Abstract
Purpose
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) orbital cellulitis (OC) has drawn increasing clinical and public health concern. We present a case series of MRSA OC encountered at four Australian tertiary institutions.
Methods
A multi-centre retrospective case series investigating MRSA OC in Australia from 2013 to 2022. Patients of all ages were included.
Results
Nine cases of culture-positive non-multi-resistant MRSA (nmMRSA) OC were identified at four tertiary institutions across Australia (7 male, 2 female). Mean age was 17.1 ± 16.7 years (range 13-days to 53-years), of which one was 13 days old, and all were immunocompetent. Eight (88.9%) patients had paranasal sinus disease, and seven (77.8%) had a subperiosteal abscess. Four (44.4%) had intracranial extension, including one (11.1%) case which was also complicated by superior sagittal sinus thrombosis. Empirical antibiotics, such as intravenous (IV) cefotaxime alone or IV ceftriaxone and flucloxacillin, were commenced. Following identification of nmMRSA, targeted therapy consisting of vancomycin and/or clindamycin was added. Nine (100%) patients underwent surgical intervention. Average hospital admission was 13.7 ± 6.9 days (range 3–25 days), with two patients requiring intensive care unit (ICU) admission due to complications related to their orbital infection. All patients had favourable prognosis, with preserved visual acuity and extraocular movements, following an average follow-up period of 4.6 months (range 2–9 months).
Conclusion
NMMRSA OC can follow an aggressive clinical course causing severe orbital and intracranial complications across a wide demographic. However, early recognition, initiation of targeted antibiotics and surgical intervention when required can effectively manage these complications and achieve favourable visual outcomes.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Orbital cellulitis (OC) is a sight-threatening infection breaching the orbital septum and is characterised by periorbital oedema, erythema, fever, pain and proptosis, often presenting with concurrent paranasal sinusitis or recent orbital trauma [1, 2]. Complications can be severe and life-threatening, including optic neuropathy, subperiosteal or intracranial abscesses, meningoencephalitis, cavernous sinus thrombosis and sepsis [1]. Thus, emergent diagnosis and prompt treatment with antibiotics and/or surgical intervention reduces mortality and morbidity [1].
Bacterial OC most commonly originates from acute rhinosinusitis, with organisms implicated including Staphylococcus aureus and Streptococcus pneumoniae. Empirical antibiotics are guided by relevant epidemiology, along with clinical features and risk factors, such as immunocompromised [1]. Recently, methicillin-resistant Staphylococcus aureus (MRSA)-associated infections have drawn increasing clinical and public health concern in both developing and developed countries, leading to an increased use of vancomycin and combination antimicrobial therapy [3, 4]. Empirical antibiotics coverage for MRSA is guided by local epidemiology and clinical suspicion, such as those with critical illness [3].
We present a case series of 9 MRSA-related OC encountered at tertiary institutions across Australia. This study aims to characterise the clinico-radiological features and outcomes associated with MRSA OC.
Methods
This was a multi-centre retrospective non-comparative case series investigating MRSA OC in Australia between 2013 and 2022. Inclusion criteria were patients of all ages with a clinico-radiological diagnosis of MRSA culture-positive OC. Pre-septal cellulitis (i.e. no clinico-radiological evidence of post-septal involvement) and microbiological isolates without MRSA were excluded.
Patients were identified from the Oculoplastics Unit at the Royal Adelaide Hospital (Adelaide, Australia), Flinders Medical Centre (Adelaide, Australia), Women’s and Children’s Hospital (Adelaide, Australia), Sydney Children’s Hospital (Randwick, Australia) and Sydney Eye Hospital (Sydney, Australia). Data collected included patient demographics (age, gender, past medical history and medications), clinical presentation, laboratory investigations (white cell count, C-reactive protein and microbiological analysis), radiological features, course of management and clinical outcomes.
Where applicable, results are expressed as means ± standard deviation (σ) and presented in relevant tables. Dimensions of lesions, as determined radiologically, are reported in the format of antero-posterior x transverse x coronal (millimetres). All research was conducted in accordance with the Declaration of Helsinki and was approved by our Institutional Review Board.
Results
We present 9 cases (7 male, 2 females) of culture-positive non-multi-resistant MRSA (nmMRSA) OC at various tertiary institutions across Australia within a 10-year period from 2013 to 2022. This included 6 children and 3 adults, with a mean age of 17.1 ± 16.7 years (range 13 days to 53 years). The mean duration of symptoms prior to presentation was 2.8 ± 2.0 days (range 1–7 days). Relevant past medical history included chronic sinusitis (2/9, 22.2%) and asthma (1/9, 11.1%). Additionally, one (11.1%) had cocaine-induced nasal cavity necrosis with a perforated septum, and nasal hardware from a previous trauma. No patients were immunocompromised, and all were defined as nmMRSA infections. A summary of the cases is outlined in Table 1.
The most common clinical features included periorbital oedema (8/9, 88.9%), pain (8/9, 88.9%), proptosis (6/9, 66.7%) and restricted extraocular movements (6/9, 66.7%). Other common findings were globe dystopia (4/9, 44.4%), mechanical ptosis (4/9, 44.4%), fever (5/9, 55.5%), conjunctival hyperaemia (4/9, 44.4%) and ocular discharge/lacrimation (3/9, 33.3%). One (11.1%) patient had optic neuropathy, which resolved at final follow-up. Two (22.2%) had neurological symptoms including fluctuating consciousness and generalised tonic–clonic seizures (1/9, 11.1%) and right facial palsy (1/9, 11.1%) which was presumed to be secondary to parotid inflammation. Two (22.2%) had a preceding upper respiratory tract infection.
Laboratory investigations showed elevated C-reactive protein in 88.9% (mean CRP: 178.0 ± 100.9 mg/L) and leucocytosis in 88.8% (mean white cell count: 17.9 ± 5.2 × 109/L). NMMRSA-positive cultures were isolated from a combination of sinus or orbital abscess swabs (6/9, 66.7%), nasal swabs (3/9, 33.3%) and blood cultures (1/9, 11.1%).
All patients underwent contrast-enhanced computed tomography (CT), and four (44.4%) also had magnetic resonance imaging (MRI) due to clinical concern for intracranial complications. Table 2 summarises the radiological features encountered. On CT and MRI, all patients demonstrated pre-septal swelling and stranding of the extraconal and/or intraconal fat. Inflammatory changes within the orbit appeared as regions of heterogeneous hyperintensity on T2-weighted fat-suppressed sequences (Fig. 1A and B). One patient had a pre-septal abscess, four patients had lacrimal gland involvement, and five had EOM involvement. The superior ophthalmic vein and cavernous sinus were patent in all cases. Eight (88.9%) patients had paranasal sinus disease, and seven (77.8%) had subperiosteal abscesses (SPA). SPAs were located along the medial (2/7, 28.6%), superolateral (2/7, 28.6%), superomedial (1/7, 14.3%), superior (1/7, 14.3%) and inferior (1/7, 14.3%) orbital walls. One (11.1%) patient also had an extraconal orbital abscess, located laterally to the lateral rectus and contiguous but not directly involving the lacrimal gland (Patient 6). Abscess volumes ranged from 325 mm3 to 4620 mm3. Of the four patients who had an MRI, diffusion restriction on diffusion-weighted imaging (DWI) was observed in all the abscesses (Fig. 2). Four (44.4%) had intracranial extension with evidence of dural/leptomeningeal enhancement and frontal subdural collections, including one patient (11.1%) with a sub-galeal abscess with no osteomyelitis and multiple extradural empyemas over the right frontal and parasagittal regions (Patient 9), and one (11.1%) had a superior sagittal sinus thrombosis, which remained stable throughout admission (Patient 5).
MR orbital imaging in Patient 4. A and B demonstrate T1 fat-suppressed contrast-enhanced MRI of the superior SPA (white arrow) with central non-enhancement indicative of an abscess. C and D demonstrate high signal (white arrow) on diffusion-weighted imaging and low signal on apparent diffusion coefficient (ADC) mapping exhibiting a low signal (white arrow), respectively, consistent with an abscess
Specific antibiotic and surgical management are outlined in Table 1. Empirical antibiotics, such as intravenous (IV) cefotaxime alone or IV ceftriaxone and flucloxacillin, were initially commenced. Nine (100%) patients underwent surgical intervention, including functional endoscopic sinus surgery (FESS) (8/9, 88.9%), SPA/orbital abscess drainage (6/9, 66.7%) and incision and drainage of a pre-septal abscess (1/9, 11.1%), which were performed alone or in combination. One (11.1%) patient underwent surgical exploration and marsupialisation of an infected dacryocele (Patient 3). The superior sagittal sinus thrombosis was treated with Enoxaparin, which was continued for three months post-discharge (Patient 5).
Average duration of admission was 13.7 ± 6.9 days (range 3–25 days). Three (33.3%) patients required Intensive Care Unit (ICU) admission, two for intracranial infection (Patients 1 and 5), while one ICU admission was unrelated to orbital infection and due to an anaphylactic reaction to codeine (Patient 7). Long-term sequelae of infection were observed including mild cognitive impairment at 4-month follow-up (Patient 4). On subsequent MRI, there was complete recanalisation of the superior sagittal sinus thrombosis following anticoagulation with no persisting neurological deficits (Patient 5). One patient had residual periorbital oedema at discharge, but full VA and EOM (Patient 9). The remaining patients had complete resolution of ocular symptoms consisting of preserved VA, no optic neuropathy or ptosis and full EOM following an average follow-up period of 4.6 months (range 2–9 months). One patient was lost to follow-up due to transfer of care to another tertiary institution upon discharge (Patient 9).
Discussion
Staphylococcus aureus and Streptococcus species have been reported as the predominant pathogens in OC, often secondary to acute rhinosinusitis. However, other organisms include Haemophilus influenzae, Moraxella catarrhalis and anaerobes [1, 3, 5]. MRSA has emerged as an important public health concern, accounting for a significant proportion of soft tissue infections, including pre-septal cellulitis [5,6,7,8,9,10]. The incidence of MRSA OC varies within the literature, ranging from 21 to 73%, and is likely affected by the changing epidemiological trends of specific institutions and geographical locations [1]. In Australia (Adelaide, South Australia), the incidence of MRSA orbital cellulitis has been reported to be 28.6% between a 10-year period (2012 to 2022), with 50% of cases identified between 2021 and 2022 [11]. Previously, MRSA had represented 21.7% of all Staphylococcus Aureus of all ocular infections (Adelaide, South Australia); however, no cases of OC were included [12]. MRSA OC has also become prevalent in various geographical locations. For example, Shih et al. reported an increasing incidence of MRSA OC from 14.5% to 37.5% over two 10-year periods between 2000–2009 and 2010–2019 in Taiwan [6]. Meanwhile, Pandian et al. reported in 2011 that MRSA was the most common organism identified, responsible for 38% of culture-positive OC at their tertiary institution in India [10]. Though rationalised antibiotic management remains a central focus in the era of antibiotic resistance, early recognition of resistant organisms in OC is essential to prevent serious complications.
This series of nmMRSA OC demonstrates a fulminant disease course with cases of intracranial extension, superior sagittal sinus thrombosis and overall complicated/prolonged hospital admission. Nevertheless, early intervention with targeted antibiotics and/or surgical intervention reduced the risk of morbidity and mortality, with good prognosis observed in our cases.
Previous studies have reported differences in the clinical features between MRSA OC and other typical organisms [2, 5]. In 2012, Mathias et al. reported a case series of 15 MRSA OC cases, surmising that the following atypical features may raise suspicion of MRSA OC: absence of preceding upper respiratory tract infection; lacrimal gland focus; multiple orbital abscesses on imaging; or absence of adjacent paranasal sinus disease [5]. However, other studies and case reports have not validated these findings [2]. These features were also largely discordant with our findings: although only one patient had a preceding upper respiratory tract infection, two had chronic sinusitis, and nine (90%) patients had radiological evidence of paranasal sinus disease. Prior literature has also reported an association with a young age of presentation < 1 year old including immunocompetent individuals [2, 8, 9, 13]. Although there was a paediatric predominance (8/11, 72.7%) in our study, only 1 infant was aged < 1 year old. Ultimately, MRSA OC may have a diverse clinico-radiological presentation, and a broad and heterogeneous patient demographic may be affected.
MRSA OC was associated with a prolonged and complicated clinical course, and this has been demonstrated in prior studies of MRSA-associated ocular infections in South Australia [12]. The incidence of SPAs in bacterial OC ranges from 15–62% [14,15,16,17,18]. However, 81.8% of our patients developed a SPA, with 4 cases located in the superior orbit. In MRSA OC, SPAs and orbital abscesses may develop rapidly, and multiple abscesses may also form in other regions of the body in cases of septicaemia [8, 9]. Septicaemia occurred in 1 case which was also complicated by pneumonia (Patient 5); however, no cases had abscesses located in other regions of the body. Intracranial extension of infection and septic cerebral venous sinus thrombosis have significant morbidity and mortality, but the exact incidence is unknown [19, 20]. The cavernous sinus is most commonly affected, with sagittal sinus thrombosis involvement remaining very rare. (14) Intracranial extension was encountered in three (30%) cases, including one patient with a superior sagittal sinus thrombosis. Staphylococcus aureus reportedly accounts for 60–70% of all septic cerebral sinus thrombosis. (14) Several case reports have detailed cavernous sinus thrombosis secondary to MRSA-related orbital infections with high rates of mortality and morbidity, including blindness and impaired ocular motility [20,21,22,23,24]. The clinical course of MRSA infections has been more aggressive compared to other microbial causes [5, 10, 25]. Various factors may complicate management of MRSA infections including antimicrobial resistance and presence of highly virulent mechanisms including production of toxins, adhesion proteins and immune evasion [26]. For example, the Panton–Valentine leucocidin (PVL) toxin is associated with abscess formation [27]. Additionally, acquired phenotypic traits observed in recently emerging MRSA strains allow them to be more virulent and more effective at colonisation [26]. The incidence of profound visual loss in OC varies, with reportedly 3–27% of patients experiencing severe vision loss to the degree of light perception or worse [5]. Several patients in our series had prolonged hospital admissions with significant complications; however, full resolution of VA and motility with no cases of visual compromise or ocular sequelae were observed.
This study had several limitations due to its retrospective nature and MRSA OC remaining relatively uncommon. Additionally, detection of MRSA colonisation on less reliable culture methods (e.g. nasal swabs) may influence initial selection of empirical antibiotics, even if other pathogens are responsible for the orbital infection. Intraoperative swabs with direct access to the abscess improve the reliability and yield of microbiological cultures [28]. Thorough clinical assessment along with awareness of and systematic updates on the local epidemiology will help guide appropriate initiation of empirical nmMRSA active antibiotics when treating OC.
In conclusion, our case series presents the clinico-radiological presentations and outcomes of nmMRSA OC. This series demonstrates that nmMRSA OC can be associated with a complex disease course and the potential to develop severe orbital and intracranial complications, necessitating prolonged admission. Early initiation of appropriate antibiotic therapy and surgical intervention can achieve a favourable visual prognosis.
References
Tsirouki T, Dastiridou AI, Ibánez Flores N, Cerpa JC, Moschos MM, Brazitikos P et al (2018) Orbital cellulitis. Surv Ophthalmol 63(4):534–553. https://doi.org/10.1016/j.survophthal.2017.12.001
Hsu J, Treister AD, Ralay Ranaivo H, Rowley AH, Rahmani B (2019) Microbiology of pediatric orbital cellulitis and trends in Methicillin-resistant Staphylococcus aureus cases. Clin Pediatr (Phila) 58(10):1056–1062. https://doi.org/10.1177/0009922819864587
Seltz LB, Smith J, Durairaj VD, Enzenauer R, Todd J (2011) Microbiology and antibiotic management of orbital cellulitis. Pediatrics 127(3):e566–e572. https://doi.org/10.1542/peds.2010-2117
Monaco M, Pimentel de Araujo F, Cruciani M, Coccia EM, Pantosti A (2017) Worldwide epidemiology and antibiotic resistance of Staphylococcus aureus. Curr Top Microbiol Immunol 409:21–56. https://doi.org/10.1007/82_2016_3
Mathias MT, Horsley MB, Mawn LA, Laquis SJ, Cahill KV, Foster J et al (2012) Atypical presentations of orbital cellulitis caused by methicillin-resistant Staphylococcus aureus. Ophthalmology 119(6):1238–1243. https://doi.org/10.1016/j.ophtha.2012.01.010
Shih EJ, Chen JK, Tsai PJ, Bee YS (2021) Differences in characteristics, aetiologies, isolated pathogens, and the efficacy of antibiotics in adult patients with preseptal cellulitis and orbital cellulitis between 2000–2009 and 2010–2019. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2021-318986
Vaska VL, Grimwood K, Gole GA, Nimmo GR, Paterson DL, Nissen MD (2011) Community-associated methicillin-resistant Staphylococcus aureus causing orbital cellulitis in Australian children. Pediatr Infect Dis J 30(11):1003–1006. https://doi.org/10.1097/INF.0b013e318224fda5
Lei TH, Huang YC, Chu YC, Lee CY, Lien R (2013) Orbital cellulitis caused by community-associated methicillin-resistant Staphylococcus aureus in a previously healthy neonate. J Microbiol Immunol Infect 46(2):136–138. https://doi.org/10.1016/j.jmii.2012.01.015
Rao LG, Rao K, Bhandary S, Shetty PR (2015) Orbital cellulitis with periorbital abscess secondary to methicillin-resistant (MRSA) sepsis in an immunocompetent neonate. BMJ Case Rep 2015:bcr2014209183. https://doi.org/10.1136/bcr-2014-209183
Pandian DG, Babu RK, Chaitra A, Anjali A, Rao VA, Srinivasan R (2011) Nine years’ review on preseptal and orbital cellulitis and emergence of community-acquired methicillin-resistant Staphylococus aureus in a tertiary hospital in India. Indian J Ophthalmol 59(6):431–435. https://doi.org/10.4103/0301-4738.86309
Ang T, Tong JY, Selva D (2023) Microbiology of bacterial orbital cellulitis-tertiary institutional experiences in South Australia: a multi-centre retrospective study. Int Ophthalmol. https://doi.org/10.1007/s10792-022-02624-8
Sun MT, Simon S, Warner M, Chehade M, Selva D (2012) Methicillin-resistant Staphylococus aureus. Ophthalmology 119(8):1719-e1. https://doi.org/10.1016/j.ophtha.2012.04.025
Anari S, Karagama YG, Fulton B, Wilson JA (2005) Neonatal disseminated methicillin-resistant Staphylococcus aureus presenting as orbital cellulitis. J Laryngol Otol 119(1):64–67. https://doi.org/10.1258/0022215053223003
Fanella S, Singer A, Embree J (2011) Presentation and management of pediatric orbital cellulitis. Can J Infect Dis Med Microbiol 22(3):97–100. https://doi.org/10.1155/2011/626809
Rahbar R, Robson CD, Petersen RA, DiCanzio J, Rosbe KW, McGill TJ et al (2001) Management of orbital subperiosteal abscess in children. Archiv Otolaryngol-Head Neck Surg 127(3):281–286. https://doi.org/10.1001/archotol.127.3.281
Elshafei AMK, Sayed MF, Abdallah RMA (2017) Clinical profile and outcomes of management of orbital cellulitis in Upper Egypt. J Ophthalmic Inflamm Infect 7(1):8. https://doi.org/10.1186/s12348-017-0126-3
Ferguson MP, McNab AA (1999) Current treatment and outcome in orbital cellulitis. Aust N Z J Ophthalmol 27(6):375–379. https://doi.org/10.1046/j.1440-1606.1999.00242.x
Pereira FJ, Velasco e Cruz AA, Anselmo-Lima WT, Elias Júnior J (2006) Computed tomographic patterns of orbital cellulitis due to sinusitis. Arq Bras Oftalmol 69(4):513–8. https://doi.org/10.1590/s0004-27492006000400011
Eustis HS, Mafee MF, Walton C, Mondonca J (1998) MR imaging and CT of orbital infections and complications in acute rhinosinusitis. Radiol Clin North Am 36(6):1165–83. https://doi.org/10.1016/s0033-8389(05)70238-4
Khatri IA, Wasay M (2016) Septic cerebral venous sinus thrombosis. J Neurol Sci 362:221–227. https://doi.org/10.1016/j.jns.2016.01.035
Snyder GM, Pothuru S (2008) Cavernous sinus thrombosis associated with MRSA bacteremia. Am J Med Sci 336(4):353. https://doi.org/10.1097/MAJ.0b013e31817b5b8b
Kotagiri R, Saunders AT (2020) Septic bilateral cavernous sinus thrombosis with persistent methicillin-resistant staphylococcus aureus bacteremia. Cureus 12(6):e8554. https://doi.org/10.7759/cureus.8554
Branson SV, McClintic E, Yeatts RP (2019) Septic cavernous sinus thrombosis associated with orbital cellulitis: a report of 6 cases and review of literature. Ophthalmic Plast Reconstr Surg 35(3):272–280. https://doi.org/10.1097/iop.0000000000001231
Rutar T, Zwick OM, Cockerham KP, Horton JC (2005) Bilateral blindness from orbital cellulitis caused by community-acquired methicillin-resistant Staphylococcus aureus. Am J Ophthalmol 140(4):740–742. https://doi.org/10.1016/j.ajo.2005.03.076
Shome D, Jain V, Natarajan S, Agrawal S, Shah K (2008) Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA)—A rare cause of fulminant orbital cellulitis. Orbit 27(3):179–181. https://doi.org/10.1080/01676830701549116
Otto M (2012) MRSA virulence and spread. Cell Microbiol 14(10):1513–1521. https://doi.org/10.1111/j.1462-5822.2012.01832.x
Watkins RR, David MZ, Salata RA (2012) Current concepts on the virulence mechanisms of meticillin-resistant Staphylococcus aureus. J Med Microbiol 61(Pt 9):1179–1193. https://doi.org/10.1099/jmm.0.043513-0
McKinley SH, Yen MT, Miller AM, Yen KG (2007) Microbiology of pediatric orbital cellulitis. Am J Ophthalmol 144(4):497–501. https://doi.org/10.1016/j.ajo.2007.04.049
Funding
Open Access funding enabled and organized by CAUL and its Member Institutions. The authors have no financial disclosures or conflicts of interest to declare.
Author information
Authors and Affiliations
Contributions
TA was responsible for the writing the protocol, extracting and analysing data, interpreting results and drafting of the manuscript. CC was involved in interpreting results and drafting of manuscript. GW, JT, JT and SP were involved in extracting data and providing feedback on the manuscript. DS provided feedback on the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
This research presented as a poster for the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) 53rd Annual Scientific Congress in 2022. There are no further conflicts of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Ang, T., Cameron, C., Tong, J.Y. et al. Methicillin-resistant Staphylococcus aureus-associated orbital cellulitis: a case series. Int Ophthalmol 43, 2925–2933 (2023). https://doi.org/10.1007/s10792-023-02698-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10792-023-02698-y