Isolates and antibiotic resistance of culture-proven endophthalmitis cases presented to a referral center in Tehran.

PURPOSE: To evaluate the spectrum of organisms causing endophthalmitis and their resistance pattern to standard antimicrobial agents.
MATERIALS AND METHODS: Medical records of culture positive eyes treated at Rassoul Akram Hospital for endophthalmitis during the past 5 years were reviewed. Specimens were obtained during pars plana vitrectomy or vitreous tap.
RESULTS: Sixty-five isolates including 36 (55.4%) gram-positive organisms, 28 gram-negative organisms (43.1%), and 1 (1.5%) fungus were studied. The most common organism identified was Coagulase-negative staphylococcus in 16 eyes (24.6%). Among the antibiotics available for intravitreal injection, the least antibiotic resistance was for vancomycin in gram-positive organisms and amikacin and ceftazidime in gram-negative isolates.
CONCLUSIONS: Gram-positive isolates were the most prevalent organisms; however, a high isolation rate for gram-negative organisms was obtained. Considering that no single antibiotic provides coverage for all of the organisms, a combination therapy using vancomycin/amikacin or vancomycin/ceftazidime seems to be useful as the initial empiric treatment of suspected bacterial endophthalmitis.

INTRODUCTION

Infectious endophthalmitis is a devastating and sight-threatening condition. It may occur after ocular surgery, ocular trauma, or by hematogenous spread of the organisms to the eye. In previous studies of infectious endophthalmitis, the microbiologic spectrum has been reported to vary depending on the clinical setting and geographic location.1–5 In addition, there are some reports of antibiotic resistance among the endophthalmitis isolates.6 Identifying the causative microorganisms has a great importance for prevention, successful management, and an appropriate treatment of endophthalmitis. In a literature search using PubMed, Scopus, and an Iranian medical database (scientific information database), only one study discussed the spectrum of endophthalmitis isolated organisms in Iran (last assessed December 2011).7 In this study, 35 of 223 eyes were culture positive; however, the pattern of in vitro antibiotic response was not reported.

The purpose of this study was to evaluate the spectrum of organisms causing culture-proven endophthalmitis and their resistance pattern to commonly used antimicrobial agents.

MATERIALS AND METHODS

Medical records of all patients admitted for the treatment of the endophthalmitis in the Rassoul Akram Hospital, Tehran, from April 2006 to May 2011 were reviewed. The institutional review board of the Rassoul Akram Eye Research Center approved the study. Only patients with a culture-positive specimen were included. All isolates were obtained from vitreous tap (at the time of antibiotic injection) or parsplana vitrectomy. Vitreous samples were obtained under sterile conditions and inoculated onto the blood agar, Sabouraud's agar, chocolate agar, and thioglycollate broth and properly incubated. Antibiotic susceptibility testing was performed by the disk diffusion method.

RESULTS

Sixty-five isolates from 33 females and 32 males with a mean age of 62.9 ± 18.7 years (range, 2 years to 89 years) were studied. [Table 1] shows the clinical settings in which culture-proven endophthalmitis occurred. The most common settings were acute post cataract surgery in 42 of 65 (64.6%) and endogenous in 9 eyes (13.8%). Endogenous endophthalmitis was associated with diabetes mellitus in three cases and immunosuppression in two patients. No specific association was found in other endogenous endophthalmitis cases. There was a history of corneal laceration secondary to sharp trauma in all eyes with post-traumatic endophthalmitis. Intraocular foreign body was found in three eyes, and the interval between injury and the onset of endophthalmitis ranged between 1 and 28 days.

Table 1

Clinical setting before endophthalmitis and the most prevalent isolated organism

Overall, 36 of 65 (55.4%) isolates were gram-positive organisms, 28 (43.1%) were gram-negative organisms, and 1 (1.5%) was fungus [Table 2]. The most common gram-positive organism was Coagulase-negative staphylococcus in 38.8%. Among the Staphylococcus aureus isolates, one methicillin-resistant isolate was found. Pseudomonas species were the most commonly identified gram-negative organism (50%). There was no significant correlation between the organisms causing endophthalmitis and the clinical settings in which the culture-proven endophthalmitis occurred (P = 0.9, chi-square test).

Table 2

Endophthalmitis causative organisms

The results of antibiogram test were not available for 15 eyes. These were all Coagulase-negative Staphylococci. Among the remaining gram-positive identified organisms (21), antibiotic resistance was observed for penicillin G in 7 isolates, oxacillin in 5 isolates, clindamycin in 4 isolates, cefalotin in 2 isolates, ceftazidime in 5 isolates, ciprofloxacin in 2 isolates, ceftriaxone in 2 isolates, and imipenem in 1 isolate. No vancomycin resistance isolate was found. Among the gram-negative organisms, antibiotic resistance was observed for ampicillin in 20 isolates, cefazolin in 14 isolates, ceftriaxone in 8 isolates, gentamycin in 5 isolates, amikacin in 2 isolates, ceftazidime in 3 isolates, ciprofloxacin in two isolates, and imipenem in 3 isolates. Ceftazidime-resistant isolates were sensitive to amikacin, and amikacin-resistant cases were sensitive to ceftazidime and ciprofloxacin.

DISCUSSION

This study reviews the causative organisms of endophthalmitis at a single, referral center over a 5-year period. The majority of the isolates were gram-positive organisms (55.4%); however, gram-negative organisms made up a larger portion (43.1%) than were found in the previous reports including the Endophthalmitis Vitrectomy Study (EVS).13589 The EVS is a hallmark study aimed at evaluating the role of pars plana vitrectomy and intravenous antibiotics in the management of postoperative bacterial endophthalmitis. In EVS the majority of isolates were gram-positive organisms (94%) and in other reports the proportion of the gram-negative organisms was less than 42%. The discrepancy between our results and those reported by EVS and the others may be explained by different inclusion criteria and geographic variation. For example, EVS evaluated only acute-onset endophthalmitis associated with cataract surgery or secondary intraocular lens placement, whereas our study included all categories of endophthalmitis. However, when we considered only acute, postoperative cases, still 45.2% of cases were caused by gram-negative organisms. One plausible explanation is that cases with low-grade endophthalmitis may be treated in the office and cured, so the more severe cases that usually are associated with more virulent organisms such as Pseudomonas were referred to us.

Our results concur with previous studies that show a 100% sensitivity of gram-positive isolates against vancomycin.1359–12 Among the antibiotics with known intravitreal dosage, amikacin and ceftazidime were the most effective antibiotics against gram-negative organisms. In contrast to previous studies that showed a high resistance rate of gram-negative organisms,39 we found low resistance rates of 10.7% and 7.1% against gram-negative isolates for ceftazidime and amikacin, respectively. This finding was similar to the EVS results; however, we did not observe any organism resistant to both. The antibacterial spectrum of the carbapenems (including imipenem) has been reported to be broader than that of any other existing antibiotic and includes both gram-positive and -negative organisms. However, carbapenem-resistant strains have been reported recently.13 We also found imipenem-resistant organisms in both gram-negative and -positive isolates.

Although the effect of topical antibiotics in preventing endophthalmitis is unknown, topical fluoroquinolones are commonly used for perioperative infection prophylaxis in patients undergoing intraocular surgery.14 Depending on the geographic location, ciprofloxacin sensitivity of the organisms were reported to be between 36% and 88%.39 We found high sensitivity for both gram-positive and -negative isolates (94.5% and 92.9%, respectively).

Our study has some limitations. The sample size is small. The bacteriology laboratory of our general hospital was not reporting the antibiogram results for Coagulase-negative Staphylococci and considering them like the blood samples as contamination.15 Our setting is a referral center and some postoperative cases may be treated in offices, hence, our results may not represent the true bacteriologic results of Iranian population. Despite these limitations, to our knowledge, this is the first and largest study reporting endophthalmitis isolates and antibiotic resistance patterns in Iran.

Empirical antibiotic treatment of endophthalmitis should provide broad-spectrum coverage for both gram-positive and gram-negative organisms. Our study supports previous reports recommending the combination treatment including vancomycin/amikacin or vancomycin/ceftazidime for the empirical treatment of endophthalmitis.116 Future larger studies are needed to confirm our results.