logging in or signing up Mycobacterial and Fungal Infections in Dialysis Pa Marigold Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 949 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: May 07, 2008 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: temefikir (14 month(s) ago) cool if it were free Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Unusual Peritonitis: Diagnosis and Management: Mycobacterial and Fungal : Unusual Peritonitis: Diagnosis and Management: Mycobacterial and Fungal Bill Salzer University of Missouri-Columbia 2/20/07 salzerw@health.missouri.eduMycobacteria: Mycobacteria Tuberculosis Human pathogen- person to person via aerosol 1/3 of the world’s population is infected US- 15,000 cases/year, >50% foreign born Controlled by cell mediated immunity Non-tuberculous mycobacteria Acquired from the environment- water, soil, dust Less virulent than TB Slide7: TB Course N Engl J Med 345:192TB in ESRD: TB in ESRD Most active cases are reactivation disease Risk of reactivation is 5-20 fold higher than non ESRD Anergy- false negative PPD common Risk is dependent on PPD+ rate- geographical Most cases occur in 1st year on dialysis Extra-pulmonary disease in >50% Atypical presentationsTB in ESRD- Clinical Features: TB in ESRD- Clinical Features Atypical presentations common, some asymptomatic Malaise-70%, fever-70%, weight loss 50% Cough and hemoptysis- 22% Abnormal CXR- 50%, atypical patterns Extra-pulmonary- lymph nodes, pleural, miliary Peritonitis- 20%, pain, ascites, hepatomegaly Diagnosis is often delayed TB Peritonitis in PD Patients: TB Peritonitis in PD Patients Reactivation disease, sometimes miliary Presents like bacterial- fever, pain, cloudy fluid Refractory to antibiotics, routine cultures usually – Concomitant bacterial peritonitis in 28% Peritoneal WBCs predominantly PMNs in ¾ Fluid AFB smears + in <20%, cultures only 50% + Delays in diagnosis common- mean 6weeks Delays increase mortality, catheter lossMycobacterial Diagnosis: Mycobacterial Diagnosis Direct smear Auramine, rhodamine- fluorescent, screen specimens Ziehl-Neelsen, Kinyoun- Acid-fast, carbol-fuchsin Cultures BACTEC- quick 1-2 weeks Solid media- Löwenstein-Jensen, Middlebrook - slow TB or not TB that is the? Biochemicals- slow DNA probes, GLC, NAP- quick MTB PCR?- smear +, 95-98% sensitive Drug susceptibility testing- old and newTB Peritonitis in PD- Diagnosis: TB Peritonitis in PD- Diagnosis AFB fluid smears positive in < 20% AFB fluid cultures positive in only 50% PPDs positive in 50%, specificity in endemic areas? Eli-spot test? Quicker and better Promising results with direct PCR of fluid Peritoneal biopsy and cultures- nearly 100% yield Caseating granulomas on biopsy Slide13: Elad, Y. et. al. N Engl J Med 1998;339:1382-1387 Epithelioid Granulomata with Multinucleated Giant Cells against a Background of Necrotic Lymphoid Tissue (Hematoxylin and Eosin, x400)TB Treatment in ESRD: TB Treatment in ESRD At least 3 or 4 drugs initially INH 300mg/d + rifampin 600mg/d + pyrazinamide 25-35mg/kg TIW + quinolone +pyridoxine 100mg/d Quinolone- moxifloxacin 400mg po/d? Modify based on drug susceptibilities ?drug resistant strains Duration 6 months Catheter removal- controversial, not always required Dose modification for ethambutol, streptomycin, quinolones, PZA as abovePrevention of TB in ESRD Patients: Prevention of TB in ESRD Patients Identify and treat latent TB infections PPD skin tests for all with ESRD, early “A decision to test is a decision to treat” Induration 10mm= +, CXR to R/O active pulmonary Preventive therapy for all positives INH 300mg/d + pyridoxine 100mg for 9 months Rifampin 600 mg/d for 4 months Rifampin 300 mg/d + PZA 25-35 mg/kg TIW for 2 months Watch for hepatitis with RF+PZA regimenQuantiferon-TB Gold: Quantiferon-TB Gold Test for latent TB infection Blood test- measures in vitro IFN-gamma production Uses ESAT-6 and CFP-10 as stimulants More specific than PPD (96-98%) in BCG pt ?more sensitive than PPD Problems Cost Availability How sensitive? Nontuberculous Mycobacteria: Nontuberculous Mycobacteria > 100 species, 60 pathogens Runyon classification- colony, growth rate, pigment Now growth rate, molecular Environmental sources No human to human transmission Less virulent than MTB Diseases, host immune status GeographyNTM- Sources: NTM- Sources Water including, tap, nosocomial Soil Animals Aerosolized Ingested Direct inoculation- trauma, surgical MAC everywhere, Malmoense, genavense- Europe M. ulcerans- tropical swamps Non-TB Mycobacterial PD Infections: Non-TB Mycobacterial PD Infections Environmental- soil, water, dust, direct contamination Predominantly rapid growers- M fortuitum, chelonei Contaminated machines, water, outbreaks Peritonitis, exit or tunnel infections, abscess Like bacterial- fever, pain, cloudy fluid Peritoneal WBCs usually predominantly PMNS Gram stain may show gram + rods- diphtheroids Culture negative, refractory to antibiotics NTM- Microbiology: NTM- Microbiology Digestion, decontamination- careful AFB smear- Auramine, Kinyoun Media- Middlebrook, BACTEC, MGIT Rapid < 7d, slow > 10d, medium 7-10 Skin source- incubate at 28-30 C- marinum et al M. genavense, malmoense, ulcerans- 10-12 weeks M. Haemophilum- needs iron, cool and slow Species- HPLC, gene probes, biochemicalsRapid Growing NTMs: Rapid Growing NTMs M. fortuitum, abscessus, chelonei Grow in < 7days Fortuitum and abscessus grow on MacConkey Chelonei like cooler temp Sources- soil, natural and tap water Nosocomial- wounds- sternal, mammoplasty, IM sites Virulence- fortuitum>abscessus>cheloneiNTBM Peritonitis- DX and RX: NTBM Peritonitis- DX and RX Gram stain may show gram + rods, AFB + Routine cultures- 2-10 days “diphtheroids” AFB cultures +- species identification takes time Peritoneal biopsy- non-caseating granulomas, culture Treatment Catheter removal usually necessary Inherently resistant to most TB drugs Clarithromycin, quinolones, doxycycline, sulfa, amikacin, tobramycin, imipenem, cefoxitin 1-2 drugs, 4-24 months durationSlide24: Infectious Disease Clinics of North America 15: number 3 p756, 2001Fungal Peritonitis in PD Patients: Fungal Peritonitis in PD Patients Filamentous fungi (molds) Environmental, catheter contamination, bad dx and rx Candida- yeast Endogenous flora- GI, GU, skin sources, nosocomial Risks Recent antibiotics- 65%, bacterial peritonitis- 48% Emergency PD Recent hospitalization HIV infection- 7 X risk of non-HIV Extra-peritoneal infection, abdominal surgeryCandida Peritonitis in PD: Candida Peritonitis in PD Via catheter, tunnel, or ? Ascending in women Like bacterial- fever, pain, cloudy fluid, > 75% PMNs Refractory to antibiotics Fluid gram stains reveal yeast in 50% Fluid cultures + 99% on routine media Fungal Peritonitis Treatment: Fungal Peritonitis Treatment ISPD Guideline 2005 Remove catheter Fluconazole 200mg/d +Flucytosine 2gm X1d,then 1gm/d Duration 2-4 weeks Check antifungal susceptibilities, species Fluconazole resistant? Oral azoles- itraconazole, voriconazole, posaconazole Amphotericin B Echinocandins- caspofungin, micafungin, anidulofunginAzole Resistance in Candida: Azole Resistance in Candida Fluconazole C albicans is the most susceptible species Tropicalis>parapsilosis>> glabrata, krusei Non-albicans species increasing in nosocomial Fluconazole failure related to species Check species, drug susceptibilities if available Newer azoles are more active on these strainsCandida albicans: Candida albicans http://www.doctorfungus.orgCandidemia- Species UMC : Candidemia- Species UMC 2/02-2/03 3/03-1/04 Totals Species cases % cases% C. Parapsilosis 7 33% 1 11 21% C. Albicans 5 24% 6 32 28% C. Tropicalis 4 19% 4 21 21% C. Glabrata 4 19% 7 37 28% C. Famata 1 5% 0 2%Slide31: Candida in vitro azoles CID 36:Fluconazole (“Diflucan”): Fluconazole (“Diflucan”) Generic- cheap now Well absorbed po, hydrophilic (CSF, urine,perotoneum) Renal excreted- dose adjustment for renal function Active candida (?glabrata,krusei) crypto, cocci Side effects GI, headache, rash, alopecia, hepatitis Drug interactions Inhibits CYP 3A4, 2C19Flucytosine: Flucytosine 5-fluorocytosine- fluorinated pyrimidine (1972) Fungal cytosine permease, cytosine deaminase- 5-FU Inhibits RNA synthesis, thymidylate synthetase PO 25-37.5 mg/kg q6h; renal excretion Monitor serum levels- 30-60 min post dose- 50-100ug/ml Renal insufficiency- 2grams day 1, then 1 gram/day CSF levels 74% of serum- hydrophilic Toxicity- hematological, GI- with high levelsItraconazole (“Sporanox”): Itraconazole (“Sporanox”) PO caps, liquid (cyclodextrin); IV Absorption capsules pH dependent, liquid not Lipophilic, hepatic metabolism Activity-candida, aspergillus, histo, blasto, sporo, cocci, dermatophytes Side effects GI, liver, rash, hypokalemia, edema, BP Drug interactions Inhibits CYP3A4 Voriconazole (“Vfend”): Voriconazole (“Vfend”) Triazole antifungal, IV and PO forms Antifungal activity like itra- candida, crypto, histo, blasto, aspergillus, other filamentous Well absorbed orally, food decreases Liver metabolism- CYP- 2C19, 2C9, 3A4 Not much in urine or CSF (like itra) IV- cyclodextrin vehicle, don’t use if GFR<50 Side effects- Visual in 30% Drug interactions- sirolimus, rifamycins, statins etcVoriconazole for Candida Peritonitis: Voriconazole for Candida Peritonitis Kleinpeter MA.AdvPeritDial 2004;20:58-61 Report of 2 cases Case 1- Exit site infection Candida species resistant to fluconazole Voriconazole po for 28 days- Success, retained cath Case 2 peritonitis Candida parapsilosis Success with cath in placePosaconazole- “Noxafil”: Posaconazole- “Noxafil” Approved in 2006 PO, liquid suspension, take with food Activity- like voriconazole + some Zygomycetes Good activity on fluconazole resistant candida Metabolized by UDP glucuronidation Inhibits CYP-3A4 No dose adjustment for renalEchinocandins: Echinocandins Inhibit Beta 1,5-D glucan synthase IV only Activity- candida species, aspergillus species No activity on other yeasts, ? Molds Class side effects Histamine reaction, flushing, prurutis, low BP Phlebitis Fever Mild LFT elevationEchinocandins- Pharmacology: Echinocandins- Pharmacology Caspofungin- “Cancidas” IV 70mg day 1, subsequently 50 mg/day Hepatic metabolism, not CYP, reduce with ESLD Drug interactions- cyclosporine, tacrolimus, rifampin Micafungin- “Mycamine” IV 50-150mg/day, probably 100 Hepatic metabolism, non CYP, Anidulofungin- “Eraxis” IV day 1 200mg, subsequently 100mg/d, < 1.1mg/min Metabolized in serum- no dose adjustmentAntifungals for PD peritonitis: Antifungals for PD peritonitis Remove catheter Fluconazole empirically, ? + flucytosine Fluconazole resistant C. glabrata, krusei- assume resistan Drug susceptibility testing Itra-, vori- or posaconazole PO Amphotericin B or echinocandin IV Filamentous fungus Remove catheter Voriconazole, posaconazole, ampho B You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Mycobacterial and Fungal Infections in Dialysis Pa Marigold Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 949 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: May 07, 2008 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: temefikir (14 month(s) ago) cool if it were free Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Unusual Peritonitis: Diagnosis and Management: Mycobacterial and Fungal : Unusual Peritonitis: Diagnosis and Management: Mycobacterial and Fungal Bill Salzer University of Missouri-Columbia 2/20/07 salzerw@health.missouri.eduMycobacteria: Mycobacteria Tuberculosis Human pathogen- person to person via aerosol 1/3 of the world’s population is infected US- 15,000 cases/year, >50% foreign born Controlled by cell mediated immunity Non-tuberculous mycobacteria Acquired from the environment- water, soil, dust Less virulent than TB Slide7: TB Course N Engl J Med 345:192TB in ESRD: TB in ESRD Most active cases are reactivation disease Risk of reactivation is 5-20 fold higher than non ESRD Anergy- false negative PPD common Risk is dependent on PPD+ rate- geographical Most cases occur in 1st year on dialysis Extra-pulmonary disease in >50% Atypical presentationsTB in ESRD- Clinical Features: TB in ESRD- Clinical Features Atypical presentations common, some asymptomatic Malaise-70%, fever-70%, weight loss 50% Cough and hemoptysis- 22% Abnormal CXR- 50%, atypical patterns Extra-pulmonary- lymph nodes, pleural, miliary Peritonitis- 20%, pain, ascites, hepatomegaly Diagnosis is often delayed TB Peritonitis in PD Patients: TB Peritonitis in PD Patients Reactivation disease, sometimes miliary Presents like bacterial- fever, pain, cloudy fluid Refractory to antibiotics, routine cultures usually – Concomitant bacterial peritonitis in 28% Peritoneal WBCs predominantly PMNs in ¾ Fluid AFB smears + in <20%, cultures only 50% + Delays in diagnosis common- mean 6weeks Delays increase mortality, catheter lossMycobacterial Diagnosis: Mycobacterial Diagnosis Direct smear Auramine, rhodamine- fluorescent, screen specimens Ziehl-Neelsen, Kinyoun- Acid-fast, carbol-fuchsin Cultures BACTEC- quick 1-2 weeks Solid media- Löwenstein-Jensen, Middlebrook - slow TB or not TB that is the? Biochemicals- slow DNA probes, GLC, NAP- quick MTB PCR?- smear +, 95-98% sensitive Drug susceptibility testing- old and newTB Peritonitis in PD- Diagnosis: TB Peritonitis in PD- Diagnosis AFB fluid smears positive in < 20% AFB fluid cultures positive in only 50% PPDs positive in 50%, specificity in endemic areas? Eli-spot test? Quicker and better Promising results with direct PCR of fluid Peritoneal biopsy and cultures- nearly 100% yield Caseating granulomas on biopsy Slide13: Elad, Y. et. al. N Engl J Med 1998;339:1382-1387 Epithelioid Granulomata with Multinucleated Giant Cells against a Background of Necrotic Lymphoid Tissue (Hematoxylin and Eosin, x400)TB Treatment in ESRD: TB Treatment in ESRD At least 3 or 4 drugs initially INH 300mg/d + rifampin 600mg/d + pyrazinamide 25-35mg/kg TIW + quinolone +pyridoxine 100mg/d Quinolone- moxifloxacin 400mg po/d? Modify based on drug susceptibilities ?drug resistant strains Duration 6 months Catheter removal- controversial, not always required Dose modification for ethambutol, streptomycin, quinolones, PZA as abovePrevention of TB in ESRD Patients: Prevention of TB in ESRD Patients Identify and treat latent TB infections PPD skin tests for all with ESRD, early “A decision to test is a decision to treat” Induration 10mm= +, CXR to R/O active pulmonary Preventive therapy for all positives INH 300mg/d + pyridoxine 100mg for 9 months Rifampin 600 mg/d for 4 months Rifampin 300 mg/d + PZA 25-35 mg/kg TIW for 2 months Watch for hepatitis with RF+PZA regimenQuantiferon-TB Gold: Quantiferon-TB Gold Test for latent TB infection Blood test- measures in vitro IFN-gamma production Uses ESAT-6 and CFP-10 as stimulants More specific than PPD (96-98%) in BCG pt ?more sensitive than PPD Problems Cost Availability How sensitive? Nontuberculous Mycobacteria: Nontuberculous Mycobacteria > 100 species, 60 pathogens Runyon classification- colony, growth rate, pigment Now growth rate, molecular Environmental sources No human to human transmission Less virulent than MTB Diseases, host immune status GeographyNTM- Sources: NTM- Sources Water including, tap, nosocomial Soil Animals Aerosolized Ingested Direct inoculation- trauma, surgical MAC everywhere, Malmoense, genavense- Europe M. ulcerans- tropical swamps Non-TB Mycobacterial PD Infections: Non-TB Mycobacterial PD Infections Environmental- soil, water, dust, direct contamination Predominantly rapid growers- M fortuitum, chelonei Contaminated machines, water, outbreaks Peritonitis, exit or tunnel infections, abscess Like bacterial- fever, pain, cloudy fluid Peritoneal WBCs usually predominantly PMNS Gram stain may show gram + rods- diphtheroids Culture negative, refractory to antibiotics NTM- Microbiology: NTM- Microbiology Digestion, decontamination- careful AFB smear- Auramine, Kinyoun Media- Middlebrook, BACTEC, MGIT Rapid < 7d, slow > 10d, medium 7-10 Skin source- incubate at 28-30 C- marinum et al M. genavense, malmoense, ulcerans- 10-12 weeks M. Haemophilum- needs iron, cool and slow Species- HPLC, gene probes, biochemicalsRapid Growing NTMs: Rapid Growing NTMs M. fortuitum, abscessus, chelonei Grow in < 7days Fortuitum and abscessus grow on MacConkey Chelonei like cooler temp Sources- soil, natural and tap water Nosocomial- wounds- sternal, mammoplasty, IM sites Virulence- fortuitum>abscessus>cheloneiNTBM Peritonitis- DX and RX: NTBM Peritonitis- DX and RX Gram stain may show gram + rods, AFB + Routine cultures- 2-10 days “diphtheroids” AFB cultures +- species identification takes time Peritoneal biopsy- non-caseating granulomas, culture Treatment Catheter removal usually necessary Inherently resistant to most TB drugs Clarithromycin, quinolones, doxycycline, sulfa, amikacin, tobramycin, imipenem, cefoxitin 1-2 drugs, 4-24 months durationSlide24: Infectious Disease Clinics of North America 15: number 3 p756, 2001Fungal Peritonitis in PD Patients: Fungal Peritonitis in PD Patients Filamentous fungi (molds) Environmental, catheter contamination, bad dx and rx Candida- yeast Endogenous flora- GI, GU, skin sources, nosocomial Risks Recent antibiotics- 65%, bacterial peritonitis- 48% Emergency PD Recent hospitalization HIV infection- 7 X risk of non-HIV Extra-peritoneal infection, abdominal surgeryCandida Peritonitis in PD: Candida Peritonitis in PD Via catheter, tunnel, or ? Ascending in women Like bacterial- fever, pain, cloudy fluid, > 75% PMNs Refractory to antibiotics Fluid gram stains reveal yeast in 50% Fluid cultures + 99% on routine media Fungal Peritonitis Treatment: Fungal Peritonitis Treatment ISPD Guideline 2005 Remove catheter Fluconazole 200mg/d +Flucytosine 2gm X1d,then 1gm/d Duration 2-4 weeks Check antifungal susceptibilities, species Fluconazole resistant? Oral azoles- itraconazole, voriconazole, posaconazole Amphotericin B Echinocandins- caspofungin, micafungin, anidulofunginAzole Resistance in Candida: Azole Resistance in Candida Fluconazole C albicans is the most susceptible species Tropicalis>parapsilosis>> glabrata, krusei Non-albicans species increasing in nosocomial Fluconazole failure related to species Check species, drug susceptibilities if available Newer azoles are more active on these strainsCandida albicans: Candida albicans http://www.doctorfungus.orgCandidemia- Species UMC : Candidemia- Species UMC 2/02-2/03 3/03-1/04 Totals Species cases % cases% C. Parapsilosis 7 33% 1 11 21% C. Albicans 5 24% 6 32 28% C. Tropicalis 4 19% 4 21 21% C. Glabrata 4 19% 7 37 28% C. Famata 1 5% 0 2%Slide31: Candida in vitro azoles CID 36:Fluconazole (“Diflucan”): Fluconazole (“Diflucan”) Generic- cheap now Well absorbed po, hydrophilic (CSF, urine,perotoneum) Renal excreted- dose adjustment for renal function Active candida (?glabrata,krusei) crypto, cocci Side effects GI, headache, rash, alopecia, hepatitis Drug interactions Inhibits CYP 3A4, 2C19Flucytosine: Flucytosine 5-fluorocytosine- fluorinated pyrimidine (1972) Fungal cytosine permease, cytosine deaminase- 5-FU Inhibits RNA synthesis, thymidylate synthetase PO 25-37.5 mg/kg q6h; renal excretion Monitor serum levels- 30-60 min post dose- 50-100ug/ml Renal insufficiency- 2grams day 1, then 1 gram/day CSF levels 74% of serum- hydrophilic Toxicity- hematological, GI- with high levelsItraconazole (“Sporanox”): Itraconazole (“Sporanox”) PO caps, liquid (cyclodextrin); IV Absorption capsules pH dependent, liquid not Lipophilic, hepatic metabolism Activity-candida, aspergillus, histo, blasto, sporo, cocci, dermatophytes Side effects GI, liver, rash, hypokalemia, edema, BP Drug interactions Inhibits CYP3A4 Voriconazole (“Vfend”): Voriconazole (“Vfend”) Triazole antifungal, IV and PO forms Antifungal activity like itra- candida, crypto, histo, blasto, aspergillus, other filamentous Well absorbed orally, food decreases Liver metabolism- CYP- 2C19, 2C9, 3A4 Not much in urine or CSF (like itra) IV- cyclodextrin vehicle, don’t use if GFR<50 Side effects- Visual in 30% Drug interactions- sirolimus, rifamycins, statins etcVoriconazole for Candida Peritonitis: Voriconazole for Candida Peritonitis Kleinpeter MA.AdvPeritDial 2004;20:58-61 Report of 2 cases Case 1- Exit site infection Candida species resistant to fluconazole Voriconazole po for 28 days- Success, retained cath Case 2 peritonitis Candida parapsilosis Success with cath in placePosaconazole- “Noxafil”: Posaconazole- “Noxafil” Approved in 2006 PO, liquid suspension, take with food Activity- like voriconazole + some Zygomycetes Good activity on fluconazole resistant candida Metabolized by UDP glucuronidation Inhibits CYP-3A4 No dose adjustment for renalEchinocandins: Echinocandins Inhibit Beta 1,5-D glucan synthase IV only Activity- candida species, aspergillus species No activity on other yeasts, ? Molds Class side effects Histamine reaction, flushing, prurutis, low BP Phlebitis Fever Mild LFT elevationEchinocandins- Pharmacology: Echinocandins- Pharmacology Caspofungin- “Cancidas” IV 70mg day 1, subsequently 50 mg/day Hepatic metabolism, not CYP, reduce with ESLD Drug interactions- cyclosporine, tacrolimus, rifampin Micafungin- “Mycamine” IV 50-150mg/day, probably 100 Hepatic metabolism, non CYP, Anidulofungin- “Eraxis” IV day 1 200mg, subsequently 100mg/d, < 1.1mg/min Metabolized in serum- no dose adjustmentAntifungals for PD peritonitis: Antifungals for PD peritonitis Remove catheter Fluconazole empirically, ? + flucytosine Fluconazole resistant C. glabrata, krusei- assume resistan Drug susceptibility testing Itra-, vori- or posaconazole PO Amphotericin B or echinocandin IV Filamentous fungus Remove catheter Voriconazole, posaconazole, ampho B