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Penicillins (Most S
...
aureus resistant
• flucloxacillin - good against Streptococcus pyogenes and S
...
influenzae without ß-lactamases or low affinity PBPs)
• Augmentin - adds activity against ß-lactamase producing S
...
influenzae, and anaerobes
• ticarcillin and piperacillin - similar activity to penicillin against staphs and streps, but also
active against some Gram- including Pseudomonas aeruginosa
...
aureus, many
coliforms, H
...
aureus
Streptococci

S
...
influenzae

Enterobacteriaceae
Streptococci
H
...
aureus
Streptococci
H
...
aeruginosa
• penicillin + gentamicin --> synergy (e
...
Strep viridans endocarditis)
Macrolides
• erythromycin - treat Strep pyogenes if patient allergic to penicillin
• roxithromycin - treat Strep pyogenes if patient allergic to penicillin
• azithromycin - main use is treatment of Chlamydia trachomatis (single dose)
• clarithromycin - used to treat atypical pneumonia
• nitrofurantoin - a nitrofuran
- only used for uncomplicated UTIs (cystitis, not pyelonephritis) - almost no tissue
penetration => highly concentrated in urine
- E
...
saprophyticus, group B Strep and Enterococci usually susceptible
• trimethoprim - only used alone for treating UTIs
- more commonly used in combination with sulphamethoxazole (as co-trimoxazole),
which has broad Gram+ and Gram- activity
• tetracycline, doxycycline, clindamycin, metronidazole, rifampicin, vancomycin, teicoplanin, fusidic acid

* Susceptibility of Pseudomonas aeruginosa:
ß-lactams

Quinolones

Aminoglycosides

Penicillins:
• ticarcillin, Timentin
• piperacillin, Tazocin

• norfloxacin (oral)
• ciprofloxacin
• (moxifloxacin)

Cephalosporins:
• ceftazidime 3rd gen
• cefepime 4th gen
• cefpirome 4th gen

• P
...
pneumoniae have ↑ MIC)
- if N
...
N
...
Site of action (bacterial ribosome) becomes protected
• QRNG (Quinolone Resistant Neisseria gonorrhoeae) - chromosomal mediated change to
both influx of quinolones and target sites (DNA gyrase and topoisomerase)
• Treat empirically (best guess) or guided by susceptibility testing
• Consider whether gono acquired locally/overseas and metro/country - Rural and remote North (eg Kimberly) can still use amoxycillin (+ probenicid to block
excretion) because PPNG, CMRNG, TRNG and QRNG are rare there
- In metro areas QRNGs are seen, so empirical choice is ceftriaxone (1 IMI)
Neisseria gonorrhoeae and Chlamydia trachomatis often infect together •
- if no lab results - ceftriaxone (for gono) + azithromycin (for C
...
trachomatis)
- culture susceptibility - ciprofloxacin or ceftriaxone (for gono) + azithromycin (C
...

• empirical treatment - oral doxycycline or clarithromycin
Infected diabetic foot ulcers:
• Need to cover - (Gram-) Enterobacteriaceae, Pseudomonas aeruginosa
- (Gram+) S
...

antibiotics often unsuccessful (poor blood supply) => debridement and/or wedge
•
resections necessary

Early infection
Augmentin (oral)
• Gram+
• Enterobacteriaceae
• not Pseudomonas aeruginosa
• anaerobes
ciprofloxacin (oral) + clindamycin (oral)
• Gram+
• broad Gram(w/ P
...
aeruginosa or ß-lactamasers

Mechanisms of bacterial resistance:
1
...
Enhance efflux of antibiotic - eg: pumps
3
...
Mutate antibiotic target - eg: transpeptidases (PBPs)
MRSA - Methicillin Resistant Staphylococcus aureus - fairly common
• mecA (chromosomal gene) encodes PBP2a, a transpeptidase resistant to all ß-lactams
• antibiotic susceptibility testing required
• for less serious infections give (oral) - erythromycin, clindamycin, co-trimoxazole,
tetracyclines or ciprofloxacin
• for more serious infections - vancomycin, teicoplanin (similar), or fusidic acid with
rifampicin (oral combination)
Resistance to expanded spectrum cephalosporins (3rd gen)
• ß-lactamase mediated resistance emerged after these drugs used heavily against Gram1
...
These mutants have been selected through use of 3rd gen
cephalosporins in hospitals
• Class 1 ß-lactamases are not destroyed by clavulanic acid
• Bacteria capable of class 1 ß-lactamase expression include:
E - Enterobacter
S - Serratia
C - Citrobacter freundii
A - Acinetobacter
P - Pseudomonas aeruginosa, Proteus vulgaris, Providencia
M - Morganella

2
...
coli, Citrobacter, Klebsiella, Proteus mirabilis
• ESBL genes found on plasmids and are transferred between Gram- rods (bad)
• ESBLs destroy - older penicillins, ticarcillin, piperacillin
- older and 3rd gen cephalosporins, also some activity against 4th gen cephalosporins
- aztreonam
• plasmid may also carry genes conferring resistance to aminoglycosides, fluoroquinolones
Class 1 ß-lactamases

ESBLs

Penicillins

R

R

1st, 2nd, 3rd gen Cephalosporins

R

R

4th gen Cephalosporins

R or S

R or S

Carbapenems

S

S

ß-lactamase inhibitor combinations

R

R or S

aztreonam

R or S

R

(need susceptibility testing)

Quinolones

R or S

R or S

Aminoglycosides

R or S

R or S

• eg: Could treat a susceptible class 1 ß-lactamase producing Enterobacter cloacae with - IV meropenem ± gentamicin
- IV ciprofloxacin ± gentamicin

MIC - minimum concentration of a given antibiotic that inhibits visible growth of a given
bacterial isolate in vitro
Routine antibiotic susceptibility testing (R or S)
• R if MIC > chosen ‘breakpoint’ MIC
• S if MIC < chosen ‘breakpoint’ MIC
• performed in simplified form - filter paper
discs with antibiotic placed on agar with
bacteria
• MIC values cluster, eg: S

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