Intestinal Exposure to Ceftiofur and Cefquinome after Intramuscular Treatment and the Impact of Ceftiofur on the Pig Fecal Microbiome and Resistome

Abstract

Optimization of antimicrobial treatment during a bacterial infection in livestock requires in-depth knowledge of the impact of antimicrobial therapy on the pathogen and commensal microbiota. Once administered antimicrobials and/or their metabolites are excreted either by the kidneys through urine and/or by the intestinal tract through feces, causing antimicrobial pressure and possibly the emergence of resistance in the gastro-intestinal tract. So far, the excretion of ceftiofur and cefquinome in the intestinal tract of pigs has not been described. The objective of this study was to investigate the excretion of ceftiofur and cefquinome in the different segments of the gut and feces after intramuscular administration. Therefore, 16 pigs were treated either with ceftiofur (n = 8) or cefquinome (n = 8), and feces were collected during the entire treatment period. The presence of ceftiofur and desfuroylceftiofuracetamide or cefquinome were quantified via liquid chromatography–tandem mass spectrometry. At the end of the treatment, pigs were euthanized, and samples from the duodenum, jejunum, ileum and cecum were analyzed. In feces, no active antimicrobial residues could be measured, except for one ceftiofur-treated pig. In the gut segments, the concentration of both antimicrobials increased from duodenum toward the ileum, with a maximum in the ileum (187.8 ± 101.7 ng·g−1 ceftiofur-related residues, 57.8 ± 37.5 ng·g−1 cefquinome) and sharply decreased in the cecum (below the limit of quantification for ceftiofur-related residues, 6.4 ± 4.2 ng·g−1 cefquinome). Additionally, long-read Nanopore sequencing and targeted quantitative polymerase chain reaction (qPCR) were performed in an attempt to clarify the discrepancy in fecal excretion of ceftiofur-related residues between pigs. In general, there was an increase in Prevotella, Bacteroides and Faecalibacterium and a decrease in Escherichia and Clostridium after ceftiofur administration (q-value < 0.05). The sequencing and qPCR could not provide an explanation for the unexpected excretion of ceftiofur-related residues in one pig out of eight. Overall, this study provides valuable information on the gut excretion of parenteral administered ceftiofur and cefquinome.

Cefquinome shows a higher impact on the pig gut microbiome and resistome compared to ceftiofur

“…tetQ and CfxA6 ) were mostly associated with either Prevotella and/or Bacteroides . This is in line with our previous study, where Prevotella and Bacteroides were the main genera of interest [ 16 ].…”

“…In our previous study, shotgun sequencing was applied to investigate both the effect of conventional ceftiofur administration on the microbiome as well as on the resistome in pig feces instead of 16S rRNA analysis [ 16 ]. Consequently, when comparing the microbiome results of this previous study and the current study, some discrepancies emerged.…”

“…Third- and fourth-generation cephalosporins are administered intramuscularly because of their low oral bioavailability. Interestingly, this route of administration prevents direct exposure of the gastro-intestinal tract to these antimicrobials, however, after absorption they may partly get excreted into the intestinal tract [ 16 ]. Studies have confirmed the selective effect on resistance of these third- and fourth-generation cephalosporins on the gut microbiome, and especially on the resistance selection in Escherichia coli [ 17 , 18 ].…”

“…Building on our previous preliminary findings, a combinational metagenomic analysis was applied to determine the effect on the microbiome and resistome after a full treatment schedule with two important veterinary cephalosporins, ceftiofur and cefquinome [ 16 ]. Here, long-read nanopore 16S rRNA gene sequencing and associated diversity and composition analyses were performed.…”

Evaluating Mosquito Biocontrol Effectiveness by Isolating and Characterizing Some Fungi Against Culex Pipiens and Anopheles Stephensi in Sothern Part of Iraq

“…The lack of a lasting effect is a major drawback, even though exposure for just one day is sufficient to result in a considerable death rate. By looking for tolerant isolates and formulations, this can be resolved (Rutjens, 2023). According to observations made by Lord et al (1987), Wilson et al (1990), andSandhu et al (1993), infection can also move from larvae to adults.…”