34 Attacking the enemy: antifungals/ antiparasitic

Question 1

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

Answer 1

Clotrimazole
Miconazole
Nystatin
Fluconazole

Oral griseofulvin required for scalp ringworm

Question 2

What are treatments for these deep mycoses?

Blastomycosis

Histoplasmosis

Answer 2

Blastomycosis - liposomal amphotericin B then itraconazole

Histoplasmosis - liposomal amphotericin B then fluconazole

Question 3

What are treatments for these deep mycoses?

Coccidiomycoses

Paracoccidioidomycosis

Answer 3

Coccidiomycoses - fluconazole

Paracoccidioidomycosis - itraconazole

Liposomal amphotericin B if severe in either infection

Question 4

What are treatments for these deep mycoses?

Cryptococcosis

Mucormycosis

Answer 4

Cryptococcosis - liposomal amphotericin B and flucytosine

Mucormycosis - liposomal amphotericin B

Question 5

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

Which diseases constitute amoebiasis?

Answer 5

Invasive dysentery/ liver abscess
Cryptosporidiosis
Cyclosporiasis
Giardiasis

Question 6

What are treatments for the following amoebiasis?

Entamoeba histolytica

Cryptosporidiosis

Answer 6

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

Cryptosporidiosis - nitazoxanide

Question 7

What are treatments for the following amoebiasis?

Cyclosporiasis

Giardiasis

Answer 7

Cyclosporiasis - co-trimoxazole

Giardiasis - metronidzole/ tindazole/ nitazoxanide

Question 8

What are treatment options for cutaneous leishmaniasis?

Answer 8

Depending on infecting species, site, and number of lesions

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

Question 9

What are treatment options for visceral leishmaniasis?

Answer 9

Liposomal amphotericin B - first choice
Sodium stibogluconate
miltefosine

Question 10

What are treatment options for East African Trypanosomiasis?

Answer 10

Suramin for haemolymphatic stage

Melarsoprol if CNS involved

Question 11

What are treatment options for West African Trypanosomiasis?

Answer 11

Pentamidine for haemolymphatic stage

Nifurtimox-eflornithine combination if CNS involved

Question 12

What are treatment options for South American Trypanosomiasis?

Answer 12

Benznidazole

Nifurtimox

Question 13

What is treatment for toxoplasmosis?

Answer 13

Pyrimethamine plus sulfadiazine

Question 14

What is treatment for microsporidiosis?

Answer 14

Albendazole

Question 15

What is treatment for Trichomoniasis?

Answer 15

Metronidazole

Tinidazole

Question 16

What are treatment options for malaria?

What is used in severe malaria?

Answer 16

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

Question 17

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

Used for vivax/ ovale only

What are risks of treatment?

Answer 17

Primaquine

haemolytic anaemia G6PD-deficiency

Question 18

What are treatment goals in malaria?

Answer 18

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

Question 19

Cestodes - tapeworms

What is treatment for these diseases?

Adult tapeworm - taenia

Answer 19

Niclosamide

Praziquantel

Question 20

Cestodes - tapeworms

What is treatment for these diseases?

Cerebral cysticercosis - larval taenia solium

Hydatid disease

Answer 20

Cerebral cysticercosis - albendazole + praziquantel under steroid cover

Hydatid disease - albendazole

Question 21

Trematodes - flukes

What is treatment for these diseases?

Schistosomiasis

Intestinal flukes

Lung fluke - paragonimus

Answer 21

Schistosomiasis - praziquantel

Intestinal flukes- praziquantel

Lung fluke - praziquantel

Question 22

Trematodes - flukes

Liver flukes - clonorchis/ opisthorcis

Liver flukes - Fasciola hepatica

Answer 22

clonorchis/ opisthorcis - praziquantel

Fasciola hepatica - triclabendazole

Question 23

Nematodes - roundworms

What is treatment for these diseases?

Ascaris

Hookworm

Trichinosis

Trichuris

Answer 23

All treatable with albendazole/ mebendazole

Question 24

Nematodes - roundworms

What is treatment for these diseases?

Strongyloides

Answer 24

Ivermectin

Albendazole - less effective

Question 25

Nematodes - roundworms What is treatment for these diseases? Cutaneous larva migrans

Answer 25

Ivermectin | Albendazole

Question 26

Nematodes - roundworms What is treatment for these diseases? Visceral larva migrans - toxocariasis

Answer 26

Albendazole Steroids if ocular involvement

Question 27

Nematodes - roundworms What is treatment for these diseases? Lymphatic filariasis

Answer 27

Diethylcarbamazine + doxycycline

Question 28

Nematodes - roundworms What is treatment for these diseases? Onchocerciasis

Answer 28

Doxycycline plus ivermectin

Question 29

What is mechanism of action of these drugs? Albendazole/ mebendazole

Answer 29

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)

Question 30

What is mechanism of action of these drugs? Praziquantel

Answer 30

Unknown Thought that is changes calcium channel ion permeability in schistosome membrane

Question 31

What is mechanism of action of these drugs? Niclosamide

Answer 31

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.

Question 32

What is mechanism of action of these drugs? Ivermectin

Answer 32

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

Question 33

What are treatment options for invasive candida?

Answer 33

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

Question 34

What is treatment duration of invasive candida?

Answer 34

``` 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

Question 35

What are treatment options for mucocutaneous/ vaginal candidiasis?

Answer 35

topical clotrimazole/ nystatin oral fluconazole

Question 36

What are treatment options for invasive aspergillus?

Answer 36

Voriconazole - first line Amphotericin B Oral - voriconazole posaconzole Consider lung surgery if source control required

Question 37

What is treatment duration for invasive aspergillus?

Answer 37

``` Source control - remove lines ECHO Ophthalmology review repeat blood cultures ``` Unclear guidelines - treat for 6-12 weeks

Question 38

Suspecting invasive fungal infection in immunocompromised patient. What are options for empirical anti-fungals?

Answer 38

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

Question 39

How to diagnose invasive aspergillus?

Answer 39

blood culture beta-d-glucan/ galactomannan BAL CT chest

Question 40

What are possible disease states associated with aspergillus infection?

Answer 40

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

Question 41

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

Answer 41

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

Question 42

What is significance of candida species in urine?

Answer 42

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

Question 43

Where are these fungal identifiers found? Beta-D-Glucan Galactomannan

Answer 43

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

Question 44

How are the following tests useful for diagnosing invasive fungal infection? Beta-D-Glucan Galactomannan

Answer 44

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

Question 45

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

Answer 45

Mucormycosis - cell wall has neither component Cryptococcus - has capsule that captures beta-d-glucan before it can enter bloodstream. Does not contain galactomannan

Question 46

What is first line treatment for PCP? Mild PaO2 >9.3kPa on air

Answer 46

Co-trimoxazole 90mg/kg TDS | 21 days

Question 47

What is first line treatment for PCP? Severe PaO2 <9.3kPa on air

Answer 47

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

Question 48

What are second line treatment options for PCP? Mild Severe

Answer 48

Mild - Clindamicin + primaquine Dapsone and trimethoprim Atovaquone Severe - Clindamicin + primaquine Pentamidine IV Check G6PD deficiency if prescribing dapsone/ primaquine, but do not delay treatment

Question 49

Patient with mild PCP, not improving on co-trimoxazole. Switched to atovaquone. Starts to deteriorate over days What is an explanation?

Answer 49

Atovaquone has poor bioavailability Taking with food increases this by 3x