Synergistic and Additive Effects of Binary Combinations of Ciprofloxacin with Origanum vulgare L. or Cinnamomum cassia (L.) J. Presl. Essential Oil Against Medically Relevant Bacteria

Background/Objectives: Bacterial resistance to antimicrobials has become a public health problem worldwide, limiting the effectiveness of conventional treatments. Therefore, combination antimicrobial therapy has been proposed as a strategy to combat multidrug-resistant bacteria. This study aimed to investigate the antibacterial effects of ciprofloxacin (CIP) in binary combinations with Cinnamomum cassia (L.) J. Presl. (CEO) and Origanum vulgare L. (OEO) essential oils against Acinetobacter baumannii, Klebsiella quasipneumoniae, Pseudomonas paraeruginosa, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA). Methods: The hemolytic activity was evaluated for the compounds individually and when combined. The antimicrobial activity was performed by broth dilution in double-antimicrobial gradient and time-kill assays. Results: The CEO–CIP and OEO–CIP combinations demonstrated hemolytic activity in human erythrocytes of 4.04 to 3.35% and 3.39 to 2.29%, respectively, and presented synergistic, additive, and indifferent antibacterial effects. The CEO–CIP combination significantly reduced CIP minimal inhibitory concentration from 256 to 0.125 µg/mL against MRSA. OEO–CIP was bactericidal against P. paraeruginosa and S. aureus; meanwhile, the CEO–CIP combination showed bactericidal activity against P. paraeruginosa, but reduced S. aureus viability by only 1.83 log after 24 h. Conclusions: These findings demonstrate the combination of CEO–CIP against A. baumannii, K. quasipneumoniae, P. paraeruginosa, S. aureus, and MRSA, in addition to hemolytic activity below 5% at the tested concentrations. Although limited to in vitro conditions, these results highlight the combination’s therapeutic potential and emphasize the necessity for further investigation into its mechanisms of action and in vivo toxicity.