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Emerging Strategies to Address the Spread of Antibiotic Resistance in Healthcare

This informative text discusses the escalating burden of antibiotic resistance in the United States, emphasizing the emergence of novel resistant pathogens in healthcare settings. It explores strategies to prevent the spread of these resistant pathogens, focusing on the rise of carbapenem-resistant Enterobacteriaceae (CRE) and the global emergence of Candida auris. The text underscores the importance of regional control measures and the rapid spread of resistance in healthcare settings. Key lessons learned and evolving strategies to control the spread of resistant pathogens are also highlighted.

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Emerging Strategies to Address the Spread of Antibiotic Resistance in Healthcare

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  1. Emerging Strategies to Address the Spread of Antibiotic Resistance in Healthcare Alex Kallen, MD, MPH, FACP. FIDSA, FSHEA, MS Chief, Prevention and Response Branch Division of Healthcare Quality Promotion August 6, 2019 No Disclosures

  2. Objectives • Describe the burden of antibiotic resistance in the United States • Understand what we are learning about how antibiotic resistance spreads in healthcare and regionally • What are the new strategiesto preventing spread of resistantpathogens

  3. Background

  4. Antibiotic resistance in the United States • Sickens >2 million people per year • Kills at least 23,000 people each year • Plus 15,000 each year from C. difficile • >$20B/year in healthcare costs

  5. Antibiotic resistance: old challenge, new opportunity

  6. Healthcare Pathogens

  7. Emerging Antibiotic-ResistantThreats

  8. Novel antimicrobial-resistant threats

  9. Enterobacteriaceae • Large family of gram negative rods with >25 recognized genera • Most common family encountered in clinical microbiology labs • Most common are Klebsiellaspp., Escherichia coli • Many historically have been susceptible to many antibiotics (including penicillins) K. pneumoniae, scanning electron micrograph http://www.ppdictionary.com/bacteria/

  10. Carbapenems • Broad spectrum “antibiotics of last resort” for highly resistant infections • Four approved carbapenems in US (imipenem, meropenem, doripenem, ertapenem) • Have always been able to rely on these for really sick people and for very resistant bacteria • Increasing use as resistant Enterobacteriaceae (ESBLs) emerged and spread in 1990’s • Resistance rare in US and due to collection of multiple mutations within the bacteria

  11. Carbapenemases • Carbapenemases are enzymes that digest carbapenems and other related antibiotics (Penicillins) • Plasmid encoded • Can pass resistance vertically and horizontally • No/minimal fitness defect • Prior to the late 1990’s, only rarely found in the US • More common outside the US, but not primary driver of carbapenem resistance

  12. Rise of Klebsiellapneumoniaecarbapenemase (KPC) • Isolate collected in 1996 during an ICU surveillance project from NC • Plasmid-mediated • Plasmid associated with resistance to lots of other classes • Some, so resistant that no options to treat with standard drugs

  13. DC* DC* DC* DC* DC* DC* DC* DC* Geographical of KPC-producing CRE, 2001-2017 KPC-CRE found in the US spread from 2 states in 2001 to 49 states, DC, and PR in 16 years 2008 2006 2005 2001 2017 2014 2012 2010 States with Klebsiella pneumoniae carbapenemase (KPC)-producing Carbapenem-resistant Enterobacteriaceae (CRE) confirmed by CDC In addition, proportion of Klebsiella resistant to carbapenems increase from <1% to>10% Division of Healthcare Quality Promotion

  14. First reports of Candida auris 2009 • Discovered during the course of a study to analyze antifungal yeast diversity in humans

  15. Global emergence of C. auris 2011 2009 2015 2013 2014

  16. Global emergence of C. auris 2011 2016 - case identified in US Retrospective review identified 6 others (first in 2013) 2009 2015 2013 2014

  17. Candidaauris • Truly novel: • No C. aurisin>7000 Candida isolates collected in U.S. 2008 –20161 • >30,000 Candida isolates collected from 4 continents, 1996-20152 • No C. aurisbefore 2009 • Causes invasive infections with high mortality (60%) • Unlike most other Candida species • Colonizes skin • Transmitted person-to-person in healthcare • Not susceptible to many disinfectants used in hospitals

  18. WGS of isolates from 4 regions South Asia • Very different across regions • 10,000s–100,000s SNPs • Virtually identical within regions • <100 SNPs South Africa South America East Asia

  19. C. aurisis highly resistant Polyenes Azoles Echinocandins

  20. A few isolates resistant to all three classes Polyenes Azoles Echinocandins 35% resistant to amphotericin B 93% resistant to fluconazole 54% resistant to voriconazole 7% resistant to echinocandins C. auris

  21. C. aurisclinicalcases reported by state, United States, May 31, 2019, n=716 An additional1342 asymptomatically colonized patients have been identified

  22. Lessons learned • Resistance can emerge and spread silently if not looking for it • Spread can happen very quickly • Healthcare settings are frequently the amplification centers • Particularly early in an epidemic

  23. What are We Learning about Controlling the Spread of Resistant Pathogens?

  24. 1. Resistance is a regional problem • Traditional Approach • Promotion of prevention efforts independently implemented by individual health care facilities • Does not account for inter-facility spread through movement of colonized/infected patients

  25. KPC outbreak in Chicago, 2008 Won et al. Clin Infect Dis 2011; 53:532-540

  26. Hospital transfers are a significant predictor of Clostridium difficileburden “Clostridium difficile burden at a hospital level can be better understood by knowing how a hospital is connected to other hospitals in terms of patient transfers” Simmering et al, Infect Control Hosp Epidemiol 2015;36:1031-37 28

  27. Projected regional prevalence of CRE over a 5-year period,10-facility model

  28. 2. Post-acute care can amplify spread SNF (n=14) 58% MDRO carriage vSNF (n=4) 76% MDRO carriage • Long lengths of stay, home-like environment • Sick patients, lots of hands-on care • Highly connected to other facilities through resident transfers McKinnell JA et al. Clin Infect Dis. 2019; Feb 11. doi: 10.1093/cid/ciz119. [Epub ahead of print]

  29. Slide courtesy of Chicago Department of Public Health.

  30. Slide courtesy of Chicago Department of Public Health.

  31. Slide courtesy of Chicago Department of Public Health.

  32. CRE Prevalence in LTCF: By Type Prevalence of CRE Carriage at admission to 4 acute care hospitals 33.3% 27.3% 8.3% 1.5% 0% from those admitted to the community Prabaker K, et al. ICHE 2012; 33:1193-1199

  33. 3. Importance of colonization • Only about 1 in 10 people with a targeted MDRO will have a positive clinical culture • Colonized patients can still serve as a reservoir for transmission but might not be subject to • Identifying colonized patients is important during a response to halt transmission

  34. 4. Aggressive approaches can decrease spread:the experience with CRE in Israel • KPCs likely originally from US identified in Israel beginning in late 2005 • By early 2006, increase in cases • Initiated National effort to control CRE (initial response) in acute care hospitals • Mandatory reporting of patients with CRE • Mandatory isolation (CP) of CRE patients • Staff and patient cohorting • Task Force developed with authority to collect data and intervene

  35. The Israel CRE experience • 79% decrease from the last month to the first month

  36. The Israel CRE experience: beyond the first year • Active surveillance for high-risk patients • Added long-term care facilities • Targeted interventions in facilities from which CRE-patients had been transferred • Intervened at 13 high-risk facilities (1/10th of LTCF beds in country) • Determine CRE prevalence among sample • Map infection control infrastructure and policies • Developed CRE control measures by ward type • Similar to acute care without cohorting or strict CP • Visited facilities to ensure implementation

  37. Schwaber MJ et al. Clin Infect Dis 2014

  38. New Interventions/Strategies to Slow the Spread of ResistantPathogens in Healthcare Settings

  39. 1. Containment • CDC’s Containment Strategy is an aggressive approach to stop the spread of emerging AR pathogens. • Based on identification of a single isolate not a cluster • Most effective when organism is rare • Often targeting a “mechanism” instead of a bacteria • CP-CRE, CP-Acinetobacter and Pseudomonas • Candida auris • Pan-resistant strains

  40. Containment strategySystematic public health response to slow the spread of emerging AR DETECTION INFECTION CONTROL CONTACT SCREENING Single case of emerging resistance: Pan-R, carbapenemase-producing organisms, Candida auris Available through ARLN Onsite assessment using standardized tools Regular infection control assessments and point prevalence surveys until transmission stops

  41. Antimicrobial Resistance Laboratory Network (ARLN):laboratory support for Containment Public Health Laboratories 50 States 5 Local Health Departments Hospitals/Clinical Laboratories Species identification Confirmatory AST Phenotypic screening for carbapenemase production Carbapenemase mechanism testing mcr-1 testing (some labs) CRE/CRPA isolates PHD Rectal Swabs Regional Lab CRE and CRPA Colonization Screening ARLN

  42. The Containment strategy

  43. 2. Addressing antibiotic resistance locally: State HAI/AR programs • In all 50 States, Puerto Rico, and 5 large cities • Work includes: • Containment • HAI/ C difficile prevention programs • Healthcare outbreak response • Surveillance • Improving antibiotic use • Improving infection control practices in facilities Detect & Contain Patient Safety Prevent Infections Improve Abx Use

  44. 3. Infection Control Assessment and Response (ICAR) activities, 2015-2019 • CDC funding and technical support to state and local health departments • Structured approach for assessing current infection prevention and control (IPC) programs using CDC developed tools • Outreach to all healthcare facilities (outpatient, NH, etc.) • Developing capacity for health departments serve as an IPC resource for healthcare facilities • Continues within CDC ELC grant • Targets high-acuity post acute care settings • F/u visit to address gaps http://www.cdc.gov/hai/prevent/infection-control-assessment-tools.html

  45. ICAR Targets: initial phase (May 2018) • 53 funded HDs targeted 4,914 facilities for ICAR assessments over 3 year period • Health department programs completed 5,411 assessments nationwide CDC unpublished data, May/June 2018

  46. ICAR: Common gaps in addressing resistantthreats (nursing homes) • Limited hand hygieneadherence and available stations/supplies • Lack of PPE availability and improper use • Lack of supplies for cleaning and disinfection • Limited interfacilitycommunication, especially regarding MDROs and precautions

  47. 4. Source control • Colonization • Transmission canoccur from colonized patients • Colonized patients may progress to clinical infection • Colonization difficult to detect or act on • sites can differ • Screening not common • Decolonization and Source Control • Decolonization: use of an antimicrobial agent often in combination with a topical antiseptic to completely eliminate organism from colonized patients • Source Control: use of antimicrobials or antiseptics to reduce the burden of colonization in patients without complete elimination

  48. Source control • MRSA - Typically done using an intranasal antistaphylococcal agent + topical antiseptic • Intranasal Mupirocin(antibiotic) • Topical Chlorhexidine • CRE – topical chlorhexidine • Future – GI tract?

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