Antimicrobial Chemotherapy Flashcards
name 10 classes of antimicrobials
penicillins (b-lactams) cephalosporins (b-lactams) aminoglycosides gylcopeptides macrolides quinolines others antifungals antivirals immunoglobulins
list 6 principles of prescribing for antibiotics
indications clinical diagnosis and severity patient characteristics antimicrobial selection regimen selection liaison with lab
name 4 mechanisms of resistance
alteration of target site to reduce/eliminate binding of drug
destruction or inactivation of antibiotic
blockage of transport into antibiotic into cell
metabolic bypass
give 6 examples of hospital bugs with increasing resistance
- Methicillin resistant S. aureus (MRSA)
- Methicillin resistant S. epidermidis (MRSE)
- Vancomycin resistant Enterococcus (VRE)
- Vancomycin intermediate S. aureus (VISA / GISA)
- Extended-spectrum (β-lactamase gram negatives (ESBL)
- Multiresistant Tuberculosis
give examples of community bugs with increasing resistance
- HIV
- Food-borne (Salmonella, Shigella, H pylori)
- Malaria
- Pneumococcus
- Hepatitis B& C
- E coli O157
- Lyme disease
- Legionnaire’s
what are the indications for antimicrobials?
therapy - empiric/directed
prophylaxis
primary - antimalaria, pre-op, PEP
secondary - to prevent a second episode
what are the patient characteristics when selecting an antimicrobial?
age renal function liver function immunocompromised pregnancy known allergies
what are the factors to consider when selecting an antimicrobial?
guideline or individualised therapy likely organism empirical therapy or result based bactericidal vs bacteriostatic drug single or combination potential adverses effects
what are the likely pathogens in a soft tissue infection?
o Streptococcus pyogenes o Staphylococcus aureus o Streptococcus group C or G o E. Coli o Pseudomonas aeruginosa o Clostridium sp.
what are the likely pathogens in pneumonia?
o Streptococcus pneumonia o Haemophilus influenzae o Staphylococcus aureus o Klebsiella pneumonia o Moraxella catarrhalis o Mycoplasma pneumonia o Legionella pneumonia o Chlamydia pneumonia
what drug class is bactericidal?
beta-lactams
how do bactericidal drugs work?
act on the cell wall to kill the organism
indications for bactericidal drugs
neutropenia
meningitis
endocarditis
what class of drugs are bacteriostatic?
macrolides
how to bacteriostatic drugs work?
inhibit protein synthesis
prevent colony growth
require host immune system to mop up residual indfection
when are bacteriostatic drugs useful?
in toxic mediated illness
what are the advantages of single antimicrobial therapy?
simpler
fewer side effects
fewer drug interactions
for what would you use combination antimicrobial therapy?
HIV and TB
Severe sepsis
Mixed orgnisms
when selecting a regimen for antimicrobials what do you need to consider?
route of administration dose ADR duration IV vs oral inpatient vs outpatient therapeutic drug monitoring
discuss route of administration in regards to antimicrobials
Oral bioavailability is the ratio of drug level when given orally compared with level when given IV. It can vary widely e.g. flucloxacillin 50-70% and linezolid 100%. The oral route can be used if not vomiting, normal GI function, no shock, and no organ dysfunction. Use the IV route if there is severe or deep-seated infection, and when the oral route is not reliable
name the potential adverse effects of antimicrobials
allergy GI Candida liver renal neurological haematological
antimicrobial ADR: allergy
immediate hypersensitivity - anaphylaxis
delayed hypersensitivity - rash, drug fever, seurm sickness, erythema nodosum, stevens-johnson syndrome
what type of antibiotics are people most likely to be allergic to?
penicillin
cephalosporin
antimicrobial ADR: GI
nausea, vomiting, diarrhoea
c, diff
antimicrobial ADR: candida
broad spectrum penicillins, cephalosporins
antimicrobial ADR: liver
all drugs, particularly tetracyclines, TB drugs
more likely if existing liver disease
antimicrobial ADR: renal
gentamicin, vancomycin
more likely if pre-existing renal disease or nephrotoxic meds
antimicrobial ADR: neurological
ototoxicity - gent, vanc
optic neuropathy - ethambutol
convulsions, encephalopathy - penicillins, cephalosporin
peripheral neuropathy - isoniazid, metronidazole
antimicrobial ADR: haematological
marrow toxicity
megaloblastic anaemia - co-triaxazole
how must you liaison with the lab in relation to antimicrobials
send appropriate specimens - culture/direct detection/serology
receiving results - preliminary culture results, sensitivity results, final results
monitoring - disease activity, therapeutic drug monitoring
what antibiotics inhibit cell wall synthesis?
B-lactams - penicillins and cephalosporins
gylcopeptides - vanc, teicoplanin
what antibiotics inhibit protein synthesis?
aminoglycosides - gent
macrolindes - clarithromycin
tetracyclines - doxy
oxazolidinones - linezoid
what antibiotics inhibit nucleic acid synthesis?
trimethoprim
sulphonamides - sulfamthoxazole
quinolones - ciprofloxacin
name 5 penicillins
benzylpenicillin V amoxicillin flucloxacillin co-amoxiclav piperacillin with tazobactam
benzylpenicillin V: acitivity
streptococci
neisseria
spirochetes
benzylpenicillin V: main uses
soft tissue pneumococcal meningococcal gonorrhoea syphilis
amoxicillin: acivity
broad spectrum but resistance common
amoxicillin: main uses
UTI
RTI
flucloxacillin: acivity
staphyloccoi
flucloxacillin: main uses
S. aureus
co-amoxiclav: activity
broad spectrum inc anaerobes
co-amoxiclav: main uses
UTRI
RTI
Soft tissue
SSI
piperacillin/tazobactam: activity
brad spectrum incl pseudomonas, anaerobes
piperacillin/tazobactam: main uses
neutropenic sepsis
name 4 cephalosporins
cefradine
cefuroxime
ceftriaxone
ceftazidime
cefradine: activity
broad spectrum, resistance
cefradine: main uses
UTI
soft tissue infection
cefuroxime: activity
broad spectrum
cefuroxime: main uses
UTRI
RTI
surfical prophylaxis
ceftriaxone: activity
broad spectrum esp gram -ve bacilli
ceftriaxone: main uses
hospital infections e.g. bacteraemia, pneumonia, abdo spesis
ceftriaxone: is a risk factor for?
MRSA
C. diff
VRE
ceftazidime: activity
broad spectrum esp gram -ve bacilli
pseudomonas
ceftazidime: main uses
pseudomonal infections in hospital and cystic fibrosis
ceftazidime: is a risk factor for?
MRSA
c. diff
VRE
name an aminoglycoside
gentamicin
gentamicin: activity
gram -ve bacilli
gentamicin: main uses
serious gram -ve infections e.g. bacteraemia, endocarditis, neutropenic sepsis
gentamicin: ADR
renal toxicity
ototoxicity
name 3 macrolides
clarithromycin
erythromycin
azithromycin
clarithromycin: activity
streptococci staphylococci mycoplasma chlamydia legionella
clarithromycin: main uses
RTI
soft tissue infection if penicillin allergic
STD
erythromycin: activity
streptococci staphylococci mycoplasma chlamydia legionella
erythromycin: main uses
RTI
soft tissue infection if penicillin allergic
STD
erythromycin: SE
Gi intolerance
azithromycin: activity
better for gram -ve e.g. haemophilus, chlamydia
azithromycin: main uses
chlamydia
name 3 quinolones
ciprofloxacin
levofloxacin
moxifloxacin
ciprofloxacin: activity
gram -ve bacilli inc pseudomonas
some activity against staph and strep
ciprofloxacin: main uses
complicated UTI
complicated hospital acquired pneumonia
some GI infections
ciprofloxacin: ADR
c. diff
may affect growing cartilage
levofloxacin/moxifloxacin: activity
enhanced activity against staph and strep, less against pseudomonas pneumococcus mycoplasma chlamydia legionella
levofloxacin/moxifloxacin: main uses
2nd/3rd line for pneumonia
name 2 glycopeptires
vancomycin
teicoplanin
vancomycin/teicoplanin: activity
gram +ve bacteria only (strep/staph)
vancomycin/teicoplanin: main uses
MRSA
penicillin allergy
oral - c.diff
vancomycin/teicoplanin: SE
nephrotoxicity
trimethoprim: activity
gram -ve bacilli
some activity against strep and staph
trimethoprim: main uses
UTI
RTI
MRSA
co-trimoxazole (trimethoprim-sulphamethoxazole): activity
broad spectrum
pneumocystis
jiroveci
co-trimoxazole (trimethoprim-sulphamethoxazole): main uses
RTI
PCP
co-trimoxazole (trimethoprim-sulphamethoxazole): SE
rash
clindamycin: activity
strep
staph
anaerobes
clindamycin: main uses
soft tissue infection
gangrene
tetracycline/doxycycline: activity
strep staph chlamydia rickettsiae brucella
tetracycline/doxycycline: main uses
Q fever brucellosis chlamydia atypical pneumonia MRSA
when is tetracycline/doxycycline contraindicated?
pregnancy and childhood
rifampicin: activity
mycobacteria
meningococcus
stapg
rifampicin: main uses
TB
MRSA
meningococcal prophylaxis
stap
meropenem: activity
broad spectrum incl anaerobes, pseudomonas
meropenem: main uses
2nd/3rd line for hospital infections
metronidazole: activity
anaerobes
protozoa e.g. giardia
metronidazole: main uses
SSR
giardiasis
amoebiasis
trichomonal infections
metronidazole: reacts with what?
alcohol
linezolid: activity
gram +ve bacteria only
strep, staph, enterococci
linezolid: main uses
2nd line for MSSA, MRSA, VRE
linezolid: SE
blood and optic neuropathy
daptomycin: activity
gram +Ve bacteria only
daptomycin: main uses
2nd line for MSSA, MRSA< VRE
when is daptomycin inactive?
lung myositis
tigecycline: activity
very broad spectrum, inc MRSA, ESBL, anaerobes
tigecycline: main uses
3rd line in intraabdo sepsis, soft tissue infection
IV tigecycline is ineffective against?
Pseudomonas
give 3 examples of azole antifungals
fluconazole
itraconazole
voriconazole
what is fluconazole active against?
candida
what is itraconazole active against?
candida + aspergillus
what is voriconazole active against?
candida + aspergillus
name 2 polyene antifungals
amphotericin
nystatin
what is amphotericin active against?
candida + aspergillus
what is nystatin active against?
candida
name 3 echinocandin antifungal
caspofungin
anidulafungin
micafungin
what are the echinocandin antifungals active against?
candida + aspergillus
what is terbinafine active against?
tinea
all antiviral drugs are? (virustatic or virucidal)
virustatic
how do viruses replicate?
obligate intracellular parasites
utilise host cell enzymes in order to replicate
what makes it hard to develop antivirals?
limited viral proteins that are potential targets
most drugs target what stages in virus replication?
intracellular
most antivirals are have what mechanism of action?
nucleoside analogues - inhibit nucleic acid synthesis
antivirals may be used for:
prophylaxis
pre-emptive therapy
overt disease
suppressive therapy
antivirals in prophylaxis
to prevent infection
acyclovir - herpes
antivirals in pre-emptive therapy
when evidence of infection detected but before symptoms
interferon/ribavirin - HCV
antivirals in overt disease
aciclovir
oseltamivir
antivirals in suppressive therapy
to keep viral replication below the rate that causes tissue damage in asymptomatic infected patient
antiretrovirals
why may suppressive antiviral treatment be needed after successful treatment?
do not eradicate virus from latently infected cells
when may you use antivirals for HSV?
mucocutaneous - oral ,genital, eye, skin
encephalitis
immunocompromised
when may you use antivirals for chicken pox?
neonate
immunocompromised
pregnant
when may you use antivirals for shingles?
only in first 72 hours of onset of symptoms to decrease post-herpetic neuralgia
what antivirals and route may you use for HSV and VSV?
o Acyclovir – oral, IV, eye ointment, cream
o Valaciclovir – oral
o Famciclovir – oral
o Foscarnet – IV
o Aciclovir like drugs are only active in herpes infected cells
describe the mechanism of action of aciclovir
Aciclovir 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
why is there a lack of cellular toxicity with aciclovir?
- Initial phosphorylation takes place only in virus-infected cells.
- Aciclovir triphosphate inhibits viral (not cellular) DNA polymerase.
discuss antivirals and 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. They may also be used to treat neonates with symptomatic congenital CMV infection. • Ganciclovir – IV, ocular implant • Valganciclovir – oral • Cidofovir – IV • Foscarnet – IV
discuss antivirals and HIV
This is a fast-changing specialist area for which UK treatment guidelines exist. Combination antiretroviral
therapy (cART), also called highly active antiretroviral therapy (HARRT), uses combinations of antiretrovirals to effectively reduce viral load. This has transformed HIV care with:
1. Restoration of immune function in AIDS
2. Decrease in opportunistic infections
discuss antivirals and chronic hep B
• Pegylated interferon alpha (SC) • Nucleoside/tide analogues o Tenofovir o Adefovir o Entecavir o Lamivudine o Emtricitabine o Telbivudine
discuss antivirals and chronic hep C
• Often 12-48weeks
• Current therapies
o Pegylated interferon alpha and ribavirin
o As above plus protease inhibitor – telaprevir or boceprevir
• New directly acting antivirals in combination
o Daclatasvir
o Sofosbuvir
o Simeprevir
discuss antivirals and respiratory infections
• Influenza A or B o Oseltamivir, zanamivir o Role in both treatment and prophylaxis o Not always indicated, but if used, start within 48 hrs of onset/contact • RSV o Ribavirin o Rarely indicated
when should you suspect resistance to herpes virus in immunocompromised patients?
no response to appropriate doses within 7 daus
if HSV and CMV are resistant to acyclovir, what is usually effective?
foscarnet
name the 9 components of the antibiotic paradox
- Antibiotics initially led to poorer hygiene
- Antibiotics increase infections
- Antibiotics can increase severity of infection
- Antibiotics increase infections and mortality in uninfected patients
- Are new antibiotics really the answer?
- Antibiotics are too cheap – even when new and branded – this encourages inappropriate use
- There are many similarities to global warming
- Non-human use is greatest
- The global village
