Antimicrobials - Bacteria and Fungi Flashcards
What are the principles of prescribing antimicrobials?
- Indications for antimicrobials
- Making a clinical diagnosis
- Patient characteristics
- Antimicrobial selection
- Regimen selection
- Liaison with laboratory
- Antimicrobial Stewardship
What are the principles of prescribing - 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 second episode e.g. PJP
What are the principles of prescribing - Diagnosis?
Diagnosis of infection:
- Clinical
- Laboratory
- None (No treatment)
Severity assessment:
- Sepsis?
- Septic shock?
What are the principles of prescribing - Patient characteristics?
> Age > Renal function > Liver function > Immunocompromised > Pregnancy > Known allergies
What are the principles of prescribing - Antimicrobial selection?
> Guideline or “individualised” therapy > Likely organism(s) > Empirical therapy or result-based therapy > Bactericidal vs. bacteriostatic drug > Single agent or combination > Potential adverse effects
What should antibiotic selection be based on?
The known or likely causative organism(s)
What are the most likely causative bacteria in soft tissue infection?
> Streptococcus pyogenes > Staphylococcus aureus > Streptococcus group C or G > E coli > Pseudomonas aeruginosa > Clostridium species
What are the most likely causative bacteria pneumonia?
> Streptococcus pneumonia > Haemophilus influenza > Staphylococcus aureus > Klebsiella pneumonia > Moraxella catarrhalis > Mycoplasma pneumonia > Legionella pneumonia > Chlamydia pneumonia
Bactericidal?
> Eg Beta-lactams
Act on the cell wall
Kill organisms
Indications: neutropenia, meningitis and endocarditis
Bacteriostatic?
> Eg Macrolides > Inhibit protein synthesis > Prevent colony growth > Require host immune system to "mop up" residual infection > Useful in toxin-mediated illness
When would combination antimicrobial therapy be used?
> HIV and TB therapy
Severe sepsis (febrile neutropenia)
Mixed organisms (faecal peritonitis)
What is the advantage of single over combination antimicrobial therapy?
> Simpler
Fewer side effects
Fewer drug interactions
What are the principles of prescribing - regimen selection?
> Route of administration
Dose
Adverse effects (side effects/toxicity)
Duration
Intravenous to oral SWITCH therapy
Inpatient or Outpatient therapy: - Outpatient parenteral antimicrobial therapy (OPAT)
Therapeutic drug monitoring
When would the oral route for antimicrobials be selected?
> No vomiting
Normal GI function
No shock
No organ dysfunction
When would the intravenous route for antimicrobials be selected?
> Severe or deep-seated infection
> Oral route is not available
What is oral bioavailability?
> Ratio of drug level when given orally compared with level when given IV
Varies widely, E.g:
- Flucloxacillin 50-70%
- Linezolid 100%
Types of adverse effects of antimicrobials?
> Allergic reactions > Gastrointestinal > Candida (Thrush) > Liver > Renal > Neurological > Haematological
Types of adverse effects of antimicrobials - Allergic reactions?
> Immediate hypersensitivity:
- Anaphylactic shock
> Delayed hypersensitivity:
- Rash
- Drug fever
- Serum sickness
- Erythema nodosum
- Stevens-Johnson syndrome
Most likely caused by penicillins and cephalosporins
Types of adverse effects of antimicrobials - Gastrointestinal?
> Nausea, vomiting, diarrhoea
> Clostridium infection
Types of adverse effects of antimicrobials - Candida (thrush)?
Caused by broad spectrum penicillins, cephalosporins
Types of adverse effects of antimicrobials - Liver?
> All drugs, particularly tetracyclines, TB drugs
> More likely if pre-existing liver disease
Types of adverse effects of antimicrobials - Renal?
> Gentamicin, Vancomycin
> More like if pre-existing renal disease or on nephrotoxic meds
Types of adverse effects of antimicrobials - Neurological?
> Ototoxicity - Gentamicin, Vancomycin
> Optic neuropathy - Ethambutol (TB)
> Convulsions, encephalopathy - Penicillins, cephalosporins
> Peripheral neuropathy - Isoniazid (TB), Metronidazole
Types of adverse effects of antimicrobials - Neurological caused by gentamicin?
Ototoxicity
Types of adverse effects of antimicrobials - Neurological caused by vancomycin?
Ototoxicity
Types of adverse effects of antimicrobials - Neurological caused by Ethambutol (TB)?
Optic neuropathy
Types of adverse effects of antimicrobials - Neurological caused by penicillins?
Convulsions, encephalopathy
Types of adverse effects of antimicrobials - Neurological caused by cephalosporins?
Convulsions, encephalopathy
Types of adverse effects of antimicrobials - Neurological caused by Isoniazid (TB)?
Peripheral neuropathy
Types of adverse effects of antimicrobials - Neurological caused by metronidazole?
Peripheral neuropathy
Types of adverse effects of antimicrobials - Heamatological?
> Marrow toxicity
> Megaloblastic anaemia (folate metabolism) - Co-trimoxazole
Types of adverse effects of antimicrobials - Penicillins?
> Allergic reactions
Candida
Convulsions, encephalopathy
Types of adverse effects of antimicrobials - cephalosporins?
> Allergic reactions
Candida
Convulsions, encephalopathy
Types of adverse effects of antimicrobials - gentamicin and vancomycin?
> Renal
> Ototoxicity
What are the principles of prescribing - liaison with laboratory?
> Sending appropriate specimens:
- culture
- direct detection
- serology
> Receiving results
- preliminary culture results
- sensitivity results
- final results
> Monitoring
- disease activity
- therapeutic drug monitoring
What are the principles of prescribing - antimicrobial stewardship?
> Antimicrobial Guidelines & Policies
Audit of quality of antimicrobial prescribing
Education
Who is involved in the antimicrobial management team?
> Pharmacists > Infectious diseases > Acute medicine > Medical microbiology > Infection prevention and control > General practice > Public partner
Outbreaks of Clostridium difficile infections often occurs due to what?
Broad spectrum antibiotics
What are the 4 C’s that are linked to C difficile?
4 antibiotics: > Ceftriaxone (and other cephalosporins) > Clindamycin > Co-amoxiclav > Ciprofloxacin (and other quinolones)
The antimicrobial classes?
> Penicillins (β-lactams) > Cephalosporins (β-lactams) > Aminoglycosides > Macrolides > Quinolones > Glycopeptides > Others > Antifungals > Antivirals
Mechanism of action - Inhibition of cell wall synthesis?
> Beta-lactams:
- Penicillins
- Cephalosporins
> Glycopeptides:
- Vancomycin
- Teicoplanin
Mechanism of action - Beta-lactams?
Inhibition of cell wall synthesis
Mechanism of action - Penicillins?
A beta lactam - Inhibition of cell wall synthesis
Mechanism of action - Cephalosporins?
A beta lactam - Inhibition of cell wall synthesis
Mechanism of action - Glycopeptides
Inhibition of cell wall synthesis
Mechanism of action - Vancomycin?
A Glycopeptides - Inhibition of cell wall synthesis
Mechanism of action - Teicoplanin?
A Glycopeptides - Inhibition of cell wall synthesis
Mechanism of action - Inhibition of Protein Synthesis?
> Aminoglycosides: gentamicin
Macrolides: clarithromycin
Tetracyclines: doxycycline
Oxazolidinones: linezolid
Mechanism of action - Aminoglycosides
Inhibition of Protein Synthesis
Mechanism of action - gentamicin?
An aminoglycoside - Inhibition of Protein Synthesis
Mechanism of action - Macrolides?
Inhibition of Protein Synthesis
Mechanism of action - clarithromycin?
A macrolide - Inhibition of Protein Synthesis
Mechanism of action - Tetracyclines?
Inhibition of Protein Synthesis
Mechanism of action - doxycycline?
A tetracycline - Inhibition of Protein Synthesis
Mechanism of action - Oxazolidinones?
Inhibition of Protein Synthesis
Mechanism of action - linezolid?
An oxazolidinones - Inhibition of Protein Synthesis
Mechanism of action - Inhibition of Nucleic acid synthesis?
> Trimethoprim
Sulfonamides: sulfamethoxazole
Quinolones: ciprofloxacin
Mechanism of action - Trimethoprim
Inhibition of Nucleic acid synthesis
Mechanism of action -Sulfonamides
Inhibition of Nucleic acid synthesis
Mechanism of action - sulfamethoxazole?
A Sulfonamide - Inhibition of Nucleic acid synthesis
Mechanism of action - Quinolones?
Inhibition of Nucleic acid synthesis
Mechanism of action - ciprofloxacin?
A Quinolone - Inhibition of Nucleic acid synthesis
Use of benzylpenicillin?
> Soft tissue > pneumococcal > meningococcal > gonorrhoea > syphilis infections
Use of penicillin V?
> Soft tissue > pneumococcal > meningococcal > gonorrhoea > syphilis infections
Pathogens targeted by benzylpenicillin?
> Streptococci,
Neisseria
Spirochetes
Pathogens targeted by penicillin V?
> Streptococci,
Neisseria
Spirochetes
Use of amoxicillin?
> UTI
> RTI
Pathogens targeted by amoxicillin?
Broad spectrum but resistance is common
Pathogens targeted by flucloxacillin?
Staphylococci (S aureus)
Pathogens targeted by co-amoxiclav?
> Broad spectrum
> Anaerobes
Use of Co-amoxiclav?
> UTI
RTI
Soft tissue infections
Surgical wounds
Risk of using co-amoxiclav?
C difficile
An example of a 1st generation cephalosporin?
Cefradine
Pathogenic activity of a 1st generation cephalosporin (Cefradine)?
> Broad spectrum
> Resistance
Uses of a 1st generation cephalosporin (Cefradine)?
> UTI
> Soft Tissue infection
An example of a 2nd generation cephalosporin?
Cefuroxime
Pathogenic activity of a 2nd generation cephalosporin (cefuroxime)?
Broad spectrum
Uses of a 2nd generation cephalosporin (cefuroxime)?
> UTI
RTI
Surgical prophylaxis
An example of a 3rd generation cephalosporin?
> Ceftriaxone
Cefotaxime
Ceftazidime
Pathogenic activity of a 3rd generation cephalosporin (ceftriaxone/
cefotaxime)?
> Broad spectrum esp good against Gram-neg bacilli
Ceftazidime
for Pseudomonas
Uses of a 3rd generation cephalosporin (ceftriaxone/
cefotaxime)?
Hospital infections eg bacteraemia, pneumonia, abdo sepsis
Uses of a 3rd generation cephalosporin (Ceftazidime)?
> Hospital infections eg bacteraemia, pneumonia, abdo sepsis
> Pseudomonal infections in hospital and in cystic fibrosis
Pathogenic activity of a 3rd generation cephalosporin (Ceftazidime)?
> Broad spectrum esp good against Gram-neg bacilli
> Pseudomonas
What are the risks of using 3rd generation cephalosporins?
Risk factor for MRSA, C. diff, VRE;
An example of an aminoglycoside?
> gentamicin
> amikacin
Pathogenic activity of an aminoglycoside?
Gram-neg bacilli
Pathogenic activity of an aminoglycoside?
Serious Gram-negative infections eg bacteraemia, endocarditis, neutropenic sepsis
What are the risks of using an aminoglycoside?
Renal and ototoxicity; measuring levels essential
What are the risks of using gentamicin?
Renal and ototoxicity; measuring levels essential
What are the risks of using amikacin?
Renal and ototoxicity; measuring levels essential
Pathogenic activity of gentamicin?
Serious Gram-negative infections eg bacteraemia, endocarditis, neutropenic sepsis
Pathogenic activity of amikacin?
Serious Gram-negative infections eg bacteraemia, endocarditis, neutropenic sepsis
Pathogenic activity of gentamicin?
Gram-neg bacilli
Pathogenic activity of amikacin?
Gram-neg bacilli
“…romycin”
Macrolide
“…acillin”
Penicillin
“…floxacin”
Quinolones
Examples of macrolides
> Clarithromycin
Erythromycin
Azithromycin
Pathogenic activity of clarithromycin?
> Streptococci > Staphylococci > Mycoplasma > Chlamydia > Legionella
Main uses of clarithromycin?
> Respiratory infection
Soft tissue infection (if penicillin allergic)
STD
Pathogenic activity of erythromycin?
> Streptococci > Staphylococci > Mycoplasma > Chlamydia > Legionella
Main uses of erythromycin?
> Respiratory infection
Soft tissue infection (if penicillin allergic)
STD
Pathogenic activity of azithromycin?
Rel better for Gram-neg e.g. Haemophilus; Chlamydia
Main uses of azithromycin?
Chlamydia
Risk of erythromycin?
GI intolerance
Is erythromycin or clarithromycin better tolerated?
Clarithromycin
Pathogenic activity of ciprofloxacin?
Gram-negative bacilli:
> Pseudomonas
> some activity against staphylococci and streptococci
Pathogenic activity of levofloxacin/
moxifloxacin?
> Enhanced activity against staphylococci/ streptococci > Pneumococcus, > Mycoplasma > Chlamydia > Legionella > Less against Pseudomonas
Main uses of ciprofloxacin?
> Complicated UTI
Complicated hospital acquired Pneumonia
GI infections
Main uses of levofloxacin/
moxifloxacin?
2nd or 3rd line agent for pneumonia
Risk of Quinolones?
> Associated with C. difficile
> May affect growing cartilage
Examples of quinolones?
> ciprofloxacin
levofloxacin
moxifloxacin
Examples of glycopeptides?
> vancomycin
> teicoplanin
Pathogenic activity of vancomycin and teicoplanin?
Gram-positive bacteria only
(streptococci,
staphylococci)
Main uses of vancomycin and teicoplanin?
> MRSA - patients allergic to penicillin (IV Vanc)
> C.difficile (oral vanc)
Risk involved with glycopeptides?
Regular drug levels required; nephrotoxicity
Examples of glycopeptides?
> Vancomycin
> Teicoplanin
Pathogenic activity of trimethoprim?
> Gram-neg bacilli;
> Some activity against Streptococci and staphylococci
Main uses of trimethoprim?
> UTI
Resp infection
MRSA
Pathogenic activity of Co-trimoxazole
(trimethoprim-sulphamethoxazole)?
> Broad spectrum
> Pneumocystis jiroveci
Main uses of Co-trimoxazole
(trimethoprim-sulphamethoxazole)?
> Respiratory infection
> PCP
Risk involved with Co-trimoxazole
(trimethoprim-sulphamethoxazole)?
Rashes
Risk involved with clindamycin?
Associated with C. difficile
Main uses of clindamycin?
> Soft tissue infection
> gangrene
Pathogenic activity of clindamycin?
> Streptococci
Staphylococci
anaerobes
Pathogenic activity of tetracycline and
doxycycline?
> Streptococci > Staphylococci > Chlamydia > rickettsiae > brucella
Main uses of tetracycline and
doxycycline?
> Q fever > Brucellosis > chlamydia > atypical pneumonia > MRSA
Risk involved with tetracycline and
doxycycline?
Contraindicated in pregnancy and childhood (effects on teeth/bones)
Main uses of linezolid?
2nd line agent for MSSA, MRSA, VRE
Pathogenic activity of linezolid?
Gram-positive bacteria only:
> Streptococci
> Staphylococci
> Enterococci
Risk involved linezolid?
Blood and optic neuropathy S/Es
Risk involved daptomycin?
Inactive in lung
Myositis S/E.
Pathogenic activity of daptomycin?
Gram-positive bacteria only:
> Streptococci
> Staphylococci
> Enterococci
Main uses of daptomycin?
2nd line agent for MSSA, MRSA, VRE
Main uses of tigecycline?
3nd line,
Intra-abdominal sepsis, soft tissue infections
Pathogenic activity of tigecycline?
Very broad spectrum:
> MRSA
> ESBL
> anaerobes
Pathogenic activity of Metronidazole?
> Anaerobes
> protozoa (eg giardia)
Main uses of Metronidazole?
> Surgical infections;
giardiasis
amoebiasis
trichomonal infections
Risk involved Metronidazole?
“Antabuse” reaction with alcohol
Risk involved meropenem?
Iv only; goof CNS penetrations
Risk involved rifampicin?
Drug interaction – enzyme inducer
Main uses of meropenem?
2nd and 2rd line for hospital infections
Main uses of rifampicin?
> TB > MRSA > meningococcal >prophylaxis > complicated staphylococcal infections
Pathogenic activity of meropenem
Broad spectrum:
> anaerobes
> pseudomonas
Pathogenic activity of rifampicin
> Mycobacteria
Meningococcus
Staphylococci
Pathogenic activity of linezolid?
Gram-positive bacteria only:
> Streptococci
> Staphylococci
> Enterococci
Pathogenic activity of daptomycin?
Gram-positive bacteria only:
> Streptococci
> Staphylococci
> Enterococci
Pathogenic activity of tigecycline?
Very broad spectrum, including:
> MRSA
> ESBL
> anaerobes
Main uses of linezolid?
2nd line agent for MSSA, MRSA, VRE
Main uses of daptomycin?
2nd line agent for MSSA, MRSA, VRE
Main uses of tigecycline?
3nd line,
Intra-abdominal sepsis, soft tissue infections
Risk involved linezolid?
Blood and optic neuropathy S/Es
Risk involved daptomycin?
Inactive in lung
Myositis S/E
Risk involved tigecycline?
Ineffective against
Pseudomonas.
Examples of azoles (antifungal)?
> Fluconazole
Itraconazole
Voriconazole
Main uses of azoles?
Candida and aspergillus
Main uses of fluconazole?
Candida, some resistance
Main uses of itraconazole?
Candida and aspergillus
Main uses of voriconazole
Candida and aspergillus
Examples of polyenes (Antifungals)?
> Amphotericin
> Nystatin
Main uses of amphotericin?
Candida and aspergillus
Main uses of nystatin?
Candida
Examples of Echinocandin (Antifungals)?
> Caspofungin
Anidulafungin
Micafungin
Main uses of Echinocandin?
Candida and Aspergillus
Main uses of Caspofungin?
Candida and Aspergillus
Main uses of Anidulafungin?
Candida and Aspergillus
Main uses of Micafungin?
Candida and Aspergillus
Main uses of terbinafine?
Tinea, nails
