Anti-microbial chemotherapy Flashcards
What are the indications for antimicrobials?
- Therapy
□ empiric - without microbiology results
□ directed - based on microbiology results - Prophylaxis
□ Primary
® anti-malarial; immunosuppressed patients
® pre-operative surgical
® post-exposure e.g. HIV, meningitis
□ Secondary
® To prevent a secondary episode e.g. PGP
What should be done to make a clinical diagnosis whne prescribing antimicrobials?
- Diagnosis of infection □ Clinical □ Laboratory □ None (no treatment) - Severity assessment □ Sepsis (qSOFA: syst BP<100, altered mental, RR>22)? □ Septic shock?
What patient charecteristics should be taken into acount when prescribing antimicrobials?
- age
- renal function
- liver function
- immunocompromised
- Pregnancy
- known allergies
What should be considered when selecting an antimicrobial?
- Guideline or “individualised” therapy
- likely organism(s)?
- empirical therapy or result-based therapy
- bactericidal vs. bacteriostatic drug
- Single agent or combination
- Potential adverse events
What is the difference between bacercidal and bacteriostatic antimicrobials?
□ Bactericidal ® e.g.. beta-lactams ® act on cell wall ® kill organisms ® indications include neutropenia, meningitis and endocarditis □ Bacteriostatic ® e.g.. macrolides ® inhibit protein synthesis ® prevent colony growth ® require host immune system to “mop up” residual infection ® useful in toxin-mediated illness
explain single and combination antimicrobial therapies
□ Single ® simpler ® fewer side effects ® fewer drug interactions □ Combination ® HIV and TB therapy ® severe sepsis (febrile neutropenia) ® mixed organisms (faecal peritonitis)
How is the rout of administration decided?
□ Oral bioavailability ® Ratio of drug level when given orally compared with level when given iv ® varies widely ◊ flucloxacillin 50-70% ◊ linezolid 100% □ Oral route if ® Not vomiting ® Normal GI function ® No shock ® No organ dysfunction □ IV route for ® Severe or deep-seated infection ® When oral route is not reliable
What allergic reactions should be thought about when prescribing?
® Immediate reaction ◊ Anaphylactic shock ® Delayed reaction ◊ Rash ◊ Drug fever ◊ Serum sickness ◊ Erythema nodosum ◊ Stevens-Johnson syndrome ® Mostly happens with penicillin and cephalosporins
What GI side effects should be considered when prescribing antimicrobials?
® Nausea, vomiting, diarrhoea
® Clostridium difficile infection
When should candida (thrush) be thought about as a side effect of an antimicrobial?
Broad spectrum penicillin, cephalosporins
When should you worry about side effects to the liver when prescribing antimicrobials?
® All drugs, particularly tetracyclines, TB drugs
® More likely if pre-existing liver disease
When should you worry about side effects to the renal system when prescribing antimicrobials?
® Gentamicin, vancomycin
® More likely if pre-existing renal disease or on nephrotoxic meds
What (and when) should you be worried about with neurological complications?
® Ototoxicity - gentamicin, vancomycin
® Optic neuropathy - ethambutol (TB)
® Convulsions, encephalopathy - penicillin, cephalosporin
® Peripheral neuropathy - isoniazid (TB), metronidazole
What (and when) should you be worried about with Haemotological complications?
® Marrow toxicity
® Megaloblastic anaemia (folate metabolism) - co-trimoxazole
What is the mode of action of penacillins
Inhibition of the cell wall
Give examples of penacillins
® Benzyl Penicillins ® Amoxicillin ® Floxacillin ® Co-amoxiclav ® Piperacillin/ tazobactam
What is the mode of action of cephlasporins?
Inhibition of the cell wall
Give examples of cephlasporins
® Cefradine
® Cefuroxime
® Ceftriaxone/ cefotaxime
® Ceftazidime
What is the mode of action of aminoglycosides?
inhibition of protein synthesis
Give an example of aminoglycosides
Gentamycin
What is the mode of action of macrolides?
Inhibit protein synthesis
When are macrolides used?
Respiratory infections
Give examples of macrolides
□ Clarithromycin
□ Erythromycin
□ Azithromycin
What is the mode of action of quinolones?
Inhibition of nucleic acid synthesis
Give examples of quinolones
□ Ciprofloxacin
□ Levofloxacin/ moxifloxacin
What is the mode of action of glycopeptides?
Inhibtion of the cell wall
When are glycopeptides used?
- MRSA
- Skin and soft tissue if allergic
What is the mode of action of teracyclines?
Inhibtion of protein synthesis
Give an example of a teracycline
Doxycycline
What is the mode of action of Oxazolidinones?
Inhibtion of protein synthesis
give an example of Oxazolidinones
Linezolid
What is the mode of action of Trimethoprim?
Inhibition of nucleic acid synthesis
What is the mode of action of Sulphonamides?
Inhibition of nucleic acid synthesis
Give examples of Azoles and state when they would be used
® fluconazole: Candida, some resistance
® itraconazole: Candida & Aspergillus
® voriconazole: Candida & Aspergillus
Give examples of Polyenes and state when they would be used
® amphotericin: Candida & Aspergillus
® nystatin: Candida
Give examples of Echinocandins and state when they would be used
caspofungin, anidulafungin, micafungin: Candida, Aspergillus
When is Terbinafine used?
tinea, nails
True or false: antivirals are all virucidal?
False: they are all virustatic
What are the stages of a virus life cycle that antivirals target?
- Most target intracellular stages
- Greater effect on viral replication than on the host cell function
What is the mode of action of most antivirals?
Inhibit nucleic acid synthesis
When may antiviral treatment be used?
- Prophylaxis (to prevent infection)
- Pre-emptive therapy (when evidence of infection detected, but before symptoms apparent)
- Overt disease
- Suppressive therapy (to keep viral replication below the rate that causes tissue damage in asymptomatic infected patient)
When would antivirals be prescribed in the case of checkenpox?
- in those at increased risk of complications…
□ neonate
□ immunocompromised
□ pregnant - immunocompetent adult…
□ only if begun within 24 hours of onset of rash
What is the effect of using antivirals in shingles?
Only decreases post-herpetic neuralgia in the immunocompetent host if begun within 72 hours of onset of symptoms
What antivirals are used in HSV and VZV?
○ Acyclovir
○ Valaciclovir
○ Famciclovir
○ Foscarnet
What is the mode of action of acyclovir?
○ Acyclovir is converted by viral thymidine kinase to ACVMP,
○ ACVMP then converted by host cell kinases to ACV-TP
○ ACV-TP, in turn, competitively inhibits and inactivates HSV-specific DNA polymerase
○ preventing further viral DNA synthesis without affecting the normal cellular processes
When are antivirals used in CMV?
○ All available drugs have significant toxicity
○ Only treat life- or sight-threatening CMV infections
-e.g. HIV patients: CMV retinitis, colitis,
- Transplant recipients: pneumonitis
○ May also be used to treat neonates with symptomatic congenital CMV infection
What antivirals are used in the treatment of CMV?
- Ganciclovir
- Valganciclovir
- Cidofovir
- Foscernet
What antivirals are used in the treatment of HIV and what is there effect?
○ Combination anti-retroviral therapy (cART), also called highly active antiretroviral therapy (HAART), uses combinations of antiretrovirals
○ Has transformed HIV care with:
- Restoration of immune function in AIDS
- Decrease in opportunistic infections
What antivirals are used to treat chronic hepatits B?
○ Pegylated interferon alpha (subcut.) ○ Nucleoside/tide analogues - Tenofovir - Adefovir - Entecavir - Lamivudine - Emtricitabine - Telbivudine
What are the antivirals used in chronic herpatis C?
○ Current therapies
- Pegylated interferon alpha (subcut.) & ribavirin (oral)
- As above, PLUS protease inhibitor (telaprevir or boceprevir)
○ New directly-acting antivirals, in combination
- Daclatasvir
- sofosbuvir
- simeprevir
How do you test for resistance to antivirals?
- Phenotypic – can virus grow in presence of compound, e.g. HSV
- Genotypic – Sequence genome and identify resistance-associated mutations, e.g. HIV
What tests are done to test for antibiotic resistancce?
- Disk diffusion method
- Etest
What are the 4 main mechanisms of antibiotic resistance?
- Enzymatic inactivation of the drug
- Modified targets for the drug
- Reduced permeability to the drug
- Efflux of the drug
What are the factors influencing antibiotic resistance?
- Widespread antibiotic use encouraging selective pressure (i.e. surviving bacteria develop resistance)
- Antibiotic use by medical professions, veterinary practices, farming
- Patients surviving linger with more complex medical conditions and hospital contact
- More invasive procedures and prosthetic devices e.g. dialysis patients
- In UK increased bed pressure encourages spread of resistant organisms
