Abstract
Antimicrobial resistance in poultry is a major global health concern. Inappropriate use of antibiotics in poultry production contributes to increased bacterial resistance and the production of broad-spectrum beta-lactamase enzymes, posing a risk to human and animal health. Enteric bacteria, including Klebsiella pneumoniae, are among the most important of these bacteria. Therefore, this study aimed to identify beta-lactamase-resistant strains of K. pneumoniae isolated from poultry farms in Salah al-Din Governorate, Iraq. Furthermore, innate immune responses and pathogenicity were assessed using a mouse infection model. Sixty cloacal swabs were collected from a poultry farm. The isolates were identified using selective culture media , biochemical assays, and the VITEK 2 system, and their antibiotic susceptibility was determined using the disc diffusion method. In addition, a multidrug-resistant ESBLs-producing isolate was used in a mouse infection model to determine the median lethal dose (LD₅₀). TLR2 and TLR4 levels were measured using an ELISA assay to assess innate immune responses , and histopathological changes in liver, kidney, and spleen organs were assessed by hematoxylin and eosin (HandE) staining. Twenty-three isolates (38.3%) were confirmed as Klebsiella pneumoniae in phenotypic ESB. All isolates exhibited complete (100%) resistance to amoxicillin/clavulanic acid, ceftazidime, and cephalexin and moderate resistance was observed to aztreonam (56.5%) and streptomycin (47.8%) , indicating the presence of multidrug-resistant strains. The median lethal dose (LD₅₀) was recorded at 3.1 × 10⁷ CFU/ml. The TLR2 and TLR4 levels through 14 days were significantly elevated throughout the infection period, indicating continued activation of the innate immune response. Furthermore, Histopathological examination revealed necrotic lesions and severe inflammation in the liver, kidneys, and spleen. Current findings indicate that poultry farms may serve as a reservoir for multidrug-resistant K. pneumoniae, producing wide-type beta-lactamases is mainly linked with antibiotic misuse on farms. The findings of this study indicate the necessity to work further to enhance the adherence of antibiotic usage and biosecurity practices, and to emphasize the One Health concept in the poultry sector in Iraq.

Key words: ESBL-Producing Klebsiella pneumonia, Growth promotion antibiotics, Histopathology, Poultry, TLR2, TLR4.