Stewardship / Resistance Scan for Dec 19, 2018

News brief

Study finds link between occasional antibiotic use and resistance

Antibiotic resistance in the United States appears to be more closely linked to occasional antibiotic use by many people rather than heavy use by few people, and resistance to certain antibiotics is higher in areas where they are used more often, according to a comprehensive study yesterday in eLife.

US and Canadian experts analyzed 99.8 million outpatient pharmacy antibiotic prescription fills among 108 million unique people (about 20% of the US population) from 2011 through 2014 using the MarketScan database. They noted that, in 2011, 34% of the people took an antibiotic, but 10% of them received 57% of all prescriptions, which is similar to previously published UK data. The distribution varied by population but was similar across all 4 years.

The researchers also examined data from 2012 to 2015 from ResistanceOpen, which tracks antibiotic resistance across the country. To correlate antibiotic use for a particular drug with rates of antibiotic resistance against that drug, the researchers looked at 72 pairs of antibiotics and bacteria.

The investigators found that the more a particular antibiotic was used, the greater the resistance. For instance, in states that use more quinolones, more infections caused by Escherichia coli tend to be resistant to quinolones.

When comparing occasional, low-intensity antibiotic use by many people to intense use by a few people, however, they found that occasional, low-intensity use was more closely associated with rates of resistance.

"Our findings suggest that combatting inappropriate antibiotic use among people who don't take many antibiotics may be just as important, or more important, to fighting resistance than focusing on high-intensity users," said lead author Scott Olesen, PhD, a postdoctoral fellow at the Harvard TH Chan School of Public Health, in a Harvard news release. "More antibiotic use generally means more antibiotic resistance, but it seems like the number of people taking antibiotics might matter more than the amount they're taking."
Dec 18 eLife abstract
Dec 18 Harvard news release


VA study: Metronidazole still appropriate for mild C diff in select patients

A study yesterday in Clinical Infectious Diseases suggests metronidazole may be considered for treating initially mild Clostridioides difficile infection (CDI) in patients 65 years old or younger.

Until recently, metronidazole was recommended as the first-line treatment option for mild-to-moderate CDI, but updated guidelines now recommend vancomycin for initial non-severe CDI. Despite these guidelines, some reports still recommend that metronidazole be considered in certain patients who have mild CDI and a low risk for disease complications. But limited data exist to identify these patients.

To answer the question of which patients can still be treated with metronidazole, researchers with the Providence Veterans Affairs (VA) Medical Center conducted a two-stage analysis in a cohort of veterans from 125 VA centers with a first episode of mild CDI. The first stage was a predictive analysis regarding which patients treated with metronidazole have successful outcomes, and the second stage compared clinical outcomes in patients treated with metronidazole versus those treated with vancomycin.

Among 3,656 patients treated with metronidazole, the researchers identified 3,282 patients with success and 374 patients without success. Younger age was the only independent predictor of success, with patients 65 and younger associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29 to 2.06) than those over 65. Among 115 propensity-score matched pairs of patients under 65, no significant differences were observed between metronidazole and vancomycin for all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.06 to 1.38), CDI recurrence (HR, 0.62; 95% CI, 0.26 to 1.49), or treatment failure (HR, 0.50; 95% CI, 0.23 to 1.07).

The authors of the study say continued work is needed to investigate which severity criteria are most useful in defining mild disease that can be successfully treated with metronidazole.
Dec 18 Clin Infect Dis abstract

Public Health England notes 28 cases of acute flaccid paralysis

Public Health England (PHE) announced today its investigation into 28 cases of acute flaccid paralysis (AFP, known in the United States as acute flaccid myelitis) reported in England this year, most of them since September.

"AFP is very rare. However, if you or your child develops weakness in any limb you should seek medical care immediately so that appropriate testing and care can be given," said Mary Ramsay, MD, head of immunizations at PHE. "We are investigating potential causes and working hard to build better awareness amongst health care professionals about how to test and manage patients with AFP."

The case count is high for England, which usually sees only a handful of cases of the polio-like illness each year.

According to PHE, 12 cases of AFP this season have been associated with an enterovirus; EV-D68 has been detected in 8, EV-C104 in 1, and coxsackie B1 in 1; in 2 cases the enterovirus was not typeable. Enteroviruses have also been linked to previous AFP cases in the US.

PHE also released "Acute flaccid paralysis: clinical management guidance," a document to guide clinicians, and an information guide for patients and their families.
Dec 19 PHE press release
Dec 19 PHE clinician guide
Dec 19 PHE
patient guide


IDSA updates flu clinical practice guidelines

The Infectious Diseases Society of America (IDSA) today released updated guidelines on diagnosing, treating, and preventing flu, marking first overhaul of its clinical practice guidance since before the 2009 H1N1 pandemic. The guidelines committee published the document in Clinical Infectious Diseases.

According to the update, pregnant women and people who are extremely obese (those with a body mass index of 40 or more) are among those at high risk for complications and should be tested and started on antiviral treatment promptly if they are sick enough to be hospitalized for flu symptoms.

People diagnosed in outpatient settings and are at high risk for complications should also be treated with antivirals as soon as possible, IDSA says. High-risk groups also include young children, women who have recently given birth, those with weakened immune systems because of medical conditions or treatment, those with neurologic or neurodevelopmental conditions, those with chronic medical conditions, American Indians, and native Alaskans.

Though antiviral treatment should begin within 2 day of symptoms onset, the guidance says these drugs should be prescribed for those at high risk, even if they have been sick for more than 2 days.

Regarding testing, the IDSA recommends newer, highly accurate molecular tests that give a result in 15 to 60 minutes rather than rapid influenza diagnostic tests, which give a quick result but are falsely negative at least 30% of the time in outpatient groups.

Physicians should prescribe antivirals for hospitalized high-risk patients without waiting for the results of molecular testing, according the guidelines. However, testing is important, the guidelines say, because doctors are most likely to treat patients with appropriate medications if they have a definite diagnosis, which reduces inappropriate antibiotic prescribing, especially in outpatients.

Timothy Uyeki, MD, MPH, IDSA guidelines committee cochair and chief medical officer of the Centers for Disease Control and Prevention's National Center for Immunization and Respiratory Diseases, said in an IDSA press release, "Annual influenza vaccination is the best way to prevent influenza, but it is not 100 percent effective. Those at high risk need to be encouraged to seek medical care right away if they develop influenza symptoms during influenza season."

Health providers should consult infectious disease (ID) physicians when high-risk patients are diagnosed with flu, according to new guidance. Andrew Pavia, MD, guidelines cochair and chief of the University of Utah's division of pediatric infectious diseases, said, "ID doctors also can provide guidance when a patient who has the flu is not responding to antiviral treatment or is getting worse."
Dec 19 Clin Infect Dis report
Dec 19 IDSA
press release


EU flu vaccination coverage rates still below target

A European Centre for Disease Prevention and Control (ECDC) report on flu vaccine coverage over the past three seasons found most nations have clear recommendations on which groups should receive it, such as those in high-risk groups, but only a few came close to meeting the European Union target of 75%. The coverage rates were provided by 19 member states.

Coverage rates for older age-groups, for example, a group at high risk for flu complications, ranged from 2% to 72.8%, with the highest levels reported by the United Kingdom.

In an ECDC press release yesterday, Pasi Penttinen, MD, PhD, MPH, head of the ECDC Influenza Disease Program, said achieving high coverage in those at risk remains a serious public health challenge. "The best way to prevent or minimize severe disease from influenza among vulnerable groups is timely vaccination, even though the effectiveness of the vaccine varies depending on the virus in circulation. Sufficient vaccination coverage also saves healthcare systems money in decreased consultation rates and hospitalisations," he said.

Meanwhile, in a positive sign, about half of reporting countries said they saw increases in the use of newer flu vaccines designed to provide broader protection—quadrivalent formulations or ones that contain an adjuvant—during the 2017-18 season.

The study also tracked antiviral recommendations, finding that most countries have issued guidance for treatment. Recommendations for prophylaxis, however, weren't common.

Based on the findings, ECDC officials recommend improving vaccination coverage rates by targeting vulnerable groups with communication campaigns and ensuring adequate and sustained funding for national vaccination programs.
Dec 18 ECDC press release
Dec 18 ECDC

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