Intramuscular (IM) injection is the administration of medications deep into specifically selected muscles. Large muscles have an abundant blood supply; therefore, the injected medication rapidly reaches the systemic circulation and its intended site of action while bypassing first-pass metabolism. Intramuscular injection is one of the most common medical procedures performed annually. However, healthcare professionals worldwide continue to demonstrate limited adherence to recommended guidelines and standardized algorithms for administering intramuscular injections. Medications may be administered intramuscularly for prophylactic purposes, including immunization, which accounts for approximately 5% of injections, and curative purposes, which account for more than 95%. The most common medications given by IM route include: Antibiotics: penicillin G, benzathine penicillin, and streptomycin. Biological agents: immunoglobulins, vaccines, and toxoids. Hormonal agents: testosterone and medroxyprogesterone . Any nonirritant and soluble drugs may be given IM during an emergency scenario.

Tumoral calcinosis is a rare disorder of ectopic calcium phosphate deposition, usually involving periarticular soft tissues around large joints. Depending on etiology, it may be associated with hyperphosphatemia, fibroblast growth factor 23 pathway abnormalities, recurrent inflammation, ulceration, secondary infection, and progressive functional limitation. Syphilis, caused by Treponema pallidum, remains one of the classic infectious mimics in clinical medicine. Secondary syphilis may present with constitutional symptoms, rash involving the palms and soles, arthralgia, periostitis, tenosynovitis, and inflammatory arthritis, thereby overlapping with the presentation of rheumatic and metabolic bone diseases. We present a case of a 37-year-old man with longstanding nodular tumoral calcinosis who presented with fatigue, generalized arthralgia, worsening discomfort at established calcification sites, and painless palmar lesions. Because of his prior history of tumoral calcinosis-associated ulceration and superficial infection, the initial clinical frame favored a typical tumoral calcinosis flare. Serologic testing, performed because of systemic symptoms and unusual palm lesions, revealed a positive Rapid Plasma Reagin (RPR) and titer of 1:32 with positive Treponema pallidum antibody. Directed sexual history elicited recent unprotected exposures. The patient was diagnosed with secondary syphilis transitioning into early latent syphilis and was treated with doxycycline 100 mg twice daily for 14 days as Penicillin G Benzathine was not available because of supply shortage. This case report highlights diagnostic overshadowing, anchoring bias, and the need to preserve a broad infectious differential when patients with established rheumatologic or metabolic disease develop atypical systemic features.

For more than 70 years, penicillin has remained the cornerstone of treatment for syphilis. While penicillin remains highly effective, there is a pressing need to develop new therapeutic options driven both by ongoing challenges in the supply of benzathine-benzylpenicillin G (BPG) and the need for therapeutics that are more suitable for use in key populations such as pregnant women and infants. Our understanding of syphilis treatment was traditionally based on studies in the rabbit model, with an absence of robust human randomized control trial data. In the last decade, the emergence of the culture model has allowed a comprehensive assessment of a wide range of alternative antibiotics, and there are now a number of phase 2 and phase 3 trials of new therapeutics planned or in progress. Despite this, trials of novel agents for syphilis continue to face a number of major challenges. Progress remains limited by our reliance on indirect diagnostic methods, the need for agents to achieve adequate concentrations in the central nervous system, and for drugs to be suitable for use in pregnancy and infants. Overcoming these challenges requires multidisciplinary research incorporating basic science, pharmacokinetics, clinical trialists, and affected populations to drive forward the therapeutic agenda.

A substantial proportion of patients treated for early syphilis fail to achieve the expected ≥4-fold decline in non-treponemal titers despite appropriate therapy. This serofast state remains a common clinical dilemma, and repeated antibiotic therapy is often ineffective. We hypothesized that persistent seroreactivity may reflect infection-associated immune dysregulation rather than ongoing infection. In this prospective study, 36 adults with early syphilis were treated with benzathine penicillin. At 6 months, 11 patients with inadequate serological response underwent cerebrospinal fluid evaluation; 3 with neurosyphilis were excluded. The remaining 33 patients were classified as serofast (n = 8) or serologically cured (n = 25). Eleven healthy individuals served as controls. Serofast patients demonstrated prolonged phospholipid-dependent coagulation assays compared with serologically cured individuals (all qBH < 0.01; δ = 0.75-0.83). They also exhibited higher BAFF levels and B-cell counts at baseline and follow-up. Posttreatment VDRL titers strongly correlated with BAFF levels, B-cell counts, and coagulation parameters. After exclusion of neurosyphilis, persistent non-treponemal seroreactivity was associated with coordinated B-cell activation and phospholipid-dependent coagulation abnormalities, suggesting an infection-triggered immune phenotype rather than ongoing Treponema pallidum infection.

Syphilitic proctitis is an uncommon presentation of Treponema pallidum infection and can closely resemble other anorectal conditions. Due to its non-specific symptoms, it is often underdiagnosed, particularly in individuals without systemic manifestations. A male patient in his 30s presented with isolated rectal bleeding. Sigmoidoscopy revealed multiple superficial ulcers over the folds of the anal canal, along with erythematous rectal mucosa and focal erosions. Given the patient's history of unprotected sexual intercourse, serological testing was performed. The Venereal Disease Research Laboratory test and histopathology from the rectal ulcers confirmed the diagnosis of syphilitic proctitis. The patient was treated successfully with intramuscular benzathine penicillin, resulting in complete resolution of symptoms. This case underscores the importance of considering T. pallidum infection in patients with unexplained rectal bleeding, particularly those with a history of unprotected sexual activity. Early recognition and appropriate antibiotic therapy are essential to prevent complications and limit transmission.

Despite available guidelines, congenital syphilis (CS) continues to burden low- and middle-income countries (LMICs), with failures occurring across multiple points. Two prior case reports from India described symptomatic infants with delayed diagnoses resulting from absent or ignored antenatal screening. We add five neonates identified prospectively at birth at a tertiary care centre in northern India (September 2024-January 2026), born to mothers with reactive syphilis serology. All were asymptomatic, but maternal treatment was adequate in only two cases. Neonatal RPR was reactive in one infant only. Based on CDC criteria, one neonate was classified as highly probable CS, three as possible, and one as less likely. Limited availability of aqueous crystalline penicillin necessitated benzathine penicillin use in all cases, and one infant left against medical advice. Together, these series map recurring, correctable failures across the entire CS prevention cascade in LMICs.

Intramuscular (IM) injection of benzathine benzylpenicillin G (BPG) forms the cornerstone of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) secondary prophylaxis. BPG is available as either a low-cost powdered formulation or a costlier pre-filled suspension. Most of the global RHD burden lies in low- and middle-income countries, which rely on the powdered formulation. Prospects of achieving RHD control targets continue to be hindered by global BPG supply issues. Guided by a preliminary consultation of global stakeholders published in 2016 which outlined the desired characteristics and changes to the existing BPG product, much progress has been made in improving tolerability of BPG for ARF/RHD secondary prophylaxis. A second stakeholder consultation of experts and consumer representatives was convened during the World Congress on Rheumatic Heart Disease in Abu Dhabi, UAE, in November 2023 with the objective of evaluating alternate delivery models and the need for new BPG formulations. Topics explored included current barriers and enablers to local secondary prophylaxis uptake, desired changes to the delivery model and ways to improve access to secondary prophylaxis in resource-limited settings. Our findings highlight inadequacies of the current one-size-fits-all approach and the need for education, access to health systems and personnel as well as flexibility and adaptability to meet individual and community needs for effective programme delivery while new and improved BPG formulations, which will overcome current barriers, are eagerly awaited.

Penicillin-allergy assessment within sexual health clinics is critical for timely, safe, and effective syphilis treatment among marginalized populations who experience multiple barriers to care. It is also an important public health measure to support antibiotic stewardship in populations at high-risk for antibiotic use. This report describes a quality improvement project in a sexual health clinic that used nursing protocols for penicillin-allergy assessment with a validated risk scoring tool (PEN-FAST) and direct oral amoxicillin challenge. In the first year of protocol implementation, just over 75% of patients with syphilis who reported penicillin allergy were treated safely with benzathine penicillin G.