Stewardship / Resistance Scan for Aug 09, 2018

Antibiotic resistance in Australia
;
New antibiotic for pneumonia, skin infections
;
Ventilator-associated pneumonia risk factors
;
Autism and early antibiotic exposure

Australian report highlights drug-resistant gonorrhea, CPE infections

Neisseria gonorrhea and carbapenamase-producing Enterobacteriaceae (CPE) remain the most commonly reported organisms with resistance to critical antibiotics in Australia, according to a report yesterday by the Australian Commission on Safety and Quality in Health Care (the Commission).

The 6-month report from the National Alert System for Critical Antimicrobial Resistance (CARAlert), covering October 2017 through March 2018, found that, of 653 strains of bacteria with some type of critical antimicrobial resistance detected, azithromycin non-susceptible N gonorrhea (46.6%) were the most frequently reported, followed by CPE (36.9%), either alone or in combination with ribosomal methyltransferases (2.1%). CPE were the most frequently detected drug-resistant organisms reported in hospital patients.

"The finding that CPE remains prevalent in Australian hospitals is concerning," John Turnidge, MBBS, FRACP, senior medical advisor for the Commission's antibiotic use and resistance surveillance system, said in a press release. "This group of bacteria has the ability to cause common infections, has limited treatment options, and can have a death rate as high as 50% for blood stream infections."

While the number of azithromycin non-susceptible N gonorrhea isolates fell by 26% from the previous reporting period, the number of CPE isolates rose by 20%, from 213 to 255. A 266% increase in multidrug-resistant Shigella species was also observed.

The report also highlights two detected N gonorrhea infections that were resistant to both ceftriaxone and azithromycin, and five additional strains with high-level azithromycin resistance. Australian health officials are concerned about the potential for an outbreak of these extensively drug-resistant strains.
July 2018 CARAlert summary report
Aug 8 Commission press release

 

FDA committee urges approval of antibiotic for pneumonia, skin infections

The Antimicrobials Drug Advisory Committee of the US Food and Drug Administration (FDA) yesterday voted in favor of approving intravenous (IV) and oral omadacycline for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP).

Omadacycline is a modernized tetracycline designed to overcome tetracycline resistance and has demonstrated activity against gram-positive and gram-negative bacterial strains. The drug was granted Qualified Infectious Disease Product Designation and Fast Track status by the FDA for the target indications of ABSSSI, CABP, and urinary tract infections.

The committee's decision was based in part on data from three completed phase 3 trials, in which IV and oral formulations of omadacycline met all FDA-designated primary and secondary outcomes for treating ABSSSI and CABP, and was generally safe and well-tolerated. Nearly 2,000 patients received the drug in those trials.

"Omadacycline has the potential to help address the urgent and growing need for new antibiotics to treat serious community-acquired infections," Michael F. Bigham, chairman and CEO of Paratek Pharmaceuticals, of Boston, said in a company press release. "With once-daily dosing and bioequivalent IV and oral formulations, omadacycline may help facilitate early discharge from the hospital or, in other cases, allow for safe and effective treatment in the outpatient setting."

The FDA is expected to make a final decision on the drug in October.
Aug 8 Paratek Pharmaceuticals press release

 

ESBL gut colonization seen as risk factors for drug-resistant pneumonia

French researchers report a significant relationship between colonization of the digestive tract with extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE) and subsequent ventilator-associated pneumonia (VAP) related to ESBLE, according to a study yesterday in PLoS One.

In the retrospective study, conducted from 2008 through 2011 at the University Hospital of Lille in France, researchers examined the risk factors for ESBLE-related VAP among patients in the intensive care unit. Because the spread of ESBLE infections has led to an increase in the use of carbapenems, the team wanted to determine how to better identify at-risk patients, in order to reduce the spectrum of initial antibiotic treatment. They also looked at the impact of ESBLE on the outcomes of VAP patients.

Among 410 patients with confirmed VAP, 43 (10.5%) had ESBLE VAP, 76 (19%) had polymicrobial VAP, and 189 (46%) had VAP related to multidrug-resistant bacteria. Among the patients with ESBLE VAP, 79% were previously identified as ESBLE carriers. Multivariate analysis identified prior ESBLE colonization of the digestive tract as the only independent risk factor for ESBLE VAP (odds ratio, 23; P < 0.001). While the positive prediction value of ESBLE digestive colonization was low (43.6%), the negative prediction value was excellent in predicting ESBLE VAP (97.3%).

Analysis of outcomes showed no significant differences between patients with ESBLE VAP and those with VAP caused by other bacteria in duration of mechanical ventilation (28 vs. 23 days), length of ICU stays (31 vs. 29 days), or mortality (55.8% vs. 50%).

Although the authors caution that further prospective studies are need to confirm the results, they write, "Our results suggest that patients without ESBLE colonization should probably not receive carbapenems as part of their initial empirical treatment to cover ESBLE. Such a strategy of restricting the use of carbapenems would be helpful to prevent subsequent resistance."
Aug 8 PLoS One study

 

Canadian study finds no link between autism, early antibiotic exposure

A new study in the International Journal of Epidemiology has found no clinically significant association between early life antibiotics exposure and the risk of autism spectrum disorders (ASD).

To test the hypothesis that early life changes to gut microbiota composition—potentially induced by antibiotic exposure—may impair the gut-brain axis and increase the risk of ASD, researchers at the University of Manitoba conducted a population-based cohort study that included all births identified in the Manitoba Health Insurance Registry from April 1998 through March 2016. Early exposure to antibiotics was defined as having filled one or more antibiotic prescriptions during the first year of life, and the main outcome during follow-up was ASD diagnosis.

Of the 214,834 subjects in the cohort, 94,024 (43.8%) filled an antibiotic prescription during the first year of life, and 2,965 children received an ASD diagnosis. After adjusting for covariates, antibiotic exposure was found to be associated with a slightly reduced risk of ASD (adjusted hazard ratio [HR], 0.91), but the researchers concluded that this observed association was not clinically meaningful. Secondary analyses showed no association between ASD and the number of treatment courses or cumulative duration of antibiotic exposure.

In an analysis based on a sibling-controlled design, conducted to address possible confounding due to environmental, genetic, and other familial or social factors, early life antibiotic exposure was not associated with ASD (adjusted HR, 1.03).
Aug 7 Int J Epidemiol abstract                     

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