Literature DB >> 30306361

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

Rosiah Muda1, Valarmathy Vayavari2, Deivanai Subbiah3, Hamisah Ishak4, Azian Adnan3, Shelina Oli Mohamed5.   

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.

Entities:  

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

Year:  2018        PMID: 30306361      PMCID: PMC6179973          DOI: 10.1186/s12348-018-0158-3

Source DB:  PubMed          Journal:  J Ophthalmic Inflamm Infect        ISSN: 1869-5760


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 [1-3], 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 infectionNo. of patientsPercent
Infected catheter119.2
Urinary tract infection2117.5
Hepatobiliary infection1210.0
Lung infection1915.8
Meningitis21.7
Infective endocarditis10.8
Gastrointestinal infection10.8
Genital infection21.7
Skin or soft tissue infection1714.2
Septic arthritis10.8
Diabetic foot ulcer32.5
Nil3025.0
Identifiable source of infection

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

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

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

Blood, other body fluids, and vitreous culture organism

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

Other body fluid culture

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

SpeciesBlood (n = patient)Other body fluids (n = patient)Vitreous (n = eyes)
Culture positive50 (42.0%)46 (38.7%)27 (22.3%)
Culture negative69 (58.0%)73 (61.3%)94 (77.7%)
Gram-positive organism20 (40.0%)11 (23.9%)10 (37.0%)
Staphylococcus aureas13 (26.0%)7 (15.2%)5 (18.5%)
 MRSA3 (6.0%)2 (4.3%)2 (7.4%)
Staphylococcus coagulase -ve2 (4.0%)0 (0.0%)2 (7.4%)
Streptococcus sp.2 (4.0%)2 (4.3%)1 (3.7%)
Gram-negative organism26 (52.0%)28 (60.9%)12 (44.4%)
Klebsiella pneumonia17 (34.0%)19 (41.3%)8 (29.6%)
Pseudomonas aeruginosa2 (4.0%)4 (8.7%)3 (11.1%)
Escherichia coli1 (2.0%)3 (6.5%)0 (0.0%)
Acinebacter sp.1 (2.0%)2 (4.3%)0 (0.0%)
Enterobacter intermedius1 (2.0%)0 (0.0%)0 (0.0%)
Bukholderia cepacia1 (2.0%)0 (0.0%)1 (3.7%)
Bukholderia pseudomallei1 (2.0%)0 (0.0%)0 (0.0%)
Elizabethkingia meningosepticum1 (2.0%)0 (0.0%)0 (0.0%)
Mycoplasma pneumonia1 (2.0%)0 (0.0%)0 (0.0%)
Fungal4 (8.0%)7 (15.2%)5 (18.5%)
Candida albicans1 (2.0%)5 (10.9%)1 (3.7%)
Candida tropicalis2 (4.0%)1 (2.2%)0 (0.0%)
Penicillium sp.0 (0.0%)0 (0.0%)2 (7.4%)
Phanerochaeta chrysosporium0 (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%)
Microbial isolates from blood, other body fluids, and vitreous The microbiology of causative organisms is summarized in Table 3.
Table 3

Microbiology of causative organism in endogenous endophthalmitis

NumberPercent
Gram-positive bacteria2732.5
Staphylococcus aureas1720.5
 MRSA33.6
Staphylococcus coagulase -ve44.8
Streptococcus sp.33.6
Gram-negative bacteria4250.6
Klebsiella pneumonia2732.5
Pseudomonas aeruginosa56.0
Escherichia coli33.6
Acinebacter sp.22.4
Enterobacter intermedius11.2
Bukholderia cepacia11.2
Bukholderia pseudomallei11.2
Elizabethkingia meningosepticum11.2
Mycoplasma pneumonia11.2
Fungal1416.9
Candida albicans56.0
Candida tropicalis33.6
Penicillium sp.22.4
Phanerochaeta chrysosporium11.2
Xylariaceae sp.11.2
 Fungal (species not available)22.4
Microbiology of causative organism in endogenous endophthalmitis

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 4

Prognostic factors associated with good visual outcomes

Prognostic factor (referent)Crude odds ratio (95% CI)p valueaAdjusted odds ratio (95% CI)p valueb
Gender (male)
 Female2 (0.92, 4.37)0.079
Age (0–50 years)
 > 50 years0.85 (0.39, 1.86)0.679
Medical illness (yes)
 No1.60 (0.55, 4.63)0.383
DM (yes)
 No2.12 (0.93, 4.85)0.071
Presenting VA (≥ CF)
 < CF0.10 (0.04, 0.25)0.0000.09 (0.021, 0.384)0.001
Fundus view (yes)
 No0.15 (0.06, 0.38)0.0000.337 (0.068, 1.675)0.184
Source of infection (yes)
 No2.61 (0.93, 7.37)0.062
Culture (positive)
 Negative1.29 (0.54, 3.07)0.566
Organism (gram+)
 Gram−0.965 (0.275–3.386)0.956
 Fungal0.185 (0.019, 1.848)0.151
Intravitreal antibiotic (yes)
 No2.85 (0.62, 13.2)0.234
Vitrectomy (yes)
 No1.13 (0.53–2.41)0.751
Early vitrectomy (≤ 2 weeks)
 > 2 weeks1.69 (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

Prognostic factors associated with good visual outcomes The clinical summary of patients were summarized in Table 5
Table 5

Clinical summary of endogenous endophthalmitis in the current study

CaseAge/sex/eyeSystemic risk factorsInitial VACultureOrganismSource of infectionSystemic antibiotics/antifungalIVT abk/antifungalVitrectomyFinal VA
BloodOther body fluidsVitreous
149/M/RCF++ SputumAcinetobacter sp.Skin infectionCiprofloxacinYesYes6/18
276/F/RPL+ Skin Candida albicans Skin infectionFluconazoleYesYesNPL
349/M/LDM4/60+ Skin Staphylococcus aureus Skin infectionUnasynYesNo6/36
446/F/LNAV+ SputumAcinetobacter sp.Lung infectionCeftriaxone, sulperazoneYesNoNAV
539/F/LLeukemia6/36Amphotericin, fluconazoleYesyes6/9
671/M/LCF+ Klebsiella pneumonia UTICefuroximeYesNo6/24
756/F/RDMNPLLung infectionCiprofloxacinYesNoNPL
856/M/LLeukemia6/60+ Enterobacter intermedius Vancomycin, moxifloxacinYesNoHM
926/M/R6/36+Not done Staphylococcus aureus IECloxacillin, gentamicinNoNo6/36
1026/M/L6/9+Not done Staphylococcus aureus IECloxacillin, gentamicinNoNo6/6
1161/M/RDMCF++ Urine Candida albicans UTIFluconazole, voriconazoleYesYes6/9
1261/M/LDM6/36++ Urine Candida albicans UTIFluconazole, voriconazoleYesYes6/9
1360/M/RDMPL+ Liver, + sputum Klebsiella pneumonia HPB infectionCiprofloxacin, cefuroxime, metronidazoleYesYesPL
1460/M/LDMPL+ Liver, + sputum Klebsiella pneumonia HPB infectionCiprofloxacin, cefuroxime, metronidazoleYesNoNPL
1549/M/RDMHM+ Urine Staphylococcus aureus DFUCiprofloxacinYesYesCF
1649/M/LDMHM+ Urine Staphylococcus aureus DFUCiprofloxacinYesYesNPL
1752/F/LDMCFCiprofloxacin, vancomycinYesNoCF
1857/M/LDM, renal failureCF+ Infected catheter+ Pseudomonas aeruginosa DFUCiprofloxacin, ceftazidime, meropenemYesYesNPL
1938/F/LDMHMHPB infectionCiprofloxacinYesYesHM
2071/F/RDMCF+Staphylococcus coagulase -veLung infectionCefuroximeYesNo6/60
2149/F/LRenal failure on steroidCFFluconazoleYesYes6/12
2268/M/LDM, malignancy6/12+ SputumNot done Pseudomonas aeruginosa Lung infectionCeftriaxone, cefuroximeNoNo6/9
2356/M/LDM, renal failure, hydronephrosis4/60+ Staphylococcus aureus Infected catheterCloxacillinYesNo4/60
2430/F/RDMPL+ Urine+ Klebsiella pneumonia UTIVancomycin, ceftazidimeYesYesPL
2565/F/R6/60UTINAVYesYes6/24
2619/F/RSLE with lupus nephritis, on steroid6/6+ Staphylococcus aureus Infected catheterVancomycinYesNo6/18
2775/F/RDM6/18+ SputumNot done Klebsiella pneumonia Lung infectionCiprofloxacinNoNo6/24
2875/F/LDMCF+ Sputum Klebsiella pneumonia Lung infectionCiprofloxacinYesYesPL
2951/F/RDMHM+ HVS Candida albicans FluconazoleYesYes6/9
3053/F/LHM+ Staphylococcus aureus CiprofloxacinYesYesCF
3149/M/LDMHMNAVNAVNAVHPB infectionNAVYesYesCF
3219/M/RHMNot doneMeningitisCiprofloxacinYesNoNAV
3365/F/LCNS lymphomaCFCiprofloxacinYesYesCF
3477/M/RCFCiprofloxacin, fluconazoleYesYes6/36
3527/F/R6/24Not doneLung infectionNAVNoNo6/9
3627/F/L6/24Not doneLung infectionNAVNoNo6/9
3756/F/R3/60+Not done Staphylococcus aureus UTIC-penicillin, unasynNoNo6/9
3862/M/RDM6/12++ UrineNot doneStreptococcus sp.UTIPiperacillin-tazobactamYesNo6/9
3962/M/LDMPL++ UrineStreptococcus sp.UTIPiperacillin-tazobactamYesNo6/18
4034/M/RRenal failureHM+ UrineNAV Klebsiella pneumonia UTISulperazoneYesNo3/60
4163/M/LDMCF+ SputumNot done Klebsiella pneumonia Lung infectionTrimethoprime, sulphamethoxazoleNoNoCF
4230/F/R6/60Skin infectionCloxacillinYesNo6/6
4330/F/L6/24Not doneSkin infectionCloxacillinYesNo6/6
4461/F/RDM, sigmoid colon carcinomaCFInfected catheterCiprofloxacin, fluconazoleYesYes6/36
4540/M/LHMHPB infectionCiprofloxacin, meropenemYesYesNPL
4653/M/RDMHMLung infectionCefoperazoneYesNo6/60
4753/M/LDMHMLung infectionCeftriaxoneYesNoHM
4857/M/RDMHM+ Staphylococcus aureus UTIVancomycinYesYesHM
4957/M/LDM3/60+ Staphylococcus aureus UTIVancomycinYesYesNPL
5070/M/RDM, hydronephrosisHM+ Staphylococcus aureus Infected catheterCloxacillin, gentamicinYesNo6/18
5170/M/LDM, hydronephrosisHM+ Staphylococcus aureus Infected catheterCloxacillin, gentamicinYesNoCF
5219/M/LTakayashu arteritis, renal failure on steroid2/60Ciprofoxacin, ceftazidimeYesNo6/18
5356/F/RDM6/18++ Liver Klebsiella pneumonia HPB infectionCefuroximeYesNo6/18
5456/M/RDMHM+MRSAInfected catheterCiprofloxacinYesNoCF
5556/M/LDMCF+ Klebsiella pneumonia Lung infectionCeftazidimeYesNoNPL
5657/M/RCFCiprofloxacinYesNo6/12
5757/M/L6/12Not doneCiprofloxacinYesNo6/12
5838/F/L6/9+ Urine Escherichia coli UTICeftazidimeNoNo6/9
5955/M/RDMCF+ Infected catheter Staphylococcus aureus Skin infectionCeftriaxoneYesNoCF
607/M/RLeukemia6/36+ Infected catheterFungal*Septic arthritisItraconazoleYesYes6/9
6142/F/RCF+ Bukholderia pseudomallei CiprofloxacinYesNo6/24
6263/F/RDMNAV++ Urine/infected catheterNot done Klebsiella pneumonia Skin infectionCiprofloxacinNoNoNPL
6371/F/LHMNAVLung infectionCiprofloxacinNAVNAVNAV
6422/F/LLeukemia6/24+Not doneFungal*VoriconazoleNoNo6/18
6545/M/LDM, renal failureNPL++ Infected catheter Staphylococcus aureus Infected catheterCloxacillinYesNoNPL
6648/M/RDMCF+ Klebsiella pneumonia Lung infectionCeftriaxone, amoxicillin-clavulanic acidYesYes6/60
6731/M/LCFCiprofloxacinYesYes6/6
6854/M/L6/60++ Sputum, CSF+ Klebsiella pneumonia Lung infectionCeftriaxone, imipenemYesNoNPL
6955/M/RDM, renal failureHM++ Infected catheter Staphylococcus aureus Skin infectionCiprofloxacinYesYes6/60
7055/M/LDM, renal failureHM++ Infected catheter Staphylococcus aureus Skin infectionCiprofloxacinYesYes6/36
7114/F/L6/36Not doneCeftazidime, trimethoprime, sulphamethoxazoleNoNo6/18
7242/F/L6/60HPB infectionCiprofloxacin, CeftazidimeYesYesCF
7330/F/R6/12+ HVSSteroptococcus sp.Genital infectionc-penicillinYesNo6/12
7467/F/LDMHMLung infectionCeftazidimeYesNoNAV
7565/M/LCF+ Liver Klebsiella pneumonia HPB infectionCiprofloxacin, imipenemYesYesCF
7634/F/RLeukemiaPL+ Candida tropicalis VoriconazoleYesNoNPL
7734/F/LLeukemiaCF+ Candida tropicalis VoriconazoleYesYes6/60
7858/M/RDM, renal failureNPL++ Urine+ Pseudomonas aeruginosa UTICiprofloxacin, metronidazoleNoNoNPL
7955/F/RDM6/60++ Bukholderia cepacia MeningitisCeftazidimeYesNo6/36
8025/M/LPL++Steroptococcus sp.CloxacillinYesYesNPL
8148/F/L6/60CeftazidimeYesNo6/18
8252/F/LDMCF++ Urine Pseudomonas aeruginosa UTICiprofloxacinYesYesCF
8355/F/LDMHM+ Klebsiella pneumonia Lung infectionAmoxicillin-clavulanic acid, azithromycinYesYesCF
8474/M/LDM, renal carcinomaCFSkin infectionCiprofloxacin, fluconazoleYesYes6/24
8537/F/RDMHM+Lung infectionCiprofloxacinYesYes5/60
8666/F/RDMPL+ Infected catheter+ Klebsiella pneumonia Skin infectionCiprofloxacinYesYesCF
8766/F/LDMPL+ Infected catheter+ Klebsiella pneumonia Skin infectionCiprofloxacinYesNoCF
8850/F/RDMHM+Staphylococcus coagulase -veUTICiprofloxacinYesNo6/9
8965/M/RDM, alcoholic liver diseaseCF+ Urine Candida albicans HPB infectionFluconazoleYesYesCF
9065/M/LDM, alcoholic liver diseaseCF+ Urine Candida albicans HPB infectionFluconazoleYesYes3/60
9149/F/LDM6/9Skin infectionCiprofloxacin, fluconazoleYesYesHM
9241/F/RLeukemia6/7.5+Not done Candida tropicalis VoriconazoleYesNo6/9
9341/F/LLeukemia6/60+ Candida tropicalis VoriconazoleYesNo6/18
9458/M/RDM, liver disease6/36CeftazidimeYesNo6/9
9555/F/RAuto-immune hepatitis on steroid and immunosuppressantCFCiprofloxacinYesNo6/12
9681/M/RHMCiprofloxacinYesYes6/12
9732/F/RLeukemia6/24+Xylariaceae sp.VoriconazoleYesYesCF
9832/F/LLeukemia6/12VoriconazoleYesYes6/12
9963/F/RHM+Staphylococcus coagulase -veSkin infectionCiprofloxacinYesYes6/9
10054/M/LDM, renal failurePL++ Infected catheter+ Staphylococcus aureus Infected catheterCiprofloxacin, amoxicillin-clavulanic acidYesNoNPL
10146/F/RDMHM+Penicillium sp.Amphotericin, fluconazoleYesYesCF
10264/M/LDM, rectal carcinomaPLCiprofloxacinYesYesHM
10366/M/LDM6/24++ Mycoplasma pneumonia Lung infectionCiprofloxacin, azithromycinYesYes6/9
10459/F/LDM, renal failureHMCiprofloxacinYesYesCF
10570/M/RDMPL+Penicillium sp.ItraconazoleYesYes6/36
10641/F/RDMHMLung infectionCiprofloxacinYesYesPL
10767/M/LDM6/9++ Urine+Escherichia coliUTICiprofloxacinYesYesCF
10863/M/R1/60++ Infected catheter+MRSASkin infectionVancomycin, ciprofloxacinYesYes6/9
10963/M/L6/24++ Infected catheterNot doneMRSASkin infectionVancomycin, ciprofloxacinNoNo6/12
11052/M/LDM, renal failureHM+ Phanerochaete chrysosporium Skin infectionVoriconazoleYesNoCF
11145/M/RDM, renal failurePL+ Staphylococcus aureus Infected catheterCloxacillinYesYesNPL
11247/M/RAlcoholic liver disease on steroid6/12+Not done Staphylococcus aureus Skin infectionCloxacillinNoNo6/9
11347/M/LAlcoholic liver disease on steroid6/12+Not done Staphylococcus aureus Skin infectionCloxacillinNoNo6/9
11458/M/LDMPL++ Infected catheter+MRSAGenital infectionCiprofloxacinYesYesHM
11567/F/R6/36+ Urine+ Klebsiella pneumonia UTICefuroximeYesYesCF
11648/M/LDMHMNot doneSkin infectionCiprofloxacinYesYes6/18
11778/F/LCF+Staphylococcus coagulase -veCiprofloxacin, ceftazidimeYesYes3/60
11861/F/LDMPL+ Urine Klebsiella pneumonia UTICiprofloxacin, meropenemYesYesCF
11955/F/LDM3/60++ Sputum Klebsiella pneumonia Lung infectionCeftazidimeYesYes6/12
12055/M/LPL++ Klebsiella pneumonia HPB infectionCeftriaxone, ciprofloxacin, metronidazoleYesNoNPL
12160/M/RDMPL++ Infected catheter+ Staphylococcus aureus Skin infectionCloxacillin, ceftazidimeYesNoHM
12260/M/LDMPL++ Infected catheter+ Staphylococcus aureus Skin infectionCloxacillin, ceftazidimeYesYesHM
12340/F/RDM/liver cirrhosis, myelodysplastic syndrome6/18++ Infected catheter Klebsiella pneumonia Lung infectionCefuroxime, piperacillin-tazobactamYesYesCF
12432/F/LDM6/60+ Klebsiella pneumonia UTICefuroximeYesNo6/12
12534/F/LDMHM+ Urine+ Candida albicans AmphoterinYesYes6/18
12657/F/RDMPL+ Klebsiella pneumonia AGECiprofloxacinYesYesNAV
12748/M/RDMPLDFUCiprofloxacin, CeftazidimeYesNoNPL
12865/F/RDM1/60+ Urine Klebsiella pneumonia UTICiprofloxacinYesNo6/60
12965/F/RDM, renal failureHMCiprofloxacinYesYesCF
13072/F/LDMHM+ Urine Escherichia coli UTICiprofloxacin, trimethoprime, sulphamethoxazoleYesNoNPL
13155/F/RDMHM+ Klebsiella pneumonia HPB infectionCeftriaxoneYesYesHM
13267/M/RAdenocarcinoma of lung and colonHMInfected catheterFluconazole, voriconazoleYesYesNPL
13368/F/LDM, renal failureCF+ Elizabethkingia meningocepticum Infected catheterCeftazidime, cefazolin, vancomycinYesNoCF
13468/F/RDM, renal failure6/24+ Elizabethkingia meningocepticum Infected catheterCeftazidime, cefazolin, vancomycinYesNo6/12
13561/F/LDM, renal failureHM+ Staphylococcus aureus Infected catheterCloxacillinYesNo6/36
13644/M/LDMPL++ Liver+ Klebsiella pneumonia HPB infectionCeftazidime, imipenemYesNoNPL
13765/M/LDM, chronic cystitisCF+ Urine Klebsiella pneumonia UTICiprofloxacinYesYesCF
13859/F/LDM, renal FailureHMSkin infectionCiprofloxacinYesYes6/18
13967/F/LHepatolithiasisPL++ Liver Klebsiella pneumonia HPB infectionCiprofloxacin, imipenemYesNoNPL
14076/M/RDMCF+ Urine Candida albicans UTIFluconazoleYesYes6/9
14176/M/LDMCF+ Urine Candida albicans UTIFluconazoleYesYes6/24
14238/F/RHM+ Pseudomonas aeruginosa Ceftriaxone, ciprofloxacin, metronidazoleYesYesHM
14369/M/LDMHM++ Urine+ Klebsiella pneumonia UTICefepime, amoxicillin-clavulanic acidYesYes1/60

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

aUnivariate logistic regression bOnly factors associated with good visual outcome in multivariate logistic regression model Clinical summary of endogenous endophthalmitis in the current study 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 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

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

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 [7-10]. 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, 12–14]. 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.
  28 in total

Review 1.  Endogenous endophthalmitis.

Authors:  S P Chee; A Jap
Journal:  Curr Opin Ophthalmol       Date:  2001-12       Impact factor: 3.761

2.  Early intravitreal treatment of endogenous bacterial endophthalmitis.

Authors:  Yoshihiro Yonekawa; R V Paul Chan; Ashok K Reddy; Cristiana G Pieroni; Thomas C Lee; Sangwoo Lee
Journal:  Clin Exp Ophthalmol       Date:  2011-04-21       Impact factor: 4.207

3.  Changes in the clinical features and prognostic factors of endogenous endophthalmitis: fifteen years of clinical experience in Korea.

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Journal:  Retina       Date:  2012-05       Impact factor: 4.256

4.  Endogenous endophthalmitis: a 10-year review of culture-positive cases in northern China.

Authors:  Han Zhang; Zheli Liu
Journal:  Ocul Immunol Inflamm       Date:  2010-04       Impact factor: 3.070

5.  Endogenous bacterial endophthalmitis. Report of a ten-year retrospective study.

Authors:  A A Okada; R P Johnson; W C Liles; D J D'Amico; A S Baker
Journal:  Ophthalmology       Date:  1994-05       Impact factor: 12.079

Review 6.  Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases.

Authors:  Timothy L Jackson; Susannah J Eykyn; Elizabeth M Graham; Miles R Stanford
Journal:  Surv Ophthalmol       Date:  2003 Jul-Aug       Impact factor: 6.048

7.  Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes.

Authors:  Vivian Schiedler; Ingrid U Scott; Harry W Flynn; Janet L Davis; Matthew S Benz; Darlene Miller
Journal:  Am J Ophthalmol       Date:  2004-04       Impact factor: 5.258

8.  Evaluation of outcome of various treatment methods for endogenous endophthalmitis.

Authors:  Tulsi Keswani; Vijay Ahuja; Manish Changulani
Journal:  Indian J Med Sci       Date:  2006-11

9.  An eleven-year retrospective study of endogenous bacterial endophthalmitis.

Authors:  Takashi Nishida; Kyoko Ishida; Yoshiaki Niwa; Hideaki Kawakami; Kiyofumi Mochizuki; Kiyofumi Ohkusu
Journal:  J Ophthalmol       Date:  2015-01-31       Impact factor: 1.909

10.  Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections.

Authors:  Jayanth Sridhar; Harry W Flynn; Ajay E Kuriyan; Darlene Miller; Thomas Albini
Journal:  J Ophthalmic Inflamm Infect       Date:  2013-09-20
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2.  Culture-proven endogenous endophthalmitis: microbiological and clinical survey.

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3.  Klebsiella pneumoniae endogenous endophthalmitis secondary to liver abscess syndrome.

Authors:  Álvaro Fernández-Vega González; Alan R Berger; David R Chow
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4.  Clinical profile and outcome of endogenous endophthalmitis at a quaternary referral centre in south India.

Authors:  Gopal S Pillai; Kiran Krishnankutty Remadevi; V Anilkumar; Natasha Radhakrishnan; Rehna Rasheed; Greeshma C Ravindran
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6.  A 14-Year Retrospective Analysis of Endogenous Endophthalmitis in a Tertiary Referral Center of Southern Thailand.

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Journal:  J Ophthalmol       Date:  2020-12-15       Impact factor: 1.909

7.  Microbial Signatures in The Rodent Eyes With Retinal Dysfunction and Diabetic Retinopathy.

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Journal:  Invest Ophthalmol Vis Sci       Date:  2022-01-03       Impact factor: 4.799

Review 8.  Endogenous Endophthalmitis-The Clinical Significance of the Primary Source of Infection.

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10.  Endogenous endophthalmitis secondary to Burkholderia cepacia: A rare presentation.

Authors:  Raji Kurumkattil; Hemant S Trehan; Kundan Tandel; Vijay K Sharma; Sanjay K Dhar; Tanmay Mahapatra
Journal:  Indian J Ophthalmol       Date:  2020-10       Impact factor: 1.848

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