Antibiotic mechanisms and indications

The mechanisms and uses for several groups or antibiotics are described below but resistance and preferred antibiotic choices may vary between local regions and hospital. Please refer to these when considering antibiotic choice for different infections.

Antibiotic group	Mechanism	Indications	Examples	Side effects and contra-indications
Penicillins (Benzylpenicillin, phenoxy-methylpenicillin)	Binds to penicillin binding protiens and inhibits the last stage of cell wall synthesis causing cell lysis.	Narrow spectrum – effective against streptococcus (e.g. group A strep, strep pneumonia, s.viridans) Occaisionally effective against non penicillinase producing staphylococcus. Aminoglycosides can be added synergistically against Group B strep, s viridans and enterococcus faecalis.	Respiratory infections. Syphilis.	Anaphylaxis/ hypersensitivity
B lactamase resistant penicillins: flucloxacillin (also methicillin and others)	Flucloxacillin is a semisynthetic penicillin which is resistant to hydrolysis by b lactamases.	Flucloxacillin: Staphylococcus infections (which mostly produce b lactamase) Also streptococcal infections	Skin + soft tissues, osteomyelitis, Otitis media, Endocarditis.	Cholestasis
co-amoxiclav (amoxicillin and clavulanate acid)	Clavulanate acid is a suicide inhibitor (irreversibly inhibits) of the b lactamase enzyme	Amoxicillin is effective against streptococcus and enterococcus with variable activity on some gram –ves. The addition of clavulanate acid makes amoxicillin effective in Staphylococcal, anaerobes, coliforms, and respiratory gram –ves.	Amoxicillin: Respiratory tract infections, otitis media, oral infections, UTIs. Coamoxiclav: Above + cellulitis, animal bites, Bone and joint infections, GU and abdominal infections	Hypersensitivity Cholestasis/jaundice
Cephalosporins	Also B lactam antibiotic less susceptible to B lactamases compared to penicillins.	1st generation (cephalexin) is effective against staphylococci and streptococci. 2nd generation (e.g. Cefuroxime) is additionally effective against coliforms and respiratory gram –ves.  With some effect on anaerobes. 3rd generation adittionally have some activity against ESBLs.  2nd and 3rd generation are less effective against gram +ves. Some 3rd generation cephalosporins such as ceftazidime are effective against pseudomonas.	Cefalexin: respiratory tract infections, UTIs, cellulitis/soft tissue, otitis media Cefuroxime: CAP, pyelonephritis, soft tissue infection. intrabdominal sepsis, prophylaxis in GI surgery. Ceftriaxone: also used in meningitis.	Hypersensitivity Liver toxixity.
Carbapenems (meropenem)	Class of b lactam antibiotic – binds to penicillin binding protein and blocks cell wall synthesis.	Broad spectrum- effective against both gram +ve and gram –ve bacteria – carbapenemase producing enterococci are resistant to carbapenems.	Hospital acquired infections, Respiratory tract infections in cystic fibrosis, meningitis.	Hypersensitivity Imipenem can induce seizures.
Glycopeptides (vancomycin, teicoplanin)	Inhibits cell wall formation by stopping NAG peptides from being incorporated into the peptidoglycan matrix	Effective against MRSA and gram +ves (strep, staph, enterococcus, gram +ve anaerobes)	Not absorbed well in gut – used in C diff orally, MRSA and other gram +ve infections when given IV.	Nephrotoxicity Ototoxicity Red man syndrome
Daptomycin	Lipopeptide antibiotic - Binds onto membrane of gram +ve bacteria causing depolarization and loss of membrane potential which affects protein, DNA and RNA synthesis.	Effective against gram +ve bacteria including MRSA.	Complicated skin and soft tissue infections.	Muscle cramp and raised CK.
Oxazolidinones (linezolid)	Binds to P site of ribosome 50s unit affecting protein synthesis.	Effective against gram +ves (strep,staph, enterococcus, gram +ve anaerobes) including MRSA  Vancomycin resistant enterococci.	Complicated soft tissue infection or other gram +ve infection where other antibiotics cannot be used.	Cytopenias Bone marrow suppression. Can cause optic neuropathy rarely. Avoid in acute confusion, Bipolar, carcinoid, pneochromocytoma, schizophrenia, uncontrolled hypertension and thyrotoxicosis.
Macrolides (Erythromycin, azithromycin, clarithromycin)	Binds to 50s ribosome units affecting protein synthesis.	Atypical bacteria e.g. mycobacteria, legionella.	Atypical pneumonias, Pertussis (whooping cough), Chlamydia, Gonorrhoea.	Thrombophlebitis, Cholestatic hepatitis
Clindamycin (macrolide)	Affects protein synthesis	Affective against staphylococcus and streptococcus	Soft tissue infection including necrotizing fasciitis.	Antibiotic associated colitis.
Aminoglycosides (gentamicin, tobramycin, amikacin)	Binds to the 30s ribosome subunit affecting protein synthesis.	Gram negative infections including pseudomonas, coliforms, ESBL – but not against anaerobes. Some gram +ve activity but not preferred due to being less effective and more toxic.	Gram –ve infections and synergistically in endocarditis. Tobramycin is used in pseudomonas and amikacin for mycobacteria.	Nephro-toxicity, ototoxicity.
Quinolones (ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin)	Inhibit topoisomeras II (DNA gyrase) and topoisomerase IV leading to inhibition of DNA sythesis	Primarily gram –ves including coliforms, respiratory gram –ves and pseudomonas. Some effect on gram +ves.	GI infections (e.g. in crohns), pseudomonal infections, in TB in combination with other drugs.	Hallucinations, psychosis, Lowers seizure threshold Tendon damage and rupture Cartilage damage in studies (avoided in children) Prolonged QT
Tetracyclines (Doxycycline)	Binds to 30s subunit blocking the binding of aminoacyl-tRNA.	Atypical bactreia with some action on some gram –ve  (coliforms and respiratory gram –ves) and staphylococcus.	Acne, Lymes disease, Chlamydia, Atypical pneumonias (e.g. mycoplasma) Rickettsia, Q fever, malaria prophylaxis	Photosensitivity, renal impairment, deposition in growing teeth and bones, dental hypoplasia.
Tigecycline	Binds to 30s ribosomal subunit blocking amino-acyl tRNA  stopping peptide chain production.	Gram +ves including MRSA, and gram –ves including anaerobes. Not effective against VRE , ESBL and pseudomonas. Effective against atypical bacteria.	Complicated skin infections including MRSA, abdominal sepsis.	Pancreatitis, Raised transaminases
Metronidazole, Tinidazole	Forms free radicals in anaerobic bacteria.	Affective against anaerobics	C diff, Amoebiasis, giardiasis.	Disulfiram like effects with alcohol.
Sulfonoamides (sulfamethoxazole, co-trimoxazole)	Anti folate – sulfamethoxazole competitively binds to dihydrofolate synthetase which convert p-aminobenzoic acid (PABA) into folic acids. Trimethoprim inhibits dihydrofolate reductase.	Some gram –ves and gram +ve, e coli and listeria.	Urinary infections, Pneumocystis Jirovecii infections	Agranulocytosis, Bone marrow suppression, stevens-johnson syndrome.
Nitrofurantoin	Damages macromolecules including ribosomes. Effects DNA, RNA, Protein and cell wall synthesis	Used in urinary infections	Urinary infections	Agranulocytosis, cholestatic jaundice, hepatitis.
Rifampicin	Inhibits RNA synthesis by binding to RNA polymerase.	Broad spectrum against many gram +ve and some gram –ve infections including MRSA (although not used alone due to resistance), pseudomonas and particulary atypicals including mycobacteria	In combination for TB and other mycobacterial infections. In combination for brucellosis, legionnaires, and MRSA infections. In combination for endocarditis.	Contraindicated in acute porphyria and jaundice. Causes orange coloration of secretions. Deranged  hepatocellular LFTs.
Chloramphenicol	Binds with L16 protein of the 50S subunit of ribosomes irreversibly inhibiting protein synthesis.	Broad spectrum against most gram +ves including MRSA, staph and strep, anerobes, and gram –ves including respiratory gram –ves and coliforms. Not effective against pseudomonas.	Conjunctivitis, Only used in life threatening infections due to risk of serious blood disorders. Haemophoilus infection, Cholera and typhoid	Avoid in acute porphyria. Aplastic anaemia and other blood disorders with reports of lukaemia. Peripheral neuritis.

References:

1) Various pages from the online BNF
2) various pages from www.drugbank.ca
3) various pages from www.passmedicine.com
4) Kalra PA (Ed), Essential Revision Notes for MRCP (4th Ed), Cheshire, Pastest, 2015