Cystic fibrosis (CF) is a lethal genetic disease, characterized by polymicrobial lung infections that are near impossible to treat due to the high level of antibiotic resistance of the pathogens. Though the multi-drug resistance of pathogens has been previously documented, the mechanisms for antibiotic resistance acquisition are still largely unknown. A prior screen of CF sputa identified the most resistant and multidrug-resistant bacterial candidates. This project aimed to identify the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against antibiotics used in CF treatment at the time of sample collection for several bacterial isolates with subsequent genome sequencing to determine the genetic basis for their resistance mechanisms. Each isolate was tested in an MIC broth dilution assay with various concentrations of each antibiotic to determine the minimum amount needed to inhibit the growth of each isolate, then plated to determine the minimum concentration to kill the isolate. Genomic DNA was isolated and sequenced with the genomes assembled by external company, SeqCenter. With collaboration from a bioinformatics specialist, the assembled genomes were searched for genes known to confer resistance mechanisms to the antibiotics screened for. Results indicate that resistant microbes including Staphylococcus aureus and fungi are able to persist in CF lung despite aggressive antibiotic treatment.