Efficacy of a New Cream Formulation of Mupirocin: Comparison with Oral and Topical Agents in Experimental Skin Infections

John Gisby; Joanna Bryant

doi:10.1128/AAC.44.2.255-260.2000

DOI: 10.1128/AAC.44.2.255-260.2000

Article Figures & Data

Tables

Table 1.

In vitro susceptibility of the infecting organisms to mupirocin and a range of commonly used antibiotics

Organism	MIC of test agents (μg/ml)
Organism	Mupirocin	Erythromycin	Flucloxacillin	Cephalexin	Fusidic acid	Neomycin	Bacitracin	Benzylpenicillin	Methicillin
S. aureusSweeting	0.12	>128	0.12		0.25			0.03	1.0
S. aureusJ1225	0.12	0.12	0.25	2.0	0.03	16	1.0	32	2.0
S. pyogenes1580	0.25	0.06	0.06		8.0			≤0.007	0.25
S. pyogenesPA52	0.25	0.06	0.06	1.0	8.0	>16	1.0	≤0.007	0.25

Table 2.

Comparison of peak serum concentrations of the systemic agents used in the mouse and the hamster with those attainable in humans after oral administration

Agent	Mouse		Hamster		Human
Agent	Dose (mg/kg)	Peak serum concn ± SD (μg/ml [range])	Dose (mg/kg)	Peak serum concn ± SD (μg/ml [range])	Dose (mg)	Peak serum concn ± SD (μg/ml [range])
Erythromycin	200	3.8 ± 2.1 [1.7–7.8]	200^a	12.1 ± 5.1 [6.2–15.2]	250^c	0.93 ± 0.23
Flucloxacillin	100	18.0 ± 13.0 [4.5–39.5]			500^d	14.5 [3.4–26.5]
Cephalexin	20	15.4 ± 2.3 [12.6–18.8]	20^b	3.7 ± 0.6 [3.2–4.5]	250^e	7.3 ± 2.5 [3.6–11.0]

↵a Dose used in efficacy tests was 100 mg/kg.
↵b Dose used in efficacy tests was 40 mg/kg.
↵c Reference 27.
↵d Reference 36.
↵e Reference 23.

Table 3.

Mean bacterial counts from surgical wound infections in the mouse following treatment with mupirocin cream, mupirocin ointment and their respective placebos

Treatment	Mean bacterial count (log₁₀CFU/wound) ± SD (no. of wounds)^d
	S. aureus		S. pyogenes
	Sweeting	J1225	1580	PA52
Implantation	∼5.0	4.64 ± 0.2	4.26 ± 0.20	3.96 ± 0.21
After 5 days
Untreated	7.23 ± 0.33 (10)	7.46 ± 0.63 (10)	6.14 ± 1.11 (9)	7.10 ± 0.60 (10)
Placebo cream	7.52 ± 0.40 (10)	7.45 ± 0.38 (10)	6.52 ± 1.33 (9)	6.85 ± 0.60 (10)
Placebo ointment	7.16 ± 0.43 (10)	7.21 ± 0.24 (10)	6.32 ± 1.40 (8)	6.56 ± 0.45 (9)
Mupirocin cream	2.51 ± 1.69^a, ^b (10)	1.55 ± 0.58^a (10)	1.34 ± 0.80^a, ^c (10)	1.90 ± 1.68^a (9)
Mupirocin ointment	4.62 ± 2.15^a (8)	2.54 ± 2.24^a (10)	3.92 ± 1.11^a (8)	2.56 ± 1.92^a (9)

↵a P < 0.001 versus respective vehicle placebo and untreated controls.
↵b P = 0.01 versus mupirocin ointment.
↵c P < 0.01 versus mupirocin ointment.
↵d Animals that had removed sutures during the treatment period were excluded from the analyses.

Table 4.

Mean bacterial counts from surgical wound infections in the mouse after treatment with mupirocin cream, mupirocin ointment, and oral and other topical agents commonly used to treat skin infections

Treatment	Mean bacterial count (log₁₀CFU/wound) ± SD (no. of wounds)^e
	S. aureus J1225		S. pyogenes PA52
	Trial 1	Trial 2	Trial 1	Trial 2
Implantation	4.60 ± 0.13	4.70 ± 0.14	4.19 ± 0.19	4.38 ± 0.41
After 5 days
Untreated	7.27 ± 0.23 (10)	7.42 ± 0.24 (10)	6.69 ± 1.54 (9)	7.77 ± 0.51 (10)
Mupirocin cream	1.89 ± 1.57^a, ^b (9)	1.45 ± 1.05^a, ^c (8)	1.00^a, ^b (10)	1.76 ± 1.11^a, ^d (9)
Mupirocin ointment	3.49 ± 1.90^a (8)	3.39 ± 2.11^a, ^c (9)	1.47 ± 0.66^a, ^b (9)	2.80 ± 1.85^a (8)
Erythromycin, 200 mg/kg (p.o.)	3.11 ± 0.98^a (10)		3.78 ± 1.27^a (10)
Flucloxacillin, 100 mg/kg (p.o.)	2.89 ± 1.96^a (10)		1.28 ± 0.65^a, ^b (9)
Cephalexin, 20 mg/kg (p.o.)		5.86 ± 0.51^a (8)		3.52 ± 1.90^a (10)
Fusidic acid cream		2.47 ± 2.11^a, ^c (8)		6.51 ± 0.72^a (6)

↵a P < 0.001 versus untreated controls.
↵b P < 0.001 versus erythromycin.
↵c P < 0.01 versus cephalexin.
↵d P < 0.01 versus fusidic acid.
↵e Animals that had removed sutures during the treatment period were excluded from the analyses. p.o., peroral.

Table 5.

Mean bacterial counts from impetigo lesions in the hamster caused by S. aureus J1225 after treatment with mupirocin cream, mupirocin ointment, and oral and other topical agents commonly used to treat skin infections

Treatment	Mean bacterial count (log₁₀CFU/lesion) ± SD (no. of lesions)^e
Treatment	Trial 1	Trial 2	Trial 3
Inoculation	7.46	6.93	7.13
After 5 days
Untreated	5.92 ± 0.73 (15)	6.20 ± 1.28 (16)	5.32 ± 1.25 (16)
Placebo cream	4.46 ± 1.24^a (16)
Placebo ointment	4.56 ± 1.16^a (14)
Mupirocin cream	2.29 ± 0.87^b, ^c (14)	2.23 ± 1.38^a, ^d (16)	2.75 ± 1.11^a (16)
Mupirocin ointment	3.32 ± 1.02^b (15)	3.11 ± 1.06^a, ^d (16)	2.93 ± 0.90^a (16)
Erythromycin, 100 mg/kg (p.o.)		4.60 ± 0.93^a (16)
Cephalexin, 40 mg/kg (p.o.)		4.66 ± 0.86^a (16)
Fusidic acid cream			2.54 ± 1.09^a (15)
Neomycin-bacitracin cream			3.15 ± 1.05^a (16)

↵a P < 0.01 versus nontreated controls.
↵b P < 0.01 versus placebo.
↵c P < 0.01 versus mupirocin ointment.
↵d P < 0.01 versus erythromycin and cephalexin.
↵e Inoculated sites that did not produce lesions were excluded from the analyses. p.o., peroral.