ASP Scan (Weekly) for Aug 03, 2018

FDA azithromycin warning
Polymyxins and kidney injury
Carbapenemase-producing Klebsiella in Greece
Pneumonia treatment in Spain
MDR infection and mortality risk
CARB-X funds C diff drug
Airborne antibiotic resistance genes

FDA issues azithromycin warning for cancer patients receiving stem cells

The US Food and Drug Administration (FDA) today issued a warning about long-term azithromycin use in cancer patients who've undergone a donor stem cell transplant.

The warning is based on the results of a clinical trial that found an increased rate of relapse in cancers affecting the blood and lymph nodes—and an increased death rate—among stem-cell transplant patients who were being treated with azithromycin to prevent bronchiolitis obliterans, a serious lung condition caused by inflammation and scarring in the airways of the lungs.

The researchers observed cancer relapse in 77 patients (32.9%) with azithromycin treatment compared with 48 patients (20.8%) taking placebo, and a total of 95 patients died in the azithromycin group compared with 66 patients in the placebo group. The investigators concluded that the risks of long-term azithromycin exposure after donor stem cell transplantation may exceed the benefits.

Although the trial could not determine why rates of cancer relapse and death were higher with azithromycin (which is not approved for preventing the condition), the FDA says healthcare providers should not prescribe long-term azithromycin to prevent bronchiolitis obliterans in patients with cancers of the blood or lymph nodes who've had a donor stem cell transplant. The agency says it's reviewing additional data and will communicate its conclusions and recommendations when the review is complete.

Pfizer, the manufacturer of Zithromax, is providing a letter on this safety issue to providers who care for patients undergoing stem cell transplants. 
Aug 3 FDA safety announcement


Study highlights clinical, financial costs of kidney injury with polymyxin

A study today in Open Forum Infectious Diseases details the impacts of acute kidney injury in patients treated with polymyxin antibiotics.

The retrospective database analysis looked at adults who received intravenous (IV) treatment with one of two polymyxin antibiotics—sodium colistimethate (CMS) or polymyxin B (PMB)—for more than 3 consecutive days. The use of polymyxins has been on the rise as gram-negative organisms have grown increasingly resistant to other antibiotics, but there are concerns about drug-induced nephrotoxicity, specifically acute kidney injury (AKI). The researchers were seeking to assess the mortality risk, inpatient length of stay, and total hospitalization costs associated with AKI among patients who receive the drugs.

A total of 4,886 patients were included: 4,103 who received CMS and 783 who received PMB. In the multivariable analysis, the presence of AKI was associated with higher in-hospital mortality in the CMS group (adjusted odds ratio [aOR], 2.3) and the PMB cohort (aOR, 2.7) than those who didn't develop AKI, and with longer hospital stays (9.7 days and 11.6 days in the CMS and PMB cohorts, respectively). Mean total hospitalization costs were also higher for patients with AKI—$47,820 higher in the CMS cohort and $35,244 higher in the PMB cohort.

"Our findings suggest that the clinical and economic burden of AKI among polymyxin recipients is substantial and polymyxin therapy should be used judiciously," the authors conclude.

The study was sponsored by Allergan plc.
Aug 3 Open Forum Infect Dis abstract


Carbapenemase-producing K pneumoniae in Greece now more resistant

Originally published by CIDRAP News Aug 2

An analysis of carbapenem-nonsusceptible Klebsiella pneumoniae isolates in Greece has found increasing resistance to last-line antibiotics.

In an article today in Eurosurveillance, Greek researchers report that, of 394 carbapenem-nonsusceptible K pneumoniae isolates collected at 15 hospitals from November 2014 through April 2016, 389 (98.7%) were carbapenemase producers. KPC enzymes were the most frequent carbapenemase, detected in 66.5% of isolates, followed by NDM enzymes (13.7%) and VIM enzymes (8.6%). OXA-48 and double carbapenemase producers remained uncommon (3.6% and 6.3%, respectively).

Antibiotic susceptibility testing revealed high resistance to last-line antibiotics. Gentamicin and colistin were the most active antibiotics in vitro, inhibiting 61.9% and 59.6% of isolates, followed by fosfomycin (58.4% susceptible) and tigecycline (51.5% susceptible). The authors of the study note that the colistin non-susceptibility rate of 40.4% is significantly higher than the 28.3% observed in a study of 36 European countries. They suggest this could be due to increased consumption of colistin in Greece.

The authors conclude, "The steeply increasing resistance to last-line antimicrobials such as colistin in Greece mandates the necessity of continuous surveillance as well as the application of strict contact precautions along with antimicrobial stewardship."
Aug 2 Eurosurveill research article


Study finds only half of Spanish seniors get proper pneumonia treatment

Originally published by CIDRAP News Aug 2

A study today in Epidemiology and Infection reports that empirical antibiotic treatment for community-acquired pneumonia (CAP) in elderly patients in Spain conforms to national guidelines roughly half the time.

The multicenter study, which included 1,857 patients age 65 and over who were hospitalized for CAP in the 2013-14 and 2014-15 influenza seasons, found that treatment was conforming with guidelines from the Spanish Society of Pulmonology and Thoracic Surgery in 51.4% of patients without intensive care unit (ICU) admission and was associated with the absence of renal failure without hemodialysis (odds ratio [OR], 1.49) and no cognitive dysfunction (OR, 1.71) when the effect of Spain's autonomous communities was controlled for. There was also a trend toward association with COPD (OR, 1.23).

In patients admitted to the ICU, treatment was conforming in 45.1% of patients and was associated with fewer than three hospital visits in the last year (OR, 2.70). There was also some evidence that conforming treatment was more associated with the 2013-14 flu season than the 2014-15 season.

Although the conforming of treatment to national guidelines in Spain was found to be higher than that found in Europe-wide studies (38.8%), the authors note that the wide variability among autonomous communities in adhering to correct CAP treatment is concerning, given that the guidelines are national. They suggest the reasons for this variability should be studied, they add.
Aug 2 Epidemiol Infect abstract


Study: Long-term risk of infection, death in patients harboring MDR bacteria

Originally published by CIDRAP News Jul 31

Harboring multidrug-resistant gram-negative bacteria (MDRGNB) significantly increases patients' long-term risk for subsequent MDRGNB infection and mortality after hospital discharge, Taiwanese researchers report today in Antimicrobial Resistance and Infection Control.

In an observational study, researchers at National Taiwan University Hospital recruited 817 patients who had been hospitalized in 2009 and discharged after receiving active microbiological surveillance cultures for MDRGNB infection or colonization. MDRGNB was defined as a gram-negative pathogen resistant to at least three antimicrobial classes. The researchers then recorded subsequent MDRGNB infection and mortality within 12 months after index hospitalization and determined the frequency and risk factors for subsequent infection and mortality associated with previous MDRGNB status.

Of the 817 patients, 125 were identified in the index hospitalization as MDRGNB culture-positive (MDRGNB-CP) and 629 were classified as MDRGNB culture-negative (MDRGNB-CN). In total, 129 patients had at least one subsequent MDRGNB infection during the follow-up period (60 MDRGNB-CP patients and 69 MDRGNB-CN patients), and 148 patients died (53 MDRGNB-CP and 95 MDRGNB-CN). Escherichia coli and Acinetobacter baumannii were the most prevalent MDR species identified during index hospitalization and in subsequent infections, while patients colonized with Proteus mirabilis and Pseudomonas aeruginosa had the highest hazard risk for developing subsequent infection.

After controlling for other confounders, positive MDRGNB culture during index hospitalization was found to be an independent predictor for subsequent MDRGNB infection (hazard ratio [HR], 5.35], all-cause mortality (HR, 2.42), and subsequent MDRGNB infection-associated mortality (HR, 4.88).

The researchers say their findings highlight the urgent need for effective approaches to prevent the spread of MDRGNB in hospitals and mitigate MDRGNB colonization burden after hospitalization.   
Jul 31 Antimicrob Resist Infect Control study


CARB-X to fund novel antibiotic alternative for C difficile infection

Originally published by CIDRAP News Jul 31

CARB-X today announced funding for a novel therapeutic to fight Clostridium difficile infection (CDI).

The award of $0.68 million to SciBac of San Francisco, CA, will support early-stage development of SCB-102, the company's oral antibiotic alternative for the prevention and treatment of recurrent CDI. The drug, which consists of three hybrid molecules, specifically targets and kills C difficile bacteria, stops its colonization of the colon, neutralizes its toxins, and prevents spore formation.

"SciBac has essentially created a new class of drugs," Jeanette Mucha, CEO of SciBac, said in a CARB-X press release. "Our patented platform technology allows us to mate different species of microbes. This means we can harness the microbiome to both treat and prevent antibiotic resistant disease, with targeted modes of action."

According to the US Centers for Disease Control and Prevention, CDI causes an estimated 15,000 deaths each year in the United States. One in five patients experiences a recurrence of the infection.

The company could receive an additional $3.08 million if certain project milestones are met.

CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) is currently funding 35 research and development projects targeting the most serious drug-resistant bacteria, and has announced awards totaling $90.1 million since it was established in 2016
Jul 31 CARB-X press release


Antibiotic resistance genes in the air

Originally published by CIDRAP News Jul 30

New research on urban air pollutants by Chinese scientists has detected antibiotic resistance genes in the air of 19 cities.

Using automobile air conditioning filters, the scientists took ambient total particulate matter samples from 19 cities in 13 countries. Testing of the samples revealed the presence of 30 antibiotic resistance gene (ARG) subtypes conferring resistance to seven common classes of antibiotics: quinolones, beta-lactams, macrolides, tetracyclines, sulfonamides, aminoglycosides, and vancomycin. Of the 19 cities surveyed, Beijing was found to have the highest diversity of ARGS, with 18 ARG subtypes, while San Francisco had the highest overall level of ARG subtypes. Genes providing resistance to beta-lactams and quinolones were the most abundant types of ARG found in all 19 cities.

In addition, the scientists examined the longitudinal dynamics of airborne antibiotic resistance in Xi'an, China, and found that from 2004 to 2014, the relative abundance of the quinolone resistance gene qepA and the beta-lactam resistance gene blaTEM in fine particulate matter increased by 26% and 178%, respectively. This finding, they note, corresponds with a 109% increase in quinolone use and a 427% increase in cephalosporin use at Xi'an Hushuan Central Hospital from 2008 to 2010, suggesting a possible link between hospital antibiotic usage and increasing abundance of airborne ARGs.

Although the consequences need to be further explored, the authors of the study say the findings highlight the potential public health threat of airborne ARGs.

"Increases in abundances of airborne ARGs inevitably could lead to increased 'second-hand' inhalation risk of ARGs for city inhabitants," the authors write. "Different from the chemical products, ARGs could transmit among people as well as bacterial species, thus increasing the susceptibility of humans or the environment to bacterial resistance."

The study was published in Environmental Science and Technology.
Jul 25 Environ Sci Technol abstract

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