Service d'Ophtalmologie, Centre Hospitalier Universitaire de Limoge, Hopital Universitaire Dupuytren, Limoges, France.
The choice of an antibacterial is based on considerations of pharmacodynamic, pharmacokinetic and bacteriological characteristics, risk of selecting resistant mutants, and cost. In this article we review 16 commercially available ophthalmic antibacterial preparations. Fusidic acid and bacitracin are selective for gram-positive bacteria whereas polymyxin B targets gram-negative species. Aminoglycosides and quinolones are broad spectrum antibacterials. The widespread use of an antibacterial increases risks of selecting resistance to it. Acquired resistance is well documented for fusidic acid and rifamycin, and newly described for quinolones. The bioavailability of an antibacterial agent depends on the target bacterial species, the site of infection and the integrity of the haemato-aqueous barrier. Some agents (fusidic acid, quinolones) penetrate the cornea, passing into the anterior chamber of normal eyes at therapeutic concentrations, whereas others (polymixin B, bacitracin) have no penetrating powers and remain at the surface of the eye. Toxicity is mostly manifested by allergic reactions to excipients or active ingredients in topical antibacterial preparations. A few cases of haematological toxicity have brought suspicion on topical chloramphenicol, but the link has yet to be proven. Erythromycin and polymyxin B are probably okay to use as topical applications in pregnant women and nursing mothers. Costs of treatment must be evaluated as a whole (regimen, drug associations). Prices for a bottle of eyedrops may vary 3-fold. The cheapest drugs include chloramphenicol, polymyxin B and gentamicin, the most expensive being fusidic acid and the quinolones.
Indian J Ophthalmol. ;59 (6):445-53 22011488
Etiology and epidemiological analysis of glaucoma-filtering bleb infections in a tertiary eye care hospital in South India.
Aravind-Zeiss Centre of Excellence in Glaucoma, Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Tirunelveli, Tamil Nadu - 627 001, India. email@example.com
PURPOSE To evaluate the microbial etiology and associated risk factors among patients with blebitis following trabeculectomy. MATERIALS AND METHODS A retrospective analysis of all culture-proven blebitis was performed in patients who underwent trabeculectomy between January 2004 and December 2008. A standardized form was filled out for each patient, documenting sociodemographic features and information pertaining to risk factors. Swabbing of the infected bleb surface was performed for all suspected cases and further subjected to microbiological analysis. RESULTS A total of 23 patients with culture-proven blebitis were treated during the study period, with a mean age of 59.2 years (59.2 ± SD: 12.8; range, 30-81 years). Duration of onset was early (≤ 36 months) in six (26%) cases and late (> 36 months) in 17 (74%) cases with a range between 15 and 144 months (mean, 82.91 months; SD: 41.89). All 23 blebs were located superiorly and of which, 21 (91%) were microcystic avascular, 1 (4%) diffuse avascular, and 1 (4%) vascular flattened. The predominant risk factor identified was bleb leak (35%; 8 of 23) followed by thin bleb (22%; 5 of 23) and blepharitis (17%; 4 of 23). Bleb leaks (100%) were recorded only in patients with late onset (≥ 9 years) of infection (P< 0.001), while the incidence of ocular surface disease (100%) occurred early (≤ 3 years)(P< 0.001). Use of topical steroids was associated frequently with cases of thin blebs (80%; 4 of 5)(P< 0.001), while topical antibiotics showed bleb leaks (88%; 7 of 8)(P< 0.001). Coagulase-positive staphylococci were frequently recovered from blebitis with thin blebs (71%; 5 of 7)(P = 0.001), Coagulase-negative staphylococci (CoNS) with bleb leak (100%; 8 of 8)(P< 0.001), Corynebacterium with blepharitis (100%; 3 of 3)(P = 0.001), and Streptococci with releasable sutures (75%; 3 of 4)(P = 0.001). CONCLUSION Bleb leak is the principal risk factor responsible for late-onset blebitis, while early-onset blebitis could be ascribed to ocular surface diseases. Streptococci were mainly responsible for early onset of infection, while the late onset was due to CoNS.
Miklós D Resch, Béla E Resch, Eszter Csizmazia, László Imre, János Németh, Piroska Szabó-Révész, Erzsébet Csányi
Department of Ophthalmology, Semmelweis University, Budapest, Hungary. firstname.lastname@example.org
PURPOSE The aim of the study was the quantitative pharmacokinetic evaluation of drug release from pretreated amniotic membrane (AM) in vitro. METHODS Cryopreserved AM pieces soaked in 3% ofloxacin ophthalmic solution were mounted in vertical Franz-diffusion cell system equipped with autosampler. In vitro release of ofloxacin was determined by quantitative absorbance measurement carried out with a UV spectrophotometer (wavelength 287 nm). Three groups were created according to the duration of soaking: 60 (Group 1), 120 (Group 2), and 180 (Group 3) minutes. Released amount of ofloxacin pro 1 cm(2) of AM (μg/cm(2)) was calculated in the period of 1 to 450 min. RESULTS Ofloxacin was detectable in the acceptor phase 1 min after mounting in all groups. Until 120 min, rapid increase of released ofloxacin could be observed. From 120 to 450 min, the amount of released ofloxacin showed a slower increasing pattern. Released ofloxacin in Group 1 was significantly lower than in Group 2 after 90 min (19.4±10.4 μg/cm(2), 51.6±20.7 μg/cm(2), respectively, P=0.044). In Group 3, cumulative drug release was higher than in Group at all timepoints. No significant difference could be demonstrated between Groups 2 and 3 at only 1 min timepoint. CONCLUSION Significant ofloxacin reservoir capacity of a single human amniotic layer could be demonstrated in vitro. AM acted as an ofloxacin slow release device for upto 7 h in vitro, depending on the duration of pretreatment of AM. Individual pretreatment of AM could increase beneficial effects of AM transplantation, especially in infectious keratitis.
A novel cell-associated protection assay demonstrates the ability of certain antibiotics to protect ocular surface cell lines from subsequent clinical Staphylococcus aureus challenge.
UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15208, USA.
In vivo effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new in vitro method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline (TET), and bacitracin (BAC) to associate with mammalian cells and to protect these cells from destruction by bacteria. Mammalian cell lines were grown to confluence using antibiotic-free medium and then incubated in medium containing a single antibiotic (0 to 512 μg/ml). After incubation, the cells were challenged with Staphylococcus aureus ocular isolates, without antibiotics added to the culture medium. Epithelial cell layer integrity was assessed by gentian violet staining, and the minimum cell layer protective concentration (MCPC) of an antibiotic sufficient to protect the mammalian cells from S. aureus was determined. Staining was also quantified and analyzed. Bacterial viability was determined by culture turbidity and growth on agar plates. Preincubation of Chang and human corneal limbal epithelial cells with AZM, ERY, and TET at ≥64 μg/ml provided protection against AZM-susceptible S. aureus strains, with increasing protection at higher concentrations. TET toxicity was demonstrated at >64 μg/ml, whereas AZM displayed toxicity to one cell line at 512 μg/ml. BAC failed to show consistent protection at any dose, despite bacterial susceptibility to BAC as determined by traditional antibiotic susceptibility testing. A range of antibiotic effectiveness was displayed in this cell association assay, providing data that may be considered in addition to traditional testing when determining therapeutic dosing regimens.
A comparison of antibacterial activity against Methicillin-Resistant Staphylococcus aureus and gram-negative organisms for antimicrobial compounds in a unique composite wound dressing.
Eastern Virginia Medical School, Norfolk, Virginia, USA.
Miklós Resch, Bela Resch, Eszter Csizmazia, Laszlo Imre, Janos Nemeth, Piroska Revesz, Erzsebet Csanyi
1st Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
Purpose: The aim of our study was to develop a model to investigate permeability of amniotic membrane (AM) to ofloxacin eye drops, a widely used topical antibiotic in ocular surface disease after AM transplantation. Methods: AM pieces on cellulose acetate filter membranes were mounted in vertical Franz-diffusion cell system equipped with autosampler. In vitro release of 300 mg of 3% commercially available ofloxacin ophthalmic solution was determined by quantitative absorbance measurement carried out with a UV spectrophotometer (wavelength 287nm). Freshly prepared and cryopreserved AMs were compared. Porafil filter membranes without AM served as positive controls. Results. Ofloxacin was detectable in the acceptor phase 1 minute after instillation, and a gradual increase of concentration could be detected in a period of 90 minutes in all groups. At 30 minutes 3.35+/-2.23% of ofloxacin penetrated through freshly prepared AM, 4.35+/-1.8 through cryopreserved AM compared to 17.52+/-3.91 filter membrane alone. At 90 minutes penetration rates of ofloxacin were 5.04+/-1.11%, 5.26+/-3.21%, 27.91+/-3.05%, respectively. Difference (p>0.05 t-test) was not significant between freshly prepared and cryopreserved AMs. Compared to control, both membranes showed significant difference (p<0.05 t-test) at all timepoints. Conclusion: The in vitro model of Franz-diffusion cell system was found to be applicable for drug permeability studies of human amniotic membranes to water based solutions. The filter membrane and AM were permeable to water based solution of ofloxacin. Significant barrier function of AM could be measured in ofloxacin permeability. Cryopreservation did not influence permeability of AM.
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
Biodegradable filaments (diameters of 250-300 microm) for the controlled delivery of dexamethasone or levofloxacin are described. Filaments are prepared by wet-spinning solutions of poly(lactide-co-glycolide)(PLGA) and drug dissolved in dimethyl sulfoxide (DMSO) into a coagulation bath of water. Compositional analyses of the filaments by independent measurements of drug, DMSO, water, and polymer give drug loadings up to 40% of filament mass and drug retention (drug in filament per drug in solution) greater than 40%. Drug release kinetics, and thermal and mechanical properties, of the filaments are reported. Three filaments with levofloxacin contents of 46+/-2, 85+/-4, and 36+/-2 microg/cm (denoted 506-L1, 506-L2, and 506-L3, respectively) are implanted in the conjunctiva of New Zealand white rabbits. The time dependent, in-vivo tear concentrations of levofloxacin from filament implants in New Zealand white rabbit eyes are in general agreement with the results from the in-vitro release profiles, with one of the filaments (506-L1) showing effective levels of levofloxacin in the tears for 6 days. The filaments are generally well tolerated by the rabbits. Filament failure occurs at 6-8 days within the rabbit eyes, essentially the same time to failure observed from in-vitro mechanical properties testing results.
Ocular Pharmacokinetics of Besifloxacin Following Topical Administration to Rabbits, Monkeys, and Humans.
Joel W Proksch, Camille P Granvil, Raphaële Siou-Mermet, Timothy L Comstock, Michael R Paterno, Keith W Ward
Global Research and Development, Bausch & Lomb, Rochester, New York.
Purpose: Studies were conducted to evaluate the ocular penetration and systemic exposure to besifloxacin, a fluoroquinolone antibiotic, following topical ocular administration to animals and humans. Methods: Besifloxacin ophthalmic suspension (0.6%) was administered as a topical ocular instillation to pigmented rabbits, cynomolgus monkeys, and human subjects. At predetermined intervals after dosing, samples of ocular tissues and plasma were collected and analyzed for besifloxacin levels using HPLC/MS/MS methods. Results: Besifloxacin demonstrated good ocular penetration in rabbits and monkeys, with rapid absorption and sustained concentrations observed in anterior ocular tissues through 24 h after a single administration. Maximum besifloxacin concentrations in conjunctiva, cornea, and aqueous humor of monkeys were 6.43 mug/g, 2.10 mug/g, and 0.796 mug/mL, respectively, after a single topical dose, and concentrations declined in these tissues with an apparent half-life of 5-14 h. Following a single topical ocular administration to humans, the maximum besifloxacin concentration in tears was 610 mug/g with concentrations decreasing to approximately 1.6 mug/g at 24 h. The resulting pharmacokinetic parameters for besifloxacin in human tears were evaluated relative to the MIC(90) values (mug/mL) for besifloxacin against Streptococcus pneumoniae (0.125), Staphylococcus aureus (0.25), Staphylococcus epidermidis (0.5), and Haemophilus influenzae (0.06). Following a single topical administration, the C(max)/MIC(90) ratios for besifloxacin in human tears were >/=1,220, and the AUC((0-24))/MIC(90) ratios were =2,500 for these relevant ocular pathogens. Following repeated 3-times daily (TID) topical ocular administration to human subjects with clinically diagnosed bacterial conjunctivitis, maximum besifloxacin concentrations in plasma were less than 0.5 ng/mL, on average. Conclusions: Taken together, the results of the current investigation provide a PK/PD-based rationale that supports the use of besifloxacin for the safe and effective treatment of ocular infections.
The in vivo behaviour of 5% gentamicin sulphate ocular mini-tablets (2-mm diameter, 6.525 mg weight) was compared with gentamicin eye drops in six ponies. Two mini-tablets were inserted on the bulbar conjunctiva of the right eye while a similar dose of gentamicin was administered via eye drops in the left eye. Irritation induced by the mini-tablets and the eye drops was evaluated using a visual analogue scale (0-10). Tears were sampled with ophthalmologic absorption triangles for 1 min for the determination of the concentration of gentamicin sulphate using a microbiological plate diffusion method. Irritation induced by the tablets was minor and clinically acceptable (overall median score of 1.7 +/- 1.4). Eye drops induced a sharp increase in gentamicin sulphate concentration (364.4 mug/mL after 5 min) followed by a fast decline (10.8 mug/mL after 60 min). The increase in concentration induced by the ocular mini-tablets was less pronounced (up to 56.2 mug/mL after 30 min) and followed by a gradual decrease; the concentration remained above 15 mug/mL for 8 h. Ocular 5% gentamicin sulphate mini-tablets are clinically well-tolerated in ponies, assuring a constant concentration in the tears for at least 8 h.
Department of Neuroscience, Ophthalmology Unit, University of Padova, Italy.
PURPOSE The purpose of this study was to assess the cytotoxic effects of the fluoquinolone ofloxacin and the aminoglycoside netilmicin on stromal human keratocytes in vitro. METHODS Cultured human keratocytes were exposed to various concentrations of ofloxacin or netilmicin (0.16-5.0 mg/mL). Both cell proliferation (MTT assay) and cell morphology (phase-contrast microscopy) were evaluated after 1, 4, 12, and 24 hours of incubation. Measurement of annexin V binding performed in association with the dye exclusion test using propidium iodide (PI) was also performed by FACS analysis after 4 hours of exposure. RESULTS Both antimicrobials induced dose- and time-dependent morphologic changes in keratocytes, yet the effects of netilmicin were minimal. After 24 hours of exposure, both drugs induced a dose-dependent inhibition of cell proliferation; however, ofloxacin demonstrated significantly more toxic effects than netilmicin (t test for ED50 values, P < 0.0001). Statistical differences between 2 antibiotics start at concentrations above 1.25 mg/mL (ANOVA with post-hoc test, P < 0.01). Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P < 0.05). CONCLUSIONS Relative effects of aminoglycosides and fluoroquinolones on stromal keratocytes appear to be different: netilmicin was shown to be significantly less toxic than ofloxacin. This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is absent or compromised, as after photorefractive keratectomy, alkali burns, or ulcerative keratitis.
Service d'ophtalmologie, CHU de Bicêtre, Le Kremlin-Bicêtre (94), Assistance Publique--Hôpitaux de Paris. email@example.com
Some eyedrops, gels or ointments may cause adverse effects as serious as those observed with systemic therapies. Because of their relatively poor penetration into eye tissue, ophthalmic drugs usually contain high concentrations of their active ingredient. Asking patients about these drugs to prevent interactions is useful when prescribing a new systemic treatment. Conversely, it is advisable to ask about ophthalmic drugs during the etiological investigation of possible iatrogenic effects.
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Service d'Ophthalmologie, C.H.U. Dupuytren, Limoges, France. firstname.lastname@example.org
Over the last 20 years eyeball replacement surgery has improved, especially with the widely accepted use of biocolonisable implants. These implants allow long-lasting biointegration, thus improving prosthesis motility and reducing the rate of postoperative exposure. In this article, we review the chemical structure, toxicity data and manufacturing procedures of the three main commercially available materials: aluminium, hydroxyapatite and porous polyethylene.
Orbit. 2003 Sep ;22 (3):183-91 12868027
Bone formation in hydroxyapatite tricalcium phosphate ceramic implants used in the treatment of the postenucleation socket syndrome.
J P Adenis, P Camezind, B Petit, F Pilon, P Y Robert, M P Boncoeur-Martel, M A Camezind-Vidal, N Ben Rayanachekir, F Labrousse
Department of Ophthalmology, Dupuytren University Hospital, Avenue Martin Luther King, 87042 Limoges, France. email@example.com
PURPOSE To determine the histopathologic changes in coralline hydroxyapatite tricalcium phosphate (HA-TCP) blocks used in the treatment of the postenucleation socket syndrome (PESS). METHODS Twenty-four patients were treated with HA-TCP blocks placed directly into the orbital fat to correct the PESS. Eight of these patients required partial removal of the material for various reasons between 32 and 371 days after the initial operation. The orbital implants were decalcified and processed for light and electron microscopic examination. RESULTS Light microscopy demonstrated fibrovascular ingrowth into the pores of the implant in all cases. Osteogenesis was observed in three cases in the periphery of the implant. Ossification occurred in the implants after a mean implantation duration of 276 days versus 67 days in cases without ossification. CONCLUSION Implants of HA-TCP, a new material used in ophthalmology, demonstrate the presence of fibrovascular ingrowth, reflecting the excellent biointegration of this material.
Department of Ophthalmology, CHU 87042 Limoges, France. firstname.lastname@example.org
New information on the physiopathology and treatment of orbital volumes pathologies is described: 1) In post-enucleation or evisceration socket syndrome placing of synthetic material (HA-TCP) directly in the intraconal orbital fat can correct most of the symptoms. However the best approach is to prevent orbital volume deficiencies during first surgery using an implant large enough to allow a future prosthesis of a volume less than 2 mL. New procedures for placing the implant after enucleation or evisceration are described. 2) In proptosis related to Graves' orbitopathy relative indications are given for orbital decompression by removal of fat or bone.
Service d'Ophtalmologie, CHRU Dupuytren, rue Martin Luther King, 87042 Limoges. email@example.com
The authors describe two new techniques of evisceration after resection of the corneal epithelium and limbus with a conservative approach of the posterior lamella of the cornea and anterior sclera after a 360 degrees dissection of the sclera behind the insertion of the oculomotor recti muscles, and with a conservative approach of the recti oculomotor muscles. The technique is called "Parachute" when the posterior sclera is removed and "Russian Doll" when the posterior sclera is not removed and placed behind the orbital implant. The implant is then introduced with "bird cage" forceps. The indications of the technique are those of evisceration when the size of the remaining globe is at least one-third of the volume of a normal eye. The main advantage is to provide safely a large volume for the implant in order to prevent post enucleation socket syndrome.
Service d'ophtalmologie, CHRU Dupuytren, 2, av. Martin Luther King, 897042 Limoges Cedex.
INTRODUCTION Cyclosporin eye-drops allow local immunoregulation without systemic side effects and is an alternate to local steroids. In this article we review specific problems of product setup and clinical studies published over the past 20 years. PRODUCT SETUP: The main problems in eye-drop preparation are sterility, pH, particles, and its lipophilic properties. Numerous excipients have been tested including oil solvents, alphacyclodextrin, collagen shields, liposomes, polyester nanocapsules, but documentation on stability of the molecule is inadequate. TOXICITY Epithelial toxicity is well known and is probably mainly due to the excipient. No endothelial toxicity has been described in vivo. Repeated doses lead to uveal reactions in animals, which could limit the indications for intraocular diseases. PHARMACOKINETICS: Bioavailability is mainly limited by the lipophilic properties. Oil excipients, the most widely used, lead to good corneal penetration but low intraocular concentrations. Cyclosporin bioavailability is improved when using hydrophilic excipients. INDICATIONS Every ocular surface disease that involves cytokines is a potential indication for cyclosporine eyedrops: keratoconjunctivitis sicca, vernal keratitis, adjuvant therapy of filtering surgery, stromal herpes keratitis, immunity limbal keratitis, and Thygeson's keratitis. There is biological evidence of efficacy, and encouraging results from many studies, yet few have tested a large number of patients. A large multicenter study on dry eye is currently in progress.
Department of Radiology, University Hospital Dupuytren, 2, avenue Martin Luther King, 87042 Limoges Cedex, France. firstname.lastname@example.org
Identification of wooden intraorbital foreign bodies (WIOFB) is crucial for avoiding severe orbital infection. Despite careful clinical examination, WIOFB are often not recognised. We report the CT findings in chronically retained WIOFB. When not initially diagnosed, WIOFB create a granulomatous inflammatory foreign-body reaction. CT demonstrates the WIOFB as a linear dense structure surrounded by a soft-tissue mass with density similar to that of muscle, corresponding to the foreign-body reaction.
EP CNRS J0118, Medical University, Limoges, France.
HLA-G transcripts have previously been detected in the ocular cell line HS738, in foetal eyes and in global ocular extract. Using RT-PCR and hybridization, we searched for HLA-G and classical HLA class I transcripts in the corneas of eye donors (n = 6) and in various components of eyes collected at time of surgery: lens (n = 3), iris (n = 2), vitreous body (n = 2) and retina (n = 2). Whereas HLA class I mRNA was abundant in the ocular tissues of all donors, we could not find HLA-G transcript in any ocular tissues obtained from subjects in vivo. The absence of HLA-G in adult eye cornea limits its interest as a possible target in corneal transplantation. Classical HLA class I transcripts were abundant in the cornea and other components of the eye. These results highlight the role of classical HLA class I antigen in eye immunity and corneal transplantation.
Treatment of the postenucleation socket syndrome with a new hydroxyapatite tricalcium phosphate ceramic implant.
Department of Ophthalmology, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
PURPOSE: Surgical correction of the postenucleation socket syndrome (PESS) is challenging. Various biomaterials are used for reconstruction of the anophthalmic orbit, often with unsatisfactory long-term results. Implants have been placed between the periorbital and the orbital floor. The authors describe a new material composed of hydroxyapatite tricalcium phosphate (HA-TCP) in the form of ceramic blocks, to be placed into the orbital fat as a new surgical site. METHODS: Ten patients with PESS underwent surgery to compensate the volume deficit of the anophthalmic orbit. Blocks of HA-TCP were created by fragmentation of a larger piece, tailored as needed, and implanted in the orbital fat. The patients were monitored regularly with clinical and radiologic examinations to evaluate the behavior of the implants. RESULTS: The volume of the HA-TCP was measured in 5 cases (mean, 2.95 +/- 1.08 ml). A significant reduction of enophthalmos was obtained: mean Hertel exophthalmometry measured 12.7 +/- 2.5 mm preoperatively and 14 +/- 2.4 mm postoperatively (p < 0.05). The average prosthesis volume was significantly reduced in the cases measured: 2.7 ml +/- 0.94 ml preoperatively and 1.8 +/- 0.7 ml postoperatively (p < 0.02). There was a negative correlation between the HA-TCP implant volume and postoperative prosthesis volume (correlation coefficient =-0.925; p < 0.05). According to photographic evaluation, correction of the enophthalmos and of the superior sulcus depression were obtained in 70% and 90% of cases, respectively. Magnetic resonance imaging seems to demonstrate that the blocks become well integrated into the surrounding orbital tissue. CONCLUSION: The HA-TCP blocks correct some anomalies of PESS. Placement of the blocks directly into the orbital fat is a promising alternative to the traditional subperiosteal location.
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Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Campus, North Mymms, Hertfordshire AL9 7TA School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX.
OBJECTIVES To provide baseline data on patterns of antimicrobial usage in dogs and cats through the analysis of data stored in electronic practice management systems. METHODS Clinical data from 11 first opinion veterinary practices were extracted for the year 2007. Descriptive statistical analysis was performed to assess the usage of antimicrobials. RESULTS Widespread usage of systemic broad-spectrum antimicrobials was observed. Antimicrobials most frequently used in both species were potentiated amoxicillin (44·4% and 46.1% in cats and dogs, respectively) and amoxicillin (14·3% and 20·7%). Cephalexin (13·4%) and cefovecin (15·0%) were also commonly used in dogs and cats, respectively. Systemic critically important antimicrobials in human medicine were widely used in dogs (60·5%) and cats (82·7%). Topical antimicrobials used in both species included fusidic acid (48·4% and 54·8%), framycetin (20·4% and 13·4%), polymyxin B (12·6% and 9·3%) and neomycin (6·5% and 6·6%). CLINICAL SIGNIFICANCE Inappropriate usage of broad-spectrum antimicrobials may contribute to the development of antimicrobial resistance and loss of efficacy of antimicrobials in veterinary settings. Data recorded in practice management systems were demonstrated to be a practical source for monitoring antimicrobial usage in pets.
Spectrum of activity, mutation rates, synergistic interactions, and the effects of pH and serum proteins for fusidic acid (CEM-102).
JMI Laboratories, North Liberty, IA 52317, USA. email@example.com
Fusidic acid (CEM-102) is a steroidal antimicrobial agent with focused Gram-positive activity that acts by preventing bacterial protein synthesis via interacting with elongation factor G. A collection of 114 wild-type isolates (> 80 species) was used to define the contemporary limits of fusidic acid spectrum against Gram-positive and Gram-negative species. Reference broth microdilution and anaerobic agar dilution methods were performed. Modifications of standardized test methods included adding 10% human serum and adjusting the medium pH to 5, 6, and 8. Synergy was assessed by the checkerboard method and time-kill studies. Mutational rates to resistance were determined at 4 x, 8 x, and 16 x MIC. Against Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 microg/mL with the greatest potency against Staphylococcus aureus, Corynebacterium spp., and Micrococcus luteus (MIC results, 0.25,< or = 0.12, and < or = 0.5 microg/mL, respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2-8 and 16-32 microg/mL, respectively). Fusidic acid activity against Gram-negative species was more limited (all MIC values,> or = 2 microg/mL) except for Empedobacter brevis, Moraxella catarrhalis and Neisseria meningitidis. A 4-fold increase in fusidic acid MIC results was observed when 10% serum was added to the broth. Decreasing medium pH to 5.0 to 6.0 negated the protein binding effects. Among the 8 antimicrobial combinations tested, gentamicin and rifampin enhanced the activity when combined with fusidic acid (no antagonism). Fusidic acid in vitro activity was most improved when combined with rifampin. Single-step mutational rates ranged from 1.2 x 10(-6) for 4x MIC to 9.8 x 10(-8) for 16 x MIC. In conclusion, these in vitro results for fusidic acid tested against contemporary strains confirm a persisting antimicrobial spectrum, especially against staphylococci and some other Gram-positive species.
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait. firstname.lastname@example.org
OBJECTIVE To investigate antibacterial resistance patterns and genetic relatedness of methicillin-resistant Staphylococcus aureus (MRSA) obtained at the Salmaniya Medical Complex in Bahrain. METHODS A total of 53 consecutive MRSA isolates obtained from 53 patients were studied using antibacterial resistance patterns, coagulase gene polymorphism, staphylococcal cassette chromosome mec (SCCmec) typing and pulsed-field gel electrophoresis (PFGE). RESULTS There was a high prevalence of resistance to fusidic acid (92.5%), ciprofloxacin (92.5%), erythromycin (90.6%), tetracycline (88.7%), trimethoprim (88.7%), streptomycin (88.7%), kanamycin (83.0%) and gentamicin (73.6%). Coagulase gene typing divided the isolates into five coagulase types comprising coagulase type 36 (86.7%), type 20 (3.8%), type 16 (3.8%), type 38 (1.9%) and type 384 (3.8%). They belonged to SCCmec type III (86.7%) and SCCmec type IV (13.3%). PFGE identified five pulsotypes (types A-E) with PFGE type A and its subtypes comprising 83% of the isolates. PFGE type A isolates were multiresistant and had the SCCmec type III and coagulase type 36 genotype. The SCCmec type IV isolates were nonmultiresistant with different genetic backgrounds. CONCLUSIONS The study identified two types of MRSA in the hospital during the study period. One type consisted of a persistent multiresistant PFGE clone with the SCCmec type III and coagulase type 36 genotypes. The second type consisted of nonmultiresistant isolates that belonged to different genetic backgrounds and were isolated less frequently.
Service d'Ophtalmologique, CHU de Grenoble, Université Joseph Fourier, Grenoble, France. email@example.com
Fortified preparations of ophthalmic antibiotics are made with commercially available antibiotics (parenteral or lyophilized preparations). These fortified eyedrops have two main advantages: the increase in the antibiotic concentration in the corneal stroma and the wide choice of available antibiotics. Fortified ophthalmic solutions are used in severe keratitis (large diameter, stroma infiltration, inflammation of the anterior chamber, old patient). The following associations are recommended: ticarcillin+gentamicin+vancomycin or cephazolin+amikacin since they provide a broad-spectrum antibiotic activity against the wide range of bacteria that may cause keratitis. The main toxicity of these preparations is the retardation effect of the epithelial-healing rate (aminoglycosides, vancomycin) and the corneal and conjunctival toxic effects (aminoglycosides). However, fortified antibiotic drops remain the standard therapy for severe bacterial keratitis, given their corneal penetration and the possibility of the synergic and combined effect of an antibiotic association.
Antibacterial resistance and their genetic location in MRSA isolated in Kuwait hospitals, 1994-2004.
Edet E Udo, Noura Al-Sweih, Eiman Mokaddas, Molly Johny, Rita Dhar, Huda H Gomaa, Inaam Al-Obaid, Vincent O Rotimi
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait. EDET@has.edu.kw
BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of serious infections in hospitals and in the community worldwide. In this study, MRSA isolated from patients in Kuwait hospitals were analyzed for resistance trends and the genetic location of their resistance determinants. METHODS Between April 1994 and December 2004, 5644 MRSA isolates obtained from different clinical samples were studied for resistance to antibacterial agents according to guidelines from the National Committee for Clinical Laboratory Standards and the British Society for Antimicrobial Chemotherapy. The genetic location of their resistance determinants was determined by curing and transfer experiments. RESULTS They were resistant to aminoglycosides, erythromycin, tetracycline, trimethoprim, fusidic acid, ciprofloxacin, chloramphenicol, rifampicin, mupirocin, cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide but susceptible to vancomycin, teicoplanin and linezolid. The proportion of the isolates resistant to erythromycin, ciprofloxacin and fusidic acid increased during the study period. In contrast, the proportion of isolates resistant to gentamicin, tetracycline, chloramphenicol and trimethoprim declined. High-level mupirocin resistance increased rapidly from 1996 to 1999 and then declined. They contained plasmids of 1.9, 2.8, 3.0, 4.4, 27 and 38 kilobases. Genetic studies revealed that they carried plasmid-borne resistance to high-level mupirocin resistance (38 kb), chloramphenicol (2.8-4.4 kb), erythromycin (2.8-3.0 kb) and cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide (27 kb) and chromosomal location for methicillin, the aminoglycosides, tetracycline, fusidic acid, ciprofloxacin and trimethoprim resistance. Thus, the 27 kb plasmids had resistance phenotypes similar to plasmids reported in MRSA isolates in South East Asia. CONCLUSION The prevalence of resistance to erythromycin, ciprofloxacin, high-level mupirocin and fusidic acid increased whereas the proportion of isolates resistant to gentamicin, tetracycline, chloramphenicol and trimethoprim declined during the study period. They contained 27-kb plasmids encoding resistance to cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide similar to plasmids isolated in MRSA from South East Asia. Molecular typing of these isolates will clarify their relationship to MRSA from South East Asia.
Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system.
Department of Ophthalmology Hermann Eye Center,University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
The purpose of this study was to compare the relative toxicity of a new topical ophthalmic glaucoma medication, travoprost 0.004% without benzalkonium chloride (BAK), with that of commercially available latanoprost 0.005%(preserved with 0.02% BAK) in immortalized human corneal epithelial cells (HCEs). Tissue culture plates (96 well) containing HCEs were divided into 6 groups. Two groups served as negative controls (70% methanol and gentamicin). Another 2 groups--1 in corneal epithelial culture media and the other in a hydroxypropyl (HP)-Guargellable lubricant eyedrop--served as live controls. The travoprost 0.004% without BAK and latanoprost 0.005% groups were exposed to 100 microL of the undiluted solutions. Cells were incubated for 25 min at 37 degree C. A live/dead assay was used to measure the effects of travoprost without BAK and of latanoprost on HCEs compared to 70% methanol and culture medium. Between the 2 glaucoma medications tested, travoprost 0.004% preserved without BAK showed significantly less toxicity on HCEs than did latanoprost 0.005%. This difference may have ramifications in terms of tolerability for patients who use these topical glaucoma drugs on a long-term basis.
Antibacterial resistance and molecular typing of methicillin-resistant Staphylococcus aureus in a Kuwaiti general hospital.
Department of Microbiology, Faculty of Medicine, Kuwait University, Safat 13110. firstname.lastname@example.org
OBJECTIVE To investigate antibiotic resistance and genetic relatedness of methicillin-resistant Staphylococcus aureus (MRSA) isolated in a general hospital in Kuwait over a period from 1996 to 1998 and 2001. MATERIAL AND METHODS The isolates were characterized by antibacterial susceptibility testing, coagulase serotyping, coagulase gene polymorphism (coag-RFLP) and pulsed-field gel electrophoresis (PFGE). RESULTS The MRSA isolates were highly resistant to gentamicin, kanamycin, ciprofloxacin, tetracycline, fusidic acid and mupirocin. The prevalence of gentamicin, kanamycin, streptomycin, tetracycline and erythromycin resistance remained high (80-96%) throughout the study period, but the prevalence of resistance to ciprofloxacin, fusidic acid and mupirocin steadily increased. The already high mupirocin resistance level increased from 12.5 in 1996, to 85.7% in 2001, and the fusidic acid resistance varied between 70.8 and 85.7%. In contrast, chloramphenicol and trimethoprim resistance declined from 25 and 29% in 1996 to 4.7 and 14.2% in 2001, respectively. The majority (91.5%) of the isolates were coagulase serotype 4. AluI restriction endonuclease analysis of amplified coagulase gene generated four coag-RFLP patterns: 92% of them were coag-RFLP type 1, while types 2, 3 and 4 were 3.5, 4.6 and 1.1% respectively. PFGE differentiated them into seven pulsotypes (PFGE types 1-7). The PFGE type 1 pulsotype constituted 90.2% of the isolates. Isolates with the type A coag-RFLP also had the type1 PFGE pulsotypes. CONCLUSION The concordant results of PFGE and coag-RFLP demonstrated the presence of a persistent MRSA clone in the hospital during the study period.
In vitro and in vivo potency of moxifloxacin and moxifloxacin ophthalmic solution 0.5%, a new topical fluoroquinolone.
Alcon Research, Ltd., Fort Worth, TX 76134-2099, USA.
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.
Katedra farmaceutické technologie Farmaceutické fakulty Univerzity Karlovy, Hradec Králové. email@example.com
One of the possibilities of how to optimize bioavailability of drugs after topical ophthalmic administration is prolongation of the period of contact of the preparation with the eye tissue. The most usual way of achieving this gaol is an increase in the viscosity of the preparation by an addition of a suitable auxiliary substance. At present besides hydrogels and mucoadhesive substances, also polymers which produce the sol-gel phase change are employed for this purpose. This so-called in situ gelation takes place in a very short period of time after contact with the eye tissue due to a change in temperature, pH, or interaction with physiological ions. The present paper aims to survey in situ gelling polymeric substances, which are examined in relation to their use in ophthalmic administration.
Laboratory of Pharmaceutical Technology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
AIM: Eye drops are the most used dosage form by the ocular route, in spite of their low bioavailability. Due to their properties and numerous advantages, microemulsions are promising systems for topical ocular drug delivery. They can increase water solubility of the drug and enhance drug absorption into the eye. The present study describes the development and characterization of an oil-in-water microemulsion containing dexamethasone and the evaluation of its pharmacokinetics in rabbits after topical ocular application. METHODS: The microemulsion was prepared by the titration technique. Its physico-chemical characteristics and stability were determined. The ocular irritation test and the pharmacokinetics of this system were studied in white rabbits. RESULTS: The developed system showed an acceptable physico-chemical behaviour and presented good stability for 3 months. The ocular irritation test used suggested that the microemulsion did not provide significant alteration to eyelids, conjunctiva, cornea and iris. This formulation showed greater penetration of dexamethasone in the anterior segment of the eye and also release of the drug for a longer time when compared with a conventional preparation. The area under the curve obtained for the microemulsion system was more than twofold higher than that of the conventional preparation (P < 0.05). CONCLUSIONS: The microemulsion-based dexamethasone eye drop is advantageous for ophthalmic use because it is well-tolerated in the eye and seemed to provide a higher degree of bioavailability. The developed system shows greater penetration in the eye, allowing the possibility of decreasing the number of applications of eye drops per day.