Highlights
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Syphilis rates in the United States are at a 70-year high.
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Treatment of syphilitic uveitis has been complicated by national penicillin shortages.
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Intravitreal ceftazidime can provide short-term control of syphilitic uveitis.
Objective
To review the clinical outcomes of patients with ocular syphilis that were treated in the short-term with intravitreal ceftazidime when definitive treatment with penicillin was delayed due to a variety of extenuating circumstances.
Design
Retrospective interventional case series.
Participants
A total of 45 patients diagnosed and treated for syphilitic posterior or panuveitis between January 2, 2019, and July 1, 2024, at a tertiary referral private practice. Of these, 10 patients ( n = 14 eyes) were treated short-term with intravitreal ceftazidime before initiating penicillin therapy. Three of these patients are presented as cases to highlight factors that might contribute to treatment delays.
Intervention
One or more intravitreal injections of 2.25 mg/0.1 mL ceftazidime.
Main Outcome Measures
Visual acuity, inflammatory grade based on Standardization for Uveitis Nomenclature criteria, causes for delay in systemic antibiotic treatment, changes in aqueous bacterial polymerase chain reaction (PCR) following ceftazidime administration, changes in multimodal imaging.
Results
Following treatment with intravitreal ceftazidime and prior to penicillin treatment, all eyes ( n = 14) had improved inflammatory parameters. Of the 9 eyes with measurable baseline Snellen vision, all improved by an average of 5.4 lines (range = +1 to 9). In the two eyes of patients for whom aqueous bacterial PCR was initially positive for Treponema pallidum , subsequent PCR was negative prior to initiation of penicillin. All patients eventually received definitive systemic antibiotic therapy and had resolution of their syphilitic uveitis.
Conclusion
Patients experienced improvements in visual acuity and inflammation when treated with intravitreal ceftazidime before the initiation of penicillin, suggesting that ceftazidime could be leveraged in care for those with syphilitic uveitis. With the increasing number of cases of syphilis nationally over the last decade, combined with the growing shortages of penicillin, it is vital to consider adjunctive therapies for treatment of syphilitic uveitis to help improve visual outcomes.
INTRODUCTION
S yphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum ( T. pallidum ). Ocular syphilis—a form of neurosyphilis—can affect any ocular structure, but most commonly results in posterior uveitis and panuveitis. , The Centers for Disease Control and Prevention (CDC) guidelines for the management of ocular syphilis in adults include administration of aqueous crystalline penicillin G 18 to 24 million units per day for 10 to 14 days or a combination of procaine penicillin plus probenecid for a similar duration. This contrasts with the treatment of primary or secondary syphilis not affecting the eye or central nervous system, where a single intramuscular dose of 2.4 million units of Benzathine penicillin G will suffice.
Historically, syphilis has had a higher prevalence in low- and middle-income countries, but there has been a growing burden in higher-income countries over the past few decades. This is partially due to increased incidence among populations at higher risk for HIV acquisition, such as men having sex with men and intravenous (IV) drug users. The CDCs 2022 sexually transmitted infection surveillance report found that between 2018 and 2022 reported cases of syphilis rose by 80%, leading to syphilis rates that equate to a 70-year high. Estimates show that incidence of syphilis in the United States increased 5-fold between 2001 and 2019. In Tennessee specifically, infection rates grew 86% between 2017 and 2021.
Penicillin shortages only further exacerbate this growing burden. Pfizer, the exclusive supplier of benzathine penicillin and procaine penicillin, reports the shortage will last at least through the end of 2024. Other barriers such as penicillin allergies, socioeconomic barriers, and an overwhelmed healthcare system during the peak of the COVID-19 pandemic have the potential to further delayed systemic treatment. With the potential for ocular complications secondary to syphilis to lead to severe vision loss, other treatment options must be examined and considered in cases where standard definitive therapy is delayed. At present, there is limited data on the utility of alternative treatments, such as intravitreal ceftazidime, as an adjunct to systemic therapy in the management of syphilitic uveitis. , In this series, we review clinical outcomes in patients with ocular syphilis who were treated in the short-term with intravitreal ceftazidime monotherapy until systemic antibiotics could be administered.
METHODS
In this single-center, retrospective interventional case series, patients were identified that were treated for syphilitic posterior or panuveitis by a single physician (AST) between January 2, 2019, and July 1, 2024. Of these patients, data was extracted for those treated with intravitreal ceftazidime monotherapy prior to initiation of systemic antibiotics. Patient demographics, baseline ocular findings, clinical outcomes, imaging characteristics, and rationale for delayed treatment with systemic antibiotics were abstracted. Uveitis was graded at all visits using the Standardization of Uveitis Nomenclature criteria. All patients received one or more intravitreal injections of 2.25 mg/0.1 mL ceftazidime and had a repeat ocular examination and multimodal imaging while awaiting initiation of systemic antibiotics. In a subset of patients, aqueous sampling was performed before injection of intravitreal ceftazidime and then at a subsequent visit. Initial aqueous samples were sent for broad-range bacterial, fungal, mycobacterial, toxoplasma, and targeted viral polymerase chain reaction (PCR) testing. Subsequent aqueous samples were sent for bacterial PCR alone to determine infection resolution. This study adhered to the tenets of the Declaration of Helsinki and was determined to be exempt from IRB approval by Western IRB.
RESULTS
Patient characteristics
Patient demographics are summarized in Table 1 . Of the 45 patients with syphilitic posterior or panuveitis identified, 10 patients (14 eyes) received intravitreal ceftazidime prior to the initiation of systemic antibiotics. Fifty percent were female, 60% were Caucasian and 40% were African American. Four patients (40%) were HIV positive, of which 3 were on highly active antiretroviral therapy at the time of uveitis diagnosis. Two patients (20%) were unhoused, five (50%) were uninsured, two (20%) were current IV drug users and three (30%) were allergic to penicillin.
| Age | Gender | Race | HIV Positive? | Eye(s) Involved | SUN Classification | Presenting Vision | RPR Titer at Initial Visit | Reason for Delay in Penicillin Treatment | Time From Diagnosis to Starting Penicillin | Number of Intravitreal Injections of Ceftazidime | Vision Following Injection Prior to Starting Penicillin | Vision at Final Follow-up |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 61 | M | C | Yes | OD | Posterior uveitis | 20/70 | 1:64 | Penicillin allergy | 2 weeks | 1 | 20/40 | 20/30 |
| 59 | F | A | No | OU | Panuveitis with retinal vasculitis | 20/100 OD, 20/200 OS | 1:128 | Penicillin shortage | 3 weeks | 2 | 20/40 OD, 20/25 OS | 20/30 OD, 20/25 OS |
| 64 | M | C | No | OS | Panuveitis with retinitis | 20/200 | 1:512 | Penicillin shortage | 2 weeks | 1 | 20/30 | 20/25 |
| 58 | M | C | Yes | OU | Panuveitis | HM OD, LP OS | 1:128 | Noncompliance | 1 week | 1 | CF OD, HM OS | 20/20 OD, 20/200 OS |
| 47 a | F | C | No | OU | Panuveitis | CF OD, HM OS | 1:256 | Penicillin allergy, no hospital beds | 6 weeks | 2 | 20/25 OD, 20/40 OS | 20/20 OD, 20/25 OS |
| 59 b | M | A | Yes | OD | Posterior uveitis | 20/50 | 1:32 | Penicillin shortage | 4 weeks | 2 | 20/40 | 20/25 |
| 51 c | F | C | No | OU | Panuveitis with retinal vasculitis | CF OU | 1:256 | Noncompliance | 3 months | 2 | 20/60 OU | 20/50 OU |
| 41 | F | C | No | OD | Posterior uveitis | 20/200 | 1:64 | No hospital beds | 6 weeks | 2 | 20/30 | 20/20 |
| 56 | M | A | Yes | OD | Posterior uveitis | CF | 1:128 | Penicillin shortage | 3 weeks | 1 | 20/100 | 20/40 |
| 49 | F | A | No | OD | Panuveitis | 20/400 | 1:512 | Penicillin allergy, noncompliance | 4 weeks | 2 | 20/80 | 20/30 |
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