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

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

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