Part 2

•Drugs

Antibiotic spectrum

Gram positive Gram negative

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pyo ESBL Atypicals

Antibiotic

MRSA and Coagulase-

negative Staph.

Enterococcus faecalis &

Enterococcus faecium

Gut bacteria

e.g. E. coli

Anaerobic Streptococci & Clostridia

Streptococcus pneumoniae &

Group A, B, C, G

Respiratory Gram -ve e.g. Haemophilus influenzae &

Moraxella catarrhalis

Extended-spectrum beta-

lactamase producers & other

resistant Gram negatives

Pseudomonas aeruginosa

Legionella, Chlamydia & Mycoplasma pneumoniae

Bacteroides fragilis

Green = Generally Sensitive; Orange = Unreliable; Red = Generally Resistant

New Antibiotics

• New antibiotics are always becoming available to fight resistance – right?

1930 1940 1950 1960 1970 1980 1990 2000 2009

Sulphonamides PenicillinAminoglycosides

ChloramphenicolTetracyclines MacrolidesGlycopeptides

QuinolonesStreptogramins

LipopeptidesOxazolidinones

OritavancinTelevancinDalbavancinCeftobiproleCeftaurolinIclaprim

Phase III trials

Antimicrobial Resistance

• Antibiotic use causes resistance through selective pressure.

• Broad spectrum antibiotics select for resistant pathogens by eradicating natural flora.

• Current problems with resistant organisms MRSA - methicillin resistant Staphylococcus aureusVRE - vancomycin resistant enterococci ESBL - extended spectrum betalactamase

PenicillinsGram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Psued ESBL

Benzylpenicillin & phenoxymethylpenicillin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Psued ESBL

Flucloxacillin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Psued ESBL

Amoxicillin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Psued ESBL

Amoxicillin-clavulanate / Co-amoxiclav (Augmentin®)

Cephalosporins

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Cefalexin (1st generation)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Cefuroxime (2nd generation)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Cefotaxime & Ceftriaxone (3nd generation)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Ceftazidime (Anti-pseudomonal)

MRSA cover

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Vancomycin & Teicoplanin (Glycopeptides)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Linezolid

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Daptomycin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Sodium fusidate (not used alone)

Tetracyclines & Anti-folates

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Doxycycline

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Tigecycline

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Trimethoprim

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Co-trimoxazole (Septrin)

Macrolides & Clindamycin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Erythromycin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Clarithromycin & Azithromycin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Clindamycin

Quinolones & Aminoglycosides

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Ciprofloxacin / Ofloxacin (Quinolones)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Gentamicin / Tobramycin / Amikacin (Aminoglycosides)

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Levofloxacin / Moxifloxacin (Quinolones)

Miscellaneous

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Nitrofurantoin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Metronidazole

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Rifampicin

Gram positive Gram negative Atypicals

MRSA Staphylococci Streptococci Ef Anaerobes Coliforms Resp Pseud ESBL

Chloramphenicol

Important side effects 1• GENERAL - nausea, vomiting, diarrhoea, rashes, thrush

• Penicillins - hypersensitivity / skin reactions

• Flucloxacillin/co-amoxiclav - cholestatic jaundice

• Macrolides - GI disturbances, hepatitis, Q-T interval

• Quinolones - Q-T interval, convulsions, tendonitis

• Aminoglycosides/glycopeptides - nephrotoxicity/ototoxicity

• Vancomycin - ‘red man’ syndrome

• Clindamycin & cephalosporins - C. difficile colitis

• Tetracyclines - hepatotoxicity, staining teeth, photosensitivity, dysphagia

• Nitrofurantoin - peripheral neuropathy

Important side effects 2• Sulphonamides - Stevens-Johnson syndrome, blood

dyscrasias• Trimethoprim - blood dyscrasias• Chloramphenicol - aplastic anaemia, grey baby• Linezolid - blood dyscrasias, MAOI, optic neuropathy• Sodium fusidate - hepatotoxicity• Rifampicin - hepatotoxicity, red colouring of body fluids• Isoniazid - hepatotoxicity, peripheral neuropathy

(+pyridoxine)• Ethambutol - visual disturbances (visual acuity pre-test)• Polymyxin (colistin) - nephrotoxicity, neurotoxicity

Important interactions• Enzyme inhibitors

– Erythromycin, clarithromycin, isoniazid, metronidazole, ciprofloxacin

• Enzyme inducers– Rifampicin

• Absorption– Tetracyclines/quinolones absorption reduced by antacids/calcium

• Entero-hepatic cycling– Broad-spectrum antimicrobials and oral contraceptives

• Vitamin K synthesis– Broad spectrum antimicrobials and warfarin (INR)

• Metronidazole - disulfiram-like interaction with alcohol• Aminoglycosides / glycopeptides / colistin and loop diuretics or ciclosporin or

tacrolimus - nephrotoxicity• Quinolones and steroids (tendonitis) or NSAIDs (convulsions)• Macrolides / quinolones and Q-T prolonging drugs