The invention generally provides methods of treating or preventing infection and/or disease associated with different fungal pathogens in a subject in need, using an isolated antiserum generated against an immunogenic peptide of one fungal pathogen that contains antibodies that cross-protect the subject from infection and/or disease associated with one or more different fungal pathogens. The antiserum may be generated against a Kexin peptide derived from one of a Pneumocystis, Aspergillus, Candida, or Cryptococcus fungal pathogen. The resulting cross-protective, isolated antiserum may be used as a therapeutic for treating or protecting a subject who receives the antiserum against infection and/or disease associated with multiple fungal pathogens, in addition to the pathogen against which the antiserum is generated. Also provided are compositions and kits for detecting or quantifying the presence of antibodies directed against a Kex peptide of one, two, three, or more of Pneumocystis, Aspergillus, Candida, or Cryptococcus in a subject.