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Staphylococcus Aureus: Keratitis: A Review of Hospital Cases
Staphylococcus Aureus: Keratitis: A Review of Hospital Cases
Cases
Sherine Jue Ong1, Yhu-Chering Huang2,3, Hsin-Yuan Tan1,3, David H. K. Ma1,3, Hsin-Chiung Lin1,3,
Lung-Kun Yeh1,3, Phil Y. F. Chen1,3, Hung-Chi Chen1,3, Chih-Chun Chuang4,5, Chee-Jen Chang6,7,
Ching-Hsi Hsiao1,3*
1 Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taiwan, 2 Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung
Memorial Hospital, Linkou, Taiwan, 3 College of Medicine, Chang Gung University, Taoyuan, Taiwan, 4 Department of Ophthalmology, Yuan-Sheng Hospital, Changhua,
Taiwan, 5 Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan, 6 Graduate Institute of Clinical Medical Science, Chang Gung University,
Taoyuan, Taiwan, 7 Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. The study
aimed to characterize the patient demographics, clinical features, antibiotic susceptibility, and clinical outcomes of keratitis
caused by S. aureus, and to make a comparison between MRSA and methicillin-sensitive S. aureus (MSSA) isolates.
Methodology/Principal findings: Patients (n = 59) with culture-proven S. aureus keratitis treated in Chang Gung Memorial
Hospital between January 1, 2006, and December 31, 2010, were included in our study. Patients demographic and clinical
data were retrospectively reviewed. Twenty-six MRSA (44%) and 33 MSSA (56%) isolates were collected. The MRSA keratitis
was significantly more common among the patients with healthcare exposure (P = 0.038), but 46.2% (12/26) of patients with
MRSA keratitis were considered to have community-associated infections. All isolates were susceptible to vancomycin.
MRSA isolates were significantly more resistant to clindamycin, erythromycin, and sulfamethoxazole/trimethoprim. Ocular
surface disease was a significant risk factor for MRSA keratitis (P = 0.011). Visual outcome did not differ significantly between
the MRSA and MSSA groups. However, age (B = 0.01, P = 0.035, 95% confidence interval [CI]: 0.0010.019) and visual acuity at
presentation (B = 0.749, P,0.001, 95% CI: 0.5730.926) were significantly correlated with visual outcome.
Conclusions/Significance: Ocular surface disease is an important predisposing factor for S. aureus keratitis, especially for
MRSA infections. Advanced age and poor visual acuity at presentation are important prognostic indicators for poor visual
outcome in S. aureus keratitis. Oxacillin resistance may not be a significant prognostic indicator.
Citation: Ong SJ, Huang Y-C, Tan H-Y, Ma DHK, Lin H-C, et al. (2013) Staphylococcus aureus Keratitis: A Review of Hospital Cases. PLoS ONE 8(11): e80119.
doi:10.1371/journal.pone.0080119
Editor: Suzanne Fleiszig, UC Berkeley, United States of America
Received May 28, 2013; Accepted September 29, 2013; Published November 11, 2013
Copyright: 2013 Ong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported in part by Chang Gung Memorial Hospital, Linkou, Taiwan, grant number CMRPG381511. No additional external funding was
received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: hsiao.chinghsi@gmail.com
Introduction
Staphylococcus aureus is one of the most important pathogens in
bacterial keratitis, a vision-threatening disease. [1,2] Although the
incidence of S. aureus keratitis varies worldwide, the increasing
trend of resistance to certain antibiotics makes this condition an
important global healthcare issue. [35]
Methicillin-resistant S. aureus (MRSA) is a term used to
describe strains of S. aureus that are resistant to all b-lactam
antibiotics. The emergence of MRSA strains is clinically
relevant because their resistance to multiple antibiotics limits
treatment options for MRSA infection. Formerly considered a
nosocomial pathogen, MRSA has reportedly increased in
prevalence among otherwise healthy patients without identified
risk factors. These infections are described as communityassociated MRSA (CA-MRSA) infections. In Western countries, the most common manifestations of ocular MRSA
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MRSA Keratitis
Methods
Ethics
Our study adhered to the guidelines of the Declaration of
Helsinki, and was approved by the Institutional Review Board of
CGMH, which granted a waiver of consent because patient
anonymity was maintained by the data source.
Statistical analysis
Participants and procedures
Results
Demographics (Table 1)
Fifty-nine cases of S. aureus keratitis were identified, including 26
(44%) caused by MRSA and 33 (56%) caused by MSSA. No
significant difference in sex, age, or laterality was observed
between the MRSA and MSSA cases. The rate of healthcareassociated infection was significantly higher in the MRSA group
(14/26, 53.8%) than that in the MSSA group (9/33, 27.3%;
P = 0.038). There was no significant difference in the mean followup period between the MRSA (1.65 6 1.41 years) and MSSA
cases (1.5761.69 years; P = 0.388).
Characteristics
MRSA (n = 26)
MSSA (n = 33)
P value
55 (283)
56 (183)
0.743
Gender: M/F
15/11
17/16
0.636
Eye: R/L/B
9/16/1
20/13/0
0.084*
Community associated/
Healthcare-associated: n. (%)
12 (46.2)/
14 (53.8)
24 (72.7)/
9 (27.3)
0.038
MRSA Keratitis
Clinical findings
MRSA (n = 26)
No. (%)
MSSA (n = 33)
No. (%)
Location
P value
0.01
Antibiotics
MRSA (n = 26)
No. (%)
MSSA (n = 33)
No. (%)
P value
0 (0)
31 (93.9)
,0.001
0 (0)
29 (87.9)
,0.001
Central
16 (61.5)
7 (21.2)
Clindamycin
Paracentral
6 (23.1)
13 (39.4)
Erythromycin
Peripheral
4 (15.4)
13 (39.4)
0.133*
Small (,2)
3 (11.5)
12 (36.3)
Medium (2,6)
20 (77.0)
18(54.6)
Large (.6)
3 (11.5)
3 (9.1)
Hypopyon
5 (19.2)
8 (25.0)
0.6
Oxacillin
0 (0)
33 (100)
,0.001
Penicillin
0 (0)
4 (12.1)
0.123{
Sulfamethoxazole/
trimethoprim
16 (61.5)
33 (100)
,0.001
Teicoplanin
26 (100)
33 (100)
Vancomycin
26 (100)
33 (100)
Ciprofloxain`
5 (62.5)
7 (77.7)
0.437{
Levofloxacin`
6 (75)
9 (100)
0.206{
Moxifloxain`
6 (75)
9 (100)
0.206{
MRSA (n = 26)
MSSA (n = 33)
P value
4 (15.4)
5 (15.2)
1{
Trauma
1 (3.8)
3 (9.1)
0.623{
21 (80.8)
16 (48.5)
0.011
Predisposing Factors
Local factors, n (%)*
10 (38.5)
13 (39.4)
0.942
9 (34.6)
6 (18.2)
0.15
Systemic comorbidities
17 (65.4)
16 (48.5)
0.194
Immunosuppressant
1 (3.8)
2 (6.1)
1{
Systemic antibiotics
2 (7.7)
3 (9.1)
1{
*: Total is greater than 100% because of some patients with multiple risk factors.
{
: P value obtained by Fishers Exact Test.
MRSA: methicillin-resistant Staphylococcus aureus, MSSA: methicillin-sensitive Staphylococcus aureus.
doi:10.1371/journal.pone.0080119.t003
MRSA Keratitis
P value
MRSA (n = 26)
MSSA (n = 33)
26 (100)
33 (100)
17 (65.4)
15 (45.5)
0.057
9 (34.6)
9 (27.3)
0.543
Admission: n (%)
13 (50)
14 (44.4)
0.922*
4 (15.4)
4 (12.1)
0.722*
1.2 (0.2,8.5)
0.83 (0.1,11.7)
0.348
At presentation
2.6 (0,3)
1.65 (0,3)
0.084
After treatment
2.3 (0,3.2)
1.7 (0,3.2)
0.449
Genotyping analysis
Eight MRSA isolates were available for genotyping analysis.
One of the HA-MRSA isolates (n = 2) was characterized as PFGE
type F/SCCmec II/PVL-negative, and the other was PFGE type
A/SCCmec IIIA/PVL-negative. These results are consistent with
those of the HA-MRSA isolates in our previous study. [23] Five of
the six CA-MRSA isolates were characterized as PFGE type C/
SCCmec IV/PVL-negative and the other was PFGE type D/
SCCmec VT/PVL positive. These CA-MRSA clones shared
genetic characteristics that were common to CA-MRSA strains
previously indentified in Taiwan. [23].
Discussion
Our data showed that MRSA and MSSA contributed almost
equally to S. aureus keratitis and nearly half of MRSA keratitis was
community-associated. S. aureus, which accounts for approximately
822% of all bacterial keratitis, is an important cause of bacterial
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MRSA Keratitis
Acknowledgments
We thank Hsiao-Jung Tseng at the Biostatistical Center for
Clinical Research, Chang Gung Memorial Hospital, Taiwan for
assistance with the statistical analyses.
MRSA Keratitis
Author Contributions
Conceived and designed the experiments: CHH. Performed the experiments: SJO. Analyzed the data: SJO CHH. Contributed reagents/
References
21. Oliveira DC, de Lencastre H (2002) Multiplex PCR strategy for rapid
identification of structural types and variants of the mec element in
methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46:
21552161.
22. Mongkolrattanothai K, Boyle S, Kahana MD, Daum RS (2003) Severe
Staphylococcus aureus infections caused by clonally related community-acquired
methicillin-susceptible and methicillin-resistant isolates. Clin Infect Dis 37:
10501058.
23. Huang YC, Chen CJ (2011) Community-associated meticillin-resistant Staphylococcus aureus in children in Taiwan, 2000s. Int J Antimicrob Agents 38: 28.
24. Bourcier T, Thomas F, Borderie V, Chaumeil C, Laroche L (2003) Bacterial
keratitis: predisposing factors, clinical and microbiological review of 300 cases.
Br J Ophthalmol 87: 834838.
25. Green M, Apel A, Stapleton F (2008) Risk factors and causative organisms in
microbial keratitis. Cornea 27: 2227.
26. Huang YC, Su LH, Wu TL, Lin TY, Huang Y-C, et al. (2006) Changing
molecular epidemiology of methicillin-resistant Staphylococcus aureus bloodstream isolates from a teaching hospital in Northern Taiwan. Journal of Clinical
Microbiology 44: 22682270.
27. McCarthy NL, Sullivan PS, Gaynes R, Rimland D (2010) Health careassociated and community-associated methicillin-resistant Staphylococcus aureus infections: A comparison of definitions. Am J Infect Control 38: 600606.
28. Hori Y, Maeda N, Sakamoto M, Inoue T, Tano Y (2008) Fluoroquinoloneresistant bacteria and methicillin-resistant Staphylococci from normal preoperative conjunctiva. Journal of Cataract & Refractive Surgery 34: 711712.
29. Fukuda M, Ohashi H, Matsumoto C, Mishima S, Shimomura Y (2002)
Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulasenegative Staphylococcus ocular surface infection efficacy of chloramphenicol eye
drops. Cornea 21: S8689.
30. Kato T, Hayasaka S (1998) Methicillin-resistant Staphylococcus aureus and
methicillin-resistant coagulase-negative staphylococci from conjunctivas of
preoperative patients. Jpn J Ophthalmol 42: 461465.
31. Asbell PA, Colby KA, Deng S, McDonnell P, Meisler DM, et al. (2008) Ocular
TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J
Ophthalmol 145: 951958.
32. Asbell PA, Sahm DF, Shaw M, Draghi DC, Brown NP (2008) Increasing
prevalence of methicillin resistance in serious ocular infections caused by
Staphylococcus aureus in the United States: 2000 to 2005. J Cataract Refract
Surg 34: 814818.
33. Goldstein MH, Kowalski RP, Gordon YJ (1999) Emerging fluoroquinolone
resistance in bacterial keratitis: a 5-year review. Ophthalmology 106: 1313
1318.
34. Mino de Kaspar H, Kreutzer TC, Aguirre-Romo I, Ta CN, Dudichum J, et al.
(2008) A prospective randomized study to determine the efficacy of preoperative
topical levofloxacin in reducing conjunctival bacterial flora. Am J Ophthalmol
145: 136142.
35. Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, et al.
(2003) Comparison of mortality associated with methicillin-resistant and
methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin
Infect Dis 36: 5359.
36. Melzer M, Eykyn SJ, Gransden WR, Chinn S (2003) Is methicillin-resistant
Staphylococcus aureus more virulent than methicillin-susceptible S. aureus? A
comparative cohort study of British patients with nosocomial infection and
bacteremia. Clin Infect Dis 37: 14531460.
37. Major JC, Jr., Engelbert M, Flynn HW, Jr., Miller D, Smiddy WE, et al. (2010)
Staphylococcus aureus endophthalmitis: antibiotic susceptibilities, methicillin
resistance, and clinical outcomes. Am J Ophthalmol 149: 278283 e271.
38. Miedziak AI, Miller MR, Rapuano CJ, Laibson PR, Cohen EJ (1999) Risk
factors in microbial keratitis leading to penetrating keratoplasty. Ophthalmology
106: 11661170; discussion 1171.