Antimicrobial agents Flashcards
What is the difference between bactericidal and bacteriostatic?
- Bactericidal actively kills bacteria whereas bacteriostatic prevents bacteria multiplying
What is the difference between an antimicrobial and an antibiotic?
An antimicrobial is any substance that is active against microbes whereas an antibiotic is a naturally occuring product active against bacteria
What do broad-spectrum bacteria kill?
Gram positives, negatives and/or negative anaerobes
What do bacteriostatic antibiotics require in order to be effective?
A functioning host immune system
What antibiotics effect the folic acid metabolism of bacteria?
- Trimethoprim
- Sulfonamides
What antibiotics effect the cell wall synthesis of bacteria?
- Beta lactams
- Glycopeptides
What do Quinolones inhibit?
DNA gyrase
What does Metronidazole inhibit?
DNA replication
What does rifampicin inhibit?
DNA-directed RNA polymerase
What antibiotics inhibit protein synthesis?
- Which ones inhibit 50S and which ones inhibit 30S
50S inhibitors - Chloramphenicol - Macrolides - Clindamycin 30S inhibitors - Aminoglycosides - Tetracycline
What do polymyxins inhibit?
Cytoplasmic membrane structure (gram negatives)
Name some mostly anti-gram-positive antimicrobials?
- Penicillins
- Fusidic acid
- Macrolides
- Clindamycin
- Glycopeptides
- Oxazolidinones
- Daptomycin
Name some mostly anti-gram-negative antimicrobials?
- Polymyxin
- Trimethoprim
- Aminoglycosides
- Monobactams (Aztreonam)
- Temocillin
Name types of broad spectrum antimicrobials?
- Beta lactams (e.g carbapenems, amoxicillin/clavulanate, piperacillin/tazobactam, cephalosporins)
- Chloramphenicol (gram positives, negatives, atypicals, anaerobes)
- Tetracycline (gram positives, negatives, atypicals and anearobes, spirochetes)
Describe the concept of the magic bullet?
A compound which would harm only the pathogen and not the host - refers to selective toxicity
What infections are difficult to treat due to inadequete penetration of antimicrobials into the target site?
- Endocarditis
- Meningitis
- Osteomyelitis
Give an example of synergistic antimicrobials?
Beta-lactams with aminoglycosides (often used to treat endocarditis)
Give examples of antagonistic antimicrobials?
- Tetracycline or chloramphenicol with Beta lactams (or 2 beta lactams together, like flucloxacillin with amoxicillin)
Give an example of drugs with high therapeutic indexes?
Beta lactams
Give an example of drugs with low/narrow therapeutic indexes?
Aminoglycosides
What type of gram negative antimicrobials are intrinsically resistant to polymyxin (colistin)?
Proteus
What can chloramphenicol be toxic to?
Bone marrow (can cause aplastic anaemia)
What is chloramphenicol mainly used for
- Eye drops
- Meningitis in those with penicillin allergy
Describe the difference between eukaryote and prokaryote ribosomes?
- Prokaryotes contain a 70S ribosome with a 50S and 30S subunit
- Eukaryotes contain an 80S ribsome with a 60S and 40S subunit
Name 2 Beta-lactamase susceptible narrow spectrum penicillins?
- Penicillin V and G
Name 2 Beta-lactamase resistant penicillins?
- Flucloxacillin
- Nafcillin
(Also Methicillin and Oxacillin, but these are not used clinically)
Name 2 Beta-lactamase susceptible broad spectrum penicillins?
- Ampicillin and Amoxicillin
Name penicillins with Beta-lactamase inhibitors?
- Amoxicillin and clavulanic acid
- Piperacillin and tazobactam (anti-pseudomonal), this is even broader spectrum
What are examples of carbapenems? (type of Beta lactams that are active against gram negatives)
- Meropenem and imipenem
- Etapenam (not anti-pseudonomal)
- Doripenam
- Faropenem
What penicillins are used at Barts Trust?
- Penicillin (oral) G (IV)
- Benzylpenicillin (IV)
- Flucloxacillin (oral and IV)
- Amoxicillin +/- clavulanic acid (a Beta lactamase inhibitor)
- Temocillin (IV)
- Pivmecillinam (oral)
What percentage of people have a penicillin allergy (immediate IgE mediated anaphylaxis)
0.05% of patients
What are side effects of penicillin?
- Jarisch Herxheimer reaction (spirochetes)
- Coombs positive haemolytic anaemia
- Interstitial nephritis
- Serum sickness
- Hepatitis
- Drug fever
Penicillins penetration into tissues?
penetrates most including meninges
What are the mechanisms of microbial resistance to penicillin?
- Beta-lactamase
- Alteration of PBPs
What can penicillin interact with?
- Allopurinol
- Methotrexate
How many times a day should penicillin be taken?
4 - 6 times a day
How often is amoxicillin given?
3 times a day
What are possible side-effects of amoxicillin?
- Rash with mononucleosis
- Increased PT
- Kounis syndrome
- Neutropenia
- Antibiotic associated diarrhoea
- Fever
What can amoxicillin interact with?
Allopurinol (rash)
What is amoxicillin given for?
Streptococcal disease except when empirically for a sore throat; listeria
What organisms are resistant to amoxicillin?
- > 80% of staphylococcus
- S pneumoniae (mainly in Spain and the USA)
- Gonococcal resistance worldwide
How often is flucloxacilin given?
4 times a day
What are the side-effects of flucloxacilin?
- Cholestasis
- Hepatitis
- Rash
- D and V
- Leukopenia
- Anemia
- Thrombocytopenia
What is flucloxacillin used to treat?
All S aureus infections except MRSA
Describe the mechanism of microbial resistance against flucloxacilin?
Alteration of penicillin binding proteins
What organisms are resistant to flucloxacilin?
- > 80% of staphylococci
- S pneumoniae in USA, Spain
- Gonococcal resistance worldwide
What is the purpose of clavulanic acid in co-amoxiclav?
Acts as a Beta-lactamase inhibitor
What is co-amoxiclav used to treat?
- Gram positive and negative
- Anti-anaerobic action also
How often is co-amoxiclav to be taken?
3 times daily
What specifically can co-amoxiclav cause as a side-effect?
Drug induced liver injury in 13-23% (mild)
- positive blood test for 1,3 beta D-gucan with IV drug
What are resistant to co-amoxiclav?
- MRSA
- Nosocomial gram negatives (including pseudomonas)
What are the clinical uses of co-amoxiclav?
- Polymicrobial infections
- Beta-lactamase producing gram positives and negatives
What is the mechanism of co-amoxiclav resistance?
- ESBLS
- Impermeability
- Efflux
- Altered PBPs
What is piptazobactam made of?
- Piperacillin
- Tazobactam
How is piptazobactam administered?
IV
How often is piptazobactam administered?
3 - 4 times a day
What are side-effects of piptazobactam use?
- Hypernatremia
- Neutropenia
- Diarrhoea
What drug can piptazobactam interact with?
Methotrexate
What organisms are resistant to piptazobactam?
- MRSA
- Hospital acquired Gram negative organisms including pseudomonas
What can Vancomycin together with piptazobactam cause?
AKI
When are first generation cephalosporins usually used and what are they?
Surgical prophylaxis
- Cephalexin
- Cephalothin
- Cefazolin
- Cefadroxil
When are second generation cephalosporins usually used and what are they?
Obstetrics and gynaecology
- Cefuroxime
- Cefotetan
- Cefomandole
- Cefoxitin (CF)
When are third generation cephalosporins usually used and what are they?
Meningitis, streptococcal infections
- Cefotaxime
- Ceftriaxone
- Ceftazidime (P. aeruginosa)
What is a fourth generation cephalosporin and what organism is it usually used against?
Cefipime
- P. aeruginosa
What organism is cefuroxime not active against? (2nd generation cephalosporin)
Pseudomonas spp
What percent of patients with penicillin allergy also have cefuroxime allergy?
~ 10%
What can cefuroxime cause as a side-effect?
- C difficile
- Diarrhoea
- Gall bladder issues, RUQ pain
What is cefuroxime not active against?
- MRSA
- Certain gram negatives
What is cefuroxime used to treat?
- Meningitis
- Pneumonia
What is ceftazidime (3rd gen) used mostly for?
- Intra-abdominal infections together with metronidazole
- UTIs - especially when pseudonomas involved
- Do not use in community acquired (S pneumoniae) pneumonia
What does ceftazidine cover?
Gram positive and negative, including pseudomonas spp
What is the route of adminstration of ceftazidine?
IV
Give an example of a carbapenem
Meropenem
What is the spectrum of action of carbapenems (such as meropenem)?
- Gram positive, negative
- Anti-anaerobic
- Anti-pseudomonal
What are possible side-effects of carbapenems (such as meropenem)?
- Rule out penicillin and cephalosporin allergy (cross allergy around 1 - 9%)
- Rash
- Seizure
When are carbapenems (such as meropenem) usually used?
- Not typically used in hospital
- ICU, polymicrobial infections
Give 2 examples of glycopeptides
- Vancomycin
- Teicoplanin
What are glycopeptides (such as Vancomycin/Teicoplanin) used to treat?
- Problem gram positive infections - such as MRSA and C. difficile
How often are glycopeptides given and by what route?
1 - 2 times per day and by IV
What organism is resistant to glycopeptides?
VRE (Vancomycin-resistant enterococcus)
Describe how VRE develops resistance to glycpeptides?
Through alteration of its binding site
Describe the penetration into tissues of glycopeptides
They are large molecules so have poor penetration, none into CSF
What class of antibiotic is inhibits protein synthesis and is bactericidal?
Aminoglycosides (e.g gentamicin and Amikacin)
What is the route of administration of aminoglycosides (such as gentamicin and amikacin)
IV
What are the clinical uses of aminoglycosides (such as gentamicin and amikacin)?
- Used against gram negatives
- Used adjunct to serious systemic sepsis including pseudomonas
- Gram negative urosepsis
- Used with B-lactams for infective endocarditis
- Group B and enterococcal sepsis
Describe aminoglycoside penetration
- 100% water soluble
- Poor lung and CNS penetration
What are side-effects of aminoglycosides (such as gentamicin and amikacin)?
- Nephrotoxicity
- Ototoxicity
How often are aminoglycosides given?
Usually once daily
Describe the mechanism of microbial resistance of aminoglycosides
- Impermeability
- Efflux
What are macrolides given for?
- Pediatric infections in those who have allergy to penicillin
- Atypical pneumonias
- STIs
- Legionella (although usually quinolones given)
What are examples of Macrolides?
- Erythromycin
- Clrithromycin
- Azithromycin
What drugs affect nucleic acid metabolism?
- Quinolones
- Rifampicin
- Metronidazole
Why do drugs which affect nucleic acid metabolism have poor selective toxicity?
- Nucleotide synthesis and polymerisation is generally similar in bacteria and mammals, hence selective toxicity is poor
What are the only oral anti-pseudomonal agents?
Quinolones (ciprofloxacin, moxifloxacin, levofloxacin)
What are the clinical uses of rifampicin?
- TB
- Staphylococcal infections
What is metronidazole active against / used against?
- Anaerobes
- Bacteriodes fragilis
Give examples of quinolones
- Ciprofloxacin (mainly GI)
- Levofloxacin (mainly respiratory)
- Moxifloxacin (mainly respiratory)
In what patients are levo and moxifloxacin mainly used?
- Patients with Beta-lactam allergy and pneumonia
- Pseudomonal infection
- Atypical microbacterial respiratory infection
What are the clinical uses of fluoroquinolones
- Respiratory infections (TB, inhaled anthrax)
- Opthalmic infection
- Prostatitis
- Prophylaxis if exposed to meningococcal disease
What are possible side-effects of fluoroquinolones?
- Not used in pregnancy
- Photosensitivity
- Seizures
- Prolonged QT
- Tendon rupture
What patients do not tolerate antifolates?
Sulphur allergy
When are antifolates used clinically?
- Soft tissue infections
- Osteomyelitis
- PCP (Pneumocystis pneumonia)
What specifically do antifolates target?
Sulphonamides target Dihydopteroate synthase
- Human cells instead contain dihydrofolate reductase
- Trimethoprim targets dihydrofolate reductase
What are examples of antifolates?
- Sulphonamides
- Trimethoprim (inhibits dihydrofolate reductase, although inhibits the bacterial enzyme far more)
Why do membrane disorganising agents show poor slective toxicity?
Bacterial and mammilian membranes are very similar
What are examples of membrane disorganising agents?
- Amphotericin (an antifungal agent)
- Colistin (a polymixin)
- Daptomycin
Desribe the ideal antibiotic (magic bullet)
- Selectively kills pathogen
- Does not destroy microbiome
- Reaches and concentrates itself in the target organ
- Reach good levels in body fluids that are infected
- Minimally toxic
- Does not select resistance
- Inexpensive
What does linezolid kill?
All gram positives (including VRE and MRSA)
Name some bacteria that have developed a large amount of resistance to antibiotics
- Neisseria gonorrhea
- M TB
- Pneumococci
- H. influenzae
- Salmonella and shigella spp
- Beta-lactamase producing coliforms
- Many UTIs, resp diseases, diarrhoeal diseases
Name some resistant nosocomial infections?
- MRSA
- coagulase negative staphylcococci
- Multi-resistant enterococci
- Multi-resistant gram negative rods including pseudomonas spp, Klebsiella spp, enterobacter spp, Acinetobacter spp
What percentage of ED patients receive an antibiotic?
25 - 33%
What other than an antibiotic is given in meningococcal or pneumococcal meningitis?
Steroid
What is an example of a point-of-care test which can tell whether a patient has a viral or bacterial infection?
Pro-calcitonin - can be used in chest infections
- More bio-markers needed in the ED!!!
What drug is sulphonamide and trimethoprim combined?
Cotrimoxazole
