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Journal of Ophthalmic Inflammation and Infection logoLink to Journal of Ophthalmic Inflammation and Infection
. 2018 Oct 11;8:14. doi: 10.1186/s12348-018-0158-3

Endogenous endophthalmitis: a 9-year retrospective study at a tertiary referral hospital in Malaysia

Rosiah Muda 1, Valarmathy Vayavari 2, Deivanai Subbiah 3, Hamisah Ishak 4, Azian Adnan 3, Shelina Oli Mohamed 5,
PMCID: PMC6179973  PMID: 30306361

Abstract

Background

The objective of this study was to determine the clinical presentation, systemic risk factors, source of infective microorganism, treatment outcomes, and prognostic indicators of endogenous endophthalmitis at a main tertiary referral hospital for uveitis in Malaysia. A retrospective review of medical records of 120 patients (143 eyes) with endogenous endophthalmitis over a period of 9 years between January 2007 and December 2015 was undertaken.

Results

Identifiable systemic risk factors were present in 79.2%, with the majority related to diabetes mellitus (60.0%). The most common source of bacteremia was urinary tract infection (17.5%). A positive culture from ocular fluid or other body fluids was obtained in 82 patients (68.9%), and the blood was the highest source among all culture-positive results (42.0%). Gram-negative organisms accounted 42 cases (50.6%) of which Klebsiella pneumonia was the most common organism isolated (32.5%). Sixty-nine eyes (48.6%) were managed medically, and 73 eyes (51.4%) underwent vitrectomy. Final visual acuity of counting fingers (CF) or better was achieved in 100 eyes (73.0%). Presenting visual acuity of CF or better was significantly associated with a better final acuity of CF or better (p = 0.001).

Conclusions

The visual prognosis of endogenous endophthalmitis is often poor, leading to blindness. As expected, gram-negative organisms specifically Klebsiella pneumonia were the most common organisms isolated. Urinary tract infection was the main source of infection. Poor presenting visual acuity was significantly associated with grave visual outcomes. A high index of suspicion, early diagnosis, and treatment are crucial to salvage useful vision.

Keywords: Endogenous, Endophthalmitis, Diabetes mellitus, Bacteria, Fungal, Intravitreal injections, Vitrectomy, Visual acuity

Background

Endogenous endophthalmitis (EE) occurs when infectious agents are hematogenously disseminated into the eye from a remote focus of infection. Even though this entity is relatively rare and accounts for approximately 2–15% of all cases of endophthalmitis [13], it is an ocular emergency and is potentially life-threatening. The causative organisms may vary depending on the geographical location. In Europe and the USA, Streptococcus species, Staphylococcus aureus, and other gram-positive bacteria account for two thirds of bacterial endogenous endophthalmitis cases and gram-negative isolates are found in only 32% of cases [3, 4]. In contrast, most cases of EE in East Asia are caused by gram-negative organisms especially Klebsiella species accounting for 80 to 90% of positive cultures [4, 5].

The outcome of endogenous endophthalmitis is often dismal. Sharma et al. reported that 60% of the eyes had a final visual acuity of hand motions or worse and as many as 29% required removals [6]. Hence, prompt diagnosis and management are essential if useful vision is to be preserved.

To the best of our knowledge, there is no large case series on endogenous endophthalmitis being reported yet from Malaysia. The current study was performed to determine the clinical profile of EE at a tertiary hospital while focusing on the clinical presentation, predisposing risk factors, source of infective microorganism, treatment outcomes and prognostic indicators.

Methods

A retrospective observational study was conducted in Selayang Hospital which was the main national tertiary referral center for uveitis in Malaysia. We reviewed the medical records of patients with endogenous endophthalmitis who were seen or referred to our hospital over a period of 9 years between January 2007 and December 2015. The diagnosis of endogenous endophthalmitis was defined as the presence of iritis and vitritis on ophthalmic examination and one or more of the following: (1) constitutional symptoms and systemic infection; (2) positive cultures of vitreous, blood, or other body fluids; (3) presence of loculation, vitreous debris, or membranous debris on ultrasound; (4) lack of ocular trauma or ocular surgery within 1 year from onset of infection or evidence of primary external ocular infection such as infectious keratitis or filtering bleb infection.

Demographic details such as age, gender and race, presenting complaints, preexisting medical illnesses, predisposing risk factors, source of infection, laterality, visual acuity, ophthalmologic examination, ultrasound findings, microbiologic profiles, treatment modalities, and final visual outcomes were collected from medical records.

The study was done according to Malaysian Good Clinical Practice (MGCP) 2nd edition January 2004 and registered in National Medical Research Register (NMRR).

Data was analyzed using the Statistical Package for Social Science (SPSS) version 22.0. Descriptive data was expressed as mean ± standard deviation (SD) for numerical data, and categorical variables were presented in frequencies and percentages. Logistic regression analysis was used to determine the factors associated with good visual outcomes. The association between presenting and final visual acuity was also analyzed using the Pearson correlation coefficient, and visual acuities were converted to logarithm of the minimal angle of resolution (logMAR) scale. For visual acuity less than counting finger (CF), the following scales were used: CF = 2.00 LogMAR units, hand motion = 2.30 LogMAR units, light perception = 2.60 LogMAR units, and no light perception = 2.90 LogMAR units. A P value of < 0.05 was considered to be significant.

Results

Demographic data

A total of 143 eyes of 120 patients were included in this study. The age of patients ranged from 7 to 81 years, and the mean age at presentation was 52.6 ± 15.1 years. The racial distribution reflected the multiracial population in our country with 72 Malays (60.0%), 33 Chinese (27.5%), 13 Indian (10.8%), and 2 others (1.7%). There was a slight female predominance (61, 50.8%) compared to males (59, 49.2%).

Systemic features

Systemic risk factors

At least one underlying medical illness was identified in 95 patients (79.2%). Diabetes mellitus was the most common medical illness (72, 60.0%), followed by renal failure (20, 16.7%), and 15 patients (12.5%) had solid organ tumor or hematologic malignancy. Six patients (5.0%) had liver disease and 3 patients (2.5%) were pregnant. Five patients (4.2%) were on systemic corticosteroids for underlying autoimmune diseases, and 1 was on systemic immunosuppressants.

Source of infection

A primary source of infection was identified in 90 patients (75.0%). Urinary tract infection (21, 17.5%) was the most common source of bacteremia followed by pulmonary infection (19, 15.8%), skin or soft tissue infection (17, 14.2%), and hepatobiliary infection (12, 10.0%). However, the source of infection could not be identified in 30 patients (25.0%), despite extensive systemic work-up and investigations (Table 1).

Table 1.

Identifiable source of infection

Source of infection No. of patients Percent
Infected catheter 11 9.2
Urinary tract infection 21 17.5
Hepatobiliary infection 12 10.0
Lung infection 19 15.8
Meningitis 2 1.7
Infective endocarditis 1 0.8
Gastrointestinal infection 1 0.8
Genital infection 2 1.7
Skin or soft tissue infection 17 14.2
Septic arthritis 1 0.8
Diabetic foot ulcer 3 2.5
Nil 30 25.0

Ocular features

Ocular symptoms

Majority of patients had unilateral disease, 97 (80.8%), and involvement of the left eye (78, 54.5%) was more common. Blurring of vision (106, 74.1%), eye redness (52, 36.4%), eye pain or discomfort (42, 29.4%), and floaters (16, 11.2%) were ocular symptoms at presentation. The blurring of vision (85, 68.5%) was the most common presenting complaint, followed by eye redness (20, 16.1%) and eye pain or discomfort (14, 11.3%).

The interval between the onset of ocular symptoms and the first presentation to an ophthalmologist was less than 1 week in 62 eyes (47.3%), 1 to 2 weeks in 40 eyes (30.5%), more than 2 weeks to 1 month in 10 eyes (14.5%), and more than 1 month in 10 eyes (7.6%). The interval was not available in 12 eyes which were from patients with no recorded ocular symptoms due to poor general medical condition or no documentation obtained from the medical records (Fig. 1).

Fig. 1.

Fig. 1

The interval between the onset of ocular symptom and first presentation and the duration between systemic and ocular symptom

Systemic symptoms were identified in 84 patients (70.0%). This data was not available in 36 patients (30.0%). The interval between the onset of systemic symptoms and the onset of ocular symptoms was identified in 101 eyes. The interval was less than 1 week in 26 eyes (25.7%), between 1 and 2 weeks in 25 eyes (24.8%), more than 2 weeks to 1 month in 12 eyes (11.9%), and more than 1 month in 38 eyes (37.6%) (Fig. 1).

Ocular findings

At presentation, based on the Standardization of Uveitis Nomenclature (SUN), the proportion of the eyes with anterior chamber cells better than grade 3 and grade 3 or worse was similar with 67 eyes (49.6%) and 68 eyes (50.4%) respectively. Twenty-seven eyes (19.0%) had hypopyon, and 42 eyes (29.6%) had fibrin. The fundal view was present in 64 out of 143 eyes (44.8%). Among this, 32 eyes (50.0%) had choroiditis or choroidal abscess, 11 eyes (17.2%) had retinitis, 6 (9.4%) had vasculitis, and 4 (6.3%) had optic disc swelling. Six eyes had a combination of choroiditis or choroidal abscess and retinitis and 2 eyes had choroiditis or choroidal abscess, vasculitis, and optic disc swelling.

Ultrasound findings were documented in 97 eyes. Fifty-five eyes (56.7%) had vitreous loculation, whereas subretinal or vitreous abscess and retinal detachment were found in 6 (6.2%) and 8 (8.2%) eyes respectively.

Microbiology

A positive culture from ocular fluid or other body fluids was obtained in 82 patients (68.9%). The culture result of 1 patient was not available as he had it done elsewhere.

The blood was the highest source among all culture-positive results (50, 42.0%). Gram-negative organisms were more common (26 patients, 52.0%) than gram-positive organisms (20 patients, 40.0%). Four patients (8.0%) had a positive fungal culture from the blood (Fig. 2).

Fig. 2.

Fig. 2

Blood, other body fluids, and vitreous culture organism

Forty-six patients (38.7%) had at least one positive culture from other body fluids. Other body fluid cultures yielded gram-positive organisms in 11 patients (23.9%), gram-negative in 28 patients (23.3%), and fungal in 7 patients (15.2%). Nineteen patients (41.3%) had a positive urine culture; 14 (30.4%) had positive cultures from infected catheter, skin, soft tissue, or joint; 8 (17.4%) had positive sputum cultures; 5 (10.9%) had positive culture from liver abscess; 3 (6.5%) had positive high vaginal swab; and 1 patient (2.1%) had positive cerebrospinal fluid (Figs. 2 and 3).

Fig. 3.

Fig. 3

Other body fluid culture

Vitreous samples were obtained from 125 eyes. Vitreous culture was positive in 27 eyes (22.3%). Of these, 22 eyes (81.4%) had bacterial and 5 eyes (18.5%) had fungal isolates. Among bacterial isolates, 10 (37.0%) were gram-positive and 12 (44.4%) were gram-negative (Fig. 2).

The causative organisms cultured from the blood, vitreous, and other body fluids are summarized in Table 2.

Table 2.

Microbial isolates from blood, other body fluids, and vitreous

Species Blood (n = patient) Other body fluids (n = patient) Vitreous (n = eyes)
Culture positive 50 (42.0%) 46 (38.7%) 27 (22.3%)
Culture negative 69 (58.0%) 73 (61.3%) 94 (77.7%)
Gram-positive organism 20 (40.0%) 11 (23.9%) 10 (37.0%)
Staphylococcus aureas 13 (26.0%) 7 (15.2%) 5 (18.5%)
 MRSA 3 (6.0%) 2 (4.3%) 2 (7.4%)
Staphylococcus coagulase -ve 2 (4.0%) 0 (0.0%) 2 (7.4%)
Streptococcus sp. 2 (4.0%) 2 (4.3%) 1 (3.7%)
Gram-negative organism 26 (52.0%) 28 (60.9%) 12 (44.4%)
Klebsiella pneumonia 17 (34.0%) 19 (41.3%) 8 (29.6%)
Pseudomonas aeruginosa 2 (4.0%) 4 (8.7%) 3 (11.1%)
Escherichia coli 1 (2.0%) 3 (6.5%) 0 (0.0%)
Acinebacter sp. 1 (2.0%) 2 (4.3%) 0 (0.0%)
Enterobacter intermedius 1 (2.0%) 0 (0.0%) 0 (0.0%)
Bukholderia cepacia 1 (2.0%) 0 (0.0%) 1 (3.7%)
Bukholderia pseudomallei 1 (2.0%) 0 (0.0%) 0 (0.0%)
Elizabethkingia meningosepticum 1 (2.0%) 0 (0.0%) 0 (0.0%)
Mycoplasma pneumonia 1 (2.0%) 0 (0.0%) 0 (0.0%)
Fungal 4 (8.0%) 7 (15.2%) 5 (18.5%)
Candida albicans 1 (2.0%) 5 (10.9%) 1 (3.7%)
Candida tropicalis 2 (4.0%) 1 (2.2%) 0 (0.0%)
Penicillium sp. 0 (0.0%) 0 (0.0%) 2 (7.4%)
Phanerochaeta chrysosporium 0 (0.0%) 0 (0.0%) 1 (3.7%)
Xylariaceae sp. 0 (0.0%) 0 (0.0%) 1 (3.7%)
 Fungal (species not available) 1 (2.0%) 1 (2.2%) 0 (0.0%)

The microbiology of causative organisms is summarized in Table 3.

Table 3.

Microbiology of causative organism in endogenous endophthalmitis

Number Percent
Gram-positive bacteria 27 32.5
Staphylococcus aureas 17 20.5
 MRSA 3 3.6
Staphylococcus coagulase -ve 4 4.8
Streptococcus sp. 3 3.6
Gram-negative bacteria 42 50.6
Klebsiella pneumonia 27 32.5
Pseudomonas aeruginosa 5 6.0
Escherichia coli 3 3.6
Acinebacter sp. 2 2.4
Enterobacter intermedius 1 1.2
Bukholderia cepacia 1 1.2
Bukholderia pseudomallei 1 1.2
Elizabethkingia meningosepticum 1 1.2
Mycoplasma pneumonia 1 1.2
Fungal 14 16.9
Candida albicans 5 6.0
Candida tropicalis 3 3.6
Penicillium sp. 2 2.4
Phanerochaeta chrysosporium 1 1.2
Xylariaceae sp. 1 1.2
 Fungal (species not available) 2 2.4

Treatment

All patients were treated with systemic antibiotics or antifungal agents aimed at the source of infection and presumed causative organism. One hundred nineteen cases (85.6%) were on systemic antibiotics, and more than half (55.1%) were treated with ciprofloxacin either as monotherapy or in combination with other antibiotics. There was no statistically significant correlation between systemic ciprofloxacin and final visual outcomes (p = 0.68). Systemic steroids were not used in any of the patients. In addition, 126 eyes (88.7%) received intravitreal antibiotics (vancomycin and ceftazidime or amikacin) or antifungal (amphotericin B) injections or both. The injections were repeated in 75 eyes (59.5%). Intravitreal injection was not given in 16 cases (11.3%), and 10 of them (62.5%) had relatively good presenting visual acuity of 6/24 or better and mild vitritis. They were treated with systemic antibiotics or antifungals with close monitoring. No intravitreal injection of steroids was given to any eye. Overall, 69 eyes (48.6%) were managed medically either with systemic or intravitreal antibiotics or antifungals or both.

Out of 143 eyes, 73 (51.4%) underwent vitrectomy. Early vitrectomy was performed within 2 weeks from diagnosis in 38 eyes (52.1%). Silicone oil was injected in 35 eyes (47.9%), gas in 3 eyes (4.1%), air in 19 eyes (26.0%), and no intraocular tamponade was used in 16 eyes (21.9%).

Outcomes

The most common presenting visual acuity was between 6/60 and counting finger (CF) (48 eyes, 34.0%), followed by hand motion (38, 27.0%) and perception of light (22 eyes, 15.6%). Only 16 eyes (11.3%) and 14 eyes (9.9%) had presented visual acuity between 6/6 to 6/18 and 6/24 to 6/36 respectively. Overall, 56% had vision of CF or better at presentation. Vision was not available in 2 patients (1.4%) who could not cooperate during a vision test. Final visual acuity was available in 138 eyes (96.5%). Three patients were transferred to their original hospitals for the continuation of treatment and follow-up. One patient defaulted follow-up, and another patient passed away due to sepsis and multiorgan failure.

After treatment, 100 eyes (73.0%) achieved final visual acuity of CF or better. Ten eyes developed panophthalmitis, and 6 eyes required evisceration. Table 4 summarizes the logistic regression analysis results of patient characteristics that may predict a good visual outcome (CF or better).

Table 5.

Clinical summary of endogenous endophthalmitis in the current study

Case Age/sex/eye Systemic risk factors Initial VA Culture Organism Source of infection Systemic antibiotics/antifungal IVT abk/antifungal Vitrectomy Final VA
Blood Other body fluids Vitreous
1 49/M/R CF + + Sputum Acinetobacter sp. Skin infection Ciprofloxacin Yes Yes 6/18
2 76/F/R PL + Skin Candida albicans Skin infection Fluconazole Yes Yes NPL
3 49/M/L DM 4/60 + Skin Staphylococcus aureus Skin infection Unasyn Yes No 6/36
4 46/F/L NAV + Sputum Acinetobacter sp. Lung infection Ceftriaxone, sulperazone Yes No NAV
5 39/F/L Leukemia 6/36 Amphotericin, fluconazole Yes yes 6/9
6 71/M/L CF + Klebsiella pneumonia UTI Cefuroxime Yes No 6/24
7 56/F/R DM NPL Lung infection Ciprofloxacin Yes No NPL
8 56/M/L Leukemia 6/60 + Enterobacter intermedius Vancomycin, moxifloxacin Yes No HM
9 26/M/R 6/36 + Not done Staphylococcus aureus IE Cloxacillin, gentamicin No No 6/36
10 26/M/L 6/9 + Not done Staphylococcus aureus IE Cloxacillin, gentamicin No No 6/6
11 61/M/R DM CF + + Urine Candida albicans UTI Fluconazole, voriconazole Yes Yes 6/9
12 61/M/L DM 6/36 + + Urine Candida albicans UTI Fluconazole, voriconazole Yes Yes 6/9
13 60/M/R DM PL + Liver, + sputum Klebsiella pneumonia HPB infection Ciprofloxacin, cefuroxime, metronidazole Yes Yes PL
14 60/M/L DM PL + Liver, + sputum Klebsiella pneumonia HPB infection Ciprofloxacin, cefuroxime, metronidazole Yes No NPL
15 49/M/R DM HM + Urine Staphylococcus aureus DFU Ciprofloxacin Yes Yes CF
16 49/M/L DM HM + Urine Staphylococcus aureus DFU Ciprofloxacin Yes Yes NPL
17 52/F/L DM CF Ciprofloxacin, vancomycin Yes No CF
18 57/M/L DM, renal failure CF + Infected catheter + Pseudomonas aeruginosa DFU Ciprofloxacin, ceftazidime, meropenem Yes Yes NPL
19 38/F/L DM HM HPB infection Ciprofloxacin Yes Yes HM
20 71/F/R DM CF + Staphylococcus coagulase -ve Lung infection Cefuroxime Yes No 6/60
21 49/F/L Renal failure on steroid CF Fluconazole Yes Yes 6/12
22 68/M/L DM, malignancy 6/12 + Sputum Not done Pseudomonas aeruginosa Lung infection Ceftriaxone, cefuroxime No No 6/9
23 56/M/L DM, renal failure, hydronephrosis 4/60 + Staphylococcus aureus Infected catheter Cloxacillin Yes No 4/60
24 30/F/R DM PL + Urine + Klebsiella pneumonia UTI Vancomycin, ceftazidime Yes Yes PL
25 65/F/R 6/60 UTI NAV Yes Yes 6/24
26 19/F/R SLE with lupus nephritis, on steroid 6/6 + Staphylococcus aureus Infected catheter Vancomycin Yes No 6/18
27 75/F/R DM 6/18 + Sputum Not done Klebsiella pneumonia Lung infection Ciprofloxacin No No 6/24
28 75/F/L DM CF + Sputum Klebsiella pneumonia Lung infection Ciprofloxacin Yes Yes PL
29 51/F/R DM HM + HVS Candida albicans Fluconazole Yes Yes 6/9
30 53/F/L HM + Staphylococcus aureus Ciprofloxacin Yes Yes CF
31 49/M/L DM HM NAV NAV NAV HPB infection NAV Yes Yes CF
32 19/M/R HM Not done Meningitis Ciprofloxacin Yes No NAV
33 65/F/L CNS lymphoma CF Ciprofloxacin Yes Yes CF
34 77/M/R CF Ciprofloxacin, fluconazole Yes Yes 6/36
35 27/F/R 6/24 Not done Lung infection NAV No No 6/9
36 27/F/L 6/24 Not done Lung infection NAV No No 6/9
37 56/F/R 3/60 + Not done Staphylococcus aureus UTI C-penicillin, unasyn No No 6/9
38 62/M/R DM 6/12 + + Urine Not done Streptococcus sp. UTI Piperacillin-tazobactam Yes No 6/9
39 62/M/L DM PL + + Urine Streptococcus sp. UTI Piperacillin-tazobactam Yes No 6/18
40 34/M/R Renal failure HM + Urine NAV Klebsiella pneumonia UTI Sulperazone Yes No 3/60
41 63/M/L DM CF + Sputum Not done Klebsiella pneumonia Lung infection Trimethoprime, sulphamethoxazole No No CF
42 30/F/R 6/60 Skin infection Cloxacillin Yes No 6/6
43 30/F/L 6/24 Not done Skin infection Cloxacillin Yes No 6/6
44 61/F/R DM, sigmoid colon carcinoma CF Infected catheter Ciprofloxacin, fluconazole Yes Yes 6/36
45 40/M/L HM HPB infection Ciprofloxacin, meropenem Yes Yes NPL
46 53/M/R DM HM Lung infection Cefoperazone Yes No 6/60
47 53/M/L DM HM Lung infection Ceftriaxone Yes No HM
48 57/M/R DM HM + Staphylococcus aureus UTI Vancomycin Yes Yes HM
49 57/M/L DM 3/60 + Staphylococcus aureus UTI Vancomycin Yes Yes NPL
50 70/M/R DM, hydronephrosis HM + Staphylococcus aureus Infected catheter Cloxacillin, gentamicin Yes No 6/18
51 70/M/L DM, hydronephrosis HM + Staphylococcus aureus Infected catheter Cloxacillin, gentamicin Yes No CF
52 19/M/L Takayashu arteritis, renal failure on steroid 2/60 Ciprofoxacin, ceftazidime Yes No 6/18
53 56/F/R DM 6/18 + + Liver Klebsiella pneumonia HPB infection Cefuroxime Yes No 6/18
54 56/M/R DM HM + MRSA Infected catheter Ciprofloxacin Yes No CF
55 56/M/L DM CF + Klebsiella pneumonia Lung infection Ceftazidime Yes No NPL
56 57/M/R CF Ciprofloxacin Yes No 6/12
57 57/M/L 6/12 Not done Ciprofloxacin Yes No 6/12
58 38/F/L 6/9 + Urine Escherichia coli UTI Ceftazidime No No 6/9
59 55/M/R DM CF + Infected catheter Staphylococcus aureus Skin infection Ceftriaxone Yes No CF
60 7/M/R Leukemia 6/36 + Infected catheter Fungal* Septic arthritis Itraconazole Yes Yes 6/9
61 42/F/R CF + Bukholderia pseudomallei Ciprofloxacin Yes No 6/24
62 63/F/R DM NAV + + Urine/infected catheter Not done Klebsiella pneumonia Skin infection Ciprofloxacin No No NPL
63 71/F/L HM NAV Lung infection Ciprofloxacin NAV NAV NAV
64 22/F/L Leukemia 6/24 + Not done Fungal* Voriconazole No No 6/18
65 45/M/L DM, renal failure NPL + + Infected catheter Staphylococcus aureus Infected catheter Cloxacillin Yes No NPL
66 48/M/R DM CF + Klebsiella pneumonia Lung infection Ceftriaxone, amoxicillin-clavulanic acid Yes Yes 6/60
67 31/M/L CF Ciprofloxacin Yes Yes 6/6
68 54/M/L 6/60 + + Sputum, CSF + Klebsiella pneumonia Lung infection Ceftriaxone, imipenem Yes No NPL
69 55/M/R DM, renal failure HM + + Infected catheter Staphylococcus aureus Skin infection Ciprofloxacin Yes Yes 6/60
70 55/M/L DM, renal failure HM + + Infected catheter Staphylococcus aureus Skin infection Ciprofloxacin Yes Yes 6/36
71 14/F/L 6/36 Not done Ceftazidime, trimethoprime, sulphamethoxazole No No 6/18
72 42/F/L 6/60 HPB infection Ciprofloxacin, Ceftazidime Yes Yes CF
73 30/F/R 6/12 + HVS Steroptococcus sp. Genital infection c-penicillin Yes No 6/12
74 67/F/L DM HM Lung infection Ceftazidime Yes No NAV
75 65/M/L CF + Liver Klebsiella pneumonia HPB infection Ciprofloxacin, imipenem Yes Yes CF
76 34/F/R Leukemia PL + Candida tropicalis Voriconazole Yes No NPL
77 34/F/L Leukemia CF + Candida tropicalis Voriconazole Yes Yes 6/60
78 58/M/R DM, renal failure NPL + + Urine + Pseudomonas aeruginosa UTI Ciprofloxacin, metronidazole No No NPL
79 55/F/R DM 6/60 + + Bukholderia cepacia Meningitis Ceftazidime Yes No 6/36
80 25/M/L PL + + Steroptococcus sp. Cloxacillin Yes Yes NPL
81 48/F/L 6/60 Ceftazidime Yes No 6/18
82 52/F/L DM CF + + Urine Pseudomonas aeruginosa UTI Ciprofloxacin Yes Yes CF
83 55/F/L DM HM + Klebsiella pneumonia Lung infection Amoxicillin-clavulanic acid, azithromycin Yes Yes CF
84 74/M/L DM, renal carcinoma CF Skin infection Ciprofloxacin, fluconazole Yes Yes 6/24
85 37/F/R DM HM + Lung infection Ciprofloxacin Yes Yes 5/60
86 66/F/R DM PL + Infected catheter + Klebsiella pneumonia Skin infection Ciprofloxacin Yes Yes CF
87 66/F/L DM PL + Infected catheter + Klebsiella pneumonia Skin infection Ciprofloxacin Yes No CF
88 50/F/R DM HM + Staphylococcus coagulase -ve UTI Ciprofloxacin Yes No 6/9
89 65/M/R DM, alcoholic liver disease CF + Urine Candida albicans HPB infection Fluconazole Yes Yes CF
90 65/M/L DM, alcoholic liver disease CF + Urine Candida albicans HPB infection Fluconazole Yes Yes 3/60
91 49/F/L DM 6/9 Skin infection Ciprofloxacin, fluconazole Yes Yes HM
92 41/F/R Leukemia 6/7.5 + Not done Candida tropicalis Voriconazole Yes No 6/9
93 41/F/L Leukemia 6/60 + Candida tropicalis Voriconazole Yes No 6/18
94 58/M/R DM, liver disease 6/36 Ceftazidime Yes No 6/9
95 55/F/R Auto-immune hepatitis on steroid and immunosuppressant CF Ciprofloxacin Yes No 6/12
96 81/M/R HM Ciprofloxacin Yes Yes 6/12
97 32/F/R Leukemia 6/24 + Xylariaceae sp. Voriconazole Yes Yes CF
98 32/F/L Leukemia 6/12 Voriconazole Yes Yes 6/12
99 63/F/R HM + Staphylococcus coagulase -ve Skin infection Ciprofloxacin Yes Yes 6/9
100 54/M/L DM, renal failure PL + + Infected catheter + Staphylococcus aureus Infected catheter Ciprofloxacin, amoxicillin-clavulanic acid Yes No NPL
101 46/F/R DM HM + Penicillium sp. Amphotericin, fluconazole Yes Yes CF
102 64/M/L DM, rectal carcinoma PL Ciprofloxacin Yes Yes HM
103 66/M/L DM 6/24 + + Mycoplasma pneumonia Lung infection Ciprofloxacin, azithromycin Yes Yes 6/9
104 59/F/L DM, renal failure HM Ciprofloxacin Yes Yes CF
105 70/M/R DM PL + Penicillium sp. Itraconazole Yes Yes 6/36
106 41/F/R DM HM Lung infection Ciprofloxacin Yes Yes PL
107 67/M/L DM 6/9 + + Urine + Escherichia coli UTI Ciprofloxacin Yes Yes CF
108 63/M/R 1/60 + + Infected catheter + MRSA Skin infection Vancomycin, ciprofloxacin Yes Yes 6/9
109 63/M/L 6/24 + + Infected catheter Not done MRSA Skin infection Vancomycin, ciprofloxacin No No 6/12
110 52/M/L DM, renal failure HM + Phanerochaete chrysosporium Skin infection Voriconazole Yes No CF
111 45/M/R DM, renal failure PL + Staphylococcus aureus Infected catheter Cloxacillin Yes Yes NPL
112 47/M/R Alcoholic liver disease on steroid 6/12 + Not done Staphylococcus aureus Skin infection Cloxacillin No No 6/9
113 47/M/L Alcoholic liver disease on steroid 6/12 + Not done Staphylococcus aureus Skin infection Cloxacillin No No 6/9
114 58/M/L DM PL + + Infected catheter + MRSA Genital infection Ciprofloxacin Yes Yes HM
115 67/F/R 6/36 + Urine + Klebsiella pneumonia UTI Cefuroxime Yes Yes CF
116 48/M/L DM HM Not done Skin infection Ciprofloxacin Yes Yes 6/18
117 78/F/L CF + Staphylococcus coagulase -ve Ciprofloxacin, ceftazidime Yes Yes 3/60
118 61/F/L DM PL + Urine Klebsiella pneumonia UTI Ciprofloxacin, meropenem Yes Yes CF
119 55/F/L DM 3/60 + + Sputum Klebsiella pneumonia Lung infection Ceftazidime Yes Yes 6/12
120 55/M/L PL + + Klebsiella pneumonia HPB infection Ceftriaxone, ciprofloxacin, metronidazole Yes No NPL
121 60/M/R DM PL + + Infected catheter + Staphylococcus aureus Skin infection Cloxacillin, ceftazidime Yes No HM
122 60/M/L DM PL + + Infected catheter + Staphylococcus aureus Skin infection Cloxacillin, ceftazidime Yes Yes HM
123 40/F/R DM/liver cirrhosis, myelodysplastic syndrome 6/18 + + Infected catheter Klebsiella pneumonia Lung infection Cefuroxime, piperacillin-tazobactam Yes Yes CF
124 32/F/L DM 6/60 + Klebsiella pneumonia UTI Cefuroxime Yes No 6/12
125 34/F/L DM HM + Urine + Candida albicans Amphoterin Yes Yes 6/18
126 57/F/R DM PL + Klebsiella pneumonia AGE Ciprofloxacin Yes Yes NAV
127 48/M/R DM PL DFU Ciprofloxacin, Ceftazidime Yes No NPL
128 65/F/R DM 1/60 + Urine Klebsiella pneumonia UTI Ciprofloxacin Yes No 6/60
129 65/F/R DM, renal failure HM Ciprofloxacin Yes Yes CF
130 72/F/L DM HM + Urine Escherichia coli UTI Ciprofloxacin, trimethoprime, sulphamethoxazole Yes No NPL
131 55/F/R DM HM + Klebsiella pneumonia HPB infection Ceftriaxone Yes Yes HM
132 67/M/R Adenocarcinoma of lung and colon HM Infected catheter Fluconazole, voriconazole Yes Yes NPL
133 68/F/L DM, renal failure CF + Elizabethkingia meningocepticum Infected catheter Ceftazidime, cefazolin, vancomycin Yes No CF
134 68/F/R DM, renal failure 6/24 + Elizabethkingia meningocepticum Infected catheter Ceftazidime, cefazolin, vancomycin Yes No 6/12
135 61/F/L DM, renal failure HM + Staphylococcus aureus Infected catheter Cloxacillin Yes No 6/36
136 44/M/L DM PL + + Liver + Klebsiella pneumonia HPB infection Ceftazidime, imipenem Yes No NPL
137 65/M/L DM, chronic cystitis CF + Urine Klebsiella pneumonia UTI Ciprofloxacin Yes Yes CF
138 59/F/L DM, renal Failure HM Skin infection Ciprofloxacin Yes Yes 6/18
139 67/F/L Hepatolithiasis PL + + Liver Klebsiella pneumonia HPB infection Ciprofloxacin, imipenem Yes No NPL
140 76/M/R DM CF + Urine Candida albicans UTI Fluconazole Yes Yes 6/9
141 76/M/L DM CF + Urine Candida albicans UTI Fluconazole Yes Yes 6/24
142 38/F/R HM + Pseudomonas aeruginosa Ceftriaxone, ciprofloxacin, metronidazole Yes Yes HM
143 69/M/L DM HM + + Urine + Klebsiella pneumonia UTI Cefepime, amoxicillin-clavulanic acid Yes Yes 1/60

Abbreviation: IVT intravitreal, abk antibiotic, DM diabetes mellitus, NAV not available, UTI urinary tract infection, IE infective endocarditis, HPB hepatobiliary, DFU diabetic foot ulcer, AGE acute gastroenteritis, MRSA methicillin-resistant Staphylococcus aureus, CF counting finger, HM hand movement, PL perception of light, NPL non-perception of light

Table 4.

Prognostic factors associated with good visual outcomes

Prognostic factor (referent) Crude odds ratio (95% CI) p valuea Adjusted odds ratio (95% CI) p valueb
Gender (male)
 Female 2 (0.92, 4.37) 0.079
Age (0–50 years)
 > 50 years 0.85 (0.39, 1.86) 0.679
Medical illness (yes)
 No 1.60 (0.55, 4.63) 0.383
DM (yes)
 No 2.12 (0.93, 4.85) 0.071
Presenting VA (≥ CF)
 < CF 0.10 (0.04, 0.25) 0.000 0.09 (0.021, 0.384) 0.001
Fundus view (yes)
 No 0.15 (0.06, 0.38) 0.000 0.337 (0.068, 1.675) 0.184
Source of infection (yes)
 No 2.61 (0.93, 7.37) 0.062
Culture (positive)
 Negative 1.29 (0.54, 3.07) 0.566
Organism (gram+)
 Gram− 0.965 (0.275–3.386) 0.956
 Fungal 0.185 (0.019, 1.848) 0.151
Intravitreal antibiotic (yes)
 No 2.85 (0.62, 13.2) 0.234
Vitrectomy (yes)
 No 1.13 (0.53–2.41) 0.751
Early vitrectomy (≤ 2 weeks)
 > 2 weeks 1.69 (0.59–4.82) 0.327

The clinical summary of patients were summarized in Table 5

aUnivariate logistic regression

bOnly factors associated with good visual outcome in multivariate logistic regression model

In univariate logistic regression analysis, factors found to be statistically significant with good visual outcome were good presenting visual acuity (crude odd ratio 0.1; 95% CI 0.021, 0.384) and presence of fundus view at presentation (crude odd ratio 0.337; 95% CI 0.068,1.675). In the multivariate logistic regression analysis, elevated risk for good visual outcome was observed only in good presenting visual acuity (adjusted odd ratio 0.09; 95% CI 0.021, 0.384). We also found a moderate correlation between presenting visual acuity and final visual acuity (Pearson r = 0.564, p < 0.001 (Fig. 4).

Fig. 4.

Fig. 4

Correlation between presenting visual acuity (LogMAR) and final visual acuity (LogMAR)

Gender, age group, presence of underlying medical illness, existing DM, source of infection, culture positivity, types of organism, intravitreal antibiotics, vitrectomy, or early vitrectomy were not significantly associated with good final visual outcomes.

Discussion

In this study, we wanted to determine whether the clinical profiles of EE at a tertiary hospital in Malaysia were similar to those reported from other countries.

Previous studies had reported a male preponderance with unilateral involvement [710]. In contrast, our results showed no difference between male and females.

Predisposing conditions are important in determining a patient’s risk for endogenous endophthalmitis. Okada et al. reported 90% of patients had a positive history of underlying medical conditions such as diabetes, cardiac disease, and malignancy [2]. A major review of endogenous endophthalmitis demonstrated underlying medical conditions predisposing to ocular infection in 56 to 68% of cases [4]. Another study conducted by Wu and colleagues revealed the identification of preexisting predisposing condition in 90.9% of patients, and the most common systemic condition found was diabetes mellitus (50%) [11]. In contrast, Connell et al. reported that intravenous drug abuse was the most common risk factor [1]. Several East Asian studies reported that diabetes mellitus was the most common, and hepatobiliary disease was the second most frequent underlying disease [5, 1214]. In a review of 57 cases of endogenous endophthalmitis in Korea, diabetes mellitus (46.5%) was the most common underlying disease followed by liver cirrhosis (20.9%) [15]. In a recent study in which all patients had one or more preexisting medical conditions, the most common was also diabetes mellitus (61.9%) [16]. Our series revealed similar results, in which diabetes mellitus was the most common systemic disease (60.0%) followed by renal failure and malignancy. However, liver diseases were identified only in 6 patients.

In a review of cases by Wong et al., it was reported that hepatobiliary tract infection was the most common source of bacteremia (13 patients, 48%) [5]. Similar results were found in other Korean case series [12, 15, 17]. Interestingly, our case series did not show similar findings with other East Asian reports. We found that urinary tract infection (21, 17.5%) was the most common source of bacteremia followed by pulmonary infection (19, 15.8%). Hepatobiliary tract infection was only identified in 12 patients (10.0%). We also found that among patients who were younger than 40 years old, and older than 60 years old, the most common systemic infection was urinary tract infection at 17.4% and 30.0% respectively. In contrast, lung infection (17.5%) followed by hepatobiliary infection (14.0%) was the commonest infections among those aged from 40 to 60 years old.

In a case series by Lim et al., the most common presenting complaint was decreased vision (68.8%) followed by ocular discomfort (44%), red eye (20.8%), and ocular pain (17.4%) [15]. Ratra et al. also reported that reduced vision (60, 98.4%), redness (47, 77%), and pain (42, 68.8%) were the three most common presenting symptoms [8]. Similar to these studies, our study too revealed blurring of vision, eye redness, and eye pain or discomfort as the main presenting ocular symptoms. However in a case series by Nishida et al., floaters was the second most common ocular symptom after blurring of vision [16].

Ratra et al. in their case series demonstrated that all eyes had severe diffuse endophthalmitis involving the posterior pole. Diffuse vitreous exudates were seen in 47 eyes (77%). Retina could be visualized in 13 eyes (21.3%), and 3 (4.9%) had retinal detachment. None had panophthalmitis [8]. In another case series in 18-year review of culture-positive cases in 34 affected eyes, the most common findings were decreased visual acuity (91.1%), vitritis (79.4%), conjunctival injection (67.6%), iritis or retinitis (61.7%), hypopyon (35.2%), and retinal detachment (5.8%) [18]. In our study, 27 eyes (19%) had hypopyon, 64 eyes (44.8%) had fundus view, and 8 eyes (8.2%) were noted to have retinal detachment on ultrasound. Lower percentage of hypopyon in our patients could be due to the application of topical steroids and antibiotics by the referring ophthalmologist.

The diagnosis of endogenous endophthamitis is typically made following microbiologic evidence of infection from intraocular samples (aqueous or vitreous). Positive cultures from the blood, cerebrospinal fluid, or any extraocular site can be highly suggestive. In our series, the organism causing endophthalmitis was identified by a positive culture from at least one body fluid source in 82 patients (68.9%). Blood culture positivity rate varies widely, from 33 to 94% [4, 19]. Previous large case series have shown higher rates of positivity following blood cultures as compared to vitreous aspirates possibly due to a larger volume sampled [2, 4, 11]. In contrast, Ratra et al. had reported that ocular fluid samples tended to give positive culture results more than blood (58.6% vs 3.4%). This is because all the patients with suspected endogenous endophthalmitis immediately underwent an aqueous tap in the outpatient department before any intravitreal therapy [8]. High rate of positive cultures from intraocular specimens was also demonstrated by Okada et al. (86%), Binder et al. (70%), and Ness et al. (81%) [2, 20, 21]. Vitrectomy has a higher diagnostic yield for culture (92%) compared to a vitreous aspirate (44%) [22]. Vitreous samples during vitrectomy were taken near the retinal surface, which can potentially explain the lower yield of needle biopsy. This is because early or localized infection located near the retinal surface might be missed by a needle biopsy [23]. We noted low vitreous yield of organisms in our study. This could be because some of our patients with systemic infection were initially managed by physicians depending on the source of infection. During the time of referral, most of them were already on systemic antibiotics or partially treated. Furthermore, the diagnosis may have been delayed in some while others were generally not stable for early vitreous tapping. Thirty-six patients (30.0%) in our series were culture negative.

Causative organisms vary geographically. Studies from the western population revealed that fungal infection was the main source in predisposed states, such as intravenous drug abusers and immunocompromised patients [1, 19, 21]. In contrast, gram-negative microbes as the causative organisms were overwhelming in the East Asian experience. In these Asian populations, Klebsiella was found to be responsible for approximately 90% of all endogenous bacteria endophthalmitis cases [5]. Studies that were conducted in Korea showed that liver abscess was the most common infection source and Klebsiella was the most common causative agent [15, 17]. A study from Japan in 2015, however, demonstrated that gram-positive organisms were more common (76.2%) than gram-negative (19.0%), contrasted to the findings from other East Asian studies [16]. K. pneumonia which is predominant in East Asia may be due to the high incidence of cholangiohepatitis. Therefore, the East Asian population is more prone to have liver abscess than Caucasians [24]. We found that gram-negative organisms were responsible for half of the cases of endogenous endophthalmitis in our case series (42 patients, 50.6%) in which K. pneumonia was the most common organism isolated (27 patients, 32.5%). Interestingly, in contrast to several East Asian studies, urinary tract infection including renal abscess (9 patients, 33.3%) was the most common source of infection caused by K. pneumonia followed by lung infection (8 patients, 29.6%) in our series. Liver abscess was identified in 7 patients (25.9%). Necrotizing fasciitis, infected wound breakdown, and acute gastroenteritis (AGE) were noted in one patient each. Apart from that, there was a relatively higher frequency of gram-positive cocci and fungal infection in our study, 32.5% and 16.9% respectively.

Most systemically administered antimicrobials that have been used in the therapy of endophthalmitis do not penetrate well into the non-inflamed vitreous humor. However, the penetration of several antibiotics into the eye may be increased by inflammation which occurs following surgery, trauma, or infection. Kowalski and colleagues compared the minimum inhibitory concentration (MIC) of bacterial isolates from 66 patients with endophthalmitis and found that all of the gram-negative isolates would have been inhibited by levels of ciprofloxacin achievable following systemic administration [25].

In endogenous endophthalmitis, the rationale for use of intravitreal injections as an adjunct to intravenous therapy is also because of reduced permeability of the retinal-pigmented epithelium to systemically administered drugs [26]. Yonekawa et al. showed that early administration, e.g., within 24 h, was associated with a favorable visual outcome [27]. Most of our patients received intravitreal injections within 24 h of diagnosis.

Vitrectomy serves as a diagnostic and therapeutic option. It is indicated in cases with severe vitreous opacities, diffuse retinal infiltration, and poor presenting visual acuity and when there is no clinical improvement with systemic and intravitreal therapy. However, the role and timing of vitrectomy remain unclear in patients with endogenous endophthalmitis. Sheu et al. reported no significant relationship between vitrectomy and visual outcome in Klebsiella endophthalmitis. However, they suggested early vitrectomy should be considered in patients whose anterior chamber inflammation did not respond well to intravitreal antibiotics [28]. On the other hand, Yoon et al. demonstrated that following early vitrectomy for Klebsiella endogenous endophthalmitis, 50% achieved a vision of CF or better after 6 months [14]. Early vitrectomy performed within 10 days of the appearance of ocular symptoms or signs resulted in a better visual prognosis (CF or better) than without vitrectomy [17]. In other studies, early vitrectomy within 2 weeks of presentation in severe cases or suspected virulent organisms was associated with good overall outcome [14, 17]. In our case series, 73 eyes (51.4%) underwent vitrectomy. Vitrectomy was performed within 2 weeks in 38 eyes (52.1%) and more than 2 weeks in 35 eyes (47.9%). The most common indication for early vitrectomy was poor presenting visual acuity of CF or worse in 31 cases (81.6%). Persistent or increased vitreous opacities or anterior chamber cells despite systemic and intravitreal antibiotics were other indications for early vitrectomy. There was no significant difference between early vitrectomy (within 2 weeks) compared to delayed vitrectomy (more than 2 weeks) for favorable visual prognosis (p = 0.327).

Generally, the visual outcome of endogenous endophthalmitis is poor due to early and extensive retinal involvement. Virulent causative organisms, poor host defense, misdiagnosis leading to delayed treatment, inadequate treatment, inappropriate therapy, and occurrence of complications such as panophthalmitis are associated with poor prognosis. Wu et al. reported that the eyes with bacterial endogenous endophthalmitis had a worse outcome compared to patients with fungal endophthalmitis [11]. Lim et al. concluded that gram-negative bacteria had worse visual outcomes compared to gram-positive bacteria or fungus [15].

Visual outcomes in Klebsiella endophthalmitis has been poor despite treatment with a combination of systemic and intravitreal antibiotics [12, 13]. Case series and literature reviews involving infection with K. pneumonia showed that visual acuity achieved was CF or better in 34.0% of eyes, and 16.0% had evisceration or enucleation [5]. Sheu et al. reported 19 eyes (35.8%) had final visual acuity of CF or better [28]. Connell et al. found that all the patients in their study needing enucleation were infected by Klebsiella [1]. In our series, 100 eyes (73.0%) achieved final visual acuity of CF or better. However, in cases with Klebsiella endogenous endophthalmitis, only 18 eyes (25.4%) achieved final visual acuity of CF or better, which is comparable with other studies. Ten eyes were complicated with panophthalmitis, and 5 of them were due to Klebsiella pneumonia.

In our series, a good presenting visual acuity was the only prognostic factor associated with good visual outcomes of CF or better. Lim et al., Nishida et al., and Binder et al. in their case series also described that a good presenting visual acuity was significantly associated with good final visual acuity [15, 16, 20]. We found that DM, presence of a source of infection, organism, and intravitreal antibiotics were not related to poor visual outcome.

Study limitation

This study is limited by the retrospective design. As the data was collected retrospectively, some of the information was not available. Apart from that, patients with culture-negative result were also included in this study which may have included those with non-infectious uveitis. In the future, we may need to use other methods such as polymerase chain reaction (PCR) with higher sensitivity and specificity. Lack of uniform guidelines and treatment protocol is another limitation. Observational and prospective case series are needed in the future to assess long-term outcomes.

Conclusions

The visual prognosis of endogenous endophthalmitis (EE) is poor. Gram-negative organisms specifically Klebsiella pneumonia were the most common organisms isolated. Urinary tract infection was the main source of infection. Poor presenting visual acuity was significantly associated with poor visual outcomes.

Acknowledgements

We would like to thank the Director General of Health Malaysia for his permission to publish this article. Last but not least, we express our gratitude to CRC Hospital Sultanah Nur Zahirah, Kuala Terengganu, and those who had extended their help in contributing to this manuscript.

Abbreviations

AGE

Acute gastroenteritis

CF

Counting fingers

EE

Endogenous Endophthalmitis

MRSA

Methicillin-resistant Staphylococcus aureus

PCR

Polymerase chain reaction

Authors’ contributions

All listed authors made a substantial contributions to the study. HI and AA participated in the design of the study. VV and DS helped in the data collection. RM involved in the data collection, data analysis, literature search, and drafting, designing, and revising of the manuscript. SOM participated and supervised everything from the study concept and design until the manuscript revision. Each of the authors approved the submission of this version for publication. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

Ethics approval was obtained by the Medical Research and Ethics Committee (MREC) prior to the initiation of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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