Analysis on Inpatients With Infectious Keratitis: Causative Organisms, Clinical Aspects and Risk Factors

Hong Park Ju; Bumm Lee Sang

doi:10.3341/jkos.2009.50.8.1152

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Ju and Sang: Analysis on Inpatients With Infectious Keratitis: Causative Organisms, Clinical Aspects and Risk Factors

Original Article

J Korean Ophthalmol Soc 2009;50(8):1152-1166.

Published online: 7 September 2009

DOI: https://doi.org/10.3341/jkos.2009.50.8.1152

Analysis on Inpatients With Infectious Keratitis: Causative Organisms, Clinical Aspects and Risk Factors

Hong Park Ju, MD, Bumm Lee Sang, MD, PhD

Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea

Address reprint requests to Sang Bumm Lee, MD, PhD Department of Ophthalmology, Yeungnam University College of Medicine #317-1 Daemyung-dong, Nam-gu, Daegu 705-717, Korea Tel: 82-53-620-3445, Fax: 82-53-626-5936, E-mail: sbummlee@med.yu.ac.kr

Received 9 February 2009 Accepted 16 June 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

To investigate the epidemiological, microbiological, and clinical characteristics of inpatients with infectious keratitis and also to elucidate risk factors for unimproved visual outcomes.

Methods:

We performed a retrospective chart review of 167 eyes in 167 patients with infectious keratitis hospitalized between January 2005 and December 2007 at Yeungnam University Hospital.

Results:

Keratitis cases were classified into four groups according to etiology: 92 bacterial, 43 herpes virus, 31 fungal, and 1 acanthamoeba. Culture positivity was 44.6% in bacterial keratitis and 22.6% in fungal keratitis, and KOH positivity of fungus was 48.4%. Of all the 55 isolated pathogens, the most commonly isolated microorganisms were S. epidermidis in Gram-positive bacteria, P. aeruginosa in Gram-negative bacteria, and Candida species in fungus. Epidemiologic characteristics such as male gender (59.9%), an age in the seventh decade (24.6%), farming occupation (40.1%), and trauma with vegetable matter (42.5%) were noted. Many fungal and bacterial keratitis cases were characterized by inadequate use of topical steroid when patients initially presented to our clinic. Visual outcomes were poorer in fungal keratitis than they were in other forms of keratitis.

Conclusions:

Risk factors for unimproved visual outcomes included an ulcer exceeding 3 mm in size and a fungal source. Therefore, a strong effort should be made to discern a differential diagnosis in infectious keratitis and to determine the appropriate early treatment for a successful treatment outcome.

Keywords: Bacterial keratitis, Fungal keratitis, Herpetic keratitis, Infectious keratitis, Microbiological test

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Table 1.

Incidence and positive culture rate of infectious keratitis

Culture	No. of cases (%)
Culture	Bacteria	Fungus	[KOH +/-]	Herpes	Amoeba
Positive	41^∗	7^†	[5/2]	0	1
Negative	51	24	[10/14]	43	0
Total	92 (55.1)	31 (18.6	6)	43 (25.7)	1 (0.6)

^∗ Two eyes had mixed bacterial and bacterial infections

^† Four eyes had mixed fungal and bacterial infections.

Table 2.

Cultured microorganisms of infectious keratitis (n=55)

Organisms			No. of isolates (%)
Organisms			N	Subtotal	Total
Bacteria					47 (85.5)
Gram (+) cocci				30 (54.5)
	Staphylococcus species
	Coagulase(−)	S. epidermidis	13
		S. haemolyticus	1
	Coagulase(+)	S. aureus	5
	Streptococcus species
		S. pneumoniae	4
	Enterococcus species
		E. faecalis	7
Gram (−) rod				17 (30.9)
	Pseudomonas species
		P. aeruginosa	5
	Serratia species
		S. marscens	4
		S. liquefaciens	1
	Enterobacter species
		E. aerogens	3
		E. cloacae	1
	Klebsiella species
		K. pnuemoniae	1
	E.coli		1
	Morganella morganii		1
Fungus					7 (12.7)
Yeasts				4 (7.3)
	Candida species
		C. albicans	3
		C. tropicalis	1
Filamentous fungi				3 (5.4)
	Fusarium species		1
	Aspergillus species		1
	Syncephalastrum species		1
Acanthamoeba		A. castellani	1		1 (1.8)

Table 3.

Frequency of isolated organisms in each age group

Organism	Age (year)
Organism	10-19	20-29	30-39	40-49	50-59	60-69	70-79	80-89	Total
Bacteria
S. epidermidis	1	1	1	2	3	3	1	1	13
E. faecalis		1	1		1	3	1		7
S. aureus	1	1		1	1	1			5
P. aeruginosa	1	4							5
Serratia spp.	2	2	1						5
S. pneumoniae					2		2		4
Enterobacter spp.		1				2	1		4
S. haemolyticus				1					1
K. pneumoniae					1				1
E. coli							1		1
Morganella morganii						1			1
Fungus
Candida spp.						1	2	1	4
Fusarium spp.					1				1
Aspergillus spp.						1			1
Syncephalastrum spp.							1		1
Acanthamoeba
A. castellani	1								1
Total	6	10	3	4	9	12	9	2	55

Table 4.

Age and sex distribution of patients with infectious keratitis

Age (year)	No. of cases (%)
	Bacteria (n=92)		Fungus (n=31)		Herpes (n=43)		Amoeba (n=1)		Total (n=167)
	Male	Female	Male	Female	Male	Female	Male	Female	Male	Female
0-9	2					1			2 (1.2)	1 (0.6)
10-19	4	3			3			1	7 (4.2)	4 (2.4)
20-29	5	13		1	1	1			6 (3.6)	15 (9.0)
30-39	7	5							7 (4.2)	5 (3.0)
40-49	7	3	1		3	1			11 (6.6)	4 (2.4)
50-59	13	7	5	1	7	2			25 (15.0)	10 (6.0)
60-69	12	4	7	4	6	8			25 (15.0)	16 (9.6)
70-79	3	2	7	3	3	5			13 (7.8)	10 (6.0)
80-89	2		1	1	1	1			4 (2.4)	2 (1.2)
Total	55	37	21	10	24	19	0	1	100 (59.9)	67 (40.1)

Table 5.

Occupation of patients with infectious keratitis

Occupation	No. of cases (%)
Occupation	Bacteria (n=92)	Fungus (n=31)	Herpes (n=43)	Amoeba (n=1)	Total (n=167)
Farmer	31	26	10		67 (40.1)
Student	17	1	4	1	23 (13.8)
Laborer	16		5		21 (12.6)
Office worker	13		2		15 (9.0)
Housewife	8		5		13 (7.8)
Unemployed	5	2	12		19 (11.4)
Unknown	2	2	5		9 (5.4)

Table 6.

Identified predisposing factors in patients with infectious keratitis

Characteristic		No. of cases^∗
Characteristic		Bacteria (n=92)	Fungus (n=31)	Herpes (n=43)	Amoeba (n=1)	Total
Trauma vector	Vegetable matter	30	18			48
	Grass	14	9			23
	Tree branch	12	7			19
	Thorn	4	2			6
	Contact lens	18		2	1	21
	Water	11	3	1		15
	Soil, Stone	6	4	1		11
	Metal	5	1			6
	Finger	2		1		3
	Cow tail	1	1			2
	Paper	1				1
	Plastic			1		1
	Unknown material	4	1			5
Previous ocular surface disease and surgery	Herpetic keratitis			13		13
	Bullous keratopathy	5	1	1		7
	Persistant epithelial defect	3	1			4
	Phlyctenular keratitis	3				3
	Recurrent erosion syndrome	1	1			2
	Trichiasis	1		1		2
	Atopic conjunctivitis	1				1
	Previous ocular surgery	13		10		23
Systemic disease	Hypertension	11	7	8		26
	Diabetes mellitus	10	2	8		20
	Heart problem	2	1	1		4
	Hepatitis B or C		2	2		4
	Cerebrovascular disease			3		3
	Rheumatic disease	1		2		3
	Asthma	2			1	3
	Atopic dermitits	1				1
	Hyperthyroidism	1				1
	Budd-chiari syndrome	1				1

^∗ Number of eyes which has been identified for predisposing factors such as trauma vector, previous ocular surface disease or surgery, and systemic disease before the time of presentation (Sum of the number of eyes with each subgroup does not add up to 100% because of no history of identified predisposing factors).

Table 7.

Annual and seasonal distribution of infectious keratitis

Characteristic		No. of cases (%)
Characteristic		Bacteria (n=92)	Fungus (n=31)	Herpes (n=43)	Amoeba (n=1)	Total (n=167)
Annual distribution	2005	32	11	18		61 (36.5)
	2006	34	10	16	1	61 (36.5)
	2007	26	10	9		45 (26.9)
Seasonal distribution	Spring (Mar-May)	22	8	12		42 (25.1)
	Summer (Jun-Aug)	25	7	4		36 (21.5)
	Autumn (Sep-Nov)	27	10	14	1	52 (31.1)
	Winter (Dec-Feb)	18	6	13		37 (22.2)

Table 8.

Characteristics of symptom durations and used topical medications prior to patient presentation to our clinic

Characteristic		No. of cases (%)
Characteristic		Bacteria	Fungus	Herpes	Amoeba	Total
Period^∗	≤ 1 week	80	14	24		118 (70.7)
	> 1 week	12	17	19	1	49 (29.3)
	N	92	31	43	1	167 (100)
Topical medication^†	Antibiotics	43	18	12	1	74
	Antifungals		1	2		3
	Antivirals		4	7		11
	Steroids	23	12	11		46
	N^§	50	25	17	1	93
Topical antibiotics^‡	Fluoroquinolone	24	21	9	1	55
	Ofloxacin 0.3%	12	12	5		29
	Levofloxacin 0.5%	8	6	3	1	18
	Gatifloxacin 0.3%, Moxifloxacin 0.5%	4	3	1		8
	Tobramycin 0.3%	24	2	2		28
	Cefmenoxime 0.5%	8	1	1		10
	Gentamycin 0.3%	1	1	1		3
	Erythromycin 2%	1	1	1		3
	N^§	43	18	12	1	74

^∗ Days between symptom onset and patient presentation at our clinic

^† Ocular topical medications used prior to clinical presentation at our clinic

^‡ Topical antibiotics identified prior to clinical presentation at our clinic

^§ N=Number of eyes which has been identified for the use of topical medication and topical antibiotics by patients before, or at the time of presentation (Sum of the number of eyes with each subgroup does not add up to 100% because of overlap of subgroups).

Table 9.

Clinical characteristics of infectious keratitis at initial presentation

Corneal lesion		No. of cases (%)
Corneal lesion		Bacteria (n=92)	Fungus (n=31)	Herpes (n=43)	Amoeba (n=1)	Total (n=167)
Location	Central^∗	40	16	18		74 (44.3)
	Paracentral^†	47	12	17	1	77 (46.1)
	Marginal^‡	4	2	8		14 (8.4)
	Total^§	1	1			2 (1.2)
Size	< 3 mm	71	15	21	1	108 (64.7)
	≥ 3 mm	21	16	22		59 (35.3)
Hypopyon	Yes	15	10	7		32 (19.2)
	No	77	21	36	1	135 (80.8)

^∗ Corneal lesion is located within 2 mm radius from the center of the cornea

^† Corneal lesion is between central and marginal cornea

^‡ Corneal lesion is located within 2 mm from the limbus

^§ Corneal lesion involved nearly total cornea.

Table 10.

Epithelial healing time, corneal perforation time point and duration of hospitalization of infectious keratitis during medical treatment

Days	Bacteria (n=92)			Fungus (n=31)			Herpes (n=43)			Amoeba (n=1)		Total (n=167)
Days	H^∗	P^†	A^‡	H	P	A	H	P	A	H	A	H	A
1-5	35	2	14	1	8		11	3	4			47 (28.1)	18 (10.8)
6-10	36	2	56	1	2	8	14	2	20			51 (30.5)	84 (50.3)
11-15	8	1	15	2	2	11	2	1	10		1	12 (7.2)	37 (22.2)
16-20	2		2	4		5	3		6			9 (5.4)	13 (7.8)
21-25	3		4	3		6	2		2			8 (4.8)	12 (7.2)
26-30	1		1	1		1	4		1			6 (3.6)	3 (1.8)
31-	2			7			1			1		11 (6.6)
Mean± SD	7.9±7.1		9.0±4.5	31.1±29.6		14.9±6.0	11.9±15.0		11.2±5.6	35	11	11.8±15.0	10.7±5.5

^∗ H=healed epithelium, number of patients with epithelial healing

^† P=perforated cornea, number of patients with corneal perforation

^‡ A=duration of hospitalization.

Table 11.

Initial and final best corrected visual acuity and improvement of visual acuity in patients with infectious keratitis

Characteristic		No. of cases (%)
		Bacteria (n=92)		Fungus (n=31)		Herpes (n=43)		Amoeba (n=1)		Total (n=167)
		Initial	Final	Initial	Final	Initial	Final	Initial	Final	Initial	Final
Snellen	≤ LP	5	5	2	12	3	4			10 (6.0)	21 (12.6)
visual acuity	HM	14	4	12	3	11	2			37 (22.2)	9 (5.4)
	<0.1	10	1	3	3	3	7			16 (9.6)	11 (6.6)
	0.1-0.2	17	8	4	5	11	7		1	32 (19.2)	21 (12.6)
	0.3-0.4	12	9	5	3	6	3	1		24 (14.4)	15 (9.0)
	0.5-0.7	11	20	4	1	7	6			22 (13.2)	27 (16.2)
	0.8-1.0	23	45	1	4	2	14			26 (15.6)	63 (37.7)
Improvement	Worsened or unimproved		22		17		12		1		50 (29.9)
of visual	1 line		20		3		7				30 (18.0)
acuity	2 line		12				4				16 (9.6)
	3-4 line		11		5		9				25 (15.0)
	5-6 line		8		1		8				17 (10.2)
	≥ 6 line		19		5		3				27 (16.2)

Table 12.

Methods of therapy in infectious keratitis

Treatment	No. of cases (%)
Treatment	Bacteria (n=92)	Fungus (n=31)	Herpes (n=43)	Amoeba (n=1)	Total (n=167)
Medical treatment	84	18	36	1	139 (83.2)
Amniotic membrane transplantatio	on 8	3	7		18 (10.8)
Conjunctival flap		5			5 (3.0)
Evisceration		5			5 (3.0)

Table 13.

Prognostic factors for unimproved visual outcome in infectious keratitis (univariate analysis)

Factor	Incidence		OR^†	95% CI^‡	p-value
Factor	No. of patients	%^∗	OR^†	95% CI^‡	p-value
Gender
Female	67	23.9	1.00
Male	100	36.0	1.79	0.28~1.12	0.099^#
Age
< 60 years	97	22.7	1.00
≥ 60 years	70	42.9	2.56	1.31~5.00	0.006^Ⅱ
Previous ocular surface disease
No or unknown	146	30.0	1.00
Yes	21	33.3	1.17	0.59~2.32	0.659
Previous ocular surgery
No or unknown	144	29.9	1.00
Yes	23	39.1	1.51	0.61~3.75	0.375
Systemic disease
No or unknown	108	36.1	1.00
Yes	59	22.0	0.50	0.24~1.04	0.450
Ocular trauma history
No or unknown	54	33.3	1.00
Yes	113	30.0	0.86	0.43~1.70	0.660
Use of steroid eyedrops
No or unknown	121	32.3	1.00
Yes	46	28.3	0.82	0.40~1.75	0.621
Symptom duration
≤ 1 week	118	27.1	1.00
> 1 week	49	40.8	1.85	0.92~3.73	0.064^#
Location
Others	93	30.1	1.00
Central	74	32.4	1.14	0.58~2.15	0.580
Size
< 3 mm	108	22.2	1.00
≥ 3 mm	59	47.5	3.16	1.60~6.26	0.001^Ⅱ
Hypopyon
No	135	29.6	1.00
Yes	32	37.5	1.43	0.64~3.19	0.389
Epithelial healing time
≤ 10 days	102	30.4	1.00
> 10 days	65	32.2	1.09	0.56~2.14	0.980
Initial BCVA^§
≥ 0.1	104	26.0	1.00
< 0.1	63	39.7	1.84	0.96~3.66	0.065^#
Culture
Negative	112	29.5	1.00
Positive	55	34.5	1.26	0.64~2.52	0.506
Organism
Others	136	25.7	1.00
Fungus	31	41.9	3.50	1.57~7.84	0.002^Ⅱ

^∗ Percentage of eyes which had unimproved visual outcome

^† OR=odds ratio

^‡ CI=confidence interval

^§ BCVA=best corrected visual acuity

^Ⅱ p<0.05

^# p<0.10.

Table 14.

Prognostic factors for unimproved visual outcome in infectious keratitis (multivariate analysis)

Factor	OR^∗	95% CI^†	p-value
Male gender	1.67	0.78-3.48	0.190
Age more than 60 years	1.68	0.77-3.63	0.187
Symptom duration more than 1 week	1.05	0.47-2.32	0.914
Size more than 3 mm	2.38	1.12-5.06	0.024^§
Initial BCVA^‡ less than 0.1	1.12	0.52-2.41	0.769
Fungal keratitis	2.44	1.01-5.91	0.048^§

^∗ OR=odds ratio

^† CI=confidence interval

^‡ BCVA=best corrected visual acuity

^§ p<0.05.

Table 15.

Comparison of microbial isolates of infectious keratitis with the results of other studies

Study	Srinivasan⁶	Laspida¹³	Toshida⁹	Keay²⁶	Hahn¹⁸	This study
Date	1994	1988-2001	1999-2003	2001-2003	1995-2000	2005-2007
Nation	India	Paraguay	Japan	Australia	Korea	Korea
No. of microbial isolates	325	639	102	112	544	55
Bacteria	51.4%	67.3%	93.1%	90.2%	81.3%	85.5%
Gram positive bacteria	40.6%	-	75.5%	64.3%	31.8%	54.5%
Gram negative bacteria	10.8%	-	17.6%	25.9%	49.4%	30.9%
Fungus	47.7%	32.7%	5.9%	6.2%	15.1%	12.7%
Amoeba	0.9%	-	1.0%	3.6%	3.6%	1.8%

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