ASP Scan (Weekly) for Dec 16, 2016

Community-associated CRE
Antibiotic de-escalation
Multidrug-resistant strep
Multiple KPE in 1 patient
Carbapenem-resistant A baumannii
Fewer hospital-acquired infections
Proton-pump inhibitors and ESBL-E
HAI communications toolkit
AMR and the sea
Colistin-resistant Klebsiella

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans


Rare community-associated CRE reported in Colorado

Investigators with the Colorado Department of Public and Environment and the Centers for Disease Control and Prevention (CDC) are reporting community-associated cases of carbapenem-resistant Enterobacteriaceae (CRE) in patients without known risk factors.

In a paper today in the CDC's Morbidity and Mortality Weekly Report (MMWR), the investigators said that six of 10 patients identified with New Delhi metallo-beta-lactamase (NDM)-producing CRE from 2014 to 2016 lacked the known CRE risk factors: hospitalization outside the United States, recent admission to short-stay and long-term acute care hospitals, residence in long-term care facilities, surgical procedures, and having indwelling devices like catheters. This is noteworthy because CRE lacking these exposures are rare in the United States.

Among the six patients identified, two had traveled internationally, two had underlying medical conditions, one was pregnant, three had no underlying comorbidities, and three had antibiotic exposure prior to positive culture. All of the patients, who ranged in age from 20 to 85, were diagnosed with urinary tract infections.

There were no epidemiologic links among the six patients, nor were there links between these patients and eight patients in Colorado diagnosed with CRE during a 2012 hospital outbreak (most of whom had the known CRE risk factors). In addition, whole genome sequencing performed at CDC labs on the isolates from the recent patients and the 2012 patients confirmed that they did not share common strains or plasmids. Among seven of the recent isolates that underwent sequencing, only two Escherichia coli ST167 isolates appeared to be related.

Carbapenemases like NDM , which can reside on mobile plasmids and be transferred among bacterial species, are believed to contribute to the increasing transmission and regional spread of CRE. As of April 2016, the authors note, Colorado had reported the second highest number of NDM-producing CRE in the United States. The identification of community-associated strains of the multidrug-resistant bugs adds another layer of concern.

"The source for the community-associated strains is unknown, but might represent transmission of multiple NDM strains outside inpatient health care settings," the authors write. "The finding that six of 10 recent NDM-producing CRE are community-associated suggests that the epidemiology of CRE could be changing." 

The authors add that further surveillance is required to determine whether the pattern continues.
Dec 16 CDC MMWR Notes from the Field


Benchmarks for antibiotic de-escalation

A recent study in BMC Infectious Diseases suggests 72 hours could be a plausible benchmark for antibiotic de-escalation.

In the retrospective observational study, researchers reviewed the randomly selected medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at Wake Forest Baptist Medical Center, an 885-bed tertiary medical center with an active antimicrobial stewardship program. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or discontinuation of antibiotics after the initiation of piperacillin/tazobactam and vancomycin therapy.

Among the 240 patients studied, the most commonly documented indications were pneumonia and sepsis. Nearly two-thirds of the patients (151) had their antibiotic regimens de-escalated by 72 hours, and nearly three-quarters (175) by 96 hours. The most common antibiotics prescribed for de-escalation were moxifloxacin and ceftriaxone. The proportion of patients de-escalated by 96 hours with positive vs. negative cultures was roughly equal—71% and 72%, respectively.

Median length of stay was 4 days shorter in the de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82). But the authors note that these associations may be surrogate markers of overall clinical status and the severity of illness, which were not controlled for in the study.

"While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation," the authors write.
Dec 12 BMC Infect Dis research article


Multidrug-resistant strep on the rise in UK, Ireland
Researchers in the United Kingdom are reporting the rise of a multidrug-resistant, non-vaccine serotype of Streptococcus pneumonia in the UK and Ireland.

According to a study yesterday in Eurosurveillance, analysis of S pneumonia isolates collected by the surveillance programs of British Society for Antimicrobial Chemotherapy (BSAC) and Public Health England (PHE) has found that serotype 15A is becoming increasingly prevalent.

While prior to 2011 serotype 15A isolates were encountered sporadically, since 2011 they have been among the 10 most prevalent serotypes in BSAC/PHE invasive isolate/bacteremia surveillance. Among BSAC respiratory isolates, 15A was the most prevalent serotype in 2013/14 and 2014/15, comprising 9% to 11% of isolates. In addition, 15A represented 29% and 32% of S pneumonia referred to PHE for reference investigation in 2013 and 2014 (before 2008, it represented 0 to 4%). 

Unlike other rising pneumococcal serotypes identified, serotype 15A isolates were found to be commonly resistant or nonsusceptible to multiple antibiotics, including macrolides, clindamycin, tetracycline, and penicillin, with around one-third of isolates showing "triple resistance" (to macrolides and tetracycline together with intermediate penicillin resistance). Triple resistance was strongly associated with ST63 and its variants. While this is a concern for patient management, the authors note that S pneumoniae 15A remains susceptible to other agents, including moxifloxacin, cefotaxime, and ampicillin.

S pneumoniae 15A is not covered by the 13-valent pneumococcal conjugate vaccine. Its rise, the authors write, implies that conjugate vaccines "will face an ongoing game of 'catch-up'" and that expansion beyond a 13-valent formulation will be necessary in the future.
Dec 15 Eurosurveill report


Canadian researchers describe patient with multiple KPE isolates
Originally published by CIDRAP News Dec 15.

Canadian researchers are reporting a case of a single patient with multiple variants of Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria.

In a letter today in the New England Journal of Medicine, the researchers report on the case of an 82-year-old man with heart failure and chronic obstructive pulmonary disease who was admitted to the same hospital 21 times between 2011 and 2015. The patient was most often grouped with other patients colonized or infected with KPC-producing Enterobacteriaceae (KPE) and received numerous courses of antibiotics during that time.

The researchers were able to identify 14 KPE isolates in the patient and sequence the genome of 9 of them. Three species were identified (K pneumoniae, K oxytoca, and Escherichia coli), and all 9 isolates were found to be carrying the KPC-3 gene on plasmids. Furthermore, several of the isolates appeared to be linked to each other by means of plasmid transfer. It's unclear, however, whether the multiple isolates arose from the spread of the resistance element within the host, from exposure to other KPE-colonized patients, or both.

The authors write that while there have been previous reports of multiple KPE colonizations or infections in a single patient, their study shows the evolution and diversity of KPE within a single patient over several years. 
Dec 15 N Engl J Med letter


ECDC report warns of rising threat from carbapenem-resistant A baumannii

Orginally published by CIDRAP News Dec 14.

European health officials are warning about an increase in carbapenem-resistant Acinetobacter baumannii infections in hospitals across the continent.

In a rapid risk assessment issued Dec 9, the European Centre for Disease Prevention and Control (ECDC) said recent data from the European survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE) and the European Antimicrobial Resistance Surveillance Network (EARS-Net) confirm that although there is already a high resistance baseline in some EU countries, there's been an overall increase in carbapenem-resistant A baumannii throughout the continent.

Acinetobacter spp. are gram-negative bacteria that are ubiquitous in the environment, with most species having low pathogenicity. But A baumannii, which can survive for long periods on dry surfaces and easily acquires resistance to different classes of antibiotics, has emerged as an important cause of outbreaks in healthcare settings.

A baumannii outbreaks typically occur in intensive care units among patients who've had invasive procedures or indwelling devices, but infections in patients admitted to conventional medical and surgical wards have been increasing. The bacteria are difficult to eradicate once they've become endemic. Over the last decade, the increasing resistance to carbapenems—traditionally the antibiotics of choice for A baumannii infections—has led to increasing use of the last-resort antibiotic colistin.

According to the data from EuSCAPE, a higher number of EU and European Economic Area (EEA) countries reported interregional spread or endemicity of carbapenem-resistant A baumannii in 2015 compared to 2013. In addition, data from EARS-Net showed that in 2015, 12 of 27 countries reported carbapenem resistance in more than 50% of their Acinetobacter spp. isolates. These findings, the ECDC report said, support the conclusion that the epidemiological situation of carbapenem-resistant A baumannii is worsening in Europe.

The ECDC said the findings highlight the need for increased efforts to reduce the clinical risk of carbapenem-resistant A baumannii infections, prevent hospital outbreaks and cross-border transmission, and improve preparedness for outbreak situations. 
Dec 9 ECDC rapid risk assessment


HHS report highlights drop in hospital-acquired conditions

Originally published by CIDRAP News Dec 14.

A new report from the Department of Health and Human Services (HHS) shows that hospital-acquired conditions (HACs) are continuing to decline, a finding that has positive implications for the battle against antibiotic resistance.

According to the National Scorecard on Rates of Hospital-Acquired Conditions, a report compiled and analyzed by the Agency for Healthcare Research and Quality (AHRQ), preliminary estimates for 2015 show a 21% decline in HACs since 2010. That translates into a cumulative total of 3.1 million fewer HAC's over 5 years than would have occurred had rates remained at the 2010 level, 125,000 fewer deaths, and approximately $28 billion in healthcare savings.

The preliminary rate for 2015 is 115 HACs per 1,000 discharges, down from 145 in 2010.

"Today's report shows us hundreds of thousands of Americans have been spared from deadly hospital acquired conditions, resulting in thousands of lives saved and billions of dollars saved," HHS Secretary Sylvia Burwell said in a news release.

While the largest cumulative reductions were in adverse drug events (a 42% reduction from 2010) and pressure ulcers (23%), there were also declines in four types of healthcare-associated infections (HAIs) whose treatment can be complicated by antibiotic-resistant bacteria: catheter-associated urinary tract infections (15.2%), surgical site infections (2.4%), central-line associated infections (1.3%), and ventilator-associated pneumonias (0.5%).

Cutting down on these types of infections is considered a critical element in efforts to combat antibiotic resistance and promote antibiotic stewardship in the US healthcare system. 
Dec 2016 AHRQ report on hospital-acquired conditions
Dec 12 AHRQ news release


Proton-pump inhibitors linked to rectal carriage of ESBL-E

Originally published by CIDRAP News Dec 14.

A study yesterday in Clinical Infectious Diseases reports that use of proton-pump inhibitors (PPIs) is independently associated with rectal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E).

The findings of the study are relevant because ESBL-E rectal carriage in the general community has become endemic globally and because PPIs, which neutralize or reduce the production of gastric acid, are among the most frequently prescribed class of drugs in the world and have been shown to increase the risk of gastrointestinal infections. But previous studies linking PPIs and ESBL-E have produced conflicting results.

In the cross-sectional study performed at an 850-bed teaching hospital in the Netherlands, investigators obtained valid rectal cultures from 570 of 702 hospitalized or day care patients. Of these 570 patients, 259 used PPIs on admission. In the PPI users, prior hospitalization and antibiotic use were more frequent, and median age was higher.

Overall, rectal carriage of ESBL-E was detected in 31 of the 570 patients, with Escherichia coli as the predominant species in 87% of the cases. Twenty-two of those patients were PPI users on admission. In a multivariable analysis, PPI users were found to have nearly four times the risk of ESBL-E rectal carriage as non-PPI users (adjusted OR, 3.89). While antibiotic use on the day of culture was not associated with ESBL-E rectal carriage, no data were available on antibiotic use prior to hospital admission.

The authors of the study say prospective studies are warranted to further explore the role of PPIs in ESBL-E infections
Dec 13 Clin Infect Dis study


Toolkit aims to help messaging around HAIs, antibiotic resistance

Originally published by CIDRAP News Dec 13.

The Association of State and Territorial Health Officials (ASTHO) and the Centers for Disease Control and Prevention (CDC) have collaborated on a toolkit to help public health departments communicate information about healthcare-associated infections (HAIs) and antibiotic resistance to the public.

The toolkit includes key messages and talking points that public health departments can use when communicating with other public health professionals, policy makers, the media, and the public. The messages focus on the impact of HAIs, the threat posed by antibiotic resistance, and what healthcare facilities can do to prevent HAIs and the spread of drug-resistant infections.

In addition to specific tips for working with the media, the toolkit contains suggestions for sustaining the public conversation around HAIs, recommendations for engaging the public through social media channels like Facebook and Twitter, and a calendar of HAI-related events that can be used to promote discussion of HAIs and antibiotic resistance.

ASTHO will be hosting a webinar to provide guidance on how to use the tools on Dec 16 from 2:00 to 3:00 pm ET.
ASTHO-CDC HAI and antibiotic resistance communication toolkit  
Dec 16 ASTHO-CDC webinar


Paper examines potential of marine products against resistant infections

Originally published by CIDRAP News Dec 13.

 A paper yesterday in The Lancet Infectious Diseases examines the potential of marine natural products (MNPs) in the treatment of antimicrobial-resistant infections.

With the emergence of antimicrobial resistance imposing a major burden on global health and economics, novel drugs from new sources possessing innovative targets are needed. And since it has already proven to be "a very rich source" of diverse natural products with antimicrobial activities, the marine environment, the authors write, "could serve as a ray of light for the therapy of drug-resistant infections."

In a review of existing literature, the paper examines the potential of MNPs in drug-resistant fungi, viruses (including drug-resistant influenza, HIV, and herpes simplex virus), and drug-resistant malaria. Though equally important, MNPs with activity against drug-resistant bacteria are not part of the review, the authors note, because their use is vast and reviewed extensively elsewhere.

The review examines the origins, activities, and physicochemical properties of several products extracted from marine algae, fungus, coral, and sponges. These include spiromastilactone D, a substance derived from a deep-sea fungus that inhibited a panel of amantadine and oseltamivir-resistant influenza strains; stachybotrin D, which was isolated from a marine sponge-associated fungus and displayed inhibitory effects on replication of drug-resistant HIV-1 strains; and haliclonacyclamine A, a product isolated from a marine sponge that has exhibited antiplasmodial activity in vitro against chloroquine-resistant strains of malaria.

While there are several challenges in turning these products into novel biomedicines—including the time and money required to develop them, insufficient investment, difficulty in isolation and purification procedures, and toxicity—the authors argue that the search for new MNPs should continue.

"Development of resistance-resistant antibiotics could be achieved via the coordinated networking of clinicians, microbiologists, natural product chemists, and pharmacologists together with pharmaceutical venture capitalist companies," the authors write.
Dec 12 Lancet Infect Dis review


Study describes colistin resistance in Carbapenem-resistant Klebsiella

Originally published by CIDRAP News Dec 12.

A new study from an ongoing investigation into patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) has found resistance to colistin in 13% of patients.

The study, published in Clinical Infectious Diseases, looked at a cohort of 246 patients nested within the Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae (CRACKLE), a prospective, multicenter observational study of patient hospitalized with CRKp. The study included patients who were tested for colistin susceptibility as part of routine clinical care from December 2011 to October 2014.

Colistin resistance is considered a grave threat in patients with severe CRKp infections because it is one of the last lines of defense against multidrug-resistant bacteria. With growing use of the drug over the past two decades, cases of colistin-resistant CRKp strains are being reported globally.

Of the 246 patients, colistin resistance was confirmed by a central research laboratory in isolates for 31 (13%), and patients with colistin-resistant CRKp were associated with a more than triple hazard for 30-day in-hospital mortality (aHR 3.48, P < 0.001). Polymerase chain reaction testing indicated a number of different strain types, a finding the authors say argues against a single clonal outbreak. None of the patients in the colistin-resistant CRKp group received colistin in the 14 days preceding the first positive culture.

The authors also say the colistin resistance observed in the isolates appears to be chromosomally mediated; analysis of the isolates did not indicate the presence of the MCR-1 or MCR-2 genes, which are carried on plasmids and can readily transfer colistin resistance to different types of bacteria. 
Dec 10 Clin Infect Dis study

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