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. 2023 Aug 31;64(4):272-283.
doi: 10.3325/cmj.2023.64.272.

The burden of bacterial antimicrobial resistance in Croatia in 2019: a country-level systematic analysis

Affiliations

The burden of bacterial antimicrobial resistance in Croatia in 2019: a country-level systematic analysis

Tomislav Meštrović et al. Croat Med J. .

Abstract

Aim: To deliver the most wide-ranging set of antimicrobial resistance (AMR) burden estimates for Croatia to date.

Methods: A complex modeling approach with five broad modeling components was used to estimate the disease burden for 12 main infectious syndromes and one residual group, 23 pathogenic bacteria, and 88 bug-drug combinations. This was represented by two relevant counterfactual scenarios: deaths/disability-adjusted life years (DALYs) that are attributable to AMR considering a situation where drug-resistant infections are substituted with sensitive ones, and deaths/DALYs associated with AMR considering a scenario where people with drug-resistant infections would instead present without any infection. The 95% uncertainty intervals (UI) were based on 1000 posterior draws in each modeling step, reported at the 2.5% and 97.5% of the draws' distribution, while out-of-sample predictive validation was pursued for all the models.

Results: The total burden associated with AMR in Croatia was 2546 (95% UI 1558-3803) deaths and 46958 (28,033-71,628) DALYs, while the attributable burden was 614 (365-943) deaths and 11321 (6,544-17,809) DALYs. The highest number of deaths was established for bloodstream infections, followed by peritoneal and intra-abdominal infections and infections of the urinary tract. Five leading pathogenic bacterial agents were responsible for 1808 deaths associated with resistance: Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa (ordered by the number of deaths). Trimethoprim/sulfamethoxazole-resistant E coli and methicillin-resistant S. aureus were dominant pathogen-drug combinations in regard to mortality associated with and attributable to AMR, respectively.

Conclusion: We showed that AMR represented a substantial public health concern in Croatia, which reflects global trends; hence, our detailed country-level findings may fast-track the implementation of multipronged strategies tailored in accordance with leading pathogens and pathogen-drug combinations.

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Figures

Figure 1
Figure 1
Death counts attributable to antimicrobial resistance (AMR) by pathogen-drug combination in Croatia in 2019. Abbreviations: 3GC - third-generation cephalosporins. 4GC - fourth-generation cephalosporins. Anti-pseudomonal - anti-pseudomonal penicillin or beta-lactamase inhibitors. BL-BLI - beta-lactam or beta-lactamase inhibitors. MDR - multidrug resistance. mono INH - isoniazid mono-resistance. mono RIF - rifampicin mono-resistance. NA - not applicable. Resistance to 1+ - resistance to one or more drug. TMP-SMX - trimethoprim-sulfamethoxazole. XDR - extensive drug resistance; AG - aminoglycosides; CP – carbapenems; FQ – fluoroquinolones; PCN – penicillin; TB – tuberculosis.
Figure 2
Figure 2
Death counts associated with antimicrobial resistance (AMR) by pathogen–drug combination in Croatia in 2019. Abbreviations: 3GC - third-generation cephalosporins. 4GC - fourth-generation cephalosporins. Anti-pseudomonal - anti-pseudomonal penicillin or beta-lactamase inhibitors. BL-BLI - beta-lactam or beta-lactamase inhibitors. MDR - multidrug resistance. mono INH - isoniazid mono-resistance. mono RIF - rifampicin mono-resistance. NA - not applicable. Resistance to 1+ - resistance to one or more drug. TMP-SMX - trimethoprim-sulfamethoxazole. XDR - extensive drug resistance; AG - aminoglycosides; CP – carbapenems; FQ – fluoroquinolones; PCN – penicillin; TB – tuberculosis.
Figure 3
Figure 3
Disability-adjusted life year (DALY) counts attributable to antimicrobial resistance (AMR) by pathogen-drug combination in Croatia in 2019. Abbreviations: 3GC - third-generation cephalosporins. 4GC - fourth-generation cephalosporins. Anti-pseudomonal - anti-pseudomonal penicillin or beta-lactamase inhibitors. BL-BLI - beta-lactam or beta-lactamase inhibitors. MDR - multidrug resistance. mono INH - isoniazid mono-resistance. mono RIF - rifampicin mono-resistance. NA - not applicable. Resistance to 1+ - resistance to one or more drug. TMP-SMX - trimethoprim-sulfamethoxazole. XDR - extensive drug resistance; AG - aminoglycosides; CP – carbapenems; FQ – fluoroquinolones; PCN – penicillin; TB – tuberculosis.
Figure 4
Figure 4
Disability-adjusted life year (DALY) counts associated with antimicrobial resistance (AMR) by pathogen-drug combination in Croatia in 2019. Abbreviations: 3GC - third-generation cephalosporins. 4GC - fourth-generation cephalosporins. Anti-pseudomonal - anti-pseudomonal penicillin or beta-lactamase inhibitors. BL-BLI - beta-lactam or beta-lactamase inhibitors. MDR - multidrug resistance. mono INH - isoniazid mono-resistance. mono RIF - rifampicin mono-resistance. NA - not applicable. Resistance to 1+ - resistance to one or more drug. TMP-SMX - trimethoprim-sulfamethoxazole. XDR - extensive drug resistance; AG - aminoglycosides; CP – carbapenems; FQ – fluoroquinolones; PCN – penicillin; TB – tuberculosis.

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