hydroxychloroquine + doxycycline

Hydroxychloroquine + doxycycline is a combination of two small-molecule drugs used primarily for the treatment of persistent infections caused by Coxiella burnetii (Q fever), particularly endocarditis and vascular infections. Hydroxychloroquine, an antimalarial and disease-modifying anti-rheumatic drug (DMARD), acts by alkalinizing the phagolysosome, thereby enhancing the bactericidal activity of doxycycline against intracellular pathogens. Doxycycline is a second-generation tetracycline antibiotic that inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. This combination is considered more effective than other regimens in reducing relapse rates and shortening therapy duration for Q fever endocarditis. Both agents also have pro-apoptotic effects on host cells, with hydroxychloroquine modulating caspase-3 activation and bcl-2/bax ratio, while doxycycline has additional anti-inflammatory properties[1][5]. The combination has also been explored in clinical trials for COVID-19 but is not standard therapy for this indication[3].