Stewardship / Resistance Scan for Sep 17, 2018

News brief

Study links seasonal macrolides use, resistance in N gonorrhoeae

Using a mathematical model that links seasonal patterns of antibiotic use with resistance, researchers from Harvard and the Centers for Disease Control and Prevention (CDC) have found that seasonal changes in population-wide macrolide use is associated with a small rise in azithromycin non-susceptibility in Neisseria gonorrhoeae isolates.

The ecological study, published in the Journal of Infectious Diseases, used the mathematical model to link seasonal variations in the use of macrolides (azithromycin, clarithromycin, and erythromycin) with seasonal minimum inhibitory concentrations (MICs) for azithromycin. Their hypothesis was that periods of above-average use would create more selection pressure and result in higher azithromycin MICs 3 months later.

The researchers measured the seasonality of macrolide use from 2011 through 2015 using a nationwide pharmacy prescription claims database and investigated N gonorrhoeae azithromycin MIC seasonality using 62,500 isolates collected as part of the CDC's Gonococcal Isolate Surveillance Project.

The results showed that year-round macrolide use was 12.8 monthly outpatient pharmacy fills per 1,000 insurance members, with seasonal amplitude of 4.8 monthly fills per 1,000 members and a peak in use in December/January. Azithromycin resistance among N gonorrhoeae isolates was seasonal, with an amplitude of 0.076 dilutions. As predicted by the model, seasonal resistance peaked in March/April, 3 months after peak macrolide use. A back-of-the-envelope calculation showed that a 10% increase in macrolide use is associated with an additive increase in mean MIC of 0.0015 micrograms per milliliter.

The authors speculate that seasonal patterns in azithromycin MICs arise because N gonorrhoeae hosts are more likely to use macrolides for respiratory conditions in the winter than in the summer. This subjects N gonorrhoeae to a seasonal "bystander effect," in which the bacteria are exposed to additional antibiotic pressure in the winter for reasons unrelated to gonorrhea. The findings could partly explain rising azithromycin MICs in N gonorrhoeae, which are threatening the efficacy of the currently recommended treatment regimen (azithromycin and ceftriaxone) for gonorrhea infections.

The researchers conclude, "The anticipated bystander effect of antibiotics used for conditions other than gonorrhea should be considered as treatment guidelines for gonococcal infections are updated."
Sep 15 J Infect Dis abstract


UK study finds reduced prescribing, persistent geographic variation

Researchers from the University of Oxford report in the Journal of Antimicrobial Chemotherapy that while overall antibiotic prescribing has decreased in primary care settings in England since 2013, considerable geographic variation persists.

Using two sources of data routinely collected by England's National Health Service (NHS)—monthly practice-level prescribing data and annual prescription cost analysis data—the researchers set out to determine antibiotic prescribing trends in primary care in England from 1998 through 2017, geographic variation in antibiotic prescribing in 2017, trends in variation between practices from 2010 through 2017, and seasonal variation. They also looked at factors associated with higher prescribing.

The results showed that the overall rate of antibiotic prescribing fell by 18% from 2010 through 2017, with the steepest after 2013. In addition, from 2006 through 2017 the percentage of broad-spectrum antibiotic prescribing was reduced from 18% to 8.4%.

While variation across general practices has declined, there was a twofold variation for total prescribing and a sevenfold variation for cephalosporin prescribing between the highest prescribing and lowest prescribing Clinical Commission Groups (CCGs)—the NHS bodies responsible for planning and commissioning of healthcare services in a local area. The CCG to which a practice belongs accounted for 12.6% of current variation in prescribing.

Higher antibiotic prescribing was associated with greater practice size, proportion of patients older than 65 and younger than 18, poorer prescribing on other measures of rural location, and deprivation. Seasonal increases declined for most antibiotics.

The researchers conclude that while the reduction in antibiotic prescribing in primary care is encouraging, better access to and use of audit data could further improve clinical care and antibiotic use.
Sep 15 J Antimicrob Chemother study


Point-of-care viral respiratory test could aid stewardship, early results show

Initial results on a point-of-care test (POCT) for respiratory viruses indicate the potential to reduce unnecessary antibiotic use and hospital admissions, according to research presented yesterday at the European Respiratory Society International Congress.

In a study conducted at West Hertfordshire Hospitals NHS Trust in England from Jan 15 to May 1, the results of the test were combined with other important clinical factors, including chest x-ray results and lack of evidence of bacterial infection, to identify 121 patients (out of 387) who were potentially suitable for avoiding hospital admission and antibiotics. Hospital admission was avoided in 25% of these patients, and unnecessary use of antibiotics was avoided in 50%.

"None of the 30 patients who avoided hospital admission and who were not prescribed antibiotics experienced adverse clinical outcomes, which is reassuring," Kay Roy, MBChB, a consultant physician in respiratory and general internal medicine, said in a press release from the European Lung Foundation. Roy also estimated that the test could save hospitals £2,000 ($2,632) per patient not admitted to hospital.

The test involves inserting a swab into a patient's nostril, collecting secretions from the back of the nose, and analyzing the sample with a compact device called the FilmArray (made by Biofire, Biomerieux). The entire process takes 50 minutes.

"The frequent underestimation of the role of viruses in respiratory admissions, both in previously well patients and those with chronic underlying disease such as COPD [chronic obstructive pulmonary disease], has hindered good antimicrobial stewardship," said Roy. "This has sometimes led to other health problems for patients, from inappropriate antibiotic use and hospital admission. We hope that quality of patient care can be improved with POCT for respiratory viruses, as well as helping to reduce the development of antibiotic resistance."

The research is not peer-reviewed.
Sep 16 European Lung Foundation press release


Study finds male gender, catheter use tied to MDR urinary tract infections

A study of 948 patients in Europe, Turkey, and Israel has found an "alarming" rate of multidrug-resistant (MDR) gram-negative bacteria in complicated urinary tract infections (cUTIs), with predictors including male gender, acquisition of cUTI in a medical facility, and having an indwelling urinary catheter.

Writing in Antimicrobial Resistance & Infection Control, researchers said they analyzed 1,074 isolates from consecutive cUTI patients from January 2013 through December 2014. Of the isolated pathogens, 559 (52.0%) were Escherichia coli, and 97 (9.0%) were Pseudomonas aeruginosa—the two most common causal organisms. Fully 54.2% of the E coli isolates were MDR, compared with 38.1% of the P aeruginosa isolates.

The investigators also found the being male increased the odds of having MDR gram-negative infections by 66% (odds ratio [OR], 1.66). Other risk factors were acquisition of cUTI in a medical facility (OR, 2.59), presence of an indwelling catheter (OR, 1.44), having had a UTI within the year (OR, 1.89), and antibiotic treatment within the previous 30 days (OR, 1.68).

The authors conclude, "The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance."
Sep 14 Antimicrob Resist Infect Control study

News Scan for Sep 17, 2018

News brief

MERS sickens 3 more in Saudi Arabia

Saudi Arabia yesterday reported three more MERS-CoV cases, including two from different cities who contracted the virus from a sick household contact.

In its yesterday report for epidemiologic week 38, the country's ministry of health (MOH) said two of the MERS-CoV (Middle East respiratory syndrome coronavirus) cases are in Riyadh province, one of which involves a 38-year-old man from Rumah, about 74 miles northeast of the capital city of Riyadh. The man's source of the virus is listed as primary, meaning he wasn't exposed to a patient diagnosed with the illness. The other is a 34-year-old man from the city of Riyadh who is listed as a household contact.

The third MERS patient is a 62-year-old man from Buraydah in Qaseem region, an area that has reported other sporadic cases over the past month. The man had been exposed to a sick household member.

All three of the men are currently hospitalized, according to the report. The new cases appear to have pushed the global MERS-CoV total to 2,254 cases since 2012, at least 798 of them fatal.
Sep 16 Saudi MOH epi week 38 update


South Korea passes day 10 with no new MERS cases

South Korea has gone 10 days without reporting any other MERS cases related to an imported case in a business traveler who was diagnosed with the virus after returning from business travel in Kuwait, according to a status report today from the Korea Centers for Disease Control and Prevention (KCDC).

The 61-year-old man's illness was confirmed on Sep 8, and he is hospitalized at Seoul National University Hospital. Health officials are following 21 close contacts who are on home quarantine. Also, health officials have identified 406 others who had less risky contact with the patient.

In a related development, the World Health Organization (WHO) continues to support South Korea with contact tracing, public communications, and information sharing under the International Health Regulations (IHRs), the WHO's Western Pacific Regional Office said today in a statement.

The WHO added that investigations are still under way in Kuwait to determine where the man may have been exposed to the virus and if there are others he came into contact with during his travels. "WHO is facilitating information-sharing between the countries," it said.

Dr. Li Ailan, WHO's regional emergency director for the Western Pacific, said in the statement that the WHO is pleased with South Korea's response so far, especially its rapid detection and timely notifications. "However, the response is still ongoing. We must maintain our vigilance," she said. "WHO will continue to facilitate collaboration among countries and to support the response."

The WHO said that, based on lessons learned in a large outbreak linked to the country's first imported case in 2015, South Korea has invested heavily in strengthening its capacity to detect and respond to infectious disease outbreaks. It also added that MERS-CoV awareness among South Korean health workers and the general public is high, which helped facilitate prompt detection of the case.
Sep 17 KCDC update (in Korean)
Sep 17 WHO Western Pacific regional office statement


Trial of new inhaled vaccine to boost H3N2 flu protection launches in kids, teens

Researchers have started enrolling healthy children ages 9 to 17 years old in a phase 1 trial to assess a new type of inhaled flu vaccine that contains a "single-replication" virus, according to a statement today from the National Institutes of Health (NIH).

The candidate vaccine was developed by FluGen, Inc., based in Madison, Wisc., and is made from a seasonal H3N2 flu virus that has been genetically engineered to replicate only once in the body. The vaccine is in a phase 2 trial in adults. The study site is the Vaccine and Treatment Evaluation Unit, which is funded by the NIH's National Institute of Allergy and Infectious Diseases (NIAID).

A goal of the study is to combine the new inhaled vaccine with one of the current licensed vaccines provides broader protection than that afforded by current vaccines when used alone. The experimental inhaled vaccine is genetically engineered to target H3N2, even when the circulating virus doesn't closely match the vaccine strain, a protection gap inherent with most current seasonal flu vaccine formulations.

Anthony Fauci, MD, NIAID director, said in the statement, "We are hopeful that newer kinds of influenza vaccines, such as the candidate being tested in this trial, will provide protection even if their components do not precisely match the currently circulating influenza virus strains."

The double-blinded trial will enroll 50 participants, half of whom will get the candidate nasal vaccine and the other half an inactive saline solution delivered as a nasal spray. Three months after receiving the nasal spray, all subjects will receive an intramuscular injection of a licensed quadrivalent flu vaccine.  Researchers will analyze blood samples at four points after the first vaccination and at 3 weeks after the second vaccination, looking for evidence of immune responses from antibody-producing cells and from the cellular part of the immune system.

Earlier animal studies suggested that the single-replication virus doesn't cause disease but triggers a robust immune response similar to natural infection.
Sep 17 NIAID press release


WHO: Cholera outbreak strikes Algerian capital area

A rapidly spreading cholera outbreak in northern Algeria in and around the capital province of Algiers that began in early August has hospitalized 217 people, including 83 confirmed case-patients and 2 deaths, the WHO said in a Sep 14 update.

The country's health ministry announced the outbreak on Aug 23, and since then, cases have been reported in 7 of Algeria's 48 provinces. The event marks Algeria's first cholera outbreak since 1996.

The Pasteur Institute in Algeria has confirmed Vibrio cholerae serogroup O1 Ogawa as the outbreak strain, and tests on 21 water sources in the affected areas found that 10 were inappropriate for human consumption. One well that was positive for V cholerae was condemned for human consumption. So far, the source of the bacteria and the transmission vehicle isn't known, but health officials said most cases are clustered within a family group.

An urban setting increases the risk of transmission, especially given that the source of the outbreak hasn't been identified, the WHO said. However, it noted that recent information from the health ministry suggests that the outbreak is slowing down. The WHO said further analysis of the V cholerae specimens should be done, including sequencing the cholera toxin gene, to see if an epidemic strain is fueling the outbreak.
Sep 14 WHO statement

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