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

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

Learning Objectives

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

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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

• There has never been a reported

case of penicillin resistance

• Addition of clindamycin provides

additional benefit

• Mortality reduction
• Increasing macrolide resistance
• Intravenous treatment:
• Penicillin G
• Cefazolin
• Ceftriaxone
• Oral options:
• Penicillin VK
• Ampicillin
• Cephalexin
• 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

20 40 60 80 100 120 140 160 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Number of Isolates

Total Invasive Group A Streptococcus Isolates from 2004-2017

0% 5% 10% 15% 20% 25% 30% 35% 40% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Percent of Total Isolates

Percent of Resistant Invasive Group A Streptococcus by Year

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

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

11 11 11 11 11 41 41 49 49 58 58 58 58 58 58 87 87 87 92 92 92 92 92

108 108 108

0% 5% 10% 15% 20% 25% 30% 35% 40% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Percent of Total Isolates

Resistant emm Types by Year

11 11 11 11 11 41 41 49 49 87 87 87 92 92 92 92 92

108 108 108

0% 5% 10% 15% 20% 25% 30% 35% 40% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Percent of Total Isolates

Resistant emm Types by Year

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 emm11
• 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