In vitro synergistic effects of chlorpromazine and sertraline in combination with amphotericin B against Cryptococcus neoformans var. grubii

Rossato, Luana; Loreto, Érico S.; Zanette, Régis A.; Chassot, Francieli; Santúrio, Jânio Morais; Alves, Sydney Hartz

doi:10.1007/s12223-016-0449-8

Cited by 33 publications

(25 citation statements)

References 37 publications

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“…Despite the diverse mechanism of action of these substances on microorganisms (TET, a 30S ribosomal subunit inhibitor [57]; CLR, a 50S ribosomal subunit inhibitor [58]; AMX, an antibiotic disrupting cell wall synthesis [59]; and MTZ, a genotoxic substance [60]), in the case of all a synergistic/additive interaction with SER was found. The non-selective, positive interaction of SER with many fungicides, including polyenes [15,18,61], echinocandins [15], and azoles [15,17,19,20,23], was also observed in experiments conducted on fungal microorganisms. The ability of this substance to increase the activity of structurally different substances may be related to the potential of SER to inhibit efflux pumps [36,37].…”

Section: Discussionmentioning

confidence: 87%

In Vitro Activity of Sertraline, an Antidepressant, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains

et al. 2019

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Antibiotic resistance of Helicobacter pylori, a spiral bacterium associated with gastric diseases, is a topic that has been intensively discussed in last decades. Recent discoveries indicate promising antimicrobial and antibiotic-potentiating properties of sertraline (SER), an antidepressant substance. The aim of the study, therefore, was to determine the antibacterial activity of SER in relation to antibiotic-sensitive and antibiotic-resistant H. pylori strains. The antimicrobial tests were performed using a diffusion-disk method, microdilution method, and time-killing assay. The interaction between SER and antibiotics (amoxicillin, clarithromycin, tetracycline, and metronidazole) was determined by using a checkerboard method. In addition, the study was expanded to include observations by light, fluorescence, and scanning electron microscopy. The growth inhibition zones were in the range of 19–37 mm for discs impregnated with 2 mg of SER. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) counted for 2–8 µg/mL and 4–8 µg/mL, respectively. The time-killing assay showed the time-dependent and concentration-dependent bactericidal activity of SER. Bacteria exposed to MBCs (but not sub-MICs and MICs ≠ MBCs) underwent morphological transformation into coccoid forms. This mechanism, however, was not protective because these cells after a 24-h incubation had a several-fold reduced green/red fluorescence ratio compared to the control. Using the checkerboard assay, a synergistic/additive interaction of SER with all four antibiotics tested was demonstrated. These results indicate that SER may be a promising anti-H. pylori compound.

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Section: Discussionmentioning

confidence: 87%

In Vitro Activity of Sertraline, an Antidepressant, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains

et al. 2019

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“…There has been recent interest in the use of sertraline to treat cryptococcal meningitis. Sertraline also appears to work synergistically with either amphotericin or fluconazole against C. neoformans in vitro . A (historically) controlled phase 2 trial of this drug in combination with amphotericin and fluconazole appeared promising, suggesting improved rates of clearance of yeast from cerebrospinal fluid, although this contrasted with a smaller controlled trial which found no difference .…”

Section: Discussionmentioning

confidence: 97%

The combination of tamoxifen with amphotericin B, but not with fluconazole, has synergistic activity against the majority of clinical isolates of Cryptococcus neoformans

Hai

Van

Ngan

et al. 2019

Mycoses

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Summary Background Cryptococcal meningitis has fatality rates of 40%‐70%, resulting in 200 000 deaths each year. The best outcomes are achieved with amphotericin combined with flucytosine but flucytosine is expensive and unavailable where most disease occurs. More effective and affordable treatments are needed. Tamoxifen, a selective oestrogen receptor modulator frequently indicated for breast cancer, has been found to have synergistic activity against the Cryptococcus neoformans type strain when combined with amphotericin or fluconazole. It is cheap, off‐licence, widely available and well‐tolerated, and thus a pragmatic potential treatment for cryptococcal disease. Objectives We wanted to determine the susceptibility of clinical isolates of C. neoformans to tamoxifen alone and in combination with other antifungals, to determine whether there is sufficient evidence of activity to justify a clinical trial. Methods We used the CLSI broth microdilution protocol to test the susceptibility of 30 randomly selected clinical isolates of C. neoformans to tamoxifen, in dual combination with amphotericin, fluconazole or flucytosine, and in triple combination with amphotericin and fluconazole. Evidence of drug interactions was assessed using the fractional inhibitory concentration index. Results The MIC50 and MIC90 of tamoxifen were 4 and 16 mg/L, respectively. The combination of tamoxifen and amphotericin suggested a synergistic interaction in 20 of 30 (67%) isolates. There was no interaction between tamoxifen and either fluconazole or flucytosine. Synergy was maintained in 3‐Dimensional chequerboard testing. There was no evidence of antagonism. Conclusions Tamoxifen may be a useful addition to treatment with amphotericin and fluconazole for cryptococcal meningitis; a trial is justified.

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“…In vitro studies have demonstrated synergistic effects with the addition of sertraline or chlorpromazine to amphotericin B for C. neoformans (70). The use of sertraline as an adjunctive therapy for management of cryptococcal meningitis was examined in a recent open-labelled dose finding study.…”

Section: Management Consideration For CD In Hiv-negative Individualsmentioning

confidence: 99%

Cryptococcosis Today: It Is Not All About HIV Infection

O’Halloran

Powderly

Spec

2017

Curr Clin Micro Rpt

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Purpose of the review Cryptococcal disease is most often thought of in the context of HIV infection. Much of our knowledge of the disease originates from its management in the HIV-positive population over the last 30 years. While the majority of cases globally continue to occur in the setting of advanced HIV, Cryptococcus species is increasingly responsible for disease in HIV-negative populations including those considered normal hosts and these HIV-negative populations will be the focus of this review Recent findings Currently available data indicated that significant differences exist in epidemiology, clinical presentation, management and outcomes of cryptococcal disease in HIV-negative populations when compared to those living with HIV. Summary Further research is required to improve our knowledge of cryptococcal disease in particular in HIV-negative cohorts so as to optimise management of the disease in the future.

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In vitro synergistic effects of chlorpromazine and sertraline in combination with amphotericin B against Cryptococcus neoformans var. grubii

Cited by 33 publications

References 37 publications

In Vitro Activity of Sertraline, an Antidepressant, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains

In Vitro Activity of Sertraline, an Antidepressant, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains

The combination of tamoxifen with amphotericin B, but not with fluconazole, has synergistic activity against the majority of clinical isolates of Cryptococcus neoformans

Cryptococcosis Today: It Is Not All About HIV Infection

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