Polymyxins, Bacitracin, Fusidic Acid, Mupirocin

Question 1

Bacitracin

Answer 1

 A polypeptide produced by Bacillus subtilis
 3 Bacitracin subgroups A, B, and C
 Subgroup A the major component of
products available

Question 2

Bacitracin

MOA

Answer 2

 Inhibits growth of bacterial cell wall by inhibiting
transfer of polysaccharides, peptidoglycans, and
lipopolysaccharides to growing cell wall
 Interferes with sterol synthesis in humans and is too
toxic for systemic use

Question 3

Bacitracin – Spectrum of Activity

Answer 3

 Gram-positive staphylococci, streptococci,
corynebacteria, and clostridia
 Resistance rare, reported in S. aureus
 Often formulated with Polymixin B (Polysporin®) ±
neomycin (Neosporin®)

Question 4

bacitracin

Adverse Effects

Answer 4

 Well tolerated topically
 Minor skin irritation, rarely contact dermatitis
 Anaphylaxis may occur rarely with open lesions in the
intraoperative setting (irrigating solution) or packing
for rhinoplasty
 Bacitracin and polymixin B are both derived from
Bacillus species and there may be cross-sensitivity

Question 5

Polymyxin B

Answer 5

 Isolated from Bacillus polymyxa
 Polymyxins are cationic branched cyclic decapeptides
 Destroy bacterial membranes with detergent-like action

not absorbed when given orally, topical or IV use

Question 6

Polymyxin – Spectrum of Activity

Answer 6

 Bactericidal against many Gram-negative organisms
• Retained activity against MDR Gram-negative
bacilli, such as P. aeruginosa, A. baumannii, and
CRE
- NOT PROTEUS SPECIES
 Antibacterial activity decreased in the presence of
divalent cations (i.e., calcium, magnesium)
 Resistance rarely develops during therapy
 No cross-resistance to other antimicrobials

G- cocci and anaerobes are generally resistant to polymixin

Question 7

Polymyxin B – Adverse Effects

Answer 7

 Binds to cell membranes with high affinity therefore
little systemic absorption
 Few reactions even when applied to open wounds
 Contact sensitization reported

Question 8

Polymyxin B

clinical use

Answer 8

 Prevention and treatment of minor skin infections
 Often in combination with bacitracin ± neomycin
not common that it will be g- on skin soft tissue infections, not preference

Question 9

Colistin polymixin E

Answer 9

 Due to multidrug resistant organisms, sometimes
utilized systemically (IV) as a “drug of last resort”
 Hypersensitivity uncommon.
 Dose-related nephrotoxixity
(30-60%; usually reversible)
and neurotoxicity
 Neurotoxicity manifested by
neuromuscular blockade, which can
result in muscle weakness and even apnea.
- more likely in renal insuff, resp paralysis can happen

Question 10

Colistin

distribution

Answer 10

 Distribution of polymyxins to the cerebrospinal fluid, biliary tract, pleural fluid, and joint fluid is poor.
 The AUC/MIC ratio appears to be the pharmacodynamic
parameter best associated with bactericidal activity. However, concerns exist for the ability to safely achieve target
concentrations.
 For these reasons, it has been suggested that it should be used
in combination with another active or synergistic drug and to
avoid long intervals between doses.

Question 11

Mupirocin (Bactroban®)

MOA

Answer 11

 Unique structure
 Short fatty acid side chain linked to monic acid by
ester linkage
 Inhibits bacterial isoleucyl-transfer RNA
(tRNA) synthetase
 Inhibits elongation of protein chains
 Bacteriostatic/bactericidal at
concentrations in topical after
24-36 hr (20,000 µg/mL

Question 12

Mupirocin – Spectrum of Activity

Answer 12

 S. aureus (including MRSA), S. epidermidis,
S. pyogenes, S. pneumoniae, S. agalactiae
 Not active against Enterobacterales or
Entercoccus
 Spares normal skin flora (Micrococcus,
Corynebacterium, and Propionibacterium)
 More active at an acidic pH (as skin)

better and more selective for actual skin pathogens, leaves normal flora alone

Question 13

Mupirocin – Resistance

Answer 13

do not use more than 7 dyas (same with other topical agents)

 Long-term use can lead to resistance with
Staphylococci
 Reported from France
 5 day course intranasal mupirocin for decolonization
of a patient with GISA failed even though strain was
susceptible
 Patient developed pneumonia from GISA and on
repeat testing had developed resistance to mupirocin
 Use with GISA requires more study

Question 14

Mupirocin – Pharmacokinetics

Answer 14

 Not appreciably absorbed from skin
 If absorbed rapidly metabolized to inactive monic acid
and eliminated in urine
 Approximately 95% protein bound therefore activity
reduced in presence of serum

Question 15

Mupirocin – Adverse Effects

Answer 15

 Well-tolerated
 Low affinity for human iso-leucyl t-RNA transferase
 Propylene glycol base may irritate mucous
membranes
 Minimal potential for contact dermatitis (only 2 cases
reported)
 Prolonged use may lead to overgrowth of fungi
 Not teratogenic or embryotoxic in animals

Question 16

Fusidic Acid (Fucidin®)

Answer 16

 Isolated from Fusidium coccineum
 Carboxylic acid belonging to group
of tetracycline terpines
 Inhibits bacterial protein synthesis by
interfering with elongation factor G

creams, ointments, opth prep

Question 17

Fusidic Acid – Spectrum of Activity

Answer 17

 Gram-positive
 Exceptionally high activity against S. aureus
 Resistance to S. aureus 1-2 %
(one report 43% after topical use)
 Streptococci
 Corynebacterium, Clostridia

not as active selective against skin apthogens, activity against corynebac

Question 18

Fusidic Acid – Topical Adverse Effects

Answer 18

 Few reports of contact sensitivity
 Although similar structure to glucocorticoids there is
no evidence of suppressive activity on pituitary axis

Question 19

Clinical Uses

(Topicals) genral

Answer 19

 Skin infections - Impetigo
(minimal lesions), folliculitis
(S. aureus, S. pyogenes)
 Decolonization of nares
(S. aureus) - varied degrees of effect
- shor term it is effective, longer term pt more likely to reaquire S aureus
 Prophylaxis in catheterrelated and surgical
site infections