• Title/Summary/Keyword: Antifungal therapy

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Synergistic Antifungal Activity against Disseminated Candidiasis by Combination Therapy of Crataegi Fructus Extract and Fluconazole (전신성 캔디다증에 대한 산사자 추출물과 Fluconazole의 병용요법에 의한 항진균 상승효과)

  • Han, Yongmoon
    • YAKHAK HOEJI
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    • v.59 no.6
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    • pp.259-265
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    • 2015
  • In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.

Novel Approaches for Efficient Antifungal Drug Action

  • Lee, Heejeong;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1771-1781
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    • 2018
  • The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

Antifungal Effect of Chitosan against Malassezia pachydermatis Isolated from the Dog with Otitis Externa (개 외이도에서 분리된 Malassezia pachydermatis에 대한 키토산의 항진균 효과)

  • Oh, Hyun-Ho;Kim, Young-In;Seo, Jeong-A;Choe, Seong-Won;Bae, Seul-Gi;Oh, Tae-Ho
    • Journal of Veterinary Clinics
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    • v.29 no.4
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    • pp.323-327
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    • 2012
  • The effect of pH of chitosan solution (w/v) on antifungal activity against Malassezia pachydermatis isolated from a dog with otitis externa was evaluated. This study was investigated to find out the optimal pH of chitosan solution that could be able to eliminate yeast cells. For comparison of antifungal activity of chitosan solution 2% chlorhexidine that have been already proved the antifungal effect against M. pachydermatis was used as positive control. The chitosan solution at different pH (2.5, 3.0, 3.5, 4.0, 4.5, 5.0) were involved this experiment. The chitosan solutions at each pH could eliminate a number of yeast cells when they were compared to other antifungal agents. In chitosan solution's antifungal effect of varying degrees according to the pH M. pachydermatis was inhibited at pH of < 5.0. Especially it has been proved an effective antifungal effect at pH 3.5. Therefore, the pH of chitosan solution had a effect on antifungal activity and the optimal pH was 3.5 in vitro. The possibility of topical therapy with acidific solution of chitosan has a potential in skin infection against M. pachydermatis.

INVASIVE ASPERGILLOSIS ON LOWER MOLAR PERIODONTAL TISSUES : CASE REPORT (하악 구치부 치주조직에 발생한 침윤성 국균증환자의 치험례)

  • Kim, Il-Kyu;Chun, Sei-Young;Oh, Sung-Seop;Choi, Jin-Ho;Chang, Keum-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.28 no.1
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    • pp.81-85
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    • 2002
  • This paper describes that invasive aspergillosis was found in oral cavity, especially in lower molar periodontium in a immunocompromised 34-year-old woman who had been admitted in hemato-oncology with the diagnosis of acute myeloid leukemia. Antifungal therapy and surgical excision of involved teeth, bone and gingiva were the treatment of choice. After treatment infected area was healed very well. We would like to report our case because we could not find any paper reporting on invasive aspergillosis occurring in lower molar periodontium.

A treatment of drug resistant denture stomatitis by microbiological analysis and adjuvant therapy: a case report (미생물학적 분석과 보조요법을 이용한 내성을 가진 의치성구내염 치료)

  • Song, Young-Gyun
    • Journal of Dental Rehabilitation and Applied Science
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    • v.38 no.2
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    • pp.120-126
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    • 2022
  • In severe cases of denture stomatitis, antifungal drugs are sometimes ineffective. This case is a 72-year-old patient who was prescribed fluconazole for five months but had no improvement in symptoms. After re-diagnosis, medication was performed, and temporary dentures were fabricated for oral rehabilitation. This report describes that microbiological analysis and adjuvant therapy can be helpful, in case does not improve symptoms even with continuous medication of antifungal agent.

Successful treatment of fungal central thrombophlebitis by surgical thrombectomy in Korea: a case report

  • Eun Ji Lee;Jihoon T. Kim
    • Journal of Trauma and Injury
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    • v.36 no.3
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    • pp.276-280
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    • 2023
  • Fungal thrombophlebitis of the central vein is a rare, life-threatening disease associated with significant morbidity and mortality. It requires immediate central venous catheter removal and intravenous antifungal therapy, combined in some cases with either anticoagulation or aggressive surgical debridement. A 70-year-old male patient injured by a falling object weighing 1,000 kg was transferred to our hospital. A contained rupture of the abdominal aorta with retroperitoneal hematoma was treated with primary aortic repair, and a small bowel perforation with mesenteric laceration was treated with resection and anastomosis. After a computed tomography scan, the patient was diagnosed with thrombophlebitis of the left internal jugular vein and brachiocephalic vein. Despite antifungal treatment, fever and candidemia persisted. Therefore, emergency debridement and thrombectomy were performed. After the operation, the patient was treated with an oral antifungal agent and direct oral anticoagulants. During a 1-year follow-up, no signs of candidemia relapse were observed. There is no optimal timing of surgical treatment for relapsed fungal central thrombophlebitis. Surgical treatment should be considered for early recovery.

Comparison of Amphotericin B and Itraconazole as Empirical Antifungal Therapy in Children with Acute Leukemia with Neutropenic Fever (발열을 동반한 호중구감소 상태의 급성백혈병 환아에서 경험적 항진균제로 투여한 Amphotericin B와 Itraconazole의 효과와 이상 반응 비교)

  • Lee, Sang-Yun;Park, Jong-Sun;Kim, Sun-Young;Yang, Keum-Jin;Park, Kyung-Deok;Kim, Hack-Ki
    • Pediatric Infection and Vaccine
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    • v.12 no.1
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    • pp.75-85
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    • 2005
  • Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

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A case of Bilateral Near Blindness Secondary to Isolated Sphenoid Sinus Aspergillosis with Headache (양측성 실명을 동반한 접형동 아스페르길루스증 1 예)

  • Yoon, Jun-Pil;Lee, Se-Jin;Lee, Jun;Kim, Ju-Hyun;Noh, Hyun-Doo
    • Journal of Yeungnam Medical Science
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    • v.24 no.1
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    • pp.79-84
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    • 2007
  • Sphenoid sinus aspergillosis is notorious for its serious complications, such as permanent cranial nerve deficits and possible death. The most common associated symptoms are headache, followed by visual changes, and cranial nerve palsies. Because of an insidious onset, frequently resulting in missed and delayed diagnosis, sphenoid sinus aspergillosis is a potentially lethal medical condition. We report a case of visual loss secondary to isolated sphenoid sinus aspergillosis. A 69-year-old man presented to our hospital with the complaint of headache. The headache started one year previously and was described as severe dull pain localized bilaterally to the temporo-orbital region. The patient took daily NSAIDs for the pain. The neurological examination was normal. The MRI of the brain showed a left sphenoid sinusitis. A transnasal endoscopic superior meatal sphenoidotomy was performed. Aspergillosis was confirmed after a surgical biopsy was obtained. The patient was discharged from hospital without antifungal therapy. One month later, the patient complained of headache and loss of vision bilaterally. The orbital MRI showed a left cavernous sinus and bilateral optic nerve invasion. The loss of visions was permanent. In our case, the diagnosis was delayed; antifungal agents were not administered after surgery and the patient lost his vision as a result. Therefore, early diagnosis and proper treatment are important. Although the treatment of an invasive type of aspergillus has not been established, surgical removal of a nidus and aggressive antifungal therapy are recommended.

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Successful Treatment of a Case with Rhino-Orbital-Cerebral Mucormycosis by the Combination of Neurosurgical Intervention and the Sequential Use of Amphotericin Band Posaconazole

  • Yoon, Young-Kyung;Kim, Min-Ja;Chung, Yang-Gu;Shin, Il-Young
    • Journal of Korean Neurosurgical Society
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    • v.47 no.1
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    • pp.74-77
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    • 2010
  • Rhino-orbital-cerebral (ROC) mucormycosis is an uncommon, acute and aggressive fungal infection. It remains a challenging problem to clinicians despite aggressive debridement surgery and antifungal therapy. The authors describe a case of ROC mucormycosis with pericranial abscess occurring in a female patient with uncontrolled diabetes mellitus. The infection initially developed in the right-sided nasal sinus and later progressed through the paranasal sinuses with the invasion of the peri-orbital and frontotemporal region, due to the delayed diagnosis and treatment. Numerous non-septate hyphae of the zygomycetes were identified by a punch biopsy from the nasal cavity and by an open biopsy of the involved dura. The patient was treated successfully with extensive debridement of her necrotic skull and surrounding tissues, drainage of her pericranial abscess and antifungal therapy, including intravenous amphotericin B for 61 days and oral posaconazole for the following 26 days. She returned to a normal life and has had no recurrence since the end of her treatment 15 months ago.

The Impact of Drug Interactions with Tyrosine Kinase Inhibitors on Adverse Event Development based on the changes of drug concentration level: Meta-analysis (Tyrosine Kinase 억제제와의 약물 상호작용이 약물 혈중농도 변화에 따라 부작용 발생에 미치는 영향: 메타분석 연구)

  • JinAh Hwang;Heeyoung Lee
    • Korean Journal of Clinical Pharmacy
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    • v.34 no.1
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    • pp.71-78
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    • 2024
  • Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience. However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA provides some guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted to understand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions: Study finds TKI-DDI not significantly linked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.