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The emergence of extensive drug-resistant (XDR)  Salmonella  in livestock animals especially in poultry represents a serious public health and therapeutic challenge. Despite the wealth of information available on  Salmonella  resistance to various antimicrobials, there have been limited data on the genetic determinants of XDR  Salmonella  exhibiting co-resistance to ciprofloxacin (CIP) and tigecycline (TIG). This study aimed to determine the prevalence and serotype diversity of XDR  Salmonella  in poultry flocks and contact workers and to elucidate the genetic determinants involved in the co-resistance to CIP and TIG. Herein, 115  Salmonella enterica  isolates of 35 serotypes were identified from sampled poultry (100/1210, 8.26%) and humans (15/375, 4.00%), with the most frequent serotype being  Salmonella  Typhimurium (26.96%). Twenty-nine (25.22%)  Salmonella enterica  isolates exhibited XDR patterns; 25 out of them (86.21%) showed CIP/TIG co-resistance. Exposure of CIP- and TIG-resistant isolates to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor resulted in an obvious reduction in their minimum inhibitory concentrations (MICs) values and restored the susceptibility to CIP and TIG in 17.24% (5/29) and 92% (23/25) of the isolates, respectively. Molecular analysis revealed that 89.66% of the isolates contained two to six plasmid-mediated quinolone resistance genes with the predominance of  qepA  gene (89.66%). Mutations in the  gyrA  gene were detected at codon S83 (34.62%) or D87 (30.77%) or both (34.62%) in 89.66% of XDR  Salmonella . The  tet (A) and  tet (X4) genes were detected in 100% and 3.45% of the XDR isolates, respectively. Twelve TIG-resistant XDR  Salmonella  had point mutations at codons 120, 121, and 181 in the  tet(A)  interdomain loop region. All CIP and TIG co-resistant XDR  Salmonella  overexpressed  ramA  gene; 17 (68%) out of them harbored 4-bp deletion in the  ramR  binding region (T-288/A-285). However, four CIP/TIG co-resistant isolates overexpressed the  oqxB  gene. In conclusion, the emergence of XDR  S. enterica  exhibiting CIP/TIG co-resistance in poultry and humans with no previous exposure to TIG warrants an urgent need to reduce the unnecessary antimicrobial use in poultry farms in Egypt.

frontiers in microbiology

Extensive Drug-Resistant Salmonella enterica Isolated From Poultry and Humans: Prevalence and Molecular Determinants Behind the Co-resistance to Ciprofloxacin and Tigecycline