ASP Scan (Weekly) for Oct 13, 2017

MDR pneumonia
ASPs in long-term care
Contact precautions for MRSA, VRE
Antimicrobial restrictions
New CARB-X funding
Preoperative antibiotics
MCR-1 in US, China patients
MDROs in nursing homes
Infections in African kids
Antibiotics for bloodstream infection

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

Study identifies MDR risk factors in hemodialysis pneumonia

A multi-hospital study in South Korea has identified risk factors for infection with multidrug-resistant (MDR) pathogens in patients with hemodialysis-associated pneumonia (HDAP), researchers reported yesterday in BMC Infectious Diseases.

The retrospective observational study identified 105 patients with HDAP at three South Korean hospitals. The responsible pathogen was identified in 53 (50.4%) of these patients, and MDR pathogens were identified in 24 (22.8%). The most frequent MDR pathogen was methicillin-resistant Staphylococcus aureus (MRSA), found in 10 patients (9.5%), followed by Pseudomonas aeruginosa (7 patients, 6.6%) and Acinetobacter baumannii (6 patients, 5.7%).

Multivariate logistic regression analysis found that the occurrence of MDR pathogens in HDAP patients was associated with recent hospitalization (adjusted odds ratio [aOR]: 3.0) and a pneumonia severity index (PSI) score of more than 147 (aOR: 1.0). Based on these findings, the investigators created a prediction tool to identify HDAP patients with MDR pathogens. The tool showed that as the number of risk factors increased, the prevalence of infection with an MDR pathogen also increased (0 risk factors, 7.6%; 1 risk factor, 28.2%; 2 risk factors, 64.2%).

The findings are noteworthy because pneumonia is a common and leading cause of death in hemodialysis patients, and early proper management of HDAP patients—such as treatment with anti-MRSA or anti-pseudomonal agents—could reduce mortality.

The authors conclude, "Although large-scale prospective studies are needed to confirm our results, our findings would be helpful for physicians' decisions to select HDAP patients harboring MDR pathogens."
Oct 12 BMC Infect Dis study


Study shows ASP is effective, sustainable, in a long-term care hospital

Originally published by CIDRAP News Oct 12

An antimicrobial stewardship program (ASP) at a long-term acute care hospital in Detroit improved antimicrobial prescribing practices, reduced costs, and has proven to be sustainable, researchers report today in the American Journal of Infection Control.

The multi-part study, led by researchers from Detroit Medical Center-Wayne State University, included a survey of healthcare workers at the Kindred Hospital Detroit to assess knowledge and attitudes toward antimicrobial resistance (AMR), a retrospective review of common antibiotic prescribing practices before the ASP was implemented, and a two-phase post-implementation evaluation of the ASP's impact on antibiotic use and expenditures. Kindred's ASP, launched in November 2011, was a seven-step pyramid approach based on the Centers for Disease Control and Prevention's (CDC's) 12 Steps to Prevent Antimicrobial Resistance Among Hospitalized Adults.

The survey found that 65% of the 26 respondents viewed AMR as a national problem, but only 38% viewed it as a problem at their facility. And while 80% were familiar with multidrug-resistant infections like MRSA, only 35% expressed confidence in caring for patients with such infections.

In the pre-ASP implementation phase, the researchers found that 43% of antibiotic courses administered to a cohort of 28 patients were inappropriate, 77% of opportunities for antibiotic de-escalation were missed, and 48% of antibiotic courses requiring early discontinuation because of misdiagnosis were not stopped. The total antibiotic cost for treating this cohort was $57,168, and the extra drug costs related to missed de-escalation opportunities and unnecessary days of therapy amounted to $23,540.

In the first post-implementation phase, there was a 42% and 58% decrease in the use daptomycin and tigecycline (the two most frequently used antibiotics in the pre-implementation phase), resulting in cost savings of $55,000. In the second post-implementation phase, the researchers demonstrated that from January through March in the years 2016 and 2017, total antibiotic costs were $26,837 and 22,397, respectively—more than $30,000 lower than the pre-ASP cost.

The authors say the findings indicate that the current ASP pilot model is effective and sustainable and can potentially be replicated at other long-term acute care hospitals. 
Oct 12 Am J Infect Control study


Analysis: Ending contact precautions for MRSA, VRE doesn't increase infections

Originally published by CIDRAP News Oct 12

A systematic review and meta-analysis of 14 studies indicates that discontinuation of contact precautions (CPs) for MRSA and vancomycin-resistant enterococci (VRE) does not increase infection rates.

While CPs for infections caused by multidrug-resistant infections are recommended by the CDC and are considered an essential element of infection control and prevention in US hospitals, there has been little evidence to support the use of gloves and gowns in the prevention of MRSA and VRE infections in endemic settings, and questions have been raised about the impact of CP on patient care and safety. As a result, several hospitals have discontinued CPs for MRSA and VRE patients, and others are considering it.

To assess the impact of this policy, researchers from the University of Iowa reviewed 14 previously published quasi-experimental studies conducted at hospitals that had discontinued CPs for MRSA and VRE. When they pooled the results of these studies, the investigators found that discontinuation of CPs for MRSA was associated with a non-significant reduction in MRSA infection rates (pooled risk ratio [pRR], 0.84) and a statistically significant reduction in VRE infection rates (pRR, 0.82). 

"We think discontinuation of CPs (as currently practiced) for MRSA and VRE can be safely accomplished, particularly in hospitals with a strong horizontal infection prevention strategy, including high levels of compliance with hand hygiene," the authors write today in the American Journal of Infection Control

They caution, however, that the results are limited by the design of the studies included in their review, and are not applicable to outbreak situations.
Oct 12 Am J Infect Control study


Research reveals opportunities for improving antimicrobial restriction

Originally published by CIDRAP News Oct 12

In a third study today in the American Journal of Infection Control, researchers with the Virginia Commonwealth University Health System report that antimicrobial restriction at an academic medical center led to significant decreases in consumption of restricted agents in more than half of the medical units studied, but in none of the surgical units.

In an analysis conducted at the 865-bed academic medical center from January 2013 through May 2015, the researchers looked at the use the restricted drugs linezolid, daptomycin, and ceftaroline and the non-restricted agent vancomycin. Use was quantified by individual hospital unit and unit type (medical vs. surgical) in days of therapy per 1,000 patient-days. A total of 11 units were analyzed.

In terms of the restricted antibiotics, significant reductions in consumption were detected in 4 of 7 medical units (57%), while increases were detected in 2 of 7 medical units (29%) and 1 of 4 surgical units (25%). No significant reductions in restricted antibiotics were detected in the surgical units. In addition, no significant reductions in vancomycin use were detected in any of the units, but significant increases were detected in 1 of 7 medical units (14%) and 1 of 4 surgical units (25%).

The authors say their analysis reveals opportunities for improving the hospital's antimicrobial restriction strategy, particularly in those units that demonstrated increases in consumption of restricted agents, and they suggest that the methodology may be useful to other programs assessing their restriction policies. 
Oct 12 Am J Infect Control study


CARB-X awards $3.8 million to Entasis to develop novel antibiotic class

Originally published by CIDRAP News Oct 12

CARB-X today awarded $3.8 million in funding to Entasis Therapeutics, Inc. to develop its penicillin-binding protein (PBP) inhibitor program, according to a company press release.

The PBP inhibitor program is a novel antibiotic class that targets PBPs—groups of proteins that are essential to bacterial cell wall synthesis. While beta-lactam antibiotics kill bacteria by binding to these proteins, many types of gram-negative bacteria have evolved to produce beta-lactamase enzymes that inactivate these antibiotics. The non-beta-lactam PBP inhibitors developed by Entasis, however, are unaffected by all four classes of beta-lactamases.  The company says current leads in the program have demonstrated potent in vivo and in vitro activity against multidrug-resistant P aeruginosa, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant A baumannii.

The award is the company's second from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership launched in 2016 to address gaps in new antibiotic development and funding, specifically in the pre-clinical phase. In March, Entasis received $2.1 million for development of ETX0282, an extended-spectrum beta-lactamase inhibitor.

"We are excited to extend our work with CARB-X following our initial partnership earlier this year and look forward to working together to bring these new anti-infective products through discovery into clinical trials," Entasis CEO Manos Perros, PhD, said in the release. 

In addition to the $3.8 million in initial funding, Entasis could receive another $6.3 million from CARB-X if it hits certain milestones.

With today's announcement, CARB-X is now supporting 19 different projects in the pre-clinical phase of development. It aims to invest more than $450 million over 5 years, with a goal of accelerating the discovery and development of at least 20 new antibacterial products.
Oct 12 Entasis press release


Antibiotics before minor surgery not shown to lead to resistant bacteria

Originally published by CIDRAP News Oct 11

Surgical patients who receive prophylactic (preventive) antibiotics before certain low-risk operations are not at an increased risk for antibiotic-resistant infections immediately after the procedure, New York City researchers reported yesterday in the Journal of the American College of Surgeons.

The investigators looked at simple surgeries such as some general surgical procedures, simple or diagnostic laparoscopy, or elective orthopedic, gynecologic, and urologic procedures for which no guidelines have been published for the use of prophylactic antibiotics to prevent surgical site infection. (Guidelines do exist for most major operations.) The scientists reviewed all 22,138 adult patients at Columbia University Medical Center who had one of these operations from 2008 to 2016. The team then focused on patients who developed an infection within 30 days of the operation.

A total of 689 patients (3.1%) developed an infection in that time frame, 550 of them (80%) had received antibiotic prophylaxis, and 338 (49%) had an infection resistant to antibiotics. Patients, though, had the same risk for developing an antibiotic-resistant infection whether they had received prophylactic antibiotics or not: 47% of patients with a resistant infection had no antibiotic prophylaxis and 49% had received antibiotics.

The only factor associated with a higher risk for a postoperative antibiotic-resistant infection was a previous antibiotic-resistant infection.

"The results of this study should be reassuring for those surgeons who choose to use antibiotic prophylaxis believing that antibiotics decrease the overall risk for infection following surgery," said principal author Daniel Freedberg, MD, of Columbia University, in an American College of Surgeons (ACS) news release.
Oct 10 J Am Coll Surg study
Oct 10 ACS 
news release


Studies describe MCR-1 cases, prevalence in US
Originally published by CIDRAP News Oct 10

Three studies presented at IDWeek 2017 in San Diego last week focused on the emerging colistin-resistance gene MCR-1 in the United States.

Two of the abstracts were case reports. In one, investigators from the Centers for Disease Control and Prevention (CDC) and the Connecticut Department of Health reported that MCR-1 was isolated from two Connecticut residents—an adult and an unrelated child—who had diarrhea. The gene was identified in an Escherichia coli isolate from the child and a Salmonella Enteritidis isolate from the adult, and the plasmids containing the gene were identical by DNA sequencing. Both patients reported recent travel to the Dominican Republic.

In the other case report, researchers from the University of Michigan Medical School and the Michigan Department of Health and Human Services described three patients from a single health system who had travel-associated colistin-resistant E coli. The presence of the MCR-1 gene in the patients' urine was confirmed by polymerase chain reaction testing. All isolates were carbapenem susceptible. No healthcare-associated epidemiologic links were identified, but all three patients had travelled internationally within the prior 6 months—one to Kenya and China, one to Lebanon, and one to Mexico.

The authors of the case reports conclude that increased surveillance is needed to understand the scope and risk factors associated with MCR-1–mediated resistance, with a particular focus on the role of international travel.

In the third abstract, investigators from the CDC and state health departments in Virginia, Tennessee, Minnesota, and Connecticut screened 70,000 nontyphoidal Salmonella isolates from humans, retail meat, and food animals for the presence of MCR-1. No Salmonella isolates with MCR-1 were found in retail meat and food animals, but four human cases of Salmonella with MCR-1 were identified: Salmonella Corvallis in an 18-year-old man from Tennessee, Salmonella Enteritidis in a 55-year-old woman from Connecticut and a 47-year-old man from Minnesota, and Salmonella Typhimurium in a 57-year-old woman from Virginia. All patients had traveled internationally in the 10 days prior to illness onset.

The researchers say the absence of MCR-1 in the retail meat and food animals is likely because colistin has not been used in food animal production in the United States.

MCR-1 was first identified in E coli samples from pigs, pork products, and humans in China in 2015. Since then, it has been detected in human, animal, food, and environmental samples in more than 30 countries.
Oct 5 IDWeek abstract 383
Oct 5 IDWeek
 abstract 384
Oct 5 IDWeek
 abstract 324


Chinese study finds 6.2% prevalence of MCR-1 in patients' fecal samples

Originally published by CIDRAP News Oct 10

Of more than 8,000 fecal samples collected from inpatients and outpatients in China in recent years, 6.2% were MCR-1–positive, and more than a third of the positive samples were resistant to third-generation cephalosporins, researchers reported today in Clinical Infectious Diseases.

The investigators analyzed 8,022 samples collected from April 2011 through March 2016 from three hospitals in Guangzhou, a port city of 14 million people. Of the total samples, 497 (6.2%) were MCR-1–positive, and 182 (2.3%) were Enterobacteriaceae that harbored MCR-1 resistant to third-generation cephalosporins, a worrisome combination. Those Enterobacteriaceae—most commonly E coli—were often multidrug resistant.

The researchers also found that the presence of MCR-1 increased from 0% to 31% over the course of the study. The MCR-1 Enterobacteriaceae resistant to third-generation cephalosporins did not appear until recent years.

Whole-genome sequencing revealed similarity with published MCR-1 plasmid sequences and pointed to spread among animal and human reservoirs. The authors concluded, "The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence."
Oct 10 Clin Infect Dis abstract


Widespread MDRO carriage found in nursing homes, long-term care

Originally published by CIDRAP News Oct 10

Two point-prevalence studies conducted in southern California suggest that multidrug-resistant organisms (MDROs) are prevalent in the region's nursing homes and long-term care facilities.

In a study conducted as part of the CDC's SHIELD (Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs) Orange County project, investigators performed point-prevalence screening on adult patients in 38 facilities (17 hospitals, 18 nursing homes, and 3 long-term acute care facilities) from September 2016 through April 2017.

They screened for MRSA, VRE, extended-spectrum beta-lactamase (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin, and peri-rectal swabs. All hospital patients were under contact precautions.

The overall prevalence of any MDRO among patients was 64% in nursing homes, 80% in long-term acute care facilities, and 64% in hospitals. MRSA infections were most common in nursing homes (42%) and hospitals (37%), while VRE infections were most common in long-term acute-care facilities (55%). Known MDRO patients also harbored another MDRO 49%, 63%, and 34% of the time in nursing homes, long-term acute care facilities, and hospitals, respectively. In the long-term acute care facilities, MDRO point prevalence was 38% higher than the usual admission prevalence. 
Oct 6 IDWeek oral abstract 1712

In the other study, investigators conducted a baseline point-prevalence study in fall 2016 of MDRO colonization in residents of 28 southern California nursing homes participating in a decolonization trial. A total of 2,797 swabs were obtained from 1,400 residents. Nasal swabs were processed for MRSA, and skin swabs were processed for MRSA, VRE, ESBL, and CRE. In addition, environmental swabs were collected from high-touch objects in resident rooms and common areas.

Overall, 48.6% of residents harbored MDROs, mainly MRSA (37%) and ESBL (16%). Resident MDRO status, however, was known for only 11% of MRSA and 18% of ESBL carriers, while only 4% of VRE and none of the CRE carriers were known to harbor the organisms. Bedbound residents were more likely to be MDRO colonized than ambulatory residents (58.7% vs. 45.7%). Environmental swabbing revealed that 93% of common area objects (nursing stations, hand rails, and drinking fountains) and 74% of resident room objects (bedside tables, bedrails, and door knobs) harbored an MDRO.

The authors of the two studies, which were presented at IDWeek 2017 in San Diego late last week, say the findings indicate that MDROs are as widespread in highly interconnected nursing homes and long-term acute care facilities as they are in hospitals, and that strategies to reduce MDRO colonization and transmission in these settings should be part of regional MDRO prevention efforts.
Oct 6 IDWeek oral abstract 1696


Gram-negative bacteria common in resistant infection in African kids

Originally published by CIDRAP News Oct 10

Though recent and high-quality data are lacking, a meta-analysis of antimicrobial resistance in children in sub-Saharan Africa found that gram-negative organisms were the predominant cause of early-onset neonatal sepsis and were also responsible for a high proportion of infections among older children, according to a study yesterday in The Lancet Infectious Diseases.

The UK and Australian researchers systematically reviewed 1,075 studies on antimicrobial resistance in African children and included 18 in their final analysis and provided data on 67,451 isolates of pathogenic bacteria.

They reported that gram-negative organisms were the predominant cause of early-onset neonatal sepsis, with a high prevalence of ESBL-producing organisms. In older children, gram-positive bacteria were responsible for a high percentage of infections, with high prevalence of non-susceptibility to treatment advocated by World Health Organization therapeutic guidelines.

The authors conclude, "There are few up-to-date or representative studies given the magnitude of the problem of antimicrobial resistance, especially regarding community-acquired infections. Research should focus on differentiating resistance in community-acquired versus hospital-acquired infections, implementation of standardised reporting systems, and pragmatic clinical trials to assess the efficacy of alternative treatment regimens."
Oct 9 Lancet Infect Dis study

Short-course antibiotics perform well in Enterobacteriaceae bacteremia

Originally published by CIDRAP News Oct 9

Scientists have determined that short courses of antibiotics yield similar clinical outcomes as prolonged courses for Enterobacteriaceae bacteremia and may protect against subsequent multidrug-resistant gram-negative bacteria, according to a new study in PLoS Medicine.

The recommended duration of antibiotic treatment for bloodstream infections caused by Enterobacteriaceae is 7 to 14 days. Researchers from the Antibacterial Resistance Leadership Group compared the outcomes of patients receiving 6 to 10 days versus 11 to 16 days of antibiotics for Enterobacteriaceae bacteremia in patients who were treated in one of three medical centers from 2008 through 2014.

The team matched 385 short-course bacteremia patients with the same number of prolonged-course patients. Median treatment duration was 8 days in the former group and 15 in the latter.

They found no difference between the groups in mortality and recurrent bloodstream infections. They detected a trend toward a protective effect of short-course antibiotic therapy on the emergence of multidrug-resistant gram-negative bacteria but not a statistically significant difference.
Oct 8 Clin Infect Dis abstract

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