Antimicrobial Chemotherapy Flashcards
What are the 7 principles for prescribing antimicrobials?
- Indications for antimicrobials
- Making a clinical diagnosis
- Patient characteristics
- Antimicrobial selection
- Regimen selection
- Liasion with laboratory
- Antimicrobial stewardship
What is empiric therapy?
Treating without microbiology results
What is directed therapy?
Treatment based on microbiology results
What are the two types of prophylaxis?
Primary, e.g. antimalarials, pre-op antibiotics etc.
Secondary (to prevent a second episode)
What may involved in assessing the severity of an infection?
qSOFA, ?septic shock
What patient characteristics may influence antimicrobial choice?
- Age
- Renal function
- Liver function
- Immunocompromised
- Pregnancy
Known allergies
What should antibiotic selection be based on?
The known or most likly causative organism(s)
What is the difference between bactericial and bacteriostatic drugs?
Bactericidal - kills
Bacteriostatic - prevents replication
What features must you consider when selecting an appropriate regimen?
- Route of administration
- Dose
- Adverse events
- Duration
- IV to oral switch therapy
- Inpatient/outpatient therapy (OPAT)
- Therapeutic drug monitoring
What is involved in antimicrobial stewardship?
Making the best use of our current antibiotics
Describe the empirical Rx of cellulitis
Cellulitis most likely to be strep pyogenes so chose antibiotic effective against that
Describe the empirical Rx of pneumonia
Most likely to be strep pneumonia (then H. influenzae, staph aureus…)
If have COPD - moraxella catarrhalis
If been in contact with contaminated water - legionella most common
Give an example of a bactericical
Beta-lactams
How do bactericidals work?
Act on cell wall
What are the indications for bactericidals?
- Neutropenia
- Meningitis
- Endocarditis
- Lifethreatening infections
Give an example of a bacteriostatic
Macrolides
How do bacteriostatic drugs work?
Inhibit protein synthesis and prevent colony growth
Require host to mop up residual infection
When are bacteriostatic drugs most useful?
In treating toxin mediated illness as they are able to switch off the proteins that the bacteria use to make toxins
Name 2 conditions that require combination antimicrobials
HIV and TB
Others: sepsis, mixed organisms
When should you give oral route for antimicrobials?
IT is preferred whereever possible if no vomiting, normal GI function, no shock, no organ dysfunction
When should you give IV route for antimicrobials?
Severe, deep seated infection and when oral route not reliable
What are some of the allergic reactions that can occur due to antibiotics?
Immediate hypersensitivity (anaphylaxis)
Delayed hypersensitivity (rash, fever, serum sickness, erythema nodosum, SJS)
GI, e.g nausea, vomiting, diarrhoea, C. diff infection
Which antibiotics shouldn’t be used in those with renal damage?
Vancomycin and gentamicin
What antimicrobials are cytotoxic?
Gentamicin and vancomycin
What antimicrobial can cause optic neuropathy?
Ethambutol
What antimicrobials can cause convulsions and encephalopathy?
Penicillins and cephalosporins
What antimicrobials can cause peripheral neuropathy?
Isonazid, metronidazole
What antimicrobial can cause megoblastic anaemia and how?
Co-trimaxazole
Poisons DNA synthesis via interrupting foltate metabolism
‘Reduce the 4 C’s and reduce C. diff’
What are the 4 C’s?
Ceftriaxone, co-amoxiclav, clindamycin ciprofloxacin
What are the classes of antimicrobial?
- Penicillins (beta-lactams)
- Cephalosporins (beta-lactams)
- Aminoglycosides
- Macrolides
- Quinolones
- Glycopeptides
- Others
- Antifungals
- Anti-virals
Which antimicrobials work by inhibiting cell wall synthesis?
Beta-lactams (peincillins and cephalosporins)
Glycopeptides (vancomycin and teicoplanin)
Which antimicrobials work by inhibiting protein synthesis?
Aminoglycosides (gentamicin)
Macrolides (clarithromycin)
Tetracyclines (doxycycline)
Oxazolidnones (linezolid)
Which antimicrobials work by inhibiting nucleic acid synthesis?
Trimethoprim
Sulfonamides (sulfamethoxazole)
Quinolones (ciprofloxacin)
How is benzyl penicillin administered?
IV/IM only
What is the activity of benzyl penicillin against?
Streptococci, Neisseria, spirochetes
What is benzyl penicillin mostly used to Rx?
Soft tissue, pneumococcal, meningococcal, gonorrhoea, syphilis infections
What is the activity of amoxicillin against?
Broad spectrum
What is amoxicillin mostly used to Rx?
UTI, RTI
What is flucloxacillin mostly used to Rx?
S. aureus infections
What is co-amoxiclav mostly used to Rx?
UTI, RTI, soft tissue infections, surgical wound infections
What is piperacillin/tazobactam mostly used to Rx?
Neutropenic sepsis
What is cefradine mostly used to Rx?
UTI, soft tissue infection
What is cefuroxime mostly used to Rx?
UTI, RTI, surgical prophylaxis
What is ceftriazone/cefotaxime mostly used to Rx?
Hospital infections, e.g. bacteraemia, pneumonia, abdo sepsis
What is cefazidine mostly used to Rx?
Pseudomonal infections in hospital and in CF
What are gentamicin/amikacin mostly used to Rx?
Serious gram -ve infections, e.g. bacteraemia, endocarditis, neutropenic sepsis
What are clarithromycin/erythromycin mostly used to treat?
Respiratory infections, soft tissue infection (if penicillin allergic), STF
What is azithromycin mainly used to treat?
Chlamydia
What is the main use of ciprofloxacin?
Complicated UTI, complicated HAI, pneumonia, some GI infections
What is the main use of levofloxacin/moxifloxacin?
2nd/3rd line for pneumonia
What are vancomycin/teicoplanin mostly used for?
MRSA, patients allergic to penicllin, C. diff
What is the main use of trimethoprim?
UTI, respiratory infection, MRSA
What is the main use of co-trimaxazole?
Respiratory infection, PCP
What is the main use of clindamycin?
Soft tissue infection gangrene
What is the main use of tetracycline/doxycyline?
Q fever, brucellosis, chlamydia, atypical pneumonia, MRSA
What is the main use of rifampicin?
TB, MRSA, meningococcal prophylaxis, complicated staph infections
What is the main use of meropenem?
2nd/3rd line for hospital infections
What is the main use of linezolid/daptomycin?
2nd line agent for MSSA, MRSA, VRE
What is the main use of tigecycline?
2nd line intra-abdominal sepsis, soft tissue infections (last resort)
What bacteria does co-amoxiclav have activity against?
Broad spectrum, incl anaerobes
What bacteria does piperacillin/tazobactam have activity against?
Broad spectrum, incl anaerobes and pseudomonas
What bacteria do the cephalosporins have activity against?
Broad spectrum
What bacteria do aminoglycosides have activity against?
Gram negatives
What bacteria does clarithromycin/erythromycin have activity against?
Strep, staph, myocplasma, chlamydia, legionella
What bacteria does azithromycin have activity against?
Better for gram -ves (incl haemophilus, chlamydia)
What bacteria does ciprofloxacin have activity against?
Gram -ve bacilli incl. pseudomonas w. some activity against staph/strep
What bacteria does levofloxacin/moxifloxacin have activity against?
Enhanced against staph/strep
Active against pneumococcus, mycoplasma, chlamydia, legionella
What bacteria do glycopeptides have activity against?
Gram +ve only (staph, strep)
What bacteria does trimethoprim have activity against?
Gram -ve bacilli, some activity against strep and staph
What bacteria does co-trimoxazole have activity against?
Broad spectrum, PJP
What bacteria does clindamycin have activity against?
Strep, staph, anaerobes
What bacteria does tetracycline/doxcycline have activity against?
Strep, staph, chlamydia, ricketassiae, brucella
What bacteria does rifampicin have activity against?
Mycobacteria, meningococcus, staph
What bacteria does meropenem have activity against?
Broad spectrum antibiotics incl anaerobes, pseudomonas
What bacteria does metronidazole have activity against?
Anaerobes, protozoa
What bacteria does linezolid/daptomycin have activity against?
Gram +ve bacterial only
What bacteria does tigecycline have activity against?
V broad spectrum, e.g. MRSA, ESBL
What is the main use of metronidazole?
Surgical infections, giardiasis, amoebiasis, trichomonal infections
Which antibiotics are in the penicillins group?
- Benzylpenicillin penicillin V
- Amoxicillin
- Flucloxacillin
- Co-amoxiclav
- Piperacillin/tazobactam
What antibiotics are in the cephalosporin group?
- Cefradine (1st)
- Cefuroxime (2nd)
- Ceftriazone/cefotaxime (3rd)
- Cefazidine
What antibiotics are aminoglycosides?
- Gentamicin
- Amikacin
What antibiotics are macrolides?
- Clarithromycin
- Erythromycin
- Azithromycin
What antibiotics are quinolones?
- Ciprofloxacin
- Levofloxacin/moxifloxacin
What antibiotics are glycopeptides?
- Vancomycin
- Teicoplanin
What are the four types of antifungal therapy?
Azoles
Polyenes
Echinocandins
Terbinafine
What are the azole drugs and what fungi are they active against?
- Fluconazole: candida, some resistance
- Itraconazole: candida, aspergillus
- Voriconazole: candida, aspergillus
What are the polyenes and what are the active against?
- Amphotericin: candida, aspergillus
- Nystatin: candida
What are the endocandins and what are the active against?
Caspofungin, anidulafungin, micafungin: candida, aspergillus
What is terbafine mostly used for?
Tinea or fungal nail infections
Delete as appropriate:
All antivirals are viruostatic/virucidal
Viruostatic
Viruses require host cell enzymes to replicate & therefore antivirals target viral proteins that do this
How do most antivirals work?
Most are nucleoside analogues
They work by inhibiting nucleic acid synthesis
What is a big problem with antivirals?
Toxicity to the host cell may lead to side effects
Only used in minority of cases because of this
What are the types of antiviral treatment?
- Prophylaxis (preventing infection)
- Pre-emptive (evidence of infection detected but before symptoms apparent)
- Overt disease
- Suppressive therapy (keep viral replication below rate that causes tissue damage in asymptomatic infected patients, e.g. antiretrovirals
When are antivirals indicated in herpes infections?
- Mucocutaneous: oral, genital, eye, skin
- Encephalitis
- Immunocompromised
What antivirals can used to treat herpes infection?
Aciclovir, famciclovir, ganciclovir
Usually use foscarnet if aciclovir resistant
What antivirals can be used to treat HCV?
Pegylated nterferon alpha (s/c)/ribavirin + protease inhibitor (e.g. telaprevir/boceprevir)
When are antivirals indicated for chickenpox?
- In those at increased risk of complications
- Neonates
- Immunocompromised
- Pregnant
- Immunocomponent adult (only if begun within 24 hours of onset of rash)
The treatment of shingles with antivirals only decreases the risk of ___________ in the immuncompetent if begun within ___hours of onset of symptoms
post-herpetic neuralgia
72
What is the mode of action of aciclovir?
Acyclovir is converted by viral thymidine kinase to AVCMP
ACVMP then converted by host cell kinases to ACV-TP via phosphorylation
ACV-TP (aciclovir triphosphate) competes for the viral DNA polymerase, becomes incorporated into the viral DNA chain and inhibits further DNA polymerase activity
Aciclovir lacks a 3’-hydroxyl group on its acyclic side-chain, and therefore cannot form a phosphodiester bond with the next nucleotide due to be added to the growing herpes DNA chain, which is terminated prematurely
This prevents further viral DNA synthesis without affecting normal cellular processes
What antiviral may be used in the treatment of respiratory syntical virus?
Ribavirin (rarely indicated)
What are the two ways to test for resistance to antivirals?
- Phenotypic – can virus grow in presence of compound
- Genotypic – sequence genome and identify resistance-associated mutations
What 3 points are included in the UK 5 Year Antimicrobial Resistance Strategy?
- Improve knowledge and understanding of AMR
- Converse and steward the effectiveness of existing treatments
- Stimulate the development of new antibiotics, diagnostics and novel therapies
What is the role of the Scottish Antimicrobial Prescribing Group (SAPG)?
Coordinates and delivers a national framework for antimicrobial stewardship to enhance the quality of antimicrobial prescribing and management in Scotland
What is IVOST?
IV to Oral Switch Therapy
Consider switching patients from IV to oral antibiotics after 48 hours, provided that patient improving clinically & able to tolerate oral formulation (can swallow, normal vital signs etc.)
