ASP Scan (Weekly) for Sep 27, 2019

Molecular test for blood infections
Rapid TB test assessment
CRE risk in Europe
Cefto-tazo for nosocomial pneumonia
XDR typhoid in Taiwan
UK antimicrobial resistance funds
CARB-X diagnostic graduate
Outpatient antibiotic prescribing
Hospital Candida auris outbreak
AMR Challenge commitments
UK prescribing letter

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

Rapid test for bloodstream infections tied to faster optimal antibiotics

Use of a rapid molecular identification test on positive blood cultures from critically ill patients with bloodstream infections was associated with significantly reduced time to optimal antibiotic treatment, Belgian researchers reported yesterday in PLOS One.

In a study conducted in the intensive care unit (ICU) of a Belgian tertiary hospital, the researchers compared two methods of blood culture management in patients who had positive blood cultures. In the 8-month pre-intervention period (P0), they performed standard blood culture management, including Gram stain, matrix-assisted laser desorption ionization time-of-flight mass spectrometry identification, and antimicrobial susceptibility testing. In the intervention period (P1), standard blood culture management was completed with the BioFire FilmArray blood culture identification (FA-BCID) panel, which can identify 24 microorganisms and three antibiotic resistance genes from whole blood in just over an hour. The primary outcome was median time to optimal antibiotic treatment.

Outcome analysis was performed on 110 bloodstream infections both in P0 and P1. Time to optimal antimicrobial treatment in P0 was 14 hour and 41 minutes, compared with 4 hours and 39 minutes in P1. FA-BCID test results led to a treatment adjustment in 35 (31.8%) of 110 P1 episodes, including 26 in which the adjustment was the optimal antimicrobial treatment. With regard to microbiologic performance, FA-BCID testing identified 96.2% of the on-panel microorganisms, thereby covering 85.2% of the ICU-strain epidemiology. Time to identification with FA-BCID testing was calculated at 1 hour and 35 minutes. Resistance detection was in complete concordance with routine results.

The authors of the study conclude that FA-BCID could be a beneficial add-on identification tool for diagnosing bloodstream infections in critically ill patients, but they add that further studies are needed in settings with high proportions of multidrug-resistant infections.
Sep 26 PLOS One study


Rapid molecular TB test shows promise in comparative study

A multicenter study by an international team has found that an automated molecular assay that rapidly detects tuberculosis (TB) and genetic mutations associated with multidrug resistance had comparable sensitivity and specificity to a widely used rapid molecular test.

In a prospective study published today in Clinical Infectious Diseases, researchers assessed the accuracy of the BD MAX MDR-TB assay performed on sputum, which was then processed for mycobacterial culture and phenotypic drug testing. The Xpert MTB/RIF assay, a rapid molecular test endorsed by the World Health Organization for use in TB-endemic countries, was also performed for comparison. Participants with TB symptoms were recruited and enrolled from study sites in Uganda, South Africa, India, and Peru from May 2017 through March 2018.

Of the 1,102 patients screened, 1,053 met the enrollment criteria. In patients with microbiologically confirmed Mycobacterium tuberculosis (MTB), BD MAX sensitivity was 93% (262 of 282; 95% confidence interval [CI], 89% to 95%), while specificity was 97% (593/610; 95% CI, 96% to 98%) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175; 98% to 100%) for smear-positive samples (fluorescence smear-microscopy), and 81% (87/107; 73% to 88%) in smear-negative samples. When both BD MAX and Xpert were compared, sensitivity was 91% (249/274; 87% to 94%) for BD MAX and 90% (246/274; 86% to 93%) for Xpert on processed sputa.

Sensitivity and specificity for rifampicin resistance compared with phenotypic drug susceptibility testing was 90% (9/10; 60% to 98%) and 95% (211/222; 91% to 97%), respectively. Sensitivity and specificity for detection of isoniazid resistance was 82% (22/27; 63% to 92%) and 100% (205/205; 98% to 100%), respectively.

The authors say new TB diagnostic tools are needed and underscore the ability of BD MAX to process more samples simultaneously than the Xpert assay. They write, "For many high-burden settings with a high-volume of testing, the BD MAX assay may represent an important automated tool for rapid detection of both MTB and drug resistance." They add that Xpert can test only for resistance mutations associated with rifampicin.

The study was sponsored by BD MAX developer Becton, Dickinson and Company.
Sep 27 Clin Infect Dis abstract


European report highlights spread of carbapenem-resistant pathogens

The European Centre for Disease Prevention and Control (ECDC) today issued an updated rapid risk assessment for carbapenem-resistant Enterobacteriaceae (CRE).

According to the assessment, data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) for 2017 show a large variability in national percentages of carbapenem-resistant Klebsiella pneumoniae in European Union/European Economic Area (EU/EEA) countries, ranging from 0% to 64%, and a statistically insignificant drop in the population-weighted mean percentage for the EU/EEA overall, from 7.3% in 2014 to 7.2% in 2017. For carbapenem-resistant Escherichia coli, national percentages ranged from 0% to 1.6% in 2017, with a slightly decreasing trend observed for the EU/EEA overall from 2014 through 2017.

Despite the low percentages of CRE isolates in many European countries, however, the ECDC reports that a national self-assessment of epidemiologic stages conducted in 2018 documented an evolving pattern of spread of carbapenemase-producing CRE (CP-CRE) in Europe, with 16 of 37 countries (43%) reporting regional or interregional spread of CP-CRE and 4 other countries reporting an endemic situation. In addition, there have been large CRE outbreaks in healthcare settings in several EU states, including some with low CRE rates. Finally, the report notes that introduction of CRE via cross-border patient transfers and travelers from high-prevalence countries might significantly contribute to the spread of these bacteria into countries with a low prevalence.

To guard against the spread of CRE, the assessment recommends that hospitals implement and adhere to infection control measures, including hand hygiene, contact precautions, and cleaning and disinfecting patient rooms; screen patients at high risk for digestive tract CRE carriage; consider enhanced control measures such as patient isolation and cohorting and dedicated nurses; and implement antimicrobial stewardship programs to curb unnecessary use of carbapenems.

In addition, the ECDC encourages hospitals involved in cross-border patient transfers to consider taking a detailed history of travels and hospitalization for every patient at hospital admission and performing pre-emptive isolation and screening in patients who've been transferred from or hospitalized in countries that have a high CRE prevalence.
Sep 27 ECDC rapid risk assessment


Study finds ceftolozane-tazobactam non-inferior for serious pneumonia

Originally published by CIDRAP News Sep 26

An international group of researchers, in a phase 3 trial, have demonstrated that ceftolozane-tazobactam—an antibiotic approved in 2014 for complicated urinary tract and intra-abdominal infections—is non-inferior to meropenem for serious cases of nosocomial (hospital-acquired) pneumonia, paving the way for a potential new tool for the disease.

Writing in The Lancet Infectious Diseases yesterday, the team detailed the randomized, controlled trial conducted at 263 hospitals in 34 countries. The scientists included 726 patients with severe nosocomial pneumonia: 71% had ventilator-associated pneumonia, and 92% required intensive care. They placed 362 in the ceftolozane–tazobactam group and 364 in the meropenem group. The former received 3 grams of the drug, while the latter received 1 gram; both antibiotics were administered every 8 hours for 8 to 14 days.

At 28 days, 87 patients (24.0%) in the ceftolozane–tazobactam group and 92 (25.3%) in the meropenem group had died. At the test-of-cure visit, 197 patients (54%) in the ceftolozane–tazobactam group and 194 (53%) in the meropenem group were clinically cured. "Ceftolozane–tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure," the authors conclude.

Citing the most common causes of nosocomial pneumonia, they add, "High-dose ceftolozane-tazobactam can be used to treat nosocomial pneumonia caused by P aeruginosa (including multidrug-resistant strains), Enterobacteriaceae (including producers of extended-spectrum β-lactamases), and other Gram-negative pathogens."

In an accompanying commentary, experts from the United States and Brazil point out that using a higher meropenem dose might have afforded a better comparison. But they write, "Ceftolozane-tazobactam is a welcome addition to the antibiotic armamentarium for nosocomial pneumonia. Still, in view of the high dose used in this trial and the limited safety data available, close monitoring and surveillance of clinical practice and phase 4 safety registries will be necessary to better define the risk-benefit profile of this new antimicrobial."
Sep 25 Lancet Infect Dis study
Sep 24 Lancet Infect Dis commentary


XDR typhoid case reported in Taiwan

Originally published by CIDRAP News Sep 26

Health officials in Taiwan have announced their first imported case of extensively drug-resistant (XDR) typhoid, according to a government statement posted and translated by Avian Flu Diary, an infectious disease news blog.

The statement from Taiwan's Department of Disease Control says the case involves a 30-year-old man who began developing symptoms (diarrhea, fever, and rash) on Aug 4, after traveling to Morocco, India, Indonesia, and Pakistan. Subsequent blood tests confirmed typhoid fever, a highly infectious illness caused by Salmonella enterica serotype Typhi. Genetic sequencing identified the strain, which is resistant to five classes of antibiotics, as originating from Pakistan.

Pakistan is currently the center of an outbreak of XDR Salmonella Typhi that originated in Sindh province in 2016. In December 2018, the World Health Organization reported that the outbreak had affected more than 5,200 people in the country, mainly in Karachi and Hyderabad. 
Sep 24 Avian Flu Diary post 


UK announces funding to boost AMR surveillance in Africa, Asia

Originally published by CIDRAP News Sep 26

The United Kingdom's outgoing chief medical officer yesterday announced £6.2 million ($7.6 million US) in funding to strengthen antimicrobial resistance (AMR) surveillance systems in Africa and Asia.

Professor Dame Sally Davies announced the funding at the United Nations General Assembly (UNGA) in New York, along with £12 million ($14.8 million US) to improve collaborations on health systems research between the UK and low- and middle-income countries. Davies is representing the UK in UNGA high-level discussions on universal health coverage.

UN member states yesterday adopted a declaration recognizing that addressing AMR and investing in innovative health research are critical strategies for achieving universal health coverage. The AMR funding, which will come from the Fleming Fund, will help improve AMR data quality, collection, and sharing in African and Asian nations, with the goal of developing policy and action from that data.

"I am delighted to announce this funding, which will catalyse regional collaboration to help strengthen AMR surveillance systems across Africa and Asia and support the next generation of health policy and systems research," Davies said in a news release from the UK government's Department of Health and Social Care (DHSC).
Sep 25 DHSC news release


CARB-X touts success of rapid diagnostic test

Originally published by CIDRAP News Sep 24

CARB-X announced today that a test designed to rapidly detect antibiotic resistance genes in whole-blood samples has become to first diagnostic to "graduate" from the CARB-X portfolio.

CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) awarded T2 Biosystems of Lexington, Mass., $2 million in 2017 to develop the T2Resistance Panel, which can detect 13 resistance genes in gram-positive and gram-negative pathogens directly from a whole-blood specimen within 3-to-5 hours. The test was granted Breakthrough Device designation by the Food and Drug Administration earlier this year, and is expected to soon be available for research use only in the United States and commercial use in Europe.

"We are incredibly grateful to CARB-X for the funding and support they provided to our team in the development of the T2 Resistance Panel over the past year and a half," T2 Biosystems chairman and CEO John McDonough said in a CARB-X press release. "Rapid identification of the genes and species associated with antibiotic resistance can help enable the reduction of unnecessary antibiotic use, which is the primary cause of resistance."

"The T2Resistance Panel will provide healthcare professionals with a new rapid test, a first of its kind, to provide timely and accurate detection of drug-resistant infections and inform treatment decisions to ensure patients are given the most appropriate care," said CARB-X executive director Kevin Outterson, JD.

The test is one of four diagnostics in the CARB-X portfolio.
Sep 24 CARB-X press release


Study highlights improper first-line antibiotic prescribing for outpatients

Originally published by CIDRAP News Sep 24

A comparison of antibiotics prescribed for pharyngitis, sinusitis, and acute otitis media in a variety of outpatient settings found that only 50% of patients received recommended first-line antibiotics—when the figure should be closer to 80%.

A research team led by Centers for Disease Control and Prevention (CDC) scientists published its findings yesterday in Antimicrobial Agents and Chemotherapy.

The researchers based their analysis on the 2014 MarketScan Commercial Database, focusing on antibiotics selected for the three conditions at retail clinics, emergency departments, urgent cares, and offices. Previous studies have profiled antibiotic prescribing patterns for the conditions at emergency departments (EDs) and offices, but evidence was lacking on antibiotic selection at retail health and urgent care centers, which make up a growing percentage of US outpatient visits.

The study included records of pediatric patients and adults up to age 65. First-line therapy was defined as amoxicillin or penicillin for pharyngitis and amoxicillin or amoxicillin-clavulanate for sinusitis and pediatric ear infection.

Overall, of antibiotic visits for the three conditions, 50% of patients received first-line therapy, but the percentage varied by setting, with first-line therapy at 70% for retail clinics, 57% for EDs, 49% in urgent care centers, and 50% in offices. First-line therapy was higher for children (62%) than adults (41%). Percentages also varied by condition, and macrolides were the most common non-first-line therapy.

When the group looked at common respiratory conditions, 50% of patients received first-line antibiotics, with retail clinics highest at 70%.

The researchers concluded that all settings can improve antibiotic selection, given that first-line therapy should be used in at least 80% of visits for the three conditions.
Sep 23 Antimicrob Agents Chemother abstract


Report puts cost of 34-case Candida auris outbreak at over $1 million

Originally published by CIDRAP News Sep 24

A 34-case outbreak of Candida auris infections at a London hospital in 2016 and 2017 spotlights how devastating the multidrug-resistant fungus can be, in both clinical impact and hospital costs, according to a study yesterday in the Journal of Infection.

Investigators with King's College Hospital identified 14 confirmed or probable infected patients from July 2016 through February 2017, as well as 20 colonized patients. Eight of the patients had C aurisbloodstream infections.

The researchers determined that infection was significantly associated with prolonged hospital stay, hemodialysis, and recent antifungal therapy. Isolates from patients demonstrated variable susceptibility to amphotericin and the triazoles, and isolates clustered with the South Asian strains of the fungus. Four patients died within 30 days of infection or colonization, including two who had infections.

They cite the lack of early identification and isolation of the index case-patient as the likely initiating factor in the outbreak.

The authors estimated that the total cost of the outbreak was £1 ($1.25 million), not including the lost opportunity cost of cancelled operations, extra consumables in the operating rooms, screening costs before a formal test was introduced in the lab, and other miscellaneous costs. In addition, the researchers reported a substantial cost associated with isolation and precautions taken for patients who were awaiting confirmation of C auris during the initial part of the outbreak but were ultimately negative.

The authors write, "In conclusion, controlling an outbreak of C. auris requires a multipronged approach which can be expensive over the short term. Implementation of hospital wide communication, detection by screening, mandatory isolation and aggressive disinfection at an early stage may help reduce transmission and morbid complications of the disease."
Sep 23 J Infect abstract


HHS, CDC celebrate commitments to fight antimicrobial resistance

Originally published by CIDRAP News Sep 23

Officials from the US Department of Health and Human Services (HHS) and the CDC said today during the United Nations General Assembly (UNGA) in New York that they've received nearly 350 commitments from corporations, non-profit organizations, and health officials in 33 countries to take specific actions against antimicrobial resistance (AMR).

The commitments are in response to the AMR Challenge, an initiative launched last year at the UNGA by HHS and the CDC. The challenge, which emphasizes a One Health approach to addressing AMR, asked public- and private-sector organizations and leaders around the world to make a commitment in one of five areas: improving antibiotic use in humans and animals; reducing antibiotics and resistant bacteria in the environment; developing new antibiotics, vaccines, and diagnostics; enhancing data collection and sharing; and improving infection prevention and control.

In a press release, the CDC said nearly half of the commitments focus on improving antibiotic use in humans and animals, and nearly 45% focus on improving infection prevention and control. More than 55 pharmaceutical and biotech groups committed to developing or providing access to products that will prevent and treat resistant infections, and 47 organizations made commitments related to safe drinking water, sanitation, and hygiene. Seventy-six of the commitments came from countries outside the United States.

"The year-long initiative we launched last year around this time, the AMR Challenge, marks a historic step and sets a promising precedent," HHS Secretary Alex Azar said in prepared remarks. "The success of the Challenge over the past year demonstrates what is possible, in the relatively short term, when we have real commitment to the fight against this pressing public health threat."
Sep 23 CDC press release
Sep 23 AMR Challenge commitments
Sep 26, 2018, CIDRAP News story "HHS, CDC issue AMR 'challenge' to public, private sectors"


Letter from 'high-profile messenger' helps cut antibiotics in England

Originally published by CIDRAP News Sep 23

A new study by Public Health England has found that a letter from England's Chief Medical Officer (CMO) to primary care physicians with high antibiotic prescribing rates reduced prescribing by more than 3%. The findings appeared in the Journal of Antimicrobial Chemotherapy.

The CMO sent the letter on antibiotic prescribing rates to general practitioners (GPs) in 1,439 practices in England that were ranked in the top 20% of prescribers in April 2017. A version of the letter, which stated that "the great majority of practices in England prescribed fewer antibiotics per head than yours," has been sent to high prescribing GPs in England annually during each winter flu season since 2014, when a randomized clinical trial found the intervention reduced prescribing by 3.3% in an intervention group. To evaluate whether the letter continues to be effective, researchers from PHE Behavioural Insights measured the average rate of antibiotics dispensed by the GPs from April 2017 to September 2017, compared to a control group of GPs that didn't receive the letter.

Using regression discontinuity design to evaluate the intervention, the researchers estimated that the practices that received the letter changed their prescribing rates by approximately -3.69% (95% CI, -2.29 to -5.10), with the biggest reduction seen among prescribers in the top 11% to 20% and a lesser effect observed in the top 10% of prescribers. Based on this reduction, an estimated 124,952 fewer antibiotics were dispensed during the intervention period.

"Our results suggest that the social norm feedback intervention can be successfully implemented multiple times," the researchers write.

The intervention has also been adopted by CMOs in Australia, Northern Ireland, and Canada, and France is planning to follow suit.
Sep 20 J Antimicrob Chemother study

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