Bacterial endophthalmitis, which is a devastating complication of intraocular surgery or eye trauma, has a poor prognosis. Intravitreal injection of antimicrobial agents has become a part of the standard treatment of endophthalmitis. The authors investigate the pharmacokinetics of intravitreal liposome-encapsulated tobramycin as a possible method of prolonging the duration of therapeutic concentrations. Tobramycin was encapsulated into liposomes of phosphatidylcholine, phosphatidic acid, and alpha-tocopherol by the reverse phase evaporation method. The final liposomal suspension contained tobramycin, 7.0 mg/ml, 60.5% encapsulated. One eye received an intravitreal injection of either liposome-encapsulated tobramycin (LET), tobramycin phosphated-buffered saline (TS) or a mixture of tobramycin and liposome-encapsulated saline (TEL), and the results were as follows: 1. Concentrations of free tobramycin were significantly lower with LET than with TS or TEL at 1 hour after intravitreal injection. 2. Concentrations of free and total tobramycin were significantly higher with LET than with TS or TEL at 5 and 8 days after intravitreal injection. Concentrations of free tobramycin with TS were lower than the minimal inhibitory concentration(MIC) of tobramycin for Pseudomonas aeruginosa at 8 days after intravitreal injection, while those with LET were higher than the MIC of tobramycin for Pseudomonas aeruginosa 18 days after injection.
Animal ; Delayed-Action Preparations ; Injections ; Liposomes ; Rabbits ; Tobramycin/administration & dosage/*pharmacokinetics ; Vitreous Body/*metabolism

Bacterial keratitis is a common ophthalmic disease. In certain cases of pseudomonas keratitis, the corneal perforation may occur within 24-48 hours of the onset. Soa suitable, massive antibiotic should be promptly used in these cases. Intensive topical therapy with fortified aminoglycoside antibiotics is a current mainstay in the treatment of bacterial keratitis because insufficient antibiotic concentrations may not inhibit bacterial growth. In 1985, Glasser and associates reported the effect of longer dosing intervals on corneal gentamicin levels with using topical fortified gentamicin solutions in rabbits. We compared peak and trough antibiotic levels achieved in the rabbit cornea by various topical administrations of tobramycin which was prepared in a concentration of 13.6mg/ml by fortifying commercially available ophthalmic tobramycin solution with injectable drug. A loading dose consists of one drop given every minute for five minutes. 1. Eyes receiving one drop every hour(Group 1) and three drops every two hours(Group 5) showed little conjunctival hyperemia. Eyes given one drop every 30 minutes(Group 2) developed minimal inflammatory responses, as did eyes given a single loading dose followed by one drop each hour(Group 4). The moderate inflammatory response occurred in eyes receiving sequential loading doses(Group 3). Abnormalities in the cornea and the iris were not seen in all studied groups. 2. Gentamicin peak level in sequential loading doses group(Group 3) was significantly higher than those achieved by one drop every hour(Group 1) or one drop every 30 minutes(Group 2). At two hours of gentamicin administration, sequential loading doses(Group 3) produced remarkably high concentrations: than those produced in Group 1, Group 2, or three drops every two hours(Group 5). During the first four hours, Group 3 represented high antibiotic levels than those produced in Group 1, Group 2, Group 5, or a single loading dose followed by one drop each hour(Group 4). There were no significant differences between trough levels with on drop every hour(Group 1) and three drops every two hours(Group 5).
Administration, Topical* ; Anti-Bacterial Agents ; Cornea ; Corneal Perforation ; Gentamicins ; Hyperemia ; Iris ; Keratitis ; Pseudomonas ; Rabbits* ; Tobramycin*

PURPOSE: To determine the best routes of administration of Tobramycin, the intracameral concentrations was assessed as time progressed after administering identical amounts and concentrations of tobramycin through various methods. METHODS: 40 eyes from 20 house rabbits were administered the same amount (200 micro liter) of 0.3% tobramycin. The first group was administered topically, and the second group was administered by subconjunctival injection. Contact lenses were soaked in tobramycin for 30 minutes and were covered over the corneas of the third group. While amniotic membranes were transplanted onto the corneas and tobramycin was topically administered in the fourth group. 100 micro liter of aqueous fluid was extracted 30 min, 1 hr, 2 hr and 3 hr after the administration and intracameral concentrations of tobramycin were measured using FPIA (fluorescence polarization immunoassay). RESULTS: After topical administration and subconjunctival injection, statistically significant decreases of average concentrations were observed after 2~3 hours. The group that was covered with flexible hydrophilic contact lenses showed high concentrations after 30 minutes, and a statistically significant increases of concentration was observed after 2 hours. The group that was topically administered with 0.3% tobramycin after amniotic transplantation on the cornea, showed a gradual increase of concentration as time progressed, and statistically significant increase of concentration was observed after 1~2 hours. CONCLUSIONS: Topical administrations with more frequent instillations increased intracameral concentrations, exceeding the MIC90 concentration of Staphylococcus aureus. while low concentration (0.3%) of subconjunctival injections did not significantly increases intracameral concentrations. Using flexible contact lenses, high concentrations were observed in the early stages, exceeding the MIC90 concentrations of Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Concentrations exceeded MIC90 concentration of Staphylococcus epidermidis 30 minutes after amniotic membranes transplantation, and continued to increases after 3 hours, Therefore, we can conclude that amniotic membrane can be used as a reservoir for transferring drugs.
Administration, Topical ; Amnion ; Aqueous Humor* ; Contact Lenses ; Contact Lenses, Hydrophilic ; Cornea ; Pseudomonas aeruginosa ; Rabbits ; Staphylococcus aureus ; Staphylococcus epidermidis ; Tobramycin*

To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts.
Achromobacter denitrificans/*isolation & purification ; Adult ; Amikacin/administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Ceftazidime/administration & dosage ; Contact Lenses, Extended-Wear/*adverse effects ; Female ; Fluoroquinolones/administration & dosage ; Gram-Negative Bacterial Infections/diagnosis/*drug therapy/*microbiology ; Humans ; Keratitis/diagnosis/*drug therapy/*microbiology ; Tobramycin/administration & dosage

BACKGROUND: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010–2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. MATERIALS AND METHODS: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. RESULTS: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. CONCLUSION: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed.
Acinetobacter baumannii* ; Acinetobacter* ; Amikacin ; Aminoglycosides ; Anti-Bacterial Agents ; Anti-Infective Agents ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Ciprofloxacin ; Colistin ; Critical Illness ; Disease Outbreaks ; Drug Resistance, Multiple ; Gentamicins ; Hospital Units ; Humans ; Imipenem ; Infection Control ; Intensive Care Units ; Pathology ; Phenotype ; Piperacillin ; Pneumonia ; Tetracycline ; Ticarcillin ; Tobramycin ; United States Food and Drug Administration