Journal of Chemotherapy

ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20

Osteo-Articular Infections in Newborns: Diagnosis

and Treatment

A. Dessì, M. Crisafulli, S. Accossu, V. Setzu & V. Fanos

To cite this article: A. Dessì, M. Crisafulli, S. Accossu, V. Setzu & V. Fanos (2008) Osteo-Articular
Infections in Newborns: Diagnosis and Treatment, Journal of Chemotherapy, 20:5, 542-550,
DOI: 10.1179/joc.2008.20.5.542

To link to this article: http://dx.doi.org/10.1179/joc.2008.20.5.542

Published online: 18 Jul 2013.

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Journal of Chemotherapy Vol. 20 - n. 5 (542-550) - 2008

REVIEW

Osteo-Articular Infections in Newborns:

Diagnosis and Treatment
A. DESSÌ - M. CRISAFULLI - S. ACCOSSU - V. SETZU - V. FANOS

Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section, University of Cagliari, Italy.
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Correspondence: Prof. Vassilios Fanos, Terapia Intensiva Neonatale, Puericultura e Nido, Università degli Studi di Cagliari,
Via Ospedale 119, 09124 Cagliari, Italy. Tel +39070 6093426. E-mail: vafanos@tiscali.it

Summary
Osteoarticular infections, although uncommon, represent a severe condition in
neonates. Infections in newborns are largely of an acute nature, transmitted by
hematogenous means. The most frequently observed etiological agents are: Staphy-
lococcus aureus, Gram negative and group B Streptococcus spp. In the majority of
acases the metaphyses of the long bone are the most commonly implicated sites, al-
though infection may spread to the contiguous epiphysis and joint in neonates. Diag-
nosis of acute septic arthritis and osteomyelitis may be hindered, especially in
neonates, due to the manifestation of less clear-cut characteristic symptoms and signs
compared to in children. When osteomyelitis is suspected, imaging techniques used in
association with blood and tissue cultures are the most reliable diagnostic tests. An-
timicrobial treatment should be administered for 3-4 weeks, initially intravenously,
later switching to oral medication. Surgery is indicated to drain acute abscesses or
when no improvement is achieved following antibiotic treatment.

Key words: Osteomyelitis, osteoarticular infections, newborn.

INTRODUCTION struction of the articular cartilage and prevent perma-

Osteomyelitis is defined as a bacterial infection of
the musculoskeletal system, specifically referring to
bone infection whereas septic arthritis refers to infec-
tion of a joint. Osteomyelitis and septic arthritis pres-
ent similar problems in terms of diagnosis and
treatment. At times they may occur simultaneously in
the same patient, or osteomyelitis may decompress
into its adjacent joint, resulting in septic arthritis ¹ and
be associated with long-term consequences.
Osteomyelitis is classified in three main categories:
acute hematogenous osteomyelitis, subacute focal dis-
ease or contiguous osteomyelitis and chronic os-
teomyelitis. Acute osteomyelitis is not a common
occurrence in adults. On the contrary, in neonates os-
teomyelitis is usually acutely manifested. Pediatric os-
teomyelitis is infrequently observed in industrialized
nations, although if overlooked it may lead to devas-
tating, lifelong consequences for the growing infant ².
Early diagnosis and subsequent appropriate medical
and surgical intervention is imperative to avoid de-
nent disability. The disease affects 0.2-1.6 children per
1000 annually, and is more common in boys than in
girls (ratio 2.5:1).
The infection reaches the bone in various ways as
presented below: hematogenous seeding; local exten-
sion from a contiguous infection; direct inoculation sec-
ondary to a penetrating wound or surgery ³.
Osteoarticular infections in children differ from the
adult forms as infection usually occurs via the
hematogenous route, frequently affecting the long
bones and the outcome tends to be better. The possi-
bility of permanent sequelae is higher if diagnosis and
treatment are delayed 4.
Some factors favor the acquisition of osteoarticular
infection, including bacteremia and other etiological
factors such as localized trauma or debilitation from a
chronic illness, malnutrition, or inadequacy of the im-
mune system 5. However, the specific cause underlying
acute hematogenous osteomyelitis remains unknown.
It should be underlined that, due to the rarity of os-
teomyelitis in neonates and paucity of signs and symp-

© E.S.I.F.T. srl - Firenze ISSN 1120-009X

 OSTEO-ARTICULAR INFECTIONS IN NEWBORNS: DIAGNOSIS AND TREATMENT
toms, the diagnosis in newborns is markedly more dif-
ficult than in older children. Moreover, the newborn is
more vulnerable to infection produced by immunologic
deficiencies involving the reticuloendothelial system,
complement, cytokines, polymorphonuclear leuko-
cytes, antibody or cell-mediated immunity 6.
Premature and sick neonates are a high-risk popu-
lation 7 in which potential sites of bacterial access are
frequently present. Accordingly, risk factors in
neonates include premature birth, perinatal asphyxia,
umbilical catheterization, sepsis and urinary tract in-
fections. Conversely, risk factors in adults include dia-
betes mellitus and a compromised immune system
(including HIV) 8. This review aims to discuss the etiol-
ogy, clinical and instrumental diagnosis, predisposing
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factors and the treatment of osteoarticular infections
in newborns.
ETIOLOGY
Over the last decades the bacteriology of acute os-
teomyelitis and septic arthritis in neonates has changed
significantly. Since the 1980s Staphylococcus aureus
has proven to be the main pathogen observed through-
out all age groups and almost all series of osteo-artic-
ular infections 9. S. aureus has been shown to bind to
bone by expressing receptors (adhesins) for compo-
nents of bone matrix (fibronectin, laminin, collagen and
bone sialoglycoprotein), with the expression of colla-
gen-bonding protein adhesin enhancing attachment of
the pathogen to cartilage 10. Previous studies have
demonstrated the prevalence of S. aureus in causing
infection. Tachdjian reported that S. aureus represents
the most commonly detected infectant throughout all
age groups ¹¹. Lyon and Evanich reported the finding
of Gram-positive infection in 80% of patients ¹². The
incidence of osteomyelitis caused by S. aureus has dra-
matically increased, partly due to the appearance of
community-acquired antibiotic-resistant strains, espe-
cially methicillin resistant S. aureus (MRSA). In
neonates, MRSA infections are capable of causing a
wide spectrum of diseases including bone and joint in-
fections associated with a high risk of sequelae.
Since the 1970s, group B Streptococcus spp. has
been the main cause of neonatal sepsis in industrial-
ized countries, emerging as a significant cause of
neonatal meningitis and osteomyelitis. Edwards et al.
reported that, prior to 1940, Streptococcus spp. was
a common cause of neonatal osteomyelitis ¹³. How-
ever, in view of prophylactic procedures enforced
today in all obstetrics wards, group B Streptococcus
spp. is now a comparatively rare finding.
In recent years, one of the major causes of os-
teomyelitis in the neonate has been infections fre-
quently implicated in the development of neonatal
sepsis, e.g. Gram-negative organisms. In a recent study
performed by Deshpande in India, in 15 cases of
neonatal septic arthritis of the hip, joint fluid culture
revealed the origin of infection as being 33% Gram-
543
negative bacteria, 20% Gram-positive bacteria, 7%
fungal, with no organisms being detected in 40% of
cases. Various Gram-negative organisms were de-
tected, including Klebsiella spp., Proteus spp., En-
terobacteriaceae and Escherichia coli 14.
The bacterial etiology of septic arthritis and os-
teomyelitis often varies with age. In neonates, S. au-
reus, Gram-negative strains and, less often, group B
Streptococcus spp. are the most commonly observed
pathogens.
Coagulase-negative staphylococci represent a
major cause of nosocomial infections in patients ad-
mitted to a neonatal intensive care unit. These infec-
tions are usually related to the presence of intravascular
devices 15. Beyond the neonatal age group, S. aureus
is the most common infecting organism in all age
groups 16. Haemophilus influenzae is implicated in up
to 10% of children under the age of 5 but is becoming
less common in areas where systematic vaccination
has been instituted (but remains an important cause of
septic arthritis in poor resource countries lacking a uni-
versal Hib vaccination program). In the child with sickle
cell disease, in addition to S. aureus, Salmonella spp.
and to a lesser extent other Gram-negative bacilli
(Shigella, E. coli, Serratia spp. etc.) are frequent
causes of septic arthritis and osteomyelitis. Immuno-
suppressed patients are at particularly high risk of in-
fection by Gram-negative bacteria. Indeed, the
particular proclivity of these children for Salmonella
infections is the result of a specific deficit of phagocy-
tosis.
Other rare pathogens reported to cause septic
arthritis include Staphylococcus pyogenes, Strepto-
coccus pneumoniae, Pseudomonas aeruginosa,
Neisseria gonorrhoeae, Neisseria meningitidis 17 and
Kingella kingae 18.
PATHOGENESIS
Hematogenous osteomyelitis is usually localized in
the long tubular bones, mainly those of the lower ex-
tremities (femur and tibia). The pathogenesis of septic
arthritis has been explored in various experimental
models. The synovial membrane is highly vascular and
lacks a limiting basement membrane, allowing bacteria
to seed the synovial space. The infection generally
originates in the metaphysis due to the scarcity of retic-
ulo-endothelial cells and peculiar vascular anatomy of
the bone. The arteries form large sinusoidal plexuses
with porous walls that join the large veins, where blood
flow is sluggish and erratic, and phagocytic activity is
deficient. The latter features create an ideal environ-
ment for the establishment and multiplication of bac-
teria 4. Septic arthritis may also result from contiguous
spread from adjacent osteomyelitis.
Differences observed in clinical presentation of the
infection in the neonate compared to older children
may partly be explained by the neonate’s blood supply
to the bone. In children over 2 years of age, the physis
 544
still prevents the spread of a metaphyseal abscess into
the epiphysis. In the newborn and young infants cir-
culation differs substantially from that of older children,
with blood vessels perforating the cartilage growth
plate. The metaphyseal vessels communicate with the
epiphyseal vessels in the cartilaginous precursor of the
ossific nucleus. This allows the infection to extend
freely into the epiphysis and joint 19-20. This new, but
well-established condition is known as septic os-
teomyelitis of the infant. The cortical bone of neonates
is thin and loose, consisting predominantly of woven
bone, which permits escape of the pressure caused by
infection but promotes rapid spread of the infection di-
rectly into the subperiosteal region. No large se-
questrum is produced in view of the absence of
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extensive infarction of the cortex; however, a large
subperiosteal abscess may develop.
The suppurative inflammation initially provokes mi-
cronecrosis of the bone. If the process persists, grad-
ual extension of the necrotic area will lead to the
formation of sequestra. The deposition of periosteal
new bone leads to the formation of an involucrum. The
fistula, sign of chronicity, is uncommon in neonates.
The persistence of osteomyelitis is fostered by de-
fective access of the immune system components and
antibiotics to a poorly irrigated tissue, reduced antimi-
crobial effectiveness in an anaerobic acidic environ-
ment and, above all, by the construction of a biofilm
that enhances bacterial resistance ²¹.
DIAGNOSIS
Early diagnosis of acute osteomyelitis is critical, the
prompt administration of antibiotic treatment being ca-
pable of preventing necrosis of bone. Clinical signs in
the newborn diverge from those displayed in children
and adults due to lower inflammatory response. A poor
correlation is observed between the severity of clinical
manifestations and the degree of bone damage. Diag-
noses in neonates are based on an index of suspicion.
Initially, typical systemic signs and symptoms of infec-
tions may not be prominent ²². Classical symptoms are
acute pain near a major limb joint associated with high
fever. However, the lack of clinical manifestations in
neonates makes diagnosis especially difficult in this age
group. In hematogenous osteomyelitis, local symptoms
referable to bone are more frequently absent in
neonates than in children. Fever and other systemic
signs of illness may be absent ²³. Septic arthritis in
neonates often presents with few systemic signs other
than irritability or poor feeding. Initially, specific signs
and symptoms of bone infection may include limited
motion and pseudoparalysis 24. Subsequently, heat,
erythema, local swelling and pain on touching the af-
fected limb may be manifested 16. The latter symptoms
reveal spreading of the infection beyond the bone to
the adjacent tissues. Contrary to neonates, children
with hematogenous osteomyelitis typically present the
following systemic symptoms and signs: abrupt fever,
A. DESSÌ - M. CRISAFULLI - S. ACCOSSU - V. SETZU - V. FANOS
lethargy, vomiting, refusal to use the affected limb and
local signs of inflammation present for 3 weeks or less.
For example, in a study conducted in Turkey by Kabak
et al. 6 on 14 newborns (mean age: 34.7 days), the
most frequent clinical signs presented were: irritability,
pain and limitation of motion. Fever and local signs
were reported less frequently. On the contrary, in an-
other study performed in Switzerland 44 on 81 children
(mean age: 6.5 years), the most frequent clinical signs
presented on admission were: pain (95%), and fever
(80%) (Table 1).
TABLE 1 - Differences in clinical symptoms between
newborns and children from studies by Kabak et al.6 and
Bonhoeffer et al.44
Symptoms % Newborns % Children
and signs in Kabak study in Bonhoeffer
study
Irritability/Poor feeding 100% n.r.
Pain 100% 95%
Limitation of motion 100% 60%
Fever 64% 80%
Erythema/Joint swelling 57% 75%
n.r.= not reported
The disease spectrum represented by neonatal sep-
tic arthritis differs from that involved in septic arthritis
in children. In view of the unique nature of the vascu-
lar supply of the neonatal skeletal system, osteomyelitis
and septic arthritis commonly occur concomitantly. In-
fants with altered immune function, undergoing inva-
sive procedures or having indwelling vascular lines are
those at greatest risk 25.
Bone and joint sepsis is more frequent in neonatal
age than during the rest of childhood. Osteomyelitis
generally affects only one single bone, although in
neonates several bones may be affected. However, a
polyarticular involvement has been reported in specific
infections caused by N. gonorrhoeae, N. meningi-
tidis, Salmonella spp and rarely S. aureus ³. Infection
is usually located in the metaphysis of the tubular long
bones. The most common long bones involved in de-
scending order are the tibia (50%), femur (30%), fibula
(12%), humerus (3%), ulna (3%) and radius (2%) 26.
LABORATORY FINDINGS
Laboratory analyses contribute considerably to
achieving a diagnosis of osteoarticular infection. Re-
sults obtained for erythrocyte sedimentation rate (ESR),
total and differential white blood cell (WBC) counts and
C-reactive protein (CRP) may be of use in indicating
the presence of infection, but, although sensitive, are
non-specific. ESR particularly reflects changes in the
concentration of fibrinogen, which increases approxi-
 OSTEO-ARTICULAR INFECTIONS IN NEWBORNS: DIAGNOSIS AND TREATMENT
mately 48-72 hours from the start of infection and
slowly returns to normal within about 4 weeks. Ac-
cordingly, ESR and CRP levels are elevated in the ma-
jority of cases of active osteomyelitis, including those in
which constitutional symptoms and leukocytosis are
lacking. These findings are not specific to os-
teomyelitis, however, and in early infections ESR may
even be normal.
Baseline values are often useful in monitoring the
efficacy of treatment and progression of the disease 27.
The CRP level is a rapid indicator of inflammation and
tissue necrosis. It is a protein created by the liver in re-
sponse to bacterial infection. CRP seems to rise earlier
than ESR, within 6-10 hours after injury to the tissue,
normalizing in approximately one week in uncompli-
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cated cases.
The WBC count has been found to be unreliable in
diagnosing osteoarticular infections. A normal WBC
count may often prove to be misleading to the clini-
cian in the presence of osteomyelitis. One of the most
valuable laboratory tests is the daily count of the ab-
solute number of neutrophils, in particular the ratio of
immature versus total neutrophils (> 0.20: established
infection).
Several studies 11-28 have demonstrated a positive
blood culture in 50% of patients, with the exception of
Lyon 12 who reported positive culture in only 21% of
his patients 14. A positive blood culture in a patient with
radiological findings consistent with osteomyelitis pre-
cludes the need to perform a biopsy in order to obtain
a specific microbiologic diagnosis.
X-RAYS
Radiographic imaging is an important component
in the diagnosis of osteoarticular infections and should
always start with plain radiographs of the affected area.
The first bone changes are not evident until at least 7-
10 days after onset of infection, with lysis being visible
2-6 weeks later. However, as early as 48 hours into
the illness, it is possible to detect signs of deep soft tis-
sue swelling, particularly obliteration of the lucent
planes between the muscles and subcutaneous edema
¹¹. Capsular swelling may be manifested at times with
obliteration and displacement of the gluteal lines and
asymmetric fullness of the iliopsoas and obturator in-
ternus soft tissue planes. Dislocation or subluxation of
the femoral head may be observed, particularly in
neonates. In osteomyelitis of the neonate joint effusion
may accompany bone findings; plain radiographs are
capable of detecting bone abnormalities earlier than in
older children in whom plain films demonstrate a
scarce sensitivity in detecting the presence of a joint
effusion 8. Subchondral bone erosions may be seen late
in the course of the infection. The appearance of scle-
rosis and decreased volume in the proximal femoral
epiphysis usually signifies the onset of avascular necro-
sis 29.
545
ULTRASONOGRAPHY
Ultrasonography procedures facilitate the detection
of soft tissue edema and subperiosteal collections in
long bone with great precision. Furthermore, ultra-
sound-guided aspiration is useful for drainage and col-
lecting material for culture. The procedure is
non-invasive, avoiding ionizing radiation, quick and in-
expensive 30. Ultrasound of the hips is the modality of
choice in suspected septic arthritis involving the hip
joint and may be useful in detecting early, less obvious
joint fluid effusions. If fluid is present, arthrocentesis
can be performed and appropriate cultures obtained.
Ultrasound-guided aspiration is an easy way of obtain-
ing fluid from the joint, providing direct visualization of
the fluid and needle during the procedure 31.
SCINTIGRAPHY
Scintigraphy enhances an earlier identification,
within the first 24-48 hours, of osteomyelitis. Ra-
dionuclide techniques are relatively quick and easy to
perform. Three-phase bone scans (99mTc-monodiphos-
phonate) afford high sensitivity ³², although often fea-
ture a low specificity, especially in the presence of
underlying bone abnormalities. False-negative results
occur in the presence of an abscess or ischemia, which
hinder bone uptake of the tracer, or following the ad-
ministration of antibiotics.
In septic arthritis, the periarticular distribution of
increased uptake is seen on both “blood-pool” and de-
layed images of the joint. A symmetric uptake typical
of septic arthritis can be observed on both sides of the
joint.
COMPUTED TOMOGRAPHY AND MAGNETIC
RESONANCE IMAGING
Magnetic Resonance Imaging (MRI) has shown
high sensitivity and specificity ³³ in the diagnosis of os-
teomyelitis. MRI reveals the replacement of normal
bone marrow fat by inflammatory exudates. This tech-
nique provides an extremely precise definition of the
location and extension of the disease, delineating bone
and soft tissue involvement 34. MRI is highly sensitive in
early detection of joint fluid, being more reliable than
Computed Tomography (CT) in delineation of soft tis-
sue structures 35. Compared with MRI, CT provides
better images of cortical destruction, sequestra and in-
traosseous gas 36.
SYNOVIAL FLUID ASPIRATION
Sterile needle aspiration of the affected area yields
an organism in approximately 60% of cases on the at-
taining of pus. Aspiration of material from the joint
space or from the affected bone should be carried out
and the contents examined for organisms by means of
Gram stained smears and culture. Synovial fluid in sep-
 546 A. DESSÌ - M. CRISAFULLI - S. ACCOSSU - V. SETZU - V. FANOS

tic arthritis is typically turbid or grossly purulent. A syn- TABLE 2 - Doses of several antibiotics used in the treat-
ovial fluid white blood cell (WBC) count exceeding ment of pediatric osteomyelitis.
50,000 cells/mm3, with a predominance of polymor- Antibiotic Dose
phonuclear neutrophils is strongly suggestive of septic
arthritis even in the presence of a negative joint fluid Cloxacillin 125 mg/kg/day orally
culture 37. Dicloxacillin 100 mg/kg/day orally
Synovial glucose may be low and protein and lac-
Mezlocillin 200-300 mg/kg/day i.v.
tate elevated; however, these tests are not sufficiently
sensitive or specific for general use. The yield of or- Nafcillin 150 mg/kg/day i.v.
ganism from joint fluid culture ranges between 50- Ticarcillin 200 -300 mg/kg/day i.v.
60%. A high WBC count may be obtained with a
Cephalexin 150 mg/kg/day orally
predominance of polymorphonuclear leukocytes. Iden-
tification of the infecting pathogen and antibiotic sen- Cephalothin 150 mg/kg/day i.v.
sitivities constitutes an aspect of considerable Cephradine 150 mg/kg/day i.v.
importance in prescribing treatment.
Cefuroxime 150 mg/kg/day i.v.
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Cefotaxime 100-150 mg/kg/day i.v.

ANTIMICROBIAL THERAPY Ceftriaxone 50-75 mg/kg/day i.v.
The success of antibiotic treatment is linked to the Ceftazidime 150 mg/kg/day i.v.
correct choice of drug to treat the specific etiological Teicoplanin 6-10 mg/kg/day i.v. or i.m.
agent, the dose prescribed and the correct duration of
Vancomycin 20-40 mg/kg/day i.v.
treatment. (Tables 2 and 3). Since selection of appro-
priate antibiotics is crucial in the therapy of osteoartic- Amikacin 15-20 mg/kg/day i.v.
ular infections, identification of the causative Gentamicin 5-7.5 mg/kg/day i.v.
microorganisms is extremely important.
Linezolid 10 mg/kg every 8h i.v.
Suboptimal concentrations of the drug in inflamed
bone, inactivation of certain compounds and biofilm (Gomis Gavilan M. et al 1999) modified
created by the bacteria are among the main reasons
for therapeutic failure 38. Every effort should be made
to ensure that initial antibiotic therapy is prescribed on
the basis of laboratory findings obtained in Gram stains In cases of septic arthritis beyond the neonatal pe-
of joint fluid or other sterile body fluid cultures. Should riod, initial empiric antimicrobial therapy should in-
no microorganisms be revealed, intravenous empiric clude adequate anti-staphylococcal coverage.
treatment should be initiated, taking into account the Accordingly, treatment should include either an anti-
age and clinical picture presented by the patient. Treat- staphylococcal agent or a beta-lactamase-resistant
ment may subsequently be modified as culture results penicillin (nafcillin or cloxacillin) and a first generation
are made available and in line with sensitivity of joint cephalosporin (cefazolin, cephalexin or cephradine) or
aspirates. Empiric treatment is usually initiated to treat clindamycin 39.
S. aureus, Group B Streptococci and Gram-negative If MRSA or penicillin-resistant pneumococci are
bacteria, particularly E. coli. Beta-lactamase-resistant suspected, vancomycin should be empirically started.
anti-staphylococcal penicillin, such as nafcillin or MRSA strains tend to be resistant to all beta-lactam
cloxacillin in combination with an aminoglycoside or agents (e.g., penicillins and cephalosporins). Thus, van-
third generation cephalosporin (such as cefotaxime, comycin remains a first-line therapy for severe infec-
ceftriaxone or ceftazidime) provide excellent coverage³. tions potentially caused by MRSA. In areas in which

TABLE 3 - Treatment according to etiology in pediatric osteomyelitis.

Microorganism Antibiotics appropriate for Newborns Antibiotics appropriate for Children

S. aureus Nafcillin or Cloxacillin + Gentamicin or Nafcillin or Cloxacillin + Cefazolin,

Cefotaxime, Ceftriaxone, Ceftazidime Cephalexin, Cephradine or Clindamycin

S. aureus (MRSA) Vancomycin or Vancomycin or

Teicoplanin + Gentamicin Teicoplanin + Gentamicin

Group A or B streptococci Gentamicin or Cefotaxime, Ceftriaxone, Clindamycin or Cefazolin, Cephalexin,

Ceftazidime + Nafcillin or Cloxacillin Cephradine + Nafcillin or Cloxacillin

Gram-negative bacteria Nafcillin or Cloxacillin + Gentamicin or Nafcillin or Cloxacillin + Gentamicin or

Cefotaxime, Ceftriaxone, Ceftazidime Cefazolin, Cephalexin, Cephradine
 OSTEO-ARTICULAR INFECTIONS IN NEWBORNS: DIAGNOSIS AND TREATMENT
MRSA are prevalent, glycopeptides - vancomycin or
teicoplanin - may represent the treatment of choice.
A study carried out in Greece by Korakaki et al.
reported two cases of acute osteomyelitis in full-term
neonates presenting no risk factors, due to MRSA.
Both were treated with vancomycin and outcome was
excellent 40. Recent data from North America indicate
that many strains of community-acquired S. aureus are
resistant to traditional anti-staphylococcal antibiotics
such as cloxacillin and cefazolin, but often susceptible
to clindamycin 41.
A new synthetic antibiotic, linezolid (a member of
oxazolidinones) has been introduced into clinical prac-
tice. The drug was the first of this class to be author-
ized by the US FDA for use first in adults and
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subsequently (December 2002) in children for the
treatment of specific vancomycin-resistant infections.
The drug was approved for use in the treatment of En-
terococcus faecium nosocomial and community-ac-
quired pneumonia produced by S. aureus or
penicillin-susceptible S. pneumoniae, complicated/
uncomplicated skin/ soft tissue infections such as
MRSA and methicillin-resistant coagulase-negative
streptococci (MRCNS) 42-43. Linezolid features good
oral bioavailability and may be indicated for future use
in the treatment of acute hematogenous osteomyelitis.
The use of intravenous antibiotic therapy and the
duration of treatment with both intravenous and oral
drugs is still the subject of considerable ongoing de-
bate4. Acute hematogenous osteomyelitis generally re-
quires high-dose parenteral treatment for a period
ranging from 4 to 6 weeks; however, following the
timely identification of the infecting microorganism
shortly after onset and a rapid response to initial par-
enteral therapy, the total duration of parenteral treat-
ment may be shortened and the patient switched to
oral antibiotics for 14 to 25 days 17-28. Oral therapy
contributes to improving the patient’s quality of life,
permitting treatment to be carried out at home when
compliance is assured, as well as to reducing the risk
and cost of nosocomial infections. Several studies
26,45,46
have demonstrated how the majority of patients
with acute hematogenous osteomyelitis can be treated
successfully with oral antibiotic therapy after a short
course of intravenous therapy. A recent study by Rueb-
ner et al. 47 in Philadelphia reported how the majority
of central venous catheter (CVC)-associated complica-
tions occurred after 2 weeks of CVC placement, thus
supporting early conversion to oral treatment. Pleas-
ant tasting formulations should be prescribed for use
in young children. Prescribed oral antibiotic doses
should be 2-3-fold greater than those used for milder
infections. Oral therapy should be carefully monitored.
Measurement of serum bactericidal activity against the
isolate correlates best with successful treatment. A
peak serum bactericidal titer of at least 1:8 obtained
the day after the start of oral therapy indicates a suc-
cess. In the case of infection caused by Streptococcus
spp., the recommended concentration is 1:32 28.
The appropriate duration of therapy for neonatal
547
septic arthritis remains a controversial issue and is
strictly associated with the infecting pathogen, the joint
involved and host defenses. However, treatment lasting
for no less than 3 to 4 weeks is advisable in uncompli-
cated cases 48. Longer treatment duration may be re-
quired for septic arthritis of the hip or shoulder
involving infection by S. aureus or Gram-negative bac-
teria than for infection of a small to medium joint such
as the knee caused by S. pneumoniae, H. influenzae
or Neisseria spp. 3 To date, however, no optimal an-
tibiotic regimen or duration of therapy has been es-
tablished and should therefore be determined on an
individual basis .
Intra-articular injections of antibiotics are not rec-
ommended due to the excellent penetration of most
antibiotics into the synovial space. Furthermore, infu-
sion of certain antimicrobial agents may trigger syn-
ovial inflammatory response.
SURGICAL TREATMENT
The role of surgery in infection remains a some-
what controversial issue. It is indicated for the decom-
pression of intra-osseous or soft-tissue abscesses and in
cases in which no improvement of signs and symptoms
is achieved after 48 hours despite adequate antimicro-
bial management. The majority of authors currently
tend to maintain a conservative approach to surgery.
Some experts view the presence of a subperiosteal ab-
scess as an indication for surgical drainage by drilling or
fenestration, even though this technique may damage
the growth plate and blood supply. However, a num-
ber of recent studies have demonstrated the feasibility
of achieving a successful outcome in acute os-
teomyelitis without surgery. Other studies published
previously justify the performing of early surgical
drilling with the aim of preventing the aforementioned
severe complication.
Danielsson et al. 49 highlighted the use of septopal
(gentamicin-polymethylmethacrylate) 3mm beads in-
troduced into the drill hole for local treatment, and to
facilitate drainage of the infected area. Beads were rou-
tinely removed after one week. Surgical debridement
including arthrotomy and drilling of the femoral neck
with introduction of septopal beads into the drill hole
combined with continued i.v. antibiotic treatment re-
sulted in normalization of the temperature and labora-
tory findings.
Early drilling lowers the intra-osseous pressure,
thereby arresting the progression of the infection/pres-
sure/necrosis chain of events. This minor surgical pro-
cedure enhances the possibility of obtaining adequate
bone biopsy cultures.
Open drainage is undeniably indicated in the hip
and the shoulder and in peripheral joints not respond-
ing to percutaneous aspiration. Open drainage is indi-
cated in systemically ill patients, and should be
considered more freely when infection by S. aureus or
a Gram-negative bacterium producing cartilage-dam-
aging enzymes is suspected.
 548
To summarize, acknowledged indications advocat-
ing open surgical drainage in children with septic
arthritis include: hip or shoulder joint disease; the pres-
ence of large amounts of pus, fibrin, debris or locula-
tion within the joint space; concomitant osteomyelitis;
in the absence of clinical improvement within 5-7 days
of repeated aspirations 50. Open drainage should be
performed using an approach providing for adequate
visualization of the joint surfaces and irrigation. Ante-
rior approaches represent the preferred technique in
treatment of the hip and shoulder. Joint surfaces
should be inspected for damage, while bearing in mind
that early cartilage damage may not be grossly appar-
ent. The capsular incision should be left open and the
remaining portion of the wound loosely closed over a
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drain placed next to the capsule 51. Other experts ad-
vocate the performing of surgical drainage on any in-
fant or young child with septic arthritis, in view of the
poorer outcome displayed by needle aspiration in very
young children 39.
PROGNOSIS
If treated early and successfully, most patients re-
spond well and present no long term problems. How-
ever, late treatment of septic arthritis in children
commonly leads to sequelae including cartilage dam-
Neonate: irritabilitity,
lethargy, limitation Suspicion of
of motion, joint osteoarticular
swelling
infections
Negative: Laboratory data:
infection unlikely (CRP,WBC,ESR)
Imaging studies:
Xrays-Ultrasound-
Observe or consider RMN-CT
other diagnosis
No effusion Effusion
Aspirate joint and
culture for bacteria
Negative Positive
A. DESSÌ - M. CRISAFULLI - S. ACCOSSU - V. SETZU - V. FANOS
age, stiff joints with poor mobility, abnormal bone
growth if the epiphysis is involved, unstable joint and
joint dislocation. Predictors of poor outcome with sep-
tic arthritis include infection in the hip and shoulder,
associated adjacent osteomyelitis, infection with S. au-
reus, young age (e.g <6 months, neonate), a delay of
4 days or more before decompression and antibiotic
therapy, and prolonged time prior to sterilization of
synovial fluid ³. Neonates in particular are at high risk
of developing sequelae in view of the immaturity of
their immune function and concomitant osteomyelitis.
In infancy, septic arthritis with concomitant os-
teomyelitis and infection due to MRSA has been asso-
ciated with an increased risk of sequelae 52. To
conclude, the most important prognostic factor in pre-
dicting a favorable outcome in neonatal septic arthritis
is represented by early diagnosis and treatment 9.
CONCLUSION
In view of the severity of the disease, septic arthri-
tis should be considered early in the differential diag-
nosis of any newborn presenting with joint
inflammation. Prompt treatment should be capable of
preventing complications and preserving normal func-
tions and future growth. Early orthopedic consultation
and a low threshold for performing arthrocentesis are
Children: high fever,
pain, erythema, joint
swelling, limitation of
motion
Positive: Empiric treatment
infection likely (intravenous)
Blood culture for
bacteria
Negative Positive
Definitive antibiotic
treatment
(intravenous-oral)
Resolution and FIGURE 1 - Flow-chart for the
recovery
management of a patient (chil-
dren or neonate) with os-
teomyelitis.
 OSTEO-ARTICULAR INFECTIONS IN NEWBORNS: DIAGNOSIS AND TREATMENT
prudent 39. Although uncommon, osteomyelitis and
septic arthritis in neonates constitute an emergency sit-
uation and should be included in the differential diag-
nosis of children presenting localized soft tissue
swelling, as well as of neonates with non-specific signs
and symptoms of bacteremia. Once a diagnosis is sus-
pected, findings obtained by imaging studies and blood
and tissue cultures represent the most valid and op-
portune diagnostic tests (Figure 1). Prolonged, appro-
priate antimicrobial treatment is warranted to achieve
optimal results. Follow-up with periodic X-rays should
be extended for at least 1 year. In neonates who may
suffer from sequelae years after the infection this pe-
riod should be substantially longer 4.
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