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 MSHPUpdated by Jennifer Wong B.Pharm, GCPC

Pharmacists,Cabrini Health

Overview

• Aminoglycosides• Beta-lactams• Vancomycin• Clindamycin• Macrolides

Metronidazole

Quinolones

Rifampicin

Tetracyclines

Aminoglycosides

• Gentamicin– 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

Aminoglycoside - Gentamicin

Not absorbed after oral administrationMust be admin parenterally to tx systemic infns

Eliminated almost entirely by glomerular filtrationT1/2 ~2hr (normal pt)

Traditional tds dosingEndocarditis, pregnancy, burns, CF

Once daily (extended interval) admin the normHigher concmore rapid & greater bacterial killingResistance less likely with higher concPAELess frequent peaks reduce nephrotoxicity

Narrow Therapeutic Margin

• 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 10-12g/mL– Trough <2 g/mL

• If post is / you adjust the dose (peak)• If pre is extend the interval (trough)

Aminoglycoside - Gentamicin

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

Beta-lactams con’t

• Carbapenems– 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

• 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

• 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.

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

• Norfloxacin 400mg bd oral

• Ciprofloxacin 500mg bd oral– Also available iv

• C/I in children and adolescents

Reduce dose in renal impairment

•A/E: photosensitivity, dizziness, confusion

•Tendon (and bone) damage

•Many drug interactions

•Prolong the QT inverval

Broad spectrum – Resistance is increasing, esp in

USA

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

Questions???

QuizName a penicillin

Ampicillin, Benzylpeniciliin (PenG), Phenoxymethypenicillin (PenV), amoxycillin, flucloxacillin, dicloxacillin

Name two side effects of gentamicinNephrotoxicity, 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 quinoloneCiprofloxacin, 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