Y.J. Gordon

Fluoroquinolones in the Treatment of Bacterial Keratitis

PURPOSE We evaluated the potential role of three topical fluoroquinolones in the treatment of bacterial keratitis by means of a laboratory database. METHODS Antibiotic susceptibilities were determined for 153 isolates from patients with bacterial keratitis. Results were analyzed for each fluoroquinolone individually and in combination with cefazolin. RESULTS Predicted susceptibility to each cefazolin-fluoroquinolone combination (98.7%) was superior to that for single-agent therapy with ofloxacin (88.2%), ciprofloxacin (82.3%), or norfloxacin (80.4%) (P = .0002). A cefazolin-fluoroquinolone combination (98.7%) was comparable to a cefazolin-gentamicin combination (97.4%). CONCLUSIONS Combination therapy with cefazolin and a fluoroquinolone offers a reasonable alternative for the treatment of bacterial keratitis. Single-agent therapy with fluoroquinolones for vision-threatening bacterial keratitis is not advised.

An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics

This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n=385) and blepharitis (n=173) using the National Committee for Clinical Laboratory Standardsapproved disk diffusion method. The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B. We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro. Established antibiotics often provided coverage comparable to the newer drugs. Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness.

A Comparison of Enzyme Immunoassay and Polymerase Chain Reaction with the Clinical Examination for Diagnosing Ocular Herpetic Disease

PURPOSE The results of two laboratory diagnostic herpes simplex virus (HSV) tests, an enzyme immunoassay (improved Herpchek [iHC]) and the polymerase chain reaction (PCR), were compared with the clinical examination in the diagnosis of HSV. We determined when diagnostic laboratory tests provided the initial diagnosis of HSV ocular disease and when they were only confirmatory. METHODS The sensitivity and specificity of iHC and PCR were determined using 22 HSV culture-positive clinical samples, 10 adenovirus culture-positive clinical samples, 5 samples from normal conjunctivas, 4 bacterial samples, and 1 sample containing Varicella zoster virus. The medical history of the 22 patients with positive HSV cultures were reviewed to determine the initial diagnosis by clinical examination and the initial therapy. RESULTS For typical presentations of ocular HSV disease, the clinical examination is as accurate as iHC (P = 0.99) and PCR (P = 0.24). However, for atypical presentations of ocular HSV disease, iHC (P = 0.000005) or PCR (P = 0.00006) were more accurate in detecting HSV infection than the clinical examination. CONCLUSION Laboratory diagnosis of HSV from ocular samples was most useful to the clinician in atypical presentations of herpetic ocular disease.

Evaluation of Immunologlic Tests for the Detection of Ocular Herpes Simplex Virus

Abstract Four immunologic tests, Herpchek (HC), latex agglutination (AGG), enzyme immunofiltration (IF), and 1 hour enzyme-linked immunoassay (1EIA), were evaluated for detecting herpes simplex virus (HSV) from ocular specimens. Compared with the standard of HSV-positive cell cultures, 24 (65%) of 37 positive HC tests and 22 (59%) of 37 positive IF tests were significantly more sensitive ( P P = 0.4) as any of the immunologic tests. In conclusion, for definitive diagnosis of HSV, the HC test seems more suitable for a central laboratory that handles a large number of viral specimens, and processes HC-negative tests with follow-up cell culture isolation. The enzyme immunofiltration test seems more suitable for a low-volume viral laboratory which confirms all IF test samples with follow-up cell culture isolation.

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.

Comparison of Direct Rapid Tests for the Detection of Adenovirus Antigen in Routine Conjunctival Specimens

Two direct rapid tests to detect adenovirus antigen, enzyme immunoassay (EIA) and immunofiltration (IF) were compared with regard to sensitivity, specificity, ease of interpretation, and technical complexity against 75 adenovirus culture-positive and 35 adenovirus culture-negative conjunctival swab specimens. Enzyme immunoassay and IF were equally sensitive (P = 0.5), with sensitivities of 80.6 and 79.0%, respectively, when swab specimens were collected from patients within 7 days of the onset of clinical symptoms of adenovirus infection. After 7 days of clinical onset, IF (46.2%) was more sensitive (P less than 0.01) than EIA (0.0%), and was able to detect residual antigen in three culture-negative specimens. Enzyme immunoassay and IF were equally specific (100%). Both tests were easy to interpret, but IF was more technically complex and is not yet commercially packaged. Enzyme immunoassay could benefit either an office practice or a central laboratory, whereas IF is better suited for the latter.

A 5-year evaluation of the adenoclone test for the rapid diagnosis of adenovirus from conjunctival swabs.

The rapid diagnosis of adenoviral ocular infections affords the opportunity to limit the transmission of virus within the community and avoid expensive, unnecessary, and ineffective therapy. This study evaluated the results of a 5-year experience with the Adenoclone test (Cambridge Biotech, Worcester, MA), an enzyme immunoassay, applied directly to conjunctival swabs obtained from infected eyes. The sensitivity of this test was determined on 372 consecutive adenovirus culture-positive ocular specimens. A subset of 106 specimens was evaluated, including a retrospective chart review to determine the relationship between the Adenoclone result and the time to viral cytopathic effect (CPE) in A549 cell culture, ocular titers (90% tissue culture infectious dose; TCID90), serotype, and associated clinical parameters. Overall, the sensitivity for Adenoclone was 38% (142 of 372), which improved to 65% (129 of 199) for samples positive in culture during the first week. A positive Adenoclone test result was associated with a shorter time to CPE in cell culture (p=0.0001). The mean ocular titers (log TCID90) associated with a positive test result were found to be at a significantly higher dilution than a negative result (-1.70 ± 0.93 vs. -0.88 ± 1.00, p<0.0001). A positive Adenoclone outcome was independent of the serotype but directly associated with a recent visit to an ophthalmologists office, follicular conjunctivitis, and conjunctival chemosis. For the rapid diagnosis of adenoviral ocular infections, the Adenoclone test remains useful, but a more sensitive test based on nonradioactive amplification is eagerly anticipated.

Evaluation of the Polymerase Chain Reaction Test for Detecting Chlamyclial DNA in Adult Chlamyclial Conjunctivitis

PURPOSE A new polymerase chain reaction (PCR) test (Amplicor, Diagnostics, Branchburg, NJ) was evaluated for its ability to detect chlamydial DNA from previously obtained adult conjunctival specimens. METHODS The sensitivity of this PCR test was determined on 42 adult conjunctival specimens that were culture-positive for Chlamydia. The specificity was determined by testing 40 true-negative specimens that included 10 normal conjunctival samples and 20 ocular specimens that were culture-positive for herpes simplex virus or adenovirus. The remaining ten samples consisted of ocular bacterial pathogens in chlamydial transport media. RESULTS Amplicor was 88% (37/42) sensitive and 100% (40/40) specific. CONCLUSIONS The authors conclude that PCR testing for chlamydial DNA from ocular specimens may be useful, especially when conditions in transport might reduce the yield of positive cultures.

Adenoviral Ocular Isolates Demonstrate Serotype-Dependent Differences in In Vitro Infectivity Titers and Clinical Course

The purpose of this study was to evaluate clinical ocular adenoviral isolates for differences among and within serotypes with respect to in vitro infectivity titers and clinical course. The study design included a retrospective chart review and the determination of in vitro infectivity titers (TCIDCKJS) of 90 clinical ocular isolates of various adenoviral serotypes. Adenovirus serotype 8 (AD8) was recovered in significantly greater numbers of patients in the second week of infection compared to all other serotypes (p<.002). AD3 and AD4 presented with the highest infectivity titers during the first week of acute infection. Up to 4 logs of variation was demonstrated in TCIDgoS among isolates of the same serotype. Among the clinical parameters studied, eyelid edema was significantly more common among AD8-infected patients as compared to all other serotypes (p<0.04). For the first time, specific, but limited serotype differences with respect to infectivity titers and clinical course were demonstrated for adenoviral ocular isolates. Important variations in isolate virulence within a given serotype were also observed.

HPMPC, a broad-spectrum topical antiviral agent, inhibits herpes simplex virus type 1 replication and promotes healing of dendritic keratitis in the New Zealand rabbit ocular model.

Previously, we demonstrated that HPMPC, a new, broad-spectrum antiviral agent, inhibited adenovirus type 5 in the New Zealand (NZ) rabbit ocular model (Cornea 1992; 11:529–33). Historically, no antiviral agent has been demonstrated to be effective against both herpes simplex virus type 1 (HSV-1) and adenovirus eye infections in an experimental animal model. In this study, we compared topical 0.2% HPMPC to 1% trifluridine and vehicle control in the NZ rabbit HSV-1 keratitis model. Using a double-masked, two-eye design, NZ rabbits were inoculated in both eyes with HSV-1 W strain (105 pfu/eye), and dendritic keratitis and HSV-1 ocular titers were measured serially. Compared with the control group, both topical 0.2% HPMPC and 1% trifluridine significantly reduced healing time of HSV-1 dendritic keratitis, lowered HSV-1 ocular titers on days 3 through 11, and shortened duration of HSV-1 shedding in the tear film. For all outcome parameters measured, topical 0.2% HPMPC was as effective as 1% trifluridine. A new concept of a broad-spectrum topical antiviral agent was shown to be effective against HSV-1 in an NZ rabbit keratitis model, and further development toward clinical application appears desirable.