News Scan for Sep 16, 2016

News brief

Florida governor allocates more money to fight Zika

In the face of stalled federal dollars to fund the fight against Zika, Florida Governor Rick Scott said he would be allocating an additional $10 million in funds from the state’s General Revenue fund to fight the mosquito-borne illness. Florida has now spent $36.2 million on Zika.

Scott's announcement came after he travelled to Washington DC, to convince Congress that urgent action was needed to successfully fight Zika. Florida has been the epicenter of Zika virus in the United States, with local transmission of the virus currently taking place in Miami-Dade County.

"Zika is non-partisan and I have been very clear that something had to get done this week," Scott said on his website. "While it doesn’t look like that is going to happen, I will not wait on the federal government to protect Floridians and our visitors."

The Associated Press (AP) reported yesterday that some congressional aides are hinting at possible progress on a Zika funding bill. Aides said Republicans would allow "Planned Parenthood affiliated clinics share in new funding to fight the virus."

Efforts to pass Zika funding have failed three times since President Obama first requested $1.9 billion in February. Lawmakers have until Oct 1 to pass legislation and prevent a government shutdown.
Sep 16 Governor Scott statement
Sep 15 AP story

First new Saudi MERS case reported in 5 days

The Saudi Ministry of Health (MOH) reported a new case of MERS today, the first in nearly a week.

A 70-year-old man from Hail was diagnosed as having MERS-CoV (Middle East respiratory syndrome coronavirus) after presenting with symptoms. He is currently in stable condition, and the MOH listed his exposure to the virus as primary, which means he did not acquire it from another patient.

On Sep 14, the World Health Organization said Saudi Arabia mitigated any MERS threat during the Hajj pilgrimage, which brought 2 million people to Mecca.

Saudi Arabia's MERS case count since 2012 has now reached 1,452, including 613 deaths. Three patients are still being treated, according to the MOH.
Sep 16 MOH report

Pew report: Better effort needed to prevent foodborne pathogens

The Pew Charitable Trust published a report earlier this week detailing the ways US food producers can limit the risk of novel foodborne pathogens, including MERS-CoV (Middle East respiratory syndrome coronavirus), as well as established pathogens which are showing emerging strains, like Listeria

To protect consumers, the report outlines several recommendations, including expanded testing of retail meats for antimicrobial-resistant bacteria, including Escherichia coli, Salmonella, Campylobacter, and Staphylococcus aureus. The report also recommends increasing funding for basic food safety research and limiting antibiotic use in agriculture.

The 77-page report concludes by emphasizing that foodborne disease is not a static threat. "New risks will continue to emerge, and it is important to improve and integrate surveillance to be able to detect and assess emerging hazards of both newly recognized EPs [emerging pathogens] and emerging strains of known pathogens. Surveillance should span food, humans, food-producing animals, and the environments in which they live."
Sep 13 Pew Charitable Trusts report

French researchers report non-MCR-1 colistin resistance in CRE

In analyzing samples from a French national database of carbapenem-resistant Enterobacteriaceae (CRE) from patients, Swiss and French scientists found that from 6% to 8% of Klebsiella and Enterobacter isolates were resistant to collagen without carrying the MCR-1 colistin-resistance gene that has now been reported in more than 30 nations.

In their report in Eurosurveillance yesterday, the investigators note that the rate is markedly lower than in other southern European countries.

Their analysis included 972 consecutive CRE isolates from 2014. Included were 577 Klebsiella (59%), 236 Escherichia coli (24%), 108 Enterobacter (11%), 50 Citrobacter (5%), and 1 Salmonella isolate (0.1%). Of 561 K. pneumoniae isolates, 35 (6.2%) were found to be resistant to colistin. And of 91 Enterobacter cloacae isolates, 7 (7.7%) were resistant to colistin and produced different types of carbapenemases.

Surprisingly, the researchers reported none of the E coli or Citrobacter isolates demonstrated resistance to colistin. They also note that the colistin resistance rate in the CRE K pneumoniae isolates was much lower than in Spain (20%) and Italy (43%).

The authors conclude, "No plasmid-encoded mcr-1 gene was identified here. Therefore it seems that it is still possible to control the spread of those multidrug-resistant isolates based on accurate identification of colistin resistance and isolation of plasmid-encoded MCR-1 producers. Amikacin and fosfomycin remained the antibiotic agents most effective against those isolates which were resistant to polymyxins and produced a carbapenemase."
Sep 15 Eurosurveill report

Results of Novavax trial of RSV vaccine in seniors disappoint

Novavax, Inc., yesterday reported disappointing phase 3 trial results in seniors for its candidate vaccine against respiratory syncytial virus (RSV), according to a press release from the company.

The company said goals of the trial of it recombinant F-protein nanoparticle candidate, conducted at 60 sites in the United States in 11,856 adults age 60 and older, were to show efficacy against moderate-to-severe RSV-linked lower respiratory disease and efficacy against all respiratory symptoms related to RSV. The vaccine failed to meet both end points.

Gregory Glen, MD, president of research and development at Novavax, said in the statement that that there doesn't appear to be problems with the trial's execution or the quality of the vaccine. One problem, though, could be that the trial took place during a mild RSV season in older adults. During the trial, investigators saw an attack rate of 2% for any RSV-linked respiratory disease, with the attack rate at 0.4% for lower respiratory disease caused by RSV. The levels were much lower than the 3% to 7% attack rates historically seen in older adults.

"We are continuing to investigate potential root causes that could have impacted the outcome of this trial," Glen said. "We continue to believe that there is a path forward for our RSV vaccine and that there is an important unmet need for an RSV vaccine in older adults."

Novavax also described early results from a phase 2 trial designed to test the efficacy of a second annual dose of the vaccine. That trial, which enrolled 1,329 older adults from 10 centers, also took place during the same low-attack-rate year, but it hints that second-season immunization was protective, even in a year with a very low attack rate. The company said it would know more after it fully evaluates the immune responses.

Stanley Erck, Novavax's president and chief executive officer, in the statement called the results unexpected, but added that the company still believes in its product. He added that the company will provide a more detailed update at an investor and analyst meeting on Oct 11.
Sep 15 Novavax press release

Low-path H5N3 avian flu found on French farm

The same day that France said it will lift restrictions in the southwestern area of the country that has been hit by at least 81 highly pathogenic avian flu outbreaks, French officials report finding the low-pathogenic version of the virus, which is not as deadly to poultry.

Low-path H5N3 avian flu was detected by surveillance efforts in a flock of 6,000 poultry on a farm in Athos-Aspis in Pyrenees-Atlantiques department in the far southwest, officials said in a report to the World Organization for Animal Health (OIE) yesterday. Samples taken on Sep 6 tested positive by both sequencing and polymerase chain reaction on Sep 13.

France has now reported eight detections of low-path H5N3 avian flu in less than a year, with the most recent previous one last month.
Sep 15 OIE report
Sep 15 Reuters story on end to restrictions

ASP Scan (Weekly) for Sep 16, 2016

News brief

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

French researchers report non-MCR-1 colistin resistance in CRE

In their report in Eurosurveillance yesterday, the investigators note that the rate is markedly lower than in other southern European countries.

NDM-1 detected in 27 Vibrio fluvialis isolates in India

Originally published Sep 15.

Although MCR-1 has often garnered drug-resistance headlines of late, an earlier gene that also confers antimicrobial resistance, NDM-1 (New Delhi metallo-beta-lactamase) has not gone away, as evidenced by a study yesterday in Emerging Infectious Diseases. Researchers reported the gene in 27Vibrio fluvialis isolates in Kolkata, India.

NDM-1 was first discovered in 2009, with the first US cases reported in 2010. It has been reported most commonly in India and Pakistan. MCR-1 was first detailed in a report late last year and renders pathogens resistant to the last-line antibiotic colistin. Most NDM-1 strains are susceptible to colistin but resistant to most commonly used antibiotics.

In the new study, Indian researchers were screening samples from hospitalized patients who had diarrhea when they identified the 27 NDM-1 V fluvialis isolates, which were resistant to all antimicrobials tested except doxycyline. The genes flanking the NDM-1 genes were identical to those identified in a comparison NDM-1 Escherichia coli bacterium isolated previously.

The scientists were also able to transfer the NDM-1-containing plasmid to other pathogens such as E coli, but those pathogens exhibited a slightly less extensive antimicrobial resistance profile.

The authors concluded, "The pathogenicity of V. fluvialis to humans and its ubiquitous presence in the environment call for constant monitoring of this species for emerging antimicrobial drug resistance."
Sep 14 Emerg Infect Dis report

Study says WHO guidelines might underestimate cure in MDR-TB patients

Originally published Sep 15.

A new study suggests that the way the World Health Organization (WHO) defines "cure" for patients with multidrug-resistant tuberculosis (MDR-TB) may underestimate how many people recover from the disease.

The study, published in the New England Journal of Medicine, evaluated treatment outcomes for 380 European MDR-TB patients according to WHO definitions and compared them with simplified definitions of treatment outcomes. Under the WHO guidelines, cure was defined as treatment completion with at least three negative cultures after the intensive phase of therapy in the absence of treatment failure. Under the simplified definition, cure was defined as a negative culture status 6 months after treatment initiation, no positive culture thereafter, and no relapse within 1 year after treatment completion.

The study found that relapse-free cure was achieved in 61% of patient with MDR-TB, 52% of patients with pre-extensively drug-resistant (XDR) TB, and 39% of patients with XDR-TB. Under the WHO definition, 31%, 27%, and 24% of patients, respectively, were considered cured.

"In conclusion, current WHO definitions may underestimate cure in patients with MDR tuberculosis," the study authors wrote. "These definitions could be simplified while incorporating the assessment of post-treatment relapse."
Sep 15 N Engl J Med correspondence

Report notes multidrug-resistant CRE after combo treatment

Originally published Sep 14.

Investigators from the University of Pittsburgh yesterday reported 3 cases of ceftazidime-avibactam resistance after 37 patients who had CRE infections were treated with the combination, according to a case series in Clinical Infectious Diseases.

The scientists reported a 59% success rate (22/37), with 9 deaths, 4 recurrent CRE infections, and 2 patients with no clinical improvement. Microbiologic failure, defined as isolation of CRE after 7 or more days of ceftazidime-avibactam therapy, occurred in 10 of the 37 patients (27%), with 5 patients having recurrent CRE at 30 days and 4 at 90 days and 1 patient having urinary colonization with CRE.

Of those 10 patients, ceftazidime-avibactam resistance was detected in 3. Ceftazidime is a third-generation cephalosporin, and avibactam is a beta-lactamase inhibitor.

An accompanying commentary by Brad Spellberg, MD, of the University of Southern California and Robert Bonomo, MD, of Case Western Reserve University in Cleveland, said the fact that the resistance developed after only 10 to 19 days of ceftazidime-avibactam therapy is especially worrisome.

"It is important not to draw firm conclusions from an uncontrolled, retrospective case series," the commentary authors wrote. "Nevertheless, this is a very important study, as it is the first meaningful clinical evaluation of the efficacy of ceftazidime-avibactam when treating CRE infections, and among a fairly large number of patients with CRE. The results are quite concerning. Mortality continues to be high, and resistance seems to emerge rapidly."
Sep 13 Clin Infect Dis abstract
Sep 13 Clin Infect Dis commentary

Study finds high rate of MDR pathogens in hospitalized Syrian children

Originally published Sep 13.

Researchers at a hospital in Israel are reporting a high rate of MDR pathogen carriage among Syrian children who were ill or wounded during the ongoing Syrian civil war.

The study, conducted at Israel's Galilee Medical Center and published in Emerging Infectious Diseases yesterday, involved 128 children admitted to the hospital for multiple trauma and acute or chronic illness from March 2013 to February 2016. Of the 128 children, 107 were screened for five MDR pathogens: extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL), CRE, methicillin-resistant Staphylococcus aureus, MDR Acinetobacter baumannii (MDR-AB), and vancomycin-resistant Enterococcus.

The researchers identified MDR pathogens in 89 of the 107 children (83%), with all five classes of pathogen being represented. Infections were present in 24 of the children (19%), with urinary tract, surgical site, and bone infections being the most prevalent. Two thirds of infections were caused by ESBL, 20% by MDR-AB, and 15% by CRE.

Previous studies have found a high rate of MDR pathogen carriage among Syrian refugees treated in Italy, Germany, and Lebanon.

The authors of the study said the findings imply that there is probably a high carriage rate of MDR pathogens among healthy children in Syria, as well as a high rate of MDR pathogen acquisition in the Syrian healthcare system. They also added that the destruction of hospital infrastructure and inadequate infection control, on top of the widespread use of antimicrobials that preceded the war, have likely made the situation worse.

They recommend that healthcare centers caring for patients from Syria isolate those patients upon admission to prevent the transmission of MDR pathogens.
Sep 12 Emerg Infect Dis letter

New antibiotic candidate for C diff diarrhea receives boost from FDA

Originally published Sep 13.

The Food and Drug Administration (FDA) has granted Qualified Infectious Disease Product (QIDP) designation to the antibiotic candidate MGB-BP-3 for the treatment of Clostridium difficile–associated diarrhea (CDAD).

According to a press release from biopharmaceutical company MGB Biopharma, The QIDP designation was granted after a phase 1 study of the oral formulation of MGB-BP-3 confirmed that the compound was well tolerated in healthy volunteers and had a noted effect on C difficile bacteria. The company says it is now preparing for a phase 2 clinical trial to investigate the compound's safety and efficacy in patients with CDAD.

The QIDP designation, created by the Generating Antibiotic Incentives Now (GAIN) Act of 2012, provides incentives for the creation of new antibacterial and anti-infective products. Those incentives include priority review and an additional 5 years of marketing exclusivity.
Sep 12 MGB Biopharma press release

Plumbing pathogens costly and increasingly resistant to antibiotics

Originally published Sep 12.

A study today in the Journal of Public Health Policy examined US hospitalizations caused by opportunistic premise plumbing pathogens (OPPP) like legionellosis from 1991 to 2006 and found they are costly, especially among those over the age of 65. Additionally, growing antibiotic resistance to OPPP raises the economic burden of disease.

After looking at 100 million Medicare records, researchers identified 617,291 hospitalized infections caused by three OPPPs: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa. Calculations showed that the three OPPP infections in elderly patients cost about $600 million per year over the study period. Antibiotic resistance was present in about 2% of those cases, but when it was present, it was resistant to multiple drugs.

The authors said that increased surveillance for OPPP is needed, especially because aging infrastructure allows pathogens to flourish in drinking water. They also note that infections with L pneumophila, which causes Legionnaires' disease, are on the rise. From 2001 to 2006 Legionella was responsible for 29% of drinking water outbreaks of OPPPs.

In related news, today the Minnesota Department of Health (MDH) said officials were investigating a cluster of five cases of Legionnaires' disease in Hopkins, Minnesota. All five patients were hospitalized. This is the first cluster of cases reported in 2016 in the state.

Investigators do not know the source of the outbreak but are looking at pumping systems, fountains, and cooling towers. Legionnaires' disease occurs when someone inhales an infected spray from a water source. It cannot be passed person-to-person.

The MDH said the state has already seen more than 60 cases this year, already surpassing the average of 50 cases per year.
Sep 12 J Public Health Policy study
Sep 9 MDH press release