EUROPE-WIDE SPREAD OF CARBAPENEM-RESISTANT BACTERIA: EPIDEMIOLOGY AND … · 2018-11-02 ·...
1
www.adelphivalues.com EUROPE-WIDE SPREAD OF CARBAPENEM-RESISTANT BACTERIA: EPIDEMIOLOGY AND DISEASE BURDEN Background and Objectives Methods > Antibiotic resistant bacteria are an established threat to global public health. 1 Though resistance is a natural phenomenon, the current spread of resistance has been exacerbated in recent years due to inappropriate prescribing, treatment non-compliance, and agricultural overuse. 1,2 > Carbapenem antibiotics have been widely used as last-line therapy for Gram-negative (GN) infections resistant to other antibiotics. 3 − Amongst GN bacteria, three – carbapenem resistant (CR) Enterobacteriaceae (including Escherichia coli and Klebsiella pneumoniae), Pseudomonas aeruginosa, and Acinetobacter baumannii – are recognised by the WHO as the highest ‘critical’ priority bacteria, requiring urgent innovative therapies to preclude widespread infection. 4 − In general, infections caused by resistant bacteria are associated with worse patient outcomes and greater economic costs than infections caused by susceptible bacteria. 5 > We conducted this research to review and present the European epidemiology of CR GN bacteria. > We obtained data on the epidemiology of GN bacteria throughout Europe via the European Antimicrobial Resistance Surveillance Network (EARS-Net). 6 − EARS-Net, from the European Centre for Disease Prevention and Control (ECDC), collates data on resistant bacteria from an extensive network of clinical laboratories across Europe. 6 In 2016, all 28 European Union (EU) member states plus Iceland and Norway from the European Economic Area (EEA) reported data to EARS-Net. 6 − These data included the total number of reported isolates and the number of CR isolates between 2007–2016, and country-specific resistance data from 2016. 6 > We also conducted a targeted literature search of electronic sources to identify reviews reporting on the mortality attributable to CR GN infections in Europe. Authors: Palmer T 1 , Collings H 1 , Tavella F 1 Affiliations: 1 Adelphi Values PROVE, Manchester, United Kingdom Abbreviations: CR: Carbapenem resistant; EARS-Net: European Antimicrobial Resistance Surveillance Network; EEA: European Economic Area; EU: European Union; GN: Gram-negative; KPC: K. pneumoniae carbapenemase. References: 1. WHO. 2017; Antimicrobial factsheet. 2. The Review on Antimicrobial Resistance Chaired by Jim O'Neill. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. 2014; 3. Papp-Wallace KM et al. Antimicrobial Agents and Chemotherapy. 2011;55(11):4943-4960. 4. WHO, 2017; Global Priority List Of Antibiotic-Resistant Bacteria To Guide Research, Discovery, And Development Of New Antibiotics. 5. Naylor N et al. Antimicrobial Resistance and Infection Control. 2018;7:58. 6. European Centre for Disease Prevention and Control (ECDC). Data from the ECDC Surveillance Atlas – Antimicrobial resistance (EARS-Net). Stockholm: ECDC; 2017. 7. Lemos EV et al. Clin Microbiol Infect. 2014; 20: 416–423. 8. Nathwani D et al. Antimicrobial Resistance and Infection Control. 2014, 3:32. 9. Ramos-Castañeda JA et al. Journal of Infection. 2018; 76:438–448. 10. Munita JM et al. Microbiol. Spectr.; 2016;4(2). Results 0% 10% 20% 30% 40% 50% 60% 0 15000 30000 45000 60000 75000 90000 105000 120000 Proportion resistant Total isolates tested 2012 2013 2014 2015 2016 Overall resistance rates > Across EU/EEA member states, ten-year data for the four GN bacteria shows stable levels of carbapenem resistance for E. coli (<1%), P. aeruginosa (20%), and K. pneumoniae (8%), and a downward, but variable, trend in the proportion of CR Acinetobacter spp. (Figure 1). Note that data on CR Acinetobacter spp. have only been collected since 2012 (in response to concern about increasing prevalence). 6 > In the EU5 (France, Germany, Italy, Spain, UK), carbapenem resistance trends in E. coli and P. aeruginosa were similar to rates across the EU/EEA, though there was a marked increase in CR K. pneumoniae from 2009 (<1% to 8%) (Figure 1). 6 The EARS-Net database contained epidemiological data for E. coli from 2000, for K. pneumoniae and P. aeruginosa from 2005, and for Acinetobacter spp. from 2012. 6 Country-specific resistance rates > Though resistance rates averaged across all countries in the EU/EEA give a broad sense of the level of resistance, this may obscure any inter-country variability. Figure 2 illustrates that the proportions of GN isolates that tested resistant were highly variable across the EU/EEA in 2016. 6 > The call-out box on each map gives the carbapenem resistance rate in the highest resistance country. 6 Figure 2. Country-specific carbapenem resistance rates in the EU/EEA in 2016, by bacteria. 6 The number of isolates vs. the proportion carbapenem resistant > High resistance rates do not necessarily translate into a high disease burden – if infections due to a highly resistant bacteria are very rare, the detrimental effect on society will be low. − Over the past five years, none of the species have exhibited both high resistance and high prevalence (Figure 3). 6 Though carbapenem resistance rates in Acinetobacter spp. were high, the number of infections were relatively low. Conversely, carbapenem resistance in E. coli were very low, but the number of infections was far greater than for the other bacteria. Acinetobacter spp. P. aeruginosa K. pneumoniae Figure 3. Comparison of the number of isolates tested vs. the proportion carbapenem resistant in the EU/EEA, 2012–2016. 6 E. coli Mortality due to CR infections > The literature search did not identify recent, high-quality systematic literature reviews analysing the attributable burden of CR GN infections in Europe. From reviews that used data from global sources, the following mortality rates were reported: − CR A. baumannii – 46% – Lemos et al., 2013. 7 − CR P. aeruginosa – 34% – Nathwani et al., 2014. 8 − CR K. pneumoniae – 41% – Ramos-Castañeda et al., 2018. 9 − CR E. coli – the search did not identify reviews reporting on the mortality attributable to CR E. coli. . Conclusions Figure 1. The average proportion of tested isolates exhibiting carbapenem resistance in the EU/EEA, 2007–2016. 6 E. coli <1.0% Romania K. pneumoniae 66.9% Greece P. aeruginosa 51.6% Romania 95.4% Greece Acinetobacter spp. 0% 10% 20% 30% 40% 50% 60% 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Proportion resistant > Rates of carbapenem resistance in GN bacteria are high in many parts of Europe, with eastern, southern, and Baltic countries most affected. 6 − The recent rise of CR bacteria is largely due to the dissemination of carbapenemases, enzymes capable of hydrolysing the antibiotic. − CR Acinetobacter spp. infections were associated with the highest mortality, though reviews using solely European data were not found. > Presently, highly resistant bacteria are not highly prevalent – this is prone to rapid change due to mutation or through gene transmission between bacteria. 10 − Should this happen, medicine will regress to a post-antibiotic era, meaning mortality from mild infections will rise, routine surgery will become highly unsafe, and the world will incur enormous economic costs. 1,2 > The insidious spread of CR GN bacteria in Europe emphasises the need for prudent antibiotic stewardship by physicians and patients, novel research by industry, and increased funding and streamlined regulatory approval for new antibiotics by decision makers and regulatory bodies. > High quality systematic literature reviews and meta-analyses on infection-associated mortality are required to fully illustrate the attributable disease burden of CR infections in Europe.
Transcript of EUROPE-WIDE SPREAD OF CARBAPENEM-RESISTANT BACTERIA: EPIDEMIOLOGY AND … · 2018-11-02 ·...
www.adelphivalues.com
EUROPE-WIDE SPREAD OF CARBAPENEM-RESISTANT BACTERIA: EPIDEMIOLOGY AND DISEASE BURDEN
Background and Objectives Methods
> Antibiotic resistant bacteria are an established threat to global public health.1 Though resistance isa natural phenomenon, the current spread of resistance has been exacerbated in recent years dueto inappropriate prescribing, treatment non-compliance, and agricultural overuse.1,2
> Carbapenem antibiotics have been widely used as last-line therapy for Gram-negative (GN)infections resistant to other antibiotics.3
− Amongst GN bacteria, three – carbapenem resistant (CR) Enterobacteriaceae (includingEscherichia coli and Klebsiella pneumoniae), Pseudomonas aeruginosa, and Acinetobacterbaumannii – are recognised by the WHO as the highest ‘critical’ priority bacteria, requiringurgent innovative therapies to preclude widespread infection.4
− In general, infections caused by resistant bacteria are associated with worse patient outcomesand greater economic costs than infections caused by susceptible bacteria.5
> We conducted this research to review and present the European epidemiology of CR GN bacteria.
> We obtained data on the epidemiology of GN bacteria throughout Europe via the EuropeanAntimicrobial Resistance Surveillance Network (EARS-Net).6
− EARS-Net, from the European Centre for Disease Prevention and Control (ECDC), collates data onresistant bacteria from an extensive network of clinical laboratories across Europe.6
In 2016, all 28 European Union (EU) member states plus Iceland and Norway from theEuropean Economic Area (EEA) reported data to EARS-Net.6
− These data included the total number of reported isolates and the number of CR isolatesbetween 2007–2016, and country-specific resistance data from 2016.6
> We also conducted a targeted literature search of electronic sources to identify reviews reportingon the mortality attributable to CR GN infections in Europe.
Authors: Palmer T1, Collings H1, Tavella F1
Affiliations: 1Adelphi Values PROVE, Manchester, United Kingdom
Abbreviations: CR: Carbapenem resistant; EARS-Net: European Antimicrobial Resistance Surveillance Network; EEA: European Economic Area; EU: European Union; GN: Gram-negative; KPC: K. pneumoniae carbapenemase. References: 1. WHO. 2017; Antimicrobial factsheet. 2. The Review on Antimicrobial Resistance Chaired by Jim O'Neill. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. 2014; 3. Papp-Wallace KM et al. Antimicrobial Agents and Chemotherapy. 2011;55(11):4943-4960. 4. WHO, 2017; Global Priority List Of Antibiotic-Resistant Bacteria To Guide Research, Discovery, AndDevelopment Of New Antibiotics. 5. Naylor N et al. Antimicrobial Resistance and Infection Control. 2018;7:58. 6. European Centre for Disease Prevention and Control (ECDC). Data from the ECDC Surveillance Atlas – Antimicrobial resistance (EARS-Net). Stockholm: ECDC; 2017. 7. Lemos EV et al. Clin Microbiol Infect. 2014; 20: 416–423. 8. Nathwani D et al. Antimicrobial Resistance and Infection Control. 2014, 3:32. 9. Ramos-Castañeda JA et al. Journal of Infection. 2018; 76:438–448. 10. Munita JM et al. Microbiol. Spectr.; 2016;4(2).
Results
0%
10%
20%
30%
40%
50%
60%
0 15000 30000 45000 60000 75000 90000 105000 120000
Proportionresistant
Total isolates tested
2012 2013 2014 2015 2016
Overall resistance rates
> Across EU/EEA member states, ten-year data for the four GN bacteria shows stable levelsof carbapenem resistance for E. coli (<1%), P. aeruginosa (20%), and K. pneumoniae (8%),and a downward, but variable, trend in the proportion of CR Acinetobacter spp. (Figure1). Note that data on CR Acinetobacter spp. have only been collected since 2012 (inresponse to concern about increasing prevalence).6
> In the EU5 (France, Germany, Italy, Spain, UK), carbapenem resistance trends in E. coliand P. aeruginosa were similar to rates across the EU/EEA, though there was a markedincrease in CR K. pneumoniae from 2009 (<1% to 8%) (Figure 1).6
The EARS-Net database contained epidemiological data for E. coli from 2000, for K. pneumoniae and P. aeruginosa from 2005, and for Acinetobacter spp. from 2012.6
Country-specific resistance rates
> Though resistance rates averaged across all countries in the EU/EEA give a broad sense ofthe level of resistance, this may obscure any inter-country variability. Figure 2 illustratesthat the proportions of GN isolates that tested resistant were highly variable across theEU/EEA in 2016.6
> The call-out box on each map gives the carbapenem resistance rate in the highestresistance country.6
Figure 2. Country-specific carbapenem resistance rates in the EU/EEA in 2016, by bacteria.6
The number of isolates vs. the proportion carbapenem resistant
> High resistance rates do not necessarily translate into a high disease burden – if infections due toa highly resistant bacteria are very rare, the detrimental effect on society will be low.− Over the past five years, none of the species have exhibited both high resistance and high
prevalence (Figure 3).6 Though carbapenem resistance rates in Acinetobacter spp. were high,the number of infections were relatively low. Conversely, carbapenem resistance in E. coli werevery low, but the number of infections was far greater than for the other bacteria.
Acinetobacter spp.
P. aeruginosa
K. pneumoniae
Figure 3. Comparison of the number of isolates tested vs. the proportion carbapenem resistant in the EU/EEA, 2012–2016.6
E. coli
Mortality due to CR infections
> The literature search did not identify recent, high-quality systematic literature reviews analysing theattributable burden of CR GN infections in Europe. From reviews that used data from global sources, thefollowing mortality rates were reported:− CR A. baumannii – 46% – Lemos et al., 2013.7
− CR P. aeruginosa – 34% – Nathwani et al., 2014.8
− CR K. pneumoniae – 41% – Ramos-Castañeda et al., 2018.9
− CR E. coli – the search did not identify reviews reporting on the mortality attributable to CR E. coli.
.
Conclusions
Figure 1. The average proportion of tested
isolates exhibiting carbapenem
resistance in the EU/EEA, 2007–2016.6
E. coli
<1.0% Romania
K. pneumoniae
66.9% Greece
P. aeruginosa
51.6% Romania
95.4% Greece
Acinetobacter spp.
0%
10%
20%
30%
40%
50%
60%
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Proportionresistant
> Rates of carbapenem resistance in GN bacteria are high in many parts of Europe, with eastern, southern,and Baltic countries most affected.6
− The recent rise of CR bacteria is largely due to the dissemination of carbapenemases, enzymes capableof hydrolysing the antibiotic.
− CR Acinetobacter spp. infections were associated with the highest mortality, though reviews usingsolely European data were not found.
> Presently, highly resistant bacteria are not highly prevalent – this is prone to rapid change due tomutation or through gene transmission between bacteria.10
− Should this happen, medicine will regress to a post-antibiotic era, meaning mortality from mildinfections will rise, routine surgery will become highly unsafe, and the world will incur enormouseconomic costs.1,2
> The insidious spread of CR GN bacteria in Europe emphasises the need for prudent antibioticstewardship by physicians and patients, novel research by industry, and increased funding andstreamlined regulatory approval for new antibiotics by decision makers and regulatory bodies.
> High quality systematic literature reviews and meta-analyses on infection-associated mortality arerequired to fully illustrate the attributable disease burden of CR infections in Europe.
