Drug Resistance of Invasive Group A Streptococcus in Alaska from - PowerPoint PPT Presentation

Drug Resistance of Invasive Group A Streptococcus in Alaska from 2004- 2017 LT FLORIN IACOB, PHARMD UNITED STATES PUBLIC HEALTH SERVICE PGY-1 PHARMACY PRACTICE RESIDENT ALASKA NATIVE MEDICAL CENTER, ANCHORAGE AK

Disclosure Statement  Florin Iacob  Potential conflict of interests: none  Sponsorship: none  Proprietary information or research results are subject to different interpretation  The presentation is educational in nature and abides by the non-commercial guidelines provided 2

The information presented does not necessarily represent the views of the Centers for Disease Control and Prevention. 3

Learning Objectives  Identify how invasive group A Streptococcus infections change from 2004 -2017 in regards to:  Drug resistance  Demographics  emm types  Trends over time 4

Alaska Native Tribal Health Consortium Alaska Native Medical Center (ANMC)  173 bed facility  Referral institution for all Alaska Tribal Health Organizations  Level II trauma center The Centers for Disease Control Arctic Investigation Program (AIP)  Part of the National Center for Emerging Zoonotic Diseases  Mission: Prevention of infectious diseases in the people of the Arctic and sub-Arctic

Assessment Questions Invasive Group A Streptococcus DOES NOT include which of the following?  Bacteremia  Necrotizing fasciitis  Pharyngitis  Meningitis The incidence of Group A Streptococcus has not changed in recent years  True  False There are _____ emm types, which can vary based on region and other factors  <50  50-75  75-100  >100

Streptococcus  Classification  Based on Lancefield grouping  Groups A – O and others  Group A Streptococcus refers to Streptococcus pyogenes  Can be further subdivided based on emm type  Gene that encodes the M protein  Morphology  Beta hemolytic gram positive cocci  Grow in chains  Most typical reservoirs are the skin and mucus membranes  Oropharynx colonization  Typical bacteria in pharyngitis and tonsillopharyngitis  Easily treated with penicillins and other beta-lactams

emm Types and Clusters  emm typing  emm gene encodes for the M protein  M protein is major virulence factor of Group A Streptococcus  Classified by sequencing the 5’ end of the emm gene  Emm types are assigned for more drastic changes within the first 30 codons encoding the mature M protein  Over 200 emm types  Different emm types are associated with invasive infections, resistance and regional prevalence  Possible vaccine development  Clusters  emm types are predictive of related emm type clusters  Clusters are indicative of M proteins that share important functional properties

Invasive Group A Streptococcus  Defined as an isolation of Group A Streptococcus in a site that would normally be sterile  Bacteremia  Endocarditis  Pneumonia  Meningitis  Necrotizing fasciitis  Toxic shock syndrome  Overall outcomes  2017: CDC estimated 1,980 deaths

Incidence of Invasive Streptococcus  Overall  3.2 cases per 100,000 in 2000  4.0 cases per 100,000 in 2010  5.8 cases per 100,000 in 2016  Alaska  5.8 cases per 100,000 in 2000-13  7.7 cases per 100,000 in 2014  12.3 cases per 100,000 in 2015  2016 - outbreak in homeless population

Treatment  Intravenous treatment:  There has never been a reported  Penicillin G case of penicillin resistance  Cefazolin  Ceftriaxone  Addition of clindamycin provides  Oral options: additional benefit  Penicillin VK  Mortality reduction  Ampicillin  Cephalexin  Increasing macrolide resistance  Clindamycin  Penicillin allergy:  Macrolides  Clindamycin  Vancomycin

Study Objectives  We aimed to analyze data collected from 2004 – 2017 to determine if there were significant differences in antibiotic resistance according to the drug, demographics and emm type.

Methodology  Invasive Group A Streptococcus surveillance  Upon identification, isolates are sent to the CDC branch in Anchorage for:  Susceptibility testing  Penicillin, Cefotaxime, Levofloxacin, Erythromycin, Tetracycline  emm typing  Demographic information  Clinical data  Data Analysis  Analyzed data using a Chi-square test and multivariate logistic regression  Fisher’s exact test was used on small number when the likelihood ratio chi -square test was no longer appropriate

Results  Baseline characteristics of affected population  People with infections were more likely to be Alaska Native or older than 65 years old  Based on comparison to general Alaska population  845 invasive Group A Streptococcus isolates reported  134 were removed due to unknown susceptibilities  141 resistant isolates  19.8% were resistant to at least one antibiotic  14.9% were resistant to erythromycin  17.2% were resistant to tetracycline  12.3% were resistant to both  No isolates were resistant to penicillin or cefotaxime

Total Invasive Group A Streptococcus Isolates from 2004-2017 160 140 120 Number of Isolates 100 80 60 40 20 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Percent of Resistant Invasive Group A Streptococcus by Year 40% 35% 30% Percent of Total Isolates 25% 20% 15% 10% 5% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Demographic Risk Factors for Resistance  Univariate and multivariate analysis was conducted separately for tetracycline and erythromycin  Results were very similar  For both tetracycline and erythromycin  In the univariate analysis (p<0.01):  Alaska Native/American Indian race  emm type  In the multivariate analysis (p<0.0001):  emm type (p<0.0001)  Resistance was not associated with any demographic factors  Race  Sex  Age  Urban location

Figure 1: Figure 2: Distribution of Distribution of emm Types from emm Types from all Isolates Resistant Isolates

Figure 4: Figure 3: Distribution of Distribution of Clusters from Clusters from Resistant all Isolates Isolates

Resistant emm Types by Year 40% 35% 108 30% Percent of Total Isolates 25% 92 108 92 20% 92 108 87 11 15% 92 87 87 11 58 10% 58 11 49 5% 49 92 58 58 41 41 11 58 58 11 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Resistant emm Types by Year 40% 35% 108 30% Percent of Total Isolates 25% 92 108 92 20% 92 108 87 11 15% 92 87 87 11 10% 11 49 5% 49 92 41 41 11 11 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Conclusion  Overall Trend  Significant increase in incidence of invasive Group A Streptococcus  Demographics  Race, age, sex and urban location were not associated with antibiotic resistant infections  Resistance  No significant increase in resistance over all years  4 of 6 clusters showed significant susceptibility to tetracycline and erythromycin  E6 cluster was associated with antibiotic resistance to tetracycline and erythromycin  Largely attributable to emm 11  Future opportunities  Comparing emm types by region  Identifying possible patterns in fluctuations of emm types

Assessment Questions  Invasive Group A Streptococcus DOES NOT include which of the following?  Bacteremia  Necrotizing fasciitis  Pharyngitis  Meningitis  The incidence of Group A Streptococcus has not changed in recent years  True  False  There are _____ emm types, which can vary based on region and other factors  <50  50-75  75-100  >100

Assessment Questions  Invasive Group A Streptococcus DOES NOT include which of the following?  Bacteremia  Necrotizing fasciitis  Pharyngitis  Meningitis  The incidence of Group A Streptococcus has not changed in recent years  True  False  There are _____ emm types, which can vary based on region and other factors  <50  50-75  75-100  >100

Acknowledgments The Centers for Disease Control and Prevention – Arctic Investigations Program  Leisha Nolen  Dana Bruden  Sara Seeman  Tammy Zulz  Mike Bruce  Alisa Reasonover  Marcella Harker-Jones  Julie Morris

Questions? Florin Iacob, PharmD United States Public Health Service PGY-1 Pharmacy Practice Resident Alaska Native Medical Center, Anchorage AK Fiacob@anthc.org