Case series describes respiratory nerve palsy in babies born with Zika

Researchers today reported a case series of four babies with congenital Zika infections who were born with right unilateral diaphragmatic paralysis, suggesting that the virus can cause additional damage in the peripheral nervous system. A team from the Mayo Clinic and Brazil published its findings in Emerging Infectious Diseases.

Three of the babies were born in Brazil and one was born to a mother from Guatemala who immigrated to the United States. All four of the babies were girls, and all of the women who delivered them were first-time mothers who reported Zika symptoms in the first trimester of pregnancy.

All of the babies had severe microcephaly and arthrogryposis (congenital joint contracture). All died from progressive respiratory failure.

The authors noted that a study of Zika virus in macaques has suggested viral tropism to peripheral nerves. They also said Guillain Barre syndrome (GBS) is known to involve the phrenic nerve and cause diaphragmatic paralysis in adults, but the condition hasn't been reported before in newborns.

They concluded that arthrogryphosis and unilateral diaphragmatic paralysis seems to be a unique constellation of clinical findings that hasn't been reported with other congenital infections. Authors wrote though it's not clear how diaphragmatic paralysis occurs in infants, or why it's unilateral and right-sided, the damaging effects might be a unique risk factor for death in babies with congenital Zika infections, given that all four babies in the case series died within the first 3 months of life.
Jul 11 Emerg Infect Dis report


CDC team pinpoints incidence of GBS after Campylobacter infection

About 8% to 12% of GBS cases in the United States may be due to Campylobacter infection, researchers from the US Centers for Disease Control and Prevention (CDC) reported yesterday in Epidemiology and Infections.

They said that although Campylobacter infection is known to be one of the common infections that precede GBS, there are few data on the risk level.

To better pinpoint how common the complication occurs following Campylobacter illness, the scientists sifted through data collected by the CDC's Emerging Infection Program during the 2009 H1N1 vaccination campaign. They compared confirmed and probable GBS cases to noncases to gauge the risk of GBS following Campylobacter infection.

Along with the 8% to 12% of GBS cases they found linked to Campylobacter infection or diarrheal illness consistent with the disease, they estimated that 434 to 650 cases of post-diarrheal GBS occur in the United States each year and that GBS occurs in 49 of 100,000 patients who have Campylobacter illnesses.

The researchers concluded that the findings provide a useful update on the incidence of GBS following Campylobacter infection and underscore the importance of measures to prevent the infections.
Jul 10 Epidemiol Infect abstract


Study: CWD prions can convert to human prions, at least in test tubes

Chronic wasting disease (CWD) prions extracted from cervids (such as deer, elk, and moose) can convert to human prions in the lab, but not efficiently. That's the takeaway from a study published today in Emerging Infectious Diseases.

The study attempted to establish how and if CWD can be transmitted to humans if they consume infected cervid meat, which would make CWD a zoonotic illness similar to bovine spongiform encephalopathy (BSE, or "mad cow" disease). CWD has been detected in Europe, North America, and South Korea.

Previous in vivo studies conducted with squirrel monkeys have shown that CWD can cross species, but other work involving transgenic mouse models have shown the prion incapable of infecting human tissue. This study used an in vitro protein misfolding cyclic amplification to investigate the compatibility of bovine, ovine, and cervid prions with full-length, glycosylated and glycosylphosphatidylinositol-anchored human prion proteins (PrP). Prions are misfolded protein particles that can be detected in the neural tissue of infected animals.

The authors of the study said prions from infected animals can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human PrP genes.

"Our data confirms that elk CWD prions can convert … at least in vitro," the authors conclude. "Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP."
Jul 11 Emerg Infect Dis study

Stewardship / Resistance Scan for Jul 11, 2018

News brief

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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