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During November to December 2020, a high rate of COVID-19-associated pneumonia with bacterial superinfections due to multidrug-resistant (MDR) pathogens was recorded in a COVID-19 hospital in Zagreb. This study analyzed the causative agents of bacterial superinfections among patients with serious forms of COVID-19. In total, 118 patients were hospitalized in the intensive care unit (ICU) of the COVID-19 hospital. Forty-six out of 118 patients (39%) developed serious bacterial infection (VAP or BSI or both) during their stay in ICU. The total mortality rate was 83/118 (70%). The mortality rate due to bacterial infection or a combination of ARDS with bacterial superinfection was 33% (40/118). Six patients had MDR organisms and 34 had XDR (extensively drug-resistant). The dominant species was Acinetobacter baumannii with all isolates (34) being carbapenem-resistant (CRAB) and positive for carbapenem-hydrolyzing oxacillinases (CHDL). One Escherichia coli causing pneumonia harboured the blaCTX-M-15 gene. It appears that the dominant resistance determinants of causative agents depend on the local epidemiology in the particular COVID center. Acinetobacter baumannii seems to easily spread in overcrowded ICUs. Croatia belongs to the 15 countries in the world with the highest mortality rate among COVID-19 patients, which could be in part attributable to the high prevalence of bacterial infections in local ICUs.

Significance and Impact of the Study: It is well-known that surgical preoperative prophylaxis with broad spectrum antibiotics can select multidrug-resistant Gram-negative bacteria and change the oral microbiome. This prompted us to analyse oral microbiome before and after prophlylactic dose of antibiotics. The main finding of the study is that the prophlylactic application of antibiotics is associated with the colonization of oral cavity with Gram-negative bacteria. Marked diversity of Gram-negative bacteria and resistance mechanisms was found. High resistance rates and acquired extended-spectrum blactamases (ESBL) and carbapenemase encoding genes were found among Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolates. The dominant resistance mechanisms were the production of ESBLs and carbapenemases.

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