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Medical Microbiology and Virology > 34 Attacking the enemy: antifungals/ antiparasitic > Flashcards

34 Attacking the enemy: antifungals/ antiparasitic Flashcards

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1
Q

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

A

Clotrimazole
Miconazole
Nystatin
Fluconazole

Oral griseofulvin required for scalp ringworm

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2
Q

What are treatments for these deep mycoses?

Blastomycosis

Histoplasmosis

A

Blastomycosis - liposomal amphotericin B then itraconazole

Histoplasmosis - liposomal amphotericin B then fluconazole

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3
Q

What are treatments for these deep mycoses?

Coccidiomycoses

Paracoccidioidomycosis

A

Coccidiomycoses - fluconazole

Paracoccidioidomycosis - itraconazole

Liposomal amphotericin B if severe in either infection

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4
Q

What are treatments for these deep mycoses?

Cryptococcosis

Mucormycosis

A

Cryptococcosis - liposomal amphotericin B and flucytosine

Mucormycosis - liposomal amphotericin B

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5
Q

Anti-parasitic agents target protozoa and helminths. Given wide variety in parasites, treatments need to be different

Which diseases constitute amoebiasis?

A

Invasive dysentery/ liver abscess
Cryptosporidiosis
Cyclosporiasis
Giardiasis

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6
Q

What are treatments for the following amoebiasis?

Entamoeba histolytica

Cryptosporidiosis

A

Metronidazole 10/7 kill liver abscess
Paromomycin/ diloxanide to remove from bowel

Cryptosporidiosis - nitazoxanide

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7
Q

What are treatments for the following amoebiasis?

Cyclosporiasis

Giardiasis

A

Cyclosporiasis - co-trimoxazole

Giardiasis - metronidzole/ tindazole/ nitazoxanide

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8
Q

What are treatment options for cutaneous leishmaniasis?

A

Depending on infecting species, site, and number of lesions

Local infiltration wit sodium stibogluconate (antimonial)
IV sodium stibogluconate
Miltefosine

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9
Q

What are treatment options for visceral leishmaniasis?

A

Liposomal amphotericin B - first choice
Sodium stibogluconate
miltefosine

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10
Q

What are treatment options for East African Trypanosomiasis?

A

Suramin for haemolymphatic stage

Melarsoprol if CNS involved

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11
Q

What are treatment options for West African Trypanosomiasis?

A

Pentamidine for haemolymphatic stage

Nifurtimox-eflornithine combination if CNS involved

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12
Q

What are treatment options for South American Trypanosomiasis?

A

Benznidazole

Nifurtimox

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13
Q

What is treatment for toxoplasmosis?

A

Pyrimethamine plus sulfadiazine

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14
Q

What is treatment for microsporidiosis?

A

Albendazole

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15
Q

What is treatment for Trichomoniasis?

A

Metronidazole

Tinidazole

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16
Q

What are treatment options for malaria?

What is used in severe malaria?

A 
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

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17
Q

Which drug is used to kill hypnozoites in liver, following treatment with other drugs.

Used for vivax/ ovale only

What are risks of treatment?

A

Primaquine

haemolytic anaemia G6PD-deficiency

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18
Q

What are treatment goals in malaria?

A

Prophylaxis for travellers
Treatment
Radical cure - prevent relapsoe vivax/ ovale
Kill gametocytes - prevents transmission

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19
Q

Cestodes - tapeworms

What is treatment for these diseases?

Adult tapeworm - taenia

A

Niclosamide

Praziquantel

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20
Q

Cestodes - tapeworms

What is treatment for these diseases?

Cerebral cysticercosis - larval taenia solium

Hydatid disease

A

Cerebral cysticercosis - albendazole + praziquantel under steroid cover

Hydatid disease - albendazole

21
Q

Trematodes - flukes

What is treatment for these diseases?

Schistosomiasis

Intestinal flukes

Lung fluke - paragonimus

A

Schistosomiasis - praziquantel

Intestinal flukes- praziquantel

Lung fluke - praziquantel

22
Q

Trematodes - flukes

Liver flukes - clonorchis/ opisthorcis

Liver flukes - Fasciola hepatica

A

clonorchis/ opisthorcis - praziquantel

Fasciola hepatica - triclabendazole

23
Q

Nematodes - roundworms

What is treatment for these diseases?

Ascaris

Hookworm

Trichinosis

Trichuris

A

All treatable with albendazole/ mebendazole

24
Q

Nematodes - roundworms

What is treatment for these diseases?

Strongyloides

A

Ivermectin

Albendazole - less effective

25
Q

Nematodes - roundworms

What is treatment for these diseases?

Cutaneous larva migrans

A

Ivermectin

Albendazole

26
Q

Nematodes - roundworms

What is treatment for these diseases?

Visceral larva migrans - toxocariasis

A

Albendazole

Steroids if ocular involvement

27
Q

Nematodes - roundworms

What is treatment for these diseases?

Lymphatic filariasis

A

Diethylcarbamazine + doxycycline

28
Q

Nematodes - roundworms

What is treatment for these diseases?

Onchocerciasis

A

Doxycycline plus ivermectin

29
Q

What is mechanism of action of these drugs?

Albendazole/ mebendazole

A

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)

30
Q

What is mechanism of action of these drugs?

Praziquantel

A

Unknown

Thought that is changes calcium channel ion permeability in schistosome membrane

31
Q

What is mechanism of action of these drugs?

Niclosamide

A

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.

32
Q

What is mechanism of action of these drugs?

Ivermectin

A

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

33
Q

What are treatment options for invasive candida?

A

Initial IV treatment -
amphotericin B - first line
voriconazole/itraconazole/ fluconazole

Once improved -
oral fluconazole/ itraconazole

34
Q

What is treatment duration of invasive candida?

A 
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

35
Q

What are treatment options for mucocutaneous/ vaginal candidiasis?

A

topical clotrimazole/ nystatin

oral fluconazole

36
Q

What are treatment options for invasive aspergillus?

A

Voriconazole - first line
Amphotericin B

Oral -
voriconazole
posaconzole

Consider lung surgery if source control required

37
Q

What is treatment duration for invasive aspergillus?

A 
Source control -
remove lines
ECHO
Ophthalmology review
repeat blood cultures

Unclear guidelines - treat for 6-12 weeks

38
Q

Suspecting invasive fungal infection in immunocompromised patient.

What are options for empirical anti-fungals?

A

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

39
Q

How to diagnose invasive aspergillus?

A

blood culture

beta-d-glucan/ galactomannan

BAL

CT chest

40
Q

What are possible disease states associated with aspergillus infection?

A

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

41
Q

What is significance of differentiating candida species, e.g Candida glabrata?

A

Certain species such as C glabrata are more resistant to certain anti-fungals e.g azoles

42
Q

What is significance of candida species in urine?

A

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

43
Q

Where are these fungal identifiers found?

Beta-D-Glucan

Galactomannan

A

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

44
Q

How are the following tests useful for diagnosing invasive fungal infection?

Beta-D-Glucan

Galactomannan

A

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

45
Q

Which important fungi do galactomannan/ Beta-d-glucan not help detect?

A

Mucormycosis - cell wall has neither component

Cryptococcus - has capsule that captures beta-d-glucan before it can enter bloodstream. Does not contain galactomannan

46
Q

What is first line treatment for PCP?

Mild PaO2 >9.3kPa on air

A

Co-trimoxazole 90mg/kg TDS

21 days

47
Q

What is first line treatment for PCP?

Severe PaO2 <9.3kPa on air

A

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
48
Q

What are second line treatment options for PCP?

Mild

Severe

A

Mild -
Clindamicin + primaquine
Dapsone and trimethoprim
Atovaquone

Severe -
Clindamicin + primaquine
Pentamidine IV

Check G6PD deficiency if prescribing dapsone/ primaquine, but do not delay treatment

49
Q

Patient with mild PCP, not improving on co-trimoxazole. Switched to atovaquone.

Starts to deteriorate over days

What is an explanation?

A

Atovaquone has poor bioavailability

Taking with food increases this by 3x

Medical Microbiology and Virology (60 decks)

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