Bone infections, including osteomyelitis, prosthetic joint infections, and fracture-related infections, represent a persistent and growing clinical problem associated with substantial morbidity, mortality, and healthcare costs. Their management is complicated by limited bone vascularization, biofilm formation, intracellular bacterial persistence, dysregulated host immune responses and reduced antibiotic delivery to the infection site, which promote chronic infection and recurrence. The limitations of conventional treatment strategies based on surgical debridement and prolonged systemic antibiotic therapy, together with their association with antimicrobial resistance and systemic toxicity, have led to growing interest in alternative and adjunctive therapeutic approaches. Local antibiotic delivery systems, such as polymethyl methacrylate, calcium sulfate, hydroxyapatite-based composites, hydrogels, antibiotic-impregnated bone grafts, and nanoparticle carriers, enable high local antimicrobial concentrations while minimizing systemic exposure. From a different therapeutic perspective, immunomodulatory strategies, including mesenchymal stem cell-based therapies, cytokine-targeted interventions, bacteriophages, quorum-sensing inhibitors, and non-antibiotic antimicrobials, represent emerging approaches aimed at improving infection control and supporting bone regeneration. Advances in biomarker profiling, molecular diagnostics, and artificial intelligence-assisted analyses further support personalized approaches to diagnosis, monitoring, and treatment. Despite encouraging early results, clinical translation remains limited by methodological and regulatory challenges, underscoring the need for integrated, innovative treatment strategies.

Infective endocarditis (IE) during pregnancy, while uncommon, is associated with substantial maternal and fetal morbidity and mortality due to the complex physiological adaptations of pregnancy. Hemodynamic alterations, including increased cardiac output and changes in vascular resistance, combined with immunological modulation, predispose pregnant individuals to increased risk of infection and associated complications. Predominant pathogens implicated in pregnancy-associated IE are Staphylococcus aureus, Streptococcus viridans, and Enterococcus faecalis, with S. aureus infections frequently leading to poorer clinical outcomes. Diagnosis remains challenging due to commonly atypical presentation and relies on microbiological identification via blood cultures in conjunction with imaging modalities such as transthoracic echocardiography. IE in pregnancy is associated with increased maternal mortality rates (5–17%) and adverse fetal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and fetal loss. Management necessitates careful selection of antimicrobial therapy to ensure efficacy while minimizing fetal toxicity, especially in settings of increased antimicrobial resistance. Anticoagulation and surgical interventions must be judiciously considered, with surgical timing individualized based on the severity of heart failure and coordinated multidisciplinary care. In conclusion, IE during pregnancy constitutes a significant clinical challenge, underscoring the need for enhanced diagnostic strategies, optimized therapeutic protocols, and the development of pregnancy-specific management guidelines to improve maternal and fetal outcomes.

Pelvic inflammatory disease (PID), although traditionally viewed as a sexually transmitted infection (STI), can also result from non-sexually transmitted microorganisms that display distinct epidemiologic and clinical characteristics. Unlike STI-related PID, these infections are less influenced by sexual behavior, often show a bimodal age distribution, and are linked to bacterial vaginosis (BV)-associated dysbiosis, iatrogenic uterine procedures, postpartum states, or inadequate access to timely screening and care. Non-STI-related PID is usually polymicrobial, predominantly involving BV-associated vaginal, enteric, or urinary commensals that ascend into the upper genital tract, while respiratory tract organisms, mycobacteria, and biofilm-associated pathogens may also play a role. Pathophysiological mechanisms include disruption of the endocervical barrier, mucus degradation, biofilm formation, hematogenous or iatrogenic seeding, and chronic cytokine-mediated inflammation and fibrosis. Clinical manifestations range from asymptomatic/subclinical disease to acute pelvic pain and tubo-ovarian abscess (TOA) and can progress to systemic infection and sepsis. Diagnosing non-STI PID is challenging due to nonspecific symptoms, negative STI tests, and inconclusive imaging findings, while management relies on broad-spectrum antimicrobials with surgery as needed. Given these complexities, this review aims to synthesize current knowledge on non-STI-related PID, clarify key considerations for its diagnosis, management, and prevention, and outline future perspectives to improve clinical outcomes.