They all died of bacterial infections or sequelae - antibiotics could have or would have been used King Tut – Staphylococcus aureus Beth March – Streptococcus pyogenes Pope John Paul II - Sepsis

Common Antibiotics Original Power Point by Nicole Morse B.Pharm MSHP Updated by Jennifer Wong B.Pharm, GCPC Pharmacists, Cabrini Health

Overview Aminoglycosides Metronidazole Beta-lactams Quinolones Vancomycin Clindamycin Macrolides Metronidazole Quinolones Rifampicin Tetracyclines

Aminoglycosides Gentamicin Amikacin Tobramycin Broad Gm-ve spectrum, incl. Ps.aeruginosa D.O.C for most cases of aerobic Gm-ve sepsis Amikacin Reserve for organisms resistant to other aminog. Tobramycin Marginally more effective on Ps.aeruginosa than gentamicin All potentially ototoxic and nephrotoxic C/I with NM-blocking agents  paralysis d.o.c = drug of choice Nephrotoxicity is possibly reversible if the use of the drugs is ceased, but otootoxicity is not

Aminoglycoside - Gentamicin Not absorbed after oral administration Must be admin parenterally to tx systemic infns Eliminated almost entirely by glomerular filtration T1/2 ~2hr (normal pt) Traditional tds dosing Endocarditis, pregnancy, burns, CF Once daily (extended interval) admin the norm Higher concmore rapid & greater bacterial killing Resistance less likely with higher conc PAE Less frequent peaks reduce nephrotoxicity Narrow Therapeutic Margin In abnormal pts half life can vary widely from 1-70hr. Pae = post antibiotic effect No info as to whether extended dosing interval reduces ototoxicity Neonates requires specialist info

Aminoglycoside - Gentamicin Extended interval dosing 3-4mg/kg (healthy, normal adults) Post-levels are done 30’ after end of infusion Pre-levels are done just prior to next infusion Usually administered over 30’ infusion Target Peak 10-12g/mL Trough <2 g/mL If post is / you adjust the dose (peak) If pre is  extend the interval (trough) Lower doses are used in endocarditis as used in a synergistic relationship with penicillins Less than 30mL/min seek specialist advice eg ID physician or ID pharmacist Unusual kinetics are patients with large volumes of distribution; eg ascitic pts etc.

Beta-lactams Penicillins Narrow-spectrum gm+ve, X by -lactamases PenicillinG iv, PenicillinV po Narrow spectrum with antistaph activity Stable to -lactamases Dicloxacillin, flucloxacillin Moderate spectrum Amoxycillin, ampicillin Also active against some gm-ve Broad spectrum Augmentin Duo Forte® Augmentin Duo Piperacillin and Ticarcillin have activity against P.aeruginosa Cilstatin is given with imipenem as it is degraded by renal dipeptidase Ertapenem is longer acting but has less activity against P.aeruginosa Aztreonam can be given to pts who are highly sensitive to other penicillins. PenV is intrinsically less active than PenG

Beta-lactams con’t Carbapenems Cephalosporins Imipenem/cilstatin, meropenem, ertapenem New doripenem (Doribax®) Gm-ve rods, P.aeruginosa, anaerobes, many gm+ve Not useful for MRSA Cephalosporins Less sensitive to penicillinases Same spectrum as the penicillins Have ‘generations’ that indicate broadening spectrum of activity Imipenem has a lowers the seizure threshold – monitor; ertapenem is once daily can be used for HITH; meropenem is better. There is a new doripenem that is more potent that meropenem. Greater bang for your buck or greater kill rate. I’m not going to bore you here with which antibiotics are in which generation

Commonly you will see: Cephalothin 1g iv QID (or cephtazidime 1g iv tds) post surgery followed by cephalexin 500mg po QID Ceftriaxone 1g iv daily with roxithromycin for empirical tx of pneumonia Ceftriaxone 2g bd or 4g daily could be indicated for empirical treatment of meningitis Regarding penicillin hypersensitivity… 10% of patients who are allergic to penicillins will be allergic to other beta-lactamases and vice-versa “A hx of an immediate hypersensitivity reaction…contraindicates use of other beta-lactams”.

Vancomycin Effective against a broad range of gram +ve organisms, not gram –ve organisms. Role in MRSA (not VRE) Role in severe infections with susceptible organisms in pt allergic to penicillin and in meningitis due to Strep.pneumoniae Not absorbed orally - For systemic infections give iv Could be given orally for treatment of Clostridium difficile Only ever used po for pseudomembranous colitis

Vancomycin TDM: Aim for trough 10mg-20mg/L sampled immediately before the next dose is administered Peak levels are commonly done but have not been proven to correlate with toxicity or efficacy Peak levels should be 25mg-40mg/L; values outside this indicate an abnormal Vd and dose adjustment is required. Stories of oto and nephrotoxicity are due to early studies of vancomycin that used impure products. Subsequent studies of more pure vancomycin have failed to substantially prove vanc ALONE is a cause of these toxicities. Perhaps with aminoglycosides this will become a problem.

Clindamycin Used in skin infections and patients allergic to penicillins. Both iv and oral Commonly 150mg-300mg tds-qid Major s/e risk is pseudomembranous colitis!! Due to overgrowth of Clostridium difficile VERY important to warn the pt of diarrhea (esp mucousy/bloody/watery) to cease and call the doctor immediately.

Macrolides Azithromycin, Roxithromycin, Erythromycin, Clarithromycin Cyp3A4 inhibitor interactions increasing along the line Community acquired infections are major indications Roxithromycin 150mg po bd or 300mg po d Erythromycin 250mg po 30ac qid or Erythromycin Ethylsuccinate 400mg swallowed whole qid irrespective of food.

Metronidazole Covers anaerobes Available as iv but excellent po absorption means tabs/supps can often be used instead. Disulfiram-like reaction with alcohol Common rx are 400mg po tds and 500mg iv tds or bd Abdominal, pelvic, oral infections Can give mouth a furry metallic taste and a black coating Both benign and reversible after ceasing therapy

Quinolones Also available iv Broad spectrum – Reduce dose in renal impairment Broad spectrum – Resistance is increasing, esp in USA A/E: photosensitivity, dizziness, confusion Tendon (and bone) damage Many drug interactions Prolong the QT inverval Norfloxacin 400mg bd oral Ciprofloxacin 500mg bd oral Also available iv C/I in children and adolescents

Rifampicin Active against gm+ve Including Staph & mycobacteria Used in: TB, MRSA, prophylaxis Hib and meningococcal Rapid emergence of resistance means it must always be used in combo with another abx (e.g. + fusidic acid is often seen) Potent CYP450 inducer Many drug interactions Colours body fluids yellow-orange

Tetracyclines Broad spectrum Gm+ve and gm-ve, Chlamydia, spirochaetes et.al. Resistance and development of other abx has reduced their value Main use is acne, CAP, PID, cholera, lyme disease C/I in children under 8y.o & pregnant & breastfeeding women Staining of teeth and bones Doxycycline is a blood schizonticide Used for malaria prophylaxis Tetracycline has to be given on an empty stomach; minocycline doesn’t have to be and has a greater range of activity but risk of benign intracranial hypertension and skin pigmentation and vestibular adverse effects.

Questions???

Quiz Name a penicillin Name two side effects of gentamicin Ampicillin, Benzylpeniciliin (PenG), Phenoxymethypenicillin (PenV), amoxycillin, flucloxacillin, dicloxacillin Name two side effects of gentamicin Nephrotoxicity, ototoxicity Which of these is potentially reversible? Nephrotoxicity Who should we not give tetracyclines to? Children under eight years old; pregnant women; breastfeeding women Name a quinolone Ciprofloxacin, norfloxacin, moxifloxacin, gatifloxacin

References Prof Gregory Peterson, UTas, UMORE Therapeutic Guidelines, Antibiotics Karen Wong B.Pharm, The Alfred Rang HP, Dale MM, Ritter JM. 1999. Pharmacology (4th ed.) Churchill Livingstone: Sydney. Wikipedia