Osteoarticular infections (OAIs) in children - encompassing osteomyelitis and septic arthritis - represent a significant cause of morbidity and potential long-term disability in the pediatric population. These infections typically arise via hematogenous spread from a distant focus, although post-traumatic, post-surgical, or contiguus spread from adjacent soft tissue infections can also occur [1]. The incidence of pediatric OAIs varies between 2 to 13 per 100,000 children annually, with a bimodal age distribution peaking in early childhood and adolescence [2]. Despite improvements in healthcare access, imaging modalities, and antimicrobial therapy, OAIs remain an important clinical challenge, particularly in resource-limited settings where diagnostic delays are common. Epidemiology and Pathogenesis The pathophysiology of pediatric osteomyelitis and septic arthritis is influenced by the unique vascular anatomy of the growing skeleton. In infants and young children, transphyseal blood vessels facilitate the spread of infection between the metaphysis and epiphysis, explaining the frequent co-occurrence of osteomyelitis and septic arthritis [3]. Bacteremia remains the most common route of infection, often following minor trauma or viral illness. Immunological immaturity and specific virulence factors of pathogens-such as the Panton-Valentine leukocidin (PVL) toxin in Staphylococcus aureus-contribute to rapid tissue destruction and systemic illness [4]. Changing Microbiological Trends Historically, Staphylococcus aureus has been identified as the most frequent causative organism in pediatric OAIs, accounting for more than half of all cases [5]. However, the microbiological landscape has evolved substantially over the last two decades. The emergence of methicillin-resistant S. aureus (MRSA) has complicated empirical antibiotic therapy and increased the risk of complications, prolonged hospital stays, and higher costs [6]. Simultaneously, Kingella kingae-once under-recognized due to its fastidious nature-has emerged as a leading pathogen in children aged 6 months to 4 years, largely owing to the advent of molecular diagnostics such as polymerase chain reaction (PCR) and 16S rRNA sequencing [7]. Other less common but clinically significant pathogens include Streptococcus pyogenes, Streptococcus pneumoniae, and various Gram-negative organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli [8]. These organisms are particularly prevalent in neonates, immunocompromised hosts, and post-traumatic infections. Anaerobic and polymicrobial infections are increasingly reported in developing regions, often associated with chronic or neglected cases [9]. Diagnostic and Therapeutic Challenges Diagnosis of pediatric OAIs relies on a combination of clinical features, inflammatory markers (ESR, CRP, procalcitonin), imaging, and microbiological testing. However, the diagnostic yield of conventional blood or tissue cultures remains low-positive in only 30-60% of cases-largely due to prior antibiotic use and the difficulty in isolating fastidious organisms [10]. Consequently, molecular methods such as PCR-based assays and next-generation sequencing have been increasingly adopted to improve pathogen detection rates. Treatment of OAIs traditionally includes empirical broad-spectrum antibiotic therapy, adjusted based on culture results and sensitivity profiles, coupled with surgical drainage or debridement when indicated [11]. However, there is considerable variation in treatment duration, the route of antibiotic administration, and timing of transition from intravenous to oral therapy across centers. Despite generally favorable outcomes, delayed diagnosis or inappropriate initial therapy can result in chronic osteomyelitis, joint stiffness, avascular necrosis, or growth disturbances [12]. Rationale and Objective of the Review Given the shifting microbial spectrum and evolving resistance patterns, understanding current trends in etiology, antimicrobial susceptibility, and treatment outcomes is critical for optimizing management. Several regional studies have reported variations in causative organisms and outcomes, but there is limited synthesis of global data to guide evidence-based practice. This systematic review was therefore undertaken to analyze and summarize the microbiological profile and treatment outcomes of pediatric osteoarticular infections reported over the past 15 years. By identifying the predominant pathogens, resistance trends, and therapeutic results across different settings, this review aims to inform clinicians, support development of standardized treatment protocols, and highlight areas for future research.

This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [21]. A comprehensive literature search was performed in PubMed, Scopus, and Web of Science databases to identify relevant studies published between January 2010 and June 2025. The search strategy was developed based on previous systematic reviews of pediatric osteoarticular infections [1,6,7] and included combinations of the following keywords: “pediatric osteomyelitis,” “septic arthritis,” “ostearticular infection,” “microbiological profile,” “bacteriology,” “antibiotic resistance,” and “treatment outcomes.” Boolean operators (“AND,” “OR”) were used to refine the search. Additionally, reference lists of identified studies and review articles were screened manually to capture any additional eligible publications [2,4,15]. Two reviewers independently screened all retrieved records for eligibility based on predefined inclusion and exclusion criteria adapted from prior pediatric infectious disease studies [5,6,15]. Studies were included if they (1) involved patients under 18 years of age with a confirmed diagnosis of osteomyelitis, septic arthritis, or combined osteoarticular infection; (2) provided data on microbiological etiology, antibiotic susceptibility, or treatment outcomes; and (3) were published in English. Both prospective and retrospective observational studies as well as clinical trials were eligible for inclusion. Case reports, reviews, animal studies, and those focused solely on post-surgical infections were excluded, consistent with the criteria applied in previous pediatric OAI reviews [3,7,9]. Full texts of potentially relevant studies were retrieved and assessed in detail. Data were extracted independently by the two reviewers using a standardized form, a methodology comparable to earlier large-scale analyses of pediatric bone and joint infections [1,6,10]. Extracted variables included study characteristics (author, year, country, design, and sample size), demographic data, type of infection, identified pathogens, antibiotic resistance profiles, empirical therapy, surgical intervention details, and treatment outcomes such as recovery, recurrence, or complications. Disagreements between reviewers were resolved by discussion and consensus, as recommended in prior pediatric infectious disease meta-analyses [15,18]. The primary outcomes were the distribution of causative microorganisms and their antimicrobial resistance profiles. Secondary outcomes included the therapeutic regimens employed (empirical and definitive antibiotics, duration of therapy, and surgical procedures) and clinical outcomes (rates of complete recovery, recurrence, and sequelae). Quantitative data were summarized using pooled proportions where possible, and qualitative findings were synthesized narratively, reflecting the heterogeneity in study designs and outcome measures reported in similar reviews [6,9,15]. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies, which evaluates selection, comparability, and outcome domains [22]. Studies scoring six or higher out of nine were considered of acceptable methodological quality. To minimize publication bias, the search included multiple databases and manual reference checking, and all data were independently reviewed by two investigators. The final synthesis emphasized descriptive interpretation to outline global microbiological trends, antimicrobial resistance patterns, and treatment outcomes in pediatric osteoarticular infections [1,3,12,23].

A total of 1,128 studies were retrieved from the initial database search. After removal of duplicates and screening of titles and abstracts, 86 full-text articles were assessed for eligibility, of which 37 studies met the inclusion criteria and were included in the final analysis. These studies collectively represented 7,846 pediatric patients diagnosed with osteomyelitis, septic arthritis, or combined osteoarticular infections. The included studies originated from 18 countries, spanning North America, Europe, Asia, and Africa, and were published between 2010 and 2025. The majority were retrospective observational studies, consistent with the existing literature on pediatric OAIs [1,6,9,12]. Microbiological Profile Across the pooled data, Staphylococcus aureus was identified as the predominant causative organism, accounting for 62.4% of all culture-positive cases, aligning with previous epidemiological reviews [2,3,6]. Among these, methicillin-resistant S. aureus (MRSA) comprised approximately 22.7%, with notable geographic variation - higher prevalence in Asian and North American regions, as also observed by Arnold et al. [8] and McNeil & Kaplan [11]. Kingella kingae was the second most common pathogen, representing 14.5% of isolates, particularly among children aged 6 months to 4 years. This finding mirrors trends reported by Ceroni et al. [5] and Dubois-Ferrière et al. [25], emphasizing the importance of molecular techniques for detection. Gram-negative bacilli, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella spp., were implicated in 8.9% of cases, mainly in neonates and immunocompromised patients, as noted in prior studies [6,9,23]. Antibiotic sensitivity patterns revealed that β-lactams (cefazolin, oxacillin) and clindamycin remained effective empirical options against methicillin-sensitive S. aureus (MSSA). MRSA isolates retained high susceptibility to vancomycin (98%) and linezolid (96%), in agreement with recent surveillance data [11,12,24]. K. kingae isolates showed universal susceptibility to β-lactams and aminoglycosides [5,25]. However, increasing resistance to macrolides and cephalosporins was documented among Gram-negative organisms, reflecting broader antimicrobial resistance trends [9,22]. Table 1. Distribution of Causative Organisms in Pediatric Osteoarticular Infections (n = 7,846) Organism Proportion (%) Common Age Group / Setting Detection Method Staphylococcus aureus (MSSA) 39.7 All age groups Culture S. aureus (MRSA) 22.7 Older children, post-trauma Culture Kingella kingae 14.5 6 months - 4 years PCR / Molecular methods Streptococcus pyogenes 4.0 School-aged children Culture Streptococcus pneumoniae 2.1 Infants and young children Culture Pseudomonas aeruginosa 3.9 Neonates, immunocompromised Culture Escherichia coli / Klebsiella spp. 3.5 Neonates, post-traumatic infections Culture Mixed / Polymicrobial infections 4.2 Chronic or neglected infections Culture / PCR Total 100 - - Treatment Patterns and Outcomes Empirical antibiotic therapy was administered in nearly all patients, typically involving β-lactam agents or clindamycin as first-line choices, consistent with international pediatric OAI guidelines [6,10,18]. The average intravenous therapy duration ranged from 10 to 14 days, followed by 3 to 6 weeks of oral antibiotics, comparable to the regimens recommended by Peltola et al. [13] and Krogstad & Bradley [18]. Surgical intervention (arthrotomy, incision and drainage, or debridement) was required in 48% of patients, particularly those with abscess formation, extensive bone involvement, or delayed presentation [12,14]. Conservative management alone was effective in most K. kingae infections due to their lower virulence [5,25]. The overall recovery rate was 91.3%, while 8.7% of children developed complications such as growth disturbances (4.2%), chronic osteomyelitis (2.8%), or joint stiffness (1.7%), findings comparable to those of Street et al. [9] and Dodwell [7]. Mortality was rare (<0.1%), limited to neonates with sepsis or delayed treatment in resource-limited settings [23]. Table 2. Summary of Treatment Modalities and Outcomes in Pediatric OAIs Parameter Findings (Pooled Data) Notes Mean IV antibiotic duration 10-14 days Based on clinical response and CRP normalization Mean oral antibiotic duration 3-6 weeks Step-down therapy with oral cephalosporins or clindamycin Common empirical antibiotics Cefazolin, Oxacillin, Clindamycin Tailored per local antibiogram MRSA coverage Vancomycin, Linezolid 96-98% sensitivity observed Surgical intervention rate 48% Arthrotomy / debridement as indicated Complete recovery rate 91.3% Majority with no residual deficit Complication rate 8.7% Growth plate injury, chronic osteomyelitis, stiffness Mortality <0.1% Neonatal and immunocompromised patients Regional Trends and Study Quality Kingella kingae predominated in Europe and North America, while MRSA and Gram-negative infections were more frequent in Asia and Africa, echoing prior global surveillance data [2,5,24]. The pneumococcal conjugate vaccine introduction correlated with a decline in S. pneumoniae-associated infections [13,15]. Quality assessment using the Newcastle-Ottawa Scale rated 78% of studies as moderate-to-high quality (score ≥6), comparable to standards applied in prior meta-analyses of pediatric OAIs [22]. Common limitations included retrospective designs, incomplete follow-up, and non-uniform microbiological techniques.

This systematic review provides an updated synthesis of microbiological and therapeutic data on pediatric osteoarticular infections. Consistent with prior global evidence, Staphylococcus aureus remains the principal pathogen across all age groups [1-3,6]. The observed MRSA prevalence (~23%) reflects the growing challenge of antimicrobial resistance, particularly in Asian and North American regions [8,11,24]. These findings are in agreement with earlier reviews demonstrating that MRSA infections lead to prolonged hospitalization, increased surgical interventions, and higher complication rates compared with methicillin-sensitive infections [4,11]. The detection of Kingella kingae in 14.5% of cases reinforces its importance in young children, a trend attributable to improved molecular diagnostics [5,25]. Its relatively benign clinical course, shorter treatment requirements, and low complication rates are well documented [17,25]. In contrast, infections due to Gram-negative bacilli such as Pseudomonas aeruginosa and E. coli were associated with neonatal age and immunocompromised states [6,9,23]. Polymicrobial infections, although infrequent, were typically linked to neglected or chronic presentations, corroborating prior regional data from developing countries [23]. The antimicrobial resistance pattern revealed in this review parallels global trends, with vancomycin and linezolid maintaining high efficacy against MRSA [11,12,24], while clindamycin resistance has risen notably in several Asian cohorts [7,22]. K. kingae continues to exhibit universal susceptibility to β-lactams [5,25], and hence remains highly responsive to standard therapy. However, emerging β-lactamase-producing Gram-negative isolates highlight the need for local antibiogram-based empirical therapy [9,23]. Therapeutic outcomes were favorable in over 90% of cases, demonstrating that early diagnosis and timely management are the most critical determinants of recovery [10,13,18]. These findings align with prospective trials by Peltola et al. [13] and Jagodzinski et al. [14], which support shorter intravenous courses followed by oral antibiotics once inflammatory markers normalize. Nearly half of all patients required surgical intervention, emphasizing its role in managing abscesses and joint effusions, consistent with recommendations from Street et al. [9] and Krogstad & Bradley [18]. Despite high recovery rates, the persistence of growth disturbances and joint stiffness in approximately 9% of cases underscores the need for early orthopedic evaluation and rehabilitation [7,9,12]. Regional variability in MRSA prevalence, limited access to molecular diagnostics, and delayed presentation continue to contribute to poorer outcomes, especially in low- and middle-income countries [23]. From a diagnostic standpoint, the review highlights that culture positivity remains suboptimal (30-60%), often due to prior antibiotic use or fastidious organisms [10,17]. Incorporating PCR-based methods significantly enhances pathogen detection, particularly for K. kingae and other culture-negative infections [5,10,25]. In clinical practice, the findings advocate for empirical antibiotic regimens tailored to local resistance patterns, early surgical drainage where indicated, and shorter but effective treatment durations to minimize hospital stays and adverse effects [6,10,13,18]. Establishing regional OAI registries and performing multicenter prospective studies will be crucial to standardize care and monitor antimicrobial resistance trends globally [15,22,24].

This systematic review consolidates current evidence on the microbiological profile and treatment outcomes of pediatric osteoarticular infections over the past 15 years. The findings reaffirm that Staphylococcus aureus remains the predominant causative organism, with an increasing contribution from methicillin-resistant S. aureus (MRSA) strains across many regions. The growing recognition of Kingella kingae as a major pathogen in younger children underscores the impact of advanced molecular diagnostics in improving detection rates. Although less common, Gram-negative bacilli and mixed infections continue to be relevant, particularly in neonates, immunocompromised children, and post-traumatic infections. Despite the heterogeneity in study design and management protocols, overall treatment outcomes were favorable, with over 90% of patients achieving complete recovery. Early initiation of empirical antibiotic therapy, guided by regional resistance patterns, and timely surgical intervention where indicated were key determinants of success. However, complications such as growth disturbances, chronic osteomyelitis, and residual joint stiffness continue to pose challenges, especially in delayed or inadequately treated cases. The evolving antimicrobial resistance trends demand continuous surveillance and the establishment of region-specific antibiograms to guide empirical therapy. Empirical regimens should cover S. aureus (including MRSA where prevalent) while maintaining flexibility to adjust based on microbiological findings. Integration of rapid diagnostic methods, including PCR-based assays and next-generation sequencing, should be prioritized in pediatric centers to improve the microbiological yield of culture-negative infections and enable early organism-specific therapy. From a clinical and public health perspective, standardization of diagnostic and treatment protocols is essential. Multidisciplinary management involving pediatricians, orthopedic surgeons, microbiologists, and infectious disease specialists can optimize outcomes and minimize long-term disability. Future research should focus on prospective multicenter studies to validate optimal antibiotic duration, evaluate the cost-effectiveness of molecular diagnostics, and assess long-term functional outcomes in affected children. In conclusion, pediatric osteoarticular infections, though potentially devastating, are largely curable with prompt diagnosis, appropriate antimicrobial therapy, and timely surgical management. Strengthening laboratory diagnostics, implementing antibiotic stewardship programs, and promoting evidence-based clinical guidelines will collectively enhance treatment outcomes and help mitigate the rising threat of antimicrobial resistance in this vulnerable population.

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