Dissecting the epidemiology of resistant Enterobacteriaceae and non-fermenters Jon Otter, PhD Centre for Clinical Infection and Diagnostics Research (CIDR), King's College London & Guy's and St. Thomas' NHS Foundation Trust, London, UK. jonathan.otter@kcl.ac.uk @jonotter www.micro-blog.info
Disclosures I am employed part-time by Bioquell. I have received payment for producing educational material for 3M. Research funding from Pfizer and the Guy s & St Thomas Charity.
Acronym minefield CPC CPE MDR-GNR ESBL MDR-GNB CRO CPE CRE CRC KPC CRAB
MRSA is a CRO!
Resistant Enterobacteriaceae v non-fermenters Enterobacteriaceae (K. pneumoniae) Non-fermenters (A. baumannii) At-risk population Primarily acute pts ICU, burns Risk factors Travel Trauma, ICU stay Epidemic potential High Low Clinical manifestation UTI VAP Attributable mortality Stark increase (CPE) Minimal increase Prevalence Emerging (rapidly) Patchy but stable Sites of colonisation GI tract Resp, GI, skin Colonization duration Months to >1 year Days to weeks Transmission routes Hands ++, Env +/- Hands +, Env ++ Resistance Mainly acquired Intrinsic & acquired Common clones KPC-producing ST258 Intl clones I-III
Risk factors & at-risk population Risk factors At-risk population Enterobacteriaceae LOS ICU stay Catheters / devices Ventilation Prior antibiotics Travel Patients in acute settings, particularly those with recent travel to areas of high prevalence. Potential for community spread. Non-fermenters LOS ICU stay Catheters / devices Ventilation Prior antibiotics Trauma (esp. burns) High-risk patients in the ICU and burns units; rare cause of communityacquired infection. ECDC CPE risk assessment, 2011. Peleg et al. Clin Microbiol Rev 2008;21:538-582.
% HCAI Clinical manifestation 70 60 50 40 30 20 10 0 Enterobacteriaceae Non-Enterobacteriaceae Klebsiella spp. Acinetobacter spp. Zarb et al. ECDC PPS. Euro Surveill 2012;17.
Attributable mortality Enterobacteriaceae Non fermenters Organism AmpC / ESBL CPE A. baumannii Attributable mortality Moderate Massive (>50%) Minimal Shorr et al. Crit Care Med 2009;37:1463-1469. Patel et al. ICHE 2008;29:1099-1106.
Invasive CR P. aeruginosa isolates (EARS-Net) 2009 2010 2011 2012
Invasive CR K. pneumoniae isolates (EARS-Net) 2009 2010 2011 2012
CR K.pneumoniae invasive isolates Invasive CR K. pneumoniae trends Greece Italy UK 70% 60% 50% 40% 30% 20% 10% 0% 2005 2006 2007 2008 2009 2010 2011 2012 ECDC EARS-Net
CR P. aeruginosa invasive isolates (EARS- Net) CR A. baumannii bacteraemias (PHE) Invasive CR non-fermenters trends Greece - CRPA UK - CRPA Italy - CRPA UK - CRAB 60% 60% 50% 40% 30% 20% 10% 50% 40% 30% 20% 10% 0% 0% 2006 2007 2008 2009 2010 2011 2012-10% P. aeruginosa: ECDC EARS-Net A. baumannii: PHE Health Protection Report 2013;7.
Emergence of CPE in the UK PHE 2011. Advice on carbapenemase producers.
% CRE CRE in the USA 12 10 8 6 K. pneumoniae / oxytoca All Enterobacteriaceae 4 2 0 2001 2011 NHSN / NNIS data; MMWR 2013;62:165-170.
% carbapenem resistant CRE and CRNF in the USA Central line-associated bloodstream infection (CLABSI) resistant to carbapenems in the national NHSN network. 1 70 60 50 40 30 20 10 0 K. pneumoniae P. aeruginoas A. baumannii Siivert et al. Infect Control Hosp Epidemiol 2013;34:1-14.
% CRE carriers CRE in the USA Long Term Acute Care (LTAC) 60 50 40 30 20 10 0 ICU LTAC Lin et al. Clin Infect Dis 2013;57:1246-1252.
% resistant to carbapenems Latin America carbapenem resistance 80 70 60 50 40 30 20 Klebsiella spp A. baumannii P. aeruginosa 10 0 97-01 04-07 08-10 2011 www.micro-blog.info
Sites of colonisation 103 CRAB patients 69% sternal skin 80% tracheal aspirate 25% urine 69% rectal Apisarnthanarak et al. Clin Infect Dis 2013;56:1057-1059.
% patients carrying CRKP Duration of colonisation - CRKP Rectal or stool specimens from 103 CRKP patients over 24 months. 1 70 60 50 40 30 20 10 0 Range of colonisation duration 6-42 days for A. baumannii. 2 1 month 3 months 6 months 12 months 24 months 1. Lubert et al. Am J Infect Control 2014;42:376-380. 2. Dijkshoorn et al. Epidemiol Infect 1987;99:659-667.
Log (10) cfu / disc Surface survival 7 6 5 4 3 2 1 C. difficile Acinetobacter K. pneumoniae 0 0 1 2 3 4 5 Time / weeks Otter & French. J Clin Microbiol 2009;47:205-207.
Odds ratio Enterobacteriaceae are less environmental 9 8 7 6 5 4 3 2 1 0 Nseir A.baumannii Nseir P.aeruginosa Nseir ESBL Ajao ESBL Nseir et al. Clin Microbiol Infect 2011;17:1201-1208. Ajao et al. Infect Control Hosp Epidemiol 2013;34:453-458.
Key questions Which interventions work? Are they different for Enterobacteriaceae and nonfermenters? (Probably, given their epidemiology.) Has our focus on CPE taken our eye off CPNF, which are the clear and present danger for many of us? What is the prevalence of CPE in the UK? How much do we believe a single negative screen? Do we need rapid molecular diagnostics? What is the duration of colonisation? Are there decolonisation strategies other than selective decontamination using abx?
Share Gram stain reaction Concerning AMR Differ Risk factors & at-risk population Potential for epidemic spread Infection profile & mortality Prevalence Colonisation site & duration Transmission routes Resistance profile & mechanisms
Summary 1.Resistant Gram-negative rods represent a more serious threat than the usual suspects, mainly due to the threat of pan-drug resistance. 2.Enterobacteriaceae (mainly K. pneumoniae) and non-fermenters (mainly A. baumannii) have fundamental differences in their epidemiology. 3.CRE and CRNF are both emerging problems, but they are not the same problem. CRO 4.The prevention and control strategy will look different for Enterobacteriaceae vs. nonfermenters.
Image credits Danger! Mines! by Save the Wild UP. Chalk and Cheese by Jackson Boyle. All images sourced under a creative commons license from Flikr.