Methods

The microbiological records for all patients with positive vitreous cultures obtained at the Bascom Palmer Eye Institute from January 1981 to December 2015 were reviewed. Patients with the same bacterial organisms identified on at least 2 consecutive vitreous cultures obtained on separate days after receiving at least 1 injection of intravitreal antibiotics were included. Patients with fungal or viral organisms, polymicrobial cultures, endogenous endophthalmitis, and incomplete medical records were excluded. The microbiological isolates and sensitivities were compared between patients with persistent infections and those with only 1 positive vitreous culture over the same time period. The consecutive, noncomparative case series was approved by the Institutional Review Board of the University of Miami Miller School of Medicine and was compliant with the Health Insurance Portability and Accountability Act of 1996. The described research adhered to the tenets of the Declaration of Helsinki.

The treatment regimen was determined by the physician based on the individual patient’s clinical course. There was no preset protocol for the timing or type of the second treatment. Patients were retreated if there were clinical signs of deterioration or no improvement in their vision, pain, hypopyon, fibrin, or vitritis. After 1995, patients who developed cataract surgery–related endophthalmitis were treated according to the recommendations of the Endophthalmitis Vitrectomy Study (EVS).

Statistical calculations were performed using the Statistical Package for the Social Sciences software (SPSS Inc, Chicago, Illinois, USA), with a P value less than .05 being considered statistically significant. Snellen visual acuity was converted to its logarithm of minimal angle of resolution (logMAR) equivalent as previously described, with counting fingers being assigned a value of 1.85, hand motion 2.3, light perception 2.7, and no light perception 3.0. The best-corrected visual acuities (BCVA) are presented as the mean logMAR ± standard deviation (SD), followed by the approximate Snellen chart equivalent. The visual acuities were analyzed using Student’s t test, one-way analysis of variance with Tukey post hoc analyses, and Fisher’s exact tests.

Results

During the 35-year study period, thirty-six eyes of 36 patients met the study criteria. The average age was 69.9 years old (median: 73, range: 17–89). There were 20 male patients (56%) and 16 right eyes (44%). The most common systemic comorbidities were hypertension (18/36, 50%) and diabetes mellitus (7/36, 19%). Two patients (6%) were immunocompromised from chronic systemic steroids. Ocular comorbidities included glaucoma (13/36, 36%) and macular degeneration (2/35, 6%).

The clinical histories and demographics are summarized in Table 1 . The clinical settings were after cataract surgery (18/36, 50%), glaucoma surgery (11/36, 31%), trauma (3/36, 8%), intravitreal injections (2/36, 6%), and penetrating keratoplasties (2/36, 6%). Two patients who had combined surgeries (cataract extractions with trabeculectomies) were categorized in the glaucoma group because they presented 2 years postoperatively with clinical features consistent with bleb-associated endophthalmitis. Thirty-four of 36 patients (94%) had hypopyons and pain on initial examinations; all patients had vitritis. Excluding the 3 patients with delayed-onset endophthalmitis (presenting more than 6 weeks after surgery or trauma), the mean time from the inciting event to the clinical diagnosis was 6.4 ± 11 days. The mean follow-up after the initial treatment was 26.5 months (range: 2 weeks to 157 months).

The clinical management is summarized in Table 2 . All 36 patients received intravitreal vancomycin, and 33 of 36 patients (92%) received additional intravitreal antibiotics on the day of their diagnoses: ceftazidime (29/36, 81%), tobramycin (2/36, 6%), amikacin (1/36, 3%), and gentamicin (1/36, 3%). Fifteen patients (42%) also received intravitreal dexamethasone with their initial intravitreal antibiotics.

Following the initial treatment, patients underwent additional procedures when their infections were deemed to be worsening or not improving. The mean time between the first and second treatment was 7.9 ± 16 days, and the average number of treatments was 2.8 ± 0.8. The mean vision at the time of the second treatment was similar to that at the initial visit ( P = .81). A vitreous culture and injection of intravitreal antibiotics (tap/inject) was performed as the first treatment in 28 of 36 patients (78%), of whom 9 (32%) underwent subsequent tap/injects and of whom 18 (64%) had subsequent pars plana vitrectomies (PPV). Eight patients (22%) had an initial PPV with intravitreal antibiotics, of whom 4 (50%) had subsequent vitrectomies with intravitreal antibiotics. A second dose of intravitreal antibiotics was administered in 34 of 36 patients (94%); all 34 received intravitreal vancomycin, and 25 (74%) also received ceftazidime. One patient improved with a tap/inject followed by a pars plana vitrectomy without additional intravitreal antibiotics. A pars plana vitrectomy was performed in 33 of 36 patients (92%). There were no adverse events directly attributed to repeated injections of intravitreal antibiotics.

All patients received adjunctive topical antibiotics. These included fortified topical vancomycin (30/36, 83%), tobramycin (21/36, 58%), gentamicin (2/36, 6%), ceftazidime (2/36, 6%), neomycin/polymyxin B sulfate/dexamethasone (2/36, 6%), moxifloxacin (2/36, 6%), and ofloxacin (2/36, 6%). Topical steroids were used within 24 hours of initiating antibiotics in 34 of 36 patients (94%). Systemic antibiotics were used in 13 of 36 patients (36%).

The microbiology data are summarized in Table 3 . Gram-positive bacteria comprised 81% (29/36) of all persistently culture-positive bacterial endophthalmitis. The most common bacteria were Staphylococcus (11/36, 31%), Streptococcus (9/36, 25%), and Enterococcus (6/36, 17%). The bacterial organisms were isolated from undiluted vitreous cultures in 64% (50/78) and from vitreous washings or vitreous cassettes in 36% (28/78).

Over the same time period, there were 1189 patients with bacterial endophthalmitis who had only 1 positive vitreous culture. Gram-positive bacteria were the most common (1028/1189, 86%). The most common isolates were Staphylococcus species (594/1189, 50%), Streptococccus species (126/1189, 11%), Enterococcus species (47/1189, 4%), and Pseudomonas species (38/1189, 3%). There was no statistically significant difference in the proportion of gram-positive or gram-negative bacteria between the persistent and nonpersistent bacterial endophthalmitis groups ( P = .46, Fisher’s exact test). However, there was a higher proportion of non- Staphylococcus gram-positive bacteria in the persistently culture-positive group, including Streptococcus and Enterococcus ( P = .032 and P = .021, respectively, Fisher’s exact test). There was no statistically significant difference in the proportions of gram-negative bacteria in patients with persistent endophthalmitis.

The antibiotic sensitivities were available in 34 patients ( Table 3 ) and were the same in repeat cultures in 94% (34/36). Of the gram-positive bacteria tested, all were sensitive to vancomycin (27/27, 100%) and 80% to ceftazidime (12/15). For the gram-negative bacteria tested, all were sensitive to amikacin (5/5, 100%) and 83% to ceftazidime (5/6). The bacteria in all cases of persistent endophthalmitis were sensitive to at least 1 of the initial empirically selected intravitreal antibiotics.

The clinical outcomes are summarized in Table 4 . The mean presenting visual acuity was 2.16 ± 0.77 logMAR (Snellen equivalent ≈20/2900). The preinfection visual acuity was known in 16 patients (mean of 0.58 ± 0.78 logMAR, ≈20/70). Only 13% of patients (2/16) recovered vision within 1 line of their preinfection visual acuity. Patients with endophthalmitis presenting 6 or more weeks after the inciting event had worse final visual acuities than those who presented more acutely (2.67 ± 0.35 logMAR, ≈20/2400, vs 2.08 ± 0.18 logMAR, ≈20/1400, P = .049).

Table 4

Summary of Visual Acuities on Initial and Last Follow-up Examinations in Patients With Persistent Vitreous Culture–Positive Endophthalmitis

	Presenting Visual Acuities		Final Visual Acuities				P Value
	Mean LogMAR VA ± SD	Mean Snellen VA (Approx)	# Patients (%)		Mean LogMAR VA ± SD	Mean Snellen VA ± SD (Approx)
			≥20/400	<20/400
Clinical scenario (no. of patients)
Cataracts (18)	2.07 ± 0.74	20/2300	8 (44)	10 (56)	1.76 ± 1.1	20/1200	.38
Uncomplicated ECCE (5)	1.76 ± 1.1	20/1200	1 (20)	4 (80)	2.08 ± 1.4	20/2400	.60
Uncomplicated phaco (7)	2.09 ± 0.6	20/2500	7 (100)	0 (0)	0.78 ± 1.0	20/120	.015
Complicated ECCE (2)	2.70 ± 0.0	LP	0 (0)	2 (100)	3.00 ± 0.0	NLP	–
Complicated phaco (4)	2.50 ± 0.23	HM-LP	0 (0)	4 (100)	2.29 ± 0.35	HM	.35
Glaucoma (11)	2.08 ± 0.98	20/2400	2 (18)	9 (82)	2.12 ± 0.44	20/2600	.58
Trabeculectomy (10)	2.04 ± 0.94	20/2200	1 (10)	9 (90)	2.41 ± 0.67	LP	.33
GDI (1)	2.70 ± 0.0	LP	1 (100)	0 (0)	0.70 ± 0.0	20/100	–
Trauma (3)	2.43 ± 0.23	HM	0 (0)	3 (100)	2.77 ± 0.4	LP	.30
Intravitreal injections (2)	2.70 ± 0.0	LP	0 (0)	2 (100)	2.50 ± 0.28	LP	.42
Corneal transplant (2)	2.28 ± 0.60	20/3800	1 (50)	1 (50)	2.10 ± 1.3	20/2600	.88
Bacterial isolates (no. of patients)
Gram-positive bacteria (29)	2.06 ± 0.80	20/2300	7 (29.2)	17 (70.8)	1.93 ± 1.1	20/1800	.57
Staphylococcus spp. (11)	2.35 ± 0.45	HM	4 (40)	6 (60)	1.88 ± 1.7	20/1500	.37
Streptococcus spp. (9)	2.02 ± 0.73	20/2100	1 (14.3)	6 (85.7)	1.97 ± 0.63	20/1900	.76
Enterococcus faecalis (7)	2.17 ± 0.95	20/2200	0 (0)	5 (100)	2.23 ± 0.73	20/3400	.79
Propionibacterium acnes (2)	0.75 ± 0.78	20/110	2 (100)	0 (0)	0.3 ± 0.28	20/40	.56
Gram-negative bacteria (7)	2.7 ± 0.23	LP	1 (33.3)	2 (66.6)	2.94 ± 1.6	LP-NLP	.66
Pseudomonas aeruginosa (2)	2.7 ± 0.0	LP	0 (0)	2 (100)	3.0 ± 0.0	NLP	–
Serratia marcesans (2)	2.11 ± 0.92	20/2600	0 (0)	1 (100)	2.26 ± 0.89	20/3600	.81
Achromobacter xylosoxidans (1)	2.70 ± 0.0	LP	0 (0)	1 (100)	2.7 ± 0.0	LP	–
Citrobacter freundii (1)	2.70 ± 0.0	LP	0 (0)	1 (100)	2.7 ± 0.0	LP	–
Stenotrophomonas maltophilia (1)	2.30 ± 0.0	HM	1 (100)	0 (0)	0.30 ± 0.0	20/40	–

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