ASP Scan (Weekly) for Sep 02, 2016

CRE cases in Wisconsin
;
ASP intervention in C diff patients
;
Antibiotic prescribing by dentists
;
Incentives for antibiotic development
;
Polymyxin resistance in Brazil
;
Antibiotic resistance and childbirth
;
MCR-1 on the Arabian Peninsula
;
Drug-resistant fungal infections

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

 

Four CRE cases reported in Wisconsin

Originally published Sep 1.

Investigators with the Centers for Disease Control and Prevention (CDC) today describe a small cluster of the worrisome "superbug" known as carbapenem-resistant Enterobacteriaceae (CRE) at two Wisconsin hospitals in Morbidity and Mortality Weekly Report (MMWR).

According to the report, officials with the Wisconsin State Laboratory of Hygiene notified the Wisconsin Division of Public Health in June 2015 that five carbapenemase-producing CRE isolates had been identified among four inpatients at two hospitals in southeastern Wisconsin. They all contained the KPC gene, which codes for Klebsiella pneumoniae carbapemenase.

The KPC-CRE isolates were identified among 49 isolates obtained from 46 patients from February to May 2015. The median age of the four patients (two men and two women) was 65, and median hospitalization length was 83 days. All four patients had been intubated and undergone a tracheostomy.

Further investigation revealed that the five isolates exhibited a high degree of genetic relatedness but did not uncover how the bacteria traveled between the two facilities. Active surveillance conducted at the two hospitals in July 2015 identified no further cases. Site visits, reviews of infection prevention protocols, and interviews with infection prevention staff members, primary care providers, and patients found no breaches in recommended practices.

The authors of the report say the findings demonstrate the importance of routine hospital- and laboratory-based surveillance for the detection of healthcare-related CRE. In this case, staff at neither of the two hospitals was aware of the possibility of CRE transmission among their patients. The authors also say the use of molecular subtyping methods (like whole-genome sequencing) to determine the genetic similarities in the isolates was particularly valuable.
Sep 2 MMWR report

 

ASP intervention not found to improve outcomes in C diff patients

Originally published Sep 1.

A study today out of the University of Michigan has found a real-time antibiotic stewardship program (ASP) intervention in patients with Clostridium difficile infection (CDI) improved process measures but did not improve outcomes.

The study, published in the American Journal of Infection Control, details the results of what the authors call a "quasiexperimental" study of adult CDI patients before and after a real-time ASP review was initiated.

In the intervention group (285 patients), an ASP pharmacist was called in after diagnosis to review each case with the medical team and make recommendations on optimal treatment, antibiotic therapy and acid-suppressing therapy, and surgical/infectious disease consultation. In the control group (307 patients), CDI treatment was left to the discretion of the patient's primary medical team. Overall, ASP pharmacists provided treatment recommendations for 129 of the 285 patients in the intervention group.

The primary measurement of the study was a composite of several outcomes—including 30-day mortality, intensive care unit admission, surgery, and CDI recurrence. But process measures that may influence outcomes in CDI patients were also measured, with researchers looking at whether acid-suppressive therapy was reduced in CDI patients and whether patients with severe CDI received infectious disease consultation and appropriate and timely antibiotic therapy.

In the end, the researchers found that ASP intervention reduced unnecessary acid-suppressing therapy when compared with the control group. And patients with severe CDI who received ASP intervention were more likely to be treated with vancomycin, receive vancomycin therapy more quickly, and receive infectious disease consultation than the patients in the pre-intervention group. This finding is in line with previous studies on ASP intervention in CDI patients.

However, the investigators were not able to demonstrate a statistically significant improvement in primary clinical outcomes among the patients who received ASP intervention. Occurrence of primary composite outcome was 14.7% in the pre-intervention group and 12.3% in the intervention groups. The authors of the study say this may be due to the low baseline rates of these outcomes among the patients.

In conclusion, the authors say their findings, when added to previous literature on the topic, raise questions about whether ASP involvement in the conventional management of CDI is worthwhile, especially in institutions with low rates of CDI-attributable complications.
Sep 1 Am J Infect Control study

 

Study: Written reports help dentists reduce antibiotic prescribing

Originally published Aug 31.

A new UK study has found that dentists prescribe fewer antibiotics to their patients after receiving a report on their past prescribing habits.

According to the study, published yesterday in PLoS Medicine, dentists prescribe roughly 10% of the antibiotics dispensed in UK community pharmacies, often in the absence of clinical need. Using dental prescribing and treatment claim data routinely collected by the UK National Health Service (NHS), researchers with the RAPiD (Reducing Antibiotic Prescribing in Dentistry) trial set out to determine whether an individualized audit and feedback intervention could have an impact on prescribing habits.

The trial included 795 dental practices in Scotland, with 632 practices in an intervention group and 163 in a control group. The intervention group was further subdivided into two groups: one that received a line graph showing an individual dentist's monthly prescribing rate, and another that received a line graph with a written "behavior change" message containing national guidelines for dental antibiotic prescribing.

At the start of trial, the rate of antibiotics prescribed per 100 NHS treatment claims was 8.3 in the control group and 8.5 in the intervention group. After 12 months, the researchers found that both groups were prescribing fewer antibiotics. But the drop in the prescribing rate in the intervention group—from 8.5 to 7.5—was 5.7% greater than it was for the control group. And the subset of dentists who received a written message saw their prescribing rate drop by an additional 6%.

The authors of the study wrote that the findings are significant because they indicate that a "relatively straightforward, low-cost public health and patient safety intervention" could help the entire healthcare system address antimicrobial resistance.
Aug 30 PLoS Med study

 

Review outlines economic incentives for antibiotic development

Originally published Aug 31.

Limited commercial returns are considered a primary factor in why pharmaceutical companies are not investing in antibiotic development. That's why a "constellation of economic incentives" will be needed to promote antibacterial drug development going forward, according to an article published yesterday in Clinical Infectious Diseases.

The article, written by members of the Trans-Atlantic Task Force on Antimicrobial Resistance (TATFAR), is a review of the various economic incentives identified in policy documents, peer-reviewed publications, organization proposals, and government-sponsored reviews that have addressed the question of how to spur new antibiotic development. In October 2015, TATFAR agreed to make an informed recommendation on a package of economic incentives to be considered and implemented in the future.

In those documents, the authors found a consensus around the idea that economic incentives must contain both "push and pull" mechanisms that will guarantee return on investment. Push incentives include subsidies (in the form of grants, public-private partnerships, and tax credits) to fund early-stage development of antimicrobials, which is often risky and expensive. The idea is to provide incentives to academic institutions and companies by providing up-front money for research and development.

Pull incentives, on the other hand, are meant to encourage antibacterial drug development by promising a substantial financial reward to companies that successfully develop new antibiotics. Examples include large milestone or prize payments, patent buy-outs, advanced market commitments, and extended market exclusivity.

Pull incentives, the authors found, will be most successful if they rely on a "de-linkage" model that would remove the motivation for pharmaceutical companies to market and oversell their product. Negating the need for high product sales, they argue, would ensure that new antibiotics are not overused, thereby linking new antibiotic development to conservation and stewardship.

Finally, the authors found widespread agreement that global coordination will be needed to administer the funding of these incentive programs. 
Aug 30 Clin Infect Dis literature review

 

Growing polymyxin resistance reported in CRE in Brazil

Originally published Aug 31.

Brazilian researchers are reporting increasing resistance to polymyxin antibiotics in clinical Klebsiella Pneumoniae strains that are already resistant to carbapenem antibiotics.

In a letter to Emerging Infectious Diseases, the researchers report on an analysis of more than 3,000 K pneumoniae isolates recovered from patients at 10 private tertiary-care hospitals in Sao Paulo from January 2011 to December 2015.

The analysis showed a dramatic increase in carbapenem resistance in the K pneumoniae isolates—from 6.8% in 2011 to 35.5% in 2015. And among the carbapenem-resistant K pneumoniae isolates, polymyxin resistance rose from 0% in 2011 to 27.1% in 2015. Polymyxin resistance among carbapenem-susceptible K pneumoniae isolates also rose, from 0.7% in 2011 to 3.9% in 2015.

The authors said the findings are worrisome because carbapenem-resistant Enterobacteriaceae (CRE) are more deadly than carbapenem-susceptible strains, and carbapenem-resistant K pneumoniae bacteria are endemic in Brazil. Furthermore, most resistant infections are treated with polymyxins.
Aug 30 Emerg Infect Dis letter

 

UN experts warn antibiotic resistance will put mothers, infants at risk

Originally published Aug 30.

Every year, more than 30,000 women and 400,000 newborns die from infections that occur shortly after a woman has given birth. And those numbers will likely grow as rising drug resistance renders antibiotics less effective.

That's the central message in a commentary yesterday by Anthony Costello, MD, WHO director of maternal, newborn, child, and adolescent health, and Stefan S. Peterson, MD, PhD, MPH, UNICEF chief of health. The global health experts write that overuse of antibiotics in humans, along with "needless use" in animals, has created a "recipe for disaster" by accelerating the process in which exposed microbes build resistance.

Antibiotic resistance, they say, will have a major impact on newborns, who lack fully developed immune systems and are therefore more susceptible to infections they might pick up from their mother or from the hospital. Even more at risk will be children born in low-income countries, where healthcare facilities often lack basic sanitary conditions and lifesaving antibiotics are scarce.

"More children in Africa die from a lack of access to antibiotics than from antibiotic-resistant infections," Costello and Peterson write. "Indeed, many still die from infections, such as bacterial pneumonia, that should be easily treatable."

To solve this problem of "access and excess" and save the lives of infants and mothers, Costello and Peterson write, healthcare providers need to begin by stopping the spread of infection and negating the need for antibiotics. This means that all healthcare facilities must have running water and basic sanitation, and that staff must follow good hygiene practices. They also recommend implementing policies to discharge mothers and newborns from the hospital sooner, in order to reduce exposure to infectious microbes.

And lastly, healthcare providers should use antibiotics only when they can confirm that they are absolutely needed. "Simply put, those who need lifesaving antibiotics must get them, and those who do not must not," they write.
Aug 29 WHO commentary

 

MCR-1 found for the first time on the Arabian Peninsula

Originally published Aug 29.

An international team of researchers is reporting the first case of the colistin-resistance gene MCR-1 on the Arabian Peninsula.

In a study published in the International Journal of Infectious Diseases, the researchers reported that out of 75 colistin-resistant Enterobacteriaceae strains isolated from clinical cases in Bahrain, Kuwait, Oman, Saudi Arabia, and the United Arab Emirates, 4 Escherichia  coli isolates were found to harbor the MCR-1 gene on mobile pieces of DNA known as plasmids. Two of the isolates were from blood samples; the two others were from urine and a bed sore.

The researchers noted that the plasmids on the four isolates all carried various genes that confer resistance to carbapenem and beta-lactam antibiotics, with one of the isolates expressing high levels of carbapenem resistance. Besides colistin—which is considered an antibiotic of last resort—all four strains were uniformly resistant to third-generation cephalosporins, tetracycline, trimetoprime/sulfamethoxasole and gentamicin.

The researchers also said that one of the plasmids identified is the first found in a human E coliisolate to carry both MCR-1 and resistance genes to other classes of antibiotics. The findings are a concern because they suggest antibiotics commonly used in humans could facilitate the spread of MCR-1-carrying bacteria.

The MCR-1 gene was first identified in China in 2015, when researchers detected its presence in E colisamples from food, food animals, and humans. Since then, it's been found in bacteria in more than 30 countries.
Aug 26 Int J Infect Dis study 

 

British scientists warn about drug-resistant fungal infections

Originally published Aug 29.

UK scientists say that fungal infections are becoming increasingly resistant to the drugs used to treat them and warn that deaths will likely increase with rising resistance.

Fungi can cause a host of illnesses, from minor skin infections such as ringworm to more dangerous conditions like valley fever. While many of these conditions can be treated easily, fungal infections become more of a threat when they occur in people with compromised immune systems, like cancer patients, HIV patients, and premature babies. They're also a bigger problem in developing nations.

The Guardian reports that UK doctors are becoming increasingly alarmed about rising resistance to a class of antifungal agents known as azoles, which are used to treat a variety of fungal infections. Fungal resistance is similar to antibiotic resistance, but experts say it may be even more worrisome because there are far fewer drugs to treat fungal infections than there are antibiotics to treat bacterial infections.

"We cannot afford to lose the few drugs we have—particularly as very little funding is being made available for research into fungi and fungal infections," said Adilia Warris, MD, co-director of the Centre for Medical Mycology at Aberdeen University.

Warris and other experts said the widespread use of fungicides on agricultural crops is one of the factors in rising fungal resistance.

Fungal infections take more than 1.3 million lives each year globally, according to Rutgers University scientists.
Aug 26 Guardian story
Dec 23, 2013 Rutgers news release "Attacking fungal infection, one of world's major killers"

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