Abstract
Objectives
Methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S aureus (MRSA) contribute to 25% of nosocomial infections, increasing complications, health care cost, and growing antibiotic resistance. Nasal decolonization (ND) can reduce the staphylococcal infection rate. A new method of laser therapy (LT) MRSA ND was tested.
Study design
This is a prospective, nonrandomized study.
Methods
Following institutional review board approvals, 25 patients colonized with MSSA/MRSA were allocated to 4 treatment arms; low-power, dual-wavelength 870-/930-nm laser alone (GR1); low-power, dual-wavelength laser followed by erythromycin (E-mycin) cream (GR2); low-power, dual-wavelength laser followed by peroxide irrigation (GR3); and high-power 940-nm laser alone (GR4). Quantitative cultures were obtained before and after in all arms. Laser therapy was performed via a laser fiber diffuser, delivering 200 to 600 J/cm² to each naris circumferentially. Patient’s distribution was 3 in GR1, 14 in GR2, 4 in GR3, and 4 in GR4 (last 10 recruited to GR4).
Results
Nasal decolonization for GR1, GR2, GR3, and GR4 was 1 of 3, 13 of 14, 2 of 4, and 4 of 4, respectively. Because LT + E-mycin cleared all first 3 patients of MRSA and MSSA, all remaining patients were treated with LT + Er with over 90% of patients clearing. No adverse events or discomfort were reported.
Conclusions
First human study using LT and topical E-mycin in ND is presented. Laser therapy can eradicate MRSA and potentially resensitization of bacteria to the antimicrobial effect of erythromycin. Although decolonization was maintained at 4 weeks posttreatment, further studies can determine the LT long-term effect.
1
Introduction
Methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S aureus (MRSA) contribute to 25% of nosocomial infections, substantially increasing complications and substantial health care costs. As reported by Klevens and Morrison , MRSA has shown an epidemiological shift as MRSA infections in intensive care units increased 3.1% per year from 35.9% in 1992 (660/1883) to 64.4% (2184/3392) in 2003 for hospitals in the National Nosocomial Infections Surveillance system.
The opportunity to prevent nosocomial staphylococcal infections was shown in several large studies. In 2002, Perl and Cullen showed a decrease in nosocomial staphylococcal infection by application of 2% nasal Bactroban; the rate of infection was reduced from 7.7% in the placebo group to 4%. A recent study performed in 2010 showed the S aureus rate of infection to be 3.4% in the Bactroban-treated group vs 7.7% in the placebo, with a quicker onset of infection in the placebo group .
Methicillin-resistant S aureus carriers, typically via nasal colonization, have demonstrated a rising incidence of developing surgical site infections. Mupirocin is commonly used for nasal decolonization of MRSA, but increased usage will undoubtedly lead to a higher resistance rate. In 1999, the rate of mupirocin resistance in New Zealand was shown to be 28%, and in 3 US hospitals that implemented universal S aureus surveillance and mupirocin-based decolonization for all inpatient MRSA carriers, mupirocin resistance substantially increased, from 4.1% to 7.2% among all MRSA isolates during a 3-year period .
An important turn in bacterial killing took form when Neuman et al discovered optical tweezers (infrared laser-based optical traps), showing that near infrared (NIR) laser light was the most effective in bacterial photodamage. Bornstein et al showed the mechanism of action to be photo-energy absorbance of bacterial chromophores leading to a decrease of plasma membrane potential in bacteria with additional generation of free oxygen radicals. Using 870- to 930-nm NIR laser activation with fluency of 5.66 W/cm 2 , a 2-log reduction in staphylococcal load was achieved in vitro, whereas fluency of 4.5 W/cm 2 achieved a 68% eradication of MRSA by colony-forming unit (CFU) counts. Krespi et al showed that a 940-nm laser with fluency of 1.69 W/cm 2 and a total of 540 J delivered could reduce Staphylococcus by 47% via optical killing without raising tissue temperature. The 940-nm diode laser illumination was also suggested to possess MRSA eradication benefits, after an MRSA-associated biofilm was disrupted with a Q-switched YAG laser–generated shockwave . Another important characteristic of laser treatment for nasal decolonization is its ability to potentiate antibiotics that were previously ineffective. The antibiotic potentiating effect on MRSA was most pronounced with erythromycin (E-mycin) cream, where a potentiation from 57% kill by laser alone to 97% when laser was followed by application of E-mycin cream (7).
The published benefits of NIR laser-activated bacterial killing, with and without concomitant antibiotic treatment, led to the present study in which the gathered knowledge was translated to a multiarm human pilot study to establish safety and potential efficacy. Our goal was to assess the possibility of nasal staphylococcal decolonization, including MRSA, by laser, and to determine the optimal laser dosimetry and duration.
2
Methods
The institutional review board–approved (New England IRB, http://www.neirb.com /) study was a nonrandomized open enrollment with the following inclusion criteria: age older than 18 years, nonlactating or pregnant state, a positive nasal vestibular culture by swab for MSSA or MRSA, no report of antibiotic use in the month before the culture, no use of mupirocin in the past 4 months, no active sinusitis or other infection necessitating control with an antibiotic, no prior hospitalization (>14 days) during the past 12 months, no ongoing outpatient hemodialysis, and no recent surgical site infection or proximity to a patient colonized or infected with MSSA or MRSA. All patients enrolling in the study provided informed consent. Using conventional culture methods designed by infections control staff, a wet cotton wool swab was used to obtain samples from each nostril and then plated for manual CFU counts. Laser therapy (LT) was delivered using an NIR laser unit and specially designed nasal diffuser with a 3-cm active cylindrical tip with specific eye protective goggles worn by the subjects and the staff. The diffuser was introduced inside a disposable glass tube to dilate the nasal vestibule and achieve uniform illumination. Laser activation was for 4 to 5 minutes at 3 to 4 W in continuous mode, delivering up to 600 J to the inner lining of each nostril. During the laser activation, the external nasal skin temperature was monitored. Maximum skin tissue temperature was allowed to raise 6°F to 8°F from baseline.
The treatment was repeated on days 3 and 5. Cultures were obtained before each treatment. The laser was activated to illuminate over the skin-lined inner vestibule of the nose with the intent of leaving the endonasal ciliary mucosa intact.
To determine the safety and efficacy of the NIR laser decolonization, a small group of patients were treated using different dosimetry with and without a topical antibacterial agent.
The 4 groups comprised the following: laser only (dual wavelength, 870–930 nm, at 200 J), laser followed by peroxide irrigation, laser and E-mycin application, and laser only (single wavelength, 940 nm at 600 J).
The first 15 patients were allocated to groups to choose the most efficient staphylococcal decolonizing treatment arm. The group with the most positive results was then used to identify the treatment for the next enrolling 10 subjects.
2
Methods
The institutional review board–approved (New England IRB, http://www.neirb.com /) study was a nonrandomized open enrollment with the following inclusion criteria: age older than 18 years, nonlactating or pregnant state, a positive nasal vestibular culture by swab for MSSA or MRSA, no report of antibiotic use in the month before the culture, no use of mupirocin in the past 4 months, no active sinusitis or other infection necessitating control with an antibiotic, no prior hospitalization (>14 days) during the past 12 months, no ongoing outpatient hemodialysis, and no recent surgical site infection or proximity to a patient colonized or infected with MSSA or MRSA. All patients enrolling in the study provided informed consent. Using conventional culture methods designed by infections control staff, a wet cotton wool swab was used to obtain samples from each nostril and then plated for manual CFU counts. Laser therapy (LT) was delivered using an NIR laser unit and specially designed nasal diffuser with a 3-cm active cylindrical tip with specific eye protective goggles worn by the subjects and the staff. The diffuser was introduced inside a disposable glass tube to dilate the nasal vestibule and achieve uniform illumination. Laser activation was for 4 to 5 minutes at 3 to 4 W in continuous mode, delivering up to 600 J to the inner lining of each nostril. During the laser activation, the external nasal skin temperature was monitored. Maximum skin tissue temperature was allowed to raise 6°F to 8°F from baseline.
The treatment was repeated on days 3 and 5. Cultures were obtained before each treatment. The laser was activated to illuminate over the skin-lined inner vestibule of the nose with the intent of leaving the endonasal ciliary mucosa intact.
To determine the safety and efficacy of the NIR laser decolonization, a small group of patients were treated using different dosimetry with and without a topical antibacterial agent.
The 4 groups comprised the following: laser only (dual wavelength, 870–930 nm, at 200 J), laser followed by peroxide irrigation, laser and E-mycin application, and laser only (single wavelength, 940 nm at 600 J).
The first 15 patients were allocated to groups to choose the most efficient staphylococcal decolonizing treatment arm. The group with the most positive results was then used to identify the treatment for the next enrolling 10 subjects.
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