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Efficacy of a povidone iodine preparation in reducing nasal methicillin-resistant Staphylococcus aureus in colonized patients

Open AccessPublished:November 14, 2019DOI:https://doi.org/10.1016/j.ajic.2019.09.014

      Highlights

      • Povidone iodine in methicillin-resistant Staphylococcus aureus (MRSA) was examined.
      • Povidone iodine is a potential alternative to mupirocin for nasal decolonization.
      • Povidone iodine reduced nasal MRSA at 1 and 6, but not 12, hours posttreatment.
      • Povidone iodine may suppress S aureus during the perioperative period.
      In a randomized, nonblinded, placebo-controlled trial, a single application of a 10% povidone iodine preparation significantly reduced nasal methicillin-resistant Staphylococcus aureus at 1 and 6 hours after application, but suppression was not sustained at 12 or 24 hours. Twice-daily treatment for 5 days did not reduce nasal methicillin-resistant S aureus measured 12 hours postdosing in comparison to controls. These results suggest that single preoperative applications of povidone iodine will be effective for short-term suppression of S aureus during the perioperative period.

      Key Words

      The topical antibiotic mupirocin is commonly used for nasal decolonization of Staphylococcus aureus.
      • McDanel JS
      • Murphy CR
      • Diekema DJ
      • Quan V
      • Kim DS
      • Peterson EM
      • et al.
      Chlorhexidine and mupirocin susceptibilities of methicillin-resistant Staphylococcus aureus from colonized nursing home residents.
      Treatment of S aureus carriers with nasal mupirocin in combination with chlorhexidine gluconate bathing has been shown to reduce surgical site infections and infections in patients in the intensive care unit.
      • McDanel JS
      • Murphy CR
      • Diekema DJ
      • Quan V
      • Kim DS
      • Peterson EM
      • et al.
      Chlorhexidine and mupirocin susceptibilities of methicillin-resistant Staphylococcus aureus from colonized nursing home residents.
      ,
      • Huang SS
      • Septimus E
      • Kleinman K
      • Moody J
      • Hickok J
      • Avery TR
      • et al.
      Targeted versus universal decolonization to prevent ICU infection.
      Decolonization of methicillin-resistant S aureus (MRSA) carriers might also be beneficial in nonintensive care unit settings for patients with devices and after hospital discharge.
      • Huang SS
      • Septimus E
      • Kleinman K
      • Moody J
      • Hickok J
      • Heim L
      • et al.
      Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial.
      ,
      • Huang SS
      • Singh R
      • McKinnell JA
      • Park S
      • Gombosev A
      • Eells SJ
      • et al.
      Decolonization to reduce postdischarge infection risk among MRSA carriers.
      Although mupirocin is effective in suppressing S aureus, emergence of resistance is a concern as strains with high-level mupirocin resistance have been reported in hospitals and nursing homes.
      • McDanel JS
      • Murphy CR
      • Diekema DJ
      • Quan V
      • Kim DS
      • Peterson EM
      • et al.
      Chlorhexidine and mupirocin susceptibilities of methicillin-resistant Staphylococcus aureus from colonized nursing home residents.
      Povidone iodine preparations are a potential alternative to mupirocin. Povidone iodine has potent and rapid activity against S aureus, and there is some evidence that this agent may reduce nasal methicillin-susceptible S aureus and MRSA in nares of surgical patients and healthy volunteers.
      • Anderson MJ
      • David ML
      • Scholz M
      • Bull SJ
      • Morse D
      • Hulse-Stevens M
      • et al.
      Efficacy of skin and nasal povidone-iodine preparation against mupirocin-resistant methicillin-resistant Staphylococcus aureus and S. aureus within the anterior nares.
      ,
      • Peng HM
      • Wang LC
      • Zhai JL
      • Weng XS
      • Feng B
      • Wang W
      Effectiveness of preoperative decolonization with nasal povidone iodine in Chinese patients undergoing elective orthopedic surgery: a prospective cross-sectional study.
      It has been suggested that there is a relatively low risk for development of resistance to povidone iodine because it has multiple cellular targets.
      • Anderson MJ
      • David ML
      • Scholz M
      • Bull SJ
      • Morse D
      • Hulse-Stevens M
      • et al.
      Efficacy of skin and nasal povidone-iodine preparation against mupirocin-resistant methicillin-resistant Staphylococcus aureus and S. aureus within the anterior nares.
      For surgical patients, it has been proposed that application of 1 or more preoperative doses by nursing staff providing temporary suppression of nasal S aureus during surgery, and might be sufficient for prevention of surgical site infections at lower cost than a 5-day course of mupirocin.
      • Peng HM
      • Wang LC
      • Zhai JL
      • Weng XS
      • Feng B
      • Wang W
      Effectiveness of preoperative decolonization with nasal povidone iodine in Chinese patients undergoing elective orthopedic surgery: a prospective cross-sectional study.
      • Phillips M
      • Rosenberg A
      • Shopsin B
      • Cuff G
      • Skeete F
      • Foti A
      • et al.
      Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution.
      • Bebko SP
      • Green DM
      • Awad SS
      Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation.
      In a recent randomized trial, 2 applications of a 5% povidone iodine preparation within 2 hours of surgery plus chlorhexidine gluconate bathing was associated with a significant reduction in deep S aureus surgical site infections in patients undergoing arthroplasty or spine fusion in comparison to 5 days of mupirocin plus chlorhexidine gluconate bathing.
      • Phillips M
      • Rosenberg A
      • Shopsin B
      • Cuff G
      • Skeete F
      • Foti A
      • et al.
      Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution.
      Another recent quasiexperimental study reported that universal use of nasal povidone iodine plus chlorhexidine gluconate bathing and oral rinse was associated with a reduction in surgical site infections in patients undergoing orthopedic surgery with hardware implantation.
      • Bebko SP
      • Green DM
      • Awad SS
      Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation.
      Given these promising results, there is a need for data on the efficacy of povidone iodine preparations. Therefore, we examined the efficacy of a commercial povidone iodine nasal sanitizer for reduction of nasal MRSA in colonized patients and assessed the duration of suppression of colonization.

      Methods

      Efficacy of a one-time application of povidone iodine nasal sanitizer

      We conducted a nonblinded, placebo-controlled randomized trial to determine the effectiveness of a one-time application of a commercial 10% povidone iodine preparation (PROFEND, Professional Disposables International, Woodcliff Lake, NJ) for reduction of MRSA in colonized patients in the hospital or long-term care facility. Patients were included if they had positive nares cultures for MRSA at the time of enrollment and had not received systemic antibiotic treatment or topical nasal antibiotics or antiseptics within the past 7 days.
      Participants (N = 11 per group) were randomly selected to receive either the povidone iodine sanitizer or phosphate-buffered saline. Saturated swabs (N = 4) were used by study staff to apply the product or phosphate-buffered saline to both nasal vestibules according to the manufacturer's instructions; for a total of 15 seconds, the swabs were rotated around the circumference of the nostril and then rotated in the anterior nares for a minimum of 6 complete revolutions with slight pressure, covering all surfaces. Two swabs were used for each nostril.
      For all participants, BBL Culture Swabs (Becton Dickinson, Franklin Lakes, NJ) were used to collect cultures from the anterior nares prior to and 1, 6, 12, and 24 hours after application. Swabs were also used to collect cultures for MRSA from the groin, axilla, and oropharynx. The swabs were vortexed in 1 mL of Dey-Engley neutralizer (Remel, San Diego, CA) and 100 µL aliquots were plated onto BBL CHROMagar (Becton Dickinson) with cefoxitin 6 µg/mL for quantification of MRSA.
      • Kanwar A
      • Cadnum JL
      • Thakur M
      • Jencson AL
      • Donskey CJ
      Contaminated clothing of methicillin-resistant Staphylococcus aureus (MRSA) carriers is a potential source of transmission.
      A standardized survey was used to collect information on adverse effects, including eye irritation, unpleasant odor or taste, and nasal itching, redness, and irritation. The study protocol was approved by the Cleveland VA Medical Center's institutional review board.

      Efficacy of repeated applications of the povidone iodine nasal sanitizer

      To determine if repeated dosing would enhance efficacy, we conducted a second nonblinded, placebo-controlled trial. Participants (N = 10 per group) were randomly selected to receive either the povidone iodine sanitizer or phosphate-buffered saline every 12 hours for 5 days (10 total doses). All applications were applied by study staff as previously described according to the manufacturer's instructions. Nares cultures were collected at baseline, immediately prior to each treatment dose, and 2 days after the final dose. Cultures were processed as previously described.

      Statistical analysis

      A prior study using skin explants and in healthy volunteers demonstrated a large treatment effect (ie, >2 log10 colony-forming unit reduction) of povidone iodine treatment.
      • Anderson MJ
      • David ML
      • Scholz M
      • Bull SJ
      • Morse D
      • Hulse-Stevens M
      • et al.
      Efficacy of skin and nasal povidone-iodine preparation against mupirocin-resistant methicillin-resistant Staphylococcus aureus and S. aureus within the anterior nares.
      Therefore, we anticipated that povidone iodine treatment might result in a large initial effect on the burden of MRSA in comparison to placebo treatment. A power calculation estimated that a small sample size of 10 per group would provide >80% power to detect a very large (interaction f >0.75) treatment-by-time effect. Repeated measures analysis of variance was used to compare the treatment and control groups. When significant effects were detected using F tests, tests of contrasts were used to determine which time points differed for treatment and control groups. All analyses were performed using R version 3.5.1 statistical software (The R Foundation for Statistical Computing, Vienna, Austria).

      Results

      Efficacy of a one-time application of povidone iodine nasal sanitizer

      Eleven patients in the povidone iodine group and 10 in the placebo group completed the study; 1 patient in the placebo group received the treatment but was not available for follow-up cultures. As shown in Figure 1, the single dose application of the povidone iodine nasal sanitizer was associated with a statistically significant reduction in mean MRSA concentrations at 1 and 6 hours after dosing, but not at 12 or 24 hours. Only 1 patient in each group had negative nasal cultures at 24 hours after application. At baseline, the frequencies of positive cultures of the groin, axilla, and oropharynx for the treatment groups were 90.9% (10 of 11), 63.6% (7 of 11), and 45.5% (5 of 11), respectively. For the control group, the frequencies of positive cultures of the groin, axilla, and oropharynx were 80.0% (8 of 10), 60.0% (6 of 10), and 80.0% (8 of 10), respectively. There were no reported adverse effects of the povidone iodine treatment.
      Fig 1
      Fig 1Effect of one-time application of a povidone iodine nasal sanitizer (N = 11 patients) versus phosphate-buffered saline (N = 10 patients) on the burden of methicillin-resistant Staphylococcus aureus in the nares of colonized patients. *P < .05. Error bars show standard error.

      Efficacy of repeated applications of the povidone iodine nasal sanitizer

      Nine patients in both groups completed the study; 1 patient in each group discontinued participation owing to the requirement for repeated study procedures. As shown in Figure 2, the povidone iodine group had lower mean nasal MRSA concentrations than the control group for measurements taken prior to each intranasal application (ie, 12 hours after the prior application) during the 5 days of treatment, but the differences were not statistically significant (P > .05). Only 2 of the 9 (22.2%) povidone iodine–treated patients had negative nasal cultures on day 7 (2 days after the final dose) versus 1 of 9 (11.1%) control patients. One patient in the povidone iodine group reported mild nasal itching during the treatment course, but there were no other reported adverse effects.
      Fig 2
      Fig 2Effect of repeated applications of a povidone iodine nasal sanitizer on the burden of methicillin-resistant Staphylococcus aureus in the nares of colonized patients (N = 9 patients per group). Nasal povidone iodine sanitizer or phosphate-buffered saline were applied every 12 hours on days 1 through 5 (10 total doses). Nares cultures were collected at baseline, immediately prior to each treatment dose (12 hours after the previous dose), and 2 days after the final dose. Error bars show standard error.

      Discussion

      In a randomized, nonblinded, placebo-controlled trial, we found that a single application of a 10% povidone iodine preparation significantly reduced nasal MRSA at 1 and 6 hours after application, but suppression was not sustained at 12 or 24 hours. Twice-daily treatment for 5 days did not reduce nasal MRSA measured 12 hours postdosing in comparison to controls. These results suggest that single preoperative applications of povidone iodine may be effective for short-term suppression of S aureus during the perioperative period.
      Several factors could potentially contribute to the lack of a sustained reduction in MRSA after povidone iodine application. First, povidone iodine concentrations may decrease rapidly after treatment due to factors such as protein binding. Second, MRSA embedded in mucus or present at the base of hair follicles may not be eliminated by povidone iodine, and may provide a site for regrowth as povidone iodine concentrations decrease.
      • Ten Broeke-Smits NJ
      • Kummer JA
      • Bleys RL
      • Fluit AC
      • Boel CH
      Hair follicles as a niche of Staphylococcus aureus in the nose; is a more effective decolonisation strategy needed?.
      Finally, S aureus could potentially be rapidly reestablished in the nares owing to reinoculation from colonized skin sites or contaminated clothing.
      • Kanwar A
      • Cadnum JL
      • Thakur M
      • Jencson AL
      • Donskey CJ
      Contaminated clothing of methicillin-resistant Staphylococcus aureus (MRSA) carriers is a potential source of transmission.
      In our study cohort, MRSA carriage was common in the groin, axilla, and oropharynx.
      Our study has some limitations. The study was conducted in 1 medical center with a predominantly male population and with a small number of subjects. Additional studies are needed in other settings and with larger cohorts of patients. We studied only a single application or 1 application every 12 hours. It is possible that more frequent dosing might be more effective in maintaining suppression of MRSA. If MRSA contamination on skin contributes to rapid recolonization of the nares, povidone iodine nasal sanitizers might be more effective when used in combination with chlorhexidine gluconate bathing. Additional studies are needed with povidone iodine used in combination with chlorhexidine gluconate bathing. Finally, we tested only 1 commercial povidone iodine product.

      Conclusions

      Our results suggest that single preoperative applications of povidone iodine may be effective for short-term suppression of S aureus during the perioperative period. It has been proposed that such temporary suppression of nasal S aureus during surgery may be sufficient to reduce the risk for surgical site infection,
      • Peng HM
      • Wang LC
      • Zhai JL
      • Weng XS
      • Feng B
      • Wang W
      Effectiveness of preoperative decolonization with nasal povidone iodine in Chinese patients undergoing elective orthopedic surgery: a prospective cross-sectional study.
      • Phillips M
      • Rosenberg A
      • Shopsin B
      • Cuff G
      • Skeete F
      • Foti A
      • et al.
      Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution.
      • Bebko SP
      • Green DM
      • Awad SS
      Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation.
      and preoperative nasal application of povidone iodine has been reported to be effective for prevention of S aureus surgical site infections in orthopedic surgery patients.
      • Phillips M
      • Rosenberg A
      • Shopsin B
      • Cuff G
      • Skeete F
      • Foti A
      • et al.
      Preventing surgical site infections: a randomized, open-label trial of nasal mupirocin ointment and nasal povidone-iodine solution.
      ,
      • Bebko SP
      • Green DM
      • Awad SS
      Effect of a preoperative decontamination protocol on surgical site infections in patients undergoing elective orthopedic surgery with hardware implantation.
      Additional studies are needed to confirm these findings and to evaluate the use of povidone iodine in patients undergoing other types of surgical procedures.

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