scholarly journals Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

2003 ◽  
Vol 47 (2) ◽  
pp. 524-528 ◽  
Author(s):  
Shannon M. Goswick ◽  
George M. Brenner
Keyword(s):  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri ◽  
Free Living Ameba ◽  
Primary Amebic Meningoencephalitis ◽  
Observation Period

ABSTRACT Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 μM (10 μg/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 μM (0.1 μg/ml). Azithromycin protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.

scholarly journals Synergistic Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

2006 ◽  
Vol 51 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Shannon M. Soltow ◽  
George M. Brenner
Keyword(s):  
Central Nervous System ◽  
Mouse Model ◽  
Amphotericin B ◽  
Fixed Combination ◽  
Central Nervous System Infection ◽  
Naegleria Fowleri ◽  
Combined Use ◽  
Nægleria Fowleri ◽  
Primary Amebic Meningoencephalitis

ABSTRACT Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM.

scholarly journals In Vitro Activity of Statins against Naegleria fowleri

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Aitor Rizo-Liendo ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Olfa Chiboub ◽  
Rubén L. Rodríguez-Expósito ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Key Factors ◽  
Key Enzyme ◽  
Liver And Kidney ◽  
Nægleria Fowleri ◽  
Coa Reductase ◽  
Effective Drugs

Naegleria fowleri causes a deadly disease called primary amoebic meningoencephalitis (PAM). Even though PAM is still considered a rare disease, the number of reported cases worldwide has been increasing each year. Among the factors to be considered for this, awareness about this disease, and also global warming, as these amoebae thrive in warm water bodies, seem to be the key factors. Until present, no fully effective drugs have been developed to treat PAM, and the current options are amphotericin B and miltefosine, which present side effects such as liver and kidney toxicity. Statins are able to inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is a key enzyme for the synthesis of ergosterol of the cell membrane of these amoebae. Therefore, the in vitro activity of a group of statins was tested in this study against two types of strains of Naegleria fowleri. The obtained results showed that fluvastatin was the most effective statin tested in this study and was able to eliminate these amoebae at concentrations of 0.179 ± 0.078 to 1.682 ± 0.775 µM depending on the tested strain of N. fowleri. Therefore, fluvastatin could be a potential novel therapeutic agent against this emerging pathogen.

scholarly journals In vitro activity of selected Ghanaian medicinal plants against parasites: Giardia lamblia, Entamoeba histolytica and Naegleria fowleri

2017 ◽  
Vol 11 (23) ◽  
pp. 279-283 ◽  
Author(s):  
Kyere-Davies Gertrude ◽  
Agyare Christian ◽  
Duah Boakye Yaw ◽  
Bains Trpta ◽  
M. Suzuki Brian ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Entamoeba Histolytica ◽  
Giardia Lamblia ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri

scholarly journals In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.

1996 ◽  
Vol 40 (8) ◽  
pp. 1910-1913 ◽  
Author(s):  
J R Perfect ◽  
G M Cox ◽  
R K Dodge ◽  
W A Schell
Keyword(s):  
Central Nervous System ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Central Nervous System Infection ◽  
Rabbit Model ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Drug Concentrations

Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug were determined, and minimum fungicidal concentrations of SCH56592 and amphotericin B were measured. MICs of SCH56592 were lower than those of amphotericin B and fluconazole but not those of itraconazole. Minimum fungicidal concentrations of SCH56592 were lower than those of amphotericin B. SCH56592 in the presence of human serum produces an in vitro fungicidal effect for Cryptococcus neoformans. The data indicate that SCH56592 might exert fungicidal as well as inhibitory properties in vivo. On the basis of these results, SCH56592 was evaluated with a rabbit model of experimental cryptococcal meningitis; SCH56592 treatment was compared with treatment with fluconazole. Despite no detectable drug concentrations in the cerebrospinal fluid, the activity of SCH56592 against C. neoformans infection was equivalent to that of fluconazole. SCH56592 has potent in vitro activity against C. neoformans and compares favorably to treatment with fluconazole for a central nervous system infection. SCH56592 should be studied for use in humans with cryptococcal infections.

scholarly journals Effect of Therapeutic Chemical Agents In Vitro and on Experimental Meningoencephalitis Due to Naegleria fowleri

2008 ◽  
Vol 52 (11) ◽  
pp. 4010-4016 ◽  
Author(s):  
Jong-Hyun Kim ◽  
Suk-Yul Jung ◽  
Yang-Jin Lee ◽  
Kyoung-Ju Song ◽  
Daeho Kwon ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Survival Rates ◽  
Laboratory Animals ◽  
Naegleria Fowleri ◽  
Time To Death ◽  
Nægleria Fowleri ◽  
Amoebic Meningoencephalitis ◽  
Mean Time

ABSTRACT Naegleria fowleri is a ubiquitous, pathogenic free-living amoeba; it is the most virulent Naegleria species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for N. fowleri infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic N. fowleri. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When N. fowleri trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 μg/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by N. fowleri, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

scholarly journals In vivo and in vitro activity of genistein in osteoporosis

2007 ◽  
Vol 39 (2) ◽  
pp. 103 ◽  
Author(s):  
Qibing Mei ◽  
Jiepin Wang ◽  
Fujun Shang ◽  
Li Liu ◽  
Siwang wang ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity

scholarly journals 1366. In Vitro and In Vivo Activity of Cefiderocol against Stenotrophomonas maltophilia Clinical Isolates

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S418-S418 ◽  
Author(s):  
Akinobu Ito ◽  
Merime Ota ◽  
Rio Nakamura ◽  
Masakatsu Tsuji ◽  
Takafumi Sato ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Systemic Infection ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Infection Model ◽  
In Vitro Activity ◽  
In Vivo Efficacy ◽  
Broth Microdilution Method

Abstract Background Cefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin against Gram-negatives, including carbapenem (CR)-resistant strains. Its spectrum includes both the Enterobacteriaceae but also nonfermenters, including Stenotrophomonas maltophilia—an opportunistic pathogen with intrinsic resistance to carbapenem antibiotics. In this study, in vitro activity and in vivo efficacy of CFDC and comparators against S. maltophilia were determined. Methods MICs of CFDC and comparators (trimethoprim/sulfamethoxazole (TMP/SMX), minocycline (MINO), tigecycline (TGC), ciprofloxacin (CPFX), cefepime (CFPM), meropenem (MEPM), and colistin (CL)) were determined by broth microdilution method as recommended by CLSI. The MIC against CFDC was determined using iron-depleted cation-adjusted Mueller–Hinton broth. In vivo efficacy of CFDC, CFPM, ceftazidime–avibactam (CAZ/AVI), MEPM, and CL was evaluated using neutropenic murine systemic infection model caused by strain SR21970. The 50% effective doses (ED50s) were calculated by the logit method using the survival number at each dose 7 days after infection. Results MIC90 of CFDC and comparators against the 216 clinical isolates from global countries collected in SIDERO-CR 2014/2016 study are shown in the table. CFDC, TMP/SMX, MINO, and TGC showed good activity with MIC90 of 0.5, 0.25/4.75, 1, and 2 µg/mL, respectively. CFDC, MINO, and TGC inhibited growth of all tested strains at ≤1, ≤4, and ≤8 µg/mL although two strains showed resistance to TMP/SMX. MICs of CFPM, CAZ/AVI, MEPM, and CL were ≥32 µg/mL. The ED50 of CFDC against S. maltophilia SR21970 with MIC of 0.125 mg/mL was 1.17 mg/kg/dose. Conversely, MICs of CFPM, CAZ/AVI, MEPM/CS, and CL against SR21970 were 32 μg/mL or higher, and ED50s were >100 mg/kg/dose, showing that CFDC had potent in vivo efficacy against S. maltophilia strain which was resistant to other antibiotics. Conclusion CFDC showed potent in vitro activity against S. maltophilia, including TMP/SMX-resistant isolates. CFDC also showed potent in vivo efficacy reflecting in vitro activity against S. maltophilia in murine systemic infection model. Disclosures A. Ito, Shionogi & Co., Ltd.: Employee, Salary. M. Ota, Shionogi & Co., Ltd.: Employee, Salary. R. Nakamura, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. T. Sato, Shionogi & Co., Ltd.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary.

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