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211 - Candidiasis
211 - Candidiasis
211 Candidiasis
also is considered important in pathogenesis. Numerous reviews of
cases of hematogenously disseminated candidiasis have identified
the predisposing factors or conditions associated with disseminated
John E. Edwards, Jr. disease (Table 211-1). Women who receive antibacterial agents may
develop vaginal candidiasis.
Innate immunity is the most important defense mechanism against
The genus Candida encompasses >150 species, only a few of which hematogenously disseminated candidiasis, and the neutrophil is the
cause disease in humans. With rare exceptions (although the excep- most important component of this defense. Macrophages also play an
tions are increasing in number), the human pathogens are C. albicans, important defensive role. STAT1, Dectin-1, CARD9, and TH1 and TH17
C. guilliermondii, C. krusei, C. parapsilosis, C. tropicalis, C. kefyr, C. lusitaniae, lymphocytes contribute significantly to innate defense (see “Clinical Man-
C. dubliniensis, C. glabrata, and C. auris. Ubiquitous in nature, they ifestations,” below). Although many immunocompetent individuals have
inhabit the gastrointestinal tract (including the mouth and orophar- antibodies to Candida, the role of these antibodies in defense against the
ynx), the female genital tract, and the skin. Although cases of candid- organism is not clear. Multiple genetic polymorphisms that predispose to
iasis have been described since antiquity in debilitated patients, the disseminated candidiasis will most likely be identified in future studies.
recurrent vaginal infections. disseminated candidiasis, probably because their neutrophil function
Other Candida skin infections include paronychia, a painful swelling remains intact.
at the nail–skin interface; onychomycosis, a fungal nail infection rarely
caused by this genus; intertrigo, an erythematous irritation with red- Deeply Invasive Candidiasis Deeply invasive Candida infec-
ness and pustules in the skin folds; balanitis, an erythematous-pustular tions may or may not be due to hematogenous seeding. Deep esophageal
Infectious Diseases
infection of the glans penis; erosio interdigitalis blastomycetica, an infec- infection may result from penetration by organisms from superficial
tion between the digits of the hands or toes; folliculitis, with pustules esophageal erosions; joint or deep-wound infection from contiguous
developing most frequently in the area of the beard; perianal candidiasis, spread of organisms from the skin; kidney infection from catheter-
a pruritic, erythematous, pustular infection surrounding the anus; initiated spread of organisms through the urinary tract; infection of
and diaper rash, a common erythematous, pustular perineal infection intraabdominal organs and the peritoneum from perforation of the gas-
in infants. Generalized disseminated cutaneous candidiasis, another form trointestinal tract; and gallbladder infection from retrograde migration of
of infection that occurs primarily in infants, is characterized by wide- organisms from the gastrointestinal tract into the biliary drainage system.
spread eruptions over the trunk, thorax, and extremities. The diagnos- However, far more commonly, deeply invasive candidiasis results
tic macronodular lesions of hematogenously disseminated candidiasis from hematogenous seeding of various organs as a complication of can-
(Fig. 211-1) indicate a high probability of dissemination to multiple didemia. Once the organism gains access to the intravascular compart-
ment (either from the gastrointestinal tract or, less often, from the skin
through the site of an indwelling intravascular catheter), it may spread
hematogenously to a variety of deep organs. The brain, chorioretina
(Fig. 211-2), heart, and kidneys are most commonly infected and the
liver and spleen less commonly so (most often in neutropenic patients).
In fact, nearly any organ can become involved, including the endocrine
glands, pancreas, heart valves (native or prosthetic), skeletal muscle,
joints (native or prosthetic), bones, and meninges. Candida organisms can
also spread hematogenously to the skin and cause classic macronodular
lesions (Fig. 211-1). Frequently, painful muscular involvement is evident
beneath the area of affected skin. Chorioretinal involvement and skin
involvement are highly significant, since both findings are associated
with a very high probability of abscess formation in multiple deep
organs as a result of generalized hematogenous seeding. Ocular involve-
ment (Fig. 211-2) may require specific treatment (e.g., partial vitrectomy
or intraocular injection of antifungal agents) to prevent permanent
blindness. An ocular examination is indicated for all patients with can-
didemia, whether or not they have ocular manifestations.
■■DIAGNOSIS
FIGURE 211-1 Macronodular skin lesions associated with hematogenously The diagnosis of Candida infection is established by visualization of pseu-
disseminated candidiasis. Candida organisms are usually but not always visible dohyphae or hyphae on wet mount (saline and 10% KOH), tissue Gram’s
on histopathologic examination. The fungi grow when a portion of the biopsied
specimen is cultured. Therefore, for optimal identification, both histopathology stain, periodic acid–Schiff stain, or methenamine silver stain in the pres-
and culture should be performed. (Image courtesy of Dr. Noah Craft and the Victor ence of inflammation. Absence of organisms on hematoxylin-eosin stain-
Newcomer collection at UCLA, archived by Logical Images, Inc.; with permission.) ing does not reliably exclude Candida infection. The most challenging
perform a partial vitrectomy. This procedure debulks the infection ■■FURTHER READING
and can preserve sight, which may otherwise be lost due to vitreal Edwards JE Jr: Candida species, in Mandell, Douglas, and Bennett’s Prin-
scarring. All patients with candidemia should undergo ophthal- ciples of Infectious Diseases, 8th ed. JE Bennett et al (eds). Philadelphia,
PART 5
mologic examination because of the relatively high frequency of Elsevier, 2015, pp 2879–2894.
this ocular complication. Not only can this examination detect a Pappas PG et al: Clinical practice guideline for the management of can-
developing eye lesion early in its course; in addition, identification didiasis. 2016 update by the Infectious Diseases Society of America.
of a lesion signifies a probability of ~90% of deep-organ abscesses Clin Infect Dis 62:e1, 2016.
Infectious Diseases
and may prompt prolongation of therapy for candidemia beyond Uppuluri P et al: Current trends in candidiasis, in Candida albicans: Cellular
the recommended 2 weeks after the last positive blood culture. and Molecular Biology, 2nd ed. R Prasad (ed). Cham, Switzerland,
Although the basis for the consensus is a very small data set, Springer, 2017, pp 5–24.
the recommended treatment for Candida meningitis is a polyene
(Table 211-3) plus flucytosine (25 mg/kg four times daily). Suc-
cessful treatment of Candida-infected prosthetic material (e.g.,
an artificial joint) nearly always requires removal of the infected
material followed by long-term administration of an antifungal
agent selected on the basis of the isolate’s sensitivity and the logistics
of administration. 212 Aspergillosis
David W. Denning
■■PROPHYLAXIS
The use of antifungal agents to prevent Candida infections has been
controversial, but some general principles have emerged. Most centers Aspergillosis is the collective term used to describe all disease enti-
administer prophylactic fluconazole (400 mg/d) to recipients of alloge- ties caused by any one of ~50 pathogenic and allergenic species of
neic stem cell transplants. High-risk liver transplant recipients also are Aspergillus. Only those species that grow at 37°C can cause invasive
given fluconazole prophylaxis in most centers. The use of prophylaxis infection, although some species without this ability can cause allergic
for neutropenic patients has varied considerably from center to center; syndromes. Each common pathogenic species is actually a complex
many centers that elect to give prophylaxis to this population use either of many species (many of them cryptic), but is referred to as a single
fluconazole (200–400 mg/d) or a lipid formulation of amphotericin B species here for simplicity. A. fumigatus is responsible for most cases
(AmBiSome, 1–2 mg/d). Caspofungin (50 mg/d) also has been recom- of invasive aspergillosis, almost all cases of chronic aspergillosis, and
mended. Some centers have used itraconazole suspension (200 mg/d). most allergic syndromes. A. flavus is more prevalent in some hospitals
Posaconazole (200 mg three times daily) has been approved by the U.S. and causes a higher proportion of cases of sinus infections, cutaneous
Food and Drug Administration for prophylaxis in neutropenic patients; infections, and keratitis than A. fumigatus. A. niger can cause invasive
it is gaining in popularity and may replace fluconazole. infection but more commonly colonizes the respiratory tract and causes
Prophylaxis is sometimes given to surgical patients at very high risk. external otitis. A. terreus causes only invasive disease, usually with a
The widespread use of prophylaxis for nearly all patients in general poor prognosis. A. nidulans occasionally causes invasive infection, pri-
surgical or medical intensive care units is not—and should not be—a marily in patients with chronic granulomatous disease.
common practice for three reasons: (1) the incidence of disseminated
candidiasis is relatively low, (2) the cost–benefit ratio is suboptimal, ■■EPIDEMIOLOGY AND ECOLOGY
and (3) increased resistance with widespread prophylaxis is a valid Aspergillus has a worldwide distribution, most commonly growing
concern. in decomposing plant materials (i.e., compost) and in bedding. This
Prophylaxis for oropharyngeal or esophageal candidiasis in hyaline (nonpigmented), septate, branching mold produces vast num-
HIV-infected patients is not recommended unless there are frequent bers of conidia (spores) on stalks above the surface of mycelial growth.
recurrences. Aspergilli are found in indoor and outdoor air, on surfaces, and in