Pharmacist-led stewardship linked to improved antibiotic prescribing

An antibiotic stewardship program (ASP) intervention led by ambulatory care pharmacists was associated with improvements in guideline-concordant antibiotic prescribing in a family medicine residency clinic, researchers reported today in Infection Control and Hospital Epidemiology.

The study, conducted at a single primary-care office in Grand Rapids, Michigan, compared antibiotic prescribing for three conditions—upper respiratory tract infections (URIs), urinary tract infections (UTIs), and skin and other soft-tissue infections (SSTIs)—before and after the implementation of the ASP intervention, which included education, guideline dissemination, and weekly audit and feedback of medical residents led by ambulatory care pharmacists. Guideline concordance was determined based on the institution's outpatient ASP guidelines.

Overall, 1,397 antibiotic prescriptions were issued over the 12-month study period, and 525 antibiotic prescriptions were audited (90 pre-intervention and 435 post-intervention). Total guideline-concordant antibiotic prescribing at baseline was 38.9% (URI, 53.3%; SSTI, 16.7%; UTI, 46.7%) and improved across all three infection types post-intervention to 57.9% (URI, 61.2%; SSTI, 57.6%; UTI, 53.5%; P = .001).

Significant improvements were seen in guideline-concordant antibiotic selection (68.9% pre-intervention vs 80.2% post-intervention; P = .018), dose (76.7% vs 86.2%; P = .023), and duration of therapy (73.3% vs 86.2%; P = .02).

The authors of the study say the findings add to the growing body of evidence showing the importance of establishing good antibiotic prescribing habits early in medical practice, and demonstrate the impact that ambulatory care pharmacists can have as antibiotic stewardship leaders.
Nov 13 Infect Control Hosp Epidemiol abstract

Few bacterial co-infections found in London COVID-19 hospital patients

A study conducted at two acute care hospitals in North West London found bacterial co-infections were infrequent in COVID-19 patients and did not have an impact on clinical outcomes, but practitioners almost universally prescribed empiric antibiotics, researchers reported today in the Journal of Antimicrobial Chemotherapy.

The retrospective observational cohort study included all adult non-pregnant patients admitted to the two hospitals from Mar 1 through Apr 30 and confirmed to have COVID-19 within 48 hours of admission. The researchers reviewed microbiologic specimens taken within 48 hours to assess their clinical significance, along with empiric antibiotic treatment, and compared demographic and clinical characteristics of patients who had and didn't have bacterial co-infections.

Of the 1,396 patients included in the study, 37 (2.7%) had clinically important bacterial co-infections within 48 hours of admission, 11 of which were respiratory tract infections. Thirty-six of the 37 patients with bacterial co-infections received empiric antibiotics at the time of admission, as did 98 of 100 randomly selected patients without co-infection.

There was no significant difference in age, gender, pre-existing illnesses, intensive care unit admission, or 30-day all-cause mortality between those with and without bacterial co-infection, but patients with bacterial co-infection had significantly higher white cell count, neutrophil count, and C-reactive protein levels.

"These results suggest that empirical antimicrobial treatment may not be necessary in patients presenting with high suspicion of COVID-19 infection, though the decision could be guided by high inflammatory markers," the authors wrote. "Furthermore, our findings suggest that presence of bacterial co-infection at the time of presentation does not affect the clinical outcome adversely."
Nov 13 J Antimicrob Chemother study

Three countries report more vaccine-derived polio cases

Three countries—Afghanistan, Chad, and Somalia—reported more polio cases this week, all of which involved circulating vaccine-derived poliovirus type 2 (cVDPV2), the Global Polio Eradication Initiative (GPEI) said in its latest weekly update.

Afghanistan reported 15 new cVDPV2 cases from seven provinces, and 8 of them were from Kandahar. The country has now reported 136 such cases for 2020.

In Africa, Chad reported 1 more case, which is from Logone Oriental province, lifting the country's total for the year to 80 from two different outbreaks. And Somalia reported 3 cases, 1 from Galbeed and 2 from Banadir, putting its total at 20 cVDPV2 cases, plus a coinfection that also involved type 3.
Nov 12 GPEI weekly update

In other polio developments, the World Health Organization (WHO) today announced the launch of a campaign to immunize 1.5 million young children in South Sudan against polio. So far this year, 15 vaccine-derived polio cases have been diagnosed in seven of the country's counties across five of its states.

The first round of the campaign will target children in seven states. The WHO added that less than 50% of the country's children are vaccinated against polio and other life-threatening diseases.
Nov 13 WHO African regional office statement

Five countries report more H5N8 avian flu poultry outbreaks

Five countries have reported more highly pathogenic H5N8 avian flu outbreaks in poultry, according to the latest notifications from the World Organization for Animal Health (OIE).

Russia, where the outbreaks began in late summer, reported five more outbreaks, all in backyard poultry in the country's southwest. Locations include Yugra region, Tartarstan, and Samara Oblast. The events began between Oct 25 and Nov 1, killing 299 of 175,634 susceptible birds. The survivors were slated for culling.

Elsewhere in Europe, the Netherlands reported one more H5N8 outbreak, which began Nov 9 at a poultry farm in Groningen province, killing 113 of 47,102 birds. All other poultry on the premises were destroyed. Meanwhile, German officials reported an outbreak involving H5N8 at a farm in Mecklenburg-Vorpommern state that housed layers, broilers, ducks, and geese. The event began on Nov 11 and killed 55 of 257 birds.

Outside of Europe, Israel reported the virus at a turkey farm in Hazafon. The outbreak started on Nov 3 and killed 500 of 28,000 birds, and authorities slaughtered the rest to curb the spread. And finally, Japan reported another H5N8 outbreak in Kagawa prefecture, which occurred at a broiler farm. It began on Nov 10 and killed 16 of 11,000 chickens, and stamping out was ordered for the rest of the flock.
Nov 13 OIE report on H5N8 in Russia
Nov 13 OIE report on H5N8 in the Netherlands
Nov 13 OIE report on H5N8 in Germany
Nov 12 OIE report on H5N8 in Israel
Nov 12 OIE report on H5N8 in Japan

In 2016, CDC investigated 174 food- and animal-derived outbreaks

In today's Mortality and Morbidity Weekly Report (MMWR), the Centers for Disease Control and Prevention (CDC) report that, in 2016, health officials investigated 174 outbreaks related to Salmonella (69.0%), Escherichia coli (E coli, 21.8%), and Listeria monocytogenes (Listeria, 9.2%), with sprouts and chicken being the leading culprits.

After investigation, only 50 events had sufficient evidence to be classified as multistate outbreaks. Thirty-nine (78% of those) were solved with at least a suspected food or animal source.

Across 118 total outbreaks that had the potential to be multistate outbreaks, there were 3,480 illnesses, 752 hospitalizations, 16 cases of hemolytic uremic syndrome, and 26 deaths.

Out of the 18 multistate foodborne disease outbreaks that had a confirmed source, the CDC issued 10 recalls, 2 market withdrawals and 1 Food Safety and Inspection Service (FSIS) health alert. Sprouts and chicken were the most commonly linked food and animal sources of outbreak-related illness, with 131 and 134 cases, respectively. Events tied to backyard chickens reached a new high, with 10 multistate outbreaks and 930 illnesses. Three outbreaks had novel food-pathogen pairs: flour and E coli, frozen vegetables and Listeria, and bagged salad and Listeria.

Of the total 230 possible multistate outbreaks that occurred in 2016, 87.0% were detected by PulseNet, 10.9% by state and local health departments, and 2.2% by the Food and Drug Administration and FSIS, which is part of the Department of Agriculture. The median duration of each investigation was 37 days.
Nov 13 MMWR report

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

Pharmacist-led stewardship linked to improved antibiotic prescribing

An antibiotic stewardship program (ASP) intervention led by ambulatory care pharmacists was associated with improvements in guideline-concordant antibiotic prescribing in a family medicine residency clinic, researchers reported today in Infection Control and Hospital Epidemiology.

The study, conducted at a single primary-care office in Grand Rapids, Michigan, compared antibiotic prescribing for three conditions—upper respiratory tract infections (URIs), urinary tract infections (UTIs), and skin and other soft-tissue infections (SSTIs)—before and after the implementation of the ASP intervention, which included education, guideline dissemination, and weekly audit and feedback of medical residents led by ambulatory care pharmacists. Guideline concordance was determined based on the institution's outpatient ASP guidelines.

Overall, 1,397 antibiotic prescriptions were issued over the 12-month study period, and 525 antibiotic prescriptions were audited (90 pre-intervention and 435 post-intervention). Total guideline-concordant antibiotic prescribing at baseline was 38.9% (URI, 53.3%; SSTI, 16.7%; UTI, 46.7%) and improved across all three infection types post-intervention to 57.9% (URI, 61.2%; SSTI, 57.6%; UTI, 53.5%; P = .001).

Significant improvements were seen in guideline-concordant antibiotic selection (68.9% pre-intervention vs 80.2% post-intervention; P = .018), dose (76.7% vs 86.2%; P = .023), and duration of therapy (73.3% vs 86.2%; P = .02).

The authors of the study say the findings add to the growing body of evidence showing the importance of establishing good antibiotic prescribing habits early in medical practice, and demonstrate the impact that ambulatory care pharmacists can have as antibiotic stewardship leaders. 
Nov 13 Infect Control Hosp Epidemiol abstract

Few bacterial co-infections found in London COVID-19 hospital patients

A study conducted at two acute care hospitals in North West London found bacterial co-infections were infrequent in COVID-19 patients and did not have an impact on clinical outcomes, but practitioners almost universally prescribed empiric antibiotics, researchers reported today in the Journal of Antimicrobial Chemotherapy.

The retrospective observational cohort study included all adult non-pregnant patients admitted to the two hospitals from Mar 1 through Apr 30 and confirmed to have COVID-19 within 48 hours of admission. The researchers reviewed microbiologic specimens taken within 48 hours to assess their clinical significance, along with empiric antibiotic treatment, and compared demographic and clinical characteristics of patients who had and didn't have bacterial co-infections.

Of the 1,396 patients included in the study, 37 (2.7%) had clinically important bacterial co-infections within 48 hours of admission, 11 of which were respiratory tract infections. Thirty-six of the 37 patients with bacterial co-infections received empiric antibiotics at the time of admission, as did 98 of 100 randomly selected patients without co-infection.

There was no significant difference in age, gender, pre-existing illnesses, intensive care unit admission, or 30-day all-cause mortality between those with and without bacterial co-infection, but patients with bacterial co-infection had significantly higher white cell count, neutrophil count, and C-reactive protein levels.

"These results suggest that empirical antimicrobial treatment may not be necessary in patients presenting with high suspicion of COVID-19 infection, though the decision could be guided by high inflammatory markers," the authors wrote. "Furthermore, our findings suggest that presence of bacterial co-infection at the time of presentation does not affect the clinical outcome adversely."
Nov 13 J Antimicrob Chemother study

Study finds frequent use of key antibiotics in 4 low-resource nations

Originally published by CIDRAP News Nov 11

A study of community-level antibiotic use in patients in four low- and middle-income countries (LMICs) found frequent use of broad-spectrum antibiotics considered at risk of becoming ineffective owing to rising antibiotic resistance, an international team of researchers reported today in Clinical Microbiology and Infection.

As part of an effort to optimize antibiotic use in LMICs, the Neglected Infectious Diseases DIAGnosis (NIDIAG)-Fever study investigated the causes of infections in patients with persistent fever who were admitted to hospitals in Cambodia, the Democratic Republic of the Congo (DRC), Sudan, and Nepal.

The researchers described the prevalence and choice of antibiotics before and at study inclusion, applying the World Health Organization's (WHO's) Access/Watch/Reserve (AWaRe) classification, which was introduced in 2017 to provide an indirect indication of the appropriateness of antibiotic use at national and global levels. They also looked at the route of administration and analyzed factors associated with prior antibiotic use.

Of 1,939 people included in the study, 428 (22.1%) reported prior use of one or more antibiotics, ranging from 6.3% in Cambodia (24 of 382) to 35.5% in Nepal (207/583). Of 545 antibiotics, the most frequently used were Watch antibiotics, which accounted for 64.4% (351/545) of antibiotics used, ranging from 23.6% in the DRC to 82.1% in Nepal. Parenteral administration ranged from 5.9% to 69.6% between study sites. Antibiotic use was most frequent among patients aged 5 to 17 years (risk ratio [RR], 1.42; 95% confidence interval [CI], 1.19 to 1.71) and men (RR, 1.29; 95% CI, 1.09 to 1.53).

No association was found between antibiotic use and specific symptoms. Of 555 antibiotics started before study inclusion, 49.5% (275) were discontinued at study inclusion.

"These findings emphasize the need to monitor and optimize community- or primary healthcare-level antibiotic use in LMICs," the authors wrote.
Nov 11 Clin Microbiol Infect abstract

CARB-X supports bacteriophage therapy for recurrent urinary infections

Originally published by CIDRAP News Nov 10

CARB-X announced today that it is awarding up to $2.05 million to Locus Biosciences of Morrisville, North Carolina, to develop a CRISPR-Cas3-enhaced bacteriophage for treating recurring urinary tract infections caused by Klebsiella pneumoniae.

The money from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) will help fund the development of LBP-KP01, a cocktail of bacteriophages that specifically target K pneumoniae bacteria and are engineered with a CRISPR-Cas3 construct that targets the K pneumoniae genome. The company says the dual phage-CRISPR mechanism makes LBP-KP01 more effective at killing K pneumoniae cells, even in strains that are antibiotic resistant, than corresponding bacteriophages.

"This approach has the potential to kill with laser-sharp precision the bacteria causing an infection without causing damage to other cells," CARB-X research and development director Erin Duffy, PhD, said in a press release. "If successful, this could transform the treatment of these serious life-threatening infections and save lives."

Locus will be eligible for an additional $10.5 million from CARB-X if certain project milestones are met.

Since its launch in 2016, CARB-X has awarded $257 million to fund early development of 72 new treatments or diagnostics for drug-resistant infections.  
Nov 10 CARB-X press release

NICU study finds high rate of nonsusceptibility in E coli infections

Originally published by CIDRAP News Nov 10

A study of infants in neonatal intensive care units (NICUs) with Escherichia coli infections found a substantial rate of nonsusceptibility to commonly administered antibiotics, researchers reported yesterday in JAMA Pediatrics.

In the study, a team led by researchers at Children's Hospital of Philadelphia assessed patterns of antibiotic susceptibility in E coli among infants admitted to NICUs at 69 hospitals. E coli is a leading cause of serious infections among infants in NICUs, including early- and late-onset sepsis, and reports of resistance to commonly used antibiotics have been emerging in recent years. But there neonatal-specific antibiotic susceptibility data for E coli in the United States are scarce.

Using data from the Premier Health Database, the researchers identified infants admitted to US NICUs from 2009 through 2017, then assessed microbiologic data on E coli isolated from infant blood, urine, and cerebrospinal fluid. The primary outcome was changes in annual antibiotic susceptibility over the study period. A total of 721 infants with at least one episode of E coli infection and available antibiotic susceptibility results were analyzed.

Nearly all isolates were tested against ampicillin (720) and gentamicin (718), the two antibiotics most commonly administered to newborns as empiric therapy. No significant changes were observed over time in the overall annual proportions of antibiotic nonsusceptibility to ampicillin, with a mean of 66.8% of isolates showing nonsusceptibility and an estimated yearly change of −0.28% (95% CI, −1.75% to 1.18%).

The proportion of isolates nonsusceptible to aminoglycosides (gentamicin) was 16.8%, with an estimated yearly change of −0.85% (95% CI, −1.93% to 0.23%), and 5% of isolates were nonsusceptible to the extended-spectrum beta-lactamase phenotype, with an estimated yearly change of 0.46% (95% CI, −0.18% to 1.11%). No isolates with nonsusceptibility to carbapenems were identified.

Among 218 infants with early-onset infection, 22 (10.1%) had isolates with nonsusceptibility to both ampicillin and gentamicin.

"Our findings emphasize the importance of ongoing surveillance of neonatal antibiotic susceptibility patterns to inform empirical antibiotic therapies for newborn infants," the authors of the study wrote.
Nov 9 JAMA Pediatr abstract

Focus groups identify major themes shaping antibiotic perceptions

Originally published by CIDRAP News Nov 10

A series of focus groups held with adult patients and parents across the United States identified four major themes in attitudes toward antibiotic use and risks, researchers reported yesterday in Open Forum Infectious Diseases.

To better understand how adult patients and parents view antibiotic risks, and how they incorporate those risks into their antibiotic use decision-making, researchers from the Centers for Disease Control and Prevention (CDC) and Emory University School of Medicine conducted 12 focus groups in states with the highest antibiotic prescribing rates in March 2017. Topics included perceptions of antibiotics, expectations for antibiotics, reaction to not receiving antibiotics when desired, knowledge and perception of antibiotic risks, and response to antibiotic message testing. Fifteen parents and 16 adult patients participated.

The first major theme identified was that participants understood that antibiotics weren't necessary for all infections, such as those caused by viruses, but were confused about when they were needed, and that emotion often influenced their desire for antibiotics. In addition, they believed that antibiotics were needed if symptoms were severe or prolonged, regardless of their clinical syndrome. Second, participants had a limited understanding of antibiotic risks. Antibiotic resistance was seen as the primary risk, but understanding of resistance varied, and it was viewed as a distant harm, while immediate adverse events, like side effects, were seen as uncommon.

The third theme identified was that participants, when weighing the risks and benefits of antibiotics, prioritized the potential benefits and instant gratification, often overestimating the benefits. The fourth theme was a willingness to defer to clinicians' decisions about antibiotics, especially if the clinician is a good communicator who provides guidance and suggestions for alternative treatments.

The authors say the information gleaned from the focus groups has been used to inform the CDC's Be Antibiotics Aware educational campaign.

"Previous public health messaging has emphasized antibiotic resistance as the main risk of antibiotic overuse; however, our findings show that this message is unlikely to reduce patient demand for antibiotics," the authors wrote. "Instead, health messaging should focus on educating patients about both the frequency and potential severity of antibiotic adverse events."
Nov 9 Open Forum Infect Dis abstract

Italian study finds daily ID consults linked to reduced hospital antibiotics

Originally published by CIDRAP News Nov 9

Daily infectious disease (ID) consultation in an Italian hospital was associated with reduced antibiotic consumption compared with weekly ID consultation, Italian researchers reported late last week in BMC Infectious Diseases.

The 2-year retrospective observational analysis of all ID consults at a large tertiary hospital in Milan, conducted by researchers at the University of Milan, compared a year of weekly ID consults (September 2016 through August 2017) with a year of ID consults provided on a daily basis (September 2017 through September 2018). The process outcomes included the number of ID consults per 100 bed-days, the time from admission to first ID consults, and the type of antibiotic intervention. The primary outcomes were the reduction of overall antibiotic consumption and the reduction of antibiotic consumption by department and antibiotic class, as expressed by defined daily dose (DDD) per 100 bed-days.

Overall, 2,552 ID consults were performed in 1,111 patients (18.6% weekly vs 81.4% daily). In the daily service, compared with the weekly service, patients were seen by the ID consultant earlier (6 days vs 10 days), and the number of ID consults increased from 0.4 per 100 bed-days to 1.5 per 100 bed-days, with the greatest increase seen in the emergency department. Total antibiotic consumption decreased from 64 to 60 DDD/100 bed-days, with the greatest reduction observed in the emergency department (132 DDD/100 bed-days with weekly consults vs 107 DDD/100 bed-days with daily consults).

According to antibiotic classes, glycopeptides consumption declined from 3.1 to 2.1 DDD/100 bed-days, while carbapenem use decreased from 3.7 to 3.1 DDD/100 bed-days. No changes in overall mortality (5.2% in 2017 vs 5.2% in 2018) and sepsis-related mortality (19.3% in 2017 vs 20.9% in 2018) were observed among the two periods.

"In our study, the availability of daily ID-consultations was associated with a global reduction in antibiotic consumption in the whole hospital in spite of a similar distribution of infections among the two time periods," the authors wrote. "This reduction was not accompanied by a worsening of clinical outcomes."
Nov 7 BMC Infect Dis study