ASP Scan (Weekly) for Sep 22, 2017

One Health stewardship
MRSA risk in the home
Resistant farm E coli in China
MDR malaria spread
Pediatric antimicrobial stewardship
New US Candida auris cases
Post-cesarean antibiotics
Point-of-care testing
Pneumonia vaccine and antibiotics
New vaginosis antibiotic
Gene sequencing for CRE
C diff and tetracyclines
Resistant E coli clone in kids
New pneumonia antibiotic
UK strep guidelines

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

FAO calls for One Health stewardship approach, cites success in Cambodia

More funding, public health efforts, and surveillance are needed to ensure responsible use of antimicrobials in food animals and humans, Maria Helena Semedo, deputy director-general with the United Nations (UN) Food and Agriculture Organization (FAO), said yesterday. She was speaking to participants at a UN General Assembly event on Antimicrobial Resistance (AMR).

"Good health, good productivity and good economies depend on safe and nutritious food. Prudent use of antimicrobials in public health and agriculture is essential to achieve this," Semedo said, according to an FAO news story. "We need surveillance on antimicrobial use and the spread of AMR — not only through hospitals, but throughout the food chain, including horticulture and the environment for more comprehensive risk assessments."

The challenge posed by AMR is also "an opportunity to unite health, agriculture and environmental concerns in collaborative global action," Semedo said, citing the FAO's experience in Cambodia.

"By strengthening collaboration between health and agriculture ministries [in Cambodia]; helping draft rules to regulate the sale of veterinary medicines; and assisting animal health labs — we helped increase awareness and greater cooperation in dealing with AMR," she said. Semedo added that Cambodia is now sharing its experience with neighboring nations, and the FAO has experienced similar success in Ghana, Kenya, Thailand, Vietnam, Zimbabwe, Latin America, and Central Asia. 
Sep 21 FAO news article


Antibiotics, biocidal cleaners may promote multidrug resistance in MRSA

People or pets taking antibiotics and the use of biocidal cleaning products like bleach may contribute to multidrug resistance (MDR) in methicillin-resistant Staphylococcus aureus (MRSA) in the home, according to a study today in Applied and Environmental Microbiology.

Contamination of the home environment may contribute to reinfection of both humans and animals with MRSA and to subsequent failure of treatment, researchers from Baltimore and Pennsylvania concluded.

In the study, the scientists collected samples from home environments and pets of households enrolled in a large randomized controlled trial, which took place over 14 months. They tested whether household-wide efforts to eradicate MRSA — which included daily use of nasal mupirocin ointment and chlorhexidine body wash — were successful in reducing recurrence of MRSA among adults and children who had been diagnosed with a MRSA skin or other soft-tissue infection. The team repeated sampling in 65 homes 3 months after the residents had been treated for MRSA, or, as a control, after they had been educated about MRSA.

"Based on the evidence, we strongly suspect that environmental contamination of the home with MRSA contributes to recurrence," said corresponding author Jonathan Shahbazian, MPH, in a news release from the American Society for Microbiology (ASM), which publishes the journal.  The investigators also suspect that household-wide selective pressures on MRSA promote the persistence of MDR strains. "We hypothesize that infected or colonized people and companion animals shed MRSA into the home environment," which then re-infect household members, he added.

Treatment with mupirocin, an antibiotic used to treat skin infections and to eradicate MRSA from patients' nasal passages, was weakly associated with mupirocin resistance in the home. That could complicate decolonization efforts that rely on the drug, said Shahbazian. He added that all MRSA isolates the investigators obtained from rural homes were MDR, suggesting that might be a risk. The study also showed that clindamycin, whether used in humans or pets, was not associated with a higher risk of MDR bacteria in the home.

"We also found the presence of domestic pets was associated with multidrug resistant MRSA in the home environment, while the presence of unwanted pests, such as mice or cockroaches, was associated with non-multidrug resistant MRSA strains," Shahbazian said.
Sep 22 Appl Environ Microbiol abstract
Sep 22 ASM news release


E coli on Chinese farm animals show high levels of antibiotic resistance

A study yesterday in PLoS One reports a 94% prevalence of resistance to at least one antimicrobial and an 83% rate of resistance to three or more classes of antimicrobials in pathogenic Escherichia coli collected from Chinese poultry and livestock.

To determine the prevalence of drug-resistant E coli, researchers working in Jiangsu, China, tested 862 clinical isolates collected from cows, pigs, ducks, and chicken from 2004 to 2012. Almost all (94%) of the samples showed resistance to one antimicrobial, and 84% showed resistance to three or more classes. All isolates collected from ducks (44) were multidrug-resistant, as were 88.2% trom chickens and 21.3% from cows.

According to the study, the highest rates of resistance (>75%) were found with tetracycline, nalidixic acid, sulfamethoxazole, ampicillin, enrofloxacin, and trimethoprim-sulfamethoxazole.

China is the biggest user of agricultural antimicrobials in the world, the study authors write. "There is growing evidence that E. coli infections of animals and people are becoming increasingly difficult to treat in China and that guidelines and regulations are urgently needed to limit and rationalize antimicrobial use."
Sep 21 PLoS One study


Multidrug malaria lineage spreads to Vietnam

Originally published by CIDRAP News Sep 21

A multidrug-resistant parasite lineage that has become dominant in Cambodia, with spread to parts of Thailand and Laos, has now spread to southern Vietnam, where it has been linked to an alarming number of treatment failures in patients who were given the nation's first-line treatment.

Researchers from Vietnam and Thailand reported the development in a letter today in The Lancet Infectious Diseases. They said the PfPailin lineage, first identified in western Cambodia in 2008, acquired resistance to piperaquine and spread east, forcing that country to switch its first-line artemisinin combination treatment back to artesunate-mefloquine.

In Vietnam, the current national first-line treatment is dihydroartemisinin-piperaquine, the same as Cambodia's former first-line combination.

According to the report, microsatellite typing of 86 of 152 Plasmodium falciparum isolates from the Binh Phuoc province in 2016 shows the same genetic markers seen in parasites in other Greater Mekong countries. In 8 years, the lineage now encompasses all four countries of the eastern Greater Mekong region.

"The evolution and subsequent transnational spread of this single fit multidrug-resistant malaria parasite lineage is of international concern," the team wrote.
October Lancet Infect Dis letter


Study shows effectiveness of pediatric antimicrobial stewardship

Originally published by CIDRAP News Sep 21

Following implementation of a pediatric antimicrobial stewardship program (ASP) at a large Tokyo hospital, carbapenem resistance rates in Pseudomonas aeruginosa dropped significantly, as did the length of hospital stay and infection-related mortality, according to a study yesterday in the International Journal of Infectious Diseases.

Scientists analyzed data from April 2010 to September 2011 (pre-intervention) and October 2011 to March 2017, the intervention period. The pre-intervention period included only consultations with infectious disease services, while the latter period included those consultations plus the ASP. The team calculated carbapenem resistance rates in gram-negative bacteria in both periods and then compared the two.

The researchers found that both the carbapenem resistance rate in P aeruginosa and the length of carbapenem therapy decreased by a statistically significant amount during the intervention phase. Length of hospital stay and infection-related mortality also dropped significantly.
Sep 20 Int J Infect Dis study


More US Candida auris cases confirmed

Originally published by CIDRAP News Sep 21

The United States now has 126 confirmed cases of Candida auris as of Aug 31, according to a new case count update from the Centers for Disease Control and Prevention (CDC). Fourteen of those cases were reported since the previous update, on Aug 21.

In addition to the 126 confirmed cases, officials have reported 27 suspected cases, and an additional 143 patients have been found to be colonized with C auris by targeted screening in four states with clinical cases. Those patients are asymptomatic.

New York and New Jersey have by far the most cases, with 86 and 26 confirmed cases, respectively. No other state has more than 4 confirmed cases. New Jersey has an additional 23 probable cases, and New York has 4 probable cases.

C auris is an emerging infectious fungus that causes severe illness in hospitalized patients. Based on limited data, the CDC reports that 30% to 60% of patients have died. The fungus has shown resistance to three major classes of antifungal drugs and can live in healthcare settings for months. 
Sep 18 CDC update


Study finds post-cesarean antibiotics effective in obese women

Originally published by CIDRAP News Sep 20

Postoperative antibiotics more than cut in half the rate of surgical site infection (SSI) within 30 days after delivery among obese women undergoing cesarean delivery, according to the results of a randomized controlled trial published yesterday in JAMA.

US researchers conducted the study on 403 women who had a prepregnancy body mass index of 30 or greater, all of whom had received preoperative cephalosporin. Obesity has been tied to a higher risk of SSI. Half (202) of the women received 500 milligrams of both cephalexin and metronidazole every 8 hours after cesarean section for 48 hours, while 201 received placebos for the same period.

The scientists found that the rate of SSI within 30 days after delivery was 15.4% in the placebo group and 6.4% in the antibiotic treatment group. The authors estimate that 12 obese women would need to receive the treatment to benefit 1 patient.

The researchers detail some limitations of the study, including that the trial was performed at a single site with a high prevalence of obese patients, which may not be generalizable to all obstetric practices.

In an accompanying editorial, two experts from Weill Cornell Medicine in New York City also note, "Given that participant enrollment for this study began almost 7 years ago and extended over a 5-year period, one consideration is whether the surgical practices and SSI prevention measures used during the study are representative of those that are widely used today."

The editorial writers also bring up antibiotic resistance. "In an era of a rapidly increasing prevalence of antimicrobial resistance among common human pathogens, a global threat to which excessive and unnecessary antimicrobial use is a contributor, the societal implications of a call for increased antimicrobial use must always be considered carefully. While 48 hours of oral antibiotics may appear to represent a minimal amount of antibiotic exposure, broad implementation of this strategy could contribute approximately 1.26 million additional days of antimicrobial therapy in the United States each year."
Sep 19 JAMA study
Sep 19 JAMA 


GAO: Multiplex testing carries implementation challenges

Originally published by CIDRAP News Sep 20

Although multiplex point-of-care technologies (MPOCTs) can help conserve antibiotics and aid patient care, developers and users disagree on the strength of evidence showing improvement in patient outcomes, and the tests carry certain implementation challenges, the US Government Accountability Office (GAO) said in a report last week.

For the report, GAO scientists examined tests of varying sizes and capacities. The MPOCTs took from 20 minutes to 2 hours to produce results, cost from $25,000 to $530,000, and had per-test operation costs ranging from $20 to $200.

The researchers talked to multiple developers, who identified several technical challenges that can slow MPOCT development and raise costs, such as lack of access to patient samples or reliable genetic databases for developing the assays. Modifying multiplex assays poses another challenge, because developers have to consider possible new interactions and go through Food and Drug Administration review before the modified test can be marketed.

Test developers and test users disagreed on the strength of evidence showing the extent of improvement on patient outcomes. Some test users called for more clinical studies to establish benefits, while developers focused on implementation challenges, including the regulatory review process. Other implementation challenges included reluctance by medical users to adopt MPOCTs because of such factors as lack of familiarity and cost.
Sep 13 GAO report


Pneumococcal vaccination tied to fewer antibiotic doses in Danish kids

Originally published by CIDRAP News Sep 20

Introduction of pneumococcal conjugate vaccines (PCVs) in national immunization programs has been linked to lower rates of antibiotic prescribing and insertion of ventilation tubes in Danish children, according to a new study in Vaccine.

Researchers looked at the years before, during, and after the implementation of the seven-valent vaccine (PCV7) in 2007 and the 13-valent version (PCV13) in 2010.

They found that the introduction of PCV7 and PCV13 correlated with changes in the prescribing rate from an almost steady increase in antibiotic prescriptions in the pre-PCV period to a decreasing incidence for all children age 15 years and younger. The 2.4 defined daily doses (DDD) per person-year in 2014 was at almost the same level as in 2000 (2.3 DDD per person-year).

For ventilation tube insertion, the investigators observed a decreasing incidence rate in the years following introduction of PCV13, ending with a slightly higher incidence, at 35 per 1,000 person-years in 2014 compared with 31 in 2000.
Sep 18 Vaccine study


FDA approves new 1-dose antibiotic for treating bacterial vaginosis

Originally published by CIDRAP News Sep 19

Symbiomix Therapeutics announced yesterday that the US Food and Drug Administration (FDA) on Sep 15 approved its antibiotic Solosec (secnidazole) for treating bacterial vaginosis (BV) in adults, the first single-dose option for the condition.

The Newark, N.J.–based company said in a news release, "The FDA approval was supported by a comprehensive set of studies, including two pivotal trials in BV and an open label safety study, which found efficacy for single-dose secnidazole 2g. All treatment-emergent adverse events were mild or moderate in intensity; no serious adverse events were reported, and no patients discontinued treatment due to adverse events."

The FDA awarded the company fast-track designation, which made Solosec eligible for priority review and at least 10 years of US market exclusivity. BV is the most common gynecologic infection in the United States, affecting 21 million girls and women aged 14 to 49 each year, Symbiomix said. The most commonly prescribed antibiotics for the condition require twice-a-day pills for 7 days.

Solosec granules are designed to be sprinkled onto applesauce, yogurt, or pudding and consumed within 30 minutes without chewing the granules.

David L. Stern, CEO of Symbiomix, said in the news release, "Solosec is the first new oral antibiotic to treat BV in more than a decade and will provide women with a new treatment option. We look forward to making this treatment available to patients in the first quarter of 2018."
Sep 18 Symbiomix news release


Whole-genome sequencing effective in tracing spread of resistant bacteria

Originally published by CIDRAP News Sep 19

Phylogenetic analysis based on whole-genome sequencing (WGS) was superior to conventional epidemiologic methods for reconstructing transmission pathways in an outbreak of carbapenem-resistant Klebsiella pneumoniae at a Leipzig hospital, German scientists reported yesterday.

From July 2010 to April 2013, Leipzig University Hospital experienced its largest-ever outbreak of carbapenem-resistant K pneumoniae infections. The researchers, writing in the American Journal of Infection Control, aimed to reconstruct transmission pathways after the outbreak ended.

The investigators performed WGS on 117 isolates from 89 outbreak patients, 5 matching environmental strains, and 24 K pneumoniae strains not linked to the outbreak. They confirmed a patient from Greece as the source of the outbreak. By applying strict definitions in an epidemiologic investigation, they were able to explain transmission pathways for 11 (12.4%) of the 89 patients. Using phylogenetics, in contrast, they were able to confirm 5 of these plus an additional 15 pathways—for a total of 20 (22.5%).

The authors conclude, "Effective phylogenetic identification of transmissions requires systematic microbiologic screening. Extensive screening and phylogenetic analysis based on WGS should be started as soon as possible in a bacterial outbreak situation."
Sep 18 Am J Infect Control study


Review: Tetracyclines pose lower risk of C difficile

Originally published by CIDRAP News Sep 19

A new meta-analysis conducted by researchers at the Mayo Clinic suggests tetracyclines offer a lower risk of Clostridium difficile infection than other antimicrobials. The findings were published yesterday in Clinical Infectious Diseases.

Researchers analyzed six studies collected from several databases. The studies included hospital patients recruited between 1993 and 2012. They found that use of tetracyclines was negatively associated with C difficile, at an odds ratio of 0.62.

The authors conclude that tetracyclines may be used as a first line treatment when prescribers are concerned about C difficile infection, a life threatening condition most commonly associated with healthcare settings. The bacteria, which flourishes after treatment and overuse of antibiotics, inflames the colon, leading to colitis.
Sep 18 Clin Infect Dis study


Study finds subclone is prominent in resistant E coli infections in kids

Originally published by CIDRAP News Sep 18

Researchers at the University of Washington report in Clinical Infectious Diseases that a subclone of the emerging global pathogen E coli sequence type (ST) 131 is not as prevalent in children as adults but is nearly as dominant in drug-resistant E coli infections in children.

E coli ST131-H30 has been recognized as a clone of significant public health importance, comprising 10% to 20% of all extra-intestinal E coli infections among US adults. But data about its epidemiology in children are lacking. To quantify the burden and identify clinical and demographic correlates of infection with E coli ST131-H30 in children, the researchers prospectively collected all extended-spectrum cephalosporin-resistant (ESC-R) E coli isolates from urine or other sterile sites identified at four US children's hospitals from 2009 to 2013, along with demographic and clinical data. For each resistant isolate, researchers collected three extended-spectrum cephalosporin-susceptible (ESC-S) isolates.

A total of 339 ESC-R isolates from 278 patients and 1,008 ESC-S isolates from 1,008 patients were available for analyses. The estimated prevalence of H30 among all clinical E coli isolates at all hospitals was 5.3%. However, H30 was the most common subclone identified among the ESC-R isolates in the study, accounting for 29.9% of all ESC-R isolates and 43.3% of all extended-spectrum beta-lactamase (ESBL)–producing isolates—a proportion close to what has been observed in US adults (about 50%).

The researchers also found that patient age was associated with infection due to H30, although the nature of the association contrasted between ESC-R and ESC-S infections. In patients with ESC-R infections, H30 was associated with younger age (0 to 5 years); in patients with ESC-S infections, H30 was associated with older age (6 to 21 years) and underlying health conditions.

The authors of the study suggest the low overall prevalence of H30 in children could be the result of low fluoroquinolone use in pediatrics. They conclude, "More densely sampled studies are needed to elucidate the reservoirs and transmission dynamics of this difficult-to-treat pathogen in a pediatric population."
Sep 15 Clin Infect Dis abstract


New antibiotic shows promise against community-acquired pneumonia

Originally published by CIDRAP News Sep 18

Initial results from a phase 3 clinical trial show that the antibiotic lefamulin compares favorably to standard therapy in patients with moderate-to-severe community-acquired bacterial pneumonia (CABP), according to a news release today from Nabriva Therapeutics, the drug's maker.

In the lefamulin evaluation against pneumonia (LEAP 1) trial, the first of two phase 3 trials for the drug, intravenous to oral lefamulin met the Food and Drug Administration (FDA) primary end point of non-inferiority (NI, 12.5% margin) compared with moxifloxacin with or without adjunctive linezolid, according to Nabriva, which is based in Dublin. Early clinical response (ECR) rates assessed 72 to 120 hours following initiation of therapy were 87.3% for lefamulin and 90.2% for moxifloxacin with or without linezolid.

The drug also met the primary end points for non-inferiority established by the European Medicines Agency (NI, 10% margin). In addition, ECR by pathogen was similar to overall response rates and was comparable between treatment arms.

The trial enrolled 551 CABP patients, with 276 and 275 randomly assigned to the lefamulin arm and the moxifloxacin with or without linezolid arm, respectively. Individuals aged 65 or older represented 47.8% of the patients in the lefamulin arm, compared with 39.3 % of the patients in the moxifloxacin arm. Linezolid was added to moxifloxacin if an investigator suspected that a patient had been infected with methicillin-resistant Staphylococcus aureus prior to randomization.

A similar rate of treatment-emergent adverse events (TEAEs) was observed in both arms—38.1% in the lefamulin patients and 37.7% in the moxifloxacin with or without linezolid patients. TEAEs occurring in more than 2% of patients included hypokalemia, nausea, insomnia, infusion-site pain, infusion-site phlebitis, alanine aminotransminase increase, and hypertension. While no cases of C difficile were reported in either treatment group, diarrhea was observed in 7.7% of patients in the moxifloxacin group, compared with 0.7% of the lefamulin group.

"These Phase 3 data provide strong evidence of the potential of lefamulin to treat adults with CABP and provide an alternative to a current gold standard treatment regimen," Nabriva Therapeutics CEO Colin Broom, MBBS, said in the release. "Due to lefamulin's flexible dosing and targeted spectrum of activity against the pathogens most commonly associated with CABP, including multidrug-resistant strains, we believe that lefamulin is well suited to be a first-line empiric monotherapy."
Sep 18 Nabriva Therapeutics press release


UK: Women in preterm labor to be offered anti-Streptococcus antibiotics

Originally published by CIDRAP News Sep 18

Women who begin labor before 37 weeks of pregnancy should be offered antibiotics to prevent a group B Streptococcus (GBS) infections in newborns, according to guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) updated last week.

GBS is the most frequent cause of severe early-onset infection in newborns, occurs naturally in the lower vaginal tract of women, and can be passed on to the babies, RCOG said in a news release. The vast majority of infants will suffer no ill effects, but a small percentage will develop an infection and fall seriously ill.

Incidence of early-onset GBS appears to be rising in the UK and around 500 babies developed the condition in 2015, RCOG said. With prompt treatment, 17 of 20 diagnosed babies will fully recover, but 2 in 20 will recover with some disability, and 1 in 20 will die. Women are at higher risk of passing GBS to their baby if they go into preterm labor, and the risk of dying from GBS can be 10 times higher in preterm babies compared with those born at full term.

For these reasons, the RCOG guidelines now recommend all women who go into preterm labor, regardless of whether their waters have broken, receive intravenous antibiotics during labor. The guidance, which has now been updated three times, the most recent in 2012, also advises that women who were known GBS carriers in a previous pregnancy can be offered a test at 35 to 37 week to see whether they are still a carrier.

The guidance does not recommend universal bacteriological screening for GBS, in line with recommendations by the UK National Screening Committee. The experts who produced the RCOG guidelines found no clear evidence to show routine testing would do more good than harm.
Sep 13 RCOG guidance
Sep 13 RCOG 
news release

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