Francis S. Mah

Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates

PURPOSE We compared the in vitro susceptibility patterns and the minimum inhibitory concentrations (MICs) of gatifloxacin (GAT) and moxifloxacin (MOX) (fourth-generation fluoroquinolones) to ciprofloxacin (CIP) and ofloxacin (OFX) (second-generation fluoroquinolones) and levofloxacin (LEV; third-generation fluoroquinolone) using bacterial keratitis isolates. The goal was to determine whether the fourth-generation fluoroquinolones offer any advantages over the second- and third-generation fluoroquinolones. DESIGN Experimental laboratory investigation. In contrast to an epidemiologic prevalence study, this study was designed to compare the relative susceptibility of each bacterial group to different fluoroquinolones by deliberate selection of representative isolates that were both susceptible and resistant to second-generation fluoroquinolones. METHODS In retrospect, the MICs of 177 bacterial keratitis isolates were determined to CIP, OFX, LEV, GAT, and MOX using E tests. A relative susceptibility analysis was performed for each bacterial group that included separate bacterial groups that were resistant to second-generation fluoroquinolones. The NCCLS susceptibility patterns and the MICs were compared statistically. Comparing MICs, the antibiotic with the lower MICs has greater antibacterial activity. RESULTS For most keratitis isolates, there were no susceptibility differences among the five fluoroquinolones. The fourth-generation fluoroquinolones did, however, demonstrate increased susceptibility for Staphylococcus aureus isolates that were resistant to CIP, LEV and OFX. In general, CIP demonstrated the lowest MICs for gram-negative bacteria. The MICs for fourth-generation fluoroquinolones were statistically lower than the second-generation fluoroquinolones for all gram-positive bacteria tested. Comparing the two fourth-generation fluoroquinolones, MOX demonstrated lower MICs for most gram-positive bacteria, whereas GAT demonstrated lower MICs for most gram-negative bacteria. CONCLUSIONS Based on in vitro testing, the fourth-generation fluoroquinolones may offer some advantages over those currently available for the treatment of bacterial keratitis. Clinical studies will be required to confirm these results.

Migration of silicone oil into the brain: a complication of intraocular silicone oil for retinal tamponade

PURPOSE To report a case in which intravitreal silicone oil migrated along the intracranial portion of the optic nerve and into the lateral ventricles of the brain after the repair of a retinal detachment secondary to cytomegalovirus retinitis. METHODS A 42-year-old man with acquired immunodeficiency syndrome (AIDS) developed a rhegmatogenous retinal detachment in his left eye secondary to a cytomegalovirus infection of the retina. The detachment was repaired using 5000 cs intraocular silicone oil for a long-term tamponade. Subsequently, the affected eye developed glaucoma, which was poorly controlled. Fifteen months after the retinal surgery, he developed a peripheral neuropathy that was thought to be AIDS related. Computed tomography and magnetic resonance imaging of the head were performed to investigate the neuropathy. RESULTS The patient was found to have a foreign substance within his lateral ventricles that shifted with position and was identical with respect to its imaging properties to the remaining intraocular silicone oil. Additional material was found along the intracranial portion of his optic nerve. CONCLUSION Under certain circumstances, intraocular silicone oil may migrate out of the eye, along the intracranial portion of the optic nerve, and into the lateral ventricles of the brain.

Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis.

Purpose: To evaluate the effect of 4 weeks of treatment with azithromycin ophthalmic solution 1% on eyelid bacterial load, tear cytokines, and signs and symptoms of blepharitis. Methods: Twenty-six subjects (mean age 64.2 years; 65% female; 100% white) with moderate to severe blepharitis received azithromycin ophthalmic solution 1% in the absence of warm compresses or eyelid scrubs for 28 days (twice a day on days 1 and 2 and once a day on days 3-28). Blepharitis signs and symptoms were evaluated at baseline (day 1) and compared with end of treatment (day 29) and 2 follow-up visits (2 and 4 weeks posttreatment). Tear collection and eyelid margin bacterial cultures were performed at baseline and end of treatment. Tear cytokines were measured by a multiplex immunobead assay. Results: Four-week azithromycin treatment demonstrated significant decreases from baseline in investigator-rated signs of meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge (P ≤ 0.002) at day 29, which persisted 4 weeks posttreatment (P ≤ 0.006). Subject-reported symptoms of eyelid itching, foreign body sensation/sandiness/grittiness, ocular dryness, ocular burning/pain, and swollen/heavy eyelids also demonstrated significant improvement from baseline (P < 0.001 for all symptoms and time points, except P = 0.037 for ocular dryness at visit 4). Eyelid margin culture exhibited significant decreases in coagulase-negative staphylococci and Corynebacterium xerosis bacteria. Changes in tear cytokine concentrations were not observed. Twelve subjects experienced 19 adverse events, 15 of which were ocular and none of which were serious. Conclusions: Azithromycin provided significant improvement in signs and symptoms of blepharitis after 4 weeks of treatment compared with baseline and persisted in the 4-week follow-up period.

Antibiotic susceptibility of conjunctival bacterial isolates from refractive surgery patients.

PURPOSE To determine the in vitro antibiotic susceptibility patterns of conjunctival bacterial flora isolated before surgery from patients undergoing refractive surgery. DESIGN In vitro laboratory investigation. PARTICIPANTS One hundred five eyes from 105 patients scheduled for refractive surgery at Balgensesang Ophthalmology Clinic between September 2005 and January 2006 were studied. Among 105 patients, 71 (67.6%) underwent LASIK using a femtosecond laser, 24 (22.9%) underwent LASIK using an automated microkeratome, 8 (7.6%) underwent LASEK, and 2 (1.9%) patients underwent phakic intraocular lens implantation. METHODS Preoperative conjunctival swab samples were inoculated directly in culture media at the bedside before topical anesthetic or antibiotic application. Blood agar, chocolate agar, thioglycolate broth, Sabouraud dextrose agar, and Ogawa media were used for bacterial, fungal, and mycobacterial cultures. MAIN OUTCOME MEASURES Minimum inhibitory concentrations (MICs) of ofloxacin (OFX), levofloxacin (LEV), gatifloxacin (GAT), moxifloxacin (MOX), gemifloxacin (GEM), and other commonly used antibiotics were determined using an E test. RESULTS From 105 patients, 73 (85%) coagulase-negative staphylococci (CNS), 2 (2.3%) Staphylococcus aureus, 1 (1.2%) Streptococcus pneumoniae, and 5 (4.8%) gram-negative bacilli were isolated. No fungi or mycobacteria were isolated. The MIC that would inhibit the growth of 90% of the tested bacterial isolates (MIC(90)) of OFX, LEV, GAT, MOX, and GEM for methicillin-susceptible CNS (n = 46) were 0.5 microg/ml, 0.19 microg/ml, 0.094 microg/ml, 0.047 microg/ml, and 0.023 microg/ml, respectively. The MIC(90) values for methicillin-resistant CNS (n = 27) were 32 microg/ml, 4 microg/ml, 1 microg/ml, 0.5 microg/ml, and 0.25 microg/ml, respectively (P<0.001). CONCLUSIONS The most effective against conjunctival bacteria isolated from refractive surgery patients were GEM, MOX, and GAT; however, resistance to earlier-generation fluoroquinolones (OFX and LEV) is increasing among methicillin-resistant CNS. It may be a therapeutic option to use newer fluoroquinolones in patients undergoing refractive eye surgery to reduce such infections as methicillin-resistant CNS. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Reshaping procedures for the surgical management of corneal ectasia.

&NA; Corneal ectasia is a progressive, degenerative, and noninflammatory thinning disorder of the cornea. Recently developed corneal reshaping techniques have expanded the treatment armamentarium available to the corneal specialist by offering effective nontransplant options. This review summarizes the current evidence base for corneal collagen crosslinking, topography‐guided photorefractive keratectomy, and intrastromal corneal ring segment implantation for the treatment of corneal ectasia by analyzing the data published between the years 2000 and 2014. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Microbial keratitis trends following refractive surgery: Results of the ASCRS infectious keratitis survey and comparisons with prior ASCRS surveys of infectious keratitis following keratorefractive procedures

&NA; In 2008, the American Society of Cataract and Refractive Surgery (ASCRS) surveyed its 9121 United States and international members to evaluate the changing trends and incidence, culture results, treatment, and visual outcomes of infectious keratitis following keratorefractive procedures worldwide. This paper presents and analyzes the results with comparisons to the data in surveys conducted in 2001 and 2004. Nineteen infections were reported by 14 surgeons who had performed an estimated 20 941 keratorefractive procedures, an incidence of 1 infection in every 1102 procedures. Sixteen cases presented in the first postoperative week, 1 case during the second week, 1 case between the second and fourth weeks, and 1 case at 1 month or later. The 16 cases that presented in the first week were diagnosed at initial presentation. The most common organism cultured was methicillin‐resistant Staphylococcus aureus (MRSA). Microbial keratitis following refractive surgery is an increasingly recognized sight‐threatening complication. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found after the text.

A comparison of moxifloxacin and levofloxacin topical prophylaxis in a fluoroquinolone-resistant Staphylococcus aureus rabbit model

PurposeMoxifloxacin, a fourth-generation fluoroquinolone (FQ), was compared to levofloxacin, a thirdgeneration FQ, for preventing FQ-resistant, methicillin-resistant Staphylococcus aureus (FQrMRSA) endophthalmitis in a rabbit model.MethodsThree regimens of topical treatments (moxifloxacin 0.5%, levofloxacin 0.5%, and saline) were tested to prevent endophthalmitis. For each regimen, drops were instilled every 15 min for 1 h into the left eyes of 15 rabbits. After anesthesia, 2 × 104 cfu of FQrMRSA was injected into the aqueous. One drop of treatment was given immediately, and another four drops were applied over 24 h. At 24 h, the eyes were clinically graded for endophthalmitis. After the rabbits were sacrificed, the aqueous and vitreous were tapped for bacterial colony counts.ResultsTopical moxifloxacin (12/15, 80%) significantly (P = 0.0001) prevented clinical endophthalmitis in more rabbits than levofloxacin (2/15, 13%) or saline (2/15, 13%). The total median clinical score for moxifloxacin treatment (1.0) was significantly (P = 0.0004) lower than that for levofloxacin (20.0) or saline (23.0). Culture-negative eyes were less frequent for levofloxacin (8/15, 53%) and saline (1/15, 7%) treatments than for moxifloxacin treatment (12/15, 80%).ConclusionThis in vivo study indicates that moxifloxacin, a fourth-generation FQ, may be more effective than levofloxacin, a third-generation FQ, in preventing experimental FQrMRSA. endophthalmitis.

Valacyclovir inhibition of recovery of ocular herpes simplex virus type 1 after experimental reactivation by laser in situ keratomileusis

Purpose: To determine whether the systemic administration of valacyclovir (Valtrex®) reduces ocular shedding of herpes simplex virus type 1 (HSV‐1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model. Setting: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Methods: New Zealand White rabbits latently infected with HSV‐1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV‐1 ocular shedding was determined from eye cultures for 7 days after LASIK. Results: The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV‐1 shedding days (1/122 and 2/122, respectively) from which HSV‐1 was recovered compared to the control group (7/16 [P = .0396] and 14/129 [P < .007], respectively). Conclusions: Systemic administration of valacyclovir significantly reduced HSV‐1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.

Hand-held force magnifier for surgical instruments

We present a novel and relatively simple method for magnifying forces perceived by an operator using a tool. A sensor measures the force between the tip of a tool and its handle held by the operators fingers. These measurements are used to create a proportionally greater force between the handle and a brace attached to the operators hand, providing an enhanced perception of forces between the tip of the tool and a target. We have designed and tested a prototype that is completely hand-held and thus can be easily manipulated to a wide variety of locations and orientations. Preliminary psychophysical evaluation demonstrates that the device improves the ability to detect and differentiate between small forces at the tip of the tool. Magnifying forces in this manner may provide an improved ability to perform delicate surgical procedures, while preserving the flexibility of a hand-held instrument.

New antibiotics for bacterial infections.

All the available ophthalmic antibiotics have strengths and weaknesses. There is not yet a magic bullet that would successfully treat all infections without harm to the host. The challenges of the future are the same as the challenges of the past: to battle bacterial infections with the least toxic, least expensive, lowest dosing frequency antibiotic and yet clear the infection more quickly. The war between humans and bacteria seems like a hopeless one because of the sheer numbers of bacteria, their incredible ability to adapt, and their unembarrassed penchant for reproduction. And yet the ingenuity and tenacity of humans cannot be overlooked. Already more than 10,000 fluoroquinolone agents have been developed and tested since the original discovery of nalidixic acid in 1962. With the newer agents soon to be available, including moxifloxacin and gatifloxacin, clinicians will be armed with the most potent antimicrobial agents yet. The not too distant future is also bright with agents coming from research of quorum sensing and genomics. Only time will tell how these newer agents will compare with the current ophthalmic antibiotics.