Purpose
To investigate the antibiotic susceptibility and clinical outcomes of endophthalmitis caused by methicillin-sensitive Staphylococcus aureus (MSSA) versus methicillin-resistant (MRSA) S. aureus.
Design
Retrospective, consecutive case series.
Methods
Charts of 32 patients with culture-proven S. aureus endophthalmitis seen at the Bascom Palmer Eye Institute from January 1, 1995, through January 1, 2008, were reviewed. Antibiotic susceptibility profiles, identified using standard microbiologic protocols, and visual acuity at 1 and 3 months were the main outcome measures.
Results
MSSA was recovered from 19 (59%) of 32 patients and MRSA was recovered from 13 (41%) of 32 patients. Causes included cataract surgery in 18 (56%) of 32 patients, endogenous in 5 (16%) of 32 patients, bleb association in 4 (13%) of 32 patients, pars plana vitrectomy and ganciclovir implantation in 3 (9%) of 32 patients, and trauma in 2 (6%) of 32 patients. All isolates were sensitive to vancomycin. MSSA isolates were sensitive to all tested antibiotics, except one that exhibited fluoroquinolone resistance. In the MRSA group, frequent resistance occurred with the fourth-generation fluoroquinolones (moxifloxacin, 5 of 13 patients [38%]; gatifloxacin, 5 of 13 patients [38%]). The median presenting visual acuity was approximately hand movements for both MSSA and MRSA eyes. All eyes received intravitreal antibiotics. Pars plana vitrectomy was performed on 47% of MSSA and 61% of MRSA patients. A final visual acuity of 20/400 or better at 3 months was achieved in 59% of MSSA and 36% of MRSA patients ( P = .5).
Conclusions
Although all MSSA and MRSA isolates were sensitive to vancomycin, fewer than half of MRSA isolates were sensitive to the fourth-generation fluoroquinolones. Visual acuity outcomes between MRSA and MSSA eyes were not significantly different.
Staphylococcus aureus is an important and frequent cause of acute-onset endophthalmitis. This bacterium is most commonly encountered after cataract surgery and often is associated with a poor outcome. S. aureus has a variety of potent virulence factors that allow it to adhere to and penetrate into host tissue, evade immune mechanisms to cause host tissue damage, and resist antimicrobial agents. Resistance may occur in clusters facilitated by the so-called pathogenicity island, or genes encoding 1 or more virulence factors that are distinct genomic islands acquired by horizontal transfer. The documented incidence of methicillin-resistant strains of S. aureus (MRSA) is of particular concern because they are also more likely to exhibit resistance to the fourth-generation fluoroquinolones. There is also a suggestion of increased virulence of certain strains of MRSA, at least in the setting of pneumonia, bacteremia, and necrotizing fasciitis. MRSA ocular infections, both in total numbers and percentage of overall S. aureus infections, are becoming increasingly prevalent.
With regard to endophthalmitis caused by S. aureus , 3 questions are of particular interest to the practicing ophthalmologist: Are these strains also more resistant to current antibiotics, such as the fourth-generation fluoroquinolones commonly used for the prevention and treatment of endophthalmitis? Are these strains still sensitive to vancomycin? And lastly, is there a difference in the pathogenicity, as measured by clinical outcomes after treatment? With these questions in mind, the antibiotic susceptibilities and clinical outcomes of MRSA versus methicillin-sensitive S. aureus (MSSA) inducing endophthalmitis from different causes in a consecutive case series were examined.
Methods
A computer search of the Bascom Palmer Eye Institute Microbiology Department data base and corresponding medical records identified 32 cases of patients with S. aureus endophthalmitis between January 1, 1995, and January 1, 2008.
Treatments consisted of either tap and inject, that is, aspiration of a vitreous specimen with subsequent injection of antibiotics (vancomycin 1.0 mg and ceftazidime 2.25 mg) or pars plana vitrectomy with subsequent injection of the same antibiotics. Treatment was at the discretion of the treating physician, which generally followed Endophthalmitis Vitrectomy Study (EVS) guidelines for cataract-associated cases, but there was no specific protocol in the current study.
Intraocular specimens had been obtained from all patients, either through needle aspiration from the vitreous during the tap-and-inject procedure or through pars plana vitrectomy. Vitreous samples were plated on thioglycolate, blood, chocolate, anaerobic blood, and Sabouraud agar and were incubated at 37 C. All isolates were incubated for 18 to 24 hours in a carbon dioxide incubator. Cultures were observed daily for up to 7 days for visible growth. Vitek automated microbial identification and susceptibility testing system (bioMérieux, Inc, Durham, North Carolina, USA) and disc diffusion were used to determine and compare susceptibility patterns. Interpretations of culture results were in accordance with guidelines from the Clinical Laboratory Standards Institute (Wayne, Pennsylvania, USA). Coagulase testing was used to identify isolates as S. aureus.
To establish S. aureus as the causative organism, growth of the organism had to be present on 2 or more culture media or semiconfluent growth on 1 or more solid media and had to demonstrate positive smear results. Cases with polymicrobial growth were excluded from the analysis.
Clinical data were compiled using a standard data collection sheet. Data collected included cause, gender, age, and time from inciting event to initial presentation where determinable. Visual acuity (VA) was recorded at presentation, as well as 1 week, 1 month, and 3 months after treatment. For statistical analysis, Snellen VA was converted into logMAR units. VA outcomes were compared between MRSA and MSSA from all causes and in the postcataract-only subgroups.
Statistical analysis was performed using Graph Pad Prism software (Graph Pad Software, Inc, La Jolla, California, USA). t Tests were used for analyzing variables with Gaussian distribution. The Mann–Whitney U test was used for nonparametric data.
Results
Thirty-two cases of endophthalmitis resulting from S. aureus were identified, including 13 (41%) caused by MRSA and 19 (59%) caused by MSSA. Men and women were distributed equally in both the MRSA and the MSSA group (7 men and 6 women in the MRSA group, 9 men and 10 women in the MSSA group). Also, there was no difference in age between the 2 groups, with a mean age of 66 years in the MRSA group and of 67 years in the MSSA group.
Overall, most endophthalmitis cases caused by S. aureus (18 of 32 cases or 56%) were associated with cataract surgery ( Table 1 ). Of these, 10 (56%) of 18 were caused by MSSA, and 8 (44%) of 18 were caused by MRSA. Five cases were endogenous (5 of 32 cases or 16%), including MRSA in 2 cases and MSSA in 3 cases. Four cases were bleb associated (12%), which were exclusively MSSA. Another 2 cases resulted from trauma (1 MSSA, 1 MRSA), 2 occurred after vitrectomy (1 MSSA, 1 MRSA), and 1 occurred after vitrectomy combined with ganciclovir implant placement (MRSA).
Cause | No. | MSSA | MRSA |
---|---|---|---|
Cataract | 18 | 10 | 8 |
Endogenous | 5 | 3 | 2 |
Bleb associated | 4 | 4 | 0 |
Trauma | 2 | 1 | 1 |
Pars plana vitrectomy | 2 | 1 | 1 |
Ganciclovir | 1 | 0 | 1 |
Total | 32 | 19 | 13 |
Of the 19 isolates in the MSSA group, 11 (68%) were resistant to penicillin, but all were sensitive to vancomycin, gentamicin, trimethoprim-sulfa, and clindamycin ( Figure 1 ). One MSSA cataract surgery-related endophthalmitis patient exhibited resistance to the fluoroquinolones (oxifloxacin, gatifloxacin, and moxifloxacin). All other MSSA isolates were sensitive to the fluoroquinolones, accounting for the 95% sensitivity ( Figure 2 ). All MRSA isolates were resistant to penicillin. Among MRSA isolates, only 7 (54%) of 13 were susceptible to gentamicin, and 8 (61%) of 13 were susceptible to clindamycin. Among all MRSA isolates, sensitivity to the fourth-generation fluoroquinolones was 38% (5/13) for gatifloxacin and moxifloxacin. MSSA isolates were 100% sensitive to trimethoprim-sulfa, whereas MRSA isolates also were sensitive at 92% (12/13). Both MRSA and MSSA isolates were still sensitive to vancomycin.
Treatment in the MSSA group consisted of initial tap and inject in 10 cases (53%) and pars plana vitrectomy followed by the same intravitreal antibiotics in the other 9 cases (47%). In contrast, in the MRSA group, only 5 patients received tap-and-inject treatment (39%), and most (8 of 13 or 61%) were treated with vitrectomy and intraocular antibiotics. Mean time to diagnosis was essentially identical in the 2 post–cataract surgery groups, the setting in which the inciting event was easiest to determine (6.1 days in the MSSA group and 5.7 days in the MRSA group).
Overall, visual acuity at presentation ranged from 20/200 to no light perception (NLP) in both the MRSA and MSSA groups. These measurements were not statistically different when comparing the MRSA and MSSA groups overall (mean logMAR visual acuity of 1.8 and 1.6, respectively; P = .87, Mann–Whitney U test; Figure 2 ). One week after presentation, VA ranged from 20/25 to NLP in the MSSA group and from 20/100 to NLP in the MRSA group. The mean VA of the MRSA and MSSA groups were identical at this point. One MRSA patient underwent enucleation 1 week after diagnosis secondary to pain after corneal perforation and a limited VA potential because of anterior ischemic optic neuropathy. One month after initial presentation, VA ranged between 20/40 and light perception for the MRSA group (n = 9 of initial 13) and 20/20 to NLP in the MSSA group (n = 18 of initial 19). Again, there was no statistically significant difference between the MRSA and MSSA groups from all causes (mean logMAR visual acuity, 1.7 and 1.2, respectively; P = .11, unpaired t test; Figure 2 ).
After 3 months, VA ranged between 20/70 and light perception in the MRSA group (n = 6 of initially 13) and 20/60 to NLP in the MSSA group (n = 9 of initially 19; mean logMAR visual acuity, 1.8 and 0.5, respectively; P = .065, unpaired t test). A small difference between the mean logMAR visual acuities in the post–cataract-only MRSA group (n = 6 of initially 8) and MSSA group (n = 5 of initially 10) was found ( Figure 2 ). Although the mean visual acuity in the MRSA group was between hand movements and 20/400 (logMAR, 1.8), visual acuity in MSSA-infected eyes was 20/60 (logMAR, 0.5). This difference approached statistical significance ( P = .065, unpaired t test). A final VA of 20/400 or better at 3 months was achieved in 59% of MSSA and 36% of MRSA patients ( P = .5). See Table 2 for a summary of visual acuity, fluoroquinolone resistance, and source of endophthalmitis.
Cause | logMAR VA p | logMAR VA 3 | Resistance to 4F (%) | Primary Source |
---|---|---|---|---|
MSSA | 1.6 | 0.5 | 5 | Postoperative ECCE |
MRSA | 1.8 | 1.8 | 62 | Postoperative ECCE |