test will provide resistance information for invasive bloodstream infections, and HelixBind will have the opportunity to receive another $1 million in funding based on project achievements.

"The world urgently needs new diagnostics, antibiotics, vaccines and other products to protect us from current and emerging drug-resistant bacteria. All the projects in the Powered by CARB-X are in the early stages of development, but if successful, they offer great potential in the fight against life-threatening drug-resistant bacteria," said Kevin Outterson, JD, executive director of CARB-X, in a press release.

HelixBind's test eschews blood cultures, potentially saving time and money for clinicians. This means patients with sepsis, a life-threatening blood infection, can be treated with appropriate antibiotics sooner.

The test is the third diagnostic assay funded by CARB-X since 2016. CARB-X's portfolio includes 27 novel antibiotics, diagnostics, and other product that address drug resistance.

Earlier this week, CARB-X hosted a webinar and addressed frequently asked questions about its funding rounds for 2018. 
Mar 15 CARB-X press release
Mar 15 CARB-X webinar and FAQs


Only 2 single antibiotics shown effective against Staphylococcus biofilms

Originally published by CIDRAP News Mar 15

A lab-based study of commonly used antibiotic combinations effective against Staphylococcus biofilms in periprosthetic joint infections (PJIs) found that gentamicin and daptomycin were the only effective single-agent treatments. Researchers from Scotland reported their findings yesterday in the Journal of Antimicrobial Chemotherapy.

Locally delivered antibiotics play a key role alongside surgical debridement in managing PJI, but there is little evidence on whether a single agent or combination of drugs is better. Commercial bone cements for PJI typically include gentamicin, either with clindamycin or vancomycin.

The investigators used the dissolvable bead microfilm assay to determine the minimum biofilm eradication concentration (MBEC) for the different medications and drug combinations against staphylococcal PJIs. Then they modified the tractional inhibitory concentration index to craft a fractional biofilm eradication concentration index to evaluate synergism or antagonism among the antibiotics.

Only gentamicin (MBED 64 milligrams per liter [mg/L]) and daptomycin (MBEC 64 mg/L) were effective at clinically achievable concentrations. The researchers also observed that other antibiotics alone or in combination were ineffective. Also, they noted that combining bactericidal antibiotics (except for daptomycin) with gentamicin showed a synergistic effect, though bacteriostatic antibiotics had an antagonistic effect when combined with gentamicin.

Though gentamicin and daptomycin have different mechanisms of action, both affect membrane integrity, which might provide an antistaphylococcal effect, including against methicillin-resistant Staphylococcus aureus, the authors wrote. "Further investigation of these findings may be useful in evaluating optimal use of antibiotic combinations in the management of PJI," they concluded.
Mar 14 J Antimicrob Chemother abstract


Studies shed more light on managing VRE bacteremia in hospital patients

Originally published by CIDRAP News Mar 14

Vancomycin-resistant enterococci (VRE) have become an increasingly common cause of healthcare-related bacteremia, and two new studies published yesterday in the Journal of Antimicrobial Chemotherapy shed new light on managing the infections, one exploring treatment with high-dose daptomycin and another that found longer exposure to vancomycin, fluoroquinolone, or meropenem was associated with that type of infection.

In the first study, a team based at the University of Texas noted that recent literature suggests that daptomycin is the preferred treatment for VRE bacteremia, though it is often used off-label for that purpose. However, optimal dosing strategies haven't been determined, despite the need for high doses and worries about toxicity.

Their review of studies on the standard-dose and high-dose treatment for VRE bacteremia found that earlier studies didn't find differences in mortality, but newer larger studies suggest an association between high-dose (greater than or equal to 9 milligrams per kilogram [mg/kg]) daptomycin and reduced mortality, compared with the standard 6 mg/kg dose. They concluded that the high-dose regimens appear to be safe and may be linked to improved microbiological outcomes.

In the second study, researchers from the University of Cambridge and Public Health England examined risk factors for VRE bacteremia, focusing on the duration of antibiotic exposure in patients at Cambridge University Hospitals, which has in the past reported the highest numbers of VRE bacteremia in England. Over the study period, the hospital had an active antimicrobial stewardship program in place. And though infection control practices targeting VRE didn't change during that time period, in the early part of the study, the hospital implemented a line-care bundle and a deep-clean program.

The study took place January 2006 through December 2012, comparing 235 patients who had their first episode of VRE bacteremia with 220 matched controls. They found that longer exposure to parenteral vancomycin, fluoroquinolones, and meropenem was independently associated with VRE bacteremia.

They concluded that targeting the use of a single antibiotic in an endemic setting isn't likely to significantly affect VRE bacteremia rates, but a combination of steps including antimicrobial stewardship that limits the duration of high-risk antibiotics along with infection control interventions could help reduce rates of the disease.
Mar 13 J Antimicrob Chemother daptomycin dosing  abstract
Mar 13 J Antimicrob Chemother multiple antibiotics and VRE risk 


Israeli study finds UTIs, antibiotic use tied to resistant bacteria in pregnancy

Originally published by CIDRAP News Mar 14

Israeli scientists have discovered that prior urinary tract infections (UTIs) and antibiotic exposure were significant risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) pathogens in the urine of pregnant women, but this finding was not associated with worse obstetric outcomes compared with non-ESBL-E pathogens, according to a matched case-control study yesterday in Epidemiology & Infection.

The study included 87 pregnant women whose urine tested positive for ESBL-E and 174 controls whose urine tested negative from 2004 through 2015.

The researchers determined that statistically significant risk factors of ESBL-E detection in urine were previous UTI or asymptomatic bacteriuria (50.6% vs. 26.3% incidence), previous isolation of ESBL-E in urine cultures (12.6% vs. 0.6%) and prior antibiotic exposure (71.3% vs. 54.0%).

They also found that previous hospitalization was not a risk factor. And they did not find a significant difference in adverse obstetric outcomes between the ESBL-E–positive group and the controls.
Mar 14 Epidemiol Infect abstract


Infection risk tool shows promise in Dutch study

Originally published by CIDRAP News Mar 12

Research by Dutch investigators suggests that a user-friendly, visual instrument for measuring the quality of infection control and antimicrobial use could be useful for targeting interventions in hospitals and nursing homes.

In a new study in Antimicrobial Resistance and Infection Control, the investigators describe the application of the Infection Risk Scan (IRIS) method at a hospital, several nursing homes, and a rehabilitation clinic in the Netherlands. IRIS consists of a bundled set of objective, reproducible measurements combining patient- and healthcare-related variables, which are used to establish a risk profile for the patient population and an improvement plot for the facility. Results are visualized in a spider plot using traffic light colors to make the results straightforward and easy to understand.

The IRIS variables include hand hygiene compliance, environmental contamination using adenosine triphosphate (ATP) measurements, prevalence of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-E), availability of infection control preconditions, personal hygiene of healthcare workers, appropriate use of indwelling medical devices, and appropriate antimicrobial use. But risk factors can be added or switched.

The implementation of IRIS at five hospital wards showed high levels of environmental contamination and provided the basis for targeted actions that resulted in measurable improvements. Hand hygiene compliance increased from 43% to 66%, and ATP levels were significantly reduced. In 19 nursing homes, large differences were observed, with environmental contamination as the common denominator. In addition, a significant difference in ESBL-E prevalence (mean 11%, range 0% to 21%) was observed. At the rehabilitation center, 17% of residents were found to be ESBL-E carriers.

"In conclusion, the bundle approach and visualization of the IRIS makes it a complete and useful infection prevention tool," the authors write. "The broader implementation of IRIS can raise the standard of infection control and make it more transparent in various healthcare settings, e.g. nursing homes."
Mar 9 Antimicrob Resist Infect Control study


High rates of multidrug resistance found in Ghana hospital

Originally published by CIDRAP News Mar 12

In another new study in Antimicrobial Resistance and Infection Control, a team of African researchers reports high rates of multidrug-resistant gram-negative bacterial infections in a teaching hospital in Ghana.

In the study, conducted at a 1,000-bed tertiary care government hospital in the Ashanti region of Ghana from February through August 2015, researchers examined 200 clinical, non-duplicate gram-negative bacteria randomly selected from urine, pus, wound swab, pleural fluid endotracheal tubes, gastric lavage, and blood specimens. Multidrug resistance was defined as isolates that were resistant to at least one agent in three or more antibiotic classes.

Of the 200 isolates obtained, Escherichia coli was the most frequent pathogen (49 isolates, 24.5%), followed by Pseudomonas aeruginosa (39, 19.5%), Klebsiella pneumoniae (38, 19%), and Enterobacter spp. (12, 6%). Multidrug resistance was observed in 89.5% of the isolates, ranging from 53.8% in Enterobacter to 100% in Acinetobacter spp. and P aeruginosa, with high resistance to ampicillin (94.4%), trimethoprim sulfamethoxazole (84.5%), cefuroxime (79%), cefotaxime (71.3%), cefoxitin (57.5%), and amoxacillin-clavulanate (51.5%).

Urinary tract infection was diagnosed in 34.5% of patients, sepsis in 14.5%, wound infection (surgical and chronic wounds) in 11%, and pulmonary tuberculosis in 9%. The largest proportion of patients were those 60 years and over (24.5%), followed by children under 10 (24%). The lowest prevalence was in those 10 to 19 years old (9.5%).

The authors of the study say the results should inform the empiric treatment of infections at the hospital.
Mar 9 Antimicrob Resist Infect Control study

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