Treatment General Approach

The approach to antifungal therapy in patients with endemic fungal infections is determined by the severity of clinical presentation, the patient's underlying immunosuppression, andpotential toxicities and drug interactions associated with antifungal treatment. Immunocompetent patients with mild disease following exposure to H. capsulatum or C. immitis often experience a benign course of infection and rarely require antifungal therapy. Typically, these patients are followed in the outpatient setting with serial antigen testing to confirm resolving infection. Patients without clinical improvement within the first month are typically treated with oral itraconazole for 6 to 12 weeks (Table 84-2).14 6 Other newer azoles such as voriconazole and posaconazole appear to have good activity against endemic fungi; however, there are currently insufficient data to recommend their routine first-line use. Fluconazole (400-800 mg/day) is somewhat less effective than itraconazole but may have fewer GI adverse effects and drug interactions than itraconazole in patients who require prolonged therapy.1'4'6 Patients with progressive symptoms longer than 2 weeks or titers greater than 1:8 of histoplasmosis or coccidioidomycosis antigen are candidates for immediate antifungal therapy.1'4 Any patient with underlying immunosuppression should also receive immediate antifungal therapy. The following signs and symptoms are considered to be indicators of severe disease that requires hospitalization and initial treatment with systemic amphotericin B (see Table 84-2).

Table 84-2 Therapeutic Approach to Endemic Fungal Infections

Ktoomnn ended Tfealimtnt fteglmtni Commits.

Hlüfiplumuta

Ulli m modera» acut? pulmonary disc«?

Mori« íH'ly spifp-p losei/we acute pulmo raí y dii ease tlvonk: cavilaiy pulnwnary disease-

MildF to moderate pr^igressJve disseminated disease

MtnKfiiely wvue lostvtie progiewiw tUsírtiInSled diwast1

Observation or

II symptoms pallet greater Hun 3 month, •tijctmiMok' 300 mg cfaljy 1 y daily (or ü days and [hen JtW nvj uriif or Tivke daily for 6-12 wMfci lipid ftiíiTMlaiiün gf AmphqUertdn&O—S

ng/kg/day IV for 1-Í weekn folksvwd by ild.K iin.j^A' IjíÜ mi;. 3 y (I.lily ft* 3 ii.iy, and then J00 mg twee daily, fof a total for II WFiks)

Nraoonaíüle (íOO mg 3 x (tally for iffcuyt and tfn.ri onw or Ivwot tliily 1or 1 I yMf?

Itraconazole 100 í^g í x dasäy fo 3 days and lhen mice il.nly lor at iMit li nwnths t tposopwl Ani|)h(Ki.TE in p (3- ivy^liii daily) k> I-.2 wwiSy lolloped by oral inacoriMole l2CK)nir? 3 vdjilyfa- 3 diyi and 1hen ,'(IU mg 1wice dally for a total of dt kvjJL II murKhsO

hraíonaTolfl r less eflettre ta CMS infections

Aniphoiertln fs dftutyrholate 107-1 nvytjgdjilV IV) is an alternative in [jatiervl s wmh low risk of nephrotoxicity Methylprednisolone (0.5-1 mg/kg daily IV) during the first 1-1 we^fat patiertt*rtfjb;Jpv^ap i^iplraiory iornpfcationi ttn/poxemla, signlfscarvi respiratory distress, etrj fllood levels of itiacoriarolí* shoi^d be Obtained jítci 1 wCíki o(Ihcupry (y ensure iitJwjudtii í-ípOSUH*

Substitution OÍ ínotlui li|i¡i.l íihfrniil.i-icfi .ir ,i dosjge oí í mg/fcg daily nwybifuiffurrfld ki some patients due to to?i tk usier ability Anipholerkln It deímycholate {0./-1 mgvfcj daity IV} ¡i anjIri^nativL" in [AJtk'rtls Willi kn»r ritkof neflhro tonicity

I ifelong supnre^rve thtífapy wrih itraconazole f?00 inq tfciilyi míy be Iftpj rrff in iinnnjívjíupfjieisítt IMiietií*. if Immuno'AipfifeíSlon csnnot be npittsed and in pjliontt vim relapsa dtjspfle rmüfii iif a^^píinfiriarí- Thfi vy ftood tevelsof itiaconarale should be obtained to iWI dkease bid stomycoii i

Mild 1ü modf-idtf: pulmoruiy diyijbif

Ufoderalefy ¿eveten) ¿eveie pulmonary disease

Mikl 1<? miKjflatPifrtimuriatPd extrapulmonary disease

Coccidioidormycoit-s WlkJ [0 (TlLKi?iSTie

[Muse pneoirraiia tu dissefnnated

Liposomal arnpholeridn B (S mg/kg daily for a 1o1al of 17S mg/hg given over 4-6 weck!) lollowod by itrooonjiok? (200 rng 2 X or 3 X daily} fw a! I yoiii and unl.il resolulkmoi CST atfioiiTuliii«; including HIStOpfaSiTiä antigen ^ recommended

IrrjounAsule, 300 ing 3 ?< per tiayluf 3 diiyi ¿rut thtrt önitüi [wk.t.L|iir dJy ioi 6-12 nioiirhs

Lipid foinKdrtlonot Amphotaicin H ji a öosage of 3-i rngvlog/day of ¿rrphotencin E deoxychülate at a dD'-mge of 0.7-1 mg/kg/daylbf l-Jweefcs or until improvemen.1 it noied. followed by oral ibaionuole, 200 mg 3 * per day for 3 days and then 300 mg 1 wke pel diy, fa nvxnh*

Irrüffifhiriile, 200 iTig SKrieriiayfofJdfly^ and thenorveor twira per dayfori-lj months

Miödiiardy sevefa lu if.fft dissorninalod extiapuifnonaiy disease

Ctö diveaw

Lipid fcfmjMlon qf Amphotfifkin & 3-5 m^tig/day, or Amphotericin E rfcttiyehotatt; 0J 1 my/kgAlijy. fcx I 2 weckvoi unrll irnpfüvcnifflil is nar«t folfcuNtid by o<al HrKoruiofcr. 300 mg 3 if pei djy (yi 3 dj/s JIH! H«.1" 200 niy ru.'iLO pci dayim a holal of ¿1 li>asi months

I ipid foimulaiion of imptKlierlf in B, 5 mg.'<?>tJay over 4-G WKiks followed by an dial aisl^

ObiftuJion Of Hr^onaitJ? JOOmg ofilty twice daily tof 6-6 months

HucfifHmlPt-li nryytgAfayoially dally

Amphotericin fl l-li mg/kg/d^' «Ith dose hetutrtcy ÜV< u 'jwti lis MnpfOvimwi «an; or lipid Amplwierkiii IS rt*rnuljlic«ii ensure jdequalcdiugexposuic' Amigifi ICvflte ifkiukl Ik.1 dtHUMd duriny IherijJy jnd fc< 13 rrcfuhi jfiii ihoraoy iii^Klod to (WTlIlM tot reLifrs** Blood levels of rHacona/ok" should b-.Lob1airv?d to LTiuirt jdequaHidiugexposuio

■Stfum kfiiL-liol idatjunjiulc1 should bt tk'tei mined jikf [he patient ItiS rediivitJ this iyent fm <j[ liasi 3wL'(Asr[tiensiurtJt)«iuiijidiu^'espösuit

Patient1, wnh osteal tktilai btotüniyco'js should receive a lolal of at least I? momtisof aitiifungal lheiapy

■¡htu^ k^'elsuf ¡(Muuriimole should tw rk'teiminod jiMf th# piiiioni his rctoivLtl this fof jt iwdis. wining

C^irioni lof arole rtaapy irludeflu^narolp. S00 mgAJai'. itraconaiiole, 300 mg 2 c* 3 * p» davi oi iiwtomdflle, .to ■itx: it*i twtce pef day, for an lern 12 months and urnlil resolution of C3F alnnnrrniiliiifi

Itratonajiili rli?nv>n4Tiiait«i roivard superiorityove< rVnoniiiafema randomiiod cwiiioKed tn.nl (tii nonnwningMl

COff Kkitiionnyrijirv: Iviiw^f, f ItKOrwumfe- ü buHtf tok?ratid fhjfl idaionaiote FltjoonarDle fiflö-1JÜ0Ö m^'iday is somelinnes rL-^umnn.'nikO ^tei ir"(ul Amp^oltikifi E tlnTjjjy fof nwningirh

Hypoxia indicated by a partial pressure of oxygen less than 80 mm Hg Hypotension (systolic blood pressure less than 90 mm Hg) Impaired mental status

Anemia (hemoglobin less than 10 g/dL [100 g/L or 6.2 mmol/L])

• Elevated hepatic transaminases (greater than five times upper limit of normal) or bilirubin (greater than 2.5 times upper limit of normal)

• Coagulopathy

• More than 10% loss in body weight

• Evidence of dissemination including cutaneous manifestations

• Meningitis

The treatment of blastomycoses is heavily dependent on the severity of clinical manifestations. Generally, patients with mild disease can be managed as outpatients with oral itraconazole.6 Patients with evidence of severe pulmonary disease or dissemination require initial treatment as inpatients with amphotericin B-based regimens until they are clinically stable, whereupon they can complete a 6- to 12-month treatment course as outpatients with oral azoles.6 Methylpredni-solone (0.5-1 mg/kg daily IV) during the first 1 to 2 weeks of antifungal therapy is often considered for patients who develop respiratory complications during initial treatment, including hypoxemia or significant respiratory distress.

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