Efficacy of skin and nasal povidone-iodine preparation against mupirocin-resistant methicillin-resistant Staphylococcus aureus and S. aureus within the anterior nares

Abstract

Mupirocin decolonization of nasal Staphylococcus aureus prior to surgery decreases surgical-site infections; however, treatment requires 5 days, compliance is low, and resistance occurs. In 2010, 3M Company introduced povidone-iodine (PVP-I)-based skin and nasal antiseptic (Skin and Nasal Prep [SNP]). SNP has rapid, broad-spectrum antimicrobial activity. We tested SNP's efficacy using full-thickness tissue (porcine mucosal [PM] and human skin) explant models and human subjects. Prior to or following infection with methicillin-resistant Staphylococcus aureus (MRSA) (mupirocin sensitive and resistant), explants were treated with Betadine ophthalmic preparation (Bet), SNP, or mupirocin (Bactroban nasal ointment [BN]) or left untreated. One hour posttreatment, explants were washed with phosphate-buffered saline (PBS) plus 2% mucin. One, 6, or 12 h later, bacteria were recovered and enumerated. Alternatively, following baseline sampling, human subjects applied two consecutive applications of SNP or saline to their anterior nares. One, 6, and 12 h after application of the preparation (postprep), nasal swabs were obtained, and S. aureus was enumerated. We observed that treatment of infected PM or human skin explants with SNP resulted in >2.0 log10 CFU reduction in MRSA, regardless of mupirocin sensitivity, which was significantly different from the values for BN- and Bet-treated explants and untreated controls 1 h, 6 h, and 12 h after being washed with PBS plus mucin. Swabbing the anterior nares of human subjects with SNP significantly reduced resident S. aureus compared to saline 1, 6, and 12 h postprep. Finally, pretreatment of PM explants with SNP, followed by a mucin rinse prior to infection, completely prevented MRSA infection. We conclude that SNP may be an attractive alternative for reducing the bioburden of anterior nares prior to surgery.

FIG 1

Efficacy of PVP-I formulations and Bactroban Nasal against MRSA infection in an ex vivo PVM model. (a) Schematic of experimental design. (b) Explants of normal PVM were infected with S. aureus Xen30, treated, washed with sterile PBS containing 2% mucin and then incubated as shown in panel a. The explants were treated with Betadine Ophthalmic, 3M SNP, or Bactroban Nasal (B. Nasal) or left untreated as a control. Following incubation for 1, 6, or 12 h, explants were transferred to a neutralization buffer containing sodium thiosulfate and vortex mixed to release surviving bacteria. Serial dilutions were made in sterile PBS and plated onto tryptic soy agar supplemented with sheep blood, using a spiral plater. The number of viable bacterial cells is expressed as log₁₀ CFU/explants recovered over time. Values are means ± SEMs (error bars). Values that are statistically significantly different (P < 0.05) from the value for the untreated control are indicated by an asterisk.

FIG 2

Efficacy of 3M SNP or Bactroban Nasal against low- and high-level mupirocin-resistant MRSA isolates. Explants of normal PVM were infected with ∼1 × 10⁶ CFU low-level Mup^r MRSA isolates (a, c, and e) or high-level Mup^r MRSA isolates (b, d, and f) for 2 h. Infected explants were then treated with SNP or Bactroban Nasal (B. Nasal) or left untreated (control) for 1 h, followed by washing with sterile PBS supplemented with 2% mucin. Washed explants were then returned to the incubator for 1 h (a and b), 6 h (c and d), or 24 h (e and f). Following incubation, explants were transferred to 2× DE broth and vortex mixed to release surviving bacteria. Serial dilutions were made in sterile PBS and plated onto tryptic soy agar supplemented with sheep blood, using a spiral plater. The number of viable bacterial cells is expressed as log₁₀ CFU/explants. Each symbol represents the value for an individual explant, and the mean (horizontal bar) ± SEM (error bar) for each group are shown. Mean values that are significantly different (P < 0.05) from the mean value for the untreated control group are indicated by an asterisk.

FIG 3

Efficacy of PVP-I formulations and Bactroban Nasal against MRSA infection in an ex vivo, full-thickness, fresh human skin model. (a) Schematic of experimental design. (b) Explants of normal human skin were infected with S. aureus Xen30, treated, washed with sterile PBS containing 2% mucin, then incubated as shown in panel a. The explants were treated with Betadine Ophthalmic, 3M SNP, or Bactroban Nasal (B. Nasal) or left untreated as a control. Following incubation for 1, 6, or 12 h, explants were transferred to 2× DE broth and vortex mixed to release surviving bacteria. Serial dilutions were made in sterile PBS and plated onto tryptic soy agar supplemented with sheep blood, using a spiral plater. The number of viable bacterial cells is expressed as log₁₀ CFU/explants recovered over time. Values are means ± SEMs (error bars). Values with different letters are significantly different (P < 0.05).

FIG 4

3M SNP reduces normal flora of human anterior nares. Thirteen to 18 human subjects (3M study EM-05-011100) applied 3M Skin and Nasal Prep (3M SNP) and seven to nine human subjects applied 0.9% saline control to their nostrils for 30 s each, followed by an immediate repeat application, for a total application time of 1 min per naris. Postprep samples were taken via swabbing the nares at 1 h, 6 h, and 12 h. Baseline samples were taken prior to the application of prep or saline. The mean baseline level of S. aureus in subjects included in this study was log₁₀ 4.77 ± 0.62 CFU. The numbers of viable bacterial cells are expressed as log₁₀ reduction from baseline level over time. Values are means ± SEMs (error bars). Mean values that are significantly different (P < 0.05) from the mean value for the untreated saline control group are indicated by an asterisk.

FIG 5

3M SNP prevents MRSA infection in an ex vivo model. (a) Schematic of experimental design. (b) Explants of normal PVM were treated with PVP-I formulations or mupirocin ointment (2%) for 5 min at room temperature (RT), followed by 15-min incubation at 37°C. Explants were then washed with sterile PBS containing 2% mucin. After the wash, explants were infected with ∼1 × 10⁶ CFU of MRSA Xen30 and incubated at 37°C for 1 h. Explants were transferred to 2× DE broth and vortex mixed to release surviving bacteria. Serial dilutions were made in sterile PBS and plated onto tryptic soy agar supplemented with sheep blood, using a spiral plater. The number of viable bacterial cells is expressed as log₁₀ CFU/explants. Values are means plus SEMs (error bars).