Stewardship / Resistance Scan for Jul 11, 2018

Fluoroquinolone safety update
Kids' fevers and antibiotics
Resistant Klebsiella in Europe
Ceftolozane-tazobactam against E coli

FDA updates safety labels for fluoroquinolones

The US Food and Drug Administration (FDA) yesterday announced that it is updating the labels for fluoroquinolone antibiotics to strengthen warnings about the risk of mental health side effects and reduced blood sugar.

The mental health side effects to be included in the updated labels for all systemic fluoroquinolones include disturbances in attention, disorientation, agitation, nervousness, memory impairment, and delirium. In addition, a subsection of the labeling on blood sugar disturbances will now be required to warn that low blood sugar levels can lead to hypoglycemic coma, particularly in older patients and patients with diabetes who are also taking drugs to reduce blood sugar. The changes were based on a comprehensive review of the FDA's adverse events reports and case reports in the medical literature.

This is not the first time the FDA has had to strengthen warnings about fluoroquinolones. In 2008, the agency added a Boxed Warning for increased risk of tendonitis and tendon rupture, and in 2016 enhanced warnings about the association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system. Warnings about the risk of worsening symptoms for patients with myasthenia gravis have also been added to the labels.

"The FDA remains committed to keeping the risk information about these products current and comprehensive to ensure that health care providers and patients consider the risks and benefits of fluoroquinolones and make an informed decision about their use," Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release.

FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin, gemifloxacin (Factive) and delafloxacin (Baxdela). There are more than 60 generic versions. 
Jul 10 FDA news release


Booklet may help reduce antibiotic prescribing for kids' fevers if used

Dutch investigators reporting in the current issue of Annals of Family Medicine say the availability of a parent-focused booklet on childhood fevers in doctors' offices didn't affect antibiotic prescribing, but it decreased prescribing if physicians actually used the booklet.

As part of a two-armed cluster-randomized trial involving 25,355 children at 20 after-hours primary care clinics in the Netherlands, family physicians in the intervention group had access to a booklet on children's fever. The booklet, designed for discussion with parents, provided advice on when to consult a physician, self-management strategies, and the duration of common childhood infections.

The researchers found that antibiotic prescribing was not significantly different in the intervention and control groups, but after they adjusted for use of the booklet, they found a statistically significant 17% reduction in antibiotic prescribing in children managed by the 3,407 family physicians who used the booklet compared with the control group. Children in the intervention group were also less likely to receive a prescription for any drug.

Though the reduction in antibiotic prescribing was modest, the authors suggest in a news release from the American Academy of Family Physicians (AAFP), which publishes the journal, that the study provides evidence of the likely "real world" benefits of the booklet. "Insight into reasons for use and nonuse may inform future interventions of this type," the authors conclude.
Jul/Aug Ann Fam Med abstract
Jul 10 AAFP news release


Carbapenemase-producing K pneumoniae detected in Nordic travelers

The European Centre for Disease Prevention and Control (ECDC) today issued a rapid risk assessment on a cluster of travelers from Sweden and Norway who carried or were infected with carbapenemase (OXA-48)–producing Klebsiella pneumoniae ST392 after being hospitalized in the Canary Islands.

The 13 patients, 4 of whom had infections, were all hospitalized in Gran Canaria in 2018; 9 of them were treated in the same hospital. Isolates from the patients all expressed the same multidrug resistance profile and contained the blaCTX-M-15 extended-spectrum beta-lactamase (ESBL) gene in addition to the blaOXA-48 carbapenemase gene. Whole-genome sequencing found that all the isolates were tightly clustered, indicating a common place of acquisition.

The report also includes four possible cases (two from Sweden and two from Finland) that were detected in 2015 and 2016 in patients with a history of travel to the Canary Islands.

Since OXA-48-producing K pneumoniae was first detected in a patient in Turkey in 2001, strains of the pathogen have caused outbreaks worldwide, with sporadic cases or outbreaks being reported in most European countries. Hospitalization abroad and cross-border transfer of patients are well-known modes of introducing carbapenemase-producing Enterobacteriaceae (CPE) from countries with high prevalence into those with a lower prevalence.

While the risk for travelers of acquiring OXA-48–producing K pneumoniae ST392 without healthcare contact is low, the concern is that if patients are colonized or infected with this cluster and subsequently admitted to a hospital in their country of origin, there is a high risk of transmission or outbreaks, especially if the pathogen goes undetected and the hospital has inadequate infection prevention and control measures.

The report recommends that European Union/European Economic Area countries should consider taking a detailed history of travels and hospitalizations for every patient, and should also perform preemptive isolation and screening for carriage of CPE in patients who were directly transferred from or hospitalized in countries with a high CPE prevalence.
Jul 11 ECDC rapid risk assessment


Ceftolozane-tazobactam shown effective against VA E coli isolates

University of Minnesota researchers have determined that ceftolozane-tazobactam (C/T), a new beta-lactamase inhibitor/antibiotic combination drug, was effective against Escherichia coli ST131 isolates from veterans—even resistant isolates—and should prove useful as a carbapenem-sparing therapy for multidrug-resistant E coli.

Writing yesterday in PLoS One, the scientists said they determined broth microdilution minimum inhibitory concentrations (MICs) for C/T and five comparators—piperacillin-tazobactam, levofloxacin, gentamicin, ceftazidime, and meropenem—for 595 clinical E coli isolates collected in 2011 from 24 Veterans Affairs Medical Centers across the United States.

They found that the prevalence of resistance was 0% for meropenem and 6% for C/T, whereas it ranged from 8% for piperacillin-tazobactam to 59% for levofloxacin. Also, except for meropenem, only a minority of comparator-resistant isolates were C/T-resistant (ranging from 9% to 38%).

The authors concluded, "C/T was broadly active against E. coli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30R1/H30Rx status, outperforming all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing therapy for multidrug-resistant E. coli ST131 infections, including in veterans."
Jul 10 PLoS One study

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