ANTIFUNGALS

SYSTEMIC ANTIFUNGALS

Class POLYENE MACROLIDE with a carboxyl group Fluorinated pyrimidine

Drug Amphotericin B Flucytosine
MOA Activity depends on capacity to bind to ergosterol. Potent antimetabolite that is used in cancer chemotherapy.

Forms aggregates that sequester and effectively extract ergosterol from lipid
bilayers like a selective sponge, disrupting membrane structure and resulting in
fungal death.
It was thought it formed pores in the wall that increased the permeability and
allowed leakage, but evidence suggests that it instead forms aggregates that
sequester ergosterol from lipid bilayers like a sponge.
Transported by cytosine permease into fungal cell, where its deaminated to
5FU.
The 5FU is converted to CFUMP and then to 5FUTP then incorporated into RNA
or converted by ribonucleotide reductase 5FdUMP, a potent inhibitor of
thymidylate synthase.

Spectrum BROADEST SPECTRUM OF ACTIVITY OF ANY AVAILABLE ANTIFUNGAL DRUGS CURRENT PRIMARY ADJUNCTIVE AGENT IN AMPHOTERICIN B IN INDUCTION
PHASE OF CRYPTOCOCCAL MENINGOENCEPHALITIS THERAPY
Candida, Cryptococcus neoformans, Blastomyces dermatitis, Histoplasma
capsulatum, Sporothrix, Schenckii, Coccidioides, Paracoccidioides bazilienziz,
Aspergillus, Penicillium marneffei (Taloromyces marnefferi, Fusarium, Mucorales.

Protozoa: Leishmania and Naegleria fowleri.

No bacterial activity

Formulatio C-AMB (conventional): formulated with bile salt deoxychlate. IV infusion.

n Lyophilized powder for injection. More tolerated in neonates than in adults and
older children. Remains an important antifungal in critical care nursery.

ABCD (amphotericin B colloid dispersion): injection. Much lower blood levels

than C-AMB, requires higher dose. Chills and hypoxia (w/ severe febrile reactions)
are common. More nephrotoxic than L-AMB.

L-AMB (liposomal amphotericin): Incorporated within a small unilamellar

liposomal vesicle formation. Causes fewer infusion-related reactions.

ABLC (amphotericin B lipid complex): Complex with 2 phospholipids. IV once

 every 2 h. Much lower blood levels. Effective in variety of mycoses with possible
exception of cryptococcal meningitis.

Compared to C-AMB, the 3 formulation appear to reduce risk of acute kidney

injury.
Resistance The mechanism for this resistance can be loss of the permease necessary for
Candida is often resistant cytosine transport or decreased activity of either UPRTase or cytosine
deaminase.
Aspergillus appears to be less susceptible
In Candida albicans, substitution of thymidine for cytosine at nucleotide 301 in
Mutations in ergosterol biosynthesis genes ERG2, ERG3, ERG5, ERG6, and ERG11 the gene encoding UPRTase (FURl) causes a cysteine to become an arginine,
reduce susceptibility to amphotericin B, likely the result of reduced ergosterol in modestly increasing flucytosine resistance.
the cell membrane of these isolate.
Flucytosine resistance is further increased if both FURl alleles in the diploid
Resistande among clinical isolates is rare because it’s a fungicidal that affects the fungus are mutated.
membrane sterol.
Candida auris is an exception; nearly one-third of clinical isolates are considered
resistant to amphotericin B based on tentative breakpoints proposed by the CDC

Indications
Tx of choice for invasive mucormycosis and combination with 5-flucytosine is the Flucytosine is used almost exclusively in combination with amphotericin B for
GOLD STANDARD for cryptococcal meningitis. the treatment of cryptococcal meningitis, and this combination, as compared
with amphotericin B alone, is associated with improved survival among patients
Severe or rapid histoplasmosis, Blastomycosis, coccidioidomycosis and with cryptococcal meningitis.
penicilliosis (talaromycosis)

Amphotericin B is a salvage therapy for patients not responding to azole therapy

for invasive aspergillosis, extracutaneous sporotrichosis, fusariosis, alternariosis,
or trichosporonosis.

Can also be given to selected patients with profound neutropenia with fever who
do not respond to broad-spectrum antibacterial agents over 5 to 7 days.

The more recently developed azoles and echinocandins are generally the drugs of
choice for such patients because of their reduced toxicity.

Candida esophagitis responds to much lower doses than deeply invasive

mycoses.

Intrathecal infusion of C-AMB appears to be useful in patients with meningitis

caused by Coccidioides.

ADME Oral administration, absorbed rapidly in GI.

GI absorption
IV  Systemic use Total water = vol. of distribution
>90% bound to plasma proteins
80% is excreted unchanged in urine
Azotemia, liver failure and hemodialysis do not have a measurable impact in
plasma concentration. Clearance approximately equivalent to creatinine

The concentration of amphotericin B (via C-AMB) in fluids from inflamed pleura, Cleared by hemodialysis
peritoneum, synovium, and aqueous humor is approximately two-thirds that of
trough concentrations in plasma.

Very little enters CSF, nevertheless, amphotericin B w/ flucytosine remains the

tx of choice for certain CNS fungal infections like cryptococcal meningitis and
Coccidioides meningoencephalitis.

Intraocular injection following pars plana vitrectomy has been used to treat
fungal endophthalmitis.

AE Most common  Infusion related fever and chills because of induction of a Bone marrow suppression  Leukopenia and thrombocytopenia
proinflammatory response in cells of the innate immune system signaling trough
TLR2 and CD14 Rash, nausea, vomiting, diarrhea, severe enterocolitis.

Fever and headache are common reactions that may be decreased by intrathecal 5% of px present elevated hepatic enzymes but this effect reverses when
administration of 10 to 15 mg of hydrocortisone. therapy is stopped.

Local injections of amphotericin B into a joint or peritoneal dialysate fluid Toxicity is more frequent in patients with AIDS or azotemia (including those
commonly produce irritation and pain. who are concurrently receiving amphotericin B) and when plasma drug
concentrations exceed 100 μg/mL. Toxicity may result from conversion of
Infused related reactions more common in ABCD flucytosine to 5FU by the microbial flora in the intestinal tract of the host.
 Tachypnea, respiratory stridor, or modest hypotension can also occur, but frank
bronchospasm and anaphylaxis are rare.

Pre-existing cardiac or pulmonary disease  Hypoxia or hypotension

Azotemia  80% px with C-AMB for deep mycoses

Renal tubulalr acidosis

Hypochromic normochromic anemia  C-AMB most likely because of reduced

production of EPO.
Interactions
Meperidine  Reaction ends epontaneouly in 30-45 min and may shorten it.

Retreatment with oral acetaminophen or ibuprofen or use of intravenous

hydrocortisone sodium succinate (hemisuccinate), 0.7 mg/kg, at the start of the
infusion decreases reactions. Febrile reactions tend to abate with subsequent
infusions.
Notes

Class Azoles
Imidazoles Triazoles
Drug Ketoconazole Itraconazole Fluconazole Voriconazole Posazonazole Isavuconazole
MOA
Inhibition of 14-a-sterol demethylase, a cytochrome P450 and the product to f gene ERG11.

Impair the synthesis of ergosterol and accumulation of the toxic product 14a-methyl-3,6-diol leading to growth arrest.

Disrupts the close packing of acyl chains of phospholipids and impairing the functions of membrane-bound enzyme systems.

Directly increase permeability of fungal cytoplasmic membrane, but the concentrations required are likely only obtained with topical use.

Spectrum C. albicans, Candida tropicalis, Candida parapsilosis, C. neoformans, Blastomyces dermatitidis, H. capsulatum, Coccidioides spp., Paracoccidioides brasiliensis, and
ringworm fungi (dermatophytes). Aspergillus spp., Scedosporium apiospermum (Pseudallescheria boydii), Fusarium, and Sporothrix schenckii are intermediate in
susceptibility.

Candida glabrata exhibits reduced susceptibility to the azoles, whereas Candida krusei and the agents of mucormycosis are more resistant. Posaconazole and
isavuconazole have modestly improved spectrum of activity in vitro against the agents of mucormycosis.

Resistance C. albicans, azole resistance can be due in part to accumulation of mutations in ERG11, the gene encoding the azole target, 14-α-sterol demethylase. Increased azole
efflux by overexpression of ABC (ATP-binding cassette) and/or major facilitator superfamily transporters impart azole resistance in C. albicans and C.
glabrata. Overexpression of these genes is due to activating mutations in genes encoding their transcriptional regulators. Mutation of the C5,6 sterol desaturase
gene ERG3 also can increase azole resistance in some species

C. glabrata and C. krusei are considered intrinsically resistant to fluconazole, whereas 90% of C. auris isolates are resistant based on tentative breakpoints

Azole resistance has been increasingly described in isolates of Aspergillus fumigatus

The most commonly characterized mechanism of resistance is due to the TR(34)/L98H mutation in the promoter region of CYP51A, which encodes the target of azoles in A. fumigatus
Indications Orally Lacks corticosteroid Oropharyngeal candidiasis Superior to C-AMB in the Invasive aspergillosis Broad exprectum
Replaced by suppression Candidemia of tx invasive aspergillosis, (tx of rescue) against modst yeast
itraconazole nonimmunosuppressed px survival is also superior. spp including
Available for topical use Has activity against Mucormycosis and Candida,
Corticosterol Aspergillus Alternative for 1st line tx of Approved for Candida infections Cryptococcus gatii
 suppression
IMPORTANT
PROPHYLACTIC AGENT TO
PREVENT MOLD
INFECTIONS IN PATIENTS
WITH GRANULOMATOUS
DISEASE
DRUG OF CHOICE FOR
INDOLENT
NONMENINGEAL
INFECTIONS due to B.
dermatitis, H. capsulatum
and P. brasiliens and
Coccidioides immitis
1st LINE TX FOR
BLASTOMYCOSIS
Indolent aspergillosis
outside the CNS after
infection tx with
amphotericin B
Subungal onychomycosis
If an infection doesn’t
respond to amphotericin B,
it’s a good tx for
pseudallescheriasis,
cutaneous and
extracutaneous
sporotrichosis, tinea
corporis and extensive
tinea versicolor.
HIV-infected patients with
disseminated
histoplasmosis or
penicilliosis have a
decreased incidence of
relapse if given prolonged
itraconazole
“maintenance” therapy.
itraconazole is also used as
Aspergillus prophylaxis in
patients with CGD.
ADME
Tablet, capsule and a
solution.
Better absorved fasting.
TABLET ONLY APPROVED
FOR ONYCHOMICHOSIS
Metabolized in liver
Inhibitor CYP3A
>99% bound to plasma
proteins
Doesn’t appear in urine or
in CSF
Severe liver disease will
increase itraconazole
plasma concentrations, but
azotemia and hemodialysis
have no effect.
an enchinocandin
Recommended as step-
down therapy
Cryptococcis:
concolidation treatment of
cryptococcal meningitis in
px with AIDS after an
induction course of IV
amphotericin B. Keep this
tx as loon as the CD4
response is maintaines.
Continuation therapy in px
with AIDS with
cryptococcal meningitis
that have responded to C-
AMP or L-AMB and
pulmonary cryptoccocis
DRUG OF CHOICE FOR
COCCIDIOIDAL
MENINGITIS BECASUEE OF
GOOD PENETRATION INTO
THE CSF AND MUCH
LOWER MORBIDITY
COMPARED TO
INTRATECAL
AMPHOTERIRICN B
Absorbed in GI tract
Unaltered with food or
gastric acidity
T1/2=25-30h
Body fluids, breast milk,
sputum, saliva, CSF can
reach 50-90% of the
plasma concentrations.
The dosage interval should
be increased from 24-48h
with a creatinine clearance
of 21-40 mL/min
esophageal candidiasis and C. neoformans
in nonneutropenic Analogue of and molds such as
patients with itraconazole with the Aspergillus and
candidemia. same broad spectrum. most Mucorales
species complex.
Approved for initial tx of Approved for
candidemia and invasive oropharyngeal Drug approved for
aspergillosis. candidiasis but tx of invasive
fluconazole is aspergillosis and
It is suggested this drug preferred because of invasive
penetrates the infected major safety and cost. mucormycosis.
brain.
Approved for
prophylaxis against
candidiasis and
aspergillosis in
patients more than 13
years of age who have
prolonged
neutropenia or severe
graft-versus-host
disease
Posaconazole as a
first-line treatment
for invasive
Aspergillus
Tablets of suspension Delayed release tablet, Prodrug
when hydrated. IV, flavoured
(oral is preferred) suspension. Available oral and
cyclodextrin-free IV
Tablets contain lactose. Tablet and IV have a formulations.
more consistent
High fat meals reduce bioavailability in the >99% binds to
bioavailability, the drug presence of proteins
should be given 1h concomitant diseases,
before or after meals. medications and Food reduces AUC
dietary considerations. 20%
Bioavailabvility  96%
Bioavailability Rapidly hydrolized
Extensive drug enhanced with food to the active form
distribution in tissues
T1/2= 25-31h T1/2 of active from
CYP2C19, 2C9, CYP3A4 130h
Protein binding >98%
T1/2 = 6h Hepatic elimination
Renal impairment by CUP3A4 and
Voriconazole exhibits doesn’t alter plasma CYP3A5
nonlinear metabolism so concnetrations.
that higher doses may <1% unchenaged in
cause greater-than- Hepatic impairment urine
 Itraconazole solution is
effective and approved for
use in oropharyngeal and
esophageal candidiasis.
AE QT prolongation, heart
failure, negative inotropic
effects, and drug
interactions
Rare  Serious
hepatotoxicity with hepatic
failure and death
Diarrhea, abdominal
cramps, anorexia and
nausea are more common
with capsules.
Hypertriglyceridemia,
hypokalemia, increased
serum aminotransferase
and rash
Adrenal insufficiency, lower
limb edema, hypertension.
One case of
rhabdomyolysis
SJ syndrome
Contraindicated for use in
onychomycosis during
pregnancy or for women
contemplating pregnancy.
linear increases in causes a modest
systemic drug exposure. increase in No renal dose
20% of Asians are poot concentrations. adjustments needed
metabolizers
80% exctreted in stool
<2% of parent drug is
recovered in urine 66% unchanged drug
80% of inactive The major metabolic
metabolites excreted in pathway is hepatic
urine UDP glucuronidation.
Dose doesn’t have to be Doesn’t remove drug
adjusted in azotemia or from circulation.
hemodialysis
Gastric acid improves
Patients with mild-to- asorption.
moderate cirrhosis
should receive the same Drugs that reduce
loading dose of gastric acid (e.g.,
voriconazole but half the cimetidine and
maintenance dose. esomeprazole)
decrease
The intravenous posaconazole
formulation of exposure by 32% to
voriconazole contains 50%.
sulfobutyl ether β-
cyclodextrin (SBECD), Diarrhea reduces the
which is excreted by the average CP by 37%
kidney.
In px receiving tx for more Generally well
than 7 days: Teratogenic in animals Nausea, vomiting, tolerated
 Nausea diarrhea, abdominal
 Headache Generally pain and headache. GI disorders
 Skin rash contraindicated in
 Vomiting pregnancy. AE in 1/3 of px Pyrexia
 Abdominal pain
 Diarrhea Generally well tolerated Coadministration with Hypokalemia
 Reversible rifabutin or phenytoin
alopecia (400 Cases of hepatotoxicity increases the plasma Headache
mg daily concentration of these
prlongued Liver function should be drugs and decreases Constipation
therapy) monitored posaconazole
Rare: Hepatic failure and SJ exposure by 2-fold. Cough
Prolongs QTc interval (in
Skeletal cardiac px with torsades increases the AUC of Increase in
deformities in babies from pointes) cyclosporine, isavuconazole AUC
women that were treated tacrolimus (121%), results when it is
with high doses Transient visual or sirolimus (790%), administered with
audiroty hallucinations midazolam (83%), and strong CYP3A4
Tetralofy of Fallor in babies are frequent after the 1st other CYP3A4 inhibitors such as
with mothers who dose usually at night substrates ketoconazole
received the drugs. Substantial
IV infusion: can prolong the QTc reductions if
AVOID DURING anaphylactoid reactions interval and should administrated with
PREGNANCY not be coadministered isavuconazole with
Rash (6%) with drugs that are rifampin.
CYP3A4 substrates
Cyclodextrin component that likewise prolong Midazolam and
of Iv infusions may be the QTc interval, such sirolimus AUCs are
toxic for the kidney. as methadone, increased by
Avoid in px with renal haloperidol, pimozide, coadministration
failure. quinidine, risperidone, with isavuconazole.
sunitinib, tacrolimus,
Voriconazole and its and halofantrine Causes a dose-
major metabolite can related shortening
increase the plasma of QTc and is
concentrations of other contraindicated in
drugs metabolized by patients with
these enzymes familial short QT
syndrome.
Coadmin. With sirolimus
is contraindicated
 because AUC increases
11-fold

When starting
voriconazole in a patient
receiving 40 mg/day or
more of omeprazole, the
dose of omeprazole
should be reduced by
half.
Interactions CYPs and substrates inhibitors
Can elevate plasma levels of coadministered drugs

Many of the interactions can result in serious toxicity from the companion drug, such as inducing potentially fatal cardiac arrhythmias when used with quinidine,
halofantrine (an orphan drug used for malaria), levomethadyl (an orphan drug used for heroin addiction), pimozide, or cisapride (available only under an
investigational limited access program in the U.S.). Other drugs may decrease itraconazole serum levels below therapeutic concentrations.

Notes Not recommended for
maintenance tx of
cryptococcal meningitis in
HIV infected patients
because of the high
incidence of relapse
Fluconazole has no useful
activity against
histoplasmosis or
sporotrichosis, and is not
effective in the prevention
or treatment of
aspergillosis. Fluconazole
has no activity in
mucormycosis.
Monitoring of the serum
concentrations,
particularly in children
because their levels of
voriconazole are
unpredictable.

Class Echinocandins
MOA Fungi that are susceptible to echinocandins include Candida and Aspergillus spp

The echinocandins inhibit 1,3-β-D-glucan synthesis, which is an essential component of the fungal cell wall and is required for in cellular integrity

The Fks1p subunit of glucan synthase appears to be the target of echinocandins, and mutations in Fks1p cause resistance to echinocandins.

Spectrum Candida  Fungicidal

Asperfillus  Gungistatic
Can cause morphological changes to filaments

Resistance mutations leading to amino acid substitutions in the Fks subunits of glucan synthase
 Mutations conferring resistance occur in two conserved “hot spot” regions of FKS1 in C. albicans and C. auris, and in FKS1 and FKS2 in C. glabrata.

Drug Caspofungin (synthesized from the fermentation Micafungin (derived from Colephoma empedri) Anidulafungin (extracted from A. nidulans)
product of Glarea lozoyensis)
Indications Candidemia including intra-abdominal
Invasive candidiasis FIRST LINE AGENT along with other Invasive candidiasis and esophageal candidiasis abscess, peritonitis and esophageal candidiasis
ehcinocandins for initial tx for candidemia.
Prophylaxis in hematopoietic stem cell transplant
It is also approved as salvage therapy for patients with recipients.
invasive aspergillosis who fail or are intolerant of
approved drugs, such as amphotericin B formulations
or voriconazole.

Caspofungin is also approved for both esophageal and

invasive candidiasis

treatment of persistently febrile neutropenic patients

with suspected fungal infections

ADME >97% protein binding

Inability to penetrate CSF
Lack of renal clearance
Slight-modest effect on hepatic insufficiency on plasma drug concentrations
Only IV
Linear pharmacokinetics Cleared from body by slow chemical
Catabolism  Hydrolisis and N-acetilation with degradation.
excretion of metabolites into the urine and feces. Small amounts of drug are metabolized in the liver by
arylsulfatase and catechol O-methyltransferase No hepatic metabolism or renal excretion
Mild and moderate hepatic insufficiency increases UAC occurs.
by 55% and 75% respectively. Hydroxylation by CYP3A4 is barely detectable.
No dose adjustment for hepatic or renal failure
Unlike caspofungin, reduction of the micafungin dose is needed.
in moderate hepatic failure is not required.

Micafungin shows age-dependent clearance in

children, with rapid clearance in premature infants and
intermediate clearance in children 2 to 8 years of age,
compared to older children and adults
AE Minimal and rearely lead to interruption of tx.
All three agents are well tolerated, with the exception of phlebitis at the infusion site.
Histamine-like effects have been reported with rapid infusions.
All three echinocandins are contraindicated in pregnancy.
Interactions Increases tacrolimus levels by 16% Mild inhibitor of CYP3A4, increasing the AUC of No clinically relevant drug interactions
nifedipine by 18% and sirolimus by 21%. Micafungin
Cyclosporines increase slightly the caspofungin levels. has no effect on tacrolimus clearance.

Rifampin and other drugs activating CYP3A4 can cause

a slight reduction in caspofungin levels.
Notes
 Class Other systemic antifungals
Drug Griseofulvin Terbinafine
Isolated from Penicillium griseofulvum
MOA Griseofulvin inhibits microtubule function and thereby disrupts assembly of the It inhibits fungal squalene epoxidase and thereby reduces ergosterol
mitotic spindle, which disrupts fungal cell division. biosynthesis.
Spectrum
Microsporum, Epidermophyton, and Trichophyton.

Efficacy is best for tinea capitis caused by Microsporum canis, Microsporum

audouinii, Trichophyton schoenleinii, and Trichophyton verrucosum.
Resistance
Indications Mycotic disease of the skin, hair, and nails due to Microsporum, Trichophyton, or Tablets  Daily for adults
Epidermophyton Somewhat more effective than itraconazole for nail onychomycosis
Duration of treatment varies with the site of infection but typically ranges
For tinea capitis in children, griseofulvin remains the drug of choice for efficacy, between 6 and 12 weeks.
safety, and availability as an oral suspension.

Its also effective for ringworm of the glabrous skin; tinea cruris and tinea corporis
caused by M. canis, Trichophyton rubrum, T. verrucosum, and Epidermophyton
floccosum; and tinea of the hands (T. rubrum and Trichophyton mentagrophytes)
and beard (Trichophyton spp.).

Also highly effective in the treatment of tinea pedis. Topical therapy is usually
efficient.

Treatment must be continued until infected tissue is replaced by normal hair, skin,
or nails, which requires 1 month for scalp and hair ringworm, 6 to 9 months for
fingernails, and at least a year for toenails. Itraconazole or terbinafine is much
more effective for onychomycosis.
ADME Oral administration Well absorbed but bioavailability is about 40% due to 1st pass metabolism in
liver.
Griseofulvin has a plasma t1/2 of about 1 day; about 50% of the oral dose can be
detected in the urine within 5 days, mostly in the form of metabolites. The drug accumulates in skin, nails, and fat.

The primary metabolite is methylgriseofulvin. Barbiturates decrease griseofulvin Terbinafine is also effective for the treatment of tinea capitis and has been
absorption from the GI tract. used for the off-label treatment of ringworm elsewhere on the body.

Griseofulvin is deposited in keratin precursor cells; when these cells differentiate,

the drug is tightly bound to, and persists in, keratin, providing prolonged resistance
to fungal invasion.

The new growth of hair or nails is the first to become free of disease.

As the fungus-containing keratin is shed, it is replaced by normal tissue.

Griseofulvin is detectable in the stratum corneum of the skin within 4 to 8 h of oral

administration.

Sweat and transepidermal fluid loss play an important role in the transfer of the
drug in the stratum corneum.

Only a very small fraction of a dose of the drug is present in body fluids and tissues.
AE Headache Mostly well tolerated
GI and nervous system manifestations
Augmentation of the effects of alcohol Low incidence of GI distress, headache or rash
Hepatotoxicity has been observed
Hematological effects: Leukopenia, neutropenia, punctate basophilia, monocytosis Very rarely  Fatal hepatotoxicity, severe neutropenia, SJ syndrome or toxic
Common renal effects: albuminuria, cylindruria epidermal necrolysis.
Cold and warm urticaria
Photosensitivity
Lichen planus
Erythema
Erythema multiforme-like rashes
Vesicular and morbilliform eruptions
Serum sickness and severe angioedema (rare)
 Sestrogen-like effects (seen in children)
Moderate but inconsistent increase of fecal protoporphyrins has been noted with
chronic use.

Interactions Food: better drug absorption with fatty meal Rifampin decreases and cimetidine increases plasma terbinafine
concentrations.
Induces hepatic CYPs: increases the rate of warfarin metabolization. Warfarin dose
should be adjusted. The efficacy for the treatment of onychomycosis can be improved by the
simultaneous use of amorolfine 5% nail lacquer
May reduce efficacy of low-estrogen oral contraceptive agents
Notes Not recommended in patients with marked azotemia or hepatic failure

Systemic terbinafine therapy for onychomycosis should be postponed until

after pregnancy is complete.

Class Agents against Microsporidia and Pneumocystis

(originally thought to be a parasite)
Drug Albendazole Fumagillin Pentamide
MOA inhibitor of α-tubulin polymerization Cyclic polyene macrolide produced by the fungus A. fumigatus.
Fumagillin and its synthetic analogue TNP-470 are toxic to
microsporidia.
Spectrum Pneumocistis juroveccii but Trimethoprim-
sulfamethoxazole is the drug of choice.

Indications Intestinal infections with Immunocompromised individuals with intestinal For 21 days for those that cannot tolerate
microsporidia. microsporidiosis due to Enterocytozoon bieneusi (which does trimethoprim sulfamethoxazole and are not
not respond as well to albendazole) can be treated successfully candidates for any other alternative agent.
with fumagillin.
As a “salvage” agent for individuals with PJP who fail
to respond to trimethoprim-sulfamethoxazole
Fumagillin is used topically to treat keratoconjunctivitis caused (pentamidine may be less effective than the
by Encephalitozoon hellem combination of clindamycin and primaquine or
atovaquone for this indication)

Pentamidine administered as an aerosol preparation

is used to prevent PJP in at-risk individuals who
cannot tolerate trimethoprim-sulfamethoxazole, such
as patients with severe bone marrow suppression.
Given monthly.

AE Abdominal cramps, nausea, vomiting and diarrhea, reversible Bronchospasms

thrombocytopenia and neutropenia.
Rapid injection: pain, irritation, cardiac arrythmias,
severe hypotension, hypoglycemia, acute
pancreatitis.

Notes Several disadvantages, including its failure to treat

any extrapulmonary sites of Pneumocystis, the lack
of efficacy against any other potential opportunistic
pathogens, and a risk for pneumothorax.

Should be limited to patients in whom Pneumocystis

is identified and should proceed with careful
monitoring for the development of adverse effects.