Concise Notes on Gram(-) MDR Market Sizing Study

Overview of Antimicrobial Resistance (AMR)

  • Overuse of antibiotics has led to increased AMR, rendering antibiotics ineffective against infections.

  • Gram-negative bacteria like K. pneumoniae, E. coli, and P. aeruginosa are major drug-resistant pathogens.

  • The spread of AMR is fueled by human and animal populations, water contamination, and international travel.

  • A UK government study in 2016 estimated 700,000 deaths annually are attributed to AMR.

  • Without action, AMR may cause 10 million deaths by 2050.

Carbapenem Resistance

  • Development of carbapenem resistance in Enterobacteriaceae is a significant concern due to limited antibiotic options.

  • Carbapenem resistance is mediated by ESBLs and carbapenemases.

  • CRE infections are mainly reported in healthcare facilities of developed countries, but are also found in low-to-mid income countries

Executive Summaries by Country

United Kingdom

  • Gram-negative bloodstream infections increased steadily from 2013-2018 but decreased by 1% in 2018.

  • E. coli, P. aeruginosa, and Klebsiella spp. cause ~75% of gram-negative BSIs.

  • The susceptible population is growing at ~5-10%, while the resistant population is increasing at ~15-17%.

  • 20-year vision and 5-year action plan to contribute to reduce the number of drug-resistant infections by 10% (5,000 infections) by 2050.

China

  • The ratio of gram-negative to gram-positive bacteria is 7:3.

  • Gram-negative bacteria account for 70.3% of isolates with a 5% growth rate.

  • E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii are leading causes of healthcare-associated infections.

  • P. aeruginosa has the highest carbapenem resistance rate among gram-negative bacteria at 20.7% in 2017.

  • ESBL prevalence was 55.8% in E. coli and 29.9% in Klebsiella spp.

  • NDM producing bacteria were identified as E. coli 31.1%, Klebsiella pneumoniae 26.7%, Acinetobacter calcoacelicus 20%.

Philippines

  • ~41.3% of the population has positive bacterial isolates, with >50% being gram-negative bacteria.

  • Leading causes of healthcare-associated bloodstream infections include E. coli, Klebsiella spp., A. baumannii, and Pseudomonas spp.

  • Carbapenem resistance rate in K. pneumoniae rose from under 6% (until 2013) to 11.9% in 2017.

  • According to a study, 36.8% of the total isolates tested (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis) were positive for ESBL production in the Philippines and have reported increase in resistance.

  • NDM is the most common type of MBL in Philippines with a prevalence of 58.5%, followed by IMP with 7.3% and VIM with 4.8%.

France

  • In 2017, 68,581 patients were hospitalized, with P. aeruginosa (15.0%) being the most frequently isolated microorganism.

  • Gram-negative BSIs are predominant: 39% hospital-acquired, 45% community-acquired, and 16% other health care-associated.

  • Carbapenemase-producing E. coli isolates multiplied fivefold between 2012-2014.

  • 5,543 deaths occurred due to multi-drug resistant bacterial infection

Mexico

  • Hospital infection frequency ranges from 2.1% to 15.8% of admitted patients.

  • Gram-negative bacilli caused 51.2% of NBSIs, with K. pneumoniae (30.4%) and E. coli (18.9%) being most common.

  • Highest MDR phenotype frequency was observed for A. baumannii (74%), followed by E. coli (40%) and P. aeruginosa (34%).

  • 1/10th of E. coli isolates produce ESBL.

Greece

  • Greece is a highly endemic area for multidrug-resistant pathogens, mainly carbapenem-resistant gram-negative bacteria.

  • E. coli is the most prevalent pathogen in community and hospital settings, with ~4% growth between 2013-2018.

  • The percentage distribution of key pathogens in 2018 is E. coli (39%), Klebsiella spp. (24%), P. aeruginosa (18%), Acinetobacter (13%), and Enterobacter spp. (6%).

  • Patients with Carbapenem-resistant increased over the last five years in Greece

India

  • Gram-negative infections account for 68% of all bacterial infections.

  • E. coli, Acinetobacter spp., P. aeruginosa, and Klebsiella spp. contribute to 82% of gram-negative BSIs.

  • In 2017, 77% of A. baumannii, 59% of K. pneumoniae, 30% of P. aeruginosa, and 18% of E. coli were carbapenem-resistant.

  • ESBL production was confirmed in 87% of all gram negative bacteria.
    Amongst isolates in the five genera (Pseudomonas* spp., Acinetobacter spp., Klebsiella spp., E. coli & Enterobacter) which were resistant to carbapenems, MBL production was confirmed in 52%

Kuwait

  • Hospitalized patient infection rate was 11%.

  • E. coli is the predominant pathogen in both CA-UTI and HA-UTI cases.

  • Prevalence of antibiotic resistance was highest in E. coli (77%) followed by K. pneumoniae (36.2%), Acinetobacter (16.7%), and P. aeruginosa (2.6%).
    *Most common ESBL producing isolates are 81% *E. coli* and 44% Klebsiella pneumoniae.

Italy

  • Gram negative bacteria accounts for more than 50% infections in Italy, E. coli (40%) being the most prevalent among gram negative bacteria

  • Anticrobial consumption is among the highest of all EU/EEA Member States in Italy

  • A. baumannii had the highest carbapenem resistance rate at 80%, followed by K. pneumoniae at 32%, P. aeruginosa at 24% and E. coli at 0.1%

  • molecular analysis revealed three types of MBL genes circulating in Italy namely, blaVIM1blaVIM-1, blaVIM2blaVIM-2, and blaIMP13blaIMP-13

Spain

  • In Spain, total infections* increased at a rate of ~2-3% during 2013-17, decreased by ~2% in 2018
    Number of patients with nosocomial infection and community based infections increased during 2013-17 while a decline was observed in 2018 by 9% & 5% resp.
    *total ESBL resistance for E. coli was 77.51% followed by K. pneumoniae (20.71%), ~91% of which belong to OXA-48 type
    *Majority of deaths in patients with MDR bacteria infections are due to Carbapenem-resistant to E. coli, K. pneumoniae and P. aeruginosa

Russia

*Hospital acquired infections (HAI) were found to be more prevalent and accounted for ~66% on an average during 2013-16
*Rates of Carbapenem resistance in Acinetobacter increased to 94% in 2017 from 61% in 2015 while E. coli showed least resistant rates
*High level of CR pattern observed in Acinetobacter from 2015-17 towards Imipenem, Doripenem & Meropenem