Moxifloxacin susceptibility mediates the relationship between causative organism and clinical outcome in bacterial keratitis.

PURPOSE: Bacterial keratitis is a sight-threatening infection of the cornea that is one of the leading causes of blindness globally. In this report, we analyze the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacteria keratitis. METHODS: A mediation analysis is used to assess the role of moxifloxacin susceptibility in the relationship between causative organisms and clinical outcome in bacterial keratitis using data collected in a randomized, controlled trial. RESULTS: In the Steroids for Corneal Ulcers Trial (SCUT), 500 corneal infections were treated with topical moxifloxacin. The outcome of 3-week best spectacle-corrected visual acuity was significantly associated with an organism (Streptococcus pneumoniae, Pseudomonas aeruginosa, etc., P = 0.008). An indirect effects mediation model suggests that MIC accounted for approximately 13% (95% confidence interval, 3%-24%, P = 0.015) of the effect of the organism on 3-week visual acuity. CONCLUSIONS: Moxifloxacin mediates the relationship between causative organisms and clinical outcome in bacterial keratitis, and is likely on the causal pathway between the organism and outcome. (ClinicalTrials.gov number, NCT00324168.).

Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis.

BACKGROUND: For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. METHODS: Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. RESULTS: Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). CONCLUSIONS: In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. CLINICAL TRIALS REGISTRATION: NCT00324168.

Etiology and epidemiological analysis of glaucoma-filtering bleb infections in a tertiary eye care hospital in South India.

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.

Etiology and antibacterial susceptibility pattern of community-acquired bacterial ocular infections in a tertiary eye care hospital in south India.

AIMS: To identify the etiology, incidence and prevalence of ocular bacterial infections, and to assess the in vitro susceptibility of these ocular bacterial isolates to commonly used antibiotics. MATERIALS AND METHODS: Retrospective analysis of consecutive samples submitted for microbiological evaluation from patients who were clinically diagnosed with ocular infections and were treated at a tertiary eye care referral center in South India between January 2002 and December 2007. RESULTS: A total of 4417 ocular samples was submitted for microbiological evaluation, of which 2599 (58.8%) had bacterial growth, 456 (10.3%) had fungal growth, 15 (0.34%) had acanthamoebic growth, 14 (0.32%) had mixed microbial growth and the remaining 1333 (30.2%) had negative growth. The rate of culture-positivity was found to be 88% (P < 0.001) in eyelids' infection, 70% in conjunctival, 69% in lacrimal apparatus, 67.4% in corneal, 51.6% in intraocular tissues, 42.9% in orbital and 39.2% in scleral infections. The most common bacterial species isolated were Staphylococcus aureus (26.69%) followed by Streptococcus pneumoniae (22.14%). Sta. aureus was more prevalent more in eyelid infections (51.22%; P = 0.001) coagulase-negative staphylococci in endophthalmitis (53.1%; P = 0.001), Str. pneumoniae in lacrimal apparatus and corneal infections (64.19%; P = 0.001), Corynebacterium species in blepharitis and conjunctivitis (71%; P = 0.001), Pseudomonas aeruginosa in keratitis and dacryocystitis (66.5%; P = 0.001), Haemophilus species in dacryocystitis and conjunctivitis (66.7%; P = 0.001), Moraxella lacunata in blepharitis (54.17%; P = 0.001) and Moraxella catarrhalis in dacryocystitis (63.83%; P = 0.001). The largest number of gram-positive isolates was susceptible to moxifloxacin (98.7%) and vancomycin (97.9%), and gram-negative isolates to amikacin (93.5%) and gatifloxacin (92.7%). CONCLUSIONS: Gram-positive cocci were the most frequent bacteria isolated from ocular infections and were sensitive to moxifloxacin and vancomycin, while gram-negative isolates were more sensitive to amikacin and gatifloxacin.

Visual prognosis, intraocular pressure control and complications in phacomorphic glaucoma following manual small incision cataract surgery.

AIMS: To evaluate intraocular pressure (IOP) control, visual prognosis and complications following manual small incision cataract surgery among eyes with phacomorphic glaucoma. MATERIALS AND METHODS: This prospective, non-randomized interventional consecutive case series included all patients with phacomorphic glaucoma who presented to a tertiary eye care referral center in South India between March 2006 and April 2007. All patients underwent slit-lamp bio-microscopy, applanation tonometry and gonioscopy of the other eye to rule out angle closure. Small incision cataract surgery with intraocular lens implantation was performed in all affected eyes. Complete ophthalmic examination was done at each follow-up visit. RESULTS: A total of 74 eyes with phacomorphic glaucoma were included in this study. The preoperative mean IOP was 38.4+/-14.3 mmHg and mean IOP at last follow-up was 12.7+/-2.4 mmHg. There was a statistically significant difference between IOP at presentation and IOP at last follow-up (P< 0.001). None of the eyes required long-term antiglaucoma medication. No significant intraoperative complications were noted. The final postoperative best corrected visual acuity was 20/40 or better in 51 patients. Eighteen eyes had corneal edema and 36 eyes had anterior chamber inflammation. Both conditions resolved with standard medical therapy. CONCLUSION: Manual small incision cataract surgery is safe and effective in controlling IOP and achieving good functional visual acuity with minimal complications in the management of phacomorphic glaucoma in developing countries.

Prevalence of bacterial pathogens causing ocular infections in South India.

BACKGROUND/AIMS: The eye may be infected from external sources or through intra-ocular invasion of micro-organisms carried by the blood stream. This study was undertaken to isolate and identify the specific bacterial pathogens causing ocular infections and to determine their in-vitro antibacterial susceptibilities to commonly used antibacterial agents. MATERIALS AND METHODS: A retrospective analysis of all patients with clinically diagnosed bacterial ocular infections such as blepharitis, conjunctivitis, internal and external hordeolum, suppurative scleritis, canaliculitis, keratitis, dacryocystitis, preseptal cellulitis, endophthalmitis and panophthalmitis presenting between January 2005 and December 2005 was performed. Extra-ocular and intra-ocular specimens were collected and were subjected to direct microscopy and culture. RESULTS: A total of 756 patients with bacterial ocular infections were analyzed, of which 462(61%) eyes had adnexal bacterial infection, 217(28.7%) had corneal infection, 6 (0.8%) had scleral involvement and the remaining 71(9.39%) eyes had infection of the intra-ocular tissues. The predominant bacterial species isolated was S. aureus (195 of 776; 25%) followed by S. pneumoniae (169 of 776; 21.78%) and coagulase negative staphylococci (142 of 776; 18.3%). The largest number of gram-positive isolates were susceptible to cefazolin (545 of 624; 87.34%), chloramphenicol (522 of 624; 83.65%) and gatifloxacin (511 of 624; 81.89%) and gram-negative isolates were to amikacin (127 of 136; 93.38%), gatifloxacin (125 of 136; 91.91%) and ofloxacin (119 of 136; 87.5%), while aerobic actinomycetes were to amikacin (100%), gatifloxacin (14 of 16; 87.5%), chloramphenicol (14 of 16; 87.5%) and ofloxacin (13 of 16; 81.25%). CONCLUSIONS: S. aureus frequently causes infections of eyelids and conjunctiva, S. pneumoniae of lacrimal apparatus and cornea and coagulase negative staphylococci causes intra-ocular infections. Of all routinely used antibacterials tested, flouroquinolones, especially gatifloxacin and ofloxacin represented a good choice for treating bacterial ocular infections.

Comparative in-vitro efficacy of fluoroquinolones against Streptococcus pneumoniae recovered from bacterial keratitis as determined by E-test.

BACKGROUND AND OBJECTIVES: The advent of new fluoroquinolones has drawn the attention for reliable methods on the in-vitro susceptibility testing of Streptococccus pneumoniae. This study attempts to determine the minimum inhibitory concentration (MIC) of second-generation (ciprofloxacin and ofloxacin), third-generation (levofloxacin) and the fourth-generation (moxifloxacin and gatifloxacin) fluoroquinolones against S. pneumoniae recovered from bacterial keratitis. MATERIALS AND METHODS: In retrospect, the MICs of 50 strains of S. pneumoniae isolated from the corneal scrapes of patients with bacterial keratitis were determined against ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin using E-tests. The National Committee of Clinical Laboratory Standards (NCCLS) susceptibility patterns and the potencies of the MICs were statistically compared. RESULTS: The median MIC of ciprofloxacin (0.25microg/ml) was found to be lower than the median MICs of ofloxacin (0.5microg/ml) (P < 0.449) and levofloxacin (1.0microg/ml) (P < 0.001). The median MICs of gatifloxacin (0.1microg/ml) was lower than the median MICs of ciprofloxacin (0.25microg/ml) (P < 0.001), ofloxacin (0.5microg/ml) (P < 0.001) and levofloxacin (1.0microg/ml) (P < 0.001). Moxifloxacin (0.06microg/ml) had showed lower median MICs than gatifloxacin (0.1microg/ml) (P < 0.001) levofloxacin (1.0microg/ml) (P < 0.001), ofloxacin (0.5microg/ml) (P < 0.001) and ciprofloxacin (0.25microg/ml) (P < 0.001). Moxifloxacin (0.06microg/ml) had a lower MIC50 (microg/ml) than gatifloxacin (0.1microg/ml), levofloxacin (1.0microg/ml), ciprofloxacin (0.25microg/ml) and ofloxacin (0.5microg/ml). MIC90 (microg/ml) of moxifloxacin (0.06microg/ml) was found to be lower than the MIC90 (microg/ml) of gatifloxacin (0.5microg/ml), levofloxacin (1.0microg/ml), ofloxacin (0.5microg/ml) and ciprofloxacin (0.5microg/ml). CONCLUSION: Based on in-vitro testing, the five portrayed fluoroquinolones 100% sensitivity to S. pneumoniae. However, the fourth-generation fluoroquinolone, moxifloxacin appeared to be more effective against S. pneumoniae than gatifloxacin, levofloxacin, ofloxacin and ciprofloxacin.

Analysis of the risk factors predisposing to fungal, bacterial & Acanthamoeba keratitis in south India.

BACKGROUND & OBJECTIVE: Infective keratitis is rare in the absence of predisposing factors. The pattern of risk factors predisposing to infective keratitis varies with geographical regions and also influences the type of infection that occurs. The present study was aimed to identify the specific risk factors that predispose the infective keratitis (non viral) and to determine the association between the risk factors identified and the microbial aetiology of infective keratitis in a geographic region (south India). METHODS: A retrospective analysis of all patients clinically diagnosed infective keratitis (non viral) presenting between September 1999 and September 2002 was performed to identify risk factors. After diagnosing infective keratitis clinically, corneal scrapes were performed and subjected to microscopy and culture. RESULTS: A total of 3295 patients with infective keratitis were evaluated, of whom, 1138 (34.5%) patients had fungal growth alone, 1066 (32.4%) had bacterial growth alone, 33 (1%) had Acanthamoeba growth alone, 83 (2.5%) had mixed microbial growth and the remaining 975 (29.6%) had no growth. Corneal injury was identified in 2356 (71.5%) patients and it accounted for 91.9 per cent in fungal keratitis (P<0.0001) (OR: 73.5; 95%CI: 61.3-98.5), 28.1 per cent in bacterial keratitis and 100 per cent in Acanthamoeba keratitis (P<0.0001). Injuries due to vegetative matter (61.2%) was identified as significant risk for fungal keratitis (P<0.0001) (OR: 15.73; 95%CI: 12.7-19.49) and mud (84.85%) for Acanthamoeba keratitis (P<0.0001) (OR: 16.52; 95%CI: 6.35-42.99). Co-existing ocular diseases predisposing to bacterial keratitis accounted for 724 (69%) patients (P<0.0001) (OR: 33.31; 95%CI: 26.98-41.12). Bacterial pathogens alone were recovered from all 35 patients with contact lens associated keratitis (100%). Co-existing ocular diseases (78.3%) were frequently documented among patients older than 50 yr (P<0.0001) (OR: 27.0; 95%CI: 25.0-28.0) and corneal injury (89.7%) was frequently recorded among patients younger than 51 yr (P<0.0001) (OR: 72.0; 95%CI: 70.0-73.0). INTERPRETATION & CONCLUSION: Corneal injury was found to be the principal risk factor for fungal and Acanthamoeba keratitis, while co-existing ocular diseases for bacterial keratitis. Corneal injury with vegetative matter was more often associated with fungal keratitis and injury with mud with Acanthamoeba keratitis.

Microbial keratitis in South India: influence of risk factors, climate, and geographical variation.

PURPOSE: To determine the influence of risk factors, climate, and geographical variation on the microbial keratitis in South India. METHODS: A retrospective analysis of all clinically diagnosed infective keratitis presenting between September 1999 and August 2002 was performed. A standardised form was filled out for each patient, documenting sociodemographic features and information pertaining to risk factors. Corneal scrapes were collected and subjected to culture and microscopy. RESULTS: A total of 3,183 consecutive patients with infective keratitis were evaluated, of which 1,043 (32.77%) were found to be of bacterial aetiology, 1,095 (34.4%) were fungal, 33 (1.04%) were Acanthamoeba, 76 (2.39%) were both fungal and bacterial, and the remaining 936 (29.41%) were found to be culture negative. The predominant bacterial and fungal pathogens isolated were Streptococcus pneumoniae (35.95%) and Fusarium spp. (41.92%), respectively. Most of the patients (66.84%) with fungal keratitis were between 21 and 50 years old, and 60.21% of the patients with bacterial keratitis were older than 50 (p < 0.0001) (95% CI: 5.19-7.19). A majority of patients (64.75%) with fungal keratitis were agricultural workers (p < 0.0001) [odds ratio (OR): 1.4; 95% CI: 1.19-1.61], whereas bacterial keratitis occurred more commonly (57.62%) in nonagricultural workers (p < 0.0001) (OR: 2.88; 95% CI: 2.47-3.36). Corneal injury was identified in 2,256 (70.88%) patients, and it accounted for 92.15% in fungal keratitis (p < 0.0001) (OR: 7.7; 95% CI: 6.12-9.85) and 100% in Acanthamoeba keratitis. Injuries due to vegetative matter (61.28%) were identified as a significant cause for fungal keratitis (p < 0.0001) (OR: 23.6; 95% CI: 19.07-29.3) and due to mud (84.85%) for Acanthamoeba keratitis (p < 0.0001) (OR: 26.01; 95% CI: 3.3-6.7). Coexisting ocular diseases predisposing to bacterial keratitis accounted for 68.17% (p < 0.0001) (OR: 33.99; 95% CI: 27.37-42.21). The incidence of fungal keratitis was higher between June and September, and bacterial keratitis was less during this period. CONCLUSION: The risk of agricultural predominance and vegetative corneal injury in fungal keratitis and associated ocular diseases in bacterial keratitis increase susceptibility to corneal infection. A hot, windy climate makes fungal keratitis more frequent in tropical zones, whereas bacterial keratitis is independent of seasonal variation and frequent in temperate zones. Microbial pathogens show geographical variation in their prevalence. Thus, the spectrum of microbial keratitis varies with geographical location influenced by the local climate and occupational risk factors.

Ulcerative keratitis associated with contact lens wear.

To review the microbiological profile of ulcerative keratitis associated with contact lens (CL)-wear, 35 patients with culture-proven CL-associated microbial keratitis were studied between September 1999 and September 2002. Corneal scrapes and CL-care products were collected and were subjected to microbiological evaluation. Gram-negative bacilli alone were recovered from the corneal scrapes of all 35 (100%) patients, all 70 (100%) CL storage case wells and also from CL-care solution of six (17.14%) of the 35 patients. There was a significantly higher number of Pseudomonas aeruginosa (71.43%) isolated from eyes with CL-related keratitis than other bacterial isolates (28.57%) (P<0.001). Microbial contamination of CL storage cases was a great risk for gram-negative bacterial infection among soft CL-wearers.

Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A three-year study.

PURPOSE: To study the epidemiological characteristics and laboratory diagnosis of fungal keratitis seen at a tertiary eye care referral centre in South India. METHODS: A retrospective review of all culture-proven fungal keratitis seen over a 3-year period, September 1999 through August 2002. RESULTS: Fungal aetiology were confirmed in 1095 (34.4%) of 3183 corneal ulcers. The predominant fungal species isolated was Fusarium spp (471; 42.82%) followed by Aspergillus spp (286; 26%). Males (712; 65.08%) were more often affected (P<0.0001). A large proportion of the patients (732; 66.85%) were in the younger age group (21 to 50 years). A majority (879; 80.27%) came from rural areas (P<0.0001), and most patients (709; 64.75%) were farmers (P<0.0001). Ocular trauma (1009; 92.15%) was a highly significant risk factor (P<0.0001) and vegetative injuries (671; 61.28%) were identified as a significant cause for fungal keratitis (P<0.0001). 172 (15.71%) patients had concurrent diabetes mellitus. The sensitivity of 10% potassium hydroxide (KOH) wet mount preparation was higher (99.23%) than Gram-stained smear (88.73%) (P<0.0001). Incidence of fungal keratitis was higher between June and September. CONCLUSION: Agricultural activity and related ocular trauma were principal causes of mycotic keratitis. A potassium hydroxide (KOH) wet mount preparation is a simple, and sensitive, method for diagnosis

In-vitro efficacy of antibacterials against bacterial isolates from corneal ulcers.

PURPOSE: To analyse the in-vitro efficacy of commonly used antibacterials against bacterial pathogens from corneal ulcers. METHODS: We evaluated 596 patients seen over 18 months, period, September 1999 through March 2001. Corneal scrapings were subjected to microscopy and cultures using standard protocols. Antibacterial susceptibility of isolated bacteria were determined by the Kirby-Bauer disc-diffusion method. RESULTS: 626 bacterial pathogens were isolated from 596 corneal ulcer cases. 411(65.65%) were gram positive cocci Streptococcus pneumoniae (41.85%) was the predominant bacterial species. The antibacterial susceptibility was: 451(72.04%) to cefazolin, 471(75.24%) to chloramphenicol; 321(51.28%) to cephaloridine; 430(68.69%) to vancomycin; 564(90.09%) to ciprofloxacin; 429(68.53%) to norfloxacin; 464(74.12%) to gentamicin and 202(32.27%) to co.trimoxazole. CONCLUSION: This study provides information on the efficacy of ocular antibacterials commonly used against bacterial pathogens of keratitis. It is hoped that this information will help decision-making in empiric initial treatment of bacterial keratitis.