Antibiotics Flashcards
(29 cards)
What antibiotics place someone at risk of C diff?
4C’s - clindamycin, cephalosporin, co-amoxiclav
Antibiotics which inhibit cell wall synthesis?
penicillin
cephalosporins
carbapenems
vancomycin
Antibiotics which inhibit folic acid metabolism?
trimethoprim
sulphonamides
Mechanism of action of ciprofloxacin?
DNA gyrase inhibitor
Mechanism of action of rifampicin?
DNA directed RNA polymerase
Inhibit protein synthesis - 50S
erythromycin
clindamycin
chloramphenicol
macrolides
Inhibit protein synthesis - 30S
Gentamicin
Amikacin
tetracycline
linezolid
Antibiotics which are bacteriostatic
ECSTaTiC
erythromycin clindamycin sulfamethoxazole trimethoprim tetracycline chloramphenicol
Antibiotics which are bacteriocidal
Very Finely Proficient At Cell Murder
V - vancomycin F - fluoroquinolones P - penicillin A - aminoglycosides C - cephalosporins M - metronidazole
What antibiotics to avoid in someone who is breastfeeding?
nitrofurantoin - may cause hemolysis in G6PD infants
ciprofloxacin
Prosthetic joint infection
- antibiotic with good bone penetration
- antibiotic with good biofilm penetration
bone - fluoroquinolones
biofilm - rifampicin
Indications for change from IV to oral route for antibiotics
Apyrexial for 48 hours (<38C) and no unexplained tachycardia
clinical improvement
oral diet tolerated and no impaired GI absorption
WBC and CRP improving
suitable oral alternative
Indications for meropenem
Febrile neutropenia (haematology/oncology sepsis protocol)
2/3rd line treatment for ventilator associated pneumonia or sepsis in ITU setting
neurosurgical patients
exacerbation of CF or bronchiectasis
Linezolid what is it good for? Indications? SE route
Gram+ve: MRSA, VRE
pneumonia, bacteraemia
Prolonges used: bone marrow suppression, optic neuropathy
oral or IV
Daptomycin what is it good for? Indications? SE route
Gram +ve: S aureus, VRE
SSTI
SE: myositis, rhabdomyolysis
Inactivated by lung surfactant
IV only
Beta-lactams
- examples
- mechanism of action
- caution
- clinical uses
- SE
Penicillin
Cephalosporins: 1st, 2nd and
3rd generation
Anti-pseudomonal penicillins
B-lactam and beta-lactamase inhibitor combinations
Carbapenems
Mechanism of action = Target PBP → stops peptidoglycan production leads to cell lysis (bactericidal)
- Inhibits enzymes that catalyse the final step in bacterial cell wall assembly
Caution - Renal excretion: adjust dose in renal impairment
Mechanisms of resistance
- Altered PBP - target reduced affinity binding (mecA in S. aureus = MRSA)
- Destruction by beta-lactamase (some can be overcome by also giving beta-lactamase inhibitor)
- Gram –ve: altered outer membrane proteins → reduced penetration
- Gram –ve: efflux pumps
Clinical examples Penicillin
Cellulitis - Expect: S. aureus; Streptococci; Use: flucloxacillin
Community-acquired pneumonia
- Expect: S. pneumonia; H. influenza
Use: Amoxicillin (empirically; until +ve culture) or co-amoxiclav based on CURB-65 score (+/- clarithromycin)
Proven sensitive S. aureus infection
- E.g. infective endocarditis, bone & joint infection
- MSSA – not MRSA
- Use: Flucloxacillin (superior choice in non-penicillin allergic patients)
Asplenic? - Lifelong penicillin V prophylaxis against S. pneumonia & N meningitides & Vaccines
Penicillin SE (similar for all beta-lactams)
Allergy - Skin rashes <10%; anaphylaxis <0.4%
Liver injury - Cholestasis or hepatitis
- Esp. flucloxacillin (hepatitis) & co-amoxiclav (cholestasis)
Interstitial nephritis - Microscopic haematuria, leucocyturia, high creatinine, low GFR
Antibiotic-associated diarrhoea
Piperacillin
- good against
- mechanism of action
- clinical uses
Anti-pseudomonal penicillins
Good against P. aeruginosa
P. aeruginosa = inherently drug resistant vie efflux pumps, altered microbial targets (e.g. topoisomerase) and production of beta-lactamases and enzymes that inactivate aminoglycosides
Comes in combination with Tazobactam (beta-lactamase inhibitor) = piperacillin-tazobactam (aka Tazocin)
Use: hospital acquired pneumonia, intra-abdominal infection, neutropenic sepsis, proven P. aeruginosa infection
Glycopeptides
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses (IV, oral)
- SE
Vancomycin (& teicoplanin)
Mechanism of action = Cell wall synthesis inhibition – prevent elongation of peptidoglycan chain by binding to D-alanyl-D-alanine tail of peptides
Spectrum
- Gram +ve; MRSA
NOT for gram –ve; VRE
IV
Severe MRSA infections (consider in nosocomial infection)
Gram +ve infections in penicillin-allergic patients
Pencillin-resistant S. pneumonia
Oral = c. difficile infection
Vancomycin
- Measure trough levels to guide dosing and dosing interval
- IV - systemic infection – no useful oral bioavailability
- Bactericidal
- Time dependent killing – want to be giving it as often as possible so reduce dose rather than increase dosing interval
- Renal excretion
SE
- Nephrotoxic – monitor renal biochem
- Ototoxic
- ‘Red man’ syndrome (if this occurs then decrease infusion rate)
Aminoglycosides
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
• Irreversible inhibition of protein synthesis
o Binds to 30S subunit of prokaryotic ribosome → interferes with mRNA translation
o O2 dependent transport – not for anaerobes
o Good against gram -ve
• Gentamicin
o Bactericidal; IV (poor oral absorption)
• Concentration dependent killing
• Renal excretion
✓ Gram –ve: Pseudomonas, S. aureus (some MRSA), enterococci
Some resistance: gram –ve, many gram +ve
o Empiric therapy – for gram –ve cover
• Sepsis of unknown origin - bacteraemia
• UTI – cystitis, pyelonephritis
• Neutropenic sepsis
o Synergistically with beta lactams/ vancomycin in endocarditis
o SE:
• Nephrotoxic (5-25%)
• Ototoxic (may be irreversible)
• Worsen myasthenia gravis – So avoid in MG
o Monitor trough levels; renal biochemistry; ask daily about tinnitus and vestibular signs (levels don’t correlate with toxicity)
o Do not use for >72 hours without discussion with micro (high risk ototoxicity)
• Routes: im or IV, topical
• PK
o Vd = ECS (25% body weight)
o Adjust maintenance dosing based upon [creatinine]
o Plasma monitoring necessary
• Used
o Pneumonia, MRSA, wide variety of Gram –ve & some gram +ve bacteria
o Upper resp. tract procedures
o Endocarditis o Bacteremia, sepsis o Skin infections (topical) o UTIs o GI / GU procedures
• SE:
o Ototoxicity; Nephrotoxicity
o Vestibular toxicity - May be reversible; Not able to walk in straight line
o NMJ blockade (high dose)
o Pregnancy – used with caution - Cat C (8th nerve) – baby’s ear
• Resistance - Aminoglycoside modifying enzymes; Modified binding site; Efflux pump
Quinolones
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
Ciprofloxacin; Levofloxacin; Moxifloxacin
Interfere with bacterial nucleic acid synthesis by inhibiting
• Bacterial DNA gyrase (DNA supercoiling) in gram –ve
• Topoisomerase IV (DNA relaxation) in gram +ve
Ciprofloxacin
• Bactericidal
o Oral or IV
o Reach high conc. in lung, bile, prostate
o Renal excretion +/- hepatic metabolism
• ✓ Gram –ve: Pseudomonas
• ✓ Atypical pneumonia organisms (Chlamydophila, mycoplasma, legionella) & TB
• ✓ Some S. aureus (inc. MRSA), anthrax
• NOT good for many gram +ve
• Clinical use
o Atypical pneumonia organisms
o Pseudomonas in CF
o Gram –ve bone and joint infections
o Pyelonephritis
o Prostatitis
o Gonorrhoea
• SE
o Diarrhoea, nausea & vomiting (common)
o Reduced seizure threshold (NOT suitable in epilepsy)
o Tendon rupture (don’t use in children)
o QT interval prolongation – consider getting baseline ECG
o High risk of precipitating C. difficile infection
Macrolides
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
• Inhibit protein synthesis by preventing peptide chain elongation - bind to 50S ribosomal sub-unit (causing dissociation of peptidyl-tRNA from the ribosome) → bacteriostatic
• Clarithromycin; Erythromycin; Azithromycin
o Once a day; Oral or IV
o Good intracellular penetration
o Hepatic metabolism → P450 enzyme inducer
• Use:
o Community acquired pneumonia
• CURB65≥2 (+ amoxicillin) for atypical organism cover
• CURB 65 0-1 if penicillin allergic
o Skin infection - Mild cellulitis if penicillin allergic
o H pylori eradication (+ amoxicillin + PPI)
o STIs
• Similar spectrum to penicillin – so good in patients with penicillin allergy
✓ Gram +ve
• Staph aureus
• Strep. Pneumoniae
• Group B streptococcus
• Bordetella pertussis
• C difficile
• Non-tuberculous mycobacteria (Mycobacterium avium-intracellulare) – immunocompromised patients
✓ Gram –ve
- Campylobacter
- N gonorrhoeae
- Chlamydia
- Legionella pneumophila
- Rickettsia
- Salmonella typhi
- H pylori
- Listeria
✓ Atypical pneumonia organisms – Chlamydophila, Mycoplasma, legionella
✓ Lyme disease – Borrelia burgdoferi
✗ most gram -ve
• SE:
o GI upset (diarrhoea, nausea, vomiting)
o Hepatotoxicity
o Rash
o Increase QT (do baseline ECG & check if other drugs also have this SE)
o Thrombophlebitis (IV)
o If administered with statin – higher risk of myositis – so stop statin
o Erythromycin – nausea
• Resistance - Efflux pump; Modified binding site
Lincosamides
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
Clindamycin
Inhibit protein synthesis by preventing peptide chain elongation via binding to 50S ribosomal sub-unit (causing dissociation of peptidyl-tRNA from the ribosome) • Bacteriostatic • Oral or IV • Good tissue penetration – esp bone • Liver & renal excretion
✓ Gram +ve: S aureus, streptococci
✓ Anaerobes
✓ Pneumocystis jirovecii
✓ Plasmodium falciparum malaria
✗ Most gram -ve
Use:
• S aureus bone & joint infection
o Not 1st /2nd line due to risk of C difficile
• Necrotising fasciitis (or very severe soft tissue infection)
o Needs urgent surgical debridement
o Clindamycin (+flucloxacillin + ben-pen + gentamicin + metronidazole)
SE: • Diarrhoea • Rash • Hepatotoxicity • Leucopenia & thrombocytopenia • High risk of precipitating C. difficile infection
Tetracyclines
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
Tetracyline (1st G)
Doxycyline (2nd G)
Tigecycline (3rd G)
Bacteriostatic – inhibit protein synthesis by blocking tRNA binding via reversibly binding to 30S ribosomal sub-unit
Tetracycline • Chlamydia trachomatis o Eye infection (trachoma), urethritis, LGV • Respiratory tract infection: o Chlamydia psittacosis o Mycoplasma pneumonia (but usually use clarithromycin) • Pharma o Oral o Renal excretion • SE o Nausea, vomiting, diarrhoea o Oesophageal irritation o Photosensitivity o Deposited in growing bones/teeth (avoid in <12 yo and pregnant/breastfeeding women) o Hepatotoxicity o Exacerbate renal impairment (not doxycycline) o Idiopathic intracranial hypertension
Doxycycline • Broad spectrum • Uses: o Resp. tract infection → CAP; HAP; COPD; LRTI • Haemophilus influenzae • Staph. Aureus • Moraxella catarrhalis • E coli • Klebsiella pneumoniae o Mild MRSA cellulitis o Bacterial pneumonia, acne vulgaris, sinusitis, SSTI (good against staph) o Atypical pneumonias – chlamydia, mycoplasma o STI – chlamydia, LGV, syphilis o Insect borne infections – rickettsia, borrelia • Oral agent • GI excretion • Good tissue penetration • Variable resistance o Gram –ve: E coli, Enterobacter, Klebsiella, Haem influenza o Gram +ve: Strep pyogenes, Strep pneumonia, Staph aureus • Problems o Phototoxicity o Upper GI symptoms o Secondary intracranial hypertension o Teratogenicity o Teeth discolouration
Tigecycline
• Broad spectrum
• MRSA, VRE
Trimethoprim
- examples
- mechanism of action
- good against? bad for?
- caution
- clinical uses
- SE
• Interferes with folate synthesis by inhibiting bacterial dihydrofolate reductase
o May be bacterio-static or –cidal
o Oral
o Good tissue penetration – kidney, lung, sputum, prostate
o Renal excretion
o Synergises with gentamicin and sulfamethoxazole
• Do not use in 1st trimester – teratogenic
• Avoid with other anti-folate drugs → methotrexate
✓ Many gram +ve (inc. MRSA)
✓ Most gram –ve
✗ Pseudomonas; anaerobes
• Indication:
o Lower UTI
• In systemically well patient
• 3 day course females; 7 day course males
o Oral MRSA treatment - Combined with rifampicin or fusidic acid
• SE:
o Nausea, vomiting, diarrhoea
o Suppression of haematopoiesis (contra-indicated: blood dyscrasias)
o serum creatinine (competitively inhibits tubular secretion of creatinine resulting in temporary – reversed when drug is stopped; no change in GFR)
o Steven Johnson syndrome (co-trimoxazole); Myelosuppresion
