Antibiotic classes Flashcards
B-Lactams (types, MoA, indications)
Drugs:
- Penicillin G
- Penicillinase resistant penicillins: fluclox
- Aminopenicillins: Ampicillin, amoxicillin
- Antipseudomonal: piperacillin, ticarcillin
- (Often combined with B-lactamase inhibitors including clavulanic acid (co-amoxyclav), tazobactam (pip-taz)
MoA:
- Bactericidal. B-lactam acts as a cell wall inhibitor by binding to PBPs
Indications:
Penicllin G:
- GPC: staph/strep/entero-cocci. Staph aureus is mostly resistant to penicillin. Strep and enterococci are sensitive.
- GPB: Clostridium mostly sensitive, except c. difficile which is not
- GNC: N meningitidis and N. gonorrhoea sensitive
- GNCB: H. influenzae sensitive
- GNB: Resistant to penicillins (eg E. Coli, Klebsiella, Enterobacter, salmonella) except syphilis is sensitive
Flucloxacillin: used in S. aureus infections
Amocillin/ampicillin: added gram negative coverage
Co-amoxyclav: improved gram positive cover eg S.aureus
Piperacillin/ticarcillin: used to treat P. aeruginosa as well as febrile neutropenia
Flucloxacillin notable side effects
Increased risk of hepatitis (monitor LFTs)
Cephalosporins: drugs, MoA, indications
Carry increasing gram negative coverage through generations
MoA: Bactericidal. Interfere with cell wall synthesis by binding to PBPs
Indications:
All don’t cover enterococcus
1st generation (cephalexin, cephazolin)
- Covers gram positives and some common gram negatives such as E. Coli
- No MRSA, enterococci or anaerobe coverage
2nd generation (rarely used)
- Covers gram positives well and also enhanced gram negative coverage - H. influenzae
- Cefoxitin has some coverage against anaerobes
3rd generation (ceftriaxone)
- Less gram positive coverage
- Enhanced gram negative activity
- If penicillin allergic, can use ceftriaxone eg in moderate community acquired pneumonia
4th generation (ceftazidime, cefepime)
- Ceftazidime: covers gram negatives such as Pseudomonas, but poor against S. aureus
- Cefepime: covers gram negatives such as Pseudomonas and has gram positive activity against S. aureus
5th generation: (rare use)
- Ceftaroline: gram positive including S. aureus, gram negative except Pseudomonas
- Ceftolazane: gram negatives including Pseudomonas
Cephalosporin side effects
Thrombophlebitis (in IV form)
Allergy (cross-reactivity 10% with penicillins)
Increased bleeding (decreased vitamin K, which is synthesized by gut microbes)
Diarrhoea
Sludge in GB and CBD
Nephrotoxicity
Glycopeptides (vancomycin): MoA, Indications
MoA: Bactericidal. Binds to the terminal D-ala-D-ala structure of peptidoglycan, hence is a cell wall inhibitor
Indications:
- GPC only
- Vancomycin is the drug of choice if treating MRSA
- Also used if anaphylactic to B-lactams
- Oral vanc can be used in in c. diff colitis, although metronidazole is first line
Vancomycin side effects
Red man syndrome - treat with anti-histamines
Thrombophlebitis - slow the infusion rate to avoid this
DRESS syndrome - Drug reaction with eosinophilia and systemic symptoms
Ototoxicity
Nephrotoxicity
Carbapenems: drugs, MoA, indications
Meropenem, imipenem
MoA: Bactericidal. Cell wall synthesis inhibitor - able to resist hydrolysis by many B-lactamases.
Indications:
Good broad spectrum cover: gram positives (except MRSA), gram negative, anaerobes
Aminoglycosides (gentamicin): Drugs, MoA, Indications
Drugs: gentamicin, tobramycin, streptomycin
MoA:
Bactericidal. Inhibit the 30S subunit of ribosomes to inhibit protein synthesis.
Indications:
Gram negative infections
Useful against S. Aureus
Used synergistically with cell wall active agent (eg penicillins) against Gram positives in:
- Enterococcal endocarditis
Streptococcal endocarditis
- Used synergistically with cell wall active agent (eg penicillins) against gram positives in enterococcal endocarditis, streptococcal endocarditis
Gentamicin side effects
Renal toxicity
- Due to ATN
- More important to save the patient and give them a renal hit as can dialyse and renal function returns (reversible)
Ototoxicity
- Irreversible damage, badly impacts balance through vestibular damage
- Can also cause cochlear damage leading to tinnitus
Need tight monitoring of levels - at 30 minutes and 2 hours post dose
Tetracyclines (doxycycline): drugs, MoA, indications
Doxycycline, minocycline
MoA:
Inhibitor of protein synthesis through inhbition of 30S subunit of ribosomes
BACTERIOSTATIC
Indications:
Used in coverage of atypical pneumonias
- Mycoplasma pneumonia
- Legionella
- Chlamydia psitacci
Chlamydia trichomonas
- First line treatment
Tick borne bacteria - Rickettsial infections
Severe acne
Faecal clearance means safe for use in kidney dysfunction
Doxycycline side effects, contraindications
S/E:
Skin photosensitivity
Suppresses normal gut flora, may cause diarrhoea and bacterial overgrowth
Absorption decreased by multivalent cations - calcium, iron, magnesium
Contraindications: pregnancy (due to teeth and bone deformities, and in children <8 due to tooth discolouration)
Lincosamides (clindamycin, lincomycin): MoA, Indications
MoA:
Inhibits the 50S subunit of ribosomes to inhibit protein synthesis. Bacteriostatic.
Indications:
Anaerobic gram-negative infections (bacteriodes, fusobacterium, prevotella)
Aerobic gram-positive cocci:
Some members of staphylococci and streptococci, but not enterococci or MRSA
Clindamycin side effects
Serious risk of C. diff colitis which limits use
(C. diff colitis mainly associated with “C” antibiotics - clindamycin, cipro, ceftriaxone)
Rash
High dose associated with metallic taste
Macrolides (-omycin): drugs, MoA, indications
Azithromycin, erythromycin, clarithromycin
MoA: Act as inhibitors of protein synthesis
- Inhibit the 50S subunit of ribosomes
- Bacteriostatic
Indications:
Often used in penicillin allergy or as alternative to tetracyclines eg in pregnancy
Community acquired pneumonia:
- Strep. Pneumoniae
- H.Influenzae
- M.Catarrhalis
Atypical pneumonia:
- M.pneumoniae
- Legionella
- Chlamydia pneumoniae
Used as a single dose for Chlamydia trichomonas (STI) (alternative to doxycyline)
Neonatal infections - C. trachomatis (pneumonia), N. gonorrheae
Diphtheria
H.Pylori triple therapy: clarithromycin, ampicillin, PPI
Macrolide side effects
Increased QT -> torsades
Increased gastric motility
Associated with cytochrome p450 inhibition
Bactrim (trimethoprim-sulfamethoxazole) MoA, indications
MoA: Folic acid synthesis inhibitors
Combined as they inhibit sequential steps in the synthesis of folate.
Selective against bacteria as humans do not synthesize folate, they acquire from diet
Bacteriostatic
Indications:
PJP pneumonia/prophylaxis
UTI
URTIs, pneumonia
Fluoroquinolones (ciprofloxacin) drugs, MoA, indications
Ciprofloxacin, norfloxacin, moxifloxacin
MoA:
Bacterial topoisomerase inhibitors (inhibit DNA replication)
Bactericidal
Work well in rapidly dividing bacteria
Indications:
- Gram negative infections and most gram positives
- Very effective against PSEUDOMONAS
- Complicated UTIs, prostatitis (if resistant to trimethoprim or cefalexin)
- Gram negative OM
- Bacillus anthracis
Ciprofloxacin side effects
Risk of prolonged QT -> can lead to torsades
Tendon/cartilage damage, particularly in the elderly and those on steroids. Risk of Achilles tendinopathy/rupture
Teratogenic: c/i in pregnancy and those <10
Metronidazole: MoA, indications
Nitroimidazoles - metro/tind-azole
MoA:
Disrupt DNA strands through interfering with electron transport, leading to formation of ROS
Bactericidal
Indications:
ANAEROBES
Good against protozoal infections: giardia, entamoeba, trichomonas vaginalis
First line in C. Diff colitis
Metronidazole side effects
Alcohol has an antabuse effect (instruct patient to cease alcohol 24 hours before and until 24 hours after last metro dose)
Chloramphenicol
Inhibits protein synthesis
Gram +, gram -, anaerobes, rickettsiae
Used to treat bacterial meningitis
Used also to treat bacterial conjunctivitis and ear infections
Rifampicin
RNA polymerase inhibitor - bactericidal
Used in TB
Turns urine, sweat, saliva orange
Contraindicated in pregnancy
Fusidic acid
Inhibits protein synthesis - bacteriostatic
Used in gram positives esp staph
Good for staph osteomyelitis
Give with another anti-staph agent
Anti-fungals: Types, MoA
Most anti-fungals currently used are membrane-active compounds
They inhibit the production of the sterol ergosterol in the cell membrane
This method works because ergosterol is a major component of the fungal, but not the human, cell membrane
Fluconazole
- The azole group of antifungals (eg fluconazole) inhibits the cyt p450 activity in the ergosterol pathway
○ May interact with other drugs (Eg cyclosporine) where the cyt p450 is also targeted
- It has excellent penetration into the CSF and peritoneum
Indicated for:
○ Candida species in surgical patients (oral fluconazole is the agent of choice in most cases)
○ Cryptococcosis in non-immunocompromised patients
○ Long-term suppressive treatment of cryptococcal meningitis
○ Oesophageal candidasis in AIDs patients
Side effects
○ Nausea, abdo pain, dry mouth, diarrhoea, skin rash
○ Dose dependent hepatotoxicity can occur (eg in AIDS patients)
Polyenes (eg amphotericin B) inhibit in some way the amount of ergosterol in the membrane
- Cells lacking in sufficient ergosterol in the membrane ‘leak’ and die
Amphotericin B has some effects on the membranes of human cells
- Well documented toxicity profile is noted
- Hence, usually reserved for situations where WCC numbers are impaired (eg neutropenia)
Nystatin (polyene) is presently only available as a cream/ointment for topical use (usually for lesions involving mouth/vagina)
- It is not absorbed from the gut following oral administration
Griseofulvin is only active against dermatophytes (ringworm fungi)
