Background: Cystic Fibrosis has been described before in Saudi Arabia and all Arab countries. The presentation is usually recurrent chest infection, failure to thrive, and electrolyte imbalance. Sepsis is a rare presentation in such a group of patient due to normal immunological status.

Method: Review of Registry data of the Saudi CF population from the years 2000-2020 and review of the literature on CF in the Arab world.

Objective: To describe the first case report of a CF patient presenting as recurrent staphylococcus Hominis and MRSA sepsis and recurrent chest infection.

Results: A 7-month-old infant presented to the local hospital with recurrent fever, diarrhea, failure to thrive with a Z score for weight/Age of (-8.2) and recurrent pneumonia monthly since the age of 2 months. He also required multiple blood transfusions. He was referred to our center to rule out immunodeficiency. He developed hypoxic Respiratory Failure requiring Intubation for 3 weeks. He developed endovascular infection with Polymicrobial CLABSI with persistent positive cultures of MRSA septiemia, but no evidence of vegetation on Echo. He developed Tension pneumothorax on top of parenchymal lung disease that required chest tube drainage. His Broncho alveolar lavage grew: Klebsiella aerogene and Stenotrophomonas maltophilia and Candida parspolosis in addition to Influenza B virus and RSV. His sepsis improved with the appropriate antimicrobial treatment and his weight improved to a Z score of -5.9 after one month of nutritional support and he was discharged in good clinical condition. His immunological workup was normal but the whole genome study confirmed the diagnosis of cystic fibrosis with homozygous c.1375_1383del p.(Ser459_Gly461del) and heterozygous (a carrier for RAG2 mutation for immunodeficiency). He was started on the proper CF management and nutritional support. He continued to improve and his weight Z score at 2 years was (-1.02).

Conclusion: CF could present with recurrent sepsis. Proper antimicrobial treatment and detailed history could prevent prolonged morbidity and mortality in this group of patients.