Amphotericin B plus fluorocytosine combined with voriconazole for the treatment of non-HIV and non-transplant-associated cryptococcal meningitis: a retrospective study

Abstract

Background Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. Methods Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). Results The first hospitalization time of Group I (median: 25 days, IQR: 20–34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29–62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43–77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43–7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23–11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). Conclusion AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.

Amphotericin B May Decrease the Serum Level of Voriconazole: A Case Report and Brief Review of Literature

“…In review of the literature, about eight literature evaluated the therapeutic efficacy of AmB combined with Voriconazole in invasive fungal infection. [1][2][3][4][5][6][7][8] Two reports are in vitro observations, 1,2 three reports are in the animal study, [3][4][5] and three reports are in patient observation. [6][7][8] The vitro observations showed combinations antifungal therapy exhibited promising results and no apparent antagonistic interaction was detected.…”

“…[1][2][3][4][5][6][7][8] Two reports are in vitro observations, 1,2 three reports are in the animal study, [3][4][5] and three reports are in patient observation. [6][7][8] The vitro observations showed combinations antifungal therapy exhibited promising results and no apparent antagonistic interaction was detected. One animal observation indicated that the efficacy of monotherapy and the two-drug combinations therapy was similar; activity was neither enhanced nor reduced with combination therapy.…”

“…6 Another two patients observation demonstrated AmB combined with Voriconazole may rapidly improve clinical manifestation, substantially shorten the hospitalization time. 7,8 The interaction between the two drugs was not mentioned in vivo studies. [1][2][3][4][5][6][7][8] None of them tested the serum level of Voriconazole.…”

“…7,8 The interaction between the two drugs was not mentioned in vivo studies. [1][2][3][4][5][6][7][8] None of them tested the serum level of Voriconazole. Here, we discovered AmB might lower the level of Voriconazole.…”

“…In review of the literature, about 8 cases reported the therapeutic efficacy of AmB in combination with Voriconazole in invasion fungal infection. [1][2][3][4][5][6][7][8] However, there is no literature on the two drug interaction. Here, we present a case of drug interaction between AmB and Voriconazole, which has not been described in the literature.…”