ASP Scan (Weekly) for Nov 30, 2018

Superbugs in Canadian ICUs
Probiotics and ESBL colonization
Antibiotics after rhinoplasty
Rapid flu diagnostic tests
CDC funding for AMR initiatives
VRE, MRSA co-colonization in nursing homes
UV disinfection for C diff
Fluoroquinolones and aortic rupture risk
Resistance action plan
Deaths from MDROs
Stewardship in a Japanese hospital
Stewardship study quality

Canadian study finds increase in ICU superbugs

An analysis of more than 8,000 isolates from Canadian intensive care units (ICUs) over 10 years shows a significant increase in the prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, researchers from the University of Manitoba reported yesterday in the Journal of Antibacterial Chemotherapy.

From 2007 through 2016, 42,938 clinically significant bacterial and fungal isolates were collected from Canadian tertiary care centers as part of the CANWARD national surveillance study; 8,130 of the isolates came from ICUs. Of the 8,130 pathogens collected, 58.2%, 36.3%, 3.1% and 2.4% were from respiratory, blood, wound and urine specimens, respectively.

The top five organisms collected accounted for 55.4% of all isolates and included S aureus (21.5%), Pseudomonas aeruginosa (10.6%), E coli (10.4%), Streptococcus pneumoniae (6.5%) and Klebsiella pneumoniae (6.4%). The most active agents against gram-negative organisms were carbapenems, tigecycline, and piperacillin-tazobactam; against gram-positive organisms, the most active agents were vancomycin, daptomycin, and linezolid.

MRSA accounted for 20.7% of S aureus collected, with the proportion of CA-MRSA genotypes compared with healthcare-associated MRSA increasing in prevalence across the study (P < 0.001), from 15.3% in 2007 to 76.2% in 2016. Multidrug resistance (MDR) and extensive drug resistance (XDR) was identified in 26.3% and 14.9% of E coli isolates, with both phenotypes demonstrating a significant increasing trend (P < 0.0001). In addition, 10.1% of E coli were identified as ESBL producers, with the proportion of ESBL-producing E coli rising from 2.5% in 2007 to 11.6% in 2016. MDR and XDR Enterobacter cloacae and K pneumoniae also increased significantly over time.

The authors of the study say the increase in ESBL-producing E coli, which could lead to increased use of carbapenems and increase selection pressure for the expansion of carbapenem-resistant Enterobacteriaceae, is a worrisome trend that must continue to be monitored.
Nov 29 J Antimicrob Chemother study


Study: Probiotics don't lower ESBL colonization risk in travelers to India

A small study by Danish researchers has found that the use of probiotics in people traveling to India did not lower the risk of colonization with ESBL-producing Enterobacteriaceae (ESBL-E). The findings appear today in Travel Medicine and Infectious Disease.

In the study, Danish travelers visiting India for 10 to 28 days were randomized to receive the probiotic species Lactobacillus Rhamnosus GG (LGG) or no probiotic at all. Because travelers to India are often colonized with ESBL-E or carbapenemase-producing Enterobacteriaceae (CPE) upon return, the researchers wanted to see if LGG could have a preventive effect on colonization.

Thirty-one travelers were randomized to the LGG group and 30 to the control group. Rectal swabs and questionnaires were collected from participants before travel, immediately after, and 6 months after return, and the swabs were tested for the presence of ESBL-E and CPE. Before traveling, 6 of 50 (12%) participants were colonized with ESBL-E. Immediately after return, 41 of the 44 (93.2%) who were not colonized before travel were colonized, and 6 months after return 11 of 36 (30.6%) were still colonized.

While the study found no statistically significant difference in the colonization rate between the LGG group and the controls, the researchers say the study confirms the high incidence of colonization with ESBL-E associated with travel to India. The investigators detected no CPE.
Nov 30 Travel Med Infect Dis abstract


Review: No support for use of postoperative antibiotics after rhinoplasty

Originally published by CIDRAP News Nov 29

A systematic review and meta-analysis published today in JAMA Facial Plastic Surgery suggests there's no evidence to support routine use of postoperative antibiotics after rhinoplasty procedures.

The review and meta-analysis of five randomized clinical trials involving a pooled sample of 589 patients found that postoperative antibiotic therapy did not significantly alter the rate of infections after rhinoplasty procedures when compared with preoperative or perioperative antibiotics or with placebo or no treatment. The pooled risk ratio (RR) for infection when comparing postoperative antibiotics with any or all other antibiotic regimens in the trials—including preoperative, perioperative, or placebo or no treatment—was 0.92 (95% confidence interval [CI], 0.35 to 2.43, P = .86). When comparing postoperative antibiotics with placebo or no treatment, the pooled RR was 0.43 (95% CI, 0.18 to 1.04, P = .06).

"The differences in RRs of infection were not statistically significant when comparing postoperative with preoperative and perioperative antibiotics or with placebo," the authors of the review write.

According to the review, the use of antibiotics following rhinoplasty to avoid infection is widespread, occurring in more than 90% of procedures. Yet several studies have found that the rate of infection after rhinoplasty is low, and evidence on the effectiveness of antibiotic prophylaxis is mixed. This is the first meta-analysis on the topic.

The authors conclude that, despite the findings, surgeons should still take into account a variety of factors when evaluating infection risk, including the scope of the surgery, the length, and the use of grafts or foreign materials. "It shall remain important to be vigilant regarding infection risk, and the above recommendations are not a replacement for clinical judgement on a case-by-case basis," they write. 
Nov 29 JAMA Facial Plast Surg study


French study finds rapid flu test in children may cut antibiotic use, costs

Originally published by CIDRAP News Nov 29

A study by French researchers published yesterday in Clinical Microbiology and Infection found that bedside use of a rapid flu diagnostic test in children with flu-like symptoms was tied to significantly reduced invasive tests, antibiotic treatment, and hospitalization.

In the prospective study, conducted in the pediatric emergency department of a French academic medical center, the researchers used a rapid influenza digital immunoassay (DIA) to detect influenza virus A and B antigens in nasopharyngeal aspirates from children with flulike symptoms. To evaluate the sensitivity, specificity, and negative and positive predictive values of the DIA, they tested the same samples with standard immunofluorescence and molecular assays.

Before using the DIA, clinicians filled out questionnaires listing the tests and treatments they would have prescribed for the children in the absence of rapid testing. The researchers then compared those answers with what was done after using the DIA. They also compared the actions taken after using the DIA with data obtained from the three previous winter seasons.

Among the 512 patients included in the study, the DIA results showed that 245 tested negative for flu and 269 tested positive. When compared with the standard tests, the sensitivity, specificity, and negative and positive and predictive values of the DIA were 95.9%, 95.2%, 95.6%, and 95.5%, respectively. When the researchers compared the actions performed during the study period with the three previous winter seasons, they observed that use of the DIA at bedside was associated with a reduction in antibiotic treatments of 70% (from 16.9% to 5.1%), prescription of blood puncture of 77.8% (21.2% to 6.6%), chest x-rays of 69% (33.3% to 10.3%), lumbar puncture of 77.8% (7% to 1.6%), and hospitalization of 25.0% (27.2% to 20.4%). Reduction of medical costs was estimated to be more than €69,000 ($78,476) per season.

"In addition to delivering a rapid aetiological diagnosis, this strategy is able to save the prescription of a considerable number of unnecessary tests, antimicrobial treatments, and hospital stay," the authors of the study write. They suggest further studies are needed to confirm the results.
Nov 28 Clin Microbiol Infect abstract


CDC announces funding for antimicrobial resistance projects

Originally published by CIDRAP News Nov 29

The US Centers for Disease Control and Prevention (CDC) announced this week that it has awarded more than $15 million in 2018 to 41 innovative projects to combat antimicrobial resistance.

Among the recipients of the CDC funds are Rush University, which is studying factors associated with Candida auris colonization in healthcare settings, and the Children's Hospital of Philadelphia, where researchers are working on a novel metric for benchmarking antibiotic use to inform outpatient stewardship efforts. Other projects include a Washington University in St. Louis study on the effects of antibiotics on infant microbiomes and Iowa State University research on multidrug-resistant Campylobacter in dogs.

The projects are being supported through the CDC's Antimicrobial Resistance Solutions Initiative, which fund efforts to improve the national infrastructure for detecting, containing, and preventing resistant infections in healthcare settings, food, and the community.
Nov 26 CDC Broad Agency Announcement


Study finds MRSA, VRE co-colonization is common in nursing homes

Originally published by CIDRAP News Nov 28

A study by researchers from the University of Michigan has found frequent co-colonization of vancomycin-resistant enterococci (VRE) and MRSA among patients in nursing facilities.

In the prospective cohort study, published yesterday in the American Journal of Infection Control, researchers analyzed microbial culture data from newly admitted patients at six nursing facilities in southeast Michigan from November 2013 through November 2015. They wanted to investigate the epidemiology of VRE and MRSA co-colonization because of concerns that MRSA can acquire the vancomycin-resistance gene vanA and develop resistance to vancomycin, which further limits treatment options.

The cultures were obtained from various anatomic sites and from open wounds and indwelling device insertion sites to determine colonization status, and demography, comorbidity, and antimicrobial use data were collected to determine factors predictive of co-colonization.

In total, 508 patients were enrolled in the study, with an average length of stay of 28.5 days. Overall prevalence of MRSA and VRE co-colonization in the patients was 8.7%, 8.9% for MRSA alone, and 23.4% for VRE alone—a number the authors note is significantly higher than previously-reported VRE prevalence estimates in post-acute care facilities (5% to 18%). Multivariate analysis found that indwelling device use (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.2 to 13.7), antibiotic use (OR, 2.5; 95% CI 1.4 to 4.2), diabetes (OR, 1.9; 95% CI, 1.0 to 3.8), and open wounds (OR, 1.9; 95% CI, 1.0 to 3.6) were independent predictors of co-colonization.

"Co-colonization with MRSA and VRE was frequent and perhaps driven by a high prevalence of VRE in our study population," the authors write. They conclude that future studies are needed to investigate the role VRE transmission, the presence of wounds, and targeted screening and prevention measures play in patient co-colonization.
Nov 27 Am J Infect Control study


Study: UV disinfection tied to lower C diff levels in high-burden units

Originally published by CIDRAP News Nov 28

Adding ultraviolet (UV) disinfection to terminal cleaning protocols was tied to reduced Clostridioides difficile infection rates, researchers from the Mayo Clinic reported yesterday in the American Journal of Infection Control.

C diff spores are known to resist standard cleaning, and hospitals are exploring other methods to cut contamination levels. The study took place in hospital wards that have high C diff burden, including hematology and bone marrow transplant units and a medical-surgical unit.  Bleach cleaning was already being used on the wards to reduce C diff levels, but infection rates still remained high.

Researchers used the UV intervention after patient discharge and terminal cleaning in three units and used three similar units as controls. At baseline, C diff infection rates were similar for both groups of units.

Intervention rooms got pulsed xenon UV disinfection for a 6-month period between October 2014 and March 2015. Disinfection was performed in three positions in 5-minute cycles after terminal cleaning and before the bed was made. Drawers and doors inside the room were left open, phone and blood pressure cuffs were hung, television remotes were on the tray table, pillows were on the window ledges, and curtains were positioned to allow the grip to be disinfected. One of the three cycles was completed in the bathroom.

After 6 months, the C diff infection rate in the intervention rooms decreased to 11.2 per 10,000 patient days, compared to 28.7 per 10,000 patient days in the control rooms. Also, researchers found a reduction in vancomycin-resistant enterococci (VRE) acquisition in units that got UV disinfection.

The team noted that the study was the first direct head-to-head comparison in the same hospital using UV disinfection in addition to bleach.

They said based on the results, the hospital continued UV disinfection in more units with high C diffburden and the devices have been well received by staff, patients, and families. However, they noted that the pulsed light was an annoyance to staff and other patients in intensive care units with glass doors. UV disinfection added about 25 minutes to room processing time, they said.

Though UV devices were expensive and incur additional costs for training, high C diff infection rates can also take a high financial toll, the group wrote. UV disinfection could be a cost-saving measure, depending on baseline C diff infection rates and performance on other healthcare-associated infection measures, they added.
Nov 27 Am J Infect Control abstract 


Study: Fluoroquinolone use common in patients at risk of aortic rupture

Originally published by CIDRAP News Nov 27

A study yesterday in Antimicrobial Agents and Chemotherapy found that patients at risk for aortic rupture are frequently exposed to fluoroquinolones during hospitalization, despite concerns that fluoroquinolone use may be associated with increased risk of aortic aneurysm and/or dissection (AAD).

In the study, investigators from Baylor College of Medicine analyzed hospital admissions data for the years 2009 through 2015 to explore how often patients with AAD or Marfan syndrome (a genetic disorder linked to increased risk of AAD) are being treated with fluoroquinolones in the acute care setting, given that these patients are already at increased risk of aortic rupture. Fluoroquinolones are among the most commonly prescribed antibiotics worldwide, but post-marketing and clinical surveillance studies have linked them with several adverse effects, and four recent observational clinical studies have suggested they may be associated with an increased risk of AAD.

Using the Advisory Board billing and administrative database, the investigators identified 136,789 admissions for AAD, which involved 99,818 unique patients, and 2,871 unique admissions for Marfan syndrome, involving 1,872 unique patients. Of the 19,818 patients with AAD, 20% were administered a fluoroquinolone during admission. Of the 7,045 patients with dissection, 18% were exposed to fluoroquinolones, and 19% of the patients who underwent aortic repair received fluoroquinolones before the surgery. In addition, 14% of the Marfan syndrome patients were exposed to fluoroquinolones.

Multi-level regression analysis to determine factors associated with fluoroquinolone use revealed that in patients with AAD, having a diagnosis of pneumonia or urinary tract infection (UTI) increased the likelihood of receiving a fluoroquinolone by 46% and 40%, respectively. Pneumonia and UTIs also increased the risk of fluoroquinolone use in Marfan syndrome patients as well.

"If the suspected deleterious effects of FQs [fluoroquinolones] on aortic integrity is substantiated, reducing FQ use in these patients should be a high priority for antibiotic stewardship and patient safety programs," the authors of the study write. "Our results help identify the patients who are most at risk of FQ exposure during hospitalization and, thus, provide a starting place for stewardship interventions."
Nov 26 Antimicrob Agents Chemother abstract


Advisory group seeks input on priorities for resistance action plan

Originally published by CIDRAP News Nov 27

The US Presidential Advisory Committee on Combating Antibiotic Resistant Bacteria (PACCARB) is seeking the public's input for an update on the US government's efforts to fight antibiotic resistance.

On Nov 23 PACCARB posted a Request for Information (RFI) in the Federal Register that will allow a wide range of stakeholders to suggest new priority areas within each of the five goals that were established in the first National Action Plan (NAP) for Combating Antibiotic-Resistant Bacteria, which covers the years 2015 to 2020.  PACCARB posted the RFI in response to a request from Department of Health and Human Services (HHS) Secretary Alex Azar to identify significant areas that have emerged since the first NAP was published in 2015.

The goals of the initial NAP included slowing the emergence of resistant bacteria and preventing the spread of resistant infections; strengthening national One Health surveillance efforts; advancing development and use of rapid and innovative diagnostic tests; accelerating research and development for new antibiotics and other therapeutics; and improving international collaboration. Azar asked PACCARB to identify three to five areas within each of these goals that should be considered for the second iteration of the NAP, which will guide action against antibiotic resistance for the period 2020-2025.

The deadline for submitting comments in Jan 7, 2019. Priority areas will be explored at the next PACCARB public meeting, scheduled for Jan 30-31, 2019. 
Nov 23 Federal Register notice
HHS online comment form


Researchers re-estimate annual deaths from multidrug-resistant infections

Originally published by CIDRAP News Nov 26

Infectious disease specialists from Washington University School of Medicine estimate that the number of deaths caused by multidrug-resistant organisms (MDROs) is more than six times higher than widely cited figures from the CDC.

In a letter published in Infection Control and Hospital Epidemiology, the researchers looked at data on inpatient and outpatient deaths in 2010 and estimated that a minimum of 153,113 deaths that year were caused by MDRO infections, with a worst-case scenario of 162,044. That would make MDROs the third-leading cause of death in the United States in 2010. The CDC estimated in a 2013 report that drug-resistant infections are responsible for 23,000 deaths a year, but because hospital codes don't specify deaths caused by MDROs, the true burden remains uncertain.

The researchers based the number of inpatient deaths caused by MDROs—70,837—on a conservative estimate of inpatient deaths due to sepsis (34.4%, 245,960) and the reported rate of MDR pathogens in sepsis cases (28.8%). The numbers for outpatient deaths—82,276 to 91,207—was determined by estimating how many outpatients died from infections in 2010 (17% to 19% of all cases, or 285,680 to 316,690 deaths) and then assuming that 28.8% were caused by MDROs.

The authors of the letter say the estimates illustrate the need for better surveillance and reporting mechanisms for MDROs infections.

"With rampant overuse of antibiotics, establishment of MDRO breeding and transmission centers (long-term acute-care hospitals and nursing facilities), and increasing rates of iatrogenic immunosuppression, the population at risk for MDRO infections and the likelihood of drug resistance will continue to increase," they write. "To address this critical issue, establishing the burden of MDROs is crucial to guide research funding allocation."
Nov 22 Infect Control Hosp Epidemiol letter


Japanese ASP reduces use of broad-spectrum antibiotics, study finds

Originally published by CIDRAP News Nov 26

Japanese researchers report in Open Forum Infectious Diseases that an antimicrobial stewardship program (ASP) centered around post-prescription review with feedback (PPRF) was tied to a reduction in the use of broad-spectrum antibiotics and the average length of stay at a Tokyo hospital over 4 years.

The before-after study conducted at Tokyo Metropolitan Tama Medical Center evaluated the impact of the ASP on antimicrobial use, patient-related outcomes, and changes in antimicrobial resistance in the inpatient setting by comparing two periods—the pre-intervention period (April 2012 to March 2014) and the intervention period (April 2014 to March 2018). The main activity in the ASP was a once-weekly PPRF meeting focused on auditing patients who were on carbapenems and piperacillin-tazobactam for more than 72 hours. Antimicrobial use was expressed as days of therapy (DOT) per 1,000 patient-days (PD).

An interrupted time series analysis showed that the monthly average use of both carbapenems (from 17.33 DOT per 1,000 PD to 8.67) and piperacillin-tazobactam (25.43 DOT/1,000 PD to 20.95) was lower in the intervention period than in the pre-intervention period. But the change in slope for carbapenem use significantly diminished over the course of the intervention period (from -0.73 to -0.003 DOT/1,000 PD [P < 0.001]), and the change in slope for piperacillin-tazobactam did not reach statistical significance (-0.04 to -0.24 DOT/1,000 PD [P = 0.16]). Post-intervention use of narrower spectrum antimicrobials was higher, but only ampicillin-sulbactam use reflected a statistically significant change (+0.58 DOT/1,000 PD [P < 0.001]).

The analysis also found that the monthly average length of hospital stay declined by -0.04 days per month (P < .001) and antimicrobial costs declined by -37.4 USD/1,000 PD per month (P < .001). Few post-intervention changes in the incidence of drug-resistant organisms were observed.

The authors conclude, "While the trends in antimicrobial use seen in the current study failed to demonstrate statistical significance, the results do suggest that PPRF for broad-spectrum antimicrobials can contribute to a sustained reduction in the use of antimicrobials and conduce to a hospital-wide de-escalation in antimicrobial use without compromising patients’ clinical outcomes."
Nov 22 Open Forum Infect Dis abstract


Review: Stewardship studies lack quality

Originally published by CIDRAP News Nov 26

A comprehensive systematic review of studies on antimicrobial stewardship has found that the overall quality is low and has not improved over time, a team of Dutch and British researchers report in Clinical Microbiology and Infection.

For the study, the researchers searched for all studies evaluating antimicrobial stewardship interventions published from 1950 through 2017. All studies underwent full-text evaluation, with reviewers assessing studies based on pre-specified design quality features (including use of randomized research design, multiple centers, and external controls) and factors that may influence design choices (including clinical setting, age-group studied, and financial support received.)

In total, 825 studies were included for review; 205 were in the community setting and 620 were in the hospital setting. Studies in the community setting fulfilled a median of 5 of 10 quality features, while studies in hospital settings fulfilled 3 of 10 quality features; none of the studies fulfilled all 10 quality features. Community setting studies were more likely to use randomization (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.8 to 9.2), external controls (OR, 5.6; 95% CI, 3.6 to 8.5), and multiple centers (OR, 10.5; 95% CI, 7.1 to 15.7). Most studies focused exclusively on process measures, with only 48% of all studies reporting clinical outcomes and only 23% reporting microbiologic outcomes. No improvement in quality design over time was observed.

The authors of the review say the findings will be used to formulate recommendations in a white paper that will "support investigators with key decisions, support funders assessing proposals for stewardship studies, and enhance the quality and impact of research in this crucial area."
Nov 23 Clin Microbiol Infect study 

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