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
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.