ASP Scan (Weekly) for Aug 31, 2018

C diff testing in the NICU
Resistant gonorrhea in Europe
ESBL bacteria in sprouts
Antibiotic resistance risk factors
Business case for stewardship
UK FMT C diff guidelines
Pharmacist-led stewardship
Typhoid vaccine as stewardship tool
Web training for antibiotic stewardship
Chest x-ray and pneumonia
New antibiotic for intra-abdominal infections
Bedaquiline for MDR-TB
Australian stewardship study

SHEA experts: No routine testing for C diff in NICU patients

A new white paper from the Society for Healthcare Epidemiology of America (SHEA) advises against routine testing for Clostridioides difficile (formerly Clostridium difficile) infection (CDI) in neonatal intensive care unit (NICU) patients.

The paper, published yesterday in Infection Control and Hospital Epidemiology, suggests instead that in NICU patients under 12 months with suspected infectious diarrhea, clinicians should first perform a thorough investigation for non-infectious causes, then test the stool for common viral pathogens, including norovirus, rotavirus, enteroviruses, and adenoviruses. A test for CDI is recommended only if there is evidence of pseudomembranous colitis or if the patient has clinically significant diarrhea and other non-infectious and infectious causes have been ruled out.

The authors, who are current and former members of the SHEA guidelines committee, say they're making the recommendation because, while infants under 12 months have a 35% rate of colonization of toxigenic C difficile, infections are rare, possibly because of protective factors in their digestive systems. Furthermore, it is difficult for clinicians to be certain that a positive test result indicates CDI, as opposed to colonization.

If clinicians are considering testing for CDI, the paper advises using a stool toxin test as part of a multistep algorithm, rather than using a nucleic acid amplification test alone.

The paper also addresses hand hygiene, contact precautions, and cleaning and disinfection strategies for CDI in the NICU. 
Aug 30 Infect Control Hosp Epidemiol white paper


ECDC reports slight increase in antibiotic-resistant gonorrhea in Europe

Neisseria gonorrhoeae, the bacterium that causes gonorrhea, continues to show high levels of resistance to azithromycin across Europe and resistance to it and another front-line antibiotic rose slightly, according to a report yesterday from the European Centre for Disease Prevention and Control (ECDC).

According to 2016 data from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 7.5% of N gonorrhoeae isolates were resistant to azithromycin, up from 7.2% in 2015. And 2.1% were resistant to cefixime, up from 1.7% in 2015. In addition, more countries reported azithromycin resistance (21, up from 18) and cefixime resistance (14, up from 9) compared with 2015.

In good news, no isolates with resistance to ceftriaxone were detected, compared with 1 in 2015, 5 in 2014, and 7 in 2013.

"While the absence of ceftriaxone resistance among the tested isolates in 2016 is encouraging," the ECDC said in a news release, "the persistent level of resistance to azithromycin is of concern as it threatens to reduce the effectiveness of the recommended dual therapy with ceftriaxone and azithromycin." European guidelines recommend dual therapy with azithromycin plus either ceftriaxone or cefixime.

The agency added, "Among those patients for whom information on their treatment course was reported in 2016, 86% were administered ceftriaxone and more than half received combined treatment with azithromycin. The use of two antimicrobials for gonorrhoea treatment has likely contributed to increased susceptibility to ceftriaxone. However, Euro-GASP data completeness for the variable 'treatment used' has still some way to go overall with just 37% in 2016."
Aug 30 ECDC news release
Aug 30 ECDC full report


Dutch researchers find 1 in 5 bean sprout samples tainted with ESBL-E

A Dutch study in PLoS One yesterday found that 19% of bean sprout samples bought from 2013 to 2016 harbored extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E).

Because community-acquired ESBL-E infections are increasing worldwide and previous research has not studied their presence in retail bean sprouts, the researchers analyzed 131 sprout samples for the antibiotic-resistant pathogens. They found that 25 samples (19.1%) were contaminated with ESBL-E, which are resistant to beta-lactam antibiotics. The detected bacteria were almost exclusively (96.2%) Klebsiella species, and the scientists found co-resistance to other antibiotics to be common.

The investigators were surprised to find no Escherichia coli among the ESBL-E–positive samples.

The researchers observed substantial genetic diversity between isolates over time. "On the other hand, isolates from samples closely matched in time were frequently clonally related, indicative of batch contamination."

They conclude, "Further investigations to the points of entry of ESBL-E into the production process and countermeasures against these entry points are warranted."
Aug 30 PLoS One study


Review identifies top risk factors for antibiotic resistance

Originally published by CIDRAP News Aug 30

A systematic review and analysis of available evidence by researchers in the United Kingdom has identified previous antibiotic exposure, underlying disease, and invasive procedures as the top risk factors for antibiotic resistance in humans.

For the review, which was published yesterday in The Lancet Infectious Diseases, researchers with Imperial College London selected and analyzed 565 studies that reported on risk factors from humans, animals, and the environment that result in antibiotic resistance in humans. Using a One Health approach, their aim was to link the quality with the quantity of data reported on antibiotic-resistant bacteria that arise from human, animal, and environmental reservoirs and identify the most evidence-based risk factors. Study quality was assessed in accordance with Cochrane recommendations.

Of the 565 studies included, 527 were reports of primary research and 38 were meta-analyses; the vast majority of the primary research studies (89%) reported on risk factors within the human reservoir, and 11% reported on risk factors arising from the relationships between animal and human reservoirs or human and environmental reservoirs. The 527 primary research studies were used to construct a map of antibiotic resistance drivers.

Of the 88 risk factors identified in these studies, previous antibiotic exposure, underlying disease, and invasive procedures were the risk factors with the most supporting evidence identified. The odds ratios of antibiotic resistance were reported to be between 2 and 4 for these risk factors when compared with their respective controls or baseline risk groups.

Overall, there was little evidence pertaining to cross-reservoir drivers; the effect of the animal reservoir on humans was the most frequently studied aspect of cross-reservoir factors, while evidence supporting the environment as a transmission source for antibiotic-resistant bacteria was scarce.
Aug 29 Lancet Infect Dis review summary


Canadian experts build business case for hospital stewardship programs

Originally published by CIDRAP News Aug 30

Canadian experts have created a business case for antimicrobial stewardship programs (ASPs) in acute care hospitals, which they say will be essential as regulatory and legislative requirements increase.

Writing in Antimicrobial Resistance & Infection Control yesterday, the scientists conducted a review of legislative requirements and outline human resource requirements for ASPs. The also met as a working group to develop the business case.

They found two sets of ASP requirements at the national level: part of the Required Organization Practice by Accreditation Canada and in the National Safety and Quality Health Service Standards required for hospital accreditation in Australia. In addition, ASP legislation was passed in 2014 in California. (The US Joint Commission developed standards in January 2017, but this was after the working group had met.)

The experts identified only one study that addressed human resource requirements. A survey of 65 hospitals in France concluded that 3.6 full-time equivalent (FTE) leads, 2.5 FTE pharmacists, and 0.6 FTE of dedicated microbiologists per 1,000 beds were needed to sustain an ASP, but the study did not provide an evidence-based rationale.

Based on the literature review and consensus development, the working group recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as FTEs per 1,000 acute care beds. The experts also developed a spreadsheet-based tool for developing a business case for hospital AFPs into which inputs can be applied to build scenarios for presentation to hospital administration.
Aug 29 Antimicrob Resist Infect Control paper


UK health groups publish guidelines for FMT in recurrent C diff patients

Originally published by CIDRAP News Aug 29

The British Society of Gastroenterology and the Healthcare Infection Society have published guidelines for the use and screening of fecal microbiota transplant (FMT) in patients with recurrent or refractory C difficile infection (CDI).

The guidelines, published yesterday in BMJ Gut and based on a review of randomized trial evidence, recommend that FMT should be offered to patients with recurrent CDI who have had at least two recurrences, or those who have had one recurrence and have risk factors for further episodes. But FMT should only be considered after recurrence of symptoms following resolution of an episode of CDI that was treated with appropriate antimicrobials for at least 10 days. Consideration of treatment with extended/pulsed vancomycin and/or fidaxomicin before considering FMT is recommended.

The guidelines also advise that FMT be considered in cases of refractory, or unmanageable, CDI (although the quality of evidence for its utility is lower than for recurrent CDI), but should not be administered as initial treatment for CDI. FMT is not recommended for treatment of irritable bowel syndrome or other gastrointestinal diseases.

For FMT donations, the guidelines recommend that FMT is best sourced from a centralized bank of frozen stool, but that related and unrelated donors should both be considered acceptable. Potential donors should be screened by questionnaire and personal interview to establish risk factors for transmissible diseases, and blood and stool screening is mandatory.  

While FMT has become an accepted treatment for recurrent CDI, the authors of the guidelines say the absence of appropriate, evidence-based protocols that take into account UK clinical practice and FMT regulation has been perceived as a barrier to FMT use in the United Kingdom in Ireland. "These guidelines seek to rectify this problem," they wrote.
Aug 28 BMJ Gut article


General pharmacists might be option for resource-limited stewardship

Originally published by CIDRAP News Aug 29

General pharmacists who underwent a short infectious diseases training course can safety implement an antibiotic approval program, thereby providing an antimicrobial stewardship program option for resource-limited settings, researchers from Thailand reported today in Infection Control and Hospital Epidemiology.

For their study, the investigators compared the effectiveness of antibiotic postprescription review and authorization (PPRA) done by infectious diseases (ID) clinical fellows with that done by trained general pharmacists. The study took place on 6 medical wards of a Bangkok hospital—3 assigned to the clinical fellow group and 3 to the pharmacist group. The researchers focused on patients who received one or more doses of targeted antibiotics: piperacillin/tazobactam, imipenem/cilastatin, and meropenem. There were 303 patients in the pharmacist PPRA group and 307 in the clinical fellow PPRA.

The researchers looked for any differences in favorable response of the patients who received the targeted antibiotics, based on whether PPRA was done by clinical fellows or trained pharmacists.

The authors found no significant difference in favorable clinical response between the two groups, but they couldn't confirm noninferiority of pharmacist PPRA in the consumption of targeted antibiotics. The team did, however, find no significant difference in consumption of targeted antibiotics, antibiotic expenditure, and other treatment outcomes.

They concluded that the strategy of using trained pharmacists appears safe, but it may not be as efficient in reducing antibiotic consumption as antibiotic approval implemented by ID clinical fellows. "Therefore, using trained general pharmacists could be an alternative to ID specialists for antibiotic approval when resources are limited," they wrote.
Aug 29 Infect Control Hosp Epidemiol abstract


Experts tout typhoid conjugate vaccine as an antibiotic stewardship tool

Originally published by CIDRAP News Aug 29

In a commentary yesterday in The Lancet Infectious Diseases, a global group of experts outlined why large-scale, more aggressive typhoid vaccination programs have the potential to reduce antibiotic overuse, a factor that should be incorporated when planning immunization campaigns.

Typhoid fever, caused by Salmonella enterica serotype Typhi bacteria, is responsible for an estimated 12 million to 20 million illnesses and more than 150,000 deaths a year. In March the World Health Organization recommended "programmatic" use of typhoid conjugate vaccines in endemic nations. Officials have formed national vaccination policies based on averted typhoid cases and their associated costs, but this paints only a partial picture, the scientists said.

"For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year," the authors write. "Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally."

The experts propose that large-scale, more aggressive typhoid vaccination programs—including catch-up campaigns in children up to 15 years old and vaccination in lower-incidence settings—may reduce the overuse of antimicrobials and thereby help stem antimicrobial resistance. "Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines," they conclude.
Aug 28 Lancet Infect Dis commentary


Internet training tied to fewer antibiotic for respiratory tract infections

Originally published by CIDRAP News Aug 28

A new study in the Journal of Antimicrobial Chemotherapy shows that Internet-based communication training might be a cost-effective way to limit primary care antibiotic prescriptions when compared with C-reactive protein (CRP) testing.

Yesterday's study, conducted by UK & Belgian scientists, measured the cost-effectiveness of interventions among primary care clinicians treating patients who had respiratory tract infections in five European countries over a 28-day period. The clinicians were either trained in the use of CRP testing, trained in Internet-based communication skills, or trained in both CRP testing and communication skills, all as a way to reduce the number of written antibiotic prescriptions.

During the month-long study, approximately 59% of participants in the usual care arm had an antibiotic prescribed, compared with 34% in the combined intervention arm. Under cost-saving analysis, Internet-based communication training was the most cost-sparring way to reduce antibiotic prescribing.

"In terms of cost per percentage reduction in antibiotic prescribing, overall, communication skills was the most cost-effective intervention," the authors conclude.
Aug 27 J Antimicrob Chemother 


Study: Chest x-ray can rule out pneumonia in kids and save antibiotics

Originally published by CIDRAP News Aug 28

Using chest radiography (CXR) to rule out pneumonia in kids allows for the safe observation of children without the initiation of antibiotic use, according to a study today in Pediatrics.

CXR has long been used in the diagnosis of pneumonia, but it can result in false-negatives if performed early in the illness or if a child is dehydrated. This prospective study took place over a 2-year period and included 683 children ages 3 months to 18 years, with a median age of 3 years.

In total, 16.5% of children had positive, 10.7% had equivocal, and 72.8% had negative CXRs. Of the 156 children with clinically diagnosed pneumonia, 78% had positive or equivocal CXRs and 22% had negative CXRs. Forty-four children (8.9%) were clinically diagnosed with pneumonia at the emergency department despite the negative radiographic findings.

Of the 411 children with negative CXRs who were not prescribed an antibiotic, only 5 (1.2%) were diagnosed as having pneumonia during a 2-week follow-up period. The negative predictive value of CXR was 98.8% (95% confidence interval, 97.0%-99.6%).

"Among children with negative CXRs who were not treated with or prescribed antibiotics, only 1.2% were subsequently diagnosed with pneumonia within 2 weeks of the ED visit," the authors said. "Our findings reveal that most children with negative results will recover fully without antibiotic use."

But in a commentary in the same journal, Matthew D. Garber, MD, and Ricardo A. Quinonez, MD, pediatricians who were not involved in the research, write that the study overemphasizes the provenance of bacterial pneumonia in children, and thus attributes too much diagnostic power to CRXs. They suggest that children who have a low clinical suspicion of pneumonia could also avoid CRX, further decreasing radiation, cost, and unnecessary antibiotics. 
Aug 28 Pediatrics study
Aug 28 Pediatrics commentary 


FDA approves antibiotic for treating complicated intra-abdominal infections

Originally published by CIDRAP News Aug 28

Tetraphase Pharmaceuticals announced yesterday that the US Food and Drug Administration (FDA) has approved its novel antibiotic eravacycline (Xerava) for treating complicated intra-abdominal infections (cIAI) in patients age 18 and older.

In a statement, the company, based in Watertown, Mass., said clinical trials have shown that the drug was well tolerated and achieved high cure rates in patients with cIAI and was statistically noninferior to two widely used drugs, ertapenem and meropenem. To reduce the development of drug-resistant bacteria and maintain eravacycline's effectiveness—and that of other drugs—it should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

Philip Barrie, MD, MBA, professor of surgery and public health at Weill Cornell Medicine, said in the statement that cIAIs are the second most prevalent infection site in intensive care units and are the second leading cause of infection-related mortality in ICUs. "With the growing crisis of antibiotic resistance, treatment options for these polymicrobial infections are limited following surgery or percutaneous drainage, and the causative pathogens may be multi-drug resistant," he said, adding that current empiric treatments for cIAIs all have limitations, creating a need for new and novel treatments. "Eravacycline has a broad spectrum of antibacterial activity and a clinical profile that addresses this unmet medical need," Barrie said.

Eravacycline dosage doesn't need to be adjusted for patients who have renal impairment, and the drug can be used in those who are allergic to penicillin, he said.

The company said it expects the drug to launch commercially in the fourth quarter of 2018.

The Biomedical Advanced Research and Development Authority (BARDA), part of the US Department of Health and Human Services (HHS) Assistant Secretary for Preparedness and Response (ASPR), has provided support for the drug's development since 2012. Rick Bright, PhD, BARDA's director, said the FDA's approval of eravacycline provides a new weapon in the battle against antibiotic resistance and addresses an unmet need for patients suffering from multidrug-resistant and other serious infections.

In an ASPR blog post yesterday, two BARDA officials said the novel, fully synthetic tetracycline antibiotic can also be used against serious gram-negative infections, including ones caused by multi-drug resistant organisms considered urgent public health threats by the Centers for Disease Control and Prevention and the World Health Organization.

They also wrote that Tetraphase conducted BARDA-supported studies needed for the FDA to consider eravacycline for emergency use authorization for treating anthrax or tularemia.
Aug 27 Tetraphase press release
Aug 27 ASPR blog post


Study: Swapping bedaquiline for injectables improves MDR-TB outcomes

Originally published by CIDRAP News Aug 27

The substitution of bedaquiline for second-line injectable antibiotics (SLIs) in a small group of patients with multidrug-resistant tuberculosis (MDR-TB) resulted in improved outcomes, South African researchers report in Clinical Infectious Diseases.

In South Africa, the oral antibiotic bedaquiline is now widely being used in MDR-TB regimens for patients who are unable to tolerate SLIs, which have been associated with significant adverse events, such as hearing loss. To determine the effectiveness of this strategy, the retrospective cohort study looked at patients with laboratory-confirmed MDR-TB who received bedaquiline as a substitute for SLIs from October 2014 through October 2016. The study also included a group of MDR-TB patients who did not receive bedaquiline.

The primary outcome measure was the proportion of patients with unfavorable outcomes at 12 months, defined as a composite of death, loss to follow-up, and failure to achieve sustained culture conversion. The patients were matched 1:1 for clinic location and time of treatment.

The study included 330 patients overall (162 patients who received bedaquiline and 168 controls), 70.6% of whom were also HIV-infected. Unfavorable outcomes occurred in 23.9% of patients (35/146) in the bedaquiline group, compared with 36.2% of patients (51/141) in the control group (relative risk [RR], 0.66). The reduction in unfavorable outcomes with bedaquiline use was mainly influenced by differences in sustained culture conversion rates: Only 5.9% of patients (7) who switched to bedaquiline failed to achieve sustained culture conversion at 12 months, compared with 17.4% of patients (19) in the control group. In addition, the number of patients with culture reversion was significantly lower in the bedaquiline group (1 patient [0.8%] vs 12 patients [10.3%] in the control group). Mortality in the two groups was similar at 12 months (11 deaths in each group).

The authors of the study say the findings provide additional evidence to support the routine inclusion of bedaquiline in MDR-TB regimens.
Aug 24 Clin Infect Dis abstract


Australian GP stewardship program reduces prescribing, saves money

Originally published by CIDRAP News Aug 27

A study of general practitioners (GPs) in Australia indicates that a multifaceted package of interventions to reduce antibiotic prescribing for acute respiratory infections (ARIs) was effective, well-received, and feasible.

The summary report of the General Practitioner Antimicrobial Stewardship Programmes Study (GAPS) describes a cluster randomized trial that compared two parallel groups of GPs in 27 clinics in Queensland before and after implementation of an evidence-based package of interventions. The interventions included a poster on antibiotic prescribing policy in GP waiting rooms or examination rooms, a patient information leaflet, an online communication training package, delayed antibiotic prescribing, patient decision aids, and near-patient testing with C-reactive protein.

The primary objective of the study was to assess the effectiveness of the package in reducing antibiotic prescribing for ARIs. The researchers also looked at the costs and cost-effectiveness of the intervention package and assessed feasibility and uptake.

While the results showed that there were measurable declines in antibiotic prescribing in both the intervention and control groups during the intervention phase compared with the baseline phase, a secondary analysis found a statistically significant reduction in prescribing rates of 7% for the intervention group compared with the control group (RR, 0.93), resulting in a net decrease of 3.8 antibiotic prescriptions per GP per month. Including the economic benefit of avoiding adverse antibiotic reactions (rashes and diarrhea) and C difficile, the researchers estimated that the cost savings from the reduced prescribing was just over $57,000.  If rolled out to 250 practices over 3 years, the researchers calculated, these savings could offset the cost of implementing the intervention package by over $200,000.

Phone interviews with GPs from the intervention practices found that the intervention package was well-received, was considered adaptable to individual practices, and provided GPs with the opportunity to reflect on their management of patients with suspected ARIs.

The authors say the findings should help inform policy for future national implementation.
Aug 27 GAPS final summary report

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