Evolution of the Gram-Negative Antibiotic Resistance Spiral over Time: A Time-Series Analysis

Abstract

We followed up the interplay between antibiotic use and resistance over time in a tertiary-care hospital in Hungary. Dynamic relationships between monthly time-series of antibiotic consumption data (defined daily doses per 100 bed-days) and of incidence densities of Gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or carbapenems were followed using vector autoregressive models sequentially built of time-series ending in 2015, 2016, 2017, 2018, and 2019. Relationships with Gram-negative bacteria as a group were fairly stable across years. At species level, association of cephalosporin use and cephalosporin resistance of E. coli was shown in 2015–2017, leading to increased carbapenem use in these years. Association of carbapenem use and carbapenem resistance, as well as of carbapenem resistance and colistin use in case of A. baumannii, were consistent throughout; associations in case of Klebsiella spp. were rarely found; associations in case of P. aeruginosa varied highly across years. This highlights the importance of temporal variations in the interplay between changes in selection pressure and occurrence of competing resistant species.

The Effect of Decreased Antipseudomonal Drug Consumption on Pseudomonas aeruginosa Incidence and Antimicrobial Susceptibility Profiles over 9 Years in a Lebanese Tertiary Care Center

“…Although some studies report a correlation between hospital resistance of PAE and carbapenem consumption levels [19], our results echo the findings of Álvarez-Marín et al (2021) showing that the correlation between carbapenem consumption and incidence density of carbapenem-resistant Pseudomonas Aeruginosa is minimal [20]. Importantly, the decrease in consumption of antibiotics was noted to have a greater impact on resistance in the case of Acinetobacter baumanii [8,[21][22][23]. All these findings show that even though antimicrobial selective pressure plays a role in antibiotic resistance [24,25], mechanisms of antimicrobial resistance of are multifactorial (such as carrying resistance genes and other mechanisms) [9,13,26], with a variable role of antimicrobial selective pressure depending on the pathogen, which is akin to the results of other studies [7,9,18,21,27].…”

“…Resistance of PAE results in delays in adequate antimicrobial therapy and unfavorable clinical outcomes [5][6][7]. Patterns of antibiotic resistance in PAE change over time [8] and differ by type of infection, sometimes resulting in limited therapeutic options [9]. More epidemiological surveillance studies on antimicrobial susceptibility profiles of PAE are needed to generate clinically significant data to better guide therapeutic options [10].…”

“…The correlation between antibiotic consumption and resistance changes dynamically over time and depends on several factors and thus should not be viewed as a constant [8]. Therefore, factors that may play a modulating role between antibiotic consumption and resistance among PAE isolates in Lebanon need to be further investigated.…”

“…Resistance of PAE results in delays in adequate antimicrobial therapy and unfavorable clinical outcomes [5][6][7]. Patterns of antibiotic resistance in PAE change over time [8] and differ by type of infection, sometimes resulting in limited therapeutic options [9].…”

Infections in the critically ill patient: new challenges of an old problem

“…Six pathogens accounted for 73.4% (66.9–78.8%) of deaths attributable to bacterial AMR and seven pathogen–drug combinations each caused more than 50 000 deaths [8]. The rising prevalence of AMR may lead to a more resistance–more antibiotic spiral, meaning a process of ever switching towards broader spectrum drugs when resistance to presently used ones is felt to be threatening, which leads to overuse of and, consequently, resistance to the replacement drug in a vicious cycle until all therapeutic options are exhausted [9].…”