Abstract: This disclosure provides methods for detecting microbial cell-free nucleic acids for use in a wide variety of contexts. In some embodiments, this disclosure provides methods of monitoring a response to treatment. In some embodiments, this disclosure provides methods applicable for detecting bacterial infections (e.g., Bartonella spp. infections) and/or fungal infections. In some embodiments, the microbial cell-free nucleic acids are detected by metagenomic next-generation sequencing.