ASP Scan (Weekly) for May 22, 2020

News brief

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

Antibiotic stewardship pharmacist review tied to better care for Staph bacteremia

Adding real-time antimicrobial stewardship (AMS) pharmacist review to infectious diseases consultation (IDC) for management of patients who have Staphylococcus aureus bacteremia (SAB) was associated with more optimal antibiotic use and better care at hospitals in Illinois, researchers reported yesterday in Open Forum Infectious Diseases.

The retrospective study included all patients with SAB treated at seven Aurora Advocate Health hospitals in Chicago from January 2016 through December 2018. The researchers compared outcomes between three time periods: pre-mandatory IDC and AMS review (period 1), post-mandatory IDC and pre-AMS review (period 2), and post-mandatory IDC and AMS review (period 3). The primary outcome was adherence to a quality care bundle, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary endpoints included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related admission, and in-hospital all-cause mortality.

A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n=241/371), 54% in period 2 (n=47/87), and 76% in period 3 (n=92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37 to 0.93; P = 0.02), and period 2 (OR, 0.37; 95% CI, 0.20 to 0.67; P = 0.0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P < 0.001), source control (34% vs 45% vs 45%; P = 0.04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P = 0.01). No differences were noted for readmission or mortality.

"This study describes an effective real-time, pharmacist-driven AMS review that was associated with improved management of SAB in the setting of pre-existing mandatory IDC," the authors of the study wrote. "Our study is unique in that it demonstrates the benefit of AMS review in addition to IDC for optimizing SAB care."
May 21 Open Forum Infect Dis study

 

Drug-resistant Salmonella Typhi in US patients linked to Pakistan, Iraq

Originally published by CIDRAP News May 21

Researchers from the Centers for Disease Control and Prevention (CDC) have identified 33 cases of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi in the United States linked to travel in Pakistan and Iraq, according to an update today in the CDC's Morbidity and Mortality Weekly Report (MMWR).

The 33 isolates of XDR Salmonella Typhi, the bacterium that causes typhoid fever, were identified during surveillance conducted from February 2018 through August 2019; none had been detected prior to 2018, when the CDC began surveillance for the pathogen.

Thirty of the isolates came from cases of XDR typhoid fever linked to travel to Pakistan, where an outbreak that began in Sindh province in 2016 has now sickened more than 10,000 people. Antimicrobial susceptibility testing and whole-genome sequencing showed that the isolates were resistant to ceftriaxone, ampicillin, chloramphenicol, ciprofloxacin, nalidixic acid, streptomycin, sulfisoxazole, and trimethoprim-sulfamethoxazole.

The three other isolates were linked to travel in Iraq and were from a strain genetically distinct from the XDR strain associated with travel in Pakistan. Like the Pakistan strain, the ceftriaxone resistance in the Iraq strain is plasmid mediated and has the potential to spread to other bacteria, but the Iraq strain is susceptible to other antibiotics, including trimethoprim-sulfamethoxazole. All 33 isolates were susceptible to azithromycin and meropenem.

The authors say US clinicians should remain vigilant for ceftriaxone-resistant Salmonella Typhi in patients who have traveled to Pakistan or Iraq.

"Clinicians should request antimicrobial susceptibility testing for all Typhi isolates and tailor patient treatment accordingly," they write. "All patients should be asked about travel, and special consideration should be given to empiric treatment for patients who have recently returned from Iraq or Pakistan."

They add that clinicians should advise patients travelling to Pakistan and Iraq to receive pre-travel typhoid vaccination and practice safe food and water precautions, as Salmonella typhi is usually transmitted by contaminated water or food.
May 21 MMWR report

 

European Commission aims to cut farm, fishery antibiotic use

Originally published by CIDRAP News May 21

The European Commission yesterday announced new targets for reducing sales of antibiotics used on farms and in aquaculture.

The targets, part of the Commission's Farm to Fork Strategy for a fair, healthy, and environmentally friendly food system, call for a 50% reduction in sales of antibiotics for farmed animals and aquaculture in European Union member states by 2030. The strategy also calls for a 50% reduction in pesticide use, a 20% reduction in the use of fertilizers, and for making 25% of agricultural land organic by 2030.

Commission officials say the strategy will enable the EU to transition to a sustainable food system that safeguards food security, ensures access to healthy diets, reduces the environmental and climate footprint of the EU food system, and strengthens resilience to future pandemics.

"The Farm to Fork Strategy will make a positive difference across the board in how we produce, buy and consume our food that will benefit the health of our citizens, societies and the environment," Stella Kyriakides, Commissioner for Health and Food Safety, said in a press release. "It offers the opportunity to reconcile our food systems with our planet's health, to ensure food security and meet the aspirations of Europeans for healthy, equitable and eco-friendly food."

The Commission says antibiotic sales will be monitored on an annual basis.
May 20 European Commission press release

 

Multimodal initiative tied to less fluoroquinolone use in healthcare network

Originally published by CIDRAP News May 21

A multimodal stewardship initiative at a healthcare network in Dallas was associated with reduced total and inappropriate fluoroquinolone prescribing in outpatient settings, researchers reported today in Open Forum Infectious Diseases.

The initiative implemented at Parkland Health & Hospital System in November 2016 involved four interventions: recurring education from an infectious diseases (ID) pharmacist on the risks, benefits, and appropriate use of fluoroquinolones; the addition of Food and Drug Administration warnings to all fluoroquinolone orders; the suppression of ciprofloxacin susceptibilities from microbiology reports when appropriate; and the creation of an outpatient order set for cystitis.

The interventions were implemented because of concerns about adverse drug events linked to fluoroquinolone use, associated risks for Clostridioides difficile infection, and rising fluoroquinolone resistance in urinary pathogens.

To measure the impact of these interventions, researchers reviewed outpatient chart orders in which a fluoroquinolone was prescribed. Inappropriate use was defined as a fluoroquinolone prescription for cystitis, bronchitis, and sinusitis in patients without a history of Pseudomonas aeruginosa or multidrug-resistant organisms and with no drug allergies that might preclude use of other antibiotics.

A review of 1,033 outpatient fluoroquinolone prescriptions found that, after all four interventions were implemented, total fluoroquinolone prescribing per 1,000 patient visits fell by 39%, with the greatest decline seen in primary care clinics (51%), followed by the emergency department (33%). Inappropriate fluoroquinolone use fell from 53% to 34%. More than 90% of inappropriate fluoroquinolone prescriptions were given for cystitis, while bronchitis and sinusitis accounted for only 4.4% and 1.6% of inappropriate indications, respectively.

"Continued efforts to support the positive effects of these interventions are likely necessary to sustain or improve the rates of appropriate fluoroquinolone use in the outpatient setting," the authors conclude.
May 21 Open Forum Infect Dis study

 

Study finds high antibiotic use in US hospitals

Originally published by CIDRAP News May 20

A retrospective study of inpatients treated at 576 US hospitals in 2016 and 2017 found that nearly two-thirds received antibiotics, and that broad-spectrum antibiotic use was common, US researchers reported in Clinical Infectious Diseases.

To measure antibiotic use at the hospitals, researchers from the University of Maryland School of Medicine and other US institutions obtained daily antibiotic charge data for each adult inpatient encounter, along with patient clinical data, facility data, and ICD-10 diagnosis codes. Each antibiotic was mapped to one of 18 mutually exclusive antibiotic classes and to spectrum of activity categories. Antibiotic usage rates were reported as total inpatient days of therapy of therapy (DOT) per 1,000 patient-days, and relationships between DOTs and hospital, case-mix, and geographic variables were evaluated in negative binomial regression models.

The study included 11,701,326 across 576 hospitals during the study period. Overall, patients received antibiotics in 65% of hospitalizations, at a crude rate of 870 DOTs per 1,000 patient-days. By class, use was highest among beta-lactam/beta-lactamase inhibitor combinations (206 DOTs/1,000 patient-days), third- and fourth-generation cephalosporins (128 DOTs/1,000 patient-days), and glycopeptides (113 DOTs/1,000 patient-days). By spectrum of activity, agents with anti-pseudomonal activity had the highest usage (245 DOTs/1,000 patient-days).

Teaching hospitals averaged lower rates of total antibiotic use than non-teaching hospitals (834 versus 957 DOTs/1,000 patient-days; P < 0.001). In adjusted models, teaching hospitals remained associated with lower use of third- and fourth-generation cephalosporins and anti-pseudomonal agents (adjusted incident rate ratios, 0.92 [0.86 to 0.97] and 0.91 [0.85 to 0.98], respectively). Significant regional differences in total and class-specific antibiotic use also persisted in adjusted models. Compared to the South Atlantic, rates of total antibiotic use were 6%, 15%, and 18% lower on average in the Pacific, New England, and the Middle Atlantic, respectively.

The authors of the study say that, given the recent focus on antibiotic stewardship, they're surprised by the antibiotic usage rate, which is similar and in some cases higher than estimates from 5 to 8 years prior. They say that could be because reductions in some antibiotics are being offset by increases in other agents. They also say it's possible that while antibiotic stewardship programs are reducing antibiotic use in hospitals, their uptake remains too limited to drive national reductions.
May 18 Clin Infect Dis abstract

 

Communication training tied to reduced prescribing in German physicians

Originally published by CIDRAP News May 20

A short communication trainings session for primary care physicians was associated with an 11% drop in antibiotic prescribing, German and Austrian researchers reported yesterday in PLOS One.

The study included a total of 1,554 German primary care physicians who received two 2-hour communication training sessions in February and March of 2016. The training was based on MAAS-Global, an instrument used in the Netherlands to measure physicians' communication skills (the German version is called MAAS-Global-D). The researchers compared antibiotic prescribing among these physicians (the intervention group) with a control group formed from observational data.

To estimate intervention effects, the researchers applied a combination of difference-in-difference (DiD) and statistical matching based on entropy balancing. They estimated a corresponding multi-level logistic regression model for the antibiotic prescribing decisions of German primary care physicians for upper respiratory tract infections (URTIs).

The reduction in the overall prescribing rate of the intervention group between the pre-intervention and post-intervention period was 11.2%. The difference between both groups in the difference between the periods was -6.5% and statistically significant. The estimated effects were nearly identical to the effects estimated for the multi-level logistic regression model with applied matching. Furthermore, for the treatment of young women, the impact of the training on the reduction of antibiotic prescription was significantly stronger.

The authors conclude, "Our results suggest that communication skills implemented via MAAS-Global-D training lead to more prudent prescribing of antibiotics for URTIs. Therefore, the MAAS-Global-D training could not only avoid unnecessary side effects but could also help to reduce the emergence of drug resistant bacteria."
May 19 PLOS One study

 

Study finds higher antibiotic appropriateness with ID consults

Originally published by CIDRAP News May 19

Even in a hospital with a high level of antibiotic appropriateness, patients who received infectious disease consultation (IDC) were more likely to receive appropriate antibiotics than those who didn't receive it, researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

In a cross-sectional study conducted at a large academic medical center with an established antibiotic stewardship program, researchers with the University of Maryland compared the appropriateness of antibiotic orders in patients with and without IDC, using propensity score matching and multivariable logistics regression. The analyses were stratified by primary care services caring for the patients.

The researchers reviewed 10,508 antimicrobial orders from 6,165 unique patient encounters at the hospital from October 2017 through March 2019. The overall appropriateness was 92%, with higher appropriateness among patients with IDC vs. without IDC (94% vs 84%, P < 0.0001).

After propensity-score matching and adjustment for certain antibiotics, organisms, syndromes, and locations, IDC was associated with a greater antimicrobial appropriateness odds ratio (OR) of 2.4 (95% CI, 1.9 to 3.0). The increased appropriateness was seen across most services, with stratification by primary service showing an OR of 2.9 (95% CI, 2.1 to 3.8) for surgical specialties and an OR of 1.6 (95% CI, 1.1 to 2.2) for medical specialties.

"Our results suggest that Infectious Diseases expertise is needed at the bedside and can be synergistic with AS [antibiotic stewardship] efforts," the authors wrote.
May 18 Antimicrob Agents Chemother abstract

 

CARB-X to fund development of anti-toxin for recurrent C difficile

Originally published by CIDRAP News May 18

CARB-X today announced an award of up to $1.26 million to Facile Therapeutics of Belmont, California, to develop a new oral drug for recurrent C difficile infections.

The money will help fund preclinical development of Ebselen, a small-molecule anti-toxin that inhibits a key biochemical function of C difficile toxins A and B, which attack the lining of the intestine. Previous studies showed Ebselen provided protection against severe intestinal damage in mice after they were exposed to virulent C difficile infections. The drug has also been tested in humans in clinical trials for stroke, and although it was not approved for that indication, it was shown to be safe.

"This is a terrific example of an attempt to repurpose a compound for use in the infectious-disease arena," CARB-X chief of research and development Erin Duffy, PhD, said in a press release. "If successful and ultimately approved for use in patients, Facile's project could represent tremendous progress in the prevention of recurrent C. difficile infections, and save many lives."

C difficile infections are traditionally treated with antibiotics, which can cure the infection but also further disrupt the microbiome and clear a path for C difficile bacteria to spread, leading to recurrent infections. At least 20% of patients who get an initial C difficile infection have a recurrent infection.

Facile could receive an additional $17 million if the project achieves certain milestones.

Since its launch in 2016, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) has awarded more than $222 million to companies developing new treatments and diagnostics for drug-resistant pathogens. 
May 18 CARB-X press release

 

Antimicrobial therapy guide linked to reduced antibiotic use in Spain

Originally published by CIDRAP News May 18

Implementation of a rigorous antimicrobial use guide and subsequent interventions were associated with substantial reductions in antibiotic prescribing in Spanish primary care settings, researchers reported in PLOS One.

In a quasi-experimental study, researchers with the Andalusian Public Health Care Service assessed the impact of the Aljarafe Antimicrobial Therapeutic Guide, which was published in 2011 and initially implemented in the Aljarafe Primary Health Care Area before being adopted by the Andalusian Public Health Care System. Andalusia sits at the southernmost tip of Spain.

Interventions carried out following adoption of the guide included the development of electronic decision support tools, local training meetings, regional workshops, creation of targets for rates of antibiotic prescribing, and the establishment of a structured educational antimicrobial stewardship program. Using an interrupted time-series analysis, the researchers measured rates of antibiotic use from 2004 through 2018, calculated in defined daily doses per 1,000 inhabitants per day (DID).

The analysis found that overall antibiotic prescribing rates were trending upward prior to the interventions. But prescribing rates dropped by 28% in the Aljarafe Area and 22% in Andalusia from 2011 through 2018 following the interventions, at rates of -0.90 DID per year (95% CI, -1.05 to -0.75) in Aljarafe, and -0.78 DID (95% CI, -0.95 to -0.60) in Andalusia.

Total penicillin use declined by 33% in Aljarafe and 25% in Andalusia, with amoxicillin clavulanate plummeting by 58% in Aljarafe and 49% in Andalusia. The prescribing of quinolones, which was decreasing before the interventions, continued to decline following interventions, with more pronounced downward trends. Use of cephalosporins also continued to decline, at a lesser extent, following interventions in Andalusia. The rate of macrolide prescribing went from a downward trend to an upward trend from 2011 to 2018.

"Reductions in antibiotic prescriptions were more pronounced in the Aljarafe Area where the guide was developed, and where additional interventions included in the local implementation plan were carried out," the authors of the study wrote. "The impact of interventions in the whole region, although with less intensity than in the Aljarafe Area, was similar in terms of the decrease of prescribing rates and decreasing tendencies."
May 15 PLOS One study

News Scan for May 22, 2020

News brief

Clinicians detail coinfections with C difficile, COVID-19 virus

A study by researchers from Detroit Medical Center and Wayne State University highlights the risk of Clostridiodes difficile infection (CDI) among COVID-19 patients linked to antibiotic use. The findings appeared in Emerging Infectious Diseases.

The researchers identified nine cases of co-infection with SARS-CoV-2 (the virus that causes COVID-19) and CDI during screening surveillance conducted from Mar 11 through Apr 22 at Detroit Medical Center. The patients were mainly elderly, predominantly female, and severely ill. Two of the patients were found to be positive for C difficile on admission, and the remaining seven had onset of diarrhea and were diagnosed with CDI after COVID-19 diagnosis. Three patients received antibiotics in the month before admission and eight received them on admission. The most commonly administered antibiotics were cefepime, ceftriaxone, meropenem, and azithromycin. Four of the patients died in the hospital.

The authors of the study said that symptoms of CDI can complicate diagnosis of COVID-19 because both conditions can have similar manifestations, and that the cases highlight the importance of judicious use of antibiotics for potential secondary infections in certain COVID-19 patients.

"All patients in our cohort were elderly, an age group at higher risk for complications from overuse of antibiotics, such as adverse events, antibiotic resistance, and concomitant infections like CDI," the authors wrote. "To prevent CDI co-infections during the COVID-19 pandemic, integrated use of antimicrobial stewardship is needed to monitor appropriate antibiotic use."
May 20 Emerg Infect Dis study

 

Antibiotic stewardship pharmacist review tied to better care for Staph bacteremia

Adding real-time antimicrobial stewardship (AMS) pharmacist review to infectious diseases consultation (IDC) for management of patients who have Staphylococcus aureus bacteremia (SAB) was associated with more optimal antibiotic use and better care at hospitals in Illinois, researchers reported yesterday in Open Forum Infectious Diseases.

The retrospective study included all patients with SAB treated at seven Aurora Advocate Health hospitals in Chicago from January 2016 through December 2018. The researchers compared outcomes between three time periods: pre-mandatory IDC and AMS review (period 1), post-mandatory IDC and pre-AMS review (period 2), and post-mandatory IDC and AMS review (period 3). The primary outcome was adherence to a quality care bundle, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary endpoints included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related admission, and in-hospital all-cause mortality.

A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n=241/371), 54% in period 2 (n=47/87), and 76% in period 3 (n=92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% CI, 0.37 to 0.93; P = 0.02), and period 2 (OR, 0.37; 95% CI, 0.20 to 0.67; P = 0.0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P < 0.001), source control (34% vs 45% vs 45%; P = 0.04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P = 0.01). No differences were noted for readmission or mortality.

"This study describes an effective real-time, pharmacist-driven AMS review that was associated with improved management of SAB in the setting of pre-existing mandatory IDC," the authors of the study wrote. "Our study is unique in that it demonstrates the benefit of AMS review in addition to IDC for optimizing SAB care."
May 21 Open Forum Infect Dis study

 

FDA: Nearby cattle farms possible source of E coli in romaine outbreaks

The US Food and Drug Administration (FDA) yesterday released its investigation findings into three Escherichia coli O157:H7 outbreaks in 2019 that were linked to romaine lettuce, which revealed that cattle proximity may be a contributing factor and a persistent source of E coli O157:H7 and other Shiga toxin-producing E coli (STEC).

According to the full report, the outbreaks were reported in November and December and sickened 188 people. Illnesses were reported in Canada, as well. Each of the three outbreaks was caused by a different strain, but trace-back investigation of illness clusters and supply chain information identified a common grower in the Salinas, California, area that had multiple ranches and fields that supplied romaine during the outbreak timeframe to busineses associated with all three events.

The same E coli strain tied to one of the outbreak was linked to two different fresh-cut salad brands that contained romaine, and the strain in that outbreak matched a fecal-soil composite sample taken from a cattle grate on public land 2 miles upslope from a produce farm with multiple fields tied to the outbreak. Other STEC strains, though not linked to the outbreaks, were found closer to where the lettuce crops were grown, including two samples from a border area where cattle were grazing and two samples from on-farm water drainage basins.

Taken together, the findings, along with those from investigations as far back as 2013, suggest cattle proximity as a possible contributing factor. Based on recurring problems, the FDA said it recently released a 2020 Leafy Greens STEC Action Plan that included a three-part approach for addressing the contamination and lays out how the FDA will work with industry and other groups to address leafy greens safety.
May 21 FDA outbreak investigation notice
FDA investigation report

 

Afghanistan, Pakistan report vaccine-related polio cases

Afghanistan and Pakistan this week both reported circulating vaccine-derived poliovirus type 2 (cVDPV2) cases, according to the latest update from the Global Polio Eradication Initiative (GPEI).

Afghanistan confirmed 5 new cVDPV2 cases, 1 in Kunar and 4 in Nangarhar province. The country has had 7 cVDPV2 cases so far this year, compared with none in all of 2019.

Pakistani officials reported 1 new cVDPV2 case, in Khyber Pakhtoon province, pushing its 2020 total to 67. Last year the country reported 22 cVDPV2 cases.

Neither country reported a case of wild poliovirus type 1 (WPV1) infection, the first time without one in many weeks. Afghanistan so far this year has confirmed 12 WPV1 cases—keeping it even with last year's pace—while Pakistan has recorded 47, compared with 25 at this point last year.
May 21 GPEI update

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