A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis.

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p = 0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction.

The role of computed tomography in the diagnosis of acute appendicitis.

BACKGROUND: Routine contrast-enhanced computed tomography (CECT) has been described as an accurate diagnostic imaging modality in patients with acute appendicitis. However, most patients with acute appendicitis can be diagnosed by clinical findings and physical exam alone. The role of CECT in patients suspected of having appendicitis but with equivocal clinical exams remains ill defined. METHODS: One hundred and seven consecutive patients who were thought to have appendicitis but with equivocal clinical findings and/or physical exams were imaged by CECT over a 12-month period. Oral and intravenous contrast-enhanced, spiral abdominal and pelvic images were obtained using 7-mm cuts. CECT images were interpreted by a board-certified radiologist. Main outcome measures included CECT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in the diagnosis of acute appendicitis, comparing CECT with ultrasound, and determining the impact of CECT on the clinical management of this patient population. RESULTS: A group of 107 patients consisting of 44 males (41%) and 63 females (59%) with a median age of 33 years (range 13 to 89 years) were imaged with CECT to evaluate suspected appendicitis. Of the 107 CECTs performed, 11 false-positive and 3 false-negative readings were identified, resulting in a sensitivity of 92%, specificity of 85%, PPV of 75%, NPV of 95%, and an overall accuracy of 90%. Forty-three patients were imaged with ultrasound and CECT, and CECT had significantly better sensitivity and accuracy (30% versus 92% and 69% versus 88%, P<0.01). With regard to clinical management, 100% (36/36) of patients with appendicitis, and 4.2% (3/71) of patients without appendicitis underwent appendectomy. Therefore, the overall negative appendectomy rate was 7.6% (3/39). CONCLUSIONS: CECT is a useful diagnostic imaging modality for patients suspected of having acute appendicitis but with equivocal clinical findings and/or physical exams. CECT is more sensitive and accurate than ultrasound and is particularly useful in excluding the diagnosis of appendicitis in those without disease.

Effectiveness of ciprofloxacin and ofloxacin in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic fluoroquinolone treatment against staphylococci in a rabbit keratitis model. METHODS: Prophylactic ciprofloxacin or ofloxacin was applied as one topical drop 15 minutes before infection or as one drop at three time points (19, 17, and 15 minutes) before infection. In a second experiment, rabbits were treated with two, three, or four drops of ciprofloxacin 1 hour before infection. Approximately 250 colony-forming units (CFUs) of Staphylococcus aureus were injected intrastromally, and CFUs were determined 5 hours after infection. RESULTS: The CFUs per cornea in all treatment groups were significantly less than the 5.6 +/- 0.11 log CFUs per cornea in the untreated group ( p < or = 0.0001). Rabbit eyes treated 15 minutes before infection with Ciloxan or Ocuflox had 0.96 +/- 0.48 log CFUs per cornea (three of six sterile corneas) or 1.26 +/- 0.31 log CFUs per cornea (one of six sterile corneas), respectively ( p = 0.5226). Eyes treated with Ciloxan 19, 17, and 15 minutes before infection had 0.0 +/- 0.0 log CFUs per cornea, and all eyes were sterile, whereas eyes treated with Ocuflox had 0.98 +/- 0.48 log CFUs per cornea and two of six eyes sterile ( p = 0.0435). Eyes treated 1 hour before infection with two, three, or four drops of Ciloxan had 2.61 +/- 0.69 log CFUs, 1.23 +/- 0.32 log CFUs, or 0.85 +/- 0.28 log CFUs per cornea, respectively, which was significantly less than untreated eyes ( p < or = 0.0001). CONCLUSIONS: Multiple topical drops of a fluoroquinolone administered prophylactically were effective for subsequent staphylococcal ocular infection.

Microbiology of normal external auditory canal.

OBJECTIVES: To isolate and characterize bacteria and fungi from the healthy ear and to obtain susceptibility profiles on each bacterial isolate. STUDY DESIGN: Prospective. METHODS: Specimens were collected from the external canals and cerumen of healthy subjects. Species-level identification was obtained by combining phenotypic and genotypic data. End-point minimal inhibitory concentration testing was performed using National Committee for Clinical Laboratory Standards recommended methods. RESULTS: One hundred sixty-four subjects were cultured. Seventeen canal and 16 cerumen specimens showed no growth. One hundred forty-eight cerumen specimens yielded 314 organisms, including 23 fungi. One hundred forty-seven canal specimens yielded 310 organisms, including 7 fungi. Of 291 bacteria isolated from cerumen, 99% were Gram-positive. Of 302 bacteria isolated from the canal, 96% were Gram-positive. Staphylococci were 63% of both the cerumen bacteria and the canal bacteria. Coryneforms represented 22% of the bacteria in cerumen and 19% in the canal. Turicellaotitidis was the primary coryneform isolated from both the canal and the cerumen. Streptococci-like bacteria were 10% from the cerumen, 7% from the canal. In both cerumen and canal, Alloiococcusotitis was more than 95% of the streptococci-like bacteria. Fifteen gram-negative organisms were isolated from the canal and cerumen, including four Pseudomonas aeruginosa strains. The percentages of Staphylococcus epidermidis isolates that had high-level resistance (> or =8 microg/mL) were as follows: to neomycin, 28% from cerumen and 11% from the canal; to oxacillin, 28% from cerumen and 25% from the canal; and to ofloxacin, 15% from cerumen and 19% from the canal. CONCLUSIONS: Turcellaotitidis and A. otitidis were present with a much higher frequency than previously described, lending evidence that they be considered normal otic flora. Corynebacterium auris, previously reported only in children, was isolated from normal adults.

U-56,407, a new antibiotic related to asukamycin: isolation and characterization.

U-56,407, a bright yellow, crystalline antibiotic was isolated from fermentations of Streptomyces hagronensis (strain 360). This antibiotic was extracted from fermentation broths with halogenated hydrocarbons and purified by silica gel chromatography and crystallization. U-56,407 is active in vitro against Gram-positive bacteria but not Gram-negative organisms. It failed to demonstrate in vivo activity in experimentally infected mice. Physical-chemical characterization of U-56,407 supports a molecular formula of C29H32N2O7 and a structure related to the antibiotic asukamycin.

Serratia marcescens keratitis: strain-specific corneal pathogenesis in rabbits.

PURPOSE: The purpose of this study was to develop an animal model of Serratia keratitis that is suitable to demonstrate the pathology of specific strains. METHODS: Serratia marcescens ocular strains 93-1399-1 and 94-EI-185-2, and an environmental strain (ATCC 14041) were characterized in vitro in terms of their motility, metabolic profiles, ribotypes, and protease production. The strains were then analyzed in the rabbit intrastromal injection model. Slit lamp examination (SLE) and enumeration of bacteria in the cornea was conducted every 6 hours for 30 hours post-infection. In vivo motilities were analyzed by quantification of bacteria in the peripheral and central areas of infected rabbit corneas. RESULTS: All strains were similar in their metabolic activity and production of extracellular proteases. The ocular isolates were distinct from the environmental strain in their ribotyping patterns and in their motility. Each strain grew logarithmically in the cornea up to 6 hours post-infection. SLE scores increased from 0 to 30 hours post-infection for strains ATCC 14041 and 93-1399-1, while the SLE score of strain 94-EI-185-2 reached its maximum at 18 hours post-infection. Strain-specific differences in pathology were noted from 18 to 30 hours post-infection. Strain 94-EI-185-2 produced iritis but only mild corneal changes. Strain 93-1399-1 produced a severe corneal infiltrate encompassing the entire corneal surface as well as severe conjunctival inflammation and iritis. Strain ATCC 14041 produced a localized, severe, exudative corneal abscess that contained infecting bacteria. CONCLUSIONS: A rabbit model of Serratia keratitis was developed in which bacterial growth kinetics and strain-specific ocular pathologic changes were reproducible.

The effectiveness of tobramycin and Ocuflox in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic antibiotic treatment prior to intra-corneal infection with Staphylococcus aureus. METHODS: One topical drop of Tobrex (0.3% tobramycin), tobramycin (0.3%) in the Tobrex vehicle with 0.05% dodecyl maltoside (DDM)/4.0% hydroxypropylmethycellulose (HPMC), Ocuflox (0.3% ofloxacin) or DDM/HPMC vehicle were applied to rabbit eyes at one or five hours prior to injection of bacteria. Approximately 500 colony-forming units (CFU) of S. aureus strain 8325-4 were injected into the corneal stroma. Rabbits were sacrificed five hours after infection and corneal homogenates were cultured to determine the number of colony forming units (CFU) per cornea. RESULTS: Rabbits treated at five hours prior to infection with tobramycin-DDM/HPMC reduced the bacterial load by approximately 2.4 log CFU/cornea as compared to the untreated control (3.47 +/- 0.98 vs. 5.71 +/- 0.14 log CFU/cornea, respectively; P = 0.0010); however, Ocuflox, Tobrex, or DDM/HPMC vehicle did not significantly reduce the log CFU (P >or= 0.4837). Rabbits treated at 1 hour prior to infection with Ocuflox or tobramycin-DDM/HPMC had significantly reduced CFU/cornea (1.31 +/- 0.86 and 0.48 +/- 0.31 log CFU/cornea, respectively) as compared to the untreated group (5.71 +/- 0.14 log CFU/cornea; P or= 0.2312). CONCLUSIONS: This pre-treatment model of Staphylococcus keratitis quantitatively measured the prophylactic effectiveness of topical antibiotic formulations. An important finding was that a tobramycin-DDM/HPMC formulation was highly effective as a prophylactic medication.

A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis.

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p=0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction. (Eur J Ophthalmol 2005; 15: 5 4 1- 9 ).

Microbial formation of 4-thiouracil.

A soil organism identified as Streptomyces libani var. soldani was found to produce 4-thiouracil. The product was isolated in a yield of 150 mug/ml of filtered beer and characterized by C-13 magnetic resonance and high-resolution mass spectroscopy. The product has a broad antibacterial spectrum but low specific activity.

Increasing bacterial resistance in pediatric acute conjunctivitis (1997-1998).

We sought to determine the current level of resistance in Haemophilus influenzae and Streptococcus pneumoniae, the primary pathogens of pediatric conjunctivitis. Between January 1997 and March 1998, we prospectively cultured acute conjunctivitis in 250 ambulatory pediatric patients from rural Kentucky whose average age was 24.3 months. In those 250 cases, 106 H. influenzae (42% of the total) and 75 S. pneumoniae (30% of the total) pathogens were isolated, with no growth or no pathogen resulting in 79 cases (32% of the total). Beta-lactamase was detected in 60 (69%) of 87 tested strains of H. influenzae. Among 65 isolates of S. pneumoniae tested for penicillin susceptibility, 44 (68%) were susceptible, 17 (26%) were resistant, and 4 (6%) were intermediate. Conjunctivitis with acute otitis media was observed in 97 patients (39%), and H. influenzae was recovered in 57% of these 97 cases. As for in vitro activity, ciprofloxacin, ofloxacin, and tetracycline were the most active; and gentamicin, tobramycin, polymyxin B-trimethoprim, and polymyxin B-neomycin were intermediately active. Sulfamethoxazole possessed no activity against either pathogen. Beta-lactamase production was detected in 69% of H. influenzae strains, which still remains the primary causative pathogen of both conjunctivitis and conjunctivitis-otitis syndrome. Penicillin-nonsusceptible S. pneumoniae was observed in 32% of 65 patients with S. pneumoniae conjunctivitis, with most strains being penicillin resistant.