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Evaluation of Topical Povidone-Iodine in Chronic Suppurative Otitis Media
C. Jaya, MBBS, MS;
Anand Job, MBBS, DLO, MS;
Elizabeth Mathai, MBBS, MD, DTM&H, MSc;
B. Antonisamy, MSc, PhD
Arch Otolaryngol Head Neck Surg. 2003;129:1098-1100.
ABSTRACT
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Objectives To evaluate if povidone-iodine (PVP-I) can be used topically in the treatment of chronic suppurative otitis media–tubotympanic disease and to compare it with ciprofloxacin hydrochloride ear drops.
Design Prospective double-blind randomized study.
Setting Academic tertiary medical center.
Patients Forty patients with chronic suppurative otitis media were randomized into 2 groups.
Intervention One group (19 patients) received 5% PVP-I ear drops, while the other group (21 patients) received 0.3% ciprofloxacin ear drops. Both were administered topically, 3 drops 3 times daily for 10 days. These patients were followed up at weekly intervals for up to 4 weeks after commencing therapy.
Results Clinical improvement at the end of study was 88% in the PVP-I group and 90% in the ciprofloxacin group. The most commonly isolated organism was Pseudomonas aeruginosa. In vitro resistance to ciprofloxacin was seen in 17% of organisms, while no resistance was seen for PVP-I.
Conclusions To our knowledge, this is the first study to evaluate the efficacy of PVP-I as a topical agent in the treatment of chronic suppurative otitis media. The results show that clinically, topical PVP-I is as effective as topical ciprofloxacin, with a superior advantage of having no in vitro drug resistance. Also, there is an added benefit of reduced cost of therapy.
INTRODUCTION
TOPICAL EAR DROPS have been the mainstay in the medical management of actively discharging chronic suppurative otitis media (CSOM) with central perforation.1 Irreversible tissue damage and fibrosis caused by infection renders systemic therapy less effective. Bacterial pathogens in CSOM vary considerably and can be a combination of both aerobic and as anaerobic bacteria.2 Gentamicin, neomycin, and polymyxin B were previously used as ototopical preparations despite being proven to be ototoxic3 until the introduction of ciprofloxacin hydrochloride. This drug is presently considered to be the gold standard, with studies proving its superior clinical and bacteriological efficacy as well as absence of ototoxicity.4-5 However, with increasing clinical usage, quinolone resistance has been reported, especially following long-term therapy.6
Povidone (polyvinyl pyrrolidone)-iodine (PVP-I) has been extensively used over the past 20 years for various clinical purposes on skin and mucosa without any serious local or systemic adverse effects.7 The antimicrobial spectrum of this agent is universal, including gram-positive and gram-negative bacteria, anaerobes, spores, mycobacteria, fungi, viruses, and protozoans.7 In contrast to other antiseptics such as chlorhexidine and benzalkonium chloride, development of resistance has not been detected for PVP-I.8 Experimental studies have demonstrated that PVP-I aqueous solution does not show any ototoxic potential.9-10 In our hospital we have been using a combination of bismuth, iodoform, and paraffin (BIPP) to pack mastoidectomy cavities following surgical procedures on the ear for over 30 years with no incidence of ototoxicity. In their study comparing xeroform and BIPPS, Chevretton et al11 have concluded that BIPPS was the mastoid dressing of choice. Povidone-iodine is readily available, chemically stable, and relatively inexpensive. On these grounds, 5% PVP-I (marketed as Betadine) was evaluated as a topical agent in the treatment of active CSOM–tubotympanic disease in comparison with topical 0.3% ciprofloxacin hydrochloride.
METHODS
A randomized double-blind prospective trial was conducted in the otolaryngology outpatient department of the Christian Medical College and Hospital, Vellore, India, between March and November 2000, to assess if 5% PVP-I could be used in the medical management of active CSOM–tubotympanic disease. The appropriate institutional review board approved the project.
Eligibility for the study was confined to patients older than 10 years and having actively discharging CSOM with moderate to large central perforation. Chronic suppurative otitis media associated with cholesteatoma, aural polyp, or impending complications was excluded. Also, patients with debilitating illness such as diabetes mellitus, tuberculosis, renal failure, or AIDS, those with known allergy to iodine or fluoroquinolone, and those who had prior systemic or topical antibiotic therapy within 10 days of starting the study were not included.
After obtaining informed consent, the 2 drugs (5% PVP-I and 0.3% ciprofloxacin) were randomly distributed among the study groups. Both drugs were colored identically and were dispensed in identical bottles, labeled with code numbers only. All 40 patients who entered the study underwent microscopic examination of ears, pus culture for aerobic pathogens, and aural suctioning. Susceptibility testing was by the disk diffusion method.12 A modified time-kill method13 was used to test the susceptibility of isolates to PVP-I. Briefly, the method is as follows: a standard suspension of a bacterial isolate was inoculated into 5% PVP-I (neat and dilutions up to 1:256) with and without serum. These were subcultured at 10 minutes and 60 minutes to test for viability. The inoculum alone was subcultured at 10 and 60 minutes to ensure viability of the organism in the absence of PVP-I.
After an audiometric assessment, the patient was given a coded bottle with ear drops and instructed to instill 3 drops 3 times daily by the tragal displacement method after dry mopping1 for a period of 10 days. These patients were followed up at weekly intervals for 4 weeks after commencing therapy. During their review visits, outcomes were evaluated by microscopic examination and graded as actively discharging or inactive. Aural toilet was done at subsequent visits for both groups of patients if the ear was producing discharge. Specific inquiries were made about any symptoms of ototoxic effects or allergy to the drug. At the end of 4 weeks, if the ear was still producing discharge, a second ear swab was sent for culture and sensitivity. A poststudy pure-tone audiogram was done in all cases. At the end of the study, the randomization code was decoded. Statistical analysis of the results was done using  2 test.
RESULTS
Of the 40 patients who entered into the study, 19 were given 5% PVP-I as ear drops, and 21, 0.3% ciprofloxacin ear drops. Table 1 summarizes the baseline characteristics of patients enrolled in the study.
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Table 1. Baseline Characteristics of Patients Enrolled in the Study*
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Outcome after treatment is given in Table 2. At the culmination of study, clinical improvement was 88% in PVP-I group and 90% in ciprofloxacin group, with the difference being statistically nonsignificant (P values ranged from .87-.81 in the 4-week period [Table 2]).
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Table 2. Outcome After Treatment With Ear Drops*
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Other factors such as age of the patient, total duration of disease, duration of present episode of ear discharge, severity of otorrhea at initial presentation, size of perforation, and status of middle ear mucosa were not found to significantly alter the outcome in both groups.
Of the 40 ear swabs taken, 32 yielded potential bacterial pathogen, and a total of 46 isolates were obtained. Pseudomonas aeruginosa (16) and Staphylococcus aureus (14) accounted for about 65% of isolates. The other isolates included coliforms (8 [Escherichia coli, Klebsiella species, Enterobacter species, and Citrobacter diversus]); nonfermenting gram-negative bacteremia (5 [2 Acinetobacter baumannii complex, 2 Pseudomonas species, and 1 not identified]); Proteus mirabilis (2); and group G  -hemolytic streptococci (1). Eight isolates from 7 patients were resistant to ciprofloxacin (5 isolates of P aeruginosa and 1 each of methicillin-resistant S aureus, A baumannii complex, and Pseudomonas species). Four of these 7 patients, all with Pseudomonas infection, belonged to the ciprofloxacin group, and the remaining 3 to the PVP-I group. Ears of 2 patients in the former group healed, while 2 remained active. Second cultures from both patients grew P aeruginosa resistant to ciprofloxacin. In the PVP-I group, 2 patients including the one with methicillin-resistant S aureus infection responded to treatment. The third patient who had A baumannii infection did not respond to PVP-I treatment. One more patient in the PVP-I group did not show clinical response. This patient had P aeruginosa susceptible to ciprofloxacin on the initial and second cultures. All of these isolates were susceptible to PVP-I.
Figure 1 shows the effect of PVP-I on 43 bacterial isolates tested. In dilutions up to 1:32 without serum, all isolates became nonviable at 10 minutes, while with serum this effect was seen in only dilutions up to 1:16. Killing effect was observed even at 1:256 dilutions for 37% of isolates tested without serum and only in 7% with serum.
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Number of isolates viable after 10 minutes of exposure to povidone-iodine in dilutions.
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No patient developed allergic manifestations or ototoxic effects. There was no deterioration of hearing as assessed by pure-tone audiometry.
COMMENT
The results of this prospective randomized study reconfirm the efficacy of repeated aural toilet and daily use of ototopical agents in the treatment of actively discharging CSOM with central perforation.14
Topical ciprofloxacin is the gold standard in the antimicrobial treatment of active disease4-5; its use can lead to emergence of resistant organisms and superinfection with fungus.4 In addition, ciprofloxacin does not have much action against anaerobic bacteria, which is now being increasingly isolated from ears with CSOM,2 and is also relatively expensive for use in developing countries. Therefore, a more cost-effective, nonantibiotic preparation with effective antimicrobial properties but with no potential to develop drug resistance and ototoxicity would be an ideal alternative in the treatment of CSOM–tubotympanic disease.
In our study, PVP-I was found to be clinically as effective as ciprofloxacin (88% vs 90%) with no adverse effects. Of the isolates, 17% showed in vitro resistance to ciprofloxacin and none to PVP-I. It is significant to note that both patients in whom ciprofloxacin treatment had failed had infections with resistant bacteria. This problem is likely to increase because of increasing prevalence of quinolone-resistant bacteria.6 The clinical response observed in patients using ciprofloxacin who had ciprofloxacin-resistant organisms may be explained by a high concentration achieved with topical preparations. This phenomenon has been well documented with gentamicin ear drops.15
In vitro, 5% PVP-I could kill all bacterial isolates tested. Even in increasing dilutions, the bactericidal activity was good; although, there was some inhibition of activity in the presence of serum as described in previous studies.8 In ears that remained active at the end of treatment with PVP-I, second cultures grew organisms that were sensitive to PVP-I. Although no definite cause for treatment failure in this group could be ascertained, it is possible that these patients were noncompliant.
This study performed on a small sample suggests that topical PVP-I is effective for treatment of CSOM and may be considered as an alternative to antibiotic therapy. Studies on larger groups of patients is recommended to confirm our results and to detect causes of persistent otorrhea not responding to this compound.
AUTHOR INFORMATION
Corresponding author and reprints: Anand Job, MBBS, DLO, MS, Department of Otorhinolaryngology and Head and Neck Surgery, Unit 1, Christian Medical College, Vellore 632 004, India (e-mail: ent1{at}cmcvellore.ac.in).
Submitted for publication January 16, 2002; final revision received December 30, 2002; accepted January 24, 2003.
From the Departments of Otorhinolaryngology and Head and Neck Surgery (Drs Jaya and Job), Clinical Microbiology (Dr Mathai), and Biostatistics (Dr Antonisamy), Christian Medical College, Vellore, India. The authors have no relevant financial interest in this article.
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