Wafaa Alhazmi

Background: Doxorubicin (DOX) is a powerful anthracycline anti-neoplastic agent, and its therapeutic application is frequently restricted because of its liver-damaging effects. In this study, we found that DOX induces acute liver toxicity in rats, and the mechanisms underlying these effects were investigated. Purpose: This study aimed to assess the hepatoprotective effects of 2,3-dichloro-6-(trifluoromethoxy) quinoxaline (DTQ) against DOX-induced acute liver toxicity in rats and to investigate the underlying mechanisms involved. Materials and Methods: Male Wistar rats were administered an intraperitoneal dose of DOX on days 12–14 of the experiment to induce acute liver toxicity. The rats received DTQ (30 and 60 mg/kg, orally) continuously from day 1 for 14 days, along with DOX on days 12–14. Different biochemical parameters (liver function enzymes, lipid peroxidation, and oxidative stress) were measured. Results: DOX treatment increased the levels of liver function enzymes, lipid peroxidation, and oxidative stress by suppressing the production of antioxidant enzymes. Additionally, DOX treatment triggered the expression of pro-inflammatory cytokines and inflammatory mediators in the liver. Histological analysis further confirmed the structural liver damage resulting from DOX treatment. Conclusion: DTQ administration offered protection against the harmful effects of DOX on the liver, as indicated by the normalization of altered biochemical parameters and reduction in oxidative stress and inflammation. The results of this study indicate that DTQ exerts liver-protective effects against DOX-induced acute liver toxicity, likely due to its strong antioxidant and anti-inflammatory properties, which modulate the cellular signaling pathways.

Achromobacter species (spp) is an emerging opportunistic organism more frequently isolated from immunocompromised patients’ and hospital settings. This bacterium was once considered an environmental bacterium, but now it is recognized as a serious cause of respiratory infections, bloodstream infections, and urinary tract infections, particularly among patients with cystic fibrosis (CF), chronic illnesses, and medical devices. The purpose of this review is to highlight Achromobacte ’s clinical significance, pathogenic mechanism, and recent approaches for diagnosis and treatment. By utilizing specific keywords relevant to Achromobacter spp., a comprehensive literature search was performed in PubMed and Google Scholar. To summarize existing knowledge and highlight gaps in the literature, peer-reviewed studies on clinical relevance, pathogenicity, antimicrobial resistance, and therapeutic approaches were gathered, screened, and narratively assembled. Among the 19 identified species, Achromobacter xylosoxidans ( A. xylosoxidans) is the most prevalent and clinically relevant, especially in CF settings. This review explores the organism’s microbiological characteristics, virulence strategies—including robust biofilm formation, motility, and secretion systems—and its alarming intrinsic and acquired resistance to antibiotics. Misidentification due to phenotypic overlap with other non-fermenting Gram-negative bacilli complicates diagnosis, while limited MALDI-TOF MS and database representation hinders species-level identification. Genotyping methods, including multi-locus sequence analysis and housekeeping gene sequencing, offer superior resolution but remain underutilized in clinical diagnostics. With rising resistance mediated by β-lactamases, efflux pumps, and adaptive genomic traits, Achromobacter spp presents a growing challenge for treatment and infection control. This review highlights the urgent need for improved diagnostic strategies, species-level clinical and microbiological data, and tailored therapeutic approaches to manage Achromobacter spp. infections effectively.

Background/Objectives: Early and accurate quantification of Human Immunodeficiency Virus type 1 (HIV-1) viral load is essential for monitoring antiretroviral therapy and guiding clinical management. Although conventional real-time polymerase chain reaction (PCR) platforms provide reliable viral load measurement, they often require centralized laboratories and longer turnaround times. Cartridge-based systems such as the GeneXpert HIV-1 Viral Load assay offer a simplified testing workflow and may facilitate decentralized molecular testing. This study aimed to evaluate the qualitative and quantitative agreement between the GeneXpert HIV-1 Viral Load assay and the Abbott Alinity m HIV-1 assay. Methods: A total of 102 residual clinical Ethylenediaminetetraacetic acid (EDTA) plasma specimens were analyzed using both the GeneXpert HIV-1 Viral Load assay and the Abbott Alinity m HIV-1 assay. Qualitative agreement was evaluated using positive percent agreement (PPA), negative percent agreement (NPA), overall agreement, and Cohen’s κ coefficient. Quantitative agreement among specimens with paired quantifiable viral load results was assessed using Pearson’s correlation and Bland–Altman analyses. Results: Overall qualitative agreement between the two assays was 95.1%, with a PPA of 92.6%, an NPA of 100.0%, and a Cohen’s κ coefficient of 0.894, indicating almost perfect agreement. Among the 57 specimens with paired quantifiable viral load results, a very strong positive correlation was observed (Pearson’s r = 0.9972; 95% CI: 0.9952–0.9984; p < 0.001). Bland–Altman analysis demonstrated a minimal mean bias of −0.018 log₁₀ IU/mL, with 95% limits of agreement ranging from −0.175 to 0.139 log₁₀ International Units per milliliter (IU/mL). All paired quantitative differences were within the clinically accepted agreement threshold of ±0.5 log₁₀ IU/mL. Conclusions: The GeneXpert HIV-1 Viral Load assay demonstrated excellent qualitative and quantitative agreement with the Abbott Alinity m HIV-1 assay. These findings support the potential use of the GeneXpert HIV-1 Viral Load assay as an alternative testing platform for routine HIV-1 viral load monitoring in appropriate clinical settings.

Background: A member of the quinoxaline family, 2,3-dimethylquinoxaline (DMQ), has been evaluated for associated nephroprotective properties in an in vivo model system to assess renal inflammation induced by the anticancer drug doxorubicin (DOX). Methods: Rats were administered DMQ at doses of 30 or 60 mg/kg body weight once daily for 7 consecutive days. Additionally, a single intraperitoneal (i.p.) dose of DOX (15 mg/kg body weight) was administered on the sixth day. DMQ-mediated nephroprotective effects were assessed by measuring renal function markers, oxidative stress markers, lipid peroxidation, renal stress markers, proinflammatory cytokines, and inflammatory mediator levels, as well as by performing histopathological examination of kidney tissues. Results: DMQ-treated rats exhibited a marked reduction in kidney toxicity markers and restoration of antioxidant enzyme levels, leading to attenuated oxidative stress. DMQ administration also reduced proinflammatory cytokines, renal stress markers, and inflammatory mediators. Furthermore, DMQ may also attenuate DOX-induced renal structural damage and help restore the dilated capsular space and other histopathological alterations in kidney tissues. Conclusion: These findings suggest that DMQ may protect against DOX-induced renal damage by alleviating oxidative stress and inflammation in a rat model, indicating the potential of DMQ as a nephroprotective agent.

Klebsiella pneumoniae is a major opportunistic pathogen responsible for a wide range of hospital- and community-acquired infections, including respiratory tract infections, urinary tract infections, meningitis, and liver abscesses. Among its emerging forms, hypervirulent K. pneumoniae (hvKp) has gained global attention due to its heightened virulence and ability to cause severe infections in healthy individuals. hvKp differs from classical K. pneumoniae (cKp) in its clinical presentation, often causing metastatic infections, liver abscesses without biliary disease, and multiple-site involvement. Despite initial antibiotic susceptibility, the recent convergence of hvKp virulence traits with antimicrobial resistance genes—especially those conferring multidrug resistance (MDR) and carbapenem resistance—poses a serious therapeutic challenge. This review highlights the epidemiological and clinical distinctions between hvKp and cKp, emphasizing the limitations of current diagnostic markers like the string test. Furthermore, it explores novel therapeutic strategies beyond conventional antibiotics, focusing on promising alternatives such as bacteriophage therapy and antimicrobial peptides (AMPs). Several phages, including PSKP16, vB_Kpn_F13, and phage cocktails, have demonstrated potent activity against hvKp strains, including biofilm-forming and carbapenem-resistant isolates. Likewise, AMPs such as Osmin, AA139-nanoformulations, and scorpion venom-derived Cm38 show efficacy in preclinical models. These emerging approaches hold potential to combat the rising threat of hvKp, especially strains that are extensively drug-resistant. Continued research and investment are essential to translate these findings into clinical practice and ensure effective management of hypervirulent and resistant K. pneumoniae infections.

The increasing prevalence of Candida infections is a major healthcare challenge, underscoring the need for novel therapeutic agents. In this study, we evaluated the antifungal and anti-inflammatory activity of 2,3-dichloro-6-(trifluoromethoxy) quinoxaline against various Candida and Aspergillus species using both in vitro and in vivo models. Using the broth microdilution method, 21 reference strains were evaluated, revealing notable fungicidal activity particularly against Candida glabrata and Candida krusei, while variable susceptibility was observed in C. albicans, C. tropicalis, and C. parapsilosis. However, no activity was detected against Aspergillus species. In the oral candidiasis mice model, significant antifungal efficacy was confirmed against C. albicans. Moreover, 2,3-dichloro-6-(trifluoromethoxy) quinoxaline exhibited pronounced anti-inflammatory effects, as evidenced by a dose-dependent reduction in pro-inflammatory markers such as IL-6, IL-1β, COX-2, iNOS, and IFN-γ (p < 0.05 at concentrations of 0.02 and 0.2 mg/mL). Taken together, these findings indicate that 2,3-dichloro-6-(trifluoromethoxy) quinoxaline has dual antifungal and anti-inflammatory potential, positioning it as a promising candidate for further preclinical development.

Methicillin-resistant Staphylococcus aureus (MRSA) surveillance in regions with mass gatherings presents unique challenges for public health systems. Saudi Arabia, hosting millions of pilgrims annually, provides a distinctive setting for studying how human mobility shapes bacterial populations, yet comprehensive genomic surveillance data from this region remain limited. Here, we present an integrated analysis of S. aureus isolates collected across seven Saudi Arabian regions, combining whole-genome sequencing with extensive antimicrobial susceptibility testing and standardized metadata following findability, accessibility, interoperability and reusability data principles. Our analysis revealed striking differences between pilgrimage and non-pilgrimage cities. Pilgrimage cities showed significantly higher genetic diversity and antimicrobial resistance rates, harbouring numerous international strains, including recognized clones from diverse geographic origins. Reported lineage dynamics are changing, expanding toward community clones. While genomic prediction of antimicrobial resistance showed high accuracy for some antibiotics, particularly beta-lactams, with varying performance for others, it highlights the necessity for phenotypic testing in clinical settings. Our findings demonstrate how mass gatherings drive bacterial population structures and emphasize the importance of integrated surveillance approaches in regions with significant global connectivity and travel.

Biofilm-associated infections pose a significant challenge in clinical settings due to their increased resistance to antibiotics and evasion of host immune responses. These infections are responsible for a large proportion of chronic and recurrent infections, leading to prolonged hospital stays, increased healthcare costs, and elevated morbidity and mortality rates. Vancomycin, a glycopeptide antibiotic, has long been a cornerstone in the treatment of infections caused by Gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In addition, vancomycin-resistant Enterococcus (VRE) represents an important group of biofilm-forming pathogens, further complicating treatment strategies. However, its efficacy against biofilms remains a subject of ongoing research and debate. The ability of vancomycin to target biofilm-embedded bacteria is often hindered by multiple resistance mechanisms, including poor antibiotic penetration, metabolic adaptation of biofilm-associated cells, and the presence of persister cells. The aim of this review is to evaluate vancomycin’s antibiofilm activity by examining its mechanism of action, pharmacokinetics, effectiveness, limitations, and potential strategies to enhance its therapeutic outcomes. Several novel approaches have been explored to augment vancomycin’s antibiofilm activity, including combination therapies, adjuvant strategies, and nanotechnology-based drug delivery systems. Understanding these factors is crucial for optimizing therapeutic strategies and overcoming the persistent challenge of biofilm-related infections. This review synthesizes current evidence and highlights areas requiring further research to enhance vancomycin’s efficacy against biofilm-associated infections.

Burkholderia pseudomallei, a gram-negative facultative intracellular bacterium, is the causative agent of melioidosis, a life-threatening infectious disease endemic to tropical and subtropical regions, particularly Southeast Asia and Northern Australia. Key risk factors such as diabetes, alcoholism, and socioeconomic challenges were identified as major contributors to disease susceptibility and treatment outcomes in melioidosis. Globally, melioidosis accounts for approximately 89,000 deaths annually and poses a significant public health concern, particularly in resource-limited settings. B. pseudomallei exhibits remarkable environmental resilience, thrives in soil and water, and is intrinsically resistant to various antibiotics. Its pathogenicity is mediated by diverse virulence factors, including type III and VI secretion systems, a protective capsule, lipopolysaccharide (LPS), and BimA-mediated actin-based motility, which facilitate intracellular survival, immune evasion, and systemic dissemination. This bacterium can cause a wide spectrum of clinical manifestations ranging from localized skin infections to severe septicemia, pneumonia, and neurological involvement. In certain cases, B. pseudomallei may persist in a latent state for years and reactivation is often triggered by immunosuppression. The treatment of melioidosis is challenging because of its intrinsic antibiotic resistance, necessitating a two-phase approach: an intensive phase with intravenous antibiotics, such as ceftazidime or meropenem, followed by a prolonged eradication phase using trimethoprim-sulfamethoxazole. However, relapse remains a concern, particularly in patients with poor adherence to the therapy. Preventive strategies, particularly in endemic regions, focus on minimizing environmental exposure through protective measures and safe water practices. Despite advancements in therapeutic approaches, there is an urgent need for novel treatment strategies, including bacteriophage therapy and vaccine development, to enhance melioidosis prevention and control. Understanding the complex pathogenic mechanisms of B. pseudomallei is essential to improve its clinical management and reduce its global burden.

Antimicrobial peptides (AMPs) are short protein fragments that function as an innate immune response across diverse life forms. Structurally, AMPs exhibit diverse configurations, including α-helical, β-sheet, mixed, and random-coil forms, enabling a variety of mechanisms to combat pathogens. The mechanisms of action of AMPs encompass membrane disruption and inhibition of critical cellular processes, highlighting their broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMP activity extends to anti-tumor and anti-HIV activities, further emphasizing their therapeutic potential. Purifying AMPs from natural sources can be challenging due to posttranslational processing. Fortunately, chemical synthesis has the advantage of producing high yield and pure AMPs, but the reaction efficiency diminishes as the molecular weight of peptides increases. Advances in computational tools and curated databases have further accelerated AMP discovery and engineering. While commercially available AMP-based antibiotics and in vivo efficacy against multidrug-resistant bacteria demonstrate their clinical relevance, several limitations still hinder the widespread use of AMPs such as low stability and toxicity to human cells. This review provides a comprehensive overview of AMP origins, characteristics, mechanisms, applications, and future prospects in combating infectious diseases with a particular focus on the clinical applicability of AMPs and their prospects as potent alternative to traditional antibiotics.