Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans

Abstract

Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter baumannii, are among the major opportunistic pathogens involved in the global antibiotic resistance epidemic. They are designated as urgent/serious threats by the Centers for Disease Control and Prevention and are part of the World Health Organization's list of critical priority pathogens. Also, Stenotrophomonas maltophilia is increasingly recognized as an emerging cause for healthcare-associated infections in intensive care units, life-threatening diseases in immunocompromised patients, and severe pulmonary infections in cystic fibrosis and COVID-19 individuals. The last annual report of the ECDC showed drastic differences in the proportions of NFGNB with resistance towards key antibiotics in different European Union/European Economic Area countries. The data for the Balkans are of particular concern, indicating more than 80% and 30% of invasive Acinetobacter spp. and P. aeruginosa isolates, respectively, to be carbapenem-resistant. Moreover, multidrug-resistant and extensively drug-resistant S. maltophilia from the region have been recently reported. The current situation in the Balkans includes a migrant crisis and reshaping of the Schengen Area border. This results in collision of diverse human populations subjected to different protocols for antimicrobial stewardship and infection control. The present review article summarizes the findings of whole-genome sequencing-based resistome analyses of nosocomial multidrug-resistant NFGNBs in the Balkan countries.

Keywords: Balkans; extensive drug resistance (XDR); multidrug resistance (MDR); non-fermenting gram-negative bacilli; resistome analysis; whole-genome sequencing.

Figure 1

Geographic distribution of invasive carbapenem-resistant Acinetobacter spp. and P. aeruginosa on the Balkans according to the 2020 annual report of the ECDC [37]. CR, carbapenem-resistant; CRPA, carbapenem-resistant P. aeruginosa; EU, European Union; SA, Schengen Area.

Figure 2

Geographic distribution of invasive multidrug-resistant Acinetobacter spp. and P. aeruginosa on the Balkans according to the 2020 annual report of the ECDC [37]. MDR, multidrug-resistant; EU, European Union; SA, Schengen Area.

Figure 3

Linear map of a typical class 1 integron. IRi marks an inverted repeat that flanks the intI1 gene encoding class 1 integrase. The dotted rectangle represents a cassette array with a variable composition. The conserved sequence in the 3′ end of the integron includes qacEΔ1 (quaternary ammonium compound efflux SMR transporter), sul1 (dihydropteroate synthase type-1), and orf5 (unknown function). Below are the two gene cassettes found in isolates SM130 and SM148. The SM130 gene cassette contains the following genes: bla_OXA-74 (OXA-10 family class D b-lactamase OXA-74), aac(6′)-Ib-cr (fluoroquinolone-acetylating aminoglycoside acetyltransferase), and cmlA7 (chloramphenicol acetyltransferase). OXA, oxacillinase; SMR, small multidrug resistance.