Erlotinib in Patients with Advanced Non-small Cell Lung Cancer in Middle Eastern Population

Background: Although erlotinib is widely used in the management of non-small cell lung cancer (NSCLC), no prior studies were conducted in Middle Eastern population. Our study aims at evaluating erlotinib prospectively in this population. Patients and Methods: This open-label, prospective, single-arm, multicenter Phase IV clinical trial of erlotinib as single agent evaluated safety and efficacy of Erlotinib in Middle Eastern patients with advanced NSCLC. Results: A total of 56 patients were enrolled in five sites in Saudi Arabia. Majority of patients were males (60%) with median age of 57 years (34–80), Stage IV (98%), and adenocarcinoma (84%). Eastern Cooperative Oncology Group performance Status III (41.1%). Epidermal growth factor receptor (EGFR) mutations were present in 24 patients out of 36 patients tested (67%). The most common reported adverse events (AEs) were rash 36 (64%), diarrhea 29 (52%), fatigue 10 (18%), and anorexia 5 (9%). Grade 4 or 5 AEs were not observed. Complete response was achieved in 2 (3.6%) and overall disease control was 60.8%. Median overall survival (OS) was significantly longer in patients with EGFR mutation than wild type (20 vs. 3 months, P = 0.002). Progression-free survival was 10 months and significantly longer in patients with EGFR mutation than wild type (16 vs. 6 months, P = 0.037). Patients with unknown EGFR status had PSF and OS better than wild-type patients and worse than patients with EGFR mutation. Cox regression analysis showed that older age (P = 0.029, HR 1.064), EGFR wild type (P = 0.014, hazard ratio [HR]: 8.497), and receiving radiation (P = 0.033, HR 6.433) significantly increase risk of death for patients receiving erlotinib. Conclusion: Erlotinib has efficacy and safety profile in Middle Eastern population similar to the reported literature. The empiric use of erlotinib in patients with unknown EGFR status in our patient population is warranted due to high prevalence of the mutation. However, it should not be used in confirmed wild-type disease

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic ‘Umrah’ ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia