ASP Scan (Weekly) for May 05, 2017

Drug resistance in hospitals
Biosynthetic penicillin
Stewardship in VA hospitals
Resistant hospital infections
Hospital CRE rate
CRISPR bacteria detection
Promising new C diff drug
Antibiotics for strep throat

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

Study finds multidrug resistance rates similar in small, large US hospitals

A study yesterday in Clinical Infectious Diseases reports no systematic differences in rates of antimicrobial resistance between large tertiary care hospitals and small community hospitals.

Using antibiotic susceptibility data obtained from The Surveillance Network Database-USA, which includes a network of clinical laboratories that serve approximately 300 hospitals across the United States, investigators compared multidrug-resistance (MDR) rates at large tertiary care hospitals (TCHs) and small community hospitals (SCHs) for five organisms: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Facilities were considered SCHs if they had fewer than 300 beds. Investigators identified 38 TCHs and 68 SCHs.

When the investigators compared MDR rates for inpatient and outpatient locations at both types of hospital for the entire study period, they found that the MDR rates were higher at SCHs for four of the organisms: E coli (26.1% vs. 24.9%), S aureus (52.7% vs. 45%), K pneumoniae (25.5% vs. 17.8%), and A baumanni (59.9% vs. 41.1%). Resistance rates in P aeruginosa were higher at TCHs (17.2% vs. 15.3%).

An examination of yearly MDR rates from 1999 to 2012, after adjustments were made for time and variability between hospitals, showed that MDR was higher in A baumannii only at small community hospitals in both patient locations, while E coli showed higher resistance at TCH inpatient locations, and S aureus was higher in SCH outpatient locations. No significant differences in resistance were found for other organisms between the two types of hospital.

The authors say they were surprised by the findings, since they hypothesized that TCHs would have higher MDR rates because they see more complex cases. But that might be balanced out by the fact they are also more likely to have antimicrobial stewardship and infection control programs than SCHs. Finding that MDR is no less of a problem at small community hospitals, they say, emphasizes the importance of ensuring those facilities have those programs as well.
May 4 Clin Infect Dis study 


Scientists develop new method to produce penicillin

Originally published by CIDRAP News May 4

Scientists in the United Kingdom say they've developed a method to produce penicillin from baker's yeast. They report their findings today in Nature Communications.

In the study, scientists from Imperial College London describe how they used genes from the fungus Penicillium chrysogenum, which naturally produces penicillin, to re-engineer the cells of the baker's yeast Saccharomyces cerevisiae. This set off a biochemical reaction process that enabled the baker's yeast, in turn, to produce small amounts of the nonribosomal peptide penicillin. They then further modified the yeast to produce more penicillin.

When added to a petri dish containing Streptococcus bacteria, the yeast actively secreted penicillin that had the same bioactivity against Streptococcus as commercially obtained penicillin.

While producing more penicillin isn't necessarily a priority, the authors of the study say their research, though still in its early stages, demonstrates that baker's yeast could be a potential vehicle for producing and testing a whole range of new antibiotics. Baker's yeast is easy to genetically re-engineer and has previously been used to create molecules with industrial and therapeutic relevance, but this is the first time it has been genetically reprogrammed to produce antibiotics.      

"We believe yeast could be the new mini-factories of the future, helping us to experiment with new compounds in the nonribosomal peptide family to develop drugs that counter antimicrobial resistance," study co-author Ali Awan, PhD, said in an Imperial College news release.
May 4 Nat Commun study
May 4 Imperial College news release


VA study identifies factors associated with antimicrobial utilization

Originally published by CIDRAP News May 3

A new study of antimicrobial stewardship efforts at Veterans Administration (VA) hospitals published in the Journal of Hospital Medicine has identified factors associated with positive and negative effects on antimicrobial utilization.

The study comes out of a 2012 survey of antimicrobial stewardship practices at 130 acute care VA facilities administered by the VA National Antimicrobial Stewardship Task Force (ASTF). From the survey results, investigators derived 57 facility characteristics considered relevant to antimicrobial utilization, then whittled that number down to 34 variables. The variables were entered into a multivariable model that was used to determine associations between the variables and four antibiotic utilization measures: aggregate acute care antimicrobial use, antimicrobial use in patients with noninfectious primary discharge diagnoses, missed opportunities to convert from parenteral to oral antimicrobial therapy, and missed opportunities to avoid double anaerobic coverage with metronidazole.

Variables associated with at least three favorable changes (ie, reduced overall or noninfectious antimicrobial use, fewer missed opportunities to convert from parenteral to oral therapy or avoid double anaerobic coverage) included the presence of postgraduate physician/pharmacy training programs, the number of antimicrobial-specific order sets, frequency of systematic de-escalation review, the presence of pharmacists and/or infectious disease (ID) attending physicians on acute care ward teams, and formal ID training of the lead antibiotic stewardship program pharmacist. Variables associated with two unfavorable changes (increases in noninfectious antimicrobial use and missed opportunities to switch from parenteral to oral therapy) included number of hospital beds, the degree to which the facility engaged with the online resources of the VA stewardship task force, and the presence of antimicrobial stop orders.

"In summary, the VA has made efforts to advance the practice of antimicrobial stewardship system-wide, including a 2014 directive that all VA facilities have an ASP," the authors of the study write. "Our study identifies areas of stewardship that may correlate with, positively or negatively, antimicrobial utilization measures that will require further investigation."
May J Hosp Med study


Drug-resistant hospital infections tied to higher death rates

Originally published by CIDRAP News May 3

Hospital-associated infections caused by multidrug-resistant organisms (MDROs) can increase mortality, readmission rates, and emergency department (ED) visits compared with those caused by susceptible strains, Spanish investigators reported yesterday in Clinical Infectious Diseases.

The team studied 324 patients with MDRO infections and 686 with drug-susceptible infections. The risk of all-cause and 30-day mortality after infection was 70% and 77% higher, respectively, in MDRO patients. Probability of readmission was more than double that of patients with susceptible infections. ED visits were significantly higher with methicillin-resistant Staphylococcus aureus(MRSA) and Escherichia coli infections, in which case the risk was about triple and double the risk in patients with susceptible infections.

The authors noted the MDROs did not appear to influence length of hospital stay or the need for hospital admission, intensive care, surgery, or diagnostic tests.
May 2 Clin Infect Dis study


Study finds 6% resistance rate in hospital Enterobacteriaceae isolates

Originally published by CIDRAP News May 3

Scientists at a Malaysian teaching hospital found a 6% rate of carbapenem resistance among Enterobacteriaceae isolates obtained from patients and high rates of the resistance gene NDM-1, according to a study yesterday in Antimicrobial Resistance & Infection Control.

The team analyzed 8,306 Enterobacteriaceae isolates collected from August 2013 to December 2015 from patients at a 700-bed tertiary teaching hospital. Of those, 477 (5.7%) were carbapenem-resistant Enterobacteriaceae (CRE). About 86% of the CRE were K pneumoniae, and 49.3% were isolated from rectal swabs, with urine (15.9%) and blood samples (9.6%) accounting for most of the rest.

Of the 136 organisms that were genotyped, 112 (82.4%) were positive for the New Delhi metallo-beta-lactamase 1 (NDM-1) gene, which was first reported in 2009.
May 2 Antimicrob Resist Infect Control report


Pathogenic bacteria identified in Germany using DIY CRISPR kit

Originally published by CIDRAP News May 2

The European Centre for Disease Prevention and Control (ECDC) said that in March of this year, Germany reported the detection of pathogenic organisms in a do-it yourself Bacterial Gene Engineering CRISPR Kit. Some of the organisms were antibiotic-resistant.

"The kit is sold over the Internet, targeting non-professional microbiology hobbyists. The detection of the pathogenic microorganisms was made as part of the control implemented by local health and food safety authorities," the ECDC report said. The kit was labeled safe for at-home use.

The genome editing kit is manufactured in the United States, and the ECDC said it does not suspect to be in wide use in Germany or elsewhere in Europe.

"The risk of infection by the contaminating strains in the kit is low for the users of the kit, assuming that they are healthy," the ECDC concluded. "The contribution of the kit to the burden of antimicrobial resistance in the EU/EEA population and environment is marginal and the risk associated with the kits is considered very low."
Apr 29 ECDC report


Novel C diff antibiotic tops vancomycin in phase 2 trial

Originally published by CIDRAP News May 1

A phase 2 trial of the novel antibiotic ridinilazole in adults with Clostridium difficile infections showed that it performed better than vancomycin, one of three drugs used to routinely treat infections, and was well tolerated, with a similar adverse event profile.

An international group of researchers, including some from Summit Therapeutics, the drug's maker, published the findings on Apr 28 in The Lancet Infectious Diseases.

From June 2014 to Aug 2015 the investigators recruited 100 patients from 33 centers in the United States and Canada, randomly assigning half to the ridinilazole group and half to receive vancomycin. Their efficacy analysis is based on 69 patients: 36 ridinilazole recipients and 33 who got vancomycin. Sustained clinical response was seen in 66.7% (24) of ridinilazole subjects compared with 42.4% (14) of those who were treated with vancomycin. Recurrence was seen in 4 (14.3%) of 28 ridinilazole patients, compared with 8 (32.8%) of 23 vancomycin patients.

The researchers also found that ridinilazole performed better than vancomycin in patients older than 75 years, those with severe disease, and those who required other antibiotics, though the differences weren't always statistically significant.

The results support further development of the drug, the team concluded.

In a related commentary in the same issue, Simon Goldenberg, MD, with King's College London, wrote that the development of new drugs to treat C diff infections is vital, and ridinilazole appears to have many qualities that make it a good candidate for further development. He noted that the study was limited by the inclusion of patients who were slightly younger than the profile of C diff patients treated in everyday practice, with few who had previous infections. "Discounting these shortcomings, it is rare for a study of an antimicrobial to show statistical superiority over the standard of care," he wrote.
Apr 28 Lancet Infect Dis abstract
Apr 28 Lancet Infect Dis commentary


Study: Prescription length for strep throat is based on history, not science

Originally published by CIDRAP News May 1

A review published today in The Pediatric Infectious Disease Journal shows that the traditional 10-day course for antibiotics prescribed for strep throat has no basis in scientific evidence. Instead, the prescription length was determined 60 years ago, and is no more efficacious than a shorter course of treatment.

Streptococcal pharyngitis is a common diagnosis for a sore throat, and rarely can lead to serious complications, including rheumatic fever. Physicians traditionally prescribe a 10-day course of penicillin for the bacterial infection, but there are no studies that prove this prescription length is clinically valuable. Instead, it's a blanket recommendation that came out of the "penicillin boom" that followed World War II, a time when rheumatic fever was much more common in the United States.

Falling rates of rheumatic fever and the rise of non-penicillin antimicrobials should prompt clinicians to reconsider the need for 10 days of penicillin, the authors said. But, the subconscious power of the number "10" and a long clinical history will make changing prescribing patterns difficult.

"The 10-day rule appears to be an example of a more general phenomenon in clinical medicine, the fierce inertia of established usage," the authors concluded.
May 1 Pediatr Infect Dis J article

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