Osteoarticular Infections in Immunocompetent Children Due to Atypical, Fastidious or Unusual Bacterial Pathogens: A Review

1. Introduction

Paediatric osteoarticular infections (OAIs) are major diagnostic and therapeutic challenges as they can lead to prolonged morbidity, systemic complications, joint damage, growth disturbances and long-term functional impairment. Accurate identification of the causative organism is central to its effective management, as it confirms the microbiological diagnosis, guides targeted antimicrobial therapy and may improve clinical outcomes. Furthermore, precise pathogen identification enables detailed assessment of the antibiotic resistance profile, which is essential for guiding antimicrobial therapy.

Before the early 2000s, pathogen detection depended mainly on traditional cultures of blood, joint fluid or bone aspirates [1,2,3]. However, despite the appropriate sampling of paediatric OAIs, culture-negative results were common: 24–68% of cases of acute haematogenous osteomyelitis and 21–70% of cases of septic arthritis [1,2,3]. These culture-negative infections may have reflected the presence of fastidious organisms, low bacterial inoculum, prior antibiotic exposure or the intrinsic limitations of conventional culture-based methods. Over the past 20 years, the greater sensitivity and specificity of nucleic acid amplification assays (NAAAs) have greatly enhanced pathogen detection in cases of paediatric OAI [4,5,6]. Beyond pathogen identification, some NAAAs can detect genes associated with antibiotic resistance mechanisms and virulence factors [7]. Next-generation sequencing, the most advanced iteration of NAAA technology, is anticipated to become a fundamental tool of clinical microbiology as pathogen characterisation transitions from traditional phenotypic approaches—such as staining, morphology and metabolic profiling—to a genomic-based framework. Plasma-based, metagenomic, next-generation sequencing is a particularly promising approach, as it may be able to detect the pathogens responsible for localised infections from circulating microbial DNA [8,9,10]. Taken together, these advances suggest that the identification and resistance profiling of causative pathogens will increasingly become routine for paediatric OAIs.

Clinicians are therefore increasingly likely to encounter a broader spectrum of uncommon, fastidious and emerging bacterial pathogens in community-acquired OAIs affecting otherwise healthy children. Due to clinicians’ limited experience with these atypical and rarely occurring pathogens, a heightened awareness of these infections is essential for accurately identifying and effectively managing them. This review examines the uncommon bacterial pathogens responsible for paediatric OAIs in immunocompetent children, with an emphasis on their microbiological features, epidemiology, clinical phenotypes and appropriate diagnostic approaches

2. Literature Search

This review was based on a targeted literature search of PubMed/MEDLINE and on the screening of relevant reference lists. Search terms included combinations of “paediatric”, “children”, “osteomyelitis”, “septic arthritis”, “osteoarticular infection”, “fastidious bacteria”, “atypical pathogens”, “unusual pathogens”, “culture-negative infection”, “molecular diagnosis”, “polymerase chain reaction”, and the names of the individual bacterial pathogens discussed in this review.

Priority was given to paediatric studies, case series, systematic reviews, narrative reviews, and clinically relevant microbiological reports. Adult data were considered only when paediatric evidence was sparse and when they provided relevant microbiological, diagnostic or epidemiological insight. Because of the rarity and heterogeneity of these pathogens, no formal systematic review or meta-analysis was performed.

3. Microbiological Basis: Fastidious & Atypical Organisms

Fastidious microorganisms have complex or specific nutritional needs and will only grow when certain nutrients are present in their environment: they are thus difficult to cultivate using standard methods. Nevertheless, the concept of fastidiousness extends well beyond the simple notion of dependency on specific nutrients. It includes the requirement for a variety of chemical signals, many of which are produced by surrounding bacterial species. As early as 1974, Lewis Thomas noted in The Lives of a Cell [11] that most microbes could not be cultivated alone because they exist in dense, interdependent communities reliant on complex chemical signals. This insight highlighted the limitations of the classic culture-based methods used to detect certain microorganisms.

Atypical bacteria are prokaryotes that differ from standard bacteria due to features such as absent or atypical cell walls, uniquely specialised growth requirements or an obligate intracellular mode of replication. Conventional Gram staining may poorly visualise or inconsistently characterise them, for the same reasons. This group typically includes organisms such as Mycoplasma spp., which lack cell walls, Chlamydia spp., which are obligate intracellular pathogens, and Legionella spp., which require specialised culture conditions [12,13,14]. Although uncommon, atypical and fastidious bacteria have been increasingly recognised as potential causes of OAIs, particularly when conventional cultures are negative. Diagnoses often depend on molecular methods instead of routine cultures because these bacteria have strict growth requirements and may be intracellular [13,14].

A growing body of case reports and small series studies has identified a diverse array of fastidious and atypical microorganisms involved in paediatric OAIs, many of which were only identified thanks to extended culture techniques or molecular diagnostics. These include HACEK group microorganisms, anaerobes, slow-growing Gram-negative bacilli and atypical bacteria, all characterised by their low or negligible culture yields using conventional methods. Knowledge of the epidemiological and clinical characteristics of these less common pathogens is becoming increasingly important since current molecular diagnostic techniques will identify them more frequently. Clinicians managing paediatric OAIs will be increasingly likely to encounter uncommon pathogens for which routine orthopaedic and paediatric practice provides limited guidance. The main uncommon, fastidious, emerging and exposure-related bacterial pathogens associated with paediatric OAIs are summarised in Table 1.

4. Hacek Group Microorganisms

The acronym HACEK refers to a group of fastidious Gram-negative microorganisms, including Haemophilus spp., Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans), Cardiobacterium hominis, Eikenella corrodens and Kingella kingae. HACEK microorganisms grow slowly in standard blood cultures, often requiring extended incubation [15]. Usually found in the oropharynx, they are primarily known for causing infective endocarditis, but they can also lead to OAIs.

4.1. Kingella Kingae

OAIs caused by K. kingae are the prototypical example of fastidious, frequently culture-negative, Gram-negative musculoskeletal infections in young children. Since the 1980s, the reported number of cases of K. kingae OAIs has markedly increased, mainly due to the use of molecular identification methods [16,17,18,19,20]. K. kingae is thus now regarded as the leading bacterial cause of paediatric OAIs, especially in children under 48 months old [21,22,23]. In addition to classic acute haematogenous osteomyelitis and septic arthritis, this pathogen can cause atypical OAIs, including spondylodiscitis [24,25,26,27,28,29], subacute osteomyelitis [30,31,32], pyomyositis [33], bursitis [34] and tendon sheath infections [35,36,37].

K. kingae septic arthritis generally involves large weight-bearing joints such as hips, knees, ankles, shoulders or elbows [17,18,21,22,23,38,39,40]. Atypical joints, such as small metacarpophalangeal and metatarsophalangeal joints and sternoclavicular, acromioclavicular or tarsal joints, are over-represented in cases of K. kingae arthritis, compared to septic arthritis, due to the presence of other pathogens [16,17,18,21,22,23,38,39,40]. The anatomical sites involved in paediatric patients with K. kingae osteomyelitis include long bones such as the femur, tibia, humerus, radius and ulna [17,18,21,22,23,38,41]. A dedicated case series focusing on K. kingae-induced septic arthritis of the knee in young children emphasised its relatively mild clinical presentation and modest biological inflammatory response [42]. Nevertheless, any bone rarely infected by other pathogens, such as the calcaneum, talus, sternum or clavicle, can also be affected by K. kingae osteomyelitis [21,22,38,39,40]. The onset of a K. kingae OAI is generally insidious, and the disease is frequently diagnosed after a considerable delay, at a time when bone lesions are already subacute in character and can present as lytic lesions [31,32]. Finally, the clinical course is usually better for children with an OAI due to K. kingae rather than other typical pathogens, as evidenced by shorter hospitalisations and fewer adverse events [21,22,38,43]

4.2. Kingella Negevensis

K. negevensis is a newly described Gram-negative bacterium closely related to K. kingae. Like K. kingae, K. negevensis can be isolated from the oropharynx of young children, and, in some cases, it is probably misidentified as K. kingae. Indeed, K. negevensis produces many of the same virulence factors as K. kingae, including a polysaccharide capsule, a secreted exopolysaccharide, a Knh-like trimeric autotransporter and type IV pili, suggesting that K. negevensis has significant pathogenic potential and can cause OAIs [44,45].

4.3. Non-Type-B Haemophilus Influenzae, Unencapsulated H. Influenzae and H. Parainfluenzae

In the post-vaccination era, Haemophilus spp. rarely cause OAIs, with H. influenzae type b (Hib) now rare in countries with widespread immunisation programmes. However, some non-typeable H. influenzae (NTHi) and other encapsulated strains (particularly serotypes a, f and e) that are not targeted by immunisation continue to cause OAIs [46,47,48,49]. At Texas Children’s Hospital, from 2011 to 2018, non-typeable strains accounted for 39.3% of invasive H. influenzae infections [50,51,52,53], and type a accounted for 29.5% [54]. H. influenzae type a is the most common serotype, although types d, e and f are also reported. Another Haemophilus species, Haemophilus parainfluenzae, is an extremely rare cause of paediatric OAIs, with only a handful of cases reported in the literature [55,56,57].

These OAIs typically affect children younger than 4 years, with the highest prevalence between 7 and 24 months old [58]; septic arthritis is the most common manifestation. Indeed, a recent systematic review of the literature documented just 21 cases of acute septic arthritis due to non-type-b H. influenzae [50]. As was often the case with OAIs due to Hib, children tended to be under 2 years old and present with a monoarticular acute septic arthritis, usually affecting the knee [50]. Acute haematogenous osteomyelitis is much less common with non-type-b H. influenzae, and it may be concurrent with acute septic arthritis in up to 40% of cases [50].

Unencapsulated strains of H. influenzae (non-typeable H. influenzae) appear to be much rarer causes of OAIs than non-type-b H. influenzae, with only scattered reports in the literature, primarily describing acute septic arthritis [59]. From a practical viewpoint, given their rarity and potentially lower virulence, isolating an unencapsulated strain of H. influenzae should prompt an immunological evaluation of the child.

4.4. Aggregatibacter Actinomycetemcomitans

Aggregatibacter actinomycetemcomitans is another member of the HACEK group. It primarily colonises the human oral cavity and is associated with aggressive periodontitis. It can also cause serious extraoral infections, including rare cases of OAIs like osteomyelitis and septic arthritis. Indeed, it has been implicated in osteomyelitis and epidural abscesses in children and adults [60], demonstrating that even slow-growing, Gram-negative microorganisms should be considered in the differential diagnosis of culture-negative OAIs, and emphasising the importance of using tissue cultures and NAAA technologies [61].

5. Other Uncommon, Fastidious and Exposure-Related Pathogens

5.1. Neisseria Meningitidis

While mostly known for causing meningitis, N. meningitidis can also cause osteoarticular disorders, such as septic arthritis, reactive arthritis and osteomyelitis. Arthritis can occur as a primary, isolated infection or can be secondary to sepsis. Joint arthritis may complicate acute meningococcal disease in 5–10% of cases [62,63,64] and commonly affects the knees and hips. Primary septic arthritis due to Neisseria meningitidis without accompanying meningitis remains extremely rare and tends to be monoarticular [65,66,67]; it affects the larger joints in patients of all ages [62,63]. Primary meningococcal arthritis has been reported with serotypes W-135, B and C [62]. Alongside septic arthritis directly due to the pathogen, an immune-mediated arthritis may also develop, often appearing later in the disease course [62,64,68] and often being polyarthritic [64]. Given the ease with which this microorganism can be treated with antimicrobial therapy, its relative contribution to septic arthritis is probably underestimated, and some cases of immune-mediated arthritis probably involve eradicated septic arthritis. Acute haematogenous osteomyelitis due to N. meningitidis is less common than primary meningococcal arthritis, likely accounting for fewer than 2% of all cases of paediatric osteomyelitis [69,70]. In otherwise healthy children, it has been reported in the tibia [71], fibula [72], acromion [73], lumbar vertebrae [74] and humerus [75]. Serogroup B N. meningitidis (for which no vaccine existed until recently) predominates in the literature [71], although serogroups C and Y have also been described [71,72,73,74,75].

5.2. Borrelia Burgdorferi

Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi, a member of the Spirochaetaceae family. Borrelia burgdorferi’s vectors are ticks of the Ixodes genus, which transmit the pathogen to human hosts while feeding on their blood. The typical clinical picture of Lyme disease includes symptoms involving the skin, joints, nervous system and, more rarely, the heart and eyes [76,77]. Lyme disease has three main stages: early localised, early disseminated and late disseminated infections. Musculoskeletal symptoms are common, but arthritis—characterised by swelling and pain in one or more large joints—is the main sign of Lyme borreliosis. Patients with confirmed borreliosis may also experience tendon, muscle or bone pain [78,79]. Joint involvement is typically asymmetrical and mostly in large joints, particularly the knees, but small joints may also be affected as components of oligoarthritis. Apart from knees, Lyme arthritis commonly also affects shoulder, elbow, wrist and ankle joints [76,78,79,80]. Lyme arthritis results from a strong inflammatory response (not from spirochete toxins) that causes subsequent host-driven aggrecan degradation and leads to cartilage damage and severe joint injury [76]. In the early localised stage of erythema migrans, almost half of patients experience migratory muscle and joint pain. The time between a tick bite and the onset of Lyme arthritis can vary greatly, ranging from a few days to several months [81,82]. If present for longer durations, Lyme arthritis can lead to the erosion and destruction of joint structures.

5.3. Brucella spp

Brucellosis is a zoonotic infection caused by species of the Brucella genus. Brucella are small, aerobic, intracellular coccobacilli that preferentially localise in the reproductive organs of host animals (mainly ruminants), causing abortions and infertility in infected animals. The bacteria are transmitted from animals to humans through the ingestion of infected food (mainly unpasteurised dairy products), direct contact with infected animal products or viscera, or the inhalation of aerosols [83,84].

Brucellosis is primarily found among children living in endemic areas, but the disease has also been reported among returning travellers or individuals residing in regions bordering endemic areas [83,85]. Travel and globalisation both increase the likelihood that patients will present with a potential Brucella infection that has moved from an endemic to a non-endemic area. Alongside the classic clinical picture, which combines several non-specific systemic features (fever, fatigue, weight loss, hepatosplenomegaly), Brucella frequently presents together with arthritis or arthralgias (up to 40–80% in some series) that can mimic the presence of septic arthritis (with invasion of the organism into the joint space) [86,87]. However, arthritis is usually reactive in nature [88], polyarticular, additive and non-migratory, typically involving the sacroiliac region, knees or hips [83,84,86,89,90]. Alongside reactive arthritis, nearly 10% of individuals infected with Brucella spp. and presenting with osteoarticular complaints have their bacterial growth confirmed by synovial fluid culture [88]. However, this microorganism’s relatively fastidious nature may preclude its more frequent isolation in culture, leading to an underestimation of the true incidence of acute septic arthritis occurring with this pathogen [91]. Knees and hips are the joints most frequently affected by culture-proven acute septic arthritis due to Brucella spp. [92]. Though less commonly reported than acute septic arthritis, acute haematogenous osteomyelitis may also be caused by Brucella spp., with cases involving osteomyelitis of the calcaneus, the sternum and olecranon, and the femur described in the literature [89,92,93,94].

The direct inoculation of synovial fluid into blood culture bottles may improve culture yield and increase the isolation rates of Brucella spp. [91]. Real-time qPCR has emerged as a rapid, sensitive and specific tool for diagnosing brucellosis, overcoming many of the limitations of traditional culture and serological methods. While bacterial culture remains the gold standard assay, it is time-consuming and not very sensitive, making qPCR the preferred alternative for quick, genus-level identification of Brucella [95,96].

5.4. Salmonella spp

OAIs caused by Salmonella spp. are rare but serious, usually manifesting as osteomyelitis or septic arthritis, often after bacteraemia in immunocompromised individuals or those with sickle cell disease. Non-typhoidal Salmonella can also cause invasive infections, but there are no risk factors in young children, especially under 1 year old [97]; a Taiwanese series found that over 60% of bacteraemia cases occurred in this age group [97]. However, the distribution of non-typhoidal Salmonella osteomyelitis in healthy children does not reveal a predominance of involvement among infants. Indeed, one series demonstrated that among the 46 cases of non-typhoidal Salmonella osteomyelitis reviewed in healthy children, only 19% were infants, with a median age of 9 years old and male predominance (61%) [98]. The most common serotypes were S. Enteritidis and S. Typhimurium. Complications were frequent and occurred in 41% of subjects, including relapses, multifocal disease or suppurative issues [98].

Acute septic arthritis with non-typhoidal Salmonella is rare. Sirinavin et al. described 82 invasive infections involving non-typhoidal Salmonella in immunocompetent children, only 2 (2.4%) of which involved acute septic arthritis [99], and Punpanich et al. reported that just 1.3% of 226 children with a culture-confirmed, invasive non-typhoidal Salmonella infection developed acute septic arthritis [100]. Acute septic arthritis due to non-typhoidal Salmonella has been reported in otherwise healthy children in elbows, sacroiliac joints, knees, metacarpophalangeal joints and shoulders [101,102,103,104,105]. Acute septic arthritis due to non-typhoidal Salmonella can be difficult to distinguish from reactive arthritis associated with gastrointestinal Salmonella infections [106,107]. Reactive arthritis due to Salmonella appears to have a slight female bias and is more common in adults than children [108]. Its incidence varied from 1.2–29.0% [108], presenting as either mono- or oligoarticular, and most commonly affecting the knee [106]

Authors should discuss the results and how they can be interpreted from the perspective of previous studies and of the working hypotheses. The findings and their implications should be discussed in the broadest context possible. Future research directions may also be highlighted.

5.5. Fusobacterium spp

Fusobacterium spp. are Gram-negative, anaerobic bacilli that are part of normal oral and gastrointestinal flora; they are usually opportunistic pathogens. OAIs due to anaerobic pathogens are rare, and, when present, Fusobacterium spp. are likely their most common cause in otherwise healthy children. Fusobacterium nucleatum and Fusobacterium necrophorum are the most frequently reported in the literature, although other species, such as Fusobacterium fusiforme, have been reported as well [109]. Fusobacterium spp. are the most common aetiological agents of Lemierre’s syndrome, which is characterised by bacteraemia involving anaerobic organisms (indeed, usually Fusobacterium spp.), internal jugular vein thrombosis, and a metastatic, suppurative spread of infection (abscess formation in various locations) [110]. Many reported cases of OAIs involving Fusobacterium spp. are associated with anaerobic sources of infection such as sinus disease, dental abscesses, mastoiditis or dog bites [111]. These infections are often polymicrobial [111], but an isolated disease, without the risk factors for an anaerobic source of infection, may also be observed, especially in children. Thus, Fusobacterium spp. may be present because of a metastatic spread of infection with acute septic arthritis [112,113] or acute haematogenous osteomyelitis [110,113]. Acute septic arthritis due to Fusobacterium spp. has been reported in hips [114,115,116] and knees [117], and acute haematogenous osteomyelitis has been reported in the pelvic region [118], hips [119] and femurs [120] without the presence of Lemierre’s syndrome or risk factors for anaerobic infection. Fusobacterium spp. have also been identified as the causative pathogens in cases of subacute osteomyelitis and pelvic OAIs with Brodie’s abscess in children [121,122]. Interestingly, patients with OAIs due to Fusobacterium spp. are often older than those with OAIs due to more typical organisms. Of the 23 cases of OAI involving Fusobacterium spp. identified in a narrative review, 19 patients (83%) were over 8 years old, suggesting that OAIs due to Fusobacterium spp. tend to occur in older children [123]. These cases are diagnostically challenging, as anaerobic cultures require specific conditions and results are frequently delayed or negative.

5.6. Actinomyces spp

Actinomyces spp. are anaerobic Gram-positive bacteria that usually colonise the mouth, gut or genital tract. Infection occurs when they invade tissue during dental work, through poor oral hygiene or due to trauma. Actinomyces is therefore another anaerobic organism occasionally associated with OAIs. Actinomyces israelii is the most commonly reported species, though Actinomyces odontolyticus, Actinomyces viscosus, Actinomyces turicensis and Actinomyces naeslundii have also been mentioned [124,125,126]. Actinomyces OAIs are chronic in character and often follow a very indolent course, mimicking tumours or tuberculosis [125]. A systematic review of osteomyelitis cases due to Actinomyces spp. demonstrated a median time to presentation of 3 months, with three cases only being recognised after 2 years [125]. Actinomyces spp. are common flora in the oral cavity, which explains why over half of all Actinomyces infections involve the cervicofacial region [110]. Because of this tendency, the mandible is the most frequently affected bone in cases of osteomyelitis, in front of spondylitis of the C1 and C2 vertebrae [124,127]. Osteomyelitis of the iliac bone has also been encountered due to the disease spreading from the pelvis. Culture attempts are essential, but given the microorganism’s fastidious nature, NAAAs or a histological analysis may be required for diagnosis [124,125,127]. Histopathological analysis of Actinomyces infections often demonstrates infiltrative spread across tissue and fascial planes, sinus tract formation, sulphur granules, and Gram-positive branching organisms with acute-angle branching [123].

5.7. Other Rare Pathogens

Group C and G Streptococci (GCGS) OAIs in children are uncommon compared to other pathogens, with these microorganisms predominantly affecting elderly adults rather than paediatric populations. GCGS OAIs in humans generally produce a less acute clinical presentation than Group A Streptococcus [128]. Indeed, many GCGS in humans belong to the Streptococcus dysgalactiae subspecies equisimilis (SDSE), which shares many virulence factors with S. pyogenes through horizontal gene transfer [129,130,131]. Thus, GCGS have not been listed among the major pathogens in recent large prospective studies of paediatric OAIs [132,133].

A few cases of OAIs due to GCGS in otherwise healthy children have nevertheless been reported in the literature, with just one case of acute haematogenous osteomyelitis and six cases of acute septic arthritis [134,135,136,137,138]. Many laboratories are unable to identify isolates down to the species level (e.g. Streptococcus dysgalactiae, S. equi) and instead use the less specific Lancefield classification. Although data are too sparse to ascribe virulence differences to different species, and although all their isolates appear susceptible to penicillin, their susceptibility to non-beta-lactam agents (as may be required in penicillin-allergic patients) is less predictable and may vary by species or subspecies [91].

Staphylococcus caprae is a coagulase-negative staphylococcus rarely implicated in bone infections. Bone and joint infections due to S. caprae have been reported, but fortunately they remain rare [139,140,141,142]. Most S. caprae OAIs are the result of infected orthopaedic devices, especially infected joint prostheses and internal osteosynthesis devices [143,144,145,146]. Only very rare cases of primary S. caprae OAIs have been described, including osteitis [139,140], subacute osteomyelitis [142], arthritis [140] and spondylodiscitis [141,147].

Bartonella henselae OAIs caused by this Gram-negative bacterium are rare and atypical complications of cat scratch disease (CSD), which usually results from a scratch or bite from a young cat [148,149]. While typically presenting as a self-limiting lymphadenopathy, it can also cause osteomyelitis or septic arthritis. Even though cases of septic arthritis have been reported with this germ [150], OAIs due to B. henselae almost exclusively present as acute haematogenous osteomyelitis and demonstrate a strong tendency to affect the axial skeleton and pelvis, with nearly 75% of published cases localised to these areas [151,152]. Although osteomyelitis is an uncommon manifestation of CSD, it is a significant atypical presentation of paediatric bartonellosis and may be under-recognised in children with subacute axial or pelvic bone lesions. Furthermore, B. henselae has been increasingly recognised as a cause of atypical subacute osteomyelitis in children and adolescents [32]. Lymphadenopathy may be seen in approximately 25% of patients with CSD, which is not typical in cases of OAI [151]. Acute and convalescent serological studies and PCR testing may assist in diagnoses, given the microorganism’s fastidious nature [151,152,153]. In a similar vein, Vazquez et al. reported on a series of paediatric patients presenting with OAIs with atypical features, thus emphasising the need to use systematic serological and PCR testing appropriate to the epidemiological context [154]. One unknown remains regarding the treatment of these OAIs: given that antibiotic treatment of Bartonella lymphadenitis has not been shown to significantly improve long-term outcomes, it is unclear to what extent the treatment of OAIs hastens disease resolution [155]. However, given the lack of observational data for OAI disease processes, as well as the risk of morbidity in childhood OAIs, many authors and clinicians have continued to use antibiotic treatments.

Bordetella holmesii is a Gram-negative, rod-shaped bacterium of the Bordetella genus. Less well-known than its more famous relative Bordetella pertussis, this pathogen is considered to be an emerging bloodstream pathogen, more likely to affect immunocompromised children, such as asplenic patients [156]. However, native septic arthritis due to B. holmesii has been reported in adolescents, particularly in the setting of underlying haematological or immune conditions [157].

Similarly, Moraxella lacunata has also been identified as the causative agent of subacute osteomyelitis in a child, highlighting that even unusual members of the oropharyngeal microbiota can produce bone infections. Moraxella and Kingella are closely related Gram-negative bacteria in the Neisseriaceae family, often appearing as coccobacilli in pairs or short chains. Both are fastidious, non-motile, oxidase-positive and catalase-negative, and they commonly inhabit the human respiratory tract as opportunistic pathogens that can cause similar infections, such as endocarditis and OAIs.

Morganella morganii is a Gram-negative, facultatively anaerobic bacterium commonly found in the human intestinal tract and the environment, and as a commensal in many animals. It is typically considered an opportunistic pathogen and a significant cause of nosocomial infections. M. morganii has been reported as the causative agent of a Brodie’s abscess in a child’s talus, a presentation that highlights the expanding bacteriological spectrum of subacute OAIs [158].

Burkholderia pseudomallei can rarely cause isolated OAIs in otherwise healthy children, particularly in Southeast Asia and northern Australia [159]. The disease is more common in lower limbs, potentially because inoculation often occurs from walking barefoot through infected soil or water [159].

Pseudomonas aeruginosa is a common, highly adaptable, Gram-negative bacterium found in soil and water. It is usually implicated in infections following puncture wounds to the foot, manifesting with a sweetish odour and a greenish discolouration [160,161]. However, this pathogen can also be a rare cause of OAIs in the absence of trauma, occasionally as tibial osteomyelitis, pelvic osteomyelitis (potentially owing to its occasional presence in faecal flora) or, given its tendency to cause otic infections, as osteomyelitis of the skull associated with complications arising from mastoiditis [162,163,164].

6. Conclusions

Advances in nucleic acid amplification assay technologies have revolutionised diagnostics for infectious diseases. These advances have enabled better identification and resistance profiling of the causative pathogens responsible for paediatric osteoarticular infections (OAIs). It has also now been increasingly observed that otherwise healthy children may present with OAIs secondary to unanticipated pathogens. Although culture-negative results may become less frequent with the broader use of molecular diagnostics, clinicians are likely to encounter an expanding spectrum of uncommon, fastidious and emerging bacterial pathogens. Due to their infrequent occurrence and limited clinical experience with these atypical pathogens, heightened awareness is essential for the accurate identification and effective management of such infections. For paediatric orthopaedic surgeons, this evolving microbiological landscape also reinforces the need to consider uncommon pathogens in culture-negative, subacute OAIs, including those at atypical sites or resulting from atypical exposures.