Clinical Analysis of Staphylococcus aureus Keratitis according to Methicillin-resistance

Hwan Ahn Jang; Lee Sang-Bumm

doi:10.3341/jkos.2017.58.8.885

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Jang and Sang-Bumm: Clinical Analysis of Staphylococcus aureus Keratitis according to Methicillin-resistance

Original Article

J Korean Ophthalmol Soc 2017;58(8):885-895.

Published online: 8 September 2017

DOI: https://doi.org/10.3341/jkos.2017.58.8.885

Clinical Analysis of Staphylococcus aureus Keratitis according to Methicillin-resistance

Hwan Ahn Jang, M.D., Lee Sang-Bumm, M.D., 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 Hospital, #170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea Tel: 82-53-620-3445, Fax: 82-53-626-5936 E-mail: sbummlee@ynu.ac.kr

* Conflicts of Interest: The authors have no conflicts to disclose.

Received 16 March 20172 May 2017 Accepted 18 July 2017

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

This study analyzed clinical characteristics of Staphylococcus aureus keratitis according to methicillin-resistance.

Methods

The authors performed a retrospective chart review of 46 isolates in 46 eyes with Staphylococcus aureus keratitis that were followed up for more than 2 months between January 1998 and December 2014. Comparative analyses of the epidemiology, predisposing factors, initial clinical manifestations, antibiotics susceptibility and clinical outcome between methicillin-resistant Staphylococcus aureus (MRSA) keratitis and methicillin-sensitive Staphylococcus aureus (MSSA) keratitis were performed. Risk factors of poor visual outcome were analyzed using logistic regression analysis.

Results

Among 46 eyes, MRSA was present in 15 eyes (33%) and MSSA in 31 eyes (67%). Male (61%) and older than 60 year-old group (48%) were common. Ocular surface disease/ocular surgery history and trauma were more common as a predisposing factor. Vancomycin was 100% sensitive to both the MRSA and MSSA groups. Antibiotics susceptibility to MRSA was significantly low in the oxacillin (0%), gentamicin (13.3%) and trimethoprim/sulfamethoxazole (53.3%) groups. Sensitivity to fluoroquinolone was 81.3% (MRSA 64.3% vs. MSSA 94.4%; p = 0.064). There were no differences in early corneal findings between the groups. The ratio of BCVA 0.5 or more was 24.4% initially and increased to 44.4% after treatment among all eyes (p = 0.046). Risk factors for poor visual outcomes included a BCVA less than 0.1 at initial evaluation (p = 0.033).

Conclusions

Among eyes with Staphylococcus aureus keratitis, 33% were MRSA. The ratio of BCVA 0.5 or more increased after treatment among all eyes. There were no differences between MRSA and MSSA eyes in terms of epidemiology, predisposing factors, initial clinical manifestations or clinical outcome, except for antibiotic susceptibility. For positive patient outcomes, a treatment approach considering methicillin-resistance as well as various factors affecting clinical course is recommended.

Keywords: Antibiotics susceptibility, Clinical outcome, Methicillin-resistant, Methicillin-sensitive, Staphylococcus aureus keratitis

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Table 1.

Comparison of demographics and clinical course of keratitis caused by MRSA and MSSA

		No. of cases (%)
Characteristics	All cases (n = 46)	MRSA (n = 15)	MSSA (n = 31)	p-value
Gender (M/F)	28/18	9/6	19/12	0.933^*
Age (year)				0.855^†
≥60	22 (47.8)	7 (46.7)	15 (48.4)
40-59	15 (32.6)	5 (33.3)	10 (32.2)
20-39	5 (10.9)	1 (6.7)	4 (12.9)
<20	4 (8.7)	2 (13.3)	2 (6.5)
Symptom to treatment interval (days)	7.7 ± 7.7	6.5 ± 7.5	8.4 ± 7.9	0.444^‡
Duration of hospitalization (days) (n = 37)^§				0.061^†
<7	4 (10.8)	2 (20.0)	2 (7.4)
7-14	28 (75.7)	5 (50.0)	23 (85.2)
>14	5 (13.5)	3 (30.0)	2 (7.4)
Seasonal distribution				0.802^†
Spring (March-May)	12 (26.1)	5 (33.3)	7 (22.6)
Summer (June-August)	13 (28.3)	3 (20.0)	10 (32.2)
Autumn (September-November)	10 (21.7)	3 (20.0)	7 (22.6)
Winter (December-February)	11 (23.9)	4 (26.7)	7 (22.6)
Average follow up period (months)	13.3 ± 21.5	16.7 ± 21.5	11.7 ± 21.7	0.464^‡

Values are presented as mean ± SD unless otherwise indicated. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus; M = male; F = female.

^* Chi-square test.

^† Fisher’s exact test.

^‡ Independent t-test.

^§ Patients were excluded who were not admitted (MRSA 5, MSSA 4).

Table 2.

Predisposing factors for MRSA and MSSA keratitis

		No. of cases (%)^‡
Predisposing factors	All cases (n = 46)	MRSA (n = 15)	MSSA (n = 31)	p-value
Ocular surface disease & ocular surgery history	18 (39.1)	7 (46.7)	11 (35.5)	0.530^*
Trauma	17 (37.0)	5 (33.3)	12 (38.7)	0.575^*
Systemic comorbidities^§	14 (30.4)	7 (46.7)	7 (22.6)	0.170^†
Previous use of topical antibiotics	12 (26.1)	3 (20.0)	9 (29.3)	0.723^†
Previous use of topical steroid	7 (15.2)	4 (26.7)	3 (9.7)	0.193^†
Contact lens wear	3 (6.5)	1 (6.7)	2 (6.5)	0.978^†
Non-identifiable	3 (6.5)	1 (6.7)	2 (6.5)	1.000^†

Values are presented as n (%) unless otherwise indicated. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus.

^* Chi-square test.

^† Fisher’s exact test.

^‡ Total can be greater than 100% because of some patients with multiple predisposing factors.

^§ Systemic comorbidities include diabetes (MRSA 4, MSSA 2), hypertension (MRSA 5, MSSA 5), thyroid disease (MRSA 1), and hepatitis (MRSA 1).

Table 3.

Initial clinical findings of MRSA and MSSA keratitis

		No. of cases (%)
Clinical findings	All cases (n = 46)	MRSA (n = 15)	MSSA (n = 31)	p-value^*
Location				0.191
Central^†	31 (67.4)	8 (53.3)	23 (74.2)
Peripheral^‡	15 (32.6)	7 (46.7)	8 (25.8)
Infiltration size (mm²)				0.169
Small (<5)	33 (71.7)	13 (86.7)	20 (64.5)
Large (≥5)	13 (28.3)	2 (13.3)	11 (35.5)
Hypopyon				0.497
Yes	13 (28.3)	3 (20.0)	10 (32.3)
No	33 (71.7)	12 (80.0)	21 (67.7)

Values are presented as n (%) unless otherwise indicated. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus.

^* Fisher’s exact test.

^† Corneal lesion is located within 1/2 radius from the center of the cornea.

^‡ Corneal lesion is located within 1/2 radius from the limbus.

Table 4.

Antibiotics susceptibility of MRSA and MSSA isolates for keratitis

Antibiotics		Susceptibility (%, n1/n2^*)		^†
Antibiotics	All cases (n = 46)	MRSA (n = 15)	MSSA (n = 31)	p-value^†
Oxacillin	67.4 (31/46)	0.0 (0/15)	100.0 (31/31)	0.000
Penicillin	13.3 (6/45)	0.0 (0/14)	19.4 (6/31)	0.077
Cephalosporin	69.4 (25/36)	8.3 (1/12)	100.0 (24/24)	0.000
Ciprofloxacin	76.9 (20/26)	50.0 (5/10)	93.8 (15/16)	0.018
FQ (3rd & 4th generation)	100.0 (6/6)	100.0 (4/4)	100.0 (2/2)	1.000
Gentamicin	54.3 (25/46)	13.3 (2/15)	74.2 (23/31)	0.000
Erythromycin	68.2 (15/22)	28.6 (2/7)	86.7 (13/15)	0.006
Clindamycin	80.0 (8/10)	50.0 (2/4)	100.0 (6/6)	0.053
Tetracycline	77.8 (7/9)	50.0 (2/4)	100.0 (5/5)	0.073
TMP/SMX	75.6 (34/45)	53.3 (8/15)	86.7 (26/30)	0.026
Teicoplanin	95.6 (43/45)	86.7 (13/15)	100.0 (30/30)	0.755
Linezolid	100.0 (22/22)	100.0 (7/7)	100.0 (15/15)	1.000
Vancomycin	100.0 (46/46)	100.0 (15/15)	100.0 (31/31)	1.000

Values are presented as n (%) unless otherwise indicated. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus; FQ = fluoroquinolone; TMP/SMX = trimethoprim/sulfamethoxazole.

^* ‘n1’ means number of isolates with susceptibility and ‘n2’ means number of tested isolates

^† Fisher’s exact test.

Table 5.

Treatment and clinical outcome of MRSA and MSSA keratitis

		No. of cases (%)
	All cases (n = 46)	MRSA (n = 15)	MSSA (n = 31)	p-value
Number of hospitalized patient	37 (80.4)	10 (66.7)	27 (87.1)	0.127^Π
Modification of antibiotics	11 (23.9)	2 (13.3)	9 (29.0)	0.296^#
Surgical intervention^*	10 (21.7)	1 (6.7)	9 (29.0)	0.132^#
Severe complications^†	6 (13.0)	1 (6.7)	5 (16.1)	1.000^#
Epithelial healing time (days) (n = 40)^‡				0.481^#
<7	10 (25.0)	5 (35.7)	5 (19.2)
8-14	15 (37.5)	5 (35.7)	10 (38.5)
>15	15 (37.5)	4 (28.6)	11 (42.3)
Initial BCVA (Snellen acuity) (n = 45)^§
≥0.5	11 (24.4)	3 (21.4)	8 (25.8)
0.1-0.4	13 (28.9)	5 (35.7)	8 (25.8)
<0.1	21 (46.7)	6 (42.9)	15 (48.4)	0.841^#
Final BCVA (Snellen acuity) (n = 45)^§
≥0.5	20 (44.4)	6 (42.9)	14 (45.2)
0.1-0.4	9 (20.0)	2 (14.2)	7 (22.6)
<0.1	16 (35.6)	6 (42.9)	10 (32.2)	0.771^#
Clinical outcome^** (n = 45)^§
Good	20 (44.4)	6 (42.9)	14 (45.2)
Moderate	7 (15.6)	2 (14.2)	5 (16.1)
Poor	18 (40.0)	6 (42.9)	12 (38.7)	1.000^#

Values are presented as n (%) unless otherwise indicated. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus; BCVA = best corrected visua acuity.

^* Surgical interventions include amniotic membrane transplantation (AMT) (AMT only 3 eyes, AMT with excimer laser phototherapeutic kera-tectomy 1 eye, AMT and evisceration 1 eye), conjunctival flap (conjunctival flap only 1 eye, conjunctival flap and evisceration 1 eye), and evis-ceration only 3 eyes.

^† Severe complications include corneal perforation and/or endophthalmitis with surgical interventions of evisceration (MRSA 1, MSSA 4) and conjunctival flap (MSSA 1).

^‡ Six eyes were excluded if severe complications occurred (1 case for MRSA and 5 cases for MSSA).

^§ One eye was excluded if the record for final BCVA was missed

^Π Chi square test

^# Fisher’s exact test

^** Good: final BCVA ≥ 0.5, and no complications or surgical intervention, and no decrease in visual acuity (VA); Moderate: final BCVA 0.1-0.4, and no complications or surgical intervention, and no decrease in VA; Poor: final BCVA < 0.1, or decrease in VA, or complication of infection, or requiring surgical intervention.¹¹

Table 6.

Multivariate logistic regression analysis for risk factors of poor visual outcome in Staphylococcus aureus keratitis

Factor		Poor visual outcome^*
Factor	Odds ratio	95% CI	p-value^†
Age ≥ 60 years	0.82	0.11-6.27	0.846
Systemic disease (+)	1.58	0.17-15.20	0.691
Central corneal lesion	0.37	0.03-4.71	0.443
Size of epithelial defect ≥5 mm²	3.01	0.17-52.91	0.452
Hypopyon (+)	8.82	0.62-124.73	0.107
Initial BCVA less than 0.1	16.82	1.26-224.03	0.033
Epithelial healing time ≥10 days	3.55	0.46-27.49	0.226

CI = Confidence interval; BCVA = best corrected visual acuity.

^* Poor visual outcome (n = 18) means the eyes which had poor visual outcome of the final best corrected visual acuity of 0.1 or less.

^† Multivariate logistic regression analysis was performed for the factors which had p-value less than 0.1 in univariate logistic regression analysis.

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