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Shri Bhagwan Mahavir A brief summary of management of endophthal- injections); trauma; endogenous; contiguous
Vitreoretinal Services, mitis is being highlighted with pertinent informa- spread (corneal ulcer, scleral abscess)
Sankara Nethralaya tion regarding the relevant and most commonly
b Onset: acute, sub-acute or chronic
used antibiotics. Endophthalmitis, in any clinical
Correspondence to presentation, should be considered as an ophthal- c Progression: rapid or gradual
Aditya Verma, mic emergency. Tailored approach to each individ-
d Symptoms: decreased vision, pain, redness,
Consultant, ual patient is warranted.
Shri Bhagwan Mahavir floaters, lacrimation, photophobia
Vitreoretinal Services, Definition: Inflammation of intraocular fluids and
e Systemic illness: uncontrolled diabetes, chronic
Sankara Nethralaya. tissues (Fig. 1), which can be either infectious or
Email: drav@snmail.org
debilitating illness, endocarditis, liver abscess,
sterile.
long-term hospitalization
Classification (based on etiology): 1
a Exogenous ( post-operative [most common],
Nuggets
traumatic, local spread). The work up of a patient with endophthalmitis
b Endogenous (metastatic): hematogenous spread. should be considered as utmost emergency, since
the highly virulent organisms and their toxins can
c Non-infectious (sterile uveitis, lens induced/ damage the ocular structures within hours.
phaco-anaphylactic, sympathetic ophthalmia).
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1. The most common etiology of
endophthalmitis is post-operative (cataract 2. Work up
extraction and bleb related endophthalmitis).2
2. The acute and fulminant presentations of a Initial ophthalmic assessment
endophthalmitis should be differentiated from i Initial visual acuity (unaided and with cor-
Toxic Anterior Segment Syndrome (TASS). rection, both eyes)
ii Examination of the lids and adnexa
Figure 1. Clinical picture of (a) post-operative endophthalmitis and (b) filtering bleb-related
endophthalmitis.
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Preferred practice pattern
c Inform the concerned medical staff (surgeon, vi Sterile cotton tip applicators
nursing staff, operation theatre) vii Protective hand gloves
d Inform the primary surgeon (in case of in- viii Lighting source (indirect ophthalmoscope
house infection) ( preferred)/slit lamp)
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Figure 2. Instruments required for anterior chamber/vitreous tap and intravitreal injections.
Figure 3. The sterile test tube container used to transfer the sample (aqueous/vitreous/others) to
microbiology laboratory.
ix Proparacaine, povidone iodine eye drops vii Plan the site of tap based on AC depth, visi-
bility, ease of access and the area of
x Eye patch
maximum exudation.
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Preferred practice pattern
xii Administer the intravitreal antibiotics (as per Drugs and treatment protocols (Table 2)
the initial smear report/empirical if a delay is
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expected in reporting) and patch with topical Primary objectives of endophthalmitis
povidone iodine. management are eradication and control of
xiii The patch should be removed after half an infection, management of complications and
restoration of vision, in that order.
hour and topicals started.
Table 2 Outlines of management of endophthalmitis based on etiology (tailored approach warranted). 7,8
Type Most common Initial systemic Initial intravitreal Need for Need for IOL
pathogens treatment antibiotic vitrectomy removal
(absolute
indication)
Acute Coagulase negative I/V** or oral V+C+D* Yes, early if May be
post-cataract Staphylococci (70%), third-generation severe
surgery other Gram-positive cephalosporin/ cases/
(25%), Gram-negative fluoro-quinolones fulminant or
(fulminant) fungal
infection
Sub-acute Propionibacterium No V (capsular bag) May be Yes
cataract acnes and D needed
surgery (Intravitreal)
Post Coagulase-negative Fluoro-quinolones or V+C+D* Rarely (if it No
intravitreal Staphylococci, viridians equivalent is severe)
injection Streptococci
Filtering bleb Streptococci, I/V** or oral 3rd V+C+D* Most cases, No
related Hemophilus influenae generation early in
cephalosporin/ fulminant
fluoro-quinolones cases
Post traumatic Bacillus cereus, I/V** Vancomycin V+C+D* Most cases, Varies (always
Coagulase negative and either (Amphotericin/ early in with fungal
Staphylococci, Fungi third-generation Voriconazole with fulminant etiology)
(vegetative matter) cephalosporins/ no steroids (if cases
fluoro-quinolones fungal))
Endogenous Staphylococcus aureus, I/V** or oral broad V+C+D* (or Mostly No
bacterial Streptococci, spectrum antibiotics amikacin) needed
Gram-negative bacilli (e. tailored to systemic
g. Klebsiella) infection
Endogenous Aspergillus, Fusarium Oral voriconazole Voriconazole or Yes Yes
fungal (I/V** if fulminant) amphotericin
(mould)
Endogenous Candida species Oral voriconazole Voriconazole or Yes if vitritis Yes
candida amphotericin
Chronic post Aspergillus species, Oral voriconazole; Voriconazole or Yes Yes
operative Candida species, rarely I/V** amphotericin B
fungal Curvularia lunata voriconazole or
Amphotericin B (highly
toxic), or oral
fluconazole
*V, vancomycin; C, ceftazidime/cephazoline, D, dexamethasone. (Most commonly used initial empirical drugs based on
clinical presentation.)
**I/V, intravenous
64 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 |
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Table 3 Intravitreal drugs, doses and preparation techniques of most commonly used antibiotics. 9,10
S. Name of Intravitreal Salient steps for preparation Remarks Frequency of
no. antibiotic dose (1 ml tuberculin syringe) (if any) repeat
(available (per 0.1 ml) injections**
dose)
1 Vancomycin 1 mg 1. Add 5 ml distilled water Do not mix with 72 hours
(500 mg) 2. Mix well (shake)—100 mg/ml other drugs, as it
3. Take 0.1 ml of drug solution gets precipitated
4. Dilute with 0.9 ml of sterile water (single dilution)
5. Mix well (moving air bubble up
and down)
6. Discard 0.9 ml
7. Use 0.1 ml for injection
2 Ceftazidime 2.25 mg 1. Add 4 ml of distilled water Can be mixed 48–72 hours
(1000 mg) (250 mg/ml) with steroid
2. Follow Steps 2–7 as in row 2 preparation in the
Use dexamethasone in Step 4 if same syringe
indicated (single dilution)
3 Amikacin 125 µg 1. Take 0.1 ml solution (12.5 mg/ Can be mixed 24–48 hours
(250 mg/2 ml) (previously 0.1 ml) with steroid
recommended 2. Follow steps 4–6 as in row 2 preparation in the
400 µg was 3. Take 0.1 ml solution same syringe
highly retinal 4. Take 0.9 ml of distilled water (Double dilution)
toxic) again and mix well
Can be mixed with dexamethasone
for final concentration (step 4)
4 Gentamycin 80 µg 1. Take 0.2 ml of Gentamycin (8 mg/ Extreme retinal 72–96 hours
(80 mg/2 ml) 0.2 ml) toxicity, rarely
2. Dilute with 0.8 ml of distilled used now (double
water dilution)
3. Mix well
4. Discard 0.9 ml of solution
5. Dilute with 0.9 ml of distilled
water and mix well
6. Discard 0.9 ml of solution
7. Use 0.1 ml for injection
5 Amphotericin 5 µg 1. Add 10 ml of distilled water and Phototoxic, ?? 48 hours
B (50 mg) mix well (5 mg/ml) dispensed in a
2. Follow steps 2–6 as in row 2 brown (double
5. Again take 0.1 ml of solution and dilution)
add 0.9 ml distilled water and mix
well
6. Discard 0.9 ml of solution
7. Use 0.1 ml for injection
6 Voriconazole 50–100 µg 1. Add 19 ml of distilled water and (One and a half 48 hours
(200 mg) mix well (10 mg/ml) dilution)
2. Take 0.1 ml solution and add
0.9 ml distilled water and mix well
2. Discard 0.5 ml of solution
5. Take 0.5 ml of sterile water and
mix well (air bubble)
6. Discard 0.9 ml of solution
7. Use 0.1 ml for injection
7 Ciprofloxacin 100 µg Directly loaded from the sterile vial Not to be loaded 12 hours
(200 mg/ and injected intraviteally, 0.05 ml from the topical
100 ml) preparation; since
half-life is approx.
6 hours, daily
injections are
needed
8 Moxifloxacin 200 µg Take 0.05 ml of 0.5% moxifloxacin Directly taken 12 hours
(preservative free) from topical
preparations
under sterile
conditions
9 Imipenem 50–100 µg 1. Dilute with 100 ml of distilled Data not
(250 mg) water available
2. Take 0.2 ml (0.5 mg)
Continued
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Table 3 Continued
S. Name of Intravitreal Salient steps for preparation Remarks Frequency of
no. antibiotic dose (1 ml tuberculin syringe) (if any) repeat
(available (per 0.1 ml) injections**
dose)
3. Dilute with 0.3 ml sterile water ??24–48
4. Inject 0.05 ml hours
10 Piperacillin/ 225 µg Data not available Data not
tazobactam available
(2.25 g)
11 Carbenicillin 2000 µg Data not available Data not
(1 g) available
12 Ticarcillin 3000 µg Data not available Data not
(with available
clavulanate
(3.1 g)
13 Aztreonam 100 µg Data not available 12 hours
**All are in Phakic, nonvitrectomized eyes. Caution must be taken in interpreting the need for repeat
intravitreals. Vitrectomized/aphakic eyes need more frequent injections whereas inflamed eyes have varied
requirements.
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Caution should be taken to avoid mixing of drugs which may get precipitated, for eg, vancomycin and
ceftazidime in a same syringe.
vi Labels for the antibiotics (for patient details), i In cases of subacute endophthalmitis with sus-
to be used later. pected Propionibacterium acnes colonies seques-
tered in the capsular bag, a 27G needle can be
b. Procedure directly introduced from the opposite quadrant at
the limbus, gently lifting the anterior capsule and
i In continuation to the steps mentioned in 3b (i–vi).
aspirating the sequestered organisms.
ii Prepare the intravitreal injections fresh main-
ii The intravitreal antibiotics can also be directly
taining adequate sterility (Table 3).
injected in the capsular bag behind the IOL
iii Mix the drug thoroughly with a small air after gently lifting the anterior capsule with
bubble to dissolve the antibiotic with solvent. the needle, taking care to inject small quan-
tities and avoiding sudden injection (to prevent
iv Remove the air completely and dispose the rupture of the capsular bag).
excess drug to prepare the required amount.
v In phakic/ pseudophakic eye: with 30G needle Nuggets
directed toward the mid-vitreous cavity, enter 1. Initial broad spectrum empirical therapy is
through pars plana ( pars plicata in children less given based on the clinical evaluation or if a delay
than 1 year age) and inject the required amount in the initial smear report is anticipated or if the
of drug (loaded in 1 ml tuberculin syringe). initial report is equivocal. This should be modified
immediately based on the microbiology study
vi In aphakic eye: limbal entry with antibiotic results.
injected into the vitreous cavity through the 2. The direct aspiration of capsular bag material
anterior chamber. increases yield of organisms (e.g.
Propionibacterium acnes).
vii Apply cotton tip applicator to the injection
site, examine the fundus and check eye pres-
sure digitally.
5. Vitreous tap
viii AC paracentesis may be needed if the IOP is
high and a second injection is needed. a To be avoided (or performed with utmost care)
in phakic non-vitrectomized eyes.
ix Label the antibiotic vial and store in refriger-
ator (do not freeze). b Indicated in recurrent/non-resolving endoph-
thalmitis in a vitrectomized eye.
x To be used within 3–5 days of preparation
(either for topical or repeat intravitreals). c Use a sterile 27G needle with 2 cc or 5 cc syringe,
enter through pars plana, aspirate gently (0.2–
c. In the bag technique 4 0.3 ml approximately), avoiding forceful suction.
66 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 |
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Table 4: Most common drugs used in endophthalmitis and their clinical profile 11,12
Drug MOA Spectrum DOC for Emerging resistance
Cephalosporin Inhibit peptide Gram −ve cocci, Gram –ve Acinetobacter,
Ceftazidime crosslinking of P. aeruginosa Anaerobes Enterococci
Ceftriaxone polysaccharide Serratia (not active against
Cefazolin chains of anaerobes), Gram +ve
peptidoglycan; bacilli, Gram –ve bacilli,
affects protiens in Enterobacter, E. coli
cell membrane Klebsiella, proteus,
H. influenzae,
Gram +ve coci, Gram −ve
bacilli, E. coli, Proteus,
H. influenza
Glycopeptide Inhibits the Gram +ve cocci, MRSA, MRSA Enterococci
Vancomycin synthesis of MDR Staph epidermidis,
precursor units of Clostridium,
bacterial cell wall; Corynebacterium
inhibits RNA diptheroids
synthesis
Aminoglycoside Blocks protein Second choice for Gram –ve Gram −ve Gram negative Bacilli
Amikacin synthesis by bacilli, Pseudomonas,
binding to 30S Enterobacter, klebsiella,
subunit of E. coli, Serratia
ribosomes
Fluoroquinolones Topoisomerase II Broad spectrum against Gram −ve Enterococcus
Ciprofloxacin inhibitors aerobic GPB, GNB, organisms faecalis,
Moxifloxacin Pseudomonas, Gram +ve Streptococcus
Streptococci, Staph. organisms pyogenes
epidermidis, Actinomyces, Multi-drug resistant
Nocardia sp. MTB, nososcomial
Gram –ve, Gram +ve, Gram –ve
anaerobes
Polyenes Binds irreversible Aspergillus sp., Cryptococcus Individual strains of
Amphotericin-B to ergosterol in cell Fusarium sp., neoformans Candida albicans,
membrane which Demateciuos fungi Candida tropicalis,
increases (Curvilaria, Bipolaris, Candida parapsilosis
membrane Alternaria etc), Candida Fusarium sp. and
permeability Sporothrix schenckii
Triazoles Inhibition of Fusarium, candida, yeasts, Fluconazole Aspergilus fumigatus
Voriconazole ergosterol filamentous fungi, resistant
synthesis which Scedosporium candidemia
increases apiospermum , Acremonium
membrane
permeability
Carbapenem Inhibit cell wall Gram +ve, Gram –ve, Pseudomonas MRSA, pseudomonas
Imipenem synthesis anaerobes aeruginosa, sp.,
Ticarcillin Prevent Gram –ve bacteria Enterococci Acinetobacter
cross-linking of Pseudomonas baumannii, some
peptidoglycan aeruginosa. Acinetobacter spp.,
during cell wall Bacteroides fragilis,
synthesis and Enterococcus
faecalis
Enterobacteceae,
H. influenzae
MOA, mechanism of action; DOC, drug of choice; MRSA, methicillin-resistant Staphylococcus aureus; MDRS,
multi-drug-resistant Staphylococcus; GPB, Gram-positive bacilli; GNB, Gram-negative bacilli
Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 67
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Figure 4. Commonly used solid and liquid culture media for inoculation of the samples.
Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 69
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broth and kept at room temperature, 25–30°C is advised, and contra-indicated in fungal
(with label). The remaining sample can also be endophthalmitis.
capped onto the needle and kept in the
refrigerator at 4°C compartment to be trans- Acknowledgements
ported at the earliest (for PCR and making The authors thank Dr. Muna Bhende, Dr. Vikram
smears). Koundanya, Dr. Vishvesh Agarwal from Shri Bhagwan
Mahavir Vitreoretinal Services. They also thank entire
team from Shri Bhagwan Mahavir Vitreoretinal
Nuggets Services, Jadhavbai Nathmal Singhvee Glaucoma
1. The initial smear report should be obtained Services and L&T Microbiology Research Centre.
at the earliest (within 45 minutes)
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How to cite this article Verma A, Muralidharan V, Nigam E. Endophthalmitis: Current Trends, Drugs and Protocols, Sci
J Med & Vis Res Foun 2015;XXXIII:61–70.
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