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Systemic candidiasis occurs when Candida yeast enters the bloodstream and may spread (becoming disseminated candidiasis) to other organs, including the central nervous system, kidneys, liver, bones, muscles, joints, spleen, or eyes. Treatment typically consists of oral or intravenous antifungal medications. In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used. Amphotericin B is another option.
Candidiasis is treated with antifungal medications; these include clotrimazole, nystatin, fluconazole, voriconazole, amphotericin B, and echinocandins. Intravenous fluconazole or an intravenous echinocandin such as caspofungin are commonly used to treat immunocompromised or critically ill individuals.
The 2016 revision of the clinical practice guideline for the management of candidiasis lists a large number of specific treatment regimens for "Candida" infections that involve different "Candida" species, forms of antifungal drug resistance, immune statuses, and infection localization and severity. Gastrointestinal candidiasis in immunocompetent individuals is treated with 100–200 mg fluconazole per day for 2–3 weeks.
Antifungal drugs are used to treat mycoses. Depending on the nature of the infection, a topical or systemic agent may be used.
Example of antifungals include: fluconazole which is the basis of many over-the-counter antifungal treatments. Another example is amphotericin B which is more potent and used in the treatment of the most severe fungal infections that show resistance to other forms of treatment and it is administered intravenously.
Drugs to treat skin infections are the azoles: ketoconazole, itraconazole, terbinafine among others.
Yeast infections in the vagina, caused by "Candida albicans", can be treated with medicated suppositories such as tioconazole and pessaries whereas skin yeast infections are treated with medicated ointments.
Antifungals are used for treatment with the specific type and dose depending on the patient's age, immune status, and specifics of the infection. For most adults, the initial treatment is an echinocandin class antifungal (caspofungin, micafungin, or anidulafungin) given intravenously. Fluconazole, amphotericin B, and other antifungals may also be used. Treatment normally continues for two weeks after resolution of signs and symptoms and "Candida" yeasts can no longer can be cultured from blood samples. Some forms of invasive candidiasis, such as infections in the bones, joints, heart, or central nervous system, usually need to be treated for a longer period. Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality.
Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended.
Persons living with AIDS often have a greater burden of disease and higher mortality (30-70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin. Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks. Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole. After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.
The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment.
Preventative antifungal treatment is supported by studies, but only for specific high-risk groups in intensive care units with conditions that put them at high risk for the disease. For example, one group would be patients recovering from abdominal surgery that may have gastrointestinal perforations or anastomotic leakage. Antifungal prophylaxis can reduce the incidence of fungemia by approximately 50%, but has not been shown to improve survival. A major challenge limiting the number of patients receiving prophylaxis to only those that can potentially benefit, thereby avoiding the creation of selective pressure that can lead to the emergence of resistance.
If mucormycosis is suspected, amphotericin B therapy should be immediately administered due to the rapid spread and high mortality rate of the disease. Amphotericin B is usually administered for an additional 4–6 weeks after initial therapy begins to ensure eradication of the infection. Isavuconazole was recently FDA approved to treat invasive aspergillosis and invasive mucormycosis.
After administration of either amphotericin B or posaconazole, surgical removal of the "fungus ball" is indicated. The disease must be monitored carefully for any signs of reemergence.
Surgical therapy can be very drastic, and in some cases of disease involving the nasal cavity and the brain, removal of infected brain tissue may be required. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures. Surgery may be extended to more than one operation. It has been hypothesized that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the organism.
Keeping the skin clean and dry, as well as maintaining good hygiene, will help larger topical mycoses. Because fungal infections are contagious, it is important to wash after touching other people or animals. Sports clothing should also be washed after use.
Chromoblastomycosis is very difficult to cure. The primary treatments of choice are:
- Itraconazole, an antifungal azole, is given orally, with or without flucytosine.
- Alternatively, cryosurgery with liquid nitrogen has also been shown to be effective.
Other treatment options are the antifungal drug terbinafine, an experimental drug posaconazole, and heat therapy.
Antibiotics may be used to treat bacterial superinfections.
Amphotericin B has also been used.
Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.
Fungal meningitis is treated with long courses of high dose antifungal medications. The duration of treatment is dependent upon the causal pathogen and the patient's ability to stave off the infection; for patients with a weaker immune system or diabetes, treatment will often take longer.
Oral candidiasis can be treated with topical anti-fungal drugs, such as nystatin, miconazole, Gentian violet or amphotericin B.
Underlying immunosuppression may be medically manageable once it is identified, and this helps prevent recurrence of candidal infections.
Patients who are immunocompromised, either with HIV/AIDS or as a result of chemotherapy, may require systemic treatment with oral or intravenous administered anti-fungals.
If candidiasis is secondary to corticosteroid or antibiotic use, then use may be stopped, although this is not always a feasible option. Candidiasis secondary to the use of inhaled steroids may be treated by rinsing out the mouth with water after taking the steroid. Use of a spacer device to reduce the contact with the oral mucosa may greatly reduce the risk of oral candidiasis.
In recurrent oral candidiasis, the use of azole antifungals risks selection and enrichment of drug-resistant strains of candida organisms. Drug resistance is increasingly more common and presents a serious problem in persons who are immunocompromised.
Prophylactic use of antifungals is sometimes employed in persons with HIV disease, during radiotherapy, during immunosuppressive or prolonged antibiotic therapy as the development of candidal infection in these groups may be more serious.
The candidal load in the mouth can be reduced by improving oral hygiene measures, such as regular toothbrushing and use of anti-microbial mouthwashes. Since smoking is associated with many of forms of oral candidiasis, cessation may be beneficial.
The current medical treatments for aggressive invasive aspergillosis include voriconazole and liposomal amphotericin B in combination with surgical debridement.
For the less aggressive allergic bronchopulmonary aspergillosis findings suggest the use of oral steroids for a prolonged period of time, preferably for 6–9 months in allergic aspergillosis of the lungs. Itraconazole is given with the steroids, as it is considered to have a "steroid sparing" effect, causing the steroids to be more effective, allowing a lower dose.,
Other drugs used, such as amphotericin B, caspofungin (in combination therapy only), flucytosine (in combination therapy only), or itraconazole,
are used to treat this fungal infection. However, a growing proportion of infections are resistant to the triazoles. "A. fumigatus", the most commonly infecting species, is intrinsically resistant to fluconazole.
Good denture hygiene involves regular cleaning of the dentures, and leaving them out of the mouth during sleep. This gives the mucosa a chance to recover, while wearing a denture during sleep is often likened to sleeping in one's shoes. In oral candidiasis, the dentures may act as a reservoir of Candida species, continually reinfecting the mucosa once antifungal medication is stopped. Therefore, they must be disinfected as part of the treatment for oral candidiasis. There are commercial denture cleaner preparations for this purpose, but it is readily accomplished by soaking the denture overnight in a 1:10 solution of sodium hypochlorite (Milton, or household bleach). Bleach may corrode metal components, so if the denture contains metal, soaking it twice daily in chlorhexidine solution can be carried out instead. An alternative method of disinfection is to use a 10% solution of acetic acid (vinegar) as an overnight soak, or to microwave the dentures in 200mL water for 3 minutes at 650 watts. Antifungal medication can also be applied to the fitting surface of the denture before it is put back in the mouth. Other problems with the dentures, such as inadequate occlusal vertical dimension may also need to be corrected in the case of angular cheilitis.
Drugs like ketoconazole,
voriconazole, and itraconazole are generally employed in treating the infection. Actinomycetes usually respond well to medical treatment, but the eumycetes are generally resistant and may require surgical interventions including amputation.
Treatment for fungal sinusitis can include surgical debridement; helps by slowing progression of disease thus allowing time for recovery additionally we see the options below:
- In the case of invasive fungal sinusitis, echinocandins, voriconazole, and amphoterecin (via IV) may be used
- For allergic fungal sinusitis, systemic corticosteroids like prednisolone, methylprednisolone are added for their anti-inflammatory effect, bronchodilators and expectorants help to clear secretions in the sinuses.
Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.
Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.
No vaccine is available. Simple hygienic precautions like wearing shoes or sandals while working in fields, and washing hands and feet at regular intervals may help prevent the disease.
Otomycosis is treated by debridment followed with topical azole antifungals, and symptomatically managed with oral antihistamines. Per a study in Iran 10cc acetic acid 2% plus 90 cc of isopropyl alcohol 70% was effective.
Prevention of aspergillosis involves a reduction of mold exposure via environmental infection-control. Anti-fungal prophylaxis can be given to high-risk patients. Posaconazole is often given as prophylaxis in severely immunocompromised patients.
The treatment of Majocchi's disease can be difficult because the condition can slowly progress and is chronic in nature. After a period of time, the lesions can reoccur. Even though the condition has improved, there is always the possibility of reoccurrence. There are treatments available to help improve the symptoms, however, there is no absolute cure for the disease. Some of these treatments include the application of topical steroids and lotions and ultraviolet therapy. The use of narrowband UVB and psoralen plus UVA have shown to be effective treatments for some patients with pigmented purpuric dermatoses. Majocchi granuloma also commonly occurs as a result of the use of potent topical steroids on unsuspected tinea. Historically, antifungal therapy has been successful in controlling MG in most instances. Therapies that have been used, included oral potassium iodide, mildly filtered local X-radiation, and topical applications of Asterol as a fungicide in both tincture and ointment forms. In modern medicine, systemic antifungals, such as griseofulvin, ketoconazole, and itraconazole, are the pillars of therapy, as they are safe and effective. The duration of therapy should be at least 4–8 weeks, and treatment should be continued until all lesions are cleared. Currently, no data about relapse rates or the complications of not treating Majocchi granuloma exist.
Most treatments are topical or oral antifungal medications.
Topical agents include ciclopirox nail paint, amorolfine or efinaconazole. Some topical treatments need to be applied daily for prolonged periods (at least 1 year). Topical amorolfine is applied weekly. Topical ciclopirox results in a cure in 6% to 9% of cases; amorolfine might be more effective. Ciclopirox when used with terbinafine appears to be better than either agent alone.
Oral medications include terbinafine (76% effective), itraconazole (60% effective) and fluconazole (48% effective). They share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed, persistence in the nail for months after discontinuation of therapy. Ketoconazole by mouth is not recommended due to side effects. Oral terbinafine is better tolerated than itraconazole. For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised.
In bovines, an infestation is difficult to cure, as systemic treatment is uneconomical. Local treatment with iodine compounds is time-consuming, as it needs scraping of crusty lesions. Moreover, it must be carefully conducted using gloves, lest the worker become infested.
There are many topical antifungal drugs useful in the treatment of athlete's foot including: miconazole nitrate, clotrimazole, tolnaftate (a synthetic thiocarbamate), terbinafine hydrochloride, butenafine hydrochloride and undecylenic acid. The fungal infection may be treated with topical antifungal agents, which can take the form of a spray, powder, cream, or gel. Topical application of an antifungal cream such as terbinafine once daily for one week or butenafine once daily for two weeks is effective in most cases of athlete's foot and is more effective than application of miconazole or clotrimazole. Plantar-type athlete's foot is more resistant to topical treatments due to the presence of thickened hyperkeratotic skin on the sole of the foot. Keratolytic and humectant medications such as urea, salicyclic acid (Whitfield's ointment), and lactic acid are useful adjunct medications and improve penetration of antifungal agents into the thickened skin. Topical glucocorticoids are sometimes prescribed to alleviate inflammation and itching associated with the infection.
A solution of 1% potassium permanganate dissolved in hot water is an alternative to antifungal drugs. Potassium permanganate is a salt and a strong oxidizing agent.
Patients with single aspergillomas generally do well with surgery to remove the aspergilloma, and are best given pre-and post-operative antifungal drugs. Often, no treatment is necessary. However, if a patient coughs up blood (haemoptysis), treatment may be required (usually angiography and embolisation, surgery or taking tranexamic acid). Angiography (injection of dye into the blood vessels) may be used to find the site of bleeding which may be stopped by shooting tiny pellets into the bleeding vessel.
For chronic cavitary pulmonary aspergillosis and chronic fibrosing pulmonary aspergillosis, lifelong use of antifungal drugs is usual. Itraconazole and voriconazole are first and second-line anti fungal agents respectively. Posaconazole can be used as third-line agent, for patients who are intolerant of or developed resistance to the first and second-line agents. Regular chest X-rays, serological and mycological parameters as well as quality of life questionnaires are used to monitor treatment progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing as individuals vary in their absorption levels of these drugs.