ASP Scan (Weekly) for Feb 24, 2017

New diagnostic tests
Antibiotic prescribing frequency
Possible Candida auris drug
MRSA pattern shifts
Resistant malaria in Africa
Antibacterial skin lotion
MDR Enterobacteriaceae in children
MCR-1 in Chinese pets
MDR-TB testing, treatment
Neonatal sepsis risk calculator
Antibiotic-free chicken
Klebsiella pneumoniae in UK, Ireland
Antibiotic resistance in Indian kids

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

FDA clears two diagnostic tests for expanded use, marketing

The US Food and Drug Administration (FDA) yesterday cleared the expanded use of a diagnostic test for lower respiratory tract infections and sepsis and allowed marketing for a test that can identify organisms that cause bloodstream infections, according to two agency news releases.

Expanded use was cleared for the Vidas Brahms PCT Assay, a test that was first approved to help clinicians predict a patient's risk of dying or becoming sicker from sepsis. Under expanded use, healthcare providers will be able to use the test determine if antibiotic treatment should be started or stopped in patients with lower respiratory tract infections, and stopped in patients with sepsis.

The test measures the amount of procalcitonin (PCT), a protein associated with the body's response to bacterial infection, in a patient's blood. High levels of PCT are an indication of a bacterial infection, while low levels suggest a viral infection. The test does not identify the exact cause of symptoms.

The decision was based on data from clinical trials that showed a significant decrease in antibiotic use for patients who received PCT-guided therapy, without affecting safety.

"Unnecessary antibiotic use may contribute to the rise in antibiotic-resistant infections," Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, said in a news release. "This test may help clinicians make antibiotic treatment decisions."

The agency allowed marketing for the PhenoTest BC Kit, the first test to identify organisms that cause bloodstream infections and provide information about antibiotics that could be effective against those organisms.

The test works by comparing the genetic material of the infection-causing organism to DNA of specific bacteria or yeast. It then mixes the organism with an antibiotic and measures its growth. If the organism doesn't grow in the presence of the antibiotic, it means that antibiotic could be used to treat the patient. The test can identify 14 different species of bacteria and two types of yeast, provide antibiotic sensitivity on 18 different antibiotics, and identify the presence of two indicators of antibiotic resistance.

The PhenoTest BC Kit is also much faster than traditional identification and antibiotic susceptibility tests, which can take 1 to 2 days. It can identify bacteria or yeast from a positive blood culture in approximately 1.5 hours.

In a primary clinical study of 1,850 positive blood cultures, the PhenoTest BC Kit correctly identified the infection-causing organism more than 95% of the time, and results for antibiotic sensitivity were also accurate when compared to traditional tests.
Feb 23 FDA news release
Feb 23 FDA news release


UK Study finds subset of sick patients getting majority of antibiotics

More than half of the antibiotics prescribed to adults in primary care settings in the United Kingdom go to less than 10% of patients, according to a new study in the Journal of Antimicrobial Chemotherapy.

Using data from a primary care database that includes records from more than 12 million UK patients registered with general practices, researchers at the University College London set out to measure variation in the rates of antibiotic prescribing between individual patients. They were looking to investigate the relationship between individual-level antibiotic prescribing and age, gender, and comorbidity, in order to determine the extent to which prescribing variation is driven by behavioral, clinical, and demographic characteristics.

Overall, the investigators included data from nearly 2 million patients over a 3-year period (from 2011 through 2013). On average, 30.1% of patients were prescribed at least one antibiotic per year. Of the total antibiotics prescribed over the 3-year period, 53.3% were prescribed to just 9% of registered patients, each of whom was prescribed at least five antibiotics.

Those patients, the investigators found, tended to be the sicker ones. The presence of at least one comorbidity increased the rate of antibiotic prescribing by 44%, while the presence of two comorbidities nearly doubled it. Individuals with heart failure, asthma, or peripheral arterial disease were prescribed 53% - 69% more antibiotics than patients without those conditions, while patients with diabetes and coronary artery disease were prescribed 47% more antibiotics.

"Our results highlight the importance of high-frequency antibiotic use in a subset of patients with high rates of comorbidity," the authors write.

Gender and age were factors as well. Rates of antibiotic prescribing in women exceeded those in men by 62% and were higher in older patients compared to younger patients, though the association was more marked in men.

The authors say assessing the feasibility of reducing antibiotic prescribing in those with the highest frequency of use should be considered in the context of antibiotic stewardship initiatives.
Feb 21 J Antimicrob Chemother study


Scientists say experimental drug may be effective against Candida auris

The hard-to-treat Candida auris may be vulnerable to an investigational drug, scientists reported yesterday in the first systematic study of the yeast species, which can cause deadly infections.

The US Centers for Disease Control and Prevention first warned the public health and medical communities about the disease last June after cases were reported in several countries. The agency then confirmed the first 13 US cases in November. The pathogen was first reported in 2009. Some strains are resistant to all commercially available antifungal drugs.

Investigators at Case Western Reserve University analyzed 16 C auris strains from infected patients in Germany, Japan, India, and South Korea. They tested the isolates against 11 drugs belonging to different classes of antifungals to identify concentrations that could fight infection. While most samples were at least partially resistant to the tested drugs, low concentrations of an investigational drug called SCY-078 "severely distorted" the fungus and impaired its growth and ability to replicate.

Previous studies have shown the drug is effective against other Candida species that cause catheter-associated infections, including C albicans and C tropicalis, according to a Case Western Reserve news release.

The researchers reported that C auris does not germinate and produce spores like other fungi, a surprise given its ability to rapidly spread in hospitals. The researchers also noted that only certain strains produce the destructive enzymes that typically aid fungi in infection.

People with long hospital stays appear to be most at risk of infection.
Feb 21 Antimicrob Agent Chemother study
Feb 22 Case Western Reserve news release
Nov 4, 2016, CIDRAP News Story "CDC reports first US cases of drug-resistant Candida auris"


German study notes MRSA decline but shifts in resistance patterns

An analysis of Staphylococcus aureus samples from a German antimicrobial surveillance system found that methicillin-resistant S aureus (MRSA) infections declined across a range of healthcare settings from 2010 to 2015, but the co-resistance profile changed markedly. A team based at the Robert Koch Institute published its findings yesterday in BMC Infectious Diseases.

The analysis covered 148,561 S aureus isolates collected over the 6-year study period. The proportion of MRSA isolates declining steady from 16% in 2010 to 10% in 2015, with the drop seen across all types of care and for most sample types, including blood culture, urine, swabs, respiratory, and lesions.

Resistance to tobramycin, ciprofloxacin, moxifloxacin, clindamycin, and erythromycin declined markedly, but resistance increased to tetracyclines (6% to 9%) and gentamicin (3% to 6%). The group also found that resistance among MRSA isolates was fortunately rare to last-line antibiotics, including linezolid, teicoplanin, tigecycline, and vancomycin.

The researchers concluded that Germany's decline in MRSA infections is consistent with other reports and that control measures have likely played a role. They noted, however, that normally occurring changes in circulating strains may also be a factor. The increased resistance they saw to tetracycline was associated with factors such as young age and samples from outpatient settings, a finding they said is consistent with livestock-associated MRSA, a finding that warrants more investigation.

They added that the change in co-resistance patterns should be explored further with genotyping studies.
Feb 23 BMC Infect Dis abstract 


Scientists report first case of artemisinin-resistant malaria in Africa

Originally published by CIDRAP News Feb 23

The first known case of malaria resistant to the essential drug artemisinin was reported yesterday in the New England Journal of Medicine.

An international team of experts said that a 43-year-old man was diagnosed as having malaria caused by the Plasmodium falciparum parasite in January 2013. He had returned to China after a 20-month stay in Equatorial Guinea the previous month, where he had been treated for the disease six times.

The researchers performed whole-genome sequencing to determine that the P falciparum was of African origin and had not been recently imported from elsewhere. Equatorial Guinea has a perennially high rate of malaria, and artemisinin combination therapy (ACT) is commonly used for treating patients, the authors note.

"The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT is the only effective and widely used antimalarial treatment at the moment," said study author Arnab Pain, PhD, according to a news release from Saudi Arabia's King Abdullah University of Science & Technology (KAUST).
Feb 22 N Engl J Med study
Feb 22 KAUST news release


Skin lotion with antibiotics derived from skin bacteria shows promise

Originally published by CIDRAP News Feb 23

Scientists have identified two new antibiotics produced from beneficial skin bacteria and added them to skin lotion to treat S aureus infections, according to a study yesterday in Science Translational Medicine.

Researchers from the University of California San Diego (UCSD) School of Medicine screened thousands of colonies of bacteria found on the skin of volunteers to find out how many demonstrated antimicrobial properties. They found that some strains of beneficial bacteria produce two types of antimicrobial peptides (AMPs), and colonization of pigskin or mice with these two AMPs reduced S aureus replication, even that of methicillin-resistant S aureus, a common resistant pathogen.

The lab-isolated AMPs were more effective at eliminating S aureus than their naturally occurring counterparts and produced the best results when administered in combination. In addition, the AMPs did not reduce healthy bacteria found on the skin, such as Propionibacterium acnesS epidermidis, and Corynebacterium minutissimum.

The researchers then conducted a small trial on five patients who had atopic dermatitis, which is exacerbated by S aureus. The phase 1trial involving personalized lotions containing the AMPs was intended to test for safety and efficacy only, but all five patients had a significant decrease in S aureuson their skin, the authors reported.

The technique has already been approved by the US Food and Drug Administration, the authors wrote, and a phase 2 trial is being launched, according to a UCSD press release.
Feb 22 Sci Transl Med study
Feb 22 UCSD press release


Study describes incidence, risk factors for MDR Enterobacteriaceae in kids

Originally published by CIDRAP News Feb 22

A study yesterday in BMC Infectious Diseases shows that critically ill children with tracheal Enterobacteriaceae infection are at risk for multidrug-resistant (MDR) infections.

The retrospective, single-center analysis was performed on ventilated patients admitted to the pediatric intensive care unit of the University Children's hospital in Tubingen, Germany, from 2005 to 2014. While mechanically ventilated pediatric patients are known to be at risk for tracheal colonization with MDR Enterobacteriaceae, the underlying risk factors are poorly understood. The investigators were looking to determine the incidence of children with suspected MDR infection and the predisposing risk factors.

During the study period, 167 Enterobacteriaceae isolates were obtained from the lower respiratory tracts of 123 intubated patients. Of those isolates, 116 (69%) were susceptible and 51 (31%) were identified as MDR Enterobacteriaceae. The most prevalent isolates were Enterobacter spp, followed by Escherichia coli and Klebsiella spp. The most prevalent MDR organisms were E coliKlebsiella, and Enterobacter spp.

Using a classification and regression tree (CRT) analysis to predict risk factors, the investigators determined that antibiotic pre-treatment for more than 7 days increased the risk of infection with an MDR isolate by 62%. In addition, they found that gastrointestinal comorbidity increased the chance of MDR infection from 25% to 40% in patients who received less than 7 days of antibiotic therapy.

"Collectively, our results imply that early identification of patients at risk, rapid microbiological diagnostics and tailored antibiotic therapy are essential to improve management of critically ill children infected with Enterobacteriaceae," the authors write.
Feb 21 BMC Infect Dis study


Researchers report MCR-1 in pets, pet food in China

Originally published by CIDRAP News Feb 22

About 9% of pets and 20% of pet food samples tested in Beijing, China, contained the MCR-1 gene, which confers resistance to the last-resort antibiotic colistin, according to a study yesterday in Emerging Infectious Diseases.

An international team of experts tested 566 Enterobacteriaceae isolates collected from cats and dogs via nasal and rectal swabs in the city from 2012 through 2016. Of the total, 49 (8.7%) of the isolates harbored the MCR-1 gene, which was first reported late last year in a 50-year-old man in China. The gene was found on 47 E coli isolates and 2 Klebsiella pneumonia samples. The overall count of colistin-resistant isolates was 79, mostly E coli.

The researchers also isolated the MCR-1 gene from 1 of 25 Enterobacteriaceae samples collected from 32 nasal swabs from pet owners. The isolate had the same genetic fingerprint as 5 of the pet samples.

In addition, the team tested 35 dog and cat food samples, 7 of which (20%) were positive for MCR-1, signifying a possible source for the animal infections.

The authors noted that colistin is not used to treat companion animals in China, and the pets tested had minimal to no contact with food-producing animals that might have been treated with the drug. They conclude, "Because of frequent and close contact between humans and companion animals, our study proposes that opportunities exist to transmit colistin-resistant Enterobacteriaceae to and from both groups."
Feb 21 Emerg Infect Dis study


Study: Xpert TB test not tied to increased rates of second-line treatment

Originally published by CIDRAP News Feb 22

A South African study yesterday concluded that the Xpert MTB/RIF tuberculosis (TB) test was associated with a reduction in treatment delay from a median of 44 days in 2011 to 22 days in 2013 for patients with drug-resistant TB but did not significantly improve the proportion of patients receiving proper antibiotics. The study appeared in PLoS Medicine.

South African and Dutch researchers aimed to assess second-line antibiotic treatment before and after the Xpert MTB/RIF test was implemented in South Africa, so they analyzed data from 2011 and 2013 on more than 5,000 TB cases resistant to the key first-line drug rifampin.

The investigators found that treatment delays were halved after Xpert implementation, from 44 to 22 days. But they found no difference in those who started second-line drug treatment within 6 months of diagnosis by Xpert (62%) and those diagnosed by other methods (64%). They also found substantial variation across the country's nine provinces in both the rate of second-line 6-month treatment initiation and the median time to treat.

Although Xpert appeared to have not improved rates of appropriate treatment, the authors wrote, "given improved case detection, a larger proportion of the total population of individuals with rifampicin-resistant TB will receive treatment." They added, "Further strategies to improve linkage to treatment for all patients diagnosed with rifampicin-resistant TB are required."
Feb 21 PLoS Med study


Neonatal sepsis risk calculator nearly halves newborn antibiotic use

Originally published by CIDRAP News Feb 21

An online calculator that predicts the risk for early onset sepsis (EOS) can cut antibiotic use in newborns nearly in half, according to a study yesterday in JAMA Pediatrics.

The online calculator, developed by researchers at Kaiser Permanente, the University of Pennsylvania, and the University of California, San Francisco, uses algorithms from two linked risk prediction models for EOS—an invasive bacterial infection in newborns caused by bacteria from the mother's genital or gastrointestinal tract. The prediction models, based on data from more than 600,000 newborns and their mothers, estimate the risk of EOS using gestational age, time from membrane rupture, maternal temperature, group B Streptococcus (GBS) carriage status, intrapartum antibiotic use, and the newborn's clinical presentation.

Under EOS management guidelines developed by the Centers for Disease Control and Prevention (CDC), the American Congress of Obstetricians and Gynecologists, and the American Academy of Pediatrics, the incidence of EOS has fallen significantly. But roughly 15% of newborns are still evaluated for sepsis, and 5% to 8% receive empirical antibiotics while awaiting results of a blood culture. The aim of the prediction models was to reduce the number of newborns who had to get blood cultures and receive antibiotics by figuring out a better way to target newborns who are at risk.

In the study, which included more than 200,000 babies born at 35 weeks or later at Kaiser Permanente hospitals in northern California, investigators compared three different periods: A baseline period (2010-2012), when EOS management was based on CDC guidelines; a learning period, during which staff familiarized themselves with the EOS risk calculator (2012-2014); and the period when the EOS risk calculator was fully implemented (2014-2015). The primary outcome was antibiotic use in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS.

In a comparison of the baseline period with the EOS calculator period, empirical antibiotic use in the first 24 hours dropped from 5% to 2.6%, and blood culture use declined from 14.5% to 4.9%. No increase in antibiotic use occurred between 24 and 72 hours after birth. The incidence of culture-confirmed EOS was similar during the three periods (0.2 to 0.3 per 1,000 births), and readmission for EOS was rare and did not differ statistically. Incidence of adverse outcomes was unchanged.

"Experts in neonatology have questioned the need for high rates of empirical antibiotic treatment among term and late pre-term newborns," the authors conclude. "Our study suggests that antibiotic stewardship can safely begin at birth."
Feb 20 JAMA Pediatrics abstract


Tyson says it will eliminate use of all antibiotics in its chicken

Originally published by CIDRAP News Feb 21

Tyson Foods Inc, the largest US chicken producer, announced today that it will eliminate the use of all antibiotics in fresh and frozen chicken products bearing the company name, according to media reports. The announcement was made at an industry conference.

The switch to chickens raised without any antibiotics will occur in June, Reuters reports. The company had previously announced, in 2015, that it would eliminate the use of all antibiotics used in human medicine from its US broiler chicken flocks by September 2017. This move takes the company's commitment to antibiotic-free chicken one step further.

Tyson processes more than one-fifth of all poultry in the United States, according to the Wall Street Journal, slaughtering about 35 million birds a week. Tyson CEO Tom Hayes told the paper that the move will make the company the world's largest supplier of poultry raised without antibiotics.

In October, Tyson competitor Perdue Farms announced it was ending the use of animal-only antibiotics in chicken production, 2 years after it had eliminated the use of medically important antibiotics in its chickens. And several fast-food chains, including McDonald's and Wendy's Co, have also made the move to antibiotic-free chicken in recent years.

Public health officials are concerned that the use of medically important antibiotics in food-producing animals is contributing to the emergence of antibiotic resistant infections, and have called on the agriculture industry to reduce their use.
Feb 21 Reuters story
Feb 21 Wall Street Journal story


Study finds high diversity, resistance in UK, Irish K pneumoniae isolates

Originally published by CIDRAP News Feb 21

A study today in mBio reports that the population of K pneumoniae isolates in the United Kingdom and Ireland is highly diverse, showing signs of recent international introductions from Europe and more distant countries and increased virulence and resistance.

To get a better sense of the diversity of K pneumoniae, and its resistance mechanisms, investigators conducted genomic and phylogenetic analysis on a systematic collection of multidrug-resistant (MDR) K pneumoniae isolates obtained from hospitals in the United Kingdom and Ireland over the past decade and compared them to global collections of K pneumoniae isolates. The analysis showed that the K pneumoniae population in the United Kingdom and Ireland is highly diverse, indicating that lineages found in the two countries are part of globally circulating lineages and could be coming from multiple sources outside the countries.

The investigators also found that the closest relatives of United Kingdom and Ireland MDR K pneumoniae were more likely to be isolates from nosocomial (hospital-acquired) infections, rather than community-acquired infections. This finding, the authors note, suggests that MDR K pneumoniae could potentially be spreading via patients transferred between countries, medical tourists, and blood products. "This highlights the importance of identifying putative reservoirs of K. pneumoniae that may be involved in the transmission of K. pneumoniae between distant hospitals and thus lead to the global circulation of K. pneumoniae," they write. 

In addition, the investigators identified novel genetic determinants conferring increased levels of resistance to beta lactam antibiotics, gentamicin, ciprofloxacin, and tetracyclines, a finding that "demonstrates that even already MDR lineages can become more resistant and disseminate rapidly."

The authors say understanding the extent of inter-hospital transmissions of MDR K pneumoniae, and identifying other potential sources or reservoirs of the pathogen, will be essential for efforts to control its spread. 
Feb 21 mBio study 


Study finds high levels of antimicrobial resistance in sick Indian children

Originally published by CIDRAP News Feb 20

A new study in the Journal of the Pediatric Infectious Diseases Society reports high rates of antimicrobial resistance in Indian neonatal and pediatric bloodstream infections.

The meta-analysis of 82 papers on antibiotic resistance in Indian children published from 2000 through 2015 included a total of 50,545 blood cultures, with the majority of bloodstream infections (78.7%) being reported from neonatal intensive care units. Among the 72 studies that reported gram-positive bacteria, the median percentage of gram-positive bacteria was 29.2%. In the 81 studies that reported on gram-negative bacteria, the median percentage among all reported positive cultures was 61%. S aureus was found to be the most common gram-positive isolates (median, 14.7%) and K pneumoniae was found to be the most common gram-negative isolate (median, 26%).

Fifty percent of the S aureus isolates were methicillin resistant, with high resistance for S aureus to erythromycin (53%), cefotaxime (57%), and cotrimoxazole (57.7%) also noted. High levels of resistance were reported in K pneumoniae to ampicillin (95.2%) and cephalosporins (over 60%). After age stratification, the median resistance of common gram-negative pathogens to the World Health Organization-recommended combination of ampicillin and gentamicin for the treatment of neonatal sepsis was found to be extremely high (K pneumoniae/ampicillin 95.9%; K pneumoniae/gentamicin 75%;  E coli/ampicillin 92.9%; E coli gentamicin 55.6%), with high resistance to cephalosporins also noted.

The authors note that while national guidelines for antimicrobial use have been launched in India, the study highlights a need for similar guidelines in neonates and children. More importantly, they write, "the awareness about the magnitude of antibiotic resistance and the essence of rational antibiotic use needs to be highlighted more urgently among practicing physicians and families."
Feb 18 J Pediatric Infect Dis Soc study

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