OXA-48 Carbapenemase-Producing Enterobacterales in Spanish Hospitals: An Updated Comprehensive Review on a Rising Antimicrobial Resistance

Abstract

Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by the WHO as high-priority pathogens given their association with morbidity and mortality and the scarce number of effective antibiotic treatments. In Spain, the frequency of OXA-48 CPE outbreaks is higher than in other European countries, representing the major resistance mechanism of CPEs. Horizontal transfer of plasmids and poor effective antibiotic treatment are additional threats to the correct prevention and control of these hospital outbreaks. One of the most important risk factors is antibiotic pressure, specifically carbapenem overuse. We explored the use of these antibiotics in Spain and analyzed the frequency, characteristics and prevention of CPE outbreaks. Future antibiotic stewardship programs along with specific preventive measures in hospitalized patients must be reinforced and updated in Spain.

Keywords: OXA-48; Spain; antibiotic stewardship; carbapenem; carbapenemase; enterobacteria; multiresistant; outbreak.

Figure 1

Classification of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE), based on the Ambler classification.

Figure 2

Prevalence of antibiotic use in hospitalized patients in the different autonomous communities in Spain in 2019. Ceuta (red) and Melilla (yellow) are located in North Africa. The percentages represent the prevalence of antibiotic use in hospitalized patients registered in the report from Spain on the prevalence of healthcare-related and community infections and the use of antibiotics (EPINE-EPPS study) in the year 2019 [68].