**5.2. Laboratory findings**

34 Neonatal Bacterial Infection

osteomyelitis [16].

**4. Pathogenesis** 

**5. Diagnosis** 

microbiological criteria.

**5.1. Clinical signs and symptoms** 

infections in the neonate [12,20,21].

frequently results from directly inoculated bacteria (secondary to heel or venipuncture, umbilical catheterization, infected cephalhematoma, etc.) [14,15]. Premature rupture of membranes and transplacental infection have also been described as risk factors for neonatal

The most common bacterial pathogen causing osteomyelitis in children is *Staphylococcus aureus* in all age groups [17]. Group B streptococcus (Streptococcus agalactiae) and gramnegative organisms (E. coli and Klebsiella pneumonia) are also important bacteria in the neonatal period [16,18,19]. Community-acquired strains of methicillin-resistant *Staphylococcus aureus* have emerged as being relevant in recent years and cause serious

Hematogenous infection of the long bones, which are most frequently affected, begins in the capillary loops of the metaphysic, adjacent to the cartilaginous growth plate (physis). These areas are very susceptible to hematogenous infection, because of its high vascularity and because the blood flow within the vessels is slow [22]. Bacteria can pass through gaps from the sinusoidal veins to the capillaries into the tissue, where they are provided an ideal environment to grow, resulting in abscess formation. These abscesses frequently rupture into the joint [23]. In neonates acute hematogenous osteomyelitis and septic arthritis co-exist in up to 76% of all cases as a result of this unique vascular anatomy of the epiphysis; the bone marrow compartment is seldom involved [10,24]. The epiphysis receives its blood supply directly from metaphyseal blood vessels (transphyseal vessels) and the adjacent cartilaginous growth plate is traversed by capillaries, allowing spread of the pathogenic bacteria to the physis, epiphysis and joint and resulting in slipped epiphyses, fractures,

Characteristics of the neonatal bone prevent many of the features of chronic osteomyelitis: cortical sequestra are often completely absorbed due to extensive bone blood supply in the newborn and, in addition, efficient vasculature of the inner layer of the periosteum encourages early development of new bone formation [26,27]. Complete destruction of joints

Diagnosis of osteomyelitis in the neonate can be challenging and is often delayed, as it is rare in the neonatal period and frequently presents with non-specific signs of illness. Diagnosis is based on clinical signs and symptoms, laboratory findings, radiological and

In general, two distinct clinical syndromes have been postulated to be associated with neonatal osteomyelitis: 1) a benign form, with little or no evidence of infection other than

premature physeal closure and chronic infection (Figure 1) [25].

is rare, but serious growth disturbances may occur.

In general, there is no specific laboratory test for osteomyelitis. Neonates with osteomyelitis frequently show normal leukocyte counts and erythrocyte sedimentation rates in the first

days. Thus, normal values do not preclude the diagnosis [30]. The C-reactive protein (CRP) is a rapid indicator of systemic inflammation and tissue damage, is useful as acute phase reactant, but not specific for skeletal infection. Procalcitonin has also been described as a potential marker in the diagnosis of osteomyelitis in children, but needs to be investigated in larger trials, especially in newborns [31,32]. Elevated values of CRP and erythrocyte sedimentation rates could be used to monitor response to therapy or identify complications.

Neonatal Osteomyelitis 37

epiphyseal separation and subluxation following septic arthritis [40]. However, ultrasound cannot exclude the diagnosis of acute osteomyelitis, and thus further imaging diagnostics

(a)

(b) **Figure 2.** Acute osteomyelitis of the right humerus. **a)** periosteal elevation and soft tissue swelling **b)**

Magnetic resonance imaging (MRI) has high specificity (94%) and sensitivity (97%) for the diagnosis of acute osteomyelitis, showing changes as early as day 3 to 5 after the onset of infection [43,44]. MRI gives excellent tissue characterization and high resolution, showing detailed anatomic presence of the inflammatory process and its complications (abscess formation, physeal involvement, septic arthritis), further allowing the assessment of involvement of the growth plate and epiphysis. MRI has been proven useful in the diagnosis of clinically suspected osteomyelitis in children [45-48], but for its use in neonatology it has several limitations: first and foremost the need for sedation and

Three-phase bone imaging, using technetium 99m is very sensitive (90%-95%) for the detection of acute osteomyelitis in the early stages of disease and allows detection within 24 to 48 hours after onset of symptoms [34,49]. Bone scintigraphy is especially useful for detecting multiple foci of infection or if the infection site is poorly localized. Technetium-99

may be required [41,42].

joint effusion and synovial thickening

transfer to the MRI unit.
