Reduction in bacterial load using hypochlorous acid hygiene solution on ocular skin.

PURPOSE: To examine the magnitude of bacterial load reduction on the surface of the periocular skin 20 minutes after application of a saline hygiene solution containing 0.01% pure hypochlorous acid (HOCl). METHODS: Microbiological specimens were collected immediately prior to applying the hygiene solution and again 20 minutes later. Total microbial colonies were counted and each unique colony morphology was processed to identify the bacterial species and to determine the susceptibility profile to 15 selected antibiotics. RESULTS: Specimens were analyzed from the skin samples of 71 eyes from 36 patients. Prior to treatment, 194 unique bacterial isolates belonging to 33 different species were recovered. Twenty minutes after treatment, 138 unique bacterial isolates belonging to 26 different species were identified. Staphylococci accounted for 61% of all strains recovered and Staphylococcus epidermidis strains comprised 60% of the staphylococcal strains. No substantial differences in the distribution of Gram-positive, Gram-negative, or anaerobic species were noted before and after treatment. The quantitative data demonstrated a >99% reduction in the staphylococcal load on the surface of the skin 20 minutes following application of the hygiene solution. The total S. epidermidis colony-forming units were reduced by 99.5%. The HOCl hygiene solution removed staphylococcal isolates that were resistant to multiple antibiotics equally well as those isolates that were susceptible to antibiotics. CONCLUSION: The application of a saline hygiene solution preserved with pure HOCl acid reduced the bacterial load significantly without altering the diversity of bacterial species remaining on the skin under the lower eyelid.

Safety and efficacy of moxifloxacin-dexamethasone eyedrops as treatment for bacterial ocular infection associated with bacterial blepharitis.

INTRODUCTION: Treatments that offer two medications in a fixed combination have the potential to offer efficacious and safe treatment with advantages such as a regimen that is simpler than administering two separate solutions. This study evaluated the safety and efficacy of fixed-combination versus concomitant moxifloxacin 0.5% and dexamethasone 0.1% ocular solutions for the treatment of bacterial ocular inflammation and infection. METHODS: The clinical study design was a randomized, double-masked, active-controlled, parallel-group trial of 102 subjects with bacterial blepharitis in which two patients also had bacterial conjunctivitis. All subjects received two bottles of study medication: either a fixed combination of moxifloxacin 0.5%/dexamethasone 0.1% ophthalmic solution and placebo eye drops (fixed-dose group), or moxifloxacin 0.5% ophthalmic solution and dexamethasone 0.1% (concomitant group). One drop of each study medication was instilled bilaterally four times per day for 7 days. Clinical resolution, signs, symptoms, and safety were assessed. Microbiological specimens were collected from the eyelid margin and conjunctivae of each eye from each patient at the time of enrollment and at the exit visit. RESULTS: Clinical resolution occurred similarly in both groups (81.6% of eyes, fixed-dose group; 82.3% of eyes, concomitant group). Moreover, the microbiological efficacy of the treatment was also similar for both the fixed-dose group (84%) and the concomitant group (83%). Ocular symptoms and signs improved over time, with no significant differences between groups after 7 days of treatment, except the fixed-dose group had significantly more eyes with clinical resolution in eyelid erythema (100%, n = 98/98, fixed-dose group; 92.7%, n = 89/96, concomitant group; P = 0.0194) and eyelid scaling/crusting (98%, n = 96/98, fixed-dose group; 89.6%; n = 86/96 eyes, concomitant group; P = 0.0337). Both regimens were safe and well tolerated. CONCLUSION: The fixed-dose combination of moxifloxacin, 0.5% and dexamethasone, 0.1% was therapeutically equivalent and as well tolerated as the concomitant dosage.

Topical ophthalmic moxifloxacin elicits minimal or no selection of fluoroquinolone resistance among bacteria isolated from the skin, nose, and throat.

PURPOSE: To investigate whether moxifloxacin therapy of bacterial conjunctivitis in children changes the moxifloxacin susceptibility of bacterial isolates in eyes, cheeks below eyes, nares, and throat. METHODS: Patients (age: 1 to 12 years, n = 105) with bacterial conjunctivitis were treated topically with moxifloxacin three times a day for 7 days. Gender- and age-matched subjects with normal eyes (age: 1 to 12 years, n = 57) served as the control group. Microbiological specimens were collected on days 1 (prior to therapy), 8 (1 day after end of therapy), and 42 (follow-up). Specimens were processed to recover total bacteria and bacteria that grew on fluoroquinolone-selective media. Bacteria were identified to the species level and susceptibility to moxifloxacin and selected other antibiotics determined. RESULTS: The primary pathogens recovered from the infected eyes on day 1 before therapy were Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. None of the pre-therapy isolates of H. influenzae and S. pneumoniae were resistant to moxifloxacin. Isolates of these two pathogenic species were also recovered primarily from the nose and eyes. Moxifloxacin-resistant S. aureus isolates (minimum inhibitory concentration 1.0 µg/mL or greater) were recovered from the nose and throat prior to topical dosing on day 1. However, there was no change in the frequency of moxifloxacin-resistant isolates of S. aureus following treatment with moxifloxacin. CONCLUSION: Treatment of conjunctivitis with topical ophthalmic moxifloxacin did not select for moxifloxacin resistance in H. influenzae, S. pneumoniae, or S. aureus in the eye or distal body sites.

Comparison of fluoroquinolone kinetics of kill in susceptible and resistant gram-positive conjunctival pathogens.

INTRODUCTION: The purpose of this study was to compare moxifloxacin's rate of kill of susceptible and resistant Gram-positive organisms with that of ciprofloxacin and ofloxacin, using concentrations found in human conjunctiva after instillation of one drop. METHODS: Staphylococcus aureus (S. aureus) and Streptococcus pneumoniae (S. pneumoniae) isolates were exposed to moxifloxacin, ciprofloxacin, or ofloxacin diluted to human conjunctival concentrations achieved after instillation of one drop. These treated isolates were cultured on blood agar plates at 0, 15, 30, and 60 minutes after exposure, and incubated to observe the number of surviving colony-forming units/mL. RESULTS: In susceptible S. pneumoniae, moxifloxacin showed the most rapid reduction of colonies at 15 and 30 minutes, with the fewest colonies at 60 minutes compared with ciprofloxacin and ofloxacin. In S. pneumoniae resistant to ciprofloxacin and ofloxacin, moxifloxacin had rapid reduction in colonies at each time point and near-eradication at 60 minutes, while ciprofloxacin and ofloxacin had an increase in colonies at 60 minutes. In susceptible S. aureus, moxifloxacin had a rapid decrease in colonies at 15 and 30 minutes, compared with a slight reduction in colonies at these intervals for the other antibiotics. In methicillin-resistant S. aureus with cross-resistance to fluoroquinolones and other antibiotics, moxifloxacin had a decrease in colonies at each time point compared with an increase at each time point for ciprofloxacin and ofloxacin. CONCLUSION: Moxifloxacin showed an increased speed of kill against both of the common susceptible Gram-positive conjunctival pathogens, compared with the inconsistency of killing activity of two other fluoroquinolones tested. In addition, at the concentration level achieved in the conjunctiva after the instillation of one drop, moxifloxacin effectively and rapidly killed resistant Gram-positive conjunctival pathogens, while ciprofloxacin and ofloxacin had no effect against these organisms.

Differences in bacteriologic treatment failures in acute otitis externa between ciprofloxacin/dexamethasone and neomycin/polymyxin B/hydrocortisone: results of a combined analysis.

OBJECTIVE: To compare treatment failure rates for the two major acute otitis externa (AOE) pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, by topical therapy with ciprofloxacin 0.3%/dexamethasone 0.1% (CDex) or neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1% (Cort) based on clinical and microbiological failure in patients positive for these pathogens at baseline. RESEARCH DESIGN AND METHODS: A combined analysis was conducted from two similar, but non-identical clinical trials involving CDex vs. Cort. Outcomes of the combined efficacy analysis were treatment failure rates and antibiotic susceptibility values for P. aeruginosa and S. aureus. The raw data for the treatment failure rates from the two studies were combined to calculate the overall treatment failure rates of each treatment group. Chi-square tests of independence were conducted to assess differences in treatment failure rates between treatment groups. RESULTS: Of the 789 patients with culture-positive ears prior to the initiation of therapy, 61.0% (n = 481) were positive for P. aeruginosa and 8.9% (n = 70) were positive for S. aureus. While treatment failure rates for S. aureus were similar for the two therapies, CDex had a significantly lower treatment failure rate than Cort (5.1 vs. 13.0%; p = 0.0044) for P. aeruginosa. All of the persisting P. aeruginosa and S. aureus isolates were susceptible to fluoroquinolones and neomycin/polymyxin B. LIMITATIONS: The analysis strength is dependent on pooled data from similar studies. CONCLUSIONS: Ototopical ciprofloxacin 0.3%/dexamethasone 0.1% more effectively eradicates P. aeruginosa compared to Cort. Eradication of S. aureus by either drug was similar. These results favor CDex as a better first-line choice in the treatment of AOE compared to Cort.

Ciprofloxacin 0.3%/dexamethasone 0.1% sterile otic suspension for the topical treatment of ear infections: a review of the literature.

The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.

The pharmacodynamic properties of azithromycin in a kinetics-of-kill model and implications for bacterial conjunctivitis treatment.

INTRODUCTION: Antibiotics have traditionally been classified as bactericidal or bacteriostatic. Azithromycin belongs to the parent class of macrolides that are characteristically bacteriostatic. Some evidence suggests that this molecule demonstrates bactericidal kill and has concentration-dependent effects. This study tests the hypothesis that azithromycin demonstrates a bactericidal, concentration-dependent antibiotic effect at concentrations corresponding to and exceeding published tear and conjunctival levels. METHODS: The antibacterial activity of different concentrations of azithromycin 1% in DuraSite(R) (AzaSite(R); Inspire Pharmaceuticals Inc, Durham, NC, USA) was evaluated using a kinetics-of-kill model. Recent conjunctivitis isolates of Staphylococcus aureus, Streptococcus pneumoniae or Haemophilus influenzae were exposed to four concentrations of azithromycin (100, 250, 500 and 750 microg/ml). Starting concentrations were similar to the maximum concentrations (Cmax) that have been demonstrated in conjunctiva (83 microg/g) and tears (288 microg/ml) following topical ocular administration. The percentage of surviving bacteria at 30 and 60 minutes following exposure to each concentration were determined. RESULTS: Azithromycin failed to demonstrate bactericidal activity (i.e. a 3-log reduction in surviving bacteria) against S. aureus, S. pneumoniae or H. influenzae. Furthermore, the rate and extent of antibacterial activity with azithromycin did not change with higher concentrations, even at the highest tested concentration of 750 microg/ml. CONCLUSION: Similar to the parent macrolide class, azithromycin demonstrates bacteriostatic activity against common conjunctival pathogens up to the maximum tested concentration of 750 microg/ml (i.e. 2.6-times and 9-times published Cmax tear and conjunctival concentration, respectively). Azithromycin's bacteriostatic effects and prolonged elimination half-life will likely lead to a corresponding increase in the emergence of macrolide-resistant isolates.

Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension.

INTRODUCTION: TobraDex ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container. METHODS: A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose. RESULTS: Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST. CONCLUSION: TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.

Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.

It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis. A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae. In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.

Virulence factor profiles and antimicrobial susceptibilities of ocular bacillus isolates.

Bacillus causes one of the most rapidly blinding intraocular infections: endophthalmitis. In this study, Bacillus spp. were isolated from ocular infection cases, taxonomically characterized by riboprint analysis, and screened for the presence of putative virulence factors. The ability of these isolates to kill retinal and corneal cells was examined, as were antibiotic susceptibility profiles. The majority of isolates belonged to the B. cereus taxonomic group of microorganisms and were identified as B. cereus (53%) or B. thuringiensis (26%). Toxins were identified in most B. thuringiensis and B. cereus isolates. Most B. cereus and B. thuringiensis killed corneal and retinal cells within 6 h. All isolates were susceptible to most antibiotics tested, with quinolones and vancomycin being the most potent. These findings represent the first report of B. thuringiensis as an important ocular pathogen, demonstrates the potential ocular toxicity of B. cereus and B. thuringiensis isolates, and identifies antibiotics whose efficacy against Bacillus were superior to those used clinically.

Pseudomonas otitidis sp. nov., isolated from patients with otic infections.

A novel Pseudomonas species, for which the name Pseudomonas otitidis sp. nov. is proposed, was identified from clinical specimens of infected human ears. Forty-one pseudomonads (34 from patients with acute otitis externa, six from patients with acute otitis media with otorrhoea and one from a patient with chronic suppurative otitis media) were recovered that did not match any known species. On the basis of genetic analyses and biochemical characterization, these isolates were shown to belong to the genus Pseudomonas. 16S rRNA gene sequence analysis and DNA-DNA hybridization studies indicated that this novel bacterium is closely related to, but different from, Pseudomonas aeruginosa. A description of this species is based on polyphasic studies of 11 clinical isolates. The type strain of Pseudomonas otitidis is MCC10330T (=ATCC BAA-1130T = DSM 17224T).

In vitro and in vivo potency of moxifloxacin and moxifloxacin ophthalmic solution 0.5%, a new topical fluoroquinolone.

Fluoroquinolones are a class of synthetic antibacterial agents that were approved for ocular therapy in 1991 and have become popular therapy for the treatment and prevention of various ocular infections. These agents are synthetic, broad-spectrum, rapidly bactericidal, and have good penetration into ocular tissues. Their main mechanism of action is the inhibition of bacterial enzymes needed for bacterial DNA synthesis. However, antibiotic resistance occurred swiftly to the earlier fluoroquinolones and better fluoroquinolones were needed. The fourth-generation fluoroquinolones, such as moxifloxacin and gatifloxacin, have enhanced activity against gram-positive bacteria while retaining potent activity against most gram-negative bacteria. These fourth-generation fluoroquinolones have improved penetration into the anterior chamber and have also demonstrated increased in vivo efficacy in several animal models of ocular infections. In addition, topical ophthalmic antibiotic products can deliver antibiotic concentrations directly to the eye that are thousands of times higher than their MICs. This article reviews published data describing the in vitro potency of moxifloxacin and its in vivo activity for treating and preventing experimental ocular infections.

Microbiology of acute otitis media with tympanostomy tubes.

OBJECTIVE: The objective was to determine the types of organisms which cause acute otitis media with a tympanostomy tube and to ascertain their frequency distribution. STUDY DESIGN AND SETTING: Prospective, randomized, multi-institutional clinical trials. Both private and academic sites were included. RESULTS: 1309 isolates were recovered from 956 draining ears. Streptococcus pneumonia was recovered from 17%, Staphylococcus aureus from 13%, H flu from 18% and Pseudomonas aeruginosa from 12%. Fungal organisms were recovered from 5% of total isolates and 4% from single isolates. CONCLUSIONS: AOMT is microbiologically different than AOM with an intact TM. There is no evidence that resistance develops as result of topical treatment. SIGNIFICANCE: The study demonstrates that AOMT is frequently caused by organisms not susceptible to oral antibiotics approved for children, but which are sensitive to topical ear drops.

Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa.

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE). STUDY DESIGN: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3-4 drops twice daily or N/P/H 3-4 drops three times daily. POPULATION: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate. OUTCOMES MEASURED: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events. RESULTS: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0.0279 and p = 0.0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients. CONCLUSIONS: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of

Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes.

OBJECTIVE: To determine whether topical administration of a corticosteroid improves resolution of acute tympanostomy tube otorrhea when combined with topical antibiotic drops. STUDY DESIGN: Randomized, patient-masked, parallel-group, multicenter trial of topical otic ciprofloxacin/dexamethasone versus topical ciprofloxacin alone in 201 children aged 6 months to 12 years with acute otitis media with tympanostomy tubes (AOMT) of less than or equal to 3 weeks' duration and visible otorrhea. METHODS: Eligible patients were randomized to receive three drops of either ciprofloxacin 0.3%/dexamethasone 0.1% or ciprofloxacin 0.3% into the affected ear or ears twice daily for 7 days. Clinical signs and symptoms of AOMT were evaluated on days 1 (baseline), 3, 8 (end-of-therapy), and 14 (test-of-cure), and twice-daily assessments of otorrhea were recorded in patient diaries. RESULTS: The mean time to cessation of otorrhea in the microbiologically culture-positive patient population (n = 167) was significantly shorter with topical ciprofloxacin/dexamethasone than with ciprofloxacin alone (4.22 vs. 5.31 days; P =.004). This resulted in significantly better clinical responses on days 3 and 8 (P <.0001 and P =.0499, respectively). However, there were no significant differences between the two treatment groups in either the clinical response or the microbial eradication rate by day 14. CONCLUSIONS: Topical otic treatment with ciprofloxacin/dexamethasone is superior to treatment with ciprofloxacin alone and results in a faster clinical resolution in children with AOMT. The contribution of the corticosteroid in achieving a 20% reduction (1.1 day) in time to cessation of otorrhea is clinically meaningful and represents an important advance over single-agent antibiotic therapy.

Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis.

PURPOSE: The purpose of this study was to determine the effectiveness of mupirocin and polymyxin B, alone and in combination, in vitro and in vivo using rabbit models of, and keratitis. METHODS: Rabbit eyes were intrastromally injected with 1,000 colony-forming units (CFUs) of or or 100 CFUs of Rabbits were then treated with 2.7 mg/mL mupirocin, 10,000 U/mL polymyxin B, a mupirocin:polymyxin B combination, or 0.3% ciprofloxacin. Vehicle and untreated controls were also included. Treatment schedules depended on the strain injected. The number of CFUs was determined for all eyes after treatment. RESULTS: The mupirocin:polymyxin B combination was effective for all three genera both in vitro and in vivo. For keratitis, the mupirocin:polymyxin B combination was more effective than either drug alone and significantly reduced the log number of bacteria in the cornea by more than 3 logs compared with the vehicle or untreated controls (p

Microbiology of acute otitis externa.

OBJECTIVE: To isolate and characterize bacteria and fungi from acute otitis externa (AOE) and to obtain susceptibility profiles on each bacterial isolate. STUDY DESIGN: Prospective core series. METHODS: Specimens were collected from the external canals of subjects with clinically diagnosed acute otitis externa. Species-level identification for each bacterial isolate recovered was obtained by combining phenotypic and genotypic data. End point mean inhibitory concentration (MIC) testing was performed using National Committee for Clinical Laboratory Standards (NCCLS) recommended methods. RESULTS: In Alcon-sponsored clinical studies conducted in 1998 to 2000, microbiology specimens were collected from 2039 subjects (2240 diseased ears) by 101 investigators throughout the United States. A total of 2838 bacteria, 32 yeast, and 17 molds were recovered from 2048 ears clinically diagnosed as acute otitis externa. Of the 202 bacterial species recovered, the species most frequently isolated was Pseudomonas aeruginosa (38%). The next 10 species most frequently isolated were: Staphylococcus epidermidis, 9.1%; Staphylococcus aureus, 7.8%; Microbacterium otitidis, 6.6%; Microbacterium alconae, 2.9%; Staphylococcus caprae, 2.6%; Staphylococcus auricularis, 2.0%; Enterococcus faecalis, 1.9%; Enterobacter cloacae, 1.6%; Staphylococcus capitis subsp. Ureolyticus,1.4%; and Staphylococcus haemolyticus, 1.3%. Susceptibility profiles of S. epidermidis isolates revealed the greatest frequency of high-level resistance to selected antibiotics (>/=8 microg/mL): 23%, neomycin-resistant; 11%, oxacillin-resistant; and 12%, ofloxacin-resistant. Susceptibility profiles of S. aureus isolates revealed a lower frequency of high-level resistance: 6.3%, neomycin-resistant; 2.7%, oxacillin-resistant; and 4.5%, ofloxacin-resistant. P. aeruginosa with high-level resistance to quinolones (>/=128 mcg/mL for ofloxacin) was recovered from only 1 subject. Likewise, resistance of P. aeruginosa to aminoglycosides was rare. Twenty isolates had neomycin MICs >/=64 mcg/mL and 10 isolates had gentamicin MICs >/=16 mcg/mL. The coryneform isolates identified as Microbacterium otitidis had an intrinsic lack of susceptibility to quinolones (ofloxacin MICs >/=16 mcg/mL) and aminoglycosides (tobramycin MICs >/=32 mcg/mL and gentamicin MICs >/=8 mcg/mL). CONCLUSIONS: Bacterial infections of the external ear canal are most often caused by P. aeruginosa. However, there are a great number of other gram-positive and gram-negative bacterial species that are recovered from patients with acute otitis externa. Because of this diverse etiology, the best topical therapeutic choice for topical therapy is for the most potent, broad-spectrum (especially anti-P. aeruginosa) antibiotic available.