A Review: Antimicrobial Therapy for Human Pythiosis

Abstract

Human pythiosis is associated with poor prognosis with significant mortality caused by Pythium insidiosum. Antimicrobials' in vitro and in vivo results against P. insidiosum are inconsistent. Although antimicrobials are clinically useful, they are not likely to achieve therapeutic success alone without surgery and immunotherapy. New therapeutic options are therefore needed. This non-exhaustive review discusses the rationale antimicrobial therapy, minimum inhibitory concentrations, and efficacy of antibacterial and antifungal agents against P. insidiosum. This review further provides insight into the immunomodulating effects of antimicrobials that can enhance the immune response to infections. Current data support using antimicrobial combination therapy for the pharmacotherapeutic management of human pythiosis. Also, the success or failure of antimicrobial treatment in human pythiosis might depend on the immunomodulatory effects of drugs. The repurposing of existing drugs is a safe strategy for anti-P. insidiosum drug discovery. To improve patient outcomes in pythiosis, we suggest further research and a deeper understanding of P. insidiosum virulence factors, host immune response, and host immune system modification by antimicrobials.

Pythiosis presenting with chronic swelling and painful subcutaneous lesion at right deltoid

“…However, combination of terbinafine and itraconazole together results in an effective treatment in many cases [17] , [18] . Azithromycin has immunomodulatory effect and can inhibit growth of P. insidosum in vivo when used alone or combined with minocycline [19] . This patient responded well to the combination of itraconazole, terbinafine, and azithromycin.…”

Treating Pythiosis with Antibacterial Drugs Targeting Protein Synthesis: An Overview

“…Surgery is considered a key strategy, particularly effective for localized, smaller, and superficial lesions, though its success can be constrained [5]. Antifungal drugs, initially used based on the microorganism's misclassification as a fungus, have demonstrated limited efficacy [10,11]. Immunotherapy emerges as a promising alternative, particularly beneficial in equine and some human cases, although its success varies depending on factors like lesion duration and antigen preparation methods [11,12].…”

Commentary

“…Antifungals such as polyenes (amphotericin B), azoles (miconazole, ketoconazole, fluconazole, itraconazole, posaconazole, and voriconazole), allylamines (terbinafine), and echinocandins (caspofungin, anidulafungin, and micafungin) have been used for managing PIK. [ 4 ] As per the literature review, antibacterials have scored more over antifungals, and antifungals have shown limited success. Antifungals still play a crucial role in treatment in resource-limited laboratories and facilities where culture facilities are inaccessible.…”

“…Pseudomonas stutzeri and Klebsiella pneumoniae metabolites have also been found to have anti-Pythium activity. [ 4 ]…”