Pneumococcal disease, atypical presentation in an atypical setting: a case report

Pneumococcal disease, atypical presentation in an atypical setting: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Pneumococcal disease, atypical presentation in an atypical setting: a case report David Lucena-López, Grisell Starita-Fajardo, Maria Eugenia Arruza-Santos, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7077728/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Endogenous endophthalmitis (EE) is an intraocular infection, frequently bacterial, acquired via hematogenous dissemination. We present the case of a patient with fever and unilateral vision loss who was diagnosed with invasive pneumococcal disease. Despite systemic and intravitreal antibiotic treatment, the patient experienced clinical deterioration which ultimately required ocular evisceration. We emphasize the need for early and aggressive intervention. Endophthalmitis Infectious Suppurative uveitis Pneumococcal pneumonia Case report Figures Figure 1 Figure 2 Figure 3 Highlights - This case highlights an uncommon presentation of invasive pneumococcal disease. - This emphasizes the importance of a multidisciplinary approach and early diagnosis, considering the relevant prognostic implications that this entails. Introduction EE is a rare condition characterized by intraocular inflammation and is mainly haematogenous in origin with predominantly unilateral involvement (70%) 1 . The most common etiology is caused by bacteria, which are influenced by various risk factors. The prognosis depends on early diagnosis and the initiation of targeted treatment, often requiring a multidisciplinary approach 2 . Case presentation A 39-year-old man from Côte d'Ivoire, resident in Spain, with no significant past medical history. He was an ex-smoker with a 20 pack-year history and denied the use of other toxic substances. He had no history of risky contacts or recent travel and was not on any regular medication. He came to the emergency department with asthenia, decreased appetite and dizziness in the previous month, together with epigastric abdominal pain, nausea and vomiting for 10 days. In this context, he has lost 10 kg of weight. The patient also experienced conjunctival erythema, pain and loss of visual acuity (VA) in the left eye (LE) for three days. He reported generalized arthralgias without arthritis. He denied having a cough, expectoration, or chest pain or palpitations. Intestinal rhythm is preserved. There were no skin lesions. He had conjunctival hyperemia, a cellular reaction in the anterior chamber of 4+, and a 1.5 mm hypopyon associated with the prepupillary fibrin meshwork in the LE (FIGURE 1). VA was 0.8 in the right eye (RE), and no light perception (NLP) was detected in the LE. The remainder of the physical examination was unremarkable, relevant, with no murmurs on cardiac auscultation, aggregate pulmonary sounds, organomegaly on abdominal palpation or skin lesions. He remained normotensive, with a controlled heart rate, and afebrile. With respect to the diagnostic tests, the following findings were highlighted: - Intraocular pressure (IOP) was 12 mmHg in the RE and 13 mmHg in the LE. - Funduscopy: Funduscopy was not possible in the LE because of media opacity. It was completed with B-mode ultrasound, which revealed dense, hyperechoic content in the vitreous cavity, with the retina applied (FIGURE 2). - Thoracic-abdomino-pelvic CT scan: Centrilobular nodules in left lower lobe, likely related to an inflammatory/infectious process. The rest of the study did not include alterations (FIGURE 3). - SARS-CoV-2 CPR was negative, and the urine antigen for pneumococcus was positive. - Vitreous culture obtained by vitrectomy: S. pneumoniae susceptible to penicillin was isolated in aerobic medium. - Blood cultures: S. pneumoniae was isolated from 2/2 of the sample and was susceptible to penicillin. - Blood tests revealed a decrease in the level of IgG subclasses at the expense of IgG2 (79.20 mg/dL), with total levels of other immunoglobulins, C3 and C4 in the normal range. Peripheral blood immunofixation revealed IgG-kappa monoclonal gammopathy, and a bone marrow biopsy confirmed the diagnosis of monoclonal gammopathy of uncertain significance (MGUS). The autoimmunity screening, renal function, liver profile and hemogram results revealed no notable findings. The patient was admitted with suspected EE, and empirical antibiotic therapy was initiated with meropenem, ceftaroline and voriconazole. After a thorough physical examination, which revealed no relevant findings beyond those already known at the ocular level, a chest X-ray was performed in which a pneumonic consolidation was detected in the left lower lobe, subsequently confirmed by a thoraco-abdomino-pelvic CT scan. The presence of a positive pneumococcal antigen and the isolation of penicillin-susceptible Streptococcus pneumoniae in two blood cultures led to the implementation of simplified monotherapy with ceftaroline. An early 25G pars plana vitrectomy was performed by the ophthalmology team for diagnostic-therapeutic purposes, which is associated with phacoemulsification without intraocular lens implantation. During surgery, both vitritis and extensive retinal necrosis were observed, and samples were obtained for culture and PCR. Intravitreal vancomycin and ceftazidime were also administered. After the operation, given the visual deterioration and lack of response to the treatments given, ocular evisceration was performed via the four-petal technique. Additional studies revealed an IgG2 subclass deficiency and IgG kappa MGUS, both of which may have contributed to the susceptibility to severe infection by an encapsulated microorganism. Discussion Endophthalmitis is defined as an infection of intraocular tissue. The route of entry can be categorized as either exogenous, which is caused by direct inoculation of microorganisms, or endogenous, which is acquired via haematogenous spread. EE accounts for approximately 5–15% of all cases of endophthalmitis, predominantly affecting the right eye because of the direct inflow of blood from the ipsilateral carotid artery 1, ². Several risk factors contribute to the development of this infection, including diabetes mellitus, cancer, and chemotherapy, all of which are related to immunosuppression in patients. Other risk contributors include parenteral drug use and iatrogenesis due to prolonged catheter use. Diabetes mellitus is the most significant risk factor, as hyperglycaemia leads to an increase in the permeability of the blood–retinal barrier, creating a favorable environment for the proliferation of microorganisms². If haematogenous dissemination is suspected, the relationship with venipuncture and/or central venous access must be considered, although the risk of a hospitalized patient presenting with EE due to bacteraemia or fungaemia is low at 0.05–0.4%¹,². The infectious processes commonly associated with EE include liver abscesses, pneumonia and endocarditis¹. In the present case, the risk factors that likely contributed to the development of disseminated infection were IgG2 deficiency and the presence of MGUS. IgG subclass deficiency (IgGSD), which occurs in approximately 1 in 10,000 people, is a subtype of primary immunodeficiency characterized by recurrent or severe respiratory infections associated with deficiency of one or more IgG subclasses 4,5 . A retrospective study of 18 patients with IgG2 deficiency revealed a higher prevalence in women, the coexistence of deficiency in other subclasses, such as IgG1 or IgG3, and the limited efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in these patients 6 . The clinical spectrum of EE is characterized by decreased visual acuity (78%), ocular pain (37%) and fever (34%), so a detailed physical examination is crucial to determine the origin of the infection. Fifty-four percent of patients had normal intraocular pressure (IOP) (10–21 mmHg), 28% had high IOP (>21 mmHg), and 18% had low IOP (<10 mmHg). Other findings included vitreous inflammation and opacity (63%), conjunctival hyperaemia (36%), retinitis (28%), anterior chamber cells (19%), corneal oedema (12%), choroiditis (8%), corneal clouding (6%) and ciliary hyperaemia (5%) 2 . In EE, fungi are the most common underlying aetiological agents, with Candida albicans and Aspergillus spp. being the most common, the latter being associated with a particularly unfavorable clinical course. The distribution of bacterial agents varies according to geographical region, with a higher prevalence of gram-negative bacilli, such as Klebsiella spp., Pseudomonas aeruginosa , Escherichia coli and Neisseria meningitidis (serogroups A, B and C), especially compared with exogenous infections 1,3 . However, gram-positive cocci, such as Streptococcus spp. and Staphylococcus aureus , remain relatively common, especially in Western countries 7 . EE caused by Klebsiella is particularly common in Asian populations. In addition, although less common, acid-fast microorganisms such as Mycobacterium tuberculosis in immunocompetent individuals, as well as atypical mycobacteria and Nocardia spp. in immunocompromised patients, may also be involved in this ocular infection 8-10 . Empirical antibiotic therapy should be initiated promptly, along with adequate source control. Drug diffusion into the vitreous humor is poor, making intravitreal antibiotherapy and often vitrectomy necessary. The most frequently used empirical coverage involves the combination of drugs against gram-positive bacteria, with vancomycin being the drug of choice, and against gram-negative bacteria, with ceftazidime taking precedence over amikacin and gentamicin. In the case of suspicion of fungal etiology, this possibility should be covered with liposomal amphotericin b or intravitreal voriconazole 1 . Although the role of vitrectomy in EE has not been clearly established and the recommendations of the Endophthalmitis Vitrectomy Study (EVS) may not be directly applicable, this intervention is considered useful in severe cases caused by virulent germs 11 . Vitrectomy not only allows the evacuation of intraocular purulent contents, acting as abscess drainage in a poorly vascularised environment, in line with the principle of " ubi pus, ibi evacua ", but also facilitates the collection of samples for culture, PCR and antibiogram, which reinforces its diagnostic value. Furthermore, several clinical series have shown that vitrectomy is associated with a better visual prognosis and less need for mutilating procedures such as evisceration or enucleation, especially when indicated in the presence of signs such as very low visual acuity at diagnosis, bilateral involvement, dense vitritis or a lack of response to initial medical treatment 12-13 . The visual prognosis of endogenous bacterial endophthalmitis is usually unfavorable, with high rates of severe complications such as evisceration or enucleation (25–50%) and associated mortality that can reach 15% 14 . Bacterial forms, especially those caused by gram-negative bacteria such as Klebsiella, tend to have a poorer visual prognosis than fungal forms do, particularly those caused by Candida spp., which have a relatively better prognosis 15 . Factors such as early diagnosis, early treatment and good initial visual acuity are associated with better visual outcomes, whereas immunosuppression, chronic disease, coinfection, prolonged hospital admission and highly virulent agents are associated with higher mortality and worse functional outcomes 16-17 . To our knowledge, this is the first reported case of endogenous endophthalmitis due to S. pneumoniae in a patient with both IgG2 deficiency and MGUS, highlighting the importance of immunological evaluation in atypical presentations. Abbreviations EE: Endogenous endophthalmitis. VA: visual acuity. LE: left eye. RE: right eye. NLP: no light perception. IOP: Intraocular pressure. MGUS: monoclonal gammopathy of uncertain significance. IgGSD: IgG subclass deficiency. PPSV23: 23-valent pneumococcal polysaccharide vaccine. EVS: Endophthalmitis Vitrectomy Study. Declarations Acknowledgements: None. Authors’ contributions: D.L.L. and G.S.F. wrote the main manuscript text. M.E.A., J.J.G. and A.R.A. provided details about the surgical treatment and visual prognosis. G.S.F. and J.J.G. reviewed the manuscript. Availability of data and materials All data generated or analyzed during this study are included in this published article. Funding: This research was supported by a Roche grant (the funder did not have a role in the conduction of the study; in the collection, management, analysis, or interpretation of data; or in the preparation of the manuscript). Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent form is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Author details: 1 Internal Medicine Department, Hospital Universitario Ramón y Cajal. IRYCIS. Madrid, España. 2 Department of Ophthalmology, Hospital Universitario Ramón y Cajal. IRYCIS. Madrid, España. References Durand, M.L. Bacterial and Fungal Endophthalmitis. Clin. Microbiol. Rev. 2017, 30, 597–613. Hu M, Liu M, Jin S, Wang X, Liu X. Clinical features, treatment and prognosis of patients with endogenous infectious endophthalmitis. Int Ophthalmol . 2024;44(1):321. Published 2024 Jul 8. doi:10.1007/s10792-024-03208-4 Vaziri, K.; Pershing, S.; Albini, T.A.; Moshfeghi, D.M.; Moshfeghi, A.A. Risk factors predictive of endogenous endophthalmitis among hospitalized patients with hematogenous infections in the United States. Am. J. Ophthalmol. 2015, 159, 498–504. Kim JH, Park S, Hwang YI, Jang SH, Jung KS, Sim YS, et al. Immunoglobulin G subclass deficiencies in adult patients with chronic airway disease. J Korean Med Sci. 2016; 31:1560–5. https://doi.org/10. 3346/jkms.2016.31.10.1560 PMID: 27550483 Khokar A, Gupta S. Clinical and immunological features of 78 adult patients with primary selective IgG subclass deficiencies. Arch Immunol Ther Exp (Warsz). 2019; 67:325–34. Barton JC, Barton JC, Bertoli LF, Acton RT. Characterization of adult patients with IgG subclass deficiency and subnormal IgG2. PLoS One. 2020;15(10):e0240522. Published 2020 Oct 13. doi:10.1371/journal.pone.0240522 Cho H, Shin YU, Siegel NH, et al. Endogenous endophthalmitis in the American and Korean population: an 8-year retrospective study. Ocul Immunol Inflamm. 2018;26(4):496–503. doi:10.1080/09273948.2016.1195000 Antaki F, Javidi S, Touma S, Aubin MJ. Endogenous tuberculous endophthalmitis and panophthalmitis: a systematic review of case reports and case series. Clin Ophthalmol (Auckland, NZ). 2020;14:3075. doi:10.2147/OPTH.S265521. Pinitpuwadol W, Tesavibul N, Boonsopon S, Sakiyalak D, Sarunket S, Choopong P. Nontuberculous mycobacterial endophthalmitis: case series and review of literature. BMC Infect Dis. 2020;20(1):1–11. doi:10.1186/s12879-020-05606-2. Milman T, Trubnik V, Shah M, McCormick SA, Finger PT. Isolated Nocardia exalbida endogenous endophthalmitis. Ocul Immunol Inflamm. 2011;19(4):237–239. doi:10.3109/09273948.2011.563898. LOBE J. Ubi pus ibi evacua; ein Beitrag aus der Praxis zum Störfeldgeschehen [Ubi pus ibi evacua; a contribution from the study of disease foci]. Dtsch Gesundheitsw. 1958 Apr 10;13(15):474-6. German. PMID: 13547748. Connell PP, O’neill EC, Fabinyi D, et al. Endogenous endophthalmitis: 10-year experience at a tertiary referral centre. Eye. 2011;25(1):66–72. doi:10.1038/eye.2010.145. Zhang H, Liu Z. Endogenous endophthalmitis: a 10-year review of culture-positive cases in northern China. Ocul Immunol Inflamm. 2010;18(2):133–138. doi:10.3109/09273940903494717. Jackson TL, Eykyn SJ, Graham EM, Stanford R. Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases. Surv Ophthalmol 2003;48: 403–423. Yang CS, Tsai HY, Sung CS, Lin KH, Lee FL, Hsu WM. Endogenous Klebsiella endophthalmitis associated with pyogenic liver abscess. Ophthalmology. 2007;114(5):876–880. doi:10.1016/j.ophtha.2006.12.035. Vaziri K, Pershing S, Albini TA, Moshfeghi DM, Moshfeghi AA. Risk factors predictive of endogenous endophthalmitis among hospitalized patients with hematogenous infections in the United States. Am J Ophthalmol. 2015;159(3):498–504. doi:10.1016/j.ajo.2014.11.032. Shenoy SB, Thotakura M, Kamath Y, Bekur R. Endogenous endophthalmitis in patients with MRSA septicemia: a case series and review of literature. Ocul Immunol Inflamm. 2016;24(5):515–520. doi:10.3109/09273948.2015.1020173. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7077728","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":493446388,"identity":"52af41ae-7d2d-4afc-a03b-21cff4d8e04c","order_by":0,"name":"David Lucena-López","email":"data:image/png;base64,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","orcid":"","institution":"Hospital Universitario Ramón y Cajal, IRYCIS.","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"","lastName":"Lucena-López","suffix":""},{"id":493446389,"identity":"1f777542-4f68-4339-ab72-213563b7818e","order_by":1,"name":"Grisell Starita-Fajardo","email":"","orcid":"","institution":"Hospital Universitario Ramón y Cajal, IRYCIS.","correspondingAuthor":false,"prefix":"","firstName":"Grisell","middleName":"","lastName":"Starita-Fajardo","suffix":""},{"id":493446390,"identity":"4555ce82-40eb-491e-b0ca-5468d002f24f","order_by":2,"name":"Maria Eugenia Arruza-Santos","email":"","orcid":"","institution":"Hospital Universitario Ramón y Cajal, IRYCIS.","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Eugenia","lastName":"Arruza-Santos","suffix":""},{"id":493446391,"identity":"a3961c0d-c1bb-44e1-a131-1ebc81ff17c5","order_by":3,"name":"Ana Rosa Albandea-Jiménez","email":"","orcid":"","institution":"Hospital Universitario Ramón y Cajal, IRYCIS.","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"Rosa","lastName":"Albandea-Jiménez","suffix":""},{"id":493446392,"identity":"ff532ccf-0239-4927-870e-6dd46f4699f7","order_by":4,"name":"Julio J. González-López","email":"","orcid":"","institution":"Hospital Universitario Ramón y Cajal, IRYCIS.","correspondingAuthor":false,"prefix":"","firstName":"Julio","middleName":"J.","lastName":"González-López","suffix":""}],"badges":[],"createdAt":"2025-07-08 19:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7077728/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7077728/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88349580,"identity":"99484dda-4603-409c-a91f-71469663bb84","added_by":"auto","created_at":"2025-08-05 14:06:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":943784,"visible":true,"origin":"","legend":"\u003cp\u003eConjunctival hyperemia, cellular reaction in the anterior chamber of 4+, and a 1.5 mm hypopyon associated with the prepupillary fibrin meshwork in the left eye.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7077728/v1/265fd76ff813d6a02b27399a.png"},{"id":88348075,"identity":"c7d92f83-3a76-4453-af0e-4da59895dea9","added_by":"auto","created_at":"2025-08-05 13:58:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":461384,"visible":true,"origin":"","legend":"\u003cp\u003eB-mode ultrasound, which revealed dense, hyperechoic content in the vitreous cavity.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7077728/v1/9b14a664aeadd14aab325483.png"},{"id":88350597,"identity":"a29e0d8a-344a-49a7-ae79-afba8c5e70d6","added_by":"auto","created_at":"2025-08-05 14:14:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":370829,"visible":true,"origin":"","legend":"\u003cp\u003eLeft basal lung opacities subsegmental atelectasis (“a” marker). Mild bilateral pleural effusion.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7077728/v1/360271129264799b2d6c4a43.png"},{"id":89252455,"identity":"131d464c-dfda-4aa5-aa8f-983ef99dbe2c","added_by":"auto","created_at":"2025-08-18 04:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2687017,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7077728/v1/0ca54963-c28c-424c-992e-b785fb26ebe6.pdf"},{"id":88348071,"identity":"c3d8b30b-cbd9-4c67-a46f-cf29e847ebff","added_by":"auto","created_at":"2025-08-05 13:58:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":720394,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7077728/v1/70243428aa2990c4fe77f70d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pneumococcal disease, atypical presentation in an atypical setting: a case report","fulltext":[{"header":"Highlights","content":"\u003cp\u003e- This case highlights an uncommon presentation of invasive pneumococcal disease.\u003c/p\u003e\n\u003cp\u003e- This emphasizes the importance of a multidisciplinary approach and early diagnosis, considering the relevant prognostic implications that this entails.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eEE is a rare condition characterized by intraocular inflammation and is mainly haematogenous in origin with predominantly unilateral involvement (70%)\u003csup\u003e1\u003c/sup\u003e. The most common etiology is caused by bacteria, which are influenced by various risk factors. The prognosis depends on early diagnosis and the initiation of targeted treatment, often requiring a multidisciplinary approach\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 39-year-old man from C\u0026ocirc;te d\u0026apos;Ivoire, resident in Spain, with no significant past medical history. He was an ex-smoker with a 20 pack-year history and denied the use of other toxic substances. He had no history of risky contacts or recent travel and was not on any regular medication.\u003c/p\u003e\n\u003cp\u003eHe came to the emergency department with asthenia, decreased appetite and dizziness in the previous month, together with epigastric abdominal pain, nausea and vomiting for 10 days. In this context, he has lost 10 kg of weight. The patient also experienced conjunctival erythema, pain and loss of visual acuity (VA) in the left eye (LE) for three days. He reported generalized arthralgias without arthritis. He denied having a cough, expectoration, or chest pain or palpitations. Intestinal rhythm is preserved. There were no skin lesions.\u003c/p\u003e\n\u003cp\u003eHe had conjunctival hyperemia, a cellular reaction in the anterior chamber of 4+, and a 1.5 mm hypopyon associated with the prepupillary fibrin meshwork in the LE (FIGURE 1). VA was 0.8 in the right eye (RE), and no light perception (NLP) was detected in the LE. The remainder of the physical examination was unremarkable, relevant, with no murmurs on cardiac auscultation, aggregate pulmonary sounds, organomegaly on abdominal palpation or skin lesions. He remained normotensive, with a controlled heart rate, and afebrile.\u003c/p\u003e\n\u003cp\u003eWith respect to the diagnostic tests, the following findings were highlighted:\u003c/p\u003e\n\u003cp\u003e- Intraocular pressure (IOP) was 12 mmHg in the RE and 13 mmHg in the LE.\u003c/p\u003e\n\u003cp\u003e- Funduscopy: Funduscopy was not possible in the LE because of media opacity. It was completed with B-mode ultrasound, which revealed dense, hyperechoic content in the vitreous cavity, with the retina applied (FIGURE 2).\u003c/p\u003e\n\u003cp\u003e- Thoracic-abdomino-pelvic CT scan: Centrilobular nodules in left lower lobe, likely related to an inflammatory/infectious process. The rest of the study did not include alterations (FIGURE 3).\u003c/p\u003e\n\u003cp\u003e- SARS-CoV-2 CPR was negative, and the urine antigen for pneumococcus was positive.\u003c/p\u003e\n\u003cp\u003e- Vitreous culture obtained by vitrectomy: \u003cem\u003eS. pneumoniae\u003c/em\u003e susceptible to penicillin was isolated in aerobic medium.\u003c/p\u003e\n\u003cp\u003e- Blood cultures: \u003cem\u003eS.\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003epneumoniae\u003c/em\u003e was isolated from 2/2 of the sample and was susceptible to penicillin.\u003c/p\u003e\n\u003cp\u003e- Blood tests revealed a decrease in the level of IgG subclasses at the expense of IgG2 (79.20 mg/dL), with total levels of other immunoglobulins, C3 and C4 in the normal range. Peripheral blood immunofixation revealed IgG-kappa monoclonal gammopathy, and a bone marrow biopsy confirmed the diagnosis of monoclonal gammopathy of uncertain significance (MGUS). The autoimmunity screening, renal function, liver profile and hemogram results revealed no notable findings.\u003c/p\u003e\n\u003cp\u003eThe patient was admitted with suspected EE, and empirical antibiotic therapy was initiated with meropenem, ceftaroline and voriconazole. After a thorough physical examination, which revealed no relevant findings beyond those already known at the ocular level, a chest X-ray was performed in which a pneumonic consolidation was detected in the left lower lobe, subsequently confirmed by a thoraco-abdomino-pelvic CT scan. The presence of a positive pneumococcal antigen and the isolation of penicillin-susceptible \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e in two blood cultures led to the implementation of simplified monotherapy with ceftaroline.\u003c/p\u003e\n\u003cp\u003eAn early 25G pars plana vitrectomy was performed by the ophthalmology team for diagnostic-therapeutic purposes, which is associated with phacoemulsification without intraocular lens implantation. During surgery, both vitritis and extensive retinal necrosis were observed, and samples were obtained for culture and PCR. Intravitreal vancomycin and ceftazidime were also administered. After the operation, given the visual deterioration and lack of response to the treatments given, ocular evisceration was performed via the four-petal technique.\u003c/p\u003e\n\u003cp\u003eAdditional studies revealed an IgG2 subclass deficiency and IgG kappa MGUS, both of which may have contributed to the susceptibility to severe infection by an encapsulated microorganism.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEndophthalmitis is defined as an infection of intraocular tissue. The route of entry can be categorized as either exogenous, which is caused by direct inoculation of microorganisms, or endogenous, which is acquired via haematogenous spread. EE accounts for approximately 5\u0026ndash;15% of all cases of endophthalmitis, predominantly affecting the right eye because of the direct inflow of blood from the ipsilateral carotid artery\u003csup\u003e1,\u003c/sup\u003e\u0026sup2;.\u003c/p\u003e\n\u003cp\u003eSeveral risk factors contribute to the development of this infection, including diabetes mellitus, cancer, and chemotherapy, all of which are related to immunosuppression in patients. Other risk contributors include parenteral drug use and iatrogenesis due to prolonged catheter use. Diabetes mellitus is the most significant risk factor, as hyperglycaemia leads to an increase in the permeability of the blood\u0026ndash;retinal barrier, creating a favorable environment for the proliferation of microorganisms\u0026sup2;. If haematogenous dissemination is suspected, the relationship with venipuncture and/or central venous access must be considered, although the risk of a hospitalized patient presenting with EE due to bacteraemia or fungaemia is low at 0.05\u0026ndash;0.4%\u0026sup1;,\u0026sup2;. The infectious processes commonly associated with EE include liver abscesses, pneumonia and endocarditis\u0026sup1;.\u003c/p\u003e\n\u003cp\u003eIn the present case, the risk factors that likely contributed to the development of disseminated infection were IgG2 deficiency and the presence of MGUS. IgG subclass deficiency (IgGSD), which occurs in approximately 1 in 10,000 people, is a subtype of primary immunodeficiency characterized by recurrent or severe respiratory infections associated with deficiency of one or more IgG subclasses\u003csup\u003e4,5\u003c/sup\u003e. A retrospective study of 18 patients with IgG2 deficiency revealed a higher prevalence in women, the coexistence of deficiency in other subclasses, such as IgG1 or IgG3, and the limited efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in these patients\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe clinical spectrum of EE is characterized by decreased visual acuity (78%), ocular pain (37%) and fever (34%), so a detailed physical examination is crucial to determine the origin of the infection. Fifty-four percent of patients had normal intraocular pressure (IOP) (10\u0026ndash;21 mmHg), 28% had high IOP (\u0026gt;21 mmHg), and 18% had low IOP (\u0026lt;10 mmHg). Other findings included vitreous inflammation and opacity (63%), conjunctival hyperaemia (36%), retinitis (28%), anterior chamber cells (19%), corneal oedema (12%), choroiditis (8%), corneal clouding (6%) and ciliary hyperaemia (5%)\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn EE, fungi are the most common underlying aetiological agents, with \u003cem\u003eCandida albicans\u003c/em\u003e and Aspergillus spp. being the most common, the latter being associated with a particularly unfavorable clinical course. The distribution of bacterial agents varies according to geographical region, with a higher prevalence of gram-negative bacilli, such as Klebsiella spp., \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eNeisseria meningitidis\u003c/em\u003e (serogroups A, B and C), especially compared with exogenous infections\u003csup\u003e1,3\u003c/sup\u003e. However, gram-positive cocci, such as Streptococcus spp. and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, remain relatively common, especially in Western countries\u003csup\u003e7\u003c/sup\u003e. EE caused by Klebsiella is particularly common in Asian populations. In addition, although less common, acid-fast microorganisms such as \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e in immunocompetent individuals, as well as atypical mycobacteria and Nocardia spp. in immunocompromised patients, may also be involved in this ocular infection\u003csup\u003e8-10\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eEmpirical antibiotic therapy should be initiated promptly, along with adequate source control. Drug diffusion into the vitreous humor is poor, making intravitreal antibiotherapy and often vitrectomy necessary. The most frequently used empirical coverage involves the combination of drugs against gram-positive bacteria, with vancomycin being the drug of choice, and against gram-negative bacteria, with ceftazidime taking precedence over amikacin and gentamicin. In the case of suspicion of fungal etiology, this possibility should be covered with liposomal amphotericin b or intravitreal voriconazole\u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAlthough the role of vitrectomy in EE has not been clearly established and the recommendations of the Endophthalmitis Vitrectomy Study (EVS) may not be directly applicable, this intervention is considered useful in severe cases caused by virulent germs\u003csup\u003e11\u003c/sup\u003e. Vitrectomy not only allows the evacuation of intraocular purulent contents, acting as abscess drainage in a poorly vascularised environment, in line with the principle of \u0026quot;\u003cem\u003eubi pus, ibi evacua\u003c/em\u003e\u0026quot;, but also facilitates the collection of samples for culture, PCR and antibiogram, which reinforces its diagnostic value. Furthermore, several clinical series have shown that vitrectomy is associated with a better visual prognosis and less need for mutilating procedures such as evisceration or enucleation, especially when indicated in the presence of signs such as very low visual acuity at diagnosis, bilateral involvement, dense vitritis or a lack of response to initial medical treatment\u003csup\u003e12-13\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe visual prognosis of endogenous bacterial endophthalmitis is usually unfavorable, with high rates of severe complications such as evisceration or enucleation (25\u0026ndash;50%) and associated mortality that can reach 15%\u003csup\u003e14\u003c/sup\u003e. Bacterial forms, especially those caused by gram-negative bacteria such as Klebsiella, tend to have a poorer visual prognosis than fungal forms do, particularly those caused by Candida spp., which have a relatively better prognosis\u003csup\u003e15\u003c/sup\u003e. Factors such as early diagnosis, early treatment and good initial visual acuity are associated with better visual outcomes, whereas immunosuppression, chronic disease, coinfection, prolonged hospital admission and highly virulent agents are associated with higher mortality and worse functional outcomes\u003csup\u003e16-17\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the first reported case of endogenous endophthalmitis due to S. pneumoniae in a patient with both IgG2 deficiency and MGUS, highlighting the importance of immunological evaluation in atypical presentations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEE:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eEndogenous endophthalmitis.\u003c/p\u003e\n\u003cp\u003eVA: visual acuity.\u003c/p\u003e\n\u003cp\u003eLE: left eye.\u003c/p\u003e\n\u003cp\u003eRE: right eye.\u003c/p\u003e\n\u003cp\u003eNLP: no light perception.\u003c/p\u003e\n\u003cp\u003eIOP: Intraocular pressure.\u003c/p\u003e\n\u003cp\u003eMGUS: monoclonal gammopathy of uncertain significance.\u003c/p\u003e\n\u003cp\u003eIgGSD: IgG subclass deficiency.\u003c/p\u003e\n\u003cp\u003ePPSV23: 23-valent pneumococcal polysaccharide vaccine.\u003c/p\u003e\n\u003cp\u003eEVS: Endophthalmitis Vitrectomy Study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD.L.L. and G.S.F. \u0026nbsp; wrote the main manuscript text. M.E.A., J.J.G. and A.R.A. provided details about the surgical treatment and visual prognosis. G.S.F. and J.J.G. reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by a Roche grant (the funder did not have a role in the conduction of the study; in the collection, management, analysis, or interpretation of data; or in the preparation of the manuscript).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations Ethics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent form is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eInternal Medicine Department, Hospital Universitario Ram\u0026oacute;n y Cajal. IRYCIS. Madrid, Espa\u0026ntilde;a. \u003csup\u003e2\u0026nbsp;\u003c/sup\u003eDepartment of Ophthalmology, Hospital Universitario Ram\u0026oacute;n y Cajal. IRYCIS. Madrid, Espa\u0026ntilde;a.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDurand, M.L. Bacterial and Fungal Endophthalmitis. Clin. Microbiol. Rev. 2017, 30, 597\u0026ndash;613.\u003c/li\u003e\n\u003cli\u003eHu M, Liu M, Jin S, Wang X, Liu X. 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Ocul Immunol Inflamm. 2016;24(5):515\u0026ndash;520. doi:10.3109/09273948.2015.1020173.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endophthalmitis, Infectious, Suppurative uveitis, Pneumococcal pneumonia, Case report","lastPublishedDoi":"10.21203/rs.3.rs-7077728/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7077728/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEndogenous endophthalmitis (EE) is an intraocular infection, frequently bacterial, acquired via hematogenous dissemination. We present the case of a patient with fever and unilateral vision loss who was diagnosed with invasive pneumococcal disease. Despite systemic and intravitreal antibiotic treatment, the patient experienced clinical deterioration which ultimately required ocular evisceration. We emphasize the need for early and aggressive intervention.\u003c/p\u003e","manuscriptTitle":"Pneumococcal disease, atypical presentation in an atypical setting: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-05 13:58:27","doi":"10.21203/rs.3.rs-7077728/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"310baf6e-3c12-470b-b8ce-6716474f522a","owner":[],"postedDate":"August 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T04:08:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-05 13:58:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7077728","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7077728","identity":"rs-7077728","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}