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Background: Surgical site infections (SSIs), especially when caused by multidrug-resistant (MDR) bacteria, are a major healthcare concern worldwide. For optimal treatment and prevention of antimicrobial resistance, it is important for clinicians to be aware of local drug-resistant bacterial pathogens that cause SSIs. Objective: To determine the frequency patterns of drug-resistant bacterial strains causing SSIs at a tertiary care hospital in Saudi Arabia. Methods: This retrospective study was conducted at the Microbiology laboratory of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, and included wound swab samples from all cases of SSI between January 01, 2017, and December 31, 2021. The swabs were processed for the identification of bacterial strains and their resistance pattern to antibiotics according to the Clinical and Laboratory Standards Institute. Results: A total of 5409 wound swabs were analyzed, of which 3604 samples (66.6%) were from male. Most samples were from the Department of Surgery (43.3%). A total of 14 bacterial strains were isolated, of which 9 were Gram-negative bacteria. The most common isolates were Klebsiella pneumoniae, followed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). In terms of MDR in 2021, the highest rate of carbapenem-resistance was in A. baumannii (97%). MDR was as follows: A. baumannii, 97%; K. pneumoniae, 81%; E. coli, 71%; MRSA, 60%; P. aeruginosa, 33%; VRE, 22%; and VRSA, 2%. Conclusion: This study showed that in the city of Makkah, Saudi Arabia, the rates of MDR bacteria are high, with the majority being Gram-negative.
RESUMO
Being the most conserved region of all hepatitis C virus (HCV) genotypes and sub-genotypes, the 5' untranslated region (5' UTR) of HCV genome signifies it's importance as a potential target for anti-mRNA based treatment strategies like RNA interference. The advent and approval of first small interference RNA (siRNA) -based treatment of hereditary transthyretin-mediated amyloidosis for clinical use has raised the hopes to test this approach against highly susceptible viruses like HCV. We investigated the antiviral potential of consensus siRNAs targeted to stem-loops (SLs) II and III nucleotide motifs of internal ribosome entry site (IRES) structure within 5' UTR of HCV sub-genotype 4a isolates from the Saudi population. siRNA inhibitory effects on viral replication and translation of full-length HCV genome were determined in a competent, persistent, and reproducible Huh-7 cell culture system maintained for one month. Maximal inhibition of RNA transcript levels of HCV-IRES clones and silencing of viral replication and translation of full-length virus genome was demonstrated by siRNAs targeted to SL-III nucleotide motifs of IRES in Huh-7 cells. siRNA Usi-169 decreased 5' UTR RNA transcript levels of HCV-IRES clones up to 75% (P < 0.001) at 24 h post-transfection and 80% (P < 0.001) at 48 h treatment in Huh-7 cells. 5' UTR-tagged GFP protein expression was significantly decreased from 70 to 80% in Huh-7 cells co-transfected with constructed vectors (i.e. pCR3.1/GFP/5' UTR) and siRNA Usi-169 at 24 h and 48 h time-span. Viral replication was inhibited by more than 90% (P < 0.001) and HCV core (C) and hypervariable envelope glycoproteins (E1 and E2) expression was also significantly degraded by intracytoplasmic siRNA Usi-169 activity in persistent Huh-7 cell culture system. The findings unveil that siRNAs targeted to 5' UTR-IRES of HCV sub-genotype 4a Saudi isolates show potent silencing of HCV replication and blocking of viral translation in a persistent in-vitro Huh-7 tissue culture system. Furthermore, we also elucidated that siRNA silencing of viral mRNA not only inhibits viral replication but also blocks viral translation. The results suggest that siRNA potent antiviral activity should be considered as an effective anti-mRNA based treatment strategies for further in-vivo investigations against less studied and harder-to-treat HCV sub-genotype 4a isolates in Saudi Arabia.