Carbapenem-Resistant Enterobacterales Characterized in Region of Middle East

The most common of carbapenem resistant enterobacterales (CRE) infections in Saudi Arabia is attributed to Klebsiela pneumoniae carrying the beta-lactamase (bla) gene blaOXA-48, in a large prospective cohort study which the investigators hope will inform future studies into prevention and treatment.

"Knowledge regarding the molecular epidemiology of CRE in Gulf countries and in the Middle East in general is limited," observed lead author Basem Alraddadi, MD, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia and colleagues.

In a review of CRE treatment considerations in this era of evolving enzymology, Maxwell Lasko, PharmD, and David Nicolau, PharmD, Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, affirm that OXA carbapenemases are endemic to the Middle East, as well as Europe and Northern Africa. They note that the Klebsiella pneumoniae carbapenemase (KPC) is the most prominent in North America and Israel, and the metallo-β-lactamase (MBL) in India, Italy and Greece.

Although a region's most prevalent carbapenemase may not be the source of an individual's treatment-resistant infection (which may not only arise from another carbapenemase, but also from non-carbapenemase mechanisms) data on prevalence could help in the choice of initial, empiric therapy. Lasko and Nicolau point out, for example, that the OXA-48 found in the Middle East is a serine-based carbapenemase which will hydrolyze carbapenems but will not counter ceftazidime and cefepime activity.

Alraddadi and colleagues note that most other studies that have identified OXA-48 the most prevalent carbapenemase in the Middle East were retrospective and based on smaller sample sizes than in the current study. In this prospective study, the investigators identified 189 patients 14 years of age or older (median 62.8 years) over a 28-month period from August 2018 through November 2020, from eight hospital systems in Saudi Arabia.

Patients had a positive CRE culture with Escherichia coli or Klebsiella pneumoniae and a clinically established infection. The interpretation of the minimum inhibitory concentration (MIC) for carbapenems was based on CLSI guidelines; with resistance to ertapenem defined at MIC ≥2μg/ml and to imipenem at ≥4μg/ml. Phenotype of CRE isolates were differentiated for the bla genes KPC, NDM, VIM and OXA-48. The primary outcome in the study was 30-day all-cause mortality; with secondary measures including length of hospital stay, relapse within 30 days and acute kidney injury.

Alraddadi and colleagues reported that the most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%); and 77 patients (40.7%) had CRE bacteremia. A clinical cure was attained in 100 patients (52.9%); 57 (30.2%) died within 30 days and 23 (12.2%) relapsed. Multivariable analysis revealed CRE bacteremia as an independent predictor of 30 day all-cause mortality.

In their review, Lasko and Nicolau describe the CRE as among the group of organisms that are the most difficult treat. "It is no surprise that the CDC considers them to be one of the top three most urgent threats, with resistance spreading rapidly in the USA and throughout the world," they wrote.

Alraddadi and colleagues indicate that their study helps to define the burden of CRE infection in the region, as well as the phenotypic epidemiology, and the therapeutic approaches being applied. "This information will inform local and global preventive and therapeutic interventoin protocols for CRE infection," they conclude.