Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs

Hughes, Carolyn E.; Harris, C; Peterson, Lance R.; Gerding, Dale N.

doi:10.1128/aac.26.6.837

Cited by 22 publications

(11 citation statements)

References 15 publications

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“…(6,16,17,26). As with PN, the above-mentioned antibacterial drugs inhibit the protein synthesis, and this could be an explanation of their positive interaction.…”

mentioning

confidence: 99%

In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

Afeltra

Dannaoui

Meis

et al. 2002

Antimicrob Agents Chemother

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To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Laboratory Standards M38-P guidelines. The interaction between the drugs was analyzed using fractional inhibitory concentration index (FICI) analysis and response surface modeling. Amphotericin B alone was inactive against all the isolates. The geometric mean MIC for pentamidine was 57 g/ml (range, 8 to 256 g/ml; MIC at which 50% of the isolates tested were inhibited [MIC 50 ], 64 g/ml; MIC 90 , 128 g/ml). The combination was synergistic against 28 of 30 isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface modeling analysis. Antagonism was not observed.The in vitro susceptibility of Scedosporium prolificans to antifungal agents has been tested in several studies (5,7,22), and although the methodological conditions differed in the various studies, in general, their results correlated with the observed poor clinical outcomes. The new azoles, such as ravuconazole, voriconazole, and posaconazole, showed poor in vitro activity (5, 7), with the exception of the experimental azole UR-9825, which showed some activity against S. prolificans (5). Pentamidine (PN) displayed good in vitro and in vivo activity against Pneumocystis carinii, a microorganism that now is believed to belong to the fungal kingdom (12,24,28). Also, in combination with amphotericin B (AMB), the drug displayed in vivo and in vitro synergistic activity against other eukaryotic microorganisms such as Leishmania donovani (21, 28). To develop new therapeutic strategies to treat invasive scedosporiosis, we investigated the in vitro activity of AMB and PN, alone or in combination, using two different criteria, the fractional inhibitory concentration index (FICI) (10) and response surface modeling (13).Thirty clinical isolates (3) of S. prolificans were tested. The isolates were subcultured on potato dextrose agar (PDA) for 5 to 7 days at 30°C. Candida parapsilosis (ATCC 22019) and Candida krusei (ATCC 6258) were used as quality control strains. All isolates were tested in duplicate on two different days. Conidia were obtained from fresh cultures each time. All solutions were prepared ex novo with powders from the same lot.MICs were determined by a broth microdilution method according to the National Committee for Clinical Laboratory Standards guidelines (M38-P) (25).Conidia were collected with a cotton stick and suspended in sterile water. After the heavy particles were allowed to settle, the turbidity of the supernatants was measured spectrophotometrically (Spectronic 20D; Milton Roy, Rochester, N.Y.) at 530 nm and the transmission was adjusted to 68 to 70% and diluted 1:50 in RPMI medium to obtain two times the desired inoculum concentration. The inoculum size was verified by determination of the number of viable CFU after plating serial dilu...

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“…(6,16,17,26). As with PN, the above-mentioned antibacterial drugs inhibit the protein synthesis, and this could be an explanation of their positive interaction.…”

mentioning

confidence: 99%

In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

Afeltra

Dannaoui

Meis

et al. 2002

Antimicrob Agents Chemother

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“…Since then, several studies demonstrated the in vitro synergisms between amphotericin B or fluconazole with azithromycin, clarithromycin, doxycycline, minocycline, or tetracycline against Aspergillus spp., Candida spp., and Fusarium spp. (18)(19)(20)(21)(22)(23), as well as other combinations of antibacterial and antifungal agents against pathogenic fungi, as reviewed by Afeltra and Verweij (24) and Liu et al (25).…”

mentioning

confidence: 99%

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

Jesus

Ferreiro

Loreto

et al. 2014

Antimicrob Agents Chemother

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We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLSI M38-A2 technique and the checkerboard microdilution method. The main synergisms observed were through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%), and micafungin (70%) and of clarithromycin with micafungin (73.33%). Pythiosis is a life-threatening disease caused by the oomycete Pythium insidiosum, which can cause infections in humans and in animals, such as horses, bovines, cats, dogs, and sheep. Clinically, the disease may manifest in cutaneous, gastrointestinal, vascular, and systemic forms and has been described in tropical and subtropical areas (1). The hyphae of P. insidiosum are morphologically similar to those of certain mucoraceous molds, but P. insidiosum is not a true fungus because it does not synthesize ergosterol, which is the target of most antifungal drugs. Despite this challenge, two cases of pythiosis in humans, one case of ocular pythiosis and one case of pleuropericarditis (2, 3), have been successfully treated using combination antifungal therapy. However, combination antifungal therapy has been ineffective in cases of vascular and disseminated human pythiosis (4).Previous studies have shown that the growth of P. insidiosum is inhibited in vitro by the glycylcycline, macrolide, and tetracycline classes of antibacterial drugs (5, 6). However, studies evaluating the antimicrobial combination of antibacterial and antifungal agents against P. insidiosum have not been performed. In this context, this study evaluated the in vitro combination of the antibacterial drugs azithromycin, clarithromycin, minocycline, or tigecycline with the antifungal drugs amphotericin B, itraconazole, voriconazole, terbinafine, anidulafungin, caspofungin, or micafungin against P. insidiosum.Twenty-eight P. insidiosum isolates obtained from Brazilian cases of equine pythiosis and the reference strains ATCC 58.637 and CBS 101555 were evaluated in this study. The identities of the clinical isolates were confirmed using PCR-based assays (7). The antibacterial drugs azithromycin (Pharma Nostra, Rio de Janeiro, Brazil), clarithromycin (Genix, Anápolis, Brazil), minocycline (Pharma Nostra), and tigecycline (Pfizer, New York, NY) and the antifungal drugs amphotericin B (Sigma-Aldrich, St. Louis, MO), itraconazole (Frangon do Brasil Farmacêutica Ltda., São Paulo, Brazil), voriconazole (Pfizer), terbinafine (Pharma Nostra), anidulafungin (Pfizer), caspofungin (Merck, Darmstadt, Germany), and micafungin (Astellas, Chuo, Japan) were obtained commercially and diluted in dimethyl sulfoxide or distilled water, as recommended, to generate stock solutions. The concentrations of the antimicrobial agents tested were 0.03 to 16 g/ml and 1 to 512 g/ml for the antibacterial and antifungal dr...

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“…Various combinations of amph B and tetracycline anti biotics (tetracycline, doxicycline, minocycline) have been studied for activity against A. fumigants [102]. Synergistic activity of amph B and minocycline was observed in each of 5 isolates: time-kill curves showed eradication of A .…”

Section: Combinations O F Amphotericin B With Other Drugsmentioning

confidence: 99%

“…Synergistic activity of amph B and minocycline was observed in each of 5 isolates: time-kill curves showed eradication of A . fu migants at concentrations of amph B that were 4-to 8-fold lower in the presence of 5 or 15 gg/ml o f minocycline than with amph B alone [102].…”

Section: Combinations O F Amphotericin B With Other Drugsmentioning

confidence: 99%

Treatment and Developmental Therapeutics in Aspergillosis. 1. Amphotericin B and Its Derivatives

Georgiev

1992

Respiration

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In recent years, the frequency of infections caused by Aspergillus sp. has been on the rise. Immunocompromised patients are especially vulnerable to such infections. The polyene antibiotic amphotericin B is currently considered to be therapeutically the most effective drug against Aspergillus-induced infections. In the present review, the clinical efficacy of amphotericin B, its toxicities and various routes of applications, are discussed. Different combinations of amphotericin B with other drugs have also been reviewed, along with the anti-Aspergillus activity of various other antibiotics and some ester derivatives of amphotericin B.

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Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs

Cited by 22 publications

References 15 publications

In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

In Vitro Synergistic Interaction between Amphotericin B and Pentamidine against Scedosporium prolificans

In Vitro Synergism Observed with Azithromycin, Clarithromycin, Minocycline, or Tigecycline in Association with Antifungal Agents against Pythium insidiosum

Treatment and Developmental Therapeutics in Aspergillosis. 1. Amphotericin B and Its Derivatives

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