Periodic acid–Schiff staining binds linked sugar groups in the fungal cell wall. This
intense magenta staining makes visualization of the fungal form easier. Likewise,
several silver precipitation stains (e.g., Gomori methenamine silver) rely on the
presence of a charged fungal surface to reduce oxidized silver to metallic silver. This
process coats the fungus with a black layer, again outlining the form.
mucicarmine stain imparts a deep red color to complex polysaccharides, such as
mucin, which can stain the thick capsule of C. neoformans. Because no other yeast
has a positive mucicarmine stain, the definitive diagnosis of cryptococcosis can be
60 The size of the organism, manner of budding, and the presence or absence of
septae all assist in the diagnosis.
Monoclonal antibodies against many fungi are now available.
Immunohistochemical procedures using these sera on biopsy specimens
allow for the identification of a number of fungal pathogens.
oligonucleotide probe hybridization to detect fungi in tissue are being developed and
will also be extremely helpful.
The most definitive method for diagnosing or monitoring a fungal infection is using
culture. Specimens should be inoculated onto several different types of fungal media,
some of which contain antibiotics to inhibit bacterial overgrowth. Swab specimens
fungi grow slowly, and 4 to 6 weeks of incubation may be necessary to isolate and
identify the organism. After growth, yeasts are usually recognized by their patterns of
metabolic activity on a variety of substrates, whereas mycelial organisms may
produce characteristic spores and fruiting bodies that are used for identification.
Occasionally, a mycelial organism will be slow in producing recognizable spores,
and immunologic testing for a characteristic isoantigen may be used for
identification. A peptide nucleic acid fluorescence in situ hybridization test more
rapidly identifies C. albicans from blood-culture bottles.
It is unclear how costeffective this test will be compared with traditional germ-tube testing.
Fungi synthesize polysaccharides that cannot be broken down by human enzymatic
systems. These polysaccharides can accumulate within the body and can be excreted
in the urine. These fungal antigens can be detected by using antibodies that
specifically recognize a particular species of fungus, thereby providing a diagnosis.
The most commonly used antigen detection test is a latex agglutination test for
cryptococcal antigen. This assay can be performed on serum or CSF. Antigenemia is
present in 80% to 100% of patients with culture-proved cryptococcal meningitis.
This test can also be used to monitor patient response to therapy by determining the
end point dilution for the positive reaction and following this end point over time
when the patient is treated. If treatment is successful, the titer will decline.
Tests (quantitative polymerase chain reaction, enzyme-linked immunosorbent
assay [ELISA], and latex agglutination) for other fungal antigens are also not
established. Latex particle agglutination tests to detect candidal antigens are
available, but their utility has not been clearly demonstrated. Assays for detecting H.
capsulatum antigen in serum and urine have been reported.
in the blood of 50% of patients and in the urine of 80% to 90% of patients with
systemic histoplasmosis. Patients with blastomycosis and paracoccidioidomycosis,
however, may also have positive cross-reactions. The ELISA for the detection of
Aspergillus galactomannan antigen (Section 78-8) and Candida (1–3)-β-D-glucan has
result in a shorter time to diagnosis and leads to significantly shorter time of illness
compared with other diagnostic tests. β-Glucan is most valuable for its negative
66 Considering the presence of false-positives or false-negatives, it
is unknown whether these assays will improve diagnostic capability for patients at a
risk for these infections. False-positives may be caused by a myriad of products
(IgG, albumen, cellulose filters, or gauze bandages) with variable outcomes
associated with pipercillin/tazobactam manufactured antibiotics. Increasing or
decreasing values can be used to monitor clinical response to antifungal therapy.
The detection of antibody can be useful for some fungal diseases, but not for others.
Serologic diagnosis of systemic candidiasis is complicated because most people
have anti-Candida antibodies. A rising titer is not specific for infection and may
indicate only colonization. Furthermore, dissemination of Candida is most likely in
people who are immunocompromised and, therefore, may not respond by producing
67 On the other hand, seropositivity can be demonstrated in more than 90%
of patients with symptomatic histoplasmosis.
68 The most important serologic tests use
the CF, immunodiffusion, and enzyme immunoassay (EIA) techniques. The
appropriate evolution of serologic results requires an understanding of the
sensitivity, specificity, and predictive value of each methodology. In general,
serologic tests allow only a presumptive diagnosis of mycotic infections.
Although any of the aforementioned tests could be ordered for L.K., a direct
examination of his blood and urine specimens along with an assessment of signs and
symptoms of disseminated candidiasis is a reasonable first step in his evaluation. A
blood specimen from L.K. should also be cultured on different fungal media. Because
a candidal infection is suspected, the culture could isolate Candida within 24 to 48
hours. Cultures and histopathologic examination of a biopsy specimen of skin lesions
are often helpful not only in confirming a diagnosis of disseminated candidal
infection, but also in monitoring response to therapy. The other fungal tests
previously described need not be ordered immediately and should await the results
from the direct examination and culture.
growing Candida species. Why is therapy necessary in L.K. with only a single positive blood culture?
Case–control studies of candidemia report an 85.6% mortality rate in untreated
patients compared with a 41.8% mortality rate in patients who received early
treatment. Isolation of Candida from a patient’s bloodstream requires the initiation of
immediate antifungal therapy. Delays in therapy are associated with a significant
increase in mortality. In fact, delaying therapy 24 hours from the time a blood culture
is positive or failure to follow IDSA treatment guidelines increases mortality nearly
69–71 Elimination of risk factors may improve the clinical outcome of
candidemia, and the removal of central venous catheters reduces morbidity and
72,73 Although discontinuation of a centrally inserted catheter may
complicate drug administration, it still should be removed. L.K.’s other risk factors
(e.g., broad-spectrum antibacterials) are perhaps of even greater importance.
TREATMENT OPTIONS AND COMBINATION THERAPY
Therapeutic options are individualized and based on the competence of a patient’s
host defenses. In immunocompetent patients, AmB formulations, an echinocandin, or
a triazole decreases morbidity and mortality associated with this disease.
Echinocandins have been demonstrated as effective as AmB formulations in
neutropenic and non-neutropenic patients; however, AmB clears the bloodstream
fluconazole 400 mg/day for 14 days. Mortality was less than 9% in both the groups
with no significant difference in successful outcomes (AmB, 80%; fluconazole,
72%). Less toxicity was noted in the fluconazole group, however.
mg/day is as effective as AmB for non-neutropenic patients infected with
susceptible Candida. Candidemic (or other mycotic infections discussed in this
chapter) patients who are clinically stable and have no evidence of deep-seated
infection should be initiated on a triazole or an echinocandin for at least 14 days.
Patients who cannot be treated with an echinocandin or an azole can be treated with
AmB 0.5 to 1.0 mg/kg/day or 3 to 5 mg/kg/day of a lipid formulation of AmB.
Alternatively, a comparison of micafungin (100 or 150 mg) with caspofungin
revealed no difference with micafungin 100 mg and caspofungin after 10 days of
therapy. However, micafungin 150 mg trended toward poorer responses.
High-dose fluconazole (12 mg/kg/day) alone or in combination with AmB for a
minimum of 3 days, followed by step-down therapy to fluconazole, was evaluated.
Outcomes were not different between treatment groups and consistent with the
previously reported success rates. Notably, the fluconazole treatment group had
higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores,
making evaluation of the comparison difficult.
In contrast, in another clinical trial,
the combination of AmB and flucytosine was suggested to be more effective than
82,83 An AmB-containing regimen may be more effective in
patients with APACHE II scores between 10 and 22.
L.K. could be treated with an echinocandin, with the total duration based on
clinical response and resolution of positive cultures (see Case 78-3, Question 6).
Therapy typically should be continued for 14 days post–last positive blood culture.
Some clinicians check cultures daily to assess this end point. Efficacy should be
monitored using patient-specific signs and symptoms of candidemia. Combination
therapy can be considered in those patients who are not responding clinically. More
importantly, a complete examination for focal sites of infection (septic thrombi or
intra-abdominal abscess) should take place.
CASE 78-3, QUESTION 5: This fungal species has now been identified as C. non-albicans. How does this
affect the therapeutic options for L.K.?
Historically, the isolation of a non-albicans Candida from blood has resulted in a
therapeutic dilemma caused by common in vitro resistance, which has been
associated with poor clinical outcomes in animal models and uncontrolled case
reports. Intrinsic resistance (i.e., Candida lusitaniae to AmB, C. parapsilosis to
echinocandins, and Candida krusei to fluconazole) or acquired resistance (C.
tropicalis or glabrata against fluconazole) has been reported.
fluconazole drug resistance is probably associated with altered fungal cell membrane
permeability, antifungal efflux pumps, and changes in CYP450 enzymes. In
observational studies, fluconazole resistance in vitro has been 9%.
multicenter study of 232 non-neutropenic patients was unable, however, to
demonstrate a relationship between yeast MIC and patient outcome.
demonstrate a relationship is probably a result of a limited understanding or
inadequate management of risk factors for infection. For example, the removal of a
colonized IV catheter is probably a more important predictor of outcome than the
MIC of the isolated yeast. A disturbing increase in acquired C. glabrata resistance to
the echinocandins via a FKS gene, first reported in 2008, should be suspected in
echinocandin treatment failures.
Therefore, the true rate of acquired clinical resistance to azoles and ultimate
failure is unknown. Vigilant monitoring and aggressive therapy of infections caused
by Candida non-albicans are recommended. In patients in whom susceptibilities are
available, fluconazole should be avoided when the MIC is greater than 16 mcg/mL.
CASE 78-3, QUESTION 6: How should amphotericin B formulation be dosed and administered to L.K.?
The AmB formulation dose and duration of therapy should be individualized based
on the severity of infection and immunocompetence of the patient. Once the patient is
stable, therapy should be changed to one of the applicable regimens discussed
previously. The dose of AmB formulations should be based on lean body mass.
Owing to the difficulty in measuring lean body mass, many clinicians, however, use
ideal body weight. Tissues that contain large numbers of macrophages sequester
significant amounts of AmB (liver, 17.5%–40.3%; spleen, 0.7%–15.6%; kidney,
0.6%–4.1%; and lung, 0.4%–13%), but it does not distribute well into adipose tissue
In fact, AmB formulations bound to cholesterol have been shown to bind
to clathrin-coated pits (low-density lipoprotein receptors or receptors of
endocytosis) on cells, facilitating intracellular incorporation and possibly reducing
85 Because L.K. is 5-feet and 8-inches tall and not obese, his ideal body
weight should be about 70 kg. Therefore, generic AmB 35 mg/day (0.5 mg/kg) should
be initiated because L.K. is not clinically stable and may require increased doses.
Half of the full dose should be given on the first day of therapy and the full dose
given on subsequent days. In more seriously ill patients, the full dose of generic AmB
can be initiated immediately. Although the optimal dosing regimen to initiate generic
AmB is not well established, most clinicians gradually titrate the dose upward to
minimize infusion-related reactions. Peak AmB serum concentrations achieved after
parenteral administration are a function of dose, frequency of dosing, and the rate of
infusion. When the AmB total dose is less than 50 mg, the serum concentration is
directly proportional to the dose; doses greater than 50 mg are associated with a
plateau in serum concentrations. After administration, AmB undergoes biphasic
elimination: Peak serum concentrations drop rapidly (initial t1/2
low concentrations (0.5–1.0 mcg/mL) are detectable for up to 2 weeks (terminal t1/2
86 The long terminal elimination half-life has been used as a justification for
the common practice of less frequent AmB dosing, in which twice the daily dose is
given every other day. Every-other-day regimens have not been carefully evaluated
but are rationalized based on the potential for reduced nephrotoxicity. Administration
of generic AmB 0.5 mg/kg/day or 1.0 mg/kg every other day results in trough AmB
concentrations with sufficient postdose antifungal effects that inhibit the common
87 Once L.K.’s clinical status has improved, the potential for renal
toxicity could outweigh the concerns of potential reduced efficacy, and
implementation of AmB every-other-day therapy should be considered.
Adverse reactions, which are common with AmB formulation administration, are
vomiting, headache, hypotension, and thrombophlebitis. Dose-related reactions also
can be acute (e.g., cardiac arrhythmias) or chronic (e.g., renal
dysfunction with secondary electrolyte imbalances and anemia). Premedication to
prevent AmB formulation, infusion-related reactions, and a test dose of AmB
formulations are not needed for L.K. Most practices of premedicating are performed
out of ritual rather than predicated on a scientific study.
before the first dose is not currently used because of the immeasurably low incidence
of anaphylactoid reactions. Until clinical trials clarify the risk–benefit ratio of
premedications, concomitant therapy should be restricted to acetaminophen for fever
or headache and heparin to prevent thrombophlebitis when possible.
Many infusion-related reactions are mediated by AmB-induced cytokine
(interleukin-1β, tumor necrosis factor, and prostaglandin E2
89,90 Hydrocortisone is extremely effective in suppressing cytokine
89 and it also blunts the fever and chills associated with AmB
91 Hydrocortisone, however, does not reduce the frequency of chronic
dose-related toxicity such as renal insufficiency, and corticosteroid-induced
immunosuppression could decrease AmB fungicidal activity.
93 NSAIDs, however, cannot be recommended for
routine use because of their potential for additive nephrotoxicity when used with
The mild-to-moderate elevations in temperature and the other infusion-related
symptoms usually subside when the infusion is completed, and tolerance to these
effects develops over 3 to 5 days. L.K. initially should be counseled that these
reactions will abate over the next few days without intervention. If assessment of the
reactions suggests the need for more aggressive premedication, a short course of
hydrocortisone 0.7 mg/kg prior to AmB or added to the infusion bag should be
91 Meperidine 25 to 50 mg by rapid IV infusion reduces AmB-induced rigors
and can be repeated every 15 minutes as required while monitoring for signs and
symptoms of opiate toxicity. Administration of an average meperidine dose of 45 mg
has been found to resolve chills 3 times faster than placebo.
Fast generic AmB infusion rates (< normal 4–6 hours) are associated with the
earlier onset of infusion-related reactions, but not with more severe infusion
Electrocardiographic evaluations of 1-hour infusions indicate that this rate of polyene
infusion is safe at currently recommended doses in patients without renal or heart
disease. Rapid infusions are not safe in all patients, however, because cardiac
arrhythmias appear to be dose- and infusion rate–related. If infused too rapidly, high
serum concentrations of AmB can precipitate severe cardiac adverse events.
Arrhythmias have been reported most often in patients who are anuric or who have
97 Continuous infusion is not recommended based on the
pharmacodynamics of this agent and the concentration dependence of activity.
CASE 78-3, QUESTION 8: On Day 4 of therapy with AmB, L.K.’s serum creatinine (SCr) and blood urea
How could AmB exacerbate L.K.’s renal dysfunction and how could it be prevented from worsening?
Renal dysfunction is the adverse event that most often limits treatment with AmB
formulations. The renal toxicity results fromAmB-mediated damage to renal tubules,
which causes electrolyte wasting and disrupts the tubuloglomerular feedback
mechanism. The clinical manifestations of AmB-induced renal damage include
azotemia, renal tubular acidosis, hypokalemia, and hypomagnesemia.
insult along with infusion-related reactions appears less severe in patients with
higher serum cholesterol. This may be associated with the clathrin binding discussed
earlier. Generally, AmB-related renal toxicity is reversible within 2 weeks after
therapy has been discontinued. Administration of normal saline (250 mL)
immediately before AmB administration reduces the risk for AmB-induced
98 and should be initiated before L.K.’s next dose. AmB formulations
should not be admixed with normal saline, however, because sodium causes AmB to
precipitate into an inactive particulate in IV admixture formulations.
99 Hypokalemia and hypomagnesemia should also be monitored
closely. These measures to prevent further renal deterioration should be
implemented, and the AmB therapy continued cautiously in this patient with systemic
candidiasis. Anemia, associated with decreased renal production of erythropoietin,
should resolve after AmB is discontinued and need not be treated.
CASE 78-3, QUESTION 9: L.K. has exhibited significant renal dysfunction resulting from acute tubular
necrosis. How should his dose of systemic antifungal drugs be altered?
Renal elimination of the antimycotics varies tremendously. For systemically
administered AmB, only 5% to 10% of unchanged drug is eliminated in urine and
bile during the first 24 hours,
88 and no evidence indicates that it is metabolized to a
significant extent. Therefore, no substantial dosage adjustment is required for patients
with chronic renal or hepatic failure. Although many clinicians will withhold AmB
doses if acute renal dysfunction develops during therapy, concerns of drug-induced
nephrotoxicity in L.K. must be balanced against the high likelihood of mortality in
untreated patients with deep-seated infections.
55,56 Alternative systemic antifungal
therapy (i.e., azoles or echinocandins) that is less nephrotoxic should also be
considered. Dosing recommendations for echinocandins are unchanged in renal
dysfunction or liver dysfunction, except for caspofungin. For patients with moderate
hepatic insufficiency (Child–Turcotte–Pugh score 7–9), a change in the maintenance
dose of caspofungin to 35 mg/day is recommended, even though the higher exposures
expected with the standard dose are generally well tolerated. No data are available
for caspofungin used in severe hepatic impairment, and a further dosage reduction
Ketoconazole and itraconazole undergo first-pass metabolism and have a biphasic
45,46 These agents are extensively metabolized and
excreted in the bile; small amounts of unchanged drug are excreted in the urine;
therefore, no need exists to adjust dosages in patients with renal dysfunction or in
101 Voriconazole is extensively metabolized by
cytochrome P450 2C19 and to a lesser extend CYP3A4 to inactive metabolites
excreted in the urine. However, the IV formulations of voriconazole and
posaconazole are solubilized in sulfobutylether-β-cyclodextrin, which is eliminated
via the kidneys. Accumulation of the cyclodextrin vehicle is associated with a
theoretical potential for renal toxicity not reported to date in patients including those
102,103 Therefore, oral therapy (or possibly isavuconazole) may
be preferred in patients who require a broad-spectrum triazole but have impaired
renal function. Fluconazole, unlike ketoconazole and itraconazole, is not extensively
metabolized. More than 90% of a fluconazole dose is excreted in urine, of which
about 80% is measured as unchanged drug and about 20% as metabolites.
Because fluconazole is excreted primarily unchanged in the urine, dosages should
be adjusted in patients with renal insufficiency (Table 78-5).
Fluconazole or voriconazole may be reasonable alternatives in L.K., but the dosage
must be adjusted for renal function based on published nomograms.
CASE 78-3, QUESTION 10: What is the role of an AmB formulated with a lipid?
Lipid formulations of AmB have been approved by the FDA for patients who are
unable to tolerate generic AmB (Table 78-6). In addition, the admixture of AmB in
10% or 20% lipid emulsion has been used for treating systemic mycotic infections.
The lipid carriers differ tremendously for each of the amphotericin formulations. The
liposomal formulation is a spherical carrier that contains AmB on both the inside and
outside of the vesicle. Imagine the lipid complex as a snowflake shape and the
colloidal dispersion shaped like a Frisbee with AmB bound to the structure. The
differences in structure appear to have no effect on therapeutic outcome but exhibit
markedly different pharmacokinetics and rates of AMB release in vivo, which may
account for difference in the rates of adverse effects observed with each
112 AmB admixture with a lipid emulsion cannot be recommended until a
stable formulation can be established.
113 Yet, similar in concept, some clinicians
administer AmB formulations with breakfast (high-cholesterol meals) to simulate or
enhance “lipid” coadministration, macrophage clathrin pit binding, and subsequent
Limited data on AmB formulation comparisons are available to assist in the
management of this case. A single large controlled trial has evaluated AmB lipid
complex for the treatment of disseminated candidiasis. Generic AmB 0.6 to 1.0
mg/kg/day for 14 days was slightly, but not significantly, superior to the lipid
complex formulation at 5 mg/kg/day for mycologic efficacy (68% vs. 63%) or
114 Renal dysfunction defined as a doubling in SCr, however, was 47% with
AmB and 28% with this lipid formulation. Because of the significant cost, some
health-care facilities reserve lipid formulations for patients who have preexisting
renal dysfunction or those who have severe adverse reactions to generic AmB.
However, most centers use lipid formulations as their formulary polyene owing to
patient acceptance and cost of AmB-associated renal dysfunction. Indications for the
lipid formulations are further reviewed in the discussion of sections on aspergillosis,
histoplasmosis, and cryptococcosis.
CASE 78-3, QUESTION 11: What measures could have been undertaken to prevent invasive fungal
In 2014, the National Institutes of Allergy and Infectious Diseases
invasive candidiasis initiated on the basis of an antigen diagnostic test (β-D-glucan)
among high-risk patients in the intensive care unit (ICU) setting.
a validated risk-prediction score for invasive candidiasis that identified 18% of
subjects admitted to the ICU with a predicted invasive candidiasis incidence rate of
greater than 10%. Caspofungin prophylaxis was not associated with a reduction in
the incidence of proven or probable invasive candidiasis or patient mortality.
Therefore, prophylaxis among non-neutropenic patients at this time should be
restricted to patient populations with proven benefit: post GI perforation, severe
Selective GI decontamination or systemic antimycotic pharmacotherapy can be
used in high-risk, immunocompromised, or surgical patients to prevent the
development of fungal infections and could have been used for L.K. In critically ill
surgical patients, the risk of invasive infection, but not mortality, may be reduced by
more than 50% with fluconazole prophylaxis.
116 Alternatively, a nonabsorbable
antifungal such as AmB or nystatin is a possible option. Oral AmB decreases
systemic candidal infections threefold to fivefold in high-risk patients.
problems of unreliable antifungal stool concentrations,
associated with the availability of generics, and poor compliance have led to
preferential azole use. Azoles are also more effective in preventing oral pharyngeal
119,120 At the present time, no well-designed studies have
compared azoles with polyene antifungals (e.g., AmB) for the prevention of
oropharyngeal or systemic candidiasis.
Prophylaxis could be initiated and continued until L.K. is no longer
immunocompromised. If L.K. is discharged from the hospital and treated as an
outpatient, a systemic azole (imidazole or triazole) administered once daily is
preferable to a polyene to improve adherence. To reemphasize, however, systemic
therapy increases the risk of resistance, adverse effects, drug interactions, and
potentially cost (Table 78-4). Therapeutic drug monitoring may be necessary in these
is 8,900 cells/μL (SI units, WBC count, 8.9 × 10
/L), and three sets of blood cultures drawn during the past 2
days are negative. How should M.Y.’s candiduria be treated?
It is difficult to differentiate among cystitis, urethritis, or systemic infection in the
presence of funguria. Similarly, it is difficult to differentiate colonization from
infection because candiduric patients are usually asymptomatic. Funguria cannot be
used to determine the location or severity of invasion. Signs and symptoms of
systemic disease should be monitored diligently until a diagnosis of colonization,
cystitis, or urethritis is confirmed and the risk of dissemination is excluded.
Eradication of fungi in the urine (specifically C. albicans) should begin with the
removal of the indwelling urinary catheter and alleviation of risk factors for fungal
disease. If catheter removal does not clear the urine within 48 hours,
pharmacotherapy should be considered. If M.Y. is scheduled for a genitourinary
procedure, he should receive systemic therapy because the rate of candidemia after
surgery is high (10.8%) in candiduric patients. In addition, any patient at a high risk
for dissemination into the blood should be considered for treatment (e.g., patients
<10 1,600–11,000 122(±48) 80–120 333–500
Manufacturer Generic Enzon Intermune Fujisawa
3.3 mg/kg 10–25 mg/kg 68 mg/kg 175 mg/kg Unknown
Peak 1.2 mcg/mL 1.7 mcg/mL 3.1 mcg/mL 31.4 mcg/mL 83.0 mcg/mL 2.13 mcg/mL
Trough 0.5 mcg/mL 0.7 mcg/mL 4.0 mcg/mL 0.42 mcg/mL
Half-life 91.1 hours 173.4 hours 28.5 hours 6.3 hours 6.8 hours 7.75 hours
5.0 L/kg 131.0 L/kg 4.3 L/kg 0.16 L/kg 0.10 L/kg 0.45 L/kg
aMolar ratio of each component, respectively.
bNo benefit for longer infusions.
cDoses greater than 10 mg/kg have no benefit.
AmB, amphotericin B; AUC, area under the curve; DMPC, dimyristoylphosphatidycholine; DMPG,
and Drug Administration; FUO, fever of unknown origin; NA, not applicable.
Bladder irrigation with AmB has been used in the past at concentrations of 150
mcg/mL, however has limited clinical utility, and is not recommended by the
Infectious Diseases Society of America.
In two comparative studies, bladder
irrigation for 5 days with AmB 50 mcg/mL was superior to fluconazole 100 mg/day
as measured by microbiologic cure rates. Clinical cure rates at 2 to 4 weeks were
equal—however, mortality rates were higher in the AmB-treated groups. It was
suggested that AmB failures may have been associated with dissemination of yeast
123,124 Systemic antifungal therapy with flucytosine 100 to 150
125 and azoles (fluconazole 0.6–1.4 mg/kg/day for 7 days)
also has been used in noncomparative or nonrandomized studies. Newer triazoles
(voriconazole, posaconazole, and isavuconazole) or echinocandins are not
recommended for the treatment of candiduria owing to their low concentrations in
urine, even though some case series have suggested that clearance of positive
cultures is possible on echinocandin therapy.
sweats but has lost 11 pounds. Her temperature is 38.2°C. A 2 cm
subcutaneous, fluctuant, tender mass is
2 ulcers with heaped-up, hyperkeratotic margins are noted on the lower extremities (Fig. 78-
/L). A chest radiograph shows a mass-like infiltrate in the right mid-lung field (Fig. 78-
likely portal of entry for C.P.’s disseminated blastomycosis? Why should it be treated?
Typical of the other endemic mycoses, the primary portal of entry for B.
dermatitidis is the lungs. A pulmonary origin for C.P.’s infection is supported by her
history of cough with purulent, blood-streaked sputum, followed a month later with
cutaneous lesions on her legs and back. An acute pulmonary infection is most often
asymptomatic and, when symptomatic, usually requires only observation. Chronic
pulmonary or extrapulmonary blastomycosis will develop in an unknown number of
these patients. C.P.’s rales at the base of her right lung and persistent pneumonia
unresponsive to antibacterials suggest a chronic pulmonary infection and a need for
treatment. Chronic pulmonary disease often presents with radiographic studies often
mistaken for tuberculosis or cancer; the mass-like infiltrate in her right lung on chest
radiograph also is consistent with chronic pulmonary disease. Extrapulmonary
infections can involve the skin (verrucous or ulcerative lesions), bone, genitourinary
system (prostatitis and epididymo-orchitis), or CNS (meningitis or brain abscess). If
untreated, these chronic pulmonary or extrapulmonary infections are fatal in at least
129 Because C.P. presents with pulmonary and cutaneous evidence of
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