Antimicrobials 1 + 2 Flashcards
What is the goal of antimicrobial therapy?
Eliminate infectious organism without toxicity to host
What is the most important thing to try and augment when treating bacterial infection?
Natural defence mechanism
Give 3 examples of natural defences and when these may be compromised
- mucociliary escalator (cystic fibrosis)
- flushing effect of urination (catheter placement)
- normal gut flora (gut dysbiosis)
What are the 4 quadrants targetted by the antimicrobial spectrum? What else may “4 quadrants” of microbes also refer to?
- G+ aerobes/ G- aerobes/ Obligate anaerobes (G+-)/Penicillinase producing staph
- G+/G- aerobes/ G+/G- anaerobes
Give 4 examples of G+ aerobes
- Strep (B haemolytic)
- Enterococcus
- Pnumococcus
- Bacilli (lactobacillus, corynebacterium, listeria, erysopalathrix, arcanobacterium)
Give 6 examples of G- aerobes
- E. Coli
- Klebsiella
- Helicobacter
- Campylobacter
- Pastuerella
- Psuedomonas
Give 5 examples of staph
- aureus
- saphrophyticus
- epidermis
- haemolyticus
- capitis
Give 4 broad examples of anaerobes
- G+ spore forming clostridium (perfringens, botulinum, tetani)
- G+ bacilli (actinomyces, lactobacillus, bifdobacterium)
- G- bacilli (fragillis or not fragillis)
- Cocci (peptococcus niger)
Give 6 examples of atypical bacteria
- Rickettsia (not uk disease)
- Mycoplasma
- Chlamydia
- Borrelia
- Bartonella
- Mycobacterium
Where are many antimicrobial substances derived from?
Fungus
Give conditions when rational antimicrobial use can be justified
- bacterial infection definitively diagnosed
- OR highly likely
- disease will progress without medical therapy
- would casue critical illness if occourred and not recognised/treated
What essentially useless treatment should be given inlieu of prescribing antibiotics as a placebo because you don’t know what else to do?
Vitamin injection
Give some clues of bacterial infection
- heat, redness, swelling
- pyrexia (could also be viral/fungal/neoplasia)
- neutrophilia (stress leukogram)
- bacterial cause COMMON?!
Give 3 examples where ABx are commonly prescribed but a bacterial aetiology is rare
- V+ D- = acute gastritis due to eating rubbish etc. No bacteria casues V+D-! except helicobacter but v. rare
- Hameaturia in young cat <10y = idiopathic cystitis usually due to stress, will resolve within 5-7d. In DOGS haematuria indicates UTI but cat urine so concentrated these are RARE.
- Haemotochezia = no evidence of need for antimicrobials unless signs of sepsis seen
What 5 factors influence the success rate of ABx Tx?
- what bugs live where?
- bacterial susceptibility
- Pharmacokinetic phase - getting the drug to the infection
- Pharmacodynamic phase - Local conditions
- Client comlpliance
Give the 3 main sources of infection with egs.
- Environment
- mycobacteria, tetanus, contaminated food (campylobacter, E. Coli) - Other animals
- Bordatella - Internal
- GI (E. Coli, G-s, Anaerobes)
- Skin (Staph - S. Aureus, Strep in horses )
How does previous ABx Tx affect the decision making for rational ABx use?
changes susceptibility profile of bugs
How do horses differ from SAs with wound infection risks?
Strep ^ risk in horses than staph/
What bacteria usually causes mastitis in cattle?
Staph
How should sepsis of unknown origin be treated?
Cover all 4 bacterial quadrants
What is the common cause of pneumonia?
Difficult to predict bacteria
What is the common cause of endocarditis, arthritis or discospondylitis?
Staph -> systemic infection from the skin
What is the exception to the rule of bacteria which are resistant to a drug in vitro being resistant in vivo?
- stats based on blood concentration of drug
- > resistence may be overcome by high concentrations achieved in urine/topically
Define MIC. How is this used clinically?
Minimum inhibitory concentration
- lowest concentration of a drug to inhibit bacterial growth
- MIC90 used as therapeutic dose (conc that inhibits 90% bacterial isolates of a specific species eg. e coli, s. pseudointermedius)
Give 3 antimicrobials that inhibit cell wall synthesis
- penicillins
- cephalosporins
- bacitracin (usually used for eyes and ears)
Give 4 antimicrobials that inhibit cell membrane function. What are their usual usage?
- polymixins (eyes) Usually antifungals: - amphotericin B - imidazoles - nystatin
Give 5 antimicrobials that inhibit protein synthesis
- chloramphenicol
- macrolides
- lincosamides
- tetracylinces
- aminoglycosides (good for ears)
Which antimicrobial class have an ^ risk of side effects and why?
Protein synthesis inhibitors (chloramphenicol, macrolides, lincosamides) as act on element of bacterial cell that is similar to mammalian.
Give 5 antimicrobial classes that inhibit nucleic acid synthesis
- sulphonamides
- trimethoprim
- quinolones (enrofloxacin etc.)
- metronidazole
- rifampin (used rarely)
Is distinguishing bacteriostatic and bacteriocidal drugs clinically relevant?
Not really - just know that bacterioSTATIC = effect reversible once drug removed, and during Tx MIC should be maintained at site of infection throughout dosing interval -> specific dosing schedule and strict instructions necessary. Can work as bactericidal if dose is sufficiently high/prolonged.
- BacterioCIDAL = preferred when concern about site of infection or host defences as technically body defence not necessary. Killing action may be both TIME and CONCENTRATION dependent
Give 5 bacteriostatic antimicrobials
- chloramphenicol
- lincosamides
- macrolides
- tetracyclines
- non-potentiated sulphonamides
Give 6 bactericidal antimicrobials. Which are TIME and which are CONCENTRATION dependent?
Time - penicillins - cephalosporins - TMPS Concentration - aminoglycosides - fluoroquinolones - metronidazole
Which antimicrobials should not be used in conjuction with bacteriostatics and why?
Time dependent bacteriocidal as bacteria need to be multiplying for drugs to be effective
Is there any advantage to achieving >2-4x MIC in time dependant ABx?
No providing MIC is maintained for long duration
How is the efficacy of concentration dependant ABx determined? How does their activity differ to time dependent ABx?
Peak concentration OR area under the curve (-> time may play a role)
- optimum ratio is 8-10x MIC
- effective against dormant bacteria (don’t need to be multiplying to be effective
- CAN be used in conjunction with bateriostatics
What are the 4 colours used to code ABx activity?
- Green (excellent against most spp. in quadrant)
- Blue (good activity against many, some spp. resistant)
- Brown (moderate activity, many spp. resistant)
- Red (no useful activity against majority of bacteria in quadrant)
Which quadrant are good at developing resistance and why?
> G- aerobes
- plasmid transfer means can bypass slow mutation based resistnace
- produce B lactamase like Staph
Which quadrant are stupid when it comes to developing resistnace?
G+ aerobes - mutation based resistnace only
In tissues with adequate blood supply, what is distribution of a drug limited by?
Perfusion
- free drug conc in plasma directly related to interstitial space conc.
What may drug distribution be limited by other than perfusion? In which tissues may this be an issue?
Permeability
- lipid membrane forms barrier to drug diffusion if no cell pores
- brian
- eye
- prostate
- bronchus
- intracellular
- blood milk barrier
- poorly vascularlised tissues eg. bone fragments and heart valves
(adequate conc usually reached in living bone and synovial fluid)
When may normally tight cell junction eg. BBB become less tight? How may this affect therapy?
When inflamed eg. in infection
- > allows more substances than would normally be able to pass through barrier
- > MAY close junctions soon as infection begins to subside, meaning poor reach of drugs once again before complete clearance of the infection
Give 6 intracellular bacteria
- Bartonella
- Brucella
- Chlamydophila
- Mycobacterium
- Rickettsia
- Staphylococcus - facultative
What may affect a drugs ability to penetrate difficult to access areas?
Hydrophilic (less penetrating) v lipophilic (More penetrating)
What is the pharmacodynamic phase dependent on?
Local conditions
- abscess
- pus inactivates TMPS
- necrotic debris
- oedema (v concentration at site of infection)
- foreign material (-> phagocytes degranutalte to try and destroy FB, intracellular bactericidal substances depleted)
- presence of Hbg v penicillin activity
- v pH -> loss of activity (erythromycin, clindamycin, fluoroquinolones)
What is a glycocalyx?
Bacteria can form a biofilm at the site of infection and foreign material can protect bacteria from ABx and phagocytosis
What does post operative infection risk depend on?
- degree of contmaination
- virulence of organism
- health of patient
- local tissue health
What are the justifications for surgical prophylactic Abx?
Wound clean or dirty
- timing of surgery
- health of patient (Shock and emaciation, age, BCS, endocrinopathy)
- level of asepsis
- presence of implants
- surgical time (>90mins)
- surigcal technique (-> trauma)
- organs involved
- anaesthesia
- propofol administration (due to multidose vial?)
- clipping pre surgery ^ risk of infection
Give situations when surgical prophylaxis is indicated
- dental procedure (possibly)
- patients with leukopenia (viral or drug induced)
- contaminated surgery
- orthopaedic/major abdo/thoracic surgery
- surgical time >90 mins
- serious consequences of infection (play it safe!)
Can antiseptics compensate for lack of aseptic technique?
No
How should surgical prophylaxis be administered?
- should be present in wound at time of contamination
- no use 3-5 hours post surgery
- only single dose needed (not 5d course)
What are the most likely contaminants of surgical wounds?
- skin: staph aureus
- GIT: anarobes and G- aerobes
What are the 2 most useless drugs for surgical prophylaxis in SA?
> Amoxycillin (aminopenicillin)
- Useless against penicillinase producing staph - most common wound infection in SA. (Not the same in horses as staph (G+ aerobe) most common infectant.
Long acting form of amoxycillin (LA)- takes 12 hrs to reach therapuetic doses
What is the commonest best drug for surgical prophylaxis? What is this influenced by?
- Influenced by type of surgery
> 2nd gen cephalosporin eg. cefuroxamine (Zinacef) [not vet registered]
> 1st gen cephalosporin [okay, not great] - give IV at time of induction if possible
- If SC/IM give at least 1-2hrs pre-surgery
