Third Generation Cephalosporin Resistant Enterobacterales Infections in Hospitalized Horses and Donkeys: A Case–Case–Control Analysis

Abstract

In human medicine, infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCRE) are associated with detrimental outcomes. In veterinary medicine, controlled epidemiological analyses are lacking. A matched case–case–control investigation (1:1:1 ratio) was conducted in a large veterinary hospital (2017–2019). In total, 29 infected horses and donkeys were matched to 29 animals with third-generation cephalosporin-susceptible Enterobacterales (3GCSE) infections, and 29 uninfected controls (overall n = 87). Despite multiple significant associations per bivariable analyses, the only independent predictor for 3GCRE infection was recent exposure to antibiotics (adjusted odds ratio (aOR) = 104, p < 0.001), but this was also an independent predictor for 3GCSE infection (aOR = 22, p < 0.001), though the correlation with 3GCRE was significantly stronger (aOR = 9.3, p = 0.04). In separated multivariable outcome models, 3GCRE infections were independently associated with reduced clinical cure rates (aOR = 6.84, p = 0.003) and with 90 days mortality (aOR = 3.6, p = 0.003). Klebsiella spp. were the most common 3GCRE (36%), and blaCTX-M-1 was the major β-lactamase (79%). Polyclonality and multiple sequence types were evident among all Enterobacterales (e.g., Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae). The study substantiates the significance of 3GCRE infections in equine medicine, and their independent detrimental impact on cure rates and mortality. Multiple Enterobacterales genera, subtypes, clones and mechanisms of resistance are prevalent among horses and donkeys with 3GCRE infections.

Characterisation of and risk factors for extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) in an equine hospital with a special reference to an outbreak caused by Klebsiella pneumoniae ST307:CTX-M-1

“…Multidrug resistance indicated by resistance to three or more different antimicrobial classes [ 32 ] was noted for all ESBL-E isolates that caused a clinical infection in our study population. The resistance to different antimicrobials was also very similar to the antibiograms published in the study by Shnaiderman-Torban [ 33 ]. The only remarkable difference was the susceptibility to amikacin; in our study 92% of the strains were susceptible to amikacin, whereas only 76% of the ESBL-E were susceptible to amikacin in the Shnaiderman-Torban study [ 33 ].…”

“…The resistance to different antimicrobials was also very similar to the antibiograms published in the study by Shnaiderman-Torban [ 33 ]. The only remarkable difference was the susceptibility to amikacin; in our study 92% of the strains were susceptible to amikacin, whereas only 76% of the ESBL-E were susceptible to amikacin in the Shnaiderman-Torban study [ 33 ]. This might reflect the habits of antimicrobial usage as horses in Finland extremely seldom receive amikacin due to financial restraints whereas in Israel most foals admitted to the hospital receive ampicillin and amikacin for broad-spectrum antimicrobial coverage [ 34 ].…”

Occurrence and Antimicrobial Susceptibility Profiles of Streptococcus equi subsp. zooepidemicus Strains Isolated from Mares with Fertility Problems

“…Fluoroquinolones, as well as third-generation cephalosporins, are considered by World Health Organization (WHO) as critically important antimicrobials in human medicine, classified with the priority criterion 1 [ 43 ]. Consequently, the growing percentage of resistance against these antibiotics represent a serious concern of public health with important implication for clinical practice both in human and veterinary medicine [ 44 , 45 ]. Traditionally sulfonamides are considered to have good antimicrobial activity against S. zooepidemicus , with low resistance rates as stated by Feary et al [ 46 ].…”

Antimicrobial resistance and genetic diversity of Klebsiella pneumoniae strains from different clinical sources in horses

“…A recent Israeli case control study on 3GC-resistant Enterobacterales infections in hospitalized horses and donkeys showed that the Klebsiella spp. were the most common 3GC-resistant Enterobacterales detected ( Shnaiderman-Torban et al, 2021 ). However, it remains difficult to detect high-risk clonal lineages of K. pneumoniae through epidemiological and genomic analyses in horses (e.g., Trigo da Roza et al, 2019 ; Loncaric et al, 2020 ; Shnaiderman-Torban et al, 2021 ).…”