34 Attacking the enemy: antifungals/ antiparasitic Flashcards
Antifungals have less selective toxicity than antibiotics, because fungi drug targets are not seen in human tissue
There is limited selection for anti-fungals, and resistance is evolving
What are treatment options for superficial mycoses?
e.g ringworm (dermatophytes), candida
Clotrimazole
Miconazole
Nystatin
Fluconazole
Oral griseofulvin required for scalp ringworm
What are treatments for these deep mycoses?
Blastomycosis
Histoplasmosis
Blastomycosis - liposomal amphotericin B then itraconazole
Histoplasmosis - liposomal amphotericin B then fluconazole
What are treatments for these deep mycoses?
Coccidiomycoses
Paracoccidioidomycosis
Coccidiomycoses - fluconazole
Paracoccidioidomycosis - itraconazole
Liposomal amphotericin B if severe in either infection
What are treatments for these deep mycoses?
Cryptococcosis
Mucormycosis
Cryptococcosis - liposomal amphotericin B and flucytosine
Mucormycosis - liposomal amphotericin B
Anti-parasitic agents target protozoa and helminths. Given wide variety in parasites, treatments need to be different
Which diseases constitute amoebiasis?
Invasive dysentery/ liver abscess
Cryptosporidiosis
Cyclosporiasis
Giardiasis
What are treatments for the following amoebiasis?
Entamoeba histolytica
Cryptosporidiosis
Metronidazole 10/7 kill liver abscess
Paromomycin/ diloxanide to remove from bowel
Cryptosporidiosis - nitazoxanide
What are treatments for the following amoebiasis?
Cyclosporiasis
Giardiasis
Cyclosporiasis - co-trimoxazole
Giardiasis - metronidzole/ tindazole/ nitazoxanide
What are treatment options for cutaneous leishmaniasis?
Depending on infecting species, site, and number of lesions
Local infiltration wit sodium stibogluconate (antimonial)
IV sodium stibogluconate
Miltefosine
What are treatment options for visceral leishmaniasis?
Liposomal amphotericin B - first choice
Sodium stibogluconate
miltefosine
What are treatment options for East African Trypanosomiasis?
Suramin for haemolymphatic stage
Melarsoprol if CNS involved
What are treatment options for West African Trypanosomiasis?
Pentamidine for haemolymphatic stage
Nifurtimox-eflornithine combination if CNS involved
What are treatment options for South American Trypanosomiasis?
Benznidazole
Nifurtimox
What is treatment for toxoplasmosis?
Pyrimethamine plus sulfadiazine
What is treatment for microsporidiosis?
Albendazole
What is treatment for Trichomoniasis?
Metronidazole
Tinidazole
What are treatment options for malaria?
What is used in severe malaria?
Chloroquine (vivax, ovale, malariae only) Quinine Mefloquine Atovaquone/ proguanil Artmether/ lumefantrine combinnation Doxycycline
Artesunate IV for severe malaria
Chloroquine and mefloquine resistance is now quite common
Which drug is used to kill hypnozoites in liver, following treatment with other drugs.
Used for vivax/ ovale only
What are risks of treatment?
Primaquine
haemolytic anaemia G6PD-deficiency
What are treatment goals in malaria?
Prophylaxis for travellers
Treatment
Radical cure - prevent relapsoe vivax/ ovale
Kill gametocytes - prevents transmission
Cestodes - tapeworms
What is treatment for these diseases?
Adult tapeworm - taenia
Niclosamide
Praziquantel
Cestodes - tapeworms
What is treatment for these diseases?
Cerebral cysticercosis - larval taenia solium
Hydatid disease
Cerebral cysticercosis - albendazole + praziquantel under steroid cover
Hydatid disease - albendazole
Trematodes - flukes
What is treatment for these diseases?
Schistosomiasis
Intestinal flukes
Lung fluke - paragonimus
Schistosomiasis - praziquantel
Intestinal flukes- praziquantel
Lung fluke - praziquantel
Trematodes - flukes
Liver flukes - clonorchis/ opisthorcis
Liver flukes - Fasciola hepatica
clonorchis/ opisthorcis - praziquantel
Fasciola hepatica - triclabendazole
Nematodes - roundworms
What is treatment for these diseases?
Ascaris
Hookworm
Trichinosis
Trichuris
All treatable with albendazole/ mebendazole
Nematodes - roundworms
What is treatment for these diseases?
Strongyloides
Ivermectin
Albendazole - less effective
Nematodes - roundworms
What is treatment for these diseases?
Cutaneous larva migrans
Ivermectin
Albendazole
Nematodes - roundworms
What is treatment for these diseases?
Visceral larva migrans - toxocariasis
Albendazole
Steroids if ocular involvement
Nematodes - roundworms
What is treatment for these diseases?
Lymphatic filariasis
Diethylcarbamazine + doxycycline
Nematodes - roundworms
What is treatment for these diseases?
Onchocerciasis
Doxycycline plus ivermectin
What is mechanism of action of these drugs?
Albendazole/ mebendazole
causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals)
What is mechanism of action of these drugs?
Praziquantel
Unknown
Thought that is changes calcium channel ion permeability in schistosome membrane
What is mechanism of action of these drugs?
Niclosamide
Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity.
What is mechanism of action of these drugs?
Ivermectin
Ivermectin causes an influx of Cl- ions through the cell membrane of invertebrates by activation of specific ivermectin-sensitive ion channels. The resultant hyperpolarization leads to muscle paralysis
What are treatment options for invasive candida?
Initial IV treatment -
amphotericin B - first line
voriconazole/itraconazole/ fluconazole
Once improved -
oral fluconazole/ itraconazole
What is treatment duration of invasive candida?
Source control - remove lines ECHO Ophthalmology review repeat blood cultures
Unclear guidelines - treat for 14 days following first negative blood culture.
Approx 7 days should be IV, or until clinically improving, then switch to oral
Prolonged course if chronically immunocompromised, or IE/ meningitis
What are treatment options for mucocutaneous/ vaginal candidiasis?
topical clotrimazole/ nystatin
oral fluconazole
What are treatment options for invasive aspergillus?
Voriconazole - first line
Amphotericin B
Oral -
voriconazole
posaconzole
Consider lung surgery if source control required
What is treatment duration for invasive aspergillus?
Source control - remove lines ECHO Ophthalmology review repeat blood cultures
Unclear guidelines - treat for 6-12 weeks
Suspecting invasive fungal infection in immunocompromised patient.
What are options for empirical anti-fungals?
Needs to cover candida, aspergillus, and ideally cryptococcus and dimorphic fungi
- Amphotericin B - covers almost all fungi, including dimorphic fungi
- Itraconazole/ voriconazole - covers almost all fungi, including dimorphic fungi
anidulafungin - only covers candida/ aspergillus
How to diagnose invasive aspergillus?
blood culture
beta-d-glucan/ galactomannan
BAL
CT chest
What are possible disease states associated with aspergillus infection?
Cavitating lung lesion - aspergilloma
Allergic bronchopulmonary aspergillosis
Chronic pulmonary aspergillosis - slowly destroys lung tissue in those with underlying airway disease e.g COPD/ TB
Invasive pulmonary aspergillosis - usually immunocompromised
What is significance of differentiating candida species, e.g Candida glabrata?
Certain species such as C glabrata are more resistant to certain anti-fungals e.g azoles
What is significance of candida species in urine?
Often seen in hospitalised patients may represent - contamination, colonization, UTI, urological abnormality or even candidemia
Correlate clinically, as most don’t require treatment. However, if untreated, can progress to systemic candida infection
Candida cystitis should be treated with fluconazole, and replacement of any catheter
Where are these fungal identifiers found?
Beta-D-Glucan
Galactomannan
Beta-D-glucan is polysaccharide occurring in cell walls of bacteria/ fungi - including aspergillus, candida, PCP
Galactomannan is component of aspergillus cell wall, released into bloodstream during angioinvasion
Can check these tests in blood or BAL
How are the following tests useful for diagnosing invasive fungal infection?
Beta-D-Glucan
Galactomannan
Beta-D-glucan is polysaccharide occurring in cell walls of bacteria/ fungi - including aspergillus, candida, PCP and can be used to diagnose/ monitor response to treatment for aspergillus/ candida/ PCP
Galactomannan is component of aspergillus cell wall, and can be used to diagnose/ monitor response to treatment for aspergillus only
Which important fungi do galactomannan/ Beta-d-glucan not help detect?
Mucormycosis - cell wall has neither component
Cryptococcus - has capsule that captures beta-d-glucan before it can enter bloodstream. Does not contain galactomannan
What is first line treatment for PCP?
Mild PaO2 >9.3kPa on air
Co-trimoxazole 90mg/kg TDS
21 days
What is first line treatment for PCP?
Severe PaO2 <9.3kPa on air
Co-trimoxazole 120mg/kg TDS IV 3 days
Co-trimoxazole 90mg/kg TDS IV 18 days
Prednisolone
- 40mg bd for 5 days
- 40mg od for 5 days
- 20mg od for 11 days
What are second line treatment options for PCP?
Mild
Severe
Mild -
Clindamicin + primaquine
Dapsone and trimethoprim
Atovaquone
Severe -
Clindamicin + primaquine
Pentamidine IV
Check G6PD deficiency if prescribing dapsone/ primaquine, but do not delay treatment
Patient with mild PCP, not improving on co-trimoxazole. Switched to atovaquone.
Starts to deteriorate over days
What is an explanation?
Atovaquone has poor bioavailability
Taking with food increases this by 3x
