New Antifungals For Systemic Fungal Infections Biology Essay


Recently, systemic fungal infections have become a common feature in our modern day hospitals. It has led to increased deaths especially in patients with neutropenia and other diseases that cause low immunity in the human body. It has become increasingly difficult for medical practitioners to prevent invasive fungal infections due to their difficulty in diagnosis and treatment. As a result, a variety of these diseases have developed resistance to the commonly used anti-fungals thereby posing an increased risk to the patients. However, with increase in medical technology in the recent past, a step has been made in understanding the body's immune response to the fungi (Burgos, 2008, p. 1290). Medical researchers have studied the epidemiology of systemic fungal infections to come up with a solution. The studies have yielded improved diagnostic tests which are able to reliably identify the diseases in good time to be treated and therefore increase the clinical outcomes after treatment. The patients are exposed to fungal infections through several ways. Air forms the major risk factor for exposure as shown in the figure below.

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Figure 1: where patients are exposed

Source: Hajjeh, R. & Warnock, D. (2004), p. 607

Various sources of infections have been identified in a hospital setting. The environment in which the patient is may harbor the fungi and thus exposure to the infections. The other source is the food in which the patients are given while admitted to the hospitals. Various forms of mould have been show to grow in wet and dampy corners in the kitchen and if proper care is not taken contamination may result. Water has been shown to harbor several types of mould which are then inhaled as vapors. The fomites which include furniture, carpets and other things also contribute to infections. In a study to find the contamination of food for neutropaenic patients the following results were obtained;

Table 1: contamination of food for neutropaenic patients


Contaminated samples (%)




Aspergillus fumigatus, A. flavus



Aspergillus fumigatus, A. niger

Freeze-dried soup


Aspergillus fumigatus, A. niger



Aspergillus fumigates



Aspergillus fumigates



Aspergillus fumigates

Grapefruit juice


Aspergillus fumigates

Source: Hajjeh, R. & Warnock, D. (2004), p. 913

New anti-fungal drugs have been developed which have proved to be effective in the treatment of systemic fungal infections (Hajjeh, & Warnock, 2004, p. 1550). These developments are encouraged through the continuous medical education that is encouraged in health institutions as a way of keeping our medical personnel updated on the current events on the medical field.

In many hospitals across the world, systemic fungal infections have been observed to occur in three instances. To begin with high cases of systemic fungal infections have been observed in neutropaenic patients. These are the patients that have been subjected to chemotherapy treatment to prevent cancer growth. As a result, their immune responses have been suppressed and they are therefore at risk of any opportunistic infections like the fungal infections. These patients have to be protected from nosocomial infections in their long stay at the hospital (Yadav et al., 2007, p. 640). The second instance where systemic fungal infections are high is in patients with Acquired Immune Deficiency Syndrome as a result of infection by the HIV virus. The virus destroys the CD4 cells of the patients thereby lowering their count in the body. These cells are involved with the body's immunological response and therefore their low numbers result in low immunity and exposure of the patients to opportunistic infections. The third case is for the patients in the Intensive Care Unit who may not be neutropaenic. These patients' skin mostly is not intact due to many factors like burns or other systemic illnesses. The skin with breaches exposes them to many pathogens in the atmosphere on wherever they come into contact with. Fungal infections pose a serious threat to patients who are undergoing transplantation procedures. In a study to determine infection by aspergillus after BMT, the following results were found;

Figure 2: infection by aspergillus after BMT

Source: Richardson, M. (2005), p.354

It has been found to cause up to 5-10% of deaths among patients undergoing lung or liver transplantation. Previous researches have suggested a sharp rise of up to 500% in infections by Candida spp. as compared to several years ago. In the recent past, major developments have been achieved in protecting these patients from fungal infections. The measures applied have served to reduce mortalities due to fungal infections and also to improve care to the patients and reduce their suffering.

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The diagnosis and treatment of systemic fungal infections is done in most cases when it's too late. The practical diagnosis applied world over of blood or infected tissue cultures caused a delay before effective treatment therapy can be offered. Many patients have been on broad spectrum antibiotics for much longer time in order to eliminate the systemic signs on their bodies. It is also common to find patients being given dosing that are not appropriate and effective to cure their infections when the treatment therapy is initiated. There had been a disagreement on when treatment should be offered for systemic fungal infections (Sendid et al., 2007, p.650). This was more so often for Candida spp. which is common and poses a high risk. Most of the health personnel offered treatment based on identification of this organism in the bloodstream of the patients. There is also a disagreement on when to replace intravascular lines if fungal attacks are detected. Most doctors use various criteria to determine the type of medication to be used. The most common are the colonization index which is the degree of infection for the patients, the number of cultures that have been positively identified, and the type of organisms among other criteria. There have been increased researches to offer more effective diagnostic tools for systemic infections. One of the developed methods is sandwich ELISA for the detection of circulating galactomannan. Maertens et al. (2005, p.1605) conducted a screening survey and were able a sensitivity and specificity of greater than 90% in the detection of Aspergillus. With such promising results, the method was given the go ahead by the US Food and Drug Administration. The application of Polymerase Chain Reaction (PCR) in detection of fungal nucleic acids has also served to improve the diagnosis of Aspergillus and to selectively identify Candida spp. infections (Arnaud et al., 2007, p. 450). To increase the sensitivity and specificity of these methods, a combination of two or more methods is applied. These methods have become quite effective in the diagnosis of various species of fungi which are known to cause systemic infections. The improvement of these methods will be a good tool to fighting infections.

Treatment of systemic mycoses has at many times been a hard task for the health fraternity. Treatment failures have been reported with the common treatment therapies used. This is due to a number of reasons which if not checked may lead systemic fungi to develop resistance towards the medication given. Many patients are given doses which are ineffective or less to eliminate the fungi from the body. The treatment therapy may also be initiated when the infections have developed for too long such that the treatment outcome is not effective. Treatment failure has been reported in up to 20-30% of patients who are infected with Candida spp. of fungi. In a study conducted on patients with candidaemia, the mortality rate was 45% which is significantly high (Seneviratne, 2008, p.3260). In patients suffering from chronic infections like AIDS, secondary resistance has been reported in cases with prolonged use of fluconazole. It is often difficult to assess the resistance levels to antifungal therapies. However, guidelines have been developed by The National Committee for Clinical Laboratory Standards which are instrumental in assessment of effectiveness of azole anti-fungals (Hachem, et al., 2008, 1380). Resistance to the drugs should be avoided at all times in order to eliminate these infections. Patients have therefore been advised to follow strictly the physician's directions strictly whenever they are under medication from anti-fungals.

Fungi infections have been known to be opportunistic infections for many years now. Amphotericin B deoxycholate was the recognized treatment therapy for the systemic fungal infections. In the past, this drug was used due to lack of a better alternative but recently there has been development of less toxic alternatives of amphotericin and azole. The azole drugs are used for prophylaxis purposes and have been instrumental in lowering the mortality rates of patients with candida albicans infection. Currently, other types of fungi especially molds like Aspergillus have been recognized to causing increased deaths. However, increased diagnostic tools have been helpful in the treatment of these types of fungi. Recent studies have strongly suggested an increased risk of fungal infections on patients undergoing transplantation (Gulshan, & Moye-Rowley, 2007, p. 1940). This has been attributed to immune lowering drugs that are given to the patients to decrease chances of graft rejection. In patients undergoing bone marrow transplant, a study found them at higher risks of mold infections compared to other patients undergoing normal treatment procedures. Other confounding factors established were the age of the patients and other underlying health conditions. Development of new diagnostic criteria has enabled early screening of the patients undergoing transplantation and therefore reducing the risks to fungal infections.

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There is importance in understanding the sources of exposure to the fungal pathogens in order to develop the preventive strategies. In the hospitals, it is common practice to employ air filtration measures and the isolation of patients to prevent any hospital related fungal exposure. Recent researches have shown the water system in the hospitals to be a source for fungal infections. The delivery pipes may contain pathogenic or non-pathogenic molds which later on find their way to the patient's rooms (Isham & Ghannoum, 2006, p. 4230). These molds have been found to be inhaled by the patients through aerosolization thereby causing nosocomial fungal infections. In one specific study in a hospital, it was found out that Aspergillus species had formed colonies in as much as 70% of the plumbing structures and water samples taken. Patients have also been shown to be living in mouldy houses which increase their risk of infection. This is as depicted in the figure below;

The water system can therefore be a potential source of infection to the patients. The various studies conducted clearly indicate the epidemiology of the fungal infections in the hospitals for both in patient and discharged patients. They have shown the multiplicity of factors leading to causation of mycoses (Medoff, 2004, p. 320). More studies are however needed to highlight on drug resistance to maximize the effectiveness of anti-fungal drugs.

The Neutrophil-mediated immunity was largely believed to be the only immunological response the body provides against fungal infections particularly attacks from Candida and Aspergillus. However, recent studies have also shown that cellular immunity also plays a major role against the invasive systemic fungi. Scientists have come to appreciate the role of T lymphocytes in prevention against molds (Brown, Sexton & Johnston, 2006, p.240). There is increasing studies being undertaken to find suitable vaccines for prevention of mould attacks especially to the hospitalized patients at risk of opportunistic infections due to their low immunity. Studies previously done on laboratory animals can now be reliably replicated in human beings with promising results. The mysteries that previously existed on immune responses to fungal infections is being unraveled as times goes on and as new medical strategies are applied and tested. They continue expounding on immunotherapies which have shown signs of effectiveness in fungal prevention.

New anti-fungals are being developed particularly to prevent against aspergillosis and candidiasis which have become common especially with immunocompromised patients (Mennink-Kersten et al., 2008, p.1395). The following table shows the various anti fungals which are in use;

Table 2: anti-fungals class and respective drugs



Polyene antifungals





Amphotericin B

























· Terbinafine

· Amorolfine

· Naftifine

· Butenafine

Source: Furukawa et al., 2006, p.453

Amphotericin B had been previously the drug of choice against a host of fungal infections. This drug is still the main antifungal drugs for severe systemic mycoses in many patients with good clinical outcomes. Amphotericin B is used in the treatment of infections from various fungi. It can be used for candida infections, blastomyces, histoplasma attacks, Cryptococcus among others. Studies have shown that this drug binds to a fungi's ergosterol in its cell membrane. This causes a disruption in the functioning of the cell membrane and consequently causes the death of the fungi. The drug has been shown to have a post anti-fungal effect of up to more than ten hours.

The systemic administration of this drug causes ranging diverse effects to the patients. It has been reported to result in high fever, vomiting, nephrotoxicity and nausea. Nephrotoxicity which includes loss of magnesium and potassium in the body is sometimes not reversible if the treatment therapy is continued for a long period of time (Furukawa et al., 2006, p.450). The use of AB has also been associated with severe hypertension in some cases. Doctors have advised for lowering of doses for the patients with renal failure. This drug has gone under various transformations to increase its effectiveness and at the same time lower its toxicity.

The other types of drugs used are fluconazoles such as azoles. These drugs work by preventing formation of ergosterol on the fungi cell membrane. Ergosterol is essential for the fungi to maintain their cellular integrity and therefore lack of it results in inhibition of fungal growth. Fluconazole is administered for the management of Candida albican species, some Cryptococcus spp and coccidiodomycosis. In patients with chronic treatment with fluconazole, C. albicans have been shown to acquire resistance to this drug. Voriconazole provided a better clinical outcome in the treatment of invasive aspergillosis and thus was recommended. In a study to demonstrate the effectiveness of voriconazole, it was found to provide a salvage therapy for aspergillus and other filamentous fungi (Gregori et al., 2007, p. 1340). This use of this drug for the treatment of candidemia is not well founded. However, voriconazole has recorded better results against non-albicans Candida spp than fluconazole. This drug is effective against a variety of mycoses which are resistance to fluconazole. The drug has been reported to cause reversible visual disturbances in 14% of the patients and caused a rise in bilirubin in others. In yet other rare cases, some patients reported rashes as a result of consuming the drug. Another drug that provided salvage therapy against aspergillosis is caspofungin. This drug has been shown to work by inhibiting the growth of hyphal cells of the fungi and therefore prevention from reproducing. Studies have shown that the use of this drug produces similar results as for amphotericin B. With increased resistance to the anti-fungals being exhibited in many patients, more profound investigations are called for to find a solution that works for all.

The common types of systemic fungal infections are Candida spp. and Aspergillus. The commonly used drug of choice is amphotericin B. With discovery of other types of azole drugs, this has changed. The AB drug main problem is its toxicity and increased resistance from a variety of fungi due to recurrent use (Sugar et al., 2003, p. 844). To reduce the harmful side effects exhibited by patients on AB therapy, various formulations of the drug have been developed like the lipid formulations. However, this has increased the cost of this drugs leading to them becoming impractical for use by many of the patients. Systemic Candida infection has been treated with high doses of fluconazole. There has been demonstrated resistance to some species of Candida due to repeated therapies especially for patients with chronic conditions like AIDS (Natsch et al., 2004, p.308). In the management of infections by Aspergillosis species, AB is still the preferred drug. However other flucoconazoles like voriconazole have also proven to be as much effective as AB. Combined therapy like use of AB with rifampicin has shown better results for the management of aspergillosis. This has been met with some controversies from various sectors especially with use of azole and other polyene anti-fungals. Azole induced inhibition of the synthesis of ergosterol might result in antagonism with AB. The controversies have been proved to be uncalled for as recent studies show that a combination of AB + fluconazole had beneficial effects. The patients on the combined therapy experienced an increased clearance of the organism from their bloodstream. There is increased urgency to initiate treatment for Aspergillus infections for patients with low immunity basing on clinical criteria rather than waiting for microbiological confirmations which may at times take longer time and the infection may worsen.

According to Sorin & Simona (2008, p.47), Candida causes infections of the oral mucous membrane and perineal skin infections in infants. This causes oral thrush and diaper dermatitis respectively in the newborns. Candidiasis has become the most common problem in intensive care units of the neonates. The drug of choice had been AB and 5-fluorocytosine but their toxicity effects have been profound. Fluconazol has provided an alternative for treatment of Candida infections and other yeasts. Due to increase of antifungal resistance, there is an increase in use and marketing of azole drugs. The dose to be used for pediatric treatment of fungal infections is still not clear.

The past few years have recorded great changes in the field of mycology. There has been development of new diagnostic tools for quick and effective diagnosis of various types of fungal infections. In addition, new antifungal drugs have been generated due to increase in medical technology. This has rekindled efforts towards prevention and the treatment of mycotic infections. There has been increase in drug resistance due to prolonged use or recurrent uses of certain anti-fungals. Low immunity status as a result of certain diseases like AIDs has also confounded on the resistance. In order to improve the clinical outcomes of patients with fungal infections, these challenges must be tackled through improvements in drug therapies. Increased investigations are therefore called for in the field of mycology.