1. Antibiotics: What are they & How they are used
Dr Rob Townsend
Consultant
Microbiology NGH

2. Uses of antibiotics 1) Treatment 2) Prophylaxis
a) Specific indications
endocarditis
post-splenectomy
b) Prevention of post-surgical infection

3. Antibiotic Prophylaxis
Timing and duration
to be effective you require highest tissue concentration of antibiotic at time of surgery.
Importance of foreign material
i.e. remove it!
Prophylaxis generally not indicated in clean surgery except for prosthetic surgery

4. Antibiotics - Overview
Many different classes of antibiotics
Biggest class are the Beta-Lactams
This group includes:
Penicillins (pen, amox, fluclox etc)
Cephalosporins (cefalexin, cefuroxime etc)
Carbapenems (meropenem)
Combinations (tazocin, augmentin)
They all target the bacterial cell wall

5. Beta-Lactams The most widely used group of antibiotics
Some are very broad spectrum (carbapenem) others much less so (penicillin)
Many predispose to C.difficile and colonisation with resistant bacteria (and candida)
Many people report “allergies” to this group particularly the penicillins
MRSA resistant to ALL Beta lactams

6. Penicillins Amoxicillin (all routes) Flucloxacillin (all routes)
Same spectrum as benzyl pen plus active against enterococci and H.influenzae
When first introduced good activity against enterobacteriaceae, most are now resistant by -lactamase production
Flucloxacillin (all routes)
Primarily anti-staphylococcal agent because of stability to penicillinase.
Introduction of amino grpup in alpha position of the side chain of ben pen confers high degree of acid stability together with enhanced activity against gram neg bact

7. -lactamase Inhibitors
Eg clavulanate, tazobactam
Main mechanism of bacterial resistance is beta-lactamase production (many types)
Can overcome some of this by combining a penicillin with a beta-lactamase inhibitor eg co-amoxiclav, tazocintm
Widens spectrum to include staphylococci, some enterobacteriaceae and anaerobes

8. Antipseudomonal penicillins
eg ticarcillin, piperacillin
IV only
Susceptible to -lactamases so usually combined with a -lactamase inhibitor eg clavulanic acid or tazobactam
Trade names – Timentin or Tazocin

9. Monobactams Aztreonam Only active against Gram negative bacilli
including pseudomonas
Generally regarded as not so active against anaerobes
Generally regarded as “safer for C.diff”
Narrow spectrum of activity.

10. Carbapenems Imipenem, Meropenem, Ertapenem
Very broad spectrum, reserved for severe hospital acquired infections
Expensive
Imipenem contraindicated in CNS disorders
Can predispose to C.diff (v.broad spectrum)

11. Cephalosporins 1st Generation Eg cefradine/cefalexin/cefazolin
Gram pos cover > Gram Neg cover
MSSA S
Streptococci S
Enterococci R
Enterobacteriaceae initially S, now many R

12. Cephalosporins 2nd Generation 3rd Generation Eg cefuroxime
As 1st generation against G+ve, but improved activity against enterobacteriaceae (more stable to -lactamases)
3rd Generation
Eg cefotaxime, ceftazidime
Much less Gram pos cover, “more” gram neg activity.
Good CNS penetration (cefotaxime)
Good Anti-pseudomonal (ceftazidime)

13. Glycopeptides Eg vancomycin or teicoplanin Gram +ve agents ONLY
IV only and toxic (Vanc)
Reserved for serious/resistant gram pos eg MRSA or in multiply allergic patients

14. Protein Synthesis Inhibitors
Chloramphenicol
Very broad spectrum except pseudomonas
Little used today because of toxicity
Idiosyncratic aplastic anaemia
Still used topically for eyes
Most PO/IV usage in Neurosurgery (STH)

15. Macrolides Eg erythromycin, clarithromycin
Good staph and strep activity
Used as an alternative to penicillins in soft tissue and throat infections in allergic patients
Active against legionella, chlamydia and mycoplasmas - atypical pneumonias
No Gram –ve cover

16. Lincosamides Eg clindamycin Active against staph, strep and anaerobes
first antibiotic to be ass. with C.diff & PMC - usage decreased dramatically
good bone concentrations and well absorbed orally

17. Tetracyclines Broad spectrum and were widely used
but resistance developed rapidly and usage declined
Used for mild MRSA infections and also useful activity against chlamydias (& malaria)

18. Aminoglycosides Eg gentamicin, tobramycin
Active against enterobacteriaceae, pseudomonas and staphylococci (inc mrsa)
Synergy with cell-wall antibiotics against streptococci and enterococci
Nephro- and oto-toxic, levels must be monitored carefully
More toxic than glycopeptides
Mostly inelderly and renal failure patients. Dose related and care must be taken to with dosage and whenever possible treatment should not exceed 7 days.

19. Fusidic acid Mainly an anti-staphylococcal agent
Must not use alone as resistance develops by a single mutation
Used in combination for serious Staph infection eg osteomyelitis

20. Oxazolidinone
Inhibitor of bacterial protein synthesis - blocks formation of the initiation complex
Active against gram pos only including MRSA and VRE
expensive and can cause bone marrow suppression with longer courses (>2wks)
Only 1 in this class - Linezolid

21. Nucleic Acid Quinolones Old: eg nalidixic acid Newer: eg ciprofloxacin
used as a urinary tract agent
resistance develops very rapidly
Newer: eg ciprofloxacin
good activity against enterobacteriaceae pseudomonas and staph moderate against strep,
Increasing resistance an issue
MRSA usually resistant - encourages heavy colonisation
Also strong assoc. with C.diff & ESBL’s

22. Rifampicin
Used primarily for TB, but good activity against many genera esp Staph’s
Resistance develops rapidly if used on its own, therefore used in combination eg in MRSA infections
Sometimes used on own for meningococcal prophylaxis - low number of organisms

23. Metronidazole Anti-anaerobic Bacteria and protozoa
Almost all sensitive, although resistance increasing

24. Folate Antagonists Broad spectrum
sulphonamides - little used in UK now because of toxicity
trimethoprim - used for UTIs but resistance steadily increasing
combination used for PCP (Septrin)

25. Treatment
UTI
Organisms: E coli (& coliforms), Staph saprophyticus, enterococci
Antibiotics: trimethoprim, amoxicillin +/- clavulanate, 1st gen cephalosporin
if more serious (ie ?bacteraemic) then 2nd/3rd gen cephalosporin or quinolone

26. Treatment - 2 Respiratory
COPD - likely organisms: H. influenzae, pneumococcus, Moraxella catarrhalis
antibiotics: amoxicillin +/- clavulanate, tetracycline, trimethoprim
Pneumonia - pneumococcus, atypicals
antibiotics : ß-lactams + erythromycin

27. Treatment - 3
Wound
likely organisms: Staph aureus, Strep pyogenes, anaerobes
antibiotics: flucloxacillin, erythromycin, co-amoxiclav
Beware MRSA if inpatient

28. Misuse of antibiotics
Use of broad spectrum agents when narrow spectrum agents are as effective
treatment for too long a time
treatment by intravenous route when oral therapy is equally effective
use of combination agents when one agent would suffice
failure to alter therapy when sens available

29. Misuse 2
Failure to use a dosage appropriate to renal and hepatic function
failure to initiate therapy based on local susceptibility of orgs in a unit
institution of antibiotics with the “worst” case scenario, ie pseudomonas or MRSA when these orgs are highly unlikely
Failure to step down once organism known

30. Dangers of misuse 1:10 inpatients have ADR to a drug they do not need.
Up to 10% potentially harmful drug interactions
ADR increases substantially with multiple drug prescribing
Errors in prescribing monitoring and administration

31. Dangers of misuse Superinfection Antibiotic resistance selection
Candida
Clostridium difficile
MRSA (esp after cipro)
Antibiotic resistance selection
MRSA
C.diff
Resistant Coliforms

32. Where to get help