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275 Cards in this Set
- Front
- Back
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polyene antifungals
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Amphotericin B, nystatin
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azole antifungals
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Imidazoles: Ketoconazole..
Triazoles: Fluconazole, itraconazole, voriconazole, posaconazole, ravuconazole |
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allylamine antifungals
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Terbinafine, butenafine
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morpholine antifungals
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Amorolfine
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fluorinated pyrimidine antifungals
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Flucytosine
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echinocandin antifungals
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Caspofungin, anidulafungin, micafungin
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peptide nucleoside antifungal
(not avail. yet) |
Nikkomycin Z
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tetraydrofuran antifungals
(not avail. yet) |
Sordarins, azasordarins
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other misc. antifungal
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Griseofulvin
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antifungal drugs by mode of action:
membrane disrupting agents |
AMB, nystatin
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antifungal drugs by mode of action:
ergosterol synthesis inhibitors |
azoles, allylamines, morpholine
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antifungal drugs by mode of action:
nucleic acid inhibitor |
flucytosine
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antifungal drugs by mode of action:
anti-mitotic(spindle disruption) |
griseofulvin
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antifungal drugs by mode of action:
glucan synthesis inhibitors |
echinocandins
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antifungal drugs by mode of action:
chitin synthesis inhibitor (not avail yet) |
nikkomycin
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antifungal drugs by mode of action:
protein synthesis inhibitor (not avail yet) |
sordarins, azasordarins
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what are the three main targets for antifungal activity?
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1. Ergosterol (cell membrane)
2.RNA/EF3(nucleic acid/protein synthesis) 3. Glucan/chitin (cell wall) |
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specific antifungal targets against ergosterol?
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Drug-ergosterol interaction
Inhibition of ergosterol synthesis |
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specific antifungal targets against nucleic acid/protein syntehsis?
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Incorporation of 5-FU in RNA
Inhibition of elongation factor 3 (EF3) |
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specific antifungal targets against glucan/chitin(cell wall)
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inhibition of glucan/chitin synthesis
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MOA nystatin
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Binds to ergosterol in the fungal cell membrane
-->Results in altered membrane permeability releasing intracellular potassium, sugars, and metabolites Disruption of the membrane = fungal cell death (fungicidal) |
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PK nystatin
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not important b/c only available topically
(No significant absorption from GI, cutaneous, or vaginal administration) |
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dosing forms of nystatin
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Topical cream, ointment, and powder
Oral suspension Intravenous liposomal nystatin (not available yet) |
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PD nystatin
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Concentration dependent ([higher] increases killing)
Fungicidal (b/c opens cell membrane) Has post-antifungal effect |
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SE oral admin of nystatin
(for gut decontamination) |
N/V, diarrhea, Gi discomfort
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spectrum of activity:
nystatin |
Candida
(Oral candidiasis, mucocutaneous infections, gut decontamination) *topical candida infections |
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nystatin resistance
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Ergosterol deficient (reduction of ergosterol content in cell membrane)
ex: Saccharomyces |
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amphotericin B (AMB) historical features
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A polyene macrolide
Isolated from Streptomyces nodosus Insoluble in water Solubilized by sodium deoxycholate Available for IV use as amphotericin B deoxycholate (Fungizone®)/AMB |
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MOA AMB
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fungicidal,
binds to ergosterol, opens cell membrane, leakage of cellular contents (cations/proteins) |
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PK AMB
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Only IV formulation is available
-->Not absorbed from GI tract 95% protein bound poof CSF penetration *no definitive adjustement recc. for hepatic/renal dysfunction b/c unsure of elimination(some renal, some bile) |
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PD AMB
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Concentration dependent
-->Cmax/MIC Fungicidal -->Organism dependent Post antifungal effect 0.5-30 hours |
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what is a post antifungal effect?
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after [antifungal] drops below the MIC, it is still able to inhibit regrowth
(ex) nystatin, AMB |
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drug interactions with AMB?
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minimal drug drug interactions:
Other nephrotoxic agents Agents that effect electrolytes Does not have major effect on other drug PK Drugs do not have major effect on Ampho-B PK |
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spectrum of activity for AMB
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***Broadest antifungal available
Candida spp. (including azole-resistant species) Aspergillus spp. Cryptococcus neoformans Mucor spp. Blastomyces dermatitidis Coccidioides immitis Histoplasma capsulatum Paracoccidioides brasiliensis |
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AMB resistance
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Any alterations that result in reduced ergosterol content
Reduced ergosterol content (defective ERG2 or ERG3 genes) |
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what organism exhibits reduced susceptibility/resistance to AMB?
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Candida lusitaniae
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clinical indications for AMB?
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systemic mycoses:
Candidiasis *Coccidioidomycosis Aspergillosis *Histoplasmosis *Cryptococcosis Paracoccidioidomycosis *Mucormycosis Sporotrichosis Blastomycosis Febrile neutropenia pts. unresponsive to antibacterial therapy |
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SE AMB
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**Nephrotoxicity
Acute infusion related reactions (Fever, chills, hypotension, tachypnea, malaise, RIGORS) |
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prevnetion of AMB nephrotoxicity
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give NS bolus prior to each AMB dose (dilute the drug, protect kidney)
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prevention of acute infusion related rxns with AMB
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Slow infusion rate, decrease drug concentration,
pre-medicate: Acetaminophen, Diphenhydramine, Meperidine (for rigors) |
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how does AMB cause nephrotoxicity?
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Constriction of the afferent
arterioles leading to decreased glomerular filtration Direct damage of distal tubular membranes leading to wasting of Na+, K+, and Mg++ Tubular-glomerular feedback: Further constriction of arterioles |
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lipid formulations of AMB:
amphotericin B lipid complex |
ABLC
Abelcet |
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lipid formulations of AMB:
amphotericin B Colloidal Dispersion |
ABCD
Amphotec |
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lipid formulations of AMB:
Liposomal amphotericin B |
L-AMB
Ambisome |
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which AMB lipid formulations are a lipid complex with the AMB suspended b/w lipid molecules?
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ABLC (Abelcet)
ABCD (Amphotec) |
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which lipid AMB formulation is the drug AMB put into a liposome?
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L-AMB
Ambisome |
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possible mechanism for L-AMB (ambisome)?
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Exact mechanism unknown
Selective uptake into RES Higher uptake, retension, and slow release by macrophages ***endocytosis, the drug released at site of action, less delivery to the kidney |
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comparative in vivo efficacy of the AMB formulations?
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Efficacy is EQUAL
better tissue penetration in increased lipophilic products, but no improved efficacy in clinical response between lipid formulations or traditional AMB deoxycholate |
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comparative nephrotoxicy between AMB formulations?
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less nephrotoxicity found with the newer lipid formulation products vs. AMB deoxycholate
(L-AMB may be better) |
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compatative rates of infusion related side effects between AMB formulations?
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ABCD was found to be WORSE than traditional AMB
L-AMB and ABLC had significantly less toxicities than older AMB deoxycholate *choose L-AMB, ABLC when possible |
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major advantages of lipid/liposomal AMB formulations?
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tolerable at higher doses
3-10mg/kg(L-AMB) vs. 0.6-1 mg/kg(AMB) -->good for CNS infections b/c higher doses needed significantly less toxic |
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major disadvantage of lipid AMB vs. traditional AMB deoxycholate?
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Expensive!!!!
~10 x's more expensive for new formulations |
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Griseofulvin MOA/uses?
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Inhibits Spindle and Cyctoplasmic Microtubule function
Old drug for superficial skin infections |
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terbinafine MOA
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inhibits ergosterol synthesis by inhibiting squalene epoxidase in the fungal cell membrane
preventing conversion of squalen to squalene- 2,3epoxide |
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Azoles MOA
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inhibit 14-alpha-demethylase enzyme, inhibiting conversion of lanosterol to ergosterol and causing accumulation of 14-alpha methylsterols and depletion of ergosterol
*inhibit ergosterol synthesis |
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enzyme terbinafine inhibits
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squalene epoxidase
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enzyme azoles inhibit
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14-alpha demethylase
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triazoles
(1st gen.) |
fluconazole
itraconazole |
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new broad spectrum azoles
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voriconazole
po/IV posaconazole po |
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PK differences of azoles:
oral absorption good, fair, ceiling effect? |
ALL are available PO, most IV
Good – Fluconazole and voriconazole 90% Fair – Itraconazole Posaconazole – Good, but has ceiling absorption effect. Cannot give more than 400 mg at one time |
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what is unique about posaconazole dosing?
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ceiling absorption, cant give more than 400 mg at a time
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PK differences of azoles:
elimination renal vs. hepatic |
Fluconazole – 90% renal
Itraconazole, voriconazole, posaconazole – Extensive liver metabolism |
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clinical pearl about IV itraconazole and IV voriconazole
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IV Itraconazole and Voriconazole contain a product called cyclodextrin
Itraconazole and voriconazole are not eliminated renally, but cyclodextrin is Cyclodextrin can accumulate in renal failure and has been shown to cause nephrotoxicity in animals *cyclodextrin vehicle accumulates in kidneys, but parent drug hepatically eliminated |
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PD azoles
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Fungistatic
AUC/MIC Most predictive of good outcome (Concentration Dependent) |
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spectrum of activity azoles:
Most narrow to most broad |
Fluconazole
Candida species (not C. krusei; C. glabrata intermediate), Cryptococcus Histoplasma, Blastomycosis, Coccidiomycosis Itraconazole All of the above + aspergillus Voriconazole and Ravuconazole All of the above + Fusarium and Scedosporium More effective against the less sensitive Candida and Aspergillus species Posaconazole All of the above + Zygomycetes More effective against the less sensitive Candida and Aspergillus species |
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list azoles from least to most broad spectrum
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fluconazole
itraconazole voriconazole/ravuconazole posaconazole |
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spectrum summary:
Key species for azoles: fluconazole |
candida
cryptococcus |
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spectrum summary:
Key species for azoles: itraconazole |
candida
cryptococcus aspergillus |
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spectrum summary:
Key species for azoles: voriconazole/ravuconazole |
candida
cryptococcus aspergillus fusarium scedosporium |
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spectrum summary:
Key species for azoles: posaconazole |
candida
cryptococcus aspergillus fusarium scedosporium zygomycetes |
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mech. of resistance azole antifungals
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#1! Alterations in the 14-alpha-demethylase enzyme
Alterations in the composition of membrane-associated sterols Alterations in the biosynthetic pathway of ergosterol Efflux |
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adverse effects all azole antifungals
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N/V, GI sx
rash hepatic dysfxn (increased ALT,AST, Alk. Phos.) |
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which azole antifungal has additional SEs to worry about?
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voriconazole
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voriconazole SEs
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Hepatic
Overall rate of 13%. ~ 2-fold more than Fluconazole Visual (difficulty seeing) |
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voriconazole monitoring
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blood levels
liver enzymes renal function (cyclodextrin accumulation) |
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voriconazole P450 interactions (many)
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Vori increases sirolimus & rifabutin: don’t mix
CsA and tacrolimus are OK, but must lower dose Phenytoin drops vori, vori raises phenytoin Dosing directions in package insert |
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CYP 3A4 inducers that have effects on azoles
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rifampin
phenytoin carbamazapine phenobarbital |
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azole reduction in blood levels due to strong CYP 3A4 induction?
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90% reduction: ketoconazole, itraconazole, voriconazole,
50% reduction: fluconazole decrease: posaconazole, ravuconazole |
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what effect do azoles have on CYP 450?
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INHIBITION
they increase the conc. of many other drugs (statins, warfarin), so decrease the dose of those drugs by about 50% |
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which azole has broadest CYP inhibition, which has the least CYP inhibition?
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broadest: ketoconazole
least: fluconazole |
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flucytosine target for antifungal activity
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RNA/EF3 (Nucleic acid/Protein synthesis)
Incorporation of 5-FU into RNA Inhibition of EF3 |
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MOA flucytosine
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cytosine deaminase in fungal cells converts flycytosine to 5-FU, which is substituted for uracil and inhibits protein synthesis
it also inhibits thymidylate synthase, inhibiting DNA synthesis |
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PK flucytosine
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Oral form only in USA
80-90% bioavailability Low protein binding ~4% Vd 0.6-0.9 L/kg Distribution into all tissues (e.g. major organs, bone, csf) Renal elimination (glomerular filtration) Half-life 3-4 hours Plasma level monitoring Peak levels – 2 hours after dose administered 30-80 mcg/ml (correlate to toxicity) |
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PD flucytosine
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Time dependent killing
Time > MIC AUC/MIC also predictive Fungistatic |
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SEs flucytosine
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Bone marrow toxicity
Hematologic Peak levels > 100 mcg/ml (monitor WBC, HCT, Hgb |
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spectrum of activity flucytosine
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Cryptococcus neoformans
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flucytosine resistance
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mutations in cellular transport proteins
cytosine deaminase (converts to 5-FU) UMP pyrophosphorylase |
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drug interactions for flucytosine
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MINIMAL
Aluminum hydroxide/magnesium hydroxide Delays flucytosine absorption Use with other bone marrow suppressive therapies might be additive in inducing adverse effects |
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Key MOA echinocandins
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*Inhibition of β-(1-3) glucan synthase...
deplete beta(1,3) glucans in the cell wall =>inhibit cell wall synthesis |
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PK echinocandins
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IV only, low bioavailability PO
Poor CSF penetration Elimination Caspofungin Hydrolysis and N-acetylation Micafungin Hepatic metabolism Anidulafungin Slow chemical degredation in the blood |
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differences in echinocandin elimination
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Elimination
Caspofungin Hydrolysis and N-acetylation Micafungin Hepatic metabolism Anidulafungin Slow chemical degredation in the blood Caspofungin and Micafungin require dose adjustment in Moderate and Severe hepatic dysfunction. **Anidulafungin does not require dose adjustment in hepatic disease** |
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PD echinocandins
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Fungicidal
Concentration dependent killing Cmax/MIC Significant post-antifungal effects Sometimes > 12 hours |
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SE echinocandins
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generally well tolerated
some infusion related rxns: phlebitis, flushing, pain |
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spectrum of activity echinocandins
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all Candida species, Aspergillus
*no cross resistance w/ azoles or AMB for candida resistance |
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primary echinocandin resistance
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Cryptococcus, Zygomycetes, Fusarium, scedosporium, trichosporon
(b/c organisms have low amts. of beta1,3glucan synthase to begin with) |
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secondary echinocandin resistance
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glucan synthase alteration
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drug interactions caspofungin
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Cyclosporine increases caspofungin AUC by 35%
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which echinocandins has the most drug interactions?
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micafungin
mild CYP 3A4 inhibitor (increase other drug conc.) |
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which echinocandin has the least drug interactions?
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anidulafungin
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what are increase in mycotic infections caused by?
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Longer life span
New and more potent antibiotics Increase in surgical procedures Increased use of parenteral therapy TPN Artificial devices Organ Transplants AIDS |
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trends in invasive mycoses::
candidiasis and aspergillosis |
candidosis trend decrease, then plateau b/c resistance
aspergillosis increased, plateau, now decrease again |
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factors involved in deveoplment of opportunistic mycoses
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barrier disruption (skin)
exposures quantitative or qualitative neutrophil dysfunciton deficits in cell mediated immunity |
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what is candida?
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Candida is ubiquitous
More than 200 species have been described. Most common cause of opportunistic mycoses worldwide Normal flora of skin, GI, and GU tracts, and also may be seen in the respiratory tract Candida is the 4th leading cause of nosocomial blood stream infections. Prolongs hospital stays and cost Not restricted to neutropenic or immunocompromised patients |
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pathogenicity of Candida
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The clinical spectrum of candidiasis is extremely diverse.
Almost any organ or system in the body can be affected Superficial and local or deep-seated and disseminated Disseminated infection arises from hematogenous spread from the primary locus Candida albicans – most pathogenic Ability to adhere to host tissues Transform from yeast to hyphal phase |
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excess mortality, LOS, associated costs of candida
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Excess mortality rates: 10%-49%
Excess LOS in hospital: 3.4-30 days Excess costs: $6200-$92,000 Average total cost of candidemia: $44,536a *1997 dollars |
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candida incidence vs. mortality in ICU
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#3 in incidence, but more higher mortality than #1, #2 coag. neg. staph and staph. aureaus
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host predisposing factors for infection with candida
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Physiologic: Pregnancy, age (elderly and infants)
Trauma: Maceration, infection, burn wound Hematologic: NEUTROPENIA, cellular immunodeficiency (leukemia, lymphoma, AIDS, aplastic anemia) Endocrine: Diabetes Mellitus, hypoparathyroidism, Addison’s disease Iatrogenic: Chemotherapeutics, corticosteroids, immunosuppressants, oral contraceptives, antibiotics, catheters, surgery Other: IVDU, malnutrition, malabsorption, thymoma |
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spectrum of disease due to Candida:
non hematogenous |
Non-hematogenous Infections
Superficial Infections Cutaneous candidiasis Oropharyngeal candidiasis Vaginitis |
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spectrum of disease due to Candida:
deep seated infections |
Deep-Seated Infections
Esophageal candidiasis Cystitis Treatment of asymptomatic candiduria in non-neutropenic pts has not been shown to be of value. Peritonitis Tracheitis/bronchitis or pneumonia Colonization of the airway and/or contamination of sputum common. Histopathological diagnosis required |
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spectrum of disease due to candida:
hematogenous infections |
Hematogenous Infections
Candidemia Endophthalmitis Vascular-access-related infection Septic thrombophlebitis Infectious endocarditis Arthritis Osteomyelitis Spondolyodiscitis Meningitis Pyelonephritis Pulmonary candidiasis Hepatosplenic candidiasis |
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common candida species
most common to least |
albicans
glabrata parapsilosis tropicalis krusei lusitaniae |
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what is C. krusei resistant to?
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fluconazole
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what is C. lusitaniae resistant to?
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AMB
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species specific differences in echinocandin MICs
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In vitro surveys have documented comparative differences in resistance between Candida sp to echinocandins
Common species: C albicans, C glabrata, and C tropicalis are highly susceptible (modal MIC, 0.015-0.06 µg/mL; 99.8%-100% S at ≤2 µg/mL) Elevated MICs (modal MIC, 0.25-1 µg/mL) are seen for C parapsilosis and C guilliermondii (90%-100% S at ≤2 µg/mL) |
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wich candida has highest mortality?
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C. krusei
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candidemia mgmt:
prophylaxis |
no disease
high risk pts (chemo, ICU) |
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candidemia mgmt:
preemptive |
markers
asymptomatic, positive culture or beta D glucan |
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candidemia mgmt:
empirical |
signs and symptoms
majority of treatment high risk, febrile pts recieving antibiotics |
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Principles of Managing
Invasive Candidiasis |
Consider the source
Establish the diagnosis Repeat cultures, pursue imaging Consider the type of patient Colonized? Trauma? Neutropenic? Future chemo? Evaluate the bug Consider species-specific features Consider susceptibility testing Remove prosthetic devices, if possible Consider options for antifungal therapy |
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traditional diagnosis candidiasis
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Blood cultures
Negative: 50% Intense research in technique improvement Biopsies and other cultures Not always feasible Contaminant vs real? limited by biology of the disease**** |
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ID high risk patients for candida infection!
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At least 1 of the following:
Use of antibiotics Presence of a central venous catheter AND at least 2 of the following: Use of TPN Any type of dialysis Any major surgery Pancreatitis Systemic steroids Other systemic immunosuppressive agents 10% risk incidence |
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advantages of candida prophylaxis in high risk pts.
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BSI 3.4 pre fluconazole, .79 with fluconazole prophylaxis....4 fold difference in high risk invasive candidemia
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eye exam with candidiasis
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Dilated eye exam
All with candidemia Particularly in prolonged fungemia Endophthalmitis Consider intravitreal treatment / vitrectomy |
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lifelines invasive candidiasis
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Lines and foreign bodies
Remove if possible—better outcomes Tunneled catheters are low risk Neutropenic patients Gut vs line? **************************** Biofilms are important Polyenes and echinocandins |
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bottom line candidemia in ICU
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Epidemiology supports importance of candidemia, particularly in ICU settings
Need for better diagnostics Need for practical rules to assess risk More than 1 thing to do with antifungals Prophylaxis Preemptive and empirical therapy Traditional treatment |
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aspergillus infections
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Aspergillus spp. are ubiquitous (mold) – found in soil, water, and decaying vegetation
3 major manifestations of disease Invasive aspergillosis Involving several organ systems (particularly pulmonary disease) Pulmonary aspergilloma Allergic bronchopulmonary aspergillosis |
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invasive aspergillosis patient profiles 2 most common risk factors
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BMT
hematologic disease |
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spectrum of diesae invasive aspergillosis
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Lungs are the most common site of disease
Sinus disease also prominent in some centers CNS is the most common secondary site of invasive disease Organism grows fast and invades blood vessels Can present as cerebral hemorrhage Cutaneous disease can occur at old IV sites or open wound sites |
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cryptococcus
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Cryptococcus is an encapsulated yeast.
identification in nature from peach juice the major environmental sources of Cryptococcus neoformans have been shown to be either soil contaminated with pigeon droppings (Cryptococcus neoformans var. neoformans) or eucalyptus trees and decaying wood forming hollows in living trees (Cryptococcus neoformans var. gattii) Cryptococcus neoformans var. gattii was also isolated from goats with pulmonary disease |
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pathogenicity of cryptococcus
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Cryptococcus neoformans: the causative agent of cryptococcosis
Given the neurotropic nature of the fungus, the most common clinical form of cryptococcosis is meningoencephalitis. The course of the infection is usually subacute or chronic. Cryptococcosis may also involve the skin, lungs, prostate gland, urinary tract, eyes, myocardium, bones, and joints |
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predisposing factors to cryptococcus
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Most common
AIDS Less common Organ transplant recipients Cancer patients receiving chemotherapy Patients on long term corticosteroid therapy |
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mucormycosis
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Mucorales (Absidia, Mucor, Rhizomucor, and Rhizopus)
Growth characteristics cultured on routine fungal media - growth within 24 - 72 hrs Ubiquitous - soil, decaying organic debris, fruit, bread High risk individuals - diabetes (DKA), leukemia, lymphoma, steroid therapy, organ transplantation, extensive burns, severe malnutrition, dialysis patients treated with deferoxamine |
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mucormycosis clinical aspects
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Acute, fulminant infection
Invasion of major blood vessels - ischemia and infarction of adjacent tissue Rhinocerebral mucormycosis local symptoms sinusitis, palatal or orbital cellulitis nasal septum - ulcerated, necrotic or even perforated, and dark, bloody nasal discharge often occurs neurologic sequelae evolve after a few days - rapidly progressive - ptosis, proptosis, dilation fixation of pupil, drainage of black pus from eye can be seen |
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AMB sensitive organisms
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Yeasts (reliable activity)
Candida spp. (except C. lusitaniae) Cryptococcus neoformans Dimorphic fungi (reliable activity) Blastomyces dermatitidis Coccidiodes immitis Histoplasma capsulatum Molds / Filamentous fungi (variable) Aspergillus Mucorales Sporothrix schenckii Fusarium Scedosporium (negligible coverage) |
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flucytosine sensitive organisms
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Yeasts
Candida spp. Cryptococcus neoformans |
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Azoles sensitive organisms
fluconazole |
Yeast
Cryptoccocus neoformans Candida albicans Candida tropicalis C. parapsilosis Dimorphic Fungi Histoplasma capsulatum (variable efficacy) Blastomyces dermatitidis Coccidiodes immitis |
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Azoles sensitive organisms
itraconazole |
Yeast
Candida spp. Cryptococcus neoformans Dimorphic fungi Blastomyces dermatitidis Histoplasma capsulatum Coccidiodes immitis Paracoccidiodes brasiliensis Filamentous fungi / molds Aspergillus spp. Zygomyces Sporothrix |
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lipid formulation AMB advantages
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Use in patients with renal dysfunction
Higher blood concentrations Use in patients with severe systemic infections (e.g. aspergillosis, mucormycosis) requiring intensive, higher dose, prolonged therapy |
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lipid formulation AMB disadvantages
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Cost
4 - 5 times the cost of conventional amphotericin B |
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comparison dosing lipid AMB
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D-AmB 0.5 - 1
ABLC 5 L-AmB 3 or 5 |
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general concepts echinocandins
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Completely independent of triazole or amphotericin targets: no antagonism & no relation to triazole or AMB resistance
Action is rapid (minutes) Candida spp. rapidly killed Aspergillus spp. severely wounded, but not killed Some activity in vitro vs endemic mycoses No activity vs. Cryptococcus spp. Prolonged postantifungal effect compared with azoles |
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caspofungin dosing/admin
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70 mg IV Loading Dose then 50 mg IV qd
renal insufficiency- no dose adjustment mild hepatic insufficiency - no dose adjustment moderate hepatic insufficiency - 70 mg LD then 35 mg qd |
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micafungin
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Formerly known as FK463
Developed by Astellas Echinocandin structural class IV only FDA Approved – March 2005 |
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anidulafungin
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Previously known as LY303366
Developed by Vicuron/Pfizer Echinocandin IV only FDA approved – February 2006 |
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voriconazole sensitive organisms
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Yeasts
Candida spp. (including C. glabrata, C. krusei) Cryptococcus neoformans Dimorphic fungi Coccidiodes immitis Blastomyces dermatitidis Histoplasma capsulatum Filamentous fungi Fusarium spp. Scedosporium spp. Aspergillus spp. |
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voriconazole dosing
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Dosing
LD (PO) 400 mg bid x 1 day MD (PO) 200 mg bid (subjects < 40kg 50% dose) LD (IV) 6mg/kg q 12h x 1 day MD (IV) 4mg/kg q12h (subjects < 40 kg 50% dose) *dilute IV solution before administration, max rate 3 mg/kg/hr if via peripheral line *IV formulation contains CYCLODEXTRAN– caution in renal insufficiency note: need BID dosing since want to keep trough above 0.5 mcg/ml |
|
|
posaconazole
|
Developed by Schering Plough Pharmaceuticals
Azole class antifungal Oral suspension only FDA approval November 2006 for prophylaxis aspergillosis Results so far: covers zygomycetes better pharmacokinetics better tolerability lower MICs |
|
|
therapeutic approach to invasive candidiasis
2008 guidelines |
AMB (amphotericin B deoxycholate or lipid formulations of AMB)
Fluconazole AMB plus fluconazole AMB then fluconazole AMB plus flucytosine Caspofungin, anidulafungin, micafungin Voriconazole |
|
|
time to therapy: invasive candidiasis mortality
|
significant decrease in mortality if treatment started within 12 hours
|
|
|
revised ISDA guidelines for candidemia
|
Choice of therapy depends on clinical status of the patient and knowledge of species
Remove all lines, if feasible Therapy Fluconazole 6 mg/kg/d (400 mg), or aCaspofungin 50 mg/d, anidulafungin 100 mg/d, or micafungin 100 mg/d, or aAMB (0.6-1.0 mg/kg/d for AMB or 3 mg/kg/d for liposomal formulations of AMB) in selected circumstances Treat 2 weeks after last positive blood culture and resolution of signs and symptoms of infection |
|
|
revised IDSA guidelines for candidemia based on type of candida
|
C glabrata
AMB 0.7 mg/kg/d or an echinocandin C krusei AMB 1 mg/kg/d, an echinocandin, or voriconazole C parapsilosis Fluconazole 6 mg/kg/d C lusitaniae Fluconazole 6 mg/kg/d or an echinocandin |
|
|
therapy considerations:
catheters/biofilms |
Azoles and AMB have poor results with catheters, but echinocandins and lipid formulations of AMB kill Candida in biofilms1
Micafungin or L-AMB aggregate success rate is similar with and without removal of catheter2 Micafungin or caspofungin aggregate success rate is 299/384 (77.9%) with removal vs 91/144 (63.2%) without removal, which is significant (P=.001)3 |
|
|
important questions to ask about candidemia
|
Under what circumstances is fluconazole still first-line therapy?
Mild-to-moderate illness, no recent azole exposure When is it appropriate to transition from an IV regimen to step-down therapy with an oral azole? Transition to fluconazole, when appropriate, is encouraged once Candida sp is known and patient is stable Is there a role for combination therapy? Data are limited to patients with endocarditis and CNS disease treated with AMB and 5-flucytosine. Utility of immunotherapy in combination with other agents to be explored (efungumab) |
|
|
summary immunocompromised patients for candidemia
|
Candida infections are not going away as we create more immunocompromised patients
Diagnostic strategies could be improved There are excellent antifungal choices for management of candidiasis Echinocandins, azoles, and polyenes |
|
|
invasive aspergillosis
|
Diagnosis
Available antifungal agents Primary treatment Salvage treatment Prophylaxis Role for Combination therapy Adjunctive treatment Surgery immunomodulation |
|
|
diagnosis of invasive aspergillosis
|
EORTC- MSG definitions
Clinical manifestations Appropriate host Laboratory diagnosis Diagnostic imaging Direct exam Culture Tissue Molecular markers Galactomannan 1,3,B –D Glucan DNA (PCR assay) |
|
|
available antifungals for aspergillosis
|
Polyenes
Amphotericin B Amphotericin B lipid formulations Triazoles Itraconazole Voriconazole Posaconazole Echinocandins Caspofungin (FDA approved) Micafungin (off label) Anidulafungin (off label) Role for Therapeutic Drug Monitoring (TDM) To evaluate therapeutic failure that could be due to sub-optimal drug exposure |
|
|
invasive aspergillosis treatment
|
Few randomized controlled trials (RCTS)
The largest RCT demonstrated that voriconazole is superior to D- AMB as primary therapy of IA (Herbrecht et al. 2002) Voriconazole is recommended as primary therapy for IA in most patients Exceptions Voriconazole intolerant patients Resource limited facilities |
|
|
recom. thearpy for invasive aspergillosis (IA)?
|
voriconazole
|
|
|
alternative tx for IA
|
A randomized controlled trial comparing two dosages of liposomal Amphotericin B (L-AMB)
3mg/kg/d vs 10mg/kg/d Showed similar efficacy in both arms for primary therapy of IA (Cornelly et al 2007) This suggests that L- AMB could be considered alternative primary treatment in some patients (contraindicated to receive voriconazole) |
|
|
COMBO therapy for primary IA therapy?
|
In vitro, in vivo, and observational clinical studies demonstrate a potential benefit of an
anti- aspergillus antifungal triazole + an echinocandin However in the absence of a RCT routine initial administration of combination therapy is not recommended. Salvage therapy? |
|
|
salvage therapy IA
|
Assessment of patients with refractory aspergillosis may be difficult
The diagnosis of invasive aspergillosis should definitely be established Dosage of primary agent should be considered Lipid formulations of Amphotericin B Posaconazole Itraconazole Caspofungin Micafungin Combination therapy |
|
|
prevention of IA
|
Posaconazole 200mg tid recommended in
hematopoetic stem cell transplant (HSCT) with graft vs host disease (GVHD) at high risk for IA (Ullmann et al. 2007) Neutropenic patients with AML or Myelodysplastic Syndrome (MDS) who are at a high risk for IA (Cornelly et al. 2007) |
|
|
prophylaxis of IA
|
Secondary Prophylaxis
Voriconazole during ongoing immunosuppression following a documented episode of aspergillosis may prevent recurrence |
|
|
adjunctive therapy in IA:
surgury |
Surgery
Certain conditions of IA warrant surgical resection of infected focus Pulmonary lesions contiguous with the heart or great vessels Invasion of chest wall Pericardial infection Endocarditis (rare) |
|
|
adjunctive therapy in IA:
immunomodulators |
Immunomodulation
Restoration of impaired host defenses is critical for improved outcome of IA Recovery from neutropenia in a persistently neutropenic host - filgrastim Reduction of corticosteroids in patients receiving high dose steroids Granulocyte transfusion may be another resource |
|
|
cryptococcus
|
Non-HIV Cryptococcosis
Pulmonary and non-CNS Disease asymptomatic nodular disease - severe acute respiratory distress syndrome (ARDS). Classic symptoms of pneumonitis cough, fever, and sputum production, may be present, or pleural symptoms may predominate. The presence of a positive serum cryptococcal antigen titer implies deep tissue invasion and a high likelihood of disseminated disease. |
|
|
cryptococcus teatment
|
Immunocompetent, asymptomatic with + culture of the lung for Cryptococcus neoformans
observe carefully or treat with fluconazole 400mg daily for 3-6 months Immunocompetent, with mild-moderate symptoms fluconazole 400mg daily for 6 -12 months Immunocompromised, with non-CNS pulmonary and extrapulmonary disease See treatment for CNS disease Objective - The goal of treatment is cure of the infection and prevention of dissemination of disease to the CNS |
|
|
cryptococcus CNS dieease
|
Meningitis and on rare occasions as single or multiple focal mass lesions.
May be associated with concurrent pneumonia or with other evidence of disseminated disease, such as focal skin lesions, but most commonly presents as solitary CNS infection without other manifestations of disease. Objective- The goal of treatment is cure of the infection (CSF sterilization) and prevention of long-term CNS system sequelae, such as cranial nerve palsies, hearing loss, and blindness |
|
|
goal of cryptococcus CNS dx treatment
|
Objective- The goal of treatment is cure of the infection (CSF sterilization) and prevention of long-term CNS system sequelae, such as cranial nerve palsies, hearing loss, and blindness
|
|
|
treatment options cyrptococcus:
immunocompetent pts |
Immunocompetent patients
induction course of IV amphotericin B (0.5-1mg/kg/d) + 5FC (100mg/kg/d) for 2 weeks, followed by consolidation therapy with fluconazole (400mg/d) for an additional 8 -10 weeks. |
|
|
treatment options cyrptococcus:
immunosuppressed pts |
Immunosuppressed patients (solid -organ transplant recipients)
IV amphotericin B ( 0.7-1mg/kg/d) for 2 weeks, followed by 8-10 weeks of fluconazole (400-800 mg/d), is followed with 6-12 months of suppressive therapy with a lower dose of fluconazole (200mg/d). |
|
|
treatment options cyrptococcus:
pts. w/ long term prednisone therapy |
Patients receiving long-term prednisone therapy
reduction of the prednisone dosage to 10mg/d, if possible, may result in improved outcome to antifungal therapy. |
|
|
cryptococcus treatment options:
sig. renal disease |
Immunocompetent and immunocompromised patients with significant renal disease
lipid formulations of amphotericin B may be substituted for amphotericin B during the induction phase. |
|
|
cryptococcus treatment options:
failed antifungal therapy |
Itrathecal or intraventricular amphotericin B may be used in refractory cases where systemic administration of antifungal therapy has failed
|
|
|
cryptococcus treatment options:
high ICP |
Serial spinal taps may be necessary in cases with very high ICP.
|
|
|
therapy for AIDS cryptococal dx:
pulmonary |
Pulmonary
Mild-moderate symptoms or culture-positive specimen from this site Fluconazole, 200-400 mg/d, lifelong Itraconazole, 200-400 mg/d, lifelong Fluconazole, 400 mg/d + 5FC 100-150 mg/kg/d for 10 w |
|
|
therapy for AIDS cryptococal dx:
CNS induction KNOW |
Induction/consolidation
Amphotericin B, 0.7-1 mg/kg/d + 5FC, 100mg/kg/d for 2w, then fluconazole, 400mg/d for minimum of 10 w |
|
|
therapy for AIDS cryptococal dx:
CNS maintenance KNOW |
Maintenance
Fluconazole, 200-400 mg po qd, lifelong |
|
|
who is travelers health for?
|
Includes
business academics Medical tourism Medical volunteerism Missionary work VFRs (Immigrants returning home to visit friends/family) 45% of all travelers |
|
|
general health advice for travel
|
Advice based on not only destination BUT ALSO assessment of risk
|
|
|
3 independent variables for assessing travel risk
|
Assessing risk requires looking at three
independent variables health status “Fitness to Fly” determined by practitioner Resource: Aerospace Medical Association Air Transport Medicine Committee specific itinerary lifestyle during travel |
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|
travel vaccine questions to ask
|
Where exactly are you going?
What exactly will you be doing? Exactly how long will you be staying? What medications are you currently taking? |
|
|
counseling points for all travelers:
general |
General
Travelers advised to consult a clinician 4-8 weeks before departure Accessing medical care abroad Traffic-related precautions, available on CDC site Safety, security, and consular issues |
|
|
counseling points for all travelers:
specific non vaccine preventalbe dx |
Specific non-vaccine preventable diseases
Traveler’s diarrhea Malaria, Dengue Fever, Chikungunya, West Nile Various: Cholera, Schistosomiasis, Tick Born, etc STDs (except HBV, HAV, and HPV) |
|
|
counseling points for all travelers:
vaccines |
Vaccinations
Routine, required, recommended |
|
|
lowest risk destinations for travelers illness
|
Resorts in Mexico
Cruises Europe China tours Australia Japan Israel Russia |
|
|
recc. vaccines/meds for travelers is based on?
|
Age
Past vaccination history Allergy status Comorbidities Past disease exposures Disease risk factors |
|
|
preventing vaccine ADRs?
|
Educate
Investigate allergy status Investigate routine vaccination status Investigate past vaccine reactions Educate on medications and those to treat reactions |
|
|
routine infant vaccines
|
DTaP, Hib, hepatitis B, conj pneumococcal, rotavirus, poliovirus, MMR, Varicella, hepatitis A, influenza
boost polio, MMR |
|
|
routine adolescent vaccines
|
Tdap, conj meningococcal, HPV, influenza
boost meningococcal |
|
|
routine adult vaccines
|
pneumococcal, influenza, Tdap or Td, zoster
boost Tdap/Td |
|
|
MMR
|
Live vaccine
Schedule childhood series some adults may need adult booster(born before 1957, 1980) Combination MMR / V Delay MMR for 1 mo: after d/c of steroids if dose is > 2 mg/kg/d of prednisone equivalent for > 14 d Recent immune globulin administration |
|
|
tetanus, diptheria, pertussis
organism/transmission |
BACTERIA
Organisms and Transmission: Clostridium tetani (soil) Corynebacterum diphtheriae (droplet, close physical contact) Bordetella pertussis (airborne discharge) |
|
|
tetanus, diptheria, pertussis vaccine
|
Primary series of three doses
Adolescent booster w/ Tdap Adult Td booster ACIP says q 10 yrs – replace one with Tdap ADRs - mild and local, unless interval between vaccinations is shorter, then more painful Interval between Td and Tdap is not absolute requirement* Elderly age restrictions in the process of being removed* |
|
|
Yellow fever vaccine requirment
|
May be required as a condition of entry or passage through countries of sub-saharan Africa and equatorial South America
Given only by state-authorized yellow fever centers and documented on official international Certificate of Vaccination. www.cdc.gov/travel/yellow fever |
|
|
yellow fever organism/transmission
|
Organism
Flavivirus (hemorrhagic) Transmission Mosquito (Aedes or Haemagogus) borne disease South America and sub-sahara Africa |
|
|
yellow fever clinical aspects
|
Clinical
Three possible transmission cycles: 2 rural, 1 urban Incubation 3-6 days, improvement within 3-4 days Symptoms not always present Severe: Multiorgan failure, hemorrhage10-14 days after presenting symptoms Morbidity/Mortality 200k cases globally annually Estimated 30,000 deaths annually, with half of the deaths occurring in children under 5 years of age. |
|
|
yellow fever vaccine certificates
|
Although a travel destination may not be endemic for Yellow Fever infection, several countries require a certificate of vaccination for entry. Advise travelers to visit their healthcare provider 4-6 weeks before departure, to ensure adequate time to immunity and avoidance of rejected admission to destination.
Certification is valid 10-days after vaccine administration. Lasts for 10 years. |
|
|
yellow fever vacine products/admin
|
Product/composition/route
YF-Vax (live attenuated) Obtained from Aventis after state health department approves Live vaccine - >90% effective Administration and Schedule 1 dose 10 year duration 0.5 ml, subQ Administer within 1-hr of reconstitution |
|
|
yellow fever vaccine CIs
|
< 6 month old
Immunocompromised (including radiation) Thymus disease Egg or chicken protein hypersensitivity |
|
|
yellow fever vaccine warnings
|
Age > 60
anaphylaxis to eggs |
|
|
yellow fever vaccine reactions
|
Serious: Reports of neurotropic or viserotropic syndrome.
Rates of 1 per 150,000-300,000 in 1st time vaccinees. Mild: local “bee sting” |
|
|
meningococcal vaccine requirement
|
Proof of protection against meningitis is required for entry into Saudi Arabia during the Hajj is required.
|
|
|
meningococcal organism/transmission
|
Organism
Neisseria meningitidis - many serogroups Serogroup B - 20% of cases in USA, not vaccine preventable Other serogroups prevalent in different parts of world Transmission Oral/Nasal secretions (coughing, kissing, fomites) Seasonal and endemic zone (Dec – June) Epidemic possible (dorms, hostels |
|
|
meningococcal clinical aspects
|
Clinical
Incubation is hours to days Purpuric lesions, headache, stiff neck, high fever, N/V, photophobia |
|
|
meningococcal vaccine serogroups/population
|
Vaccination (tetravalent in U.S.)
Serogroups A, C, Y, W-135 Boosters recommended q 5 years Targeted populations: adolescents 11-18 years old Asplenia, complement deficiency travelers to “meningitis belt” of Africa Required for Hajj pilgrimage (or Umrah) to Mecca |
|
|
meningococcal vaccine formulations
|
Menactra and Menveo (conjugate) given IM
FDA indication 2-55 years of age Conjugate duration ~ 5 years Menomune (polysaccharide) given subQ FDA indication > 2 years of age Revaccinate every 3-5 years depending on age Both 0.5 mL dose ADRs - mild local reactions |
|
|
commonly used travel vaccines
|
Travel vaccines (commonly used)
hepatitis A, hepatitis B, typhoid fever, polio, meningococcal, influenza |
|
|
rarely used travel vaccines
|
Travel vaccines (rarely used)
Japanese encephalitis, rabies |
|
|
seasonal influenze vaccine
|
Possibly the most common vaccine-preventable infection in travelers.
Occurs year-round in tropics Patterns are opposite in the southern and northern hemispheres. Travelers to Southeast Asia, Alaska, NW Canada, cruise-ship should be vaccinated regardless of the time of year. If the flu vaccine is not available at the time of departure, contact a travel health clinic regarding influenza anti-viral protection. |
|
|
where does flu occur year round?
|
tropics
|
|
|
hep. A disease
|
Organism is a picornavirus (RNA)
Clinical S/Sx = nausea, jaundice, fever, malaise, anorexia; children – asx, but adults – sx; no chronic state, rarely fulminant Transmission is fecal/Oral through contaminated food and water Incubation 14-50 days, or on average 1 month Past HAV infection = lifelong immunity |
|
|
hep A. vaccine recommendations
|
Childhood series (routine)
MSM (recommended) Areas where risk is moderate to high are particularly important travelers to vaccinate. Screen for immunity by age, birthplace |
|
|
hep A vaccine
|
Dose
children - 0.5 ml IM; adults – 1 ml IM ADRs mild local reactions common Contraindications hypersensitivity to Al, AlOH Immune globulin (0.02 mL/kg) for: Post exposure prophylaxis (if within 2 weeks of exposure) Vaccine-allergic patients Persons > 40 or immunocompromised, chronic liver dx, other comorbidity and < 2 weeks before departure (simultaneously give vaccine also at separate anatomical site.) |
|
|
hep B. disease
|
Organism
DNA virus Transmission Blood or OPIM Lack of screened blood for emergency transfusion Clinical Incubation 6 weeks – 6 months Fever, malaise, headache, myalgia |
|
|
hep B. vaccine product/admin
|
Product/composition/route
Recombivax HB – recombinant - IM Engerix B – recombinant – IM Administration and schedule Both: 0, 6 months or 0, 1, 4 months* Engerix-B: 0, 1, 2, 12 months (FDA approved) Accelerated: 0, 1, 3 weeks + 12 months |
|
|
hep B vaccine ADRs
|
mild local reactions common
small possibility of myalgias, low grade fever |
|
|
hep B vaccine CIs
|
anaphylactic history to yeast
|
|
|
combo hep A/B vaccine
|
Adult approved only, mainly for high risk travelers
Combo (Havrix and Engerix-B) Only 720 IU of hepatitis A vaccine vs 1414 adult formulation Regular Adult strength Hep B Vaccine 0, 1, 6-12 month schedule FDA-approved accelerated schedule in 2007 (0, 1, 3 weeks + 12 months) |
|
|
polio disease
|
Organism
Virus Transmission Fecal-oral, but today it is primary transmitted person-to-person in developing nations Year-round in the tropics Clinical Incubation period is within 1 month Less than 0.5% have severe disease sequelae Paralysis and death may occur |
|
|
polio endemic countries
|
Afghanistan
India Nigeria Pakistan |
|
|
polio countries w/ virus transmission >12 mos
|
Countries with poliovirus transmission of > 12 months:
Angolia Chad Democratic Rep of the Congo Sudan |
|
|
polio vaccine: live vs. inactivated
|
Live oral polio vaccine (OPV):
VAPP no longer used in USA Inactivated polio vaccine (IPOL): 0.5 ml SQ no risk of VAPP CI: anaphylaxis to neomycin, streptomycin |
|
|
polio target population
|
Targeted population
Routine childhood series - 3 doses + 1 booster Recommended for international travelers to Africa, India, mid-East |
|
|
polio vaccine schedule
|
Schedule
Unvaccinated adults (0, 1, 2 months) Adults (no domestic indication) Vaccinated Travelers to above (one lifetime booster |
|
|
typohoid fever disease
|
Organism
Salmonella typhi Susceptible to antibiotics, but resistance to FLQ is growing Transmission Fecal-oral Contaminated food (food handlers) Risk based (rural, adventurous eater, etc.) Clinical Incubation 1 -3 weeks Fever, fatigue, headache, myalgia, constipation, coma, death 80% of U.S. cases report international travel and no vaccination! |
|
|
areas of typhoid fever
|
Central America
Costa Rica Nicaragua South America Brazil Argentina Venezuela Peru India Africa Kenya Tanzania Mali Southeast Asia Malaysia Burma Thailand Indonesia |
|
|
typhoid fever vaccine: oral
|
Vivotif ®
Oral, live vaccine with ~ 70% effective 4 doses - 1 cap qod, 1 h before meals, w/ cool water. Requires refrigeration Drug Interactions: ANTIBIOTICS (see below) Boost every 5 years, 10 days prior to exposure ADRs – GI!! CDC, WHO, and PI have diff info regarding abx Chloroquine does not interact Mefloquine inhibits in vitro growth of S. typhi, separate by 24 hr do not give to immunocompromised or <6 yo |
|
|
typhoid fever vaccine: injectable
|
Injectable vaccine (Typhim Vi® – Sanofi)
inactivated vaccine ~ 70% effective 0.5 ml IM, 1 dose dose should be given 2 weeks prior to trip 2 year duration; booster needed ADRs - mild local sx common, possible flu-like s/s only for use in pts >2 yo |
|
|
typhoid fever vaccine: oral contraindications
|
dailiy antibiotics (weekly sep., by 24 hrs), immunocompromised, < 6 yo
|
|
|
typhoid fever vaccine: injectable CIs
|
<2 yo
|
|
|
rabies disease
|
Organism:
Viral (ss RNA Virus, Rhabdoviridae family) Transmission can occur via any animal bite in developing nation Clinical Incubation is 5 days to over 1 year Convulsions, coma, and encephalitis leading to death 100% fatal if not treated |
|
|
rabies highly endemic canine areas
|
Mexico Philippines Sri Lanka India Thailand vietnam
|
|
|
rabies vaccine targeted populations
|
Targeted Populations
Probable animal contact Working with animals, cavers, exposure to bats Prolonged travel to risk areas |
|
|
rabies vaccine products
|
Inactivated, cell-culture vaccines administered IM route
RabAvert®: Novartis –PCEC (purified chick embryo cell): opaque, colorless upon reconstitution Imovax Rabies®: Sanofi Pasteur-HDCV (human diploid cell vaccine): pink/red solution after reconstitution |
|
|
rabies vaccine admin/schedule
|
Administration and schedule
Pre-exposure = 3 doses at 0, 7, 21 or 28 days 2 additional doses required if bitten If bit: Wash, wash, wash; seek medical attention immediately |
|
|
rabies post exposure prophylaxis
|
4 doses of vaccine and immune globulin (used to be 5 doses)
|
|
|
rabies vaccine clinical pearls
|
Boosters and serology testing available, recommended with consultation of specialists, health department
Clinicians with limited experience administering vaccine should consult with state or local Health Department. Both vaccines contain neomycin; egg allergy (Novartis) |
|
|
rabies vaccine ADRs
|
mild local and systemic reactions possible
rare neurologic complications - temporary |
|
|
japanese encephalitis (JE) disease
|
Organism
RNA Flavivirus Leading cause of viral encephalitis in Asia West Nile Virus is an RNA flavivirus that belongs to the JE serocomplex Transmission Culex mosquito rice paddies, marshes, pig farming Clinical Incubation 5-15 days 30-40% die 50% neurologic complications |
|
|
JE target population for vaccine
|
intensive short term exposure(< 1mo)
moderate long term exposure (>1 mo) people traveling to endemic areas w/out specific activity itinerary |
|
|
JE vaccine product
|
Product/composition/route
Ixiaro (inactivated, adsorbed), IM Replacing JE-VAX, which is available in limited supply Series of 2, 28 days apart 0.5 mL IM > 17 y/o |
|
|
JE vaccine CIs
|
Contraindications/Precautions
patients with previous anaphylaxis to JE vaccine |
|
|
JE vaccine ADRs
|
Adverse Reactions (20%)
H/A, myalgias, fever, injection site pain |
|
|
misc vaccines:
anthrax |
Anthrax
military use numerous doses |
|
|
misc. vaccines:
not available in US |
Not available in USA
Cholera Tick Borne Encephalitis (TBE) or meningitis – Europe, Russia, Scandinavia, Greece Arbovirus Vaccine available in U.K. and Canada |
|
|
travelers diarrhea defn:
|
> 3 unformed stools/day
|
|
|
travelers diarrhea pointers:
|
More associated with foods than water
peel it, boil it, cook it or forget it meats are OK if cooked thoroughly breads are OK if baked thoroughly |
|
|
travelers diarrhea causative organisms
|
E. coli, Campylobacter, salmonella, Shigella, rotavirus, norovirus
|
|
|
travelers diarrrhea treatment
|
Bismuth subsalicylate only ~ 60% effective
Antibiotics for treatment NOT prophylaxis Three day treatment regimen Fluoroquinolones (Cholera, E. coli, some Campylobacter) Azithromycin (resistant Campylobacter) Rifaximin (E.coli) Nitazoxanide Metronidazole SMX/TMP no longer Loperamide (as long as no blood in stools or fever) as adjunctive therapy |
|
|
malaria causative organism
|
mosquito borne, but caused by PARASITE transmission
|
|
|
malaria disease
|
#1 parasitic disease worldwide
Mosquito borne; transmitted by the bite of an infected female Anopheles mosquito Severity of disease depends on species Plasmodium falciparum, P. vivax, P. malariae, P. ovale, P. knowlesi Non-respiratory symptoms mimic Influenza, and also include sweating |
|
|
malaria behavior protection
|
Behavioral
Staying indoors in air conditioning/in tact doors and windows during evening hours Avoiding peak biting times |
|
|
malaria physical/personal protection
|
Physical /Personal
DEET spray as repellant Permethrin 0.5% on clothes, nets, walls as insecticide Chemoprophylaxis Follow CDC recommendations Does not replace repellants Controversy rising secondary to increased resistance. |
|
|
areas where malaria prevalent
|
Central America
Nicaragua Honduras South America Brazil Venezuela Peru India Africa Kenya Tanzania Mali Southeast Asia Malaysia Burma Thailand |
|
|
malaria prophulaxis:
primaquine |
Primaquine
For “vivax-species” Malaria Not for G6PD deficient, must be tested before taking 2 tabs once daily 1-2 days before leaving and through 7-days after leaving risk area. Drug interactions: 3A4 substrate; 1A2 strong inhibitor May be used for children Do not use in pregnancy |
|
|
what test must be done for primaquine to be used?
|
G6PD deficiency test
|
|
|
malaria prophylaxis:
chloroquine |
Chloroquine
used only in Central America, Argentina due to resistance 500 mg po qweek starting 1 week before trip stop 4 weeks after leaving area GI ADRs possible, CNS, cardiac unlikely Substrate 2D6, 3A4; 2D6 inhibitor |
|
|
malaria prophylaxis:
mefloquine |
Mefloquine:
used in areas of chloroquine resistance, but duel resistance seen in parts of SE Asia 250 mg po qweek starting 1 week before trip through 4 weeks after leaving area Take with food CNS rxns - HA, insomnia, vivid dreams rarely seizures, psychosis possible cardiac effects - cardiac rhythm drugs Drug Interactions: 3A4 substrate; 2D6 and 3A4 weak inhibitor |
|
|
malaria prophylaxis:
doxycycline |
Doxycycline:
For Borders Thailand, Cambodia, Myanmar/ Burma 100 mg po qd starting 1 day before trip stop 4 weeks after leaving area ADRs - vaginal yeast infxns, GI do not use in children < 8 yo, pregnancy Counsel of Photosensitivity |
|
|
malaria prophylaxis:
atovaquone/proguanil |
Atovaquone / Proguanil (Malarone)
active against mefloquine resistance well tolerated more expensive for most trips no more effective than other agents once daily, 1 day prior through 7 days after |
|
|
malaria prevention stats
|
Prevention, prevention, prevention
Statistics 1,528 U.S. cases of imported malaria in 2005 ******68% no chemoprophylaxis (7 died) 32% took chemoprophylaxis 43% reported noncompliance 79% got the wrong drug |
|
|
misc. travel concerns:
schistosomiasis |
Schistosomiasis – worms!
Avoid fresh water bathing, swimming in tropical regions |
|
|
misc. travel concerns:
Dengue fever, chikungunya |
Dengue Fever and Chikungunya (CHIKV)
Aedes mosquitos Dengue fever causes hemorrhagic complications CHIKV infx is rarely fatal, but joint symptoms are severe and often debilitating |
|
|
misc. travel concerns:
STDs |
Sexually Transmitted Diseases
Use condoms, vaccinate against vaccine-preventable STDs |
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misc. travel concerns:
motion sickness |
Motion sickness
dimenhydrinate, meclizine, promethazine Pyridoxine hydrochloride + doxylamine succinate Transderm-Scop patches |
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misc. travel concerns:
altitude sickness |
Altitude sickness
keep hydrated gradual ascent acetazolamide dexamethasone |
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Case1: A 22 year old male is going to Cancun for Spring Break. He takes minocycline for acne. He tells you the only sickness he wants to have to worry about is a hangover
vaccines/meds? non drug recc? |
hep A, hep B, STDs, typhoid
no malaria trav. diarrhea, loperamid, Abx if gets illness condoms, bottled H2O, sunscreen, mosquito repellant |
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54 year old male going to the Holy land for the Hajj. He has CAD but is otherwise healthy.
vaccines/prevention? non pharm? |
meningococcal, flu vaccine, hep A, hep B, typhoid, up to date on routine vaccines, no malaria proph. needed
mosquto repellant, bottled H2O, avoid stray animals, no swimming in fresh water, suncreen, refill CAD meds before leave |
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travelers medical kit general contents
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Scissors, tweezers, bandages
Analgesics Antidiarrheal agent Antibiotic for self-treatment of TD Antihistamines Laxatives Oral rehydration salts Broad spectrum sunscreen DEET-containing repellent Permethrin Antimalarial drug (if necessary) Longer term travelers may need additional broad spectrum ABX, antibacterial eye and skin ointment, antifungal cream. |
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A 45 year old veteran nurse is going to Brazil for a medical mission trip. She will be spending time in rural areas and is leaving in 1 week
vaccines? nonpharm? |
hep A, immune globulin
hep B (she probably already has it), typhoid, yellow fever, malaria prevention(chloroquine) mos. repellent, bottled H2O, same as previous non pharm cases answers |
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A 20 year old female on is considering travel to Cambodia to see Ankor Wat. She has no medical conditions and takes Yaz for contraception
when to consult travel specialist? vaccine? nonpharm? |
consult 6-8 wks
hep A/B, typhoid, JE if rural areas, malaria proph., refill Rx before leave avoid strays, insect repellant, bottled H2O, sunscreen, condoms |
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A 70 years old male is traveling to China in 8 weeks to see the Great Wall. He will be staying in Beijing for 2 weeks before coming back. He got pneumococcal vaccine 6 years ago. He takes methotrexate and Humira for RA, lisinopril for HTN, and albuterol inhaler for asthma (1-2 times weekly
vaccines? nonpharm? |
routine vaccines up to date, Tdap, flu, penumococcal, hep A/immune globulin, hep B, typhoid(inactivated b/c on mtx), no JE, no malaria proph.
avoid strays, bottled H2O, insect repellent |
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Group of friends would like to plan a motorcycle tour of Europe. All are relatively fit men and women in 20’s and 30’s
recommendations? |
tick borne encephalitis, leishmaniasis:
wear long sleeve, bug bed nets, insect repellent, avoid unpasteurized dairy products |
