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With the widespread use of broad-spectrum antibiotics and immunosuppressants, invasive fungal infections are becoming more common in the respiratory department. The clinical status of fungal infections has become increasingly prominent and has become an important component of nosocomial infections.

 

Common clinical pathogenic fungi

Common infection fungi can be divided into pathogenic fungi and conditional pathogenic fungi:

Pathogenic fungi: or infectious fungi, are primary pathogenic bacteria, often leading to primary exogenous fungal infections, can invade normal immune function hosts, patients with impaired immune function are prone to systemic dissemination; pathogenic fungi are mainly Organized cytoplasmic bacteria, coccidioides, paraspora, dermatitis buds, foot bacillus and spores.

Conditional pathogenic fungi: or opportunistic fungi, such as Candida, Aspergillus, Cryptococcus, Mucor and Penicillium, Rhizopus, Absidia, Fusarium and Pneumocystis. These are mostly saprophytic or phytopathogenic bacteria, which are pathogenic to the human body, but when the host has a predisposing factor for fungal infection, it can cause deep fungal infection.

 

Common antifungal drugs

Fungal infections should not be underestimated. For invasive pulmonary fungi, the condition is more serious and the mortality rate is high. Timely and effective antifungal treatment is of great significance in relieving the disease and improving the prognosis. The most commonly used antifungal drugs in the respiratory department are as follows:

Polyene antifungal drugs

1. Amphotericin

Antibacterial spectrum: After the approval of the amphotericin B in 1958, it has been nearly half a century since its introduction. The drug has antibacterial activity for almost all fungi, and is similar to Candida, Cryptococcus, Aspergillus, and biphasic fungi. Strong inhibition. Fusarium is not sensitive, and S. cerevisiae and Trichophyton are resistant.

Amphotericin B is not absorbed by the mucosa. The gastrointestinal tract only absorbs a small amount, so only the intravenous preparation has a long half-life (24 hours) and can be administered once a day. Tissue penetration is weak, but it is not easy to enter the cerebrospinal fluid through the blood-brain barrier. If the drug is used alone to treat fungal meningitis, it can be administered intrathecally.

Clinically used for the treatment of systemic candidiasis, cryptococcosis, especially cryptococcal meningitis, aspergillosis, mucormycosis, spore silk disease, fusarium disease, dark filament mold, colored germination, Trichosporon infection, Penicillium marneffei, can also treat blastomycosis, paracoccal disease, coccidioidomycosis, histoplasmosis.

Dosage: generally starting from a small amount, initial 0.5-1 mg per day, adding 5% glucose solution 500 ml slowly, in the dark, no less than 6-8 h, 2 mg on the 2nd and 3rd day And 5 mg, if the patient does not have a serious reaction, increase 5 mg per day. The highest dose for adults is 50 mg. For most deep fungal infections, amphotericin B is used for 6-8 weeks with a total dose of 1-2 g.

The drug is dose-dependent. If blood urea nitrogen and creatinine are higher than normal, dosing should be administered every other day or suspended to prevent kidney damage.

2. Amphotericin B lipid preparation

Since amphotericin B often causes toxic side effects such as infusion reaction and kidney damage, the advent of amphotericin B liposome solves this problem. The liposome is well tolerated, and the effect on amphotericin B is poor. And the preparation of serious toxic side effects can be used.

3. Nystatin

Antibacterial spectrum: In vitro tests showed that Candida albicans, Cryptococcus neoformans, capsular histoplasma, dermatitis buds and dermatophytes were sensitive to them.

Oral is not easy to absorb, almost all discharged from the stool, skin and mucous membrane medication is not easy to absorb, it is only used to treat candidiasis of oral mucosa, gastrointestinal tract and vagina.

More clinically, the tablets are dissolved in the mouth of the water to reduce the chance of opportunistic infections of oral fungi and to rule out the possibility of false positives of the fungus.

Triazole drugs

1. Fluconazole

Antibacterial spectrum: It is a broad-spectrum antifungal drug with antibacterial activity against dermatitis buds, coccidioides, and capsular histoplasma, and is effective against Cryptococcus neoformans, most Candida, and dermatophytes. Not sensitive to Candida krusei and Candida glabrata.

Fluconazole can be administered orally or intravenously. The bioavailability of oral and intravenous administration is similar, more than 90%, and food does not affect absorption. Oral and intravenous administration can produce the same blood concentration, and within a large dose range, the plasma concentration increases with increasing dose. It can pass through the blood-brain barrier and can be worn in human dialysate. Unlike other azole antifungal drugs, fluconazole has a low self-binding rate (about 12%).

Common doses: 400 mg on day 1, followed by 200 mg per day, the daily dose to severely ill patients can be increased to 400 mg. The usual dose for the treatment of invasive cryptococcosis is 400 mg daily. The course of treatment is determined according to the clinical treatment response, and the course of cryptococcosis is generally not less than 6 to 8 weeks. The dosage range for prophylactic use is 50-400 mg per day, depending on the risk of developing a fungal infection in the patient. For patients with high risk factors for systemic fungal infections such as severe or prolonged neutropenia, a recommended preventive dose of 400 mg daily is recommended.

2. Itraconazole:

Antibacterial spectrum: including pathogenic fungi such as Candida, Aspergillus, Cryptococcus and Histoplasma, which have low activity against Fusarium and are ineffective against Mucor infection.

Itaconazole has capsules, solutions and intravenous injections; its capsule preparation is not completely absorbed orally (about 55%), and it can be absorbed by taking it together with food. Oral solution preparations have higher bioavailability after taking them on an empty stomach. Therefore, itraconazole oral solution is best taken on an empty stomach; itraconazole has a high protein binding rate and is widely distributed in various tissues in the lungs. The concentration of drugs in the liver and bone is 2-3 times higher than in plasma.

It can be used clinically for the treatment of fungal infections caused by Aspergillus, Candida, Cryptococcus and Histoplasma, as well as the prevention of Aspergillus and Candida infections. The recommended dose is 200 mg/time on days 1 and 2, 2 intravenous infusions per day, and 200 mg intravenous infusion on the 3rd to 14th day, once a day. The infusion time is not less than 1 h.

3. Voriconazole

The second generation of triazole antifungal drugs, marketed in 2002, has a broad-spectrum antifungal effect, its antifungal activity is 10-500 times stronger than fluconazole, antibacterial spectrum against Aspergillus, Cryptococcus, Candida and fluconazole The resistant K. krusei and Candida glabrata have bactericidal activity. In addition, there are some rare anti-bacterial activities of S. cerevisiae and Alternaria.

Dosage form is divided into oral tablets (50 mg, 200 mg / tablet) and injection powder (200 mg / bottle), intravenously administered 6 mg / kg on the first day, (or 400 mg, <40 kg for weight > 40 kg) 200mg), once/12h; from the second day, 200mg, once/12h (half the amount of <40 kg).

It can be used clinically to treat infections caused by candidiasis (including infections caused by fluconazole-resistant Candida), invasive aspergillosis, and Fusarium.

4. Posaconazole

It is a new type of triazole broad-spectrum antifungal drug, which is derived from the structure of itraconazole and currently only has oral preparations.

Antibacterial spectrum: It has good antifungal activity against Candida, Cryptococcus neoformans, Aspergillus, Trichosporon, zygomycetes, histoplasma, Fusarium, but has poor curative effect on Candida glabrata and Candida krusei .

It is mainly used to treat fungal infections caused by Aspergillus, Fusarium and Bacterial bacteria, refractory to other drugs, or resistant to other drugs.

Echinocandins

It is a new antifungal drug for injection. This class of drugs is a glucan synthase inhibitor of the fungal cell wall, which inhibits the synthesis of fungal cell walls. Less toxic to humans. Commonly used are caspofungin, micafungin and so on.

1. Caspofungin

Antibacterial spectrum: It has good antibacterial activity against Aspergillus and Candida, and also has effect on K. sphaericus, and has effects on fluconazole, amphotericin B or fluorocytosine-resistant bacterium. However, it has no effect on Cryptococcus, Fusarium, Trichosporon, dermatophytes, and zygomycetes;

This product is not absorbed orally, and it is 9-11 hours after the intravenous infusion. 70 mg on day 1 and 50 mg on day 2, once daily for 1 hour.

Clinically, it is mainly used for invasive Aspergillus infection, which is ineffective or intolerable by other antifungal drugs. Caspofungin is a safer alternative to invasive aspergillosis patients who are ineffective or intolerant of traditional medications.

2. Micafungin

Antibacterial spectrum: Sensitive to Candida albicans (including fluconazole-resistant strains) and most non-Candida albicans and Aspergillus (including amphotericin-resistant Aspergillus sp.). Inactive to Cryptococcus neoformans.

It can be used clinically for the treatment and prevention of respiratory, gastrointestinal and blood infections caused by Candida and Aspergillus. Micafungin is usually used in the treatment of candidiasis 50 mg once daily for intravenous infusion. The usual dosage for the treatment of aspergillosis is 50-150 mg once daily, intravenous drip. Patients with severe and refractory candidiasis or aspergillosis can be carefully increased to 300 mg/d depending on the condition.

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