engleski

Causative agents of bloodstream infections in two Croatian hospitals and their resistance mechanisms

Bloodstream infections (BSI) are life-threatening conditions. Inappropriate initial antimicrobial therapy leads to higher mortality in patients with septic shock [1]. Infections due to multidrug resistant (MDR) pathogens are prone to treatment failures and inappropriate empiric antimicrobial therapy, but whether drug resistance alone increases mortality in the setting of appropriate therapy is unclear. Bacterial resistance to antibiotics is growing up day by day, in both community and hospital setting, increasing morbidity and mortality. Therapy of invasive infections due to MDR Gram-negative bacteria is challenging, and some of the few active drugs are not available in many countries. Global spread of multiresistant pathogens and the lack of new antibiotics are limiting clinicians in the therapy of septicemia. Particularly important are ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species [2, 3]. Therapeutic failures are usually associated with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), extended-spectrum β- lactamase (ESBL) producing Enterobacterales, carbapenem-resistant Enterobacterales (CRE), carbapenem resistant Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB) [3]. Risk factors for acquiring bloodstream infections with MDR bacteria are: frequent antibiotic treatments, indwelling urinary and intravascular catheters, recent surgical procedures and stay in the hospital ICU. ESBLs hydrolyse expanded- spectrum cephalosporins (ESC) and render them inactive. The spread of plasmids carrying CTX-M type genes in the community beginning mostly in the 2000s is the main driver of ESBL dissemination in infections associated with Enterobacterales, including BSI isolates and replaced other ESBL enzymes (TEM and SHV) that were identified in hospital infections in the past [4, 5]. Previous studies revealed very high rates of ESBL producing Enterobacteriaceae associated with BSI in South America, the Far East and Mediterranean countries [6–8]. The rate of ESBLs in the previous studies ranged from 3% to 15%. CTX-M-15 ESBL was found in E. coli causing bloodstream infections in Croatia [9]. The isolates exhibited resistance to expanded-spectrum cephalosporins (ESC), gentamicin and ciprofloxacin. CTX-M- ESBLs are also dominant in South America [6, 7], but the SHV and TEM type are still present in some geographic areas such as the Far East [8]. In the previous studies the clinical outcome did not differ between patients with ESBL- positive and ESBL- negative infections. However, the prior usage of antibiotics and inappropriate empirical therapy was more frequent among patients with ESBL- positive organisms [8]. Haematologic malignancies and recent chemotherapy were more frequent in the ESBL- positive group (35% vs 8, 3%) and (54% vs 34%) respectively. A high level of resistance to ESC, gentamicin, and ciprofloxacin was noticed. Except for ESBLs, multidrug- resistant AmpC- producing organisms such as Enterobacter spp, Serratia spp and Citrobacter spp can also cause septicaemia and are challenging for treatment [10]. Carbapenems are usually the antibiotics of choice for the treatment of BSI due to ESBL- or AmpC- producing organisms. Recently, carbapenem-resistant isolates, associated with carbapenemases belonging to class A, B or D, were reported to be associated with BSI, particularly in developing countries [11, 12], contributing to the poor outcome. Carbapenem resistance in P. aeruginosa was shown to cause increased mortality in BSI [13]. In this study, blood samples were collected alongside with routine blood cultures (BC) from the patients with suspected sepsis, to evaluate the prevalence of different causative agents/positive BCs in patients with suspected bacteraemia, taken in the frames of the European FAPIC project (Fast assay for pathogen identification and characterization, Horizon, 2020).

multidrug-resistant bacteria ; Klebsiella pneumoniae ; Acinetobacter baumannii ; bloodstream infections ; extended-spectrum β-lactamases

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