Hospital Infections with Fungi
Fungi are found everywhere. Hospitals are not the clean, germ free places we would like them to be. Instead, hospitals concentrate pathogenic organisms including fungi. Hospital also concentrate patients whose immune defenses are compromised, even shut down so that infections of all kinds are very common.
The two most prevalent fungal infections in hospitals are caused by Candida and Aspergillus species. The prevention of fungal infections in hospitals should be a priority but in practice few preventive measures are deployed. Diagnosis and treatment remain difficult at best.
Pappas stated: "Invasive fungal infections are an increasingly important consideration in the medical care of critically ill patients and in patients with immunosuppression. New methods may increase the rate and accuracy of the diagnosis of invasive fungal infections, and the use of scoring systems that consider the risk factors for the development of invasive fungal infections may allow earlier therapy, a critical component of the successful treatment of these serious infections.
Husain et al studied fungal infections in 53 liver and heart transplant recipients: Invasive mycelial infections were due to Aspergillus species in 69.8% of patients, to non-Aspergillus hyalohyphomycetes in 9.4%, to phaeohyphomycetes in 9.4%, to zygomycetes in 5.7%, and to other causes in 5.7%. Overall mortality at 90 days was 54.7%. The associated mortality rate was 100% for zygomycosis, 80% for non-Aspergillus hyalohyphomycosis, 54% for aspergillosis, and 20% for phaeohyphomycosis. Thus, non-Aspergillus molds have emerged as significant pathogens in organ transplant recipients. These molds are more likely to be associated with disseminated infections and to be associated with poorer outcomes than is aspergillosis. Clin Infect Dis. 2003; 37(2):221-9 (ISSN: 1537-6591)
A concern is the emergence of more resistant fungi; better selection of at risk patients for antifungal prophylaxis will reduce indiscriminate drug use and reduce the rate of fungal evolution. According to the US Centers for Disease Control: " Invasive fungal infections cause substantial morbidity and mortality and are a costly, common problem in healthcare settings. The fungus Candida is the most common cause of healthcare-associated bloodstream infections in the United States. Some Candida are becoming increasingly resistant to first-line and second-line antifungal medications, namely, fluconazole and echinocandins (anidulafungin, caspofungin, and micafungin). Approximately 7% of all Candida bloodstream isolates tested at CDC are resistant to fluconazole, most of which are Candida glabrata. CDC’s surveillance data indicate that the proportion of Candida isolates that are resistant to fluconazole has remained fairly constant over the past twenty years. Echinocandin resistance, however, appears to be on the rise, especially among Candida glabrata." (New CDC Expert Commentary on Medscape Accessed Online June 2017 https://www.cdc.gov/fungal/antifungal-resistance.html)
Candida albicans is the most common fungal pathogen among immune-compromised, hospitalized patients, accounting for roughly 50-60% of all bloodstream fungal isolates. Candida species are an important cause of infection in intensive care units increased by 207% from 1979 to 2000. Risk factors include chemotherapy, organ transplants, abdominal surgery, central vascular lines, often used in ICU patients; the use of multiple or broad-spectrum antibiotics; total parenteral nutrition (TPN). The incidence of candida infection increases the longer a patient stays in hospital with peak incidence of infection around day 10.
Waknine reported that makers of tumor necrosis factor (TNF)-blocking agents were ordered to strengthen warnings regarding the risk for histoplasmosis and other invasive fungal infections by the US Food and Drug Administration. Since the initial approval of the 4 TNF blockers, the prescribing information for these drugs has included information about the risk of serious infections, including fungal infections; however physician are not recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment.
The US FDA has received 240 reports of histoplasmosis in patients receiving infliximab (Remicade); 207 cases from etanercept (Enbrel);and adalimumab (Humira) 16 cases. 1 case occurred during treatment with certolizumab pegol (Cimziac), approved in 2008. Missed diagnoses in 21 patients led to treatment delays and 12 deaths. Fatal cases of coccidioidomycosis and blastomycosis have also been reported. Healthcare professionals are advised to closely monitor patients for signs and symptoms of fungal infection during and after treatment with anti-TNF drugs. Patients who develop fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates on X-ray, or serious systemic illness should undergo a "complete diagnostic workup."
The FDA advised that a high index of suspicion should be maintained for invasive fungal infections in symptomatic patients. If possible, the decision to initiate empiric antifungal therapy should be made in conjunction with an infectious diseases specialist. An infectious disease consultation is also recommended when determining the duration of antifungal therapy and whether anti-TNF therapy should be resumed on recovery, particularly for patients who reside in regions of endemic mycoses. TNF blockers are immunosuppressive agents approved to treat immune system diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ankylosing spondylitis.
Yael Waknine. Patient Deaths Spark Stronger Warnings for TNF Blockers. Medscape Medical News 2008. Accessed online September 4, 2008. In the US, adverse events related to use of anti-TNF agents should be reported to the FDA's MedWatch reporting program.
Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161-189.
Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006;173:707-717
Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348-359
A profusion of fungi exists in the environment. Some fungi are able to cause an invasive infection in otherwise healthy individuals. Other fungi are opportunistic fungi that become invasive when immune defenses are compromised. Diagnosis of fungal infection is difficult. There are many problems when you try to connect a test result to a disease. Fungi are so abundant and there are so many varieties in every environment that it is seldom easy to pick just one cause among many. Fungi are inhaled and ingested. Foods always contain fungal spores and actively growing molds. Attempts to culture fungi often fail; only a small number grow in the culture media commonly used. Some new methods of detecting fungal DNA may be useful but development of reliable tests is slow and expensive.
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