ASP Scan (Weekly) for Dec 15, 2017

Rifampicin for Staph bacteremia
VRE in the ICU
ICU antibiotic stewardship
More puppy Campylobacter
Better antibiotic drug trials
Vaccines to fight AMR
Asymptomatic bacteriuria treatment guide
Antimicrobial resistance workshop

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

Study: No benefit from adding rifampicin to S aureus bacteremia treatment

The results of a large randomized trial show that adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with Staphylococcus aureus bacteremia, UK researchers reported yesterday in The Lancet.

For many years, the researchers explain, it's been hypothesized that adding rifampicin to the standard treatment for S aureus bacteremia (either an anti-staphylococcal penicillin or a glycopeptide if the bacteria are resistant to methicillin) might improve outcomes for the infection, which is one of the most common and serious community- and hospital-acquired infections worldwide. That belief has led to widespread use of rifampicin for treatment of S aureus bacteremia, even though the evidence to support the benefit is weak.

To test the hypothesis that adjunctive rifampicin is beneficial for S aureus bacteremia patients, the researchers conducted a multicenter, randomized, double-blind, placebo-controlled trial of adults with S aureus bacteremia treated at 29 UK hospitals from December 2012 through October 2016. The participants were randomized 1:1 to receive either rifampicin or a placebo for 2 weeks, plus standard antibiotic therapy as chosen by the attending physician. The primary outcome was bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomization to 12 weeks.

Of the 758 eligible participants, 370 received rifampicin and 388 received a placebo in addition to standard therapy. Standard antibiotics were given for a median duration of 29 days, and 619 participants (82%) received flucloxacillin. By week 12, bacteriologically confirmed treatment failure or disease recurrence, or death, had occurred in 62 participants (17%) in the rifampicin group compared with 71 patients (18%) in the placebo group (absolute risk difference -1.4%, hazard ratio 0.96). While there was a small but significant reduction in disease recurrence associated with rifampicin, that effect had no impact on short-term or long-term mortality. In addition, patients treated with rifampicin had more adverse events than those treated with placebo (17% vs. 10%) and were more likely to have drug interactions that complicated their treatment (6% vs. 2%)

"In summary, adjunctive rifampicin did not improve outcomes from S aureus bacteraemia, with the exception of a modest reduction in disease recurrence," the authors conclude. 
Dec 14 Lancet study
Dec 14 Lancet commentary


Irish study finds VRE contamination common in the ICU

Irish researchers report that intensive care unit (ICU) environmental contamination with vancomycin-resistant enterococci (VRE) in areas near patients is common, even in non-outbreak settings, according to a study yesterday in Infection Control and Hospital Epidemiology.

In the single-center study, conducted in the ICU of an 820-bed teaching hospital in Dublin, investigators took samples from the ICU environment and patients during seven sampling periods from October 2012 through June 2014. The aim of the study was to identify potential reservoirs of VRE, investigate the clinical and molecular epidemiology of VRE outside of outbreaks, and assess the role of active surveillance cultures (ASCs) in identifying VRE patients in this setting. Ireland has the highest rate of VRE bloodstream infections in Europe at 45.8%.

Of 289 sampling occasions involving 157 patients and their bed spaces, VRE isolates were recovered from patient bed spaces, clinical samples, or both on 114 of 289 sampling occasions (39.4%). The patient and their bed space were positive for VRE on 34 of 114 VRE-associated sampling occasions (29.8%). Thirty of the 157 patients (19%) were VRE-colonized.

Of 1,647 environment samples, 107 sites (6.5%) were VRE positive, with significantly greater VRE recovery from isolation rooms than from the open-plan area (9.1% vs 4.1%). The most frequently VRE-contaminated sites were the drip stand, bed control panel, and chart holders, which together accounted for 61% of contaminated sites. The use of ASCs resulted in a 172% increase in identification of VRE-colonized patients. Molecular typing revealed two environmental clusters, one involving three patients and generally greater heterogeneity of patient isolates compared to environmental isolates.

The authors conclude that better infection control policies that limit environmental transmission of VRE in the ICU are needed. 
Dec 14 Infect Control Hosp Epidemiol study


Palestinian study finds good response to ICU stewardship intervention

A prospective audit-and-feedback antimicrobial stewardship program (ASP) in a Palestinian ICU found a high acceptance rate for the ASP team's recommendations, according to a study this week in the British Journal of Clinical Pharmacology.

The ASP program was begun at the Palestinian Medical Complex in September 2015. The investigators analyzed data from the 4 months before and the 4 months after implementation.

They found that, of 176 recommendations made by the ASP team, 78.4% were accepted. The most often accepted interventions were dose optimization (87%) and de-escalation based on culture results (84.4%). In addition, interventions were associated with a 24.3% reduction in antimicrobial use, shorter length of stay, and significantly reduced duration of therapy. 
Dec 13 Br J Clin Pharmacol study


More cases of puppy-linked Campylobacter reported in several states

Originally published by CIDRAP News Dec 13

The Centers for Disease Control and Prevention (CDC), in an update on an ongoing outbreak of multi-drug resistant Campylobacter infections linked to puppies sold in pet shops today, confirmed 30 new cases reported since the last outbreak update published on Oct 30.

As of yesterday, officials have reported that 97 people in 17 states have laboratory-confirmed infections or symptoms consistent with Campylobacter infection. A total of 22 people have been hospitalized, but no deaths have been reported. The first cases were reported to the CDC in June.

The vast majority of patients (98%) reported contact with a puppy in the week preceding illness. Ninety percent of people interviewed said they had contact with a puppy from a Petland store, or had contact with a person who became sick after contact with a puppy from a Petland store. Twenty-one ill people worked at a Petland store.

Using whole genome sequencing, the CDC identified multiple antimicrobial resistance genes and mutations in most isolates from 35 ill people and 9 puppies, including resistance to azithromycin, ciprofloxacin, clindamycin, erythromycin, nalidixic acid, telithromycin, and tetracycline.
Dec 13 CDC update


Clinicians call for more inclusive trials for new antibiotics

Originally published by CIDRAP News Dec 12

A letter today in the Journal of Infectious Diseases argues for relaxed criteria for patient exclusion in randomized controlled trials (RCTs) for new drugs to treat multidrug-resistant infections.

The letter, written by two Israeli clinicians, describes three patients with severe infections caused by carbapenem-resistant bacteria that presented during a single day at a hospital in Haifa. None of the three patients, the authors note, was eligible for an ongoing RCT at the hospital to assess the antibiotic cefiderocol—a novel siderophore cephalosporin in late-stage development—versus the best available therapy for bloodstream and other severe multidrug-resistant infections. All were treated with colistin as the only covering antibiotic.

These cases, the authors argue, point out a paradox. While it's estimated that more than 700,000 patients die each year from infections caused by multidrug-resistant pathogens, and plenty of patients with carbapenem-resistant infections are described in epidemiologic studies, finding patients for drug approval RCTs is difficult. That's because RCTs are often biased toward uncomplicated patients with a low risk of death, and the patients with the types of conditions described in their letter—neutropenia, severe sepsis, and organ failure—are often excluded from such studies. Yet these are the patients who may have the greatest need for new treatments.

While efforts to improve testing and approval requirements of new drugs for unmet needs have been commendable, the authors write, "We would like a discussion about the changes in regulatory guidance to the industry that would relax criteria for patient exclusion to ensure that the patients in [an] RTC resemble a bit more the patients in need of the antibiotic under study."
Dec 12 J Infect Dis letter


Commentary: Vaccines needed in the fight against AMR

Originally published by CIDRAP News Dec 12

Vaccines could and should play a key role in stemming the antimicrobial resistance (AMR) crisis, according to a commentary today in Nature.

The commentary, co-authored by the chief scientist at GlaxoSmithKline Vaccines and professors from Harvard T.H. Chan School of Public Health and Cincinnati Children's Hospital, calls for a global strategic effort to prioritize development of a portfolio of vaccines to target AMR.

Their reasoning is based on several factors. For one, they argue, vaccines almost never prompt bacteria to develop resistance. In addition, scientists have had much more success over the last 30 years developing new vaccines than they've had discovering new antibiotics. Since the 1980s, 22 new vaccines have been deployed in the clinic, while no new truly new class of antibiotics has been discovered or engineered. And vaccine technology continues to evolve.

Given this reality, and the fact that several current vaccines—such as the pneumococcal and influenza vaccines—have already helped directly and indirectly reduce the need for antibiotics, the authors say vaccines must be considered an essential element of the fight against AMR, along with new antibiotics, diagnostics, surveillance, and stewardship. Launching an effort to develop a portfolio of vaccines against AMR, they say, will require policymakers and stakeholders to raise awareness about the potential of vaccines to combat AMR, to persuade governments and drug companies of the cost-effectiveness of investing in vaccines, and to prioritize which bacterial strains should be targeted.

"Over the past few years, key institutional stakeholders — notably the [World Health Organization], the [United Nations General Assembly], the World Bank, the G20 group of countries, the European Union and the UK and US governments — have called for researchers to develop new antibiotics to expand our arsenal in the war against superbugs," the authors write. "We appeal to these organizations to call now for a multi-layered strategy that prioritizes the development of vaccines to target resistant strains."
Dec 12 Nature comment


Interventions to reduce overtreatment of asymptomatic bacteriuria noted

Originally published by CIDRAP News Dec 11

A paper today in JAMA Internal Medicine proposes an evidence-based implementation guide to help reduce inappropriate treatment of asymptomatic bacteriuria (ASB).

Despite efforts to reduce the practice, treatment of ASB—defined as isolation of bacteria in an uncontaminated urine specimen in the absence of urinary tract infection symptoms—remains prevalent across settings and frequently leads to inappropriate antibiotic prescribing. A multicenter retrospective review of three US hospitals found that 38% of in patients with ASB were treated with antibiotics the day of a positive urine culture report, and 43% were treated by the fourth day.

To come up with an implementation guide that could help clinicians reduce ASB overtreatment, a team of researchers from Johns Hopkins, Sinai Health System, and the University of Toronto first reviewed the evidence behind supporting reduced treatment of ASB. Based on that evidence, they determined that efforts to reduce inappropriate treatment of ASB in low-risk populations (excluding pregnant women and patients undergoing invasive urologic procedures) can reduce preventable harm from unnecessary antibiotic exposure.

The team then looked at safety and quality outcomes data for different interventions aimed at reducing ASB treatment. From those data, they determined that the most successful interventions used a multimodal approach that combined the following elements: education, audit and feedback, withholding routine urine culture reports, and clinical decision support tools and protocols.

"While the interventions described in this guide have proven efficacy in certain settings, we acknowledge the importance of context and encourage teams to select and adapt specific interventions that best suit the needs and resources specific to the institution," the authors write. "In reality, a bundle of interventions may be needed to address different contributors to the problem specific to the local setting."
Dec 11 JAMA Internal Med paper


New National Academies publication details AMR workshop proceedings

Originally published by CIDRAP News Dec 11

The National Academies of Sciences, Engineering, and Medicine (NAS) have released a new document summarizing the presentations and discussions at a 2-day workshop on antimicrobial resistance (AMR) held earlier this year.

The workshop, held Jun 20 and 21 in Washington, DC, brought together experts in infectious disease, microbiology, and human and animal health to explore the issue of AMR through the One Health lens, which views the health of humans, animals, and the environment as interconnected. The workshop was convened to examine short-term actions and research needs that are feasible and cost-effective and will have the greatest effect on reducing AMR.

Among the topics explored were the implications and effects on human health of the movement of resistance genes across different ecosystems; the expected effect of new US regulatory policies regarding the use of antibiotics in food animals; the role and effectiveness of antibiotic stewardship programs in reducing and preventing AMR, and the importance of data availability and data sharing for evaluating stewardship strategies; strategies for maintaining the effectiveness of existing drugs, for developing new drugs and diagnostics, and for implementing disease prevention steps; and the need for national and international collaboration.

The document contains the opinion of the presenters, but it does not reflect the conclusions of the Health and Medicine Division of the NAS.
Dec 8 National Academies proceedings of AMR workshop

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