1. 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

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

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

4. 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

5. 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

6. 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.

7. 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

8. 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

9. 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”.

10. 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

11. 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.

12. 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.

13. 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.

14. 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

15. 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

16. 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

17. 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.

18. Questions???

19. 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

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