Markus Pääkkönen

Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases.

Background: Considerable uncertainty exists on the optimal duration of antimicrobials for acute hematogenous osteomyelitis (AHOM) in children. Often they are administered for 1 to 2 months, the first 1 to 2 weeks intravenously, and decompressive surgery is usually added. No prospective, randomized, sufficiently powered comparative trial has been available. Methods: Children aged 3 months to 15 years with culture-positive AHOM were randomly assigned to receive clindamycin or a first-generation cephalosporin for 20 or 30 days, including an intravenous phase for the first 2 to 4 days. Surgery was kept at minimum. Illness was monitored with preset criteria. Antimicrobial was discontinued once most signs had subsided and serum C-reactive protein decreased ≤20 mg/L. The primary end point was full recovery without need for further antimicrobial therapy because of an osteoarticular indication during the 12 months after the primary therapy. Results: Of the 131 cases, 18% also involved the adjacent joint. Staphylococcus aureus caused 89% of cases, and all strains were methicillin susceptible. The median duration of treatment was 20 days for 67 children, and 30 days for 64 children. Most children underwent only the diagnostic percutaneous aspiration or drilling, and 24% had no surgery. Except for 1 mild sequela in both treatment groups, all patients recovered entirely. Conclusions: Most cases of childhood AHOM can be treated for 20 days, including a short period intravenously, with large doses of a well-absorbed antimicrobial such as clindamycin or a first-generation cephalosporin, provided the clinical response is good and C-reactive protein normalizes within 7 to 10 days. Extensive surgery is rarely needed.

Acute Osteomyelitis in Children

Unless acute osteomyelitis in children is diagnosed promptly and treated appropriately, it can be a devastating or even fatal disease. This review summarizes the current approach to the treatment of acute osteomyelitis in children.

Bone and Joint Infections

An acute osteoarticular infection in a child is most often hematogenous. The infection manifests as osteomyelitis or septic arthritis. The most common causative organism is Staphylococcus aureus. Medical advice is usually sought within 2 to 6 days from the onset of symptoms. A child with an osteomyelitis in a lower extremity characteristically presents with limping with or without notable local tenderness, whereas acute septic arthritis is often readily visible because the joint is red, tender, and swollen. Early diagnosis and prompt treatment remain pivotal in avoiding complications in acute bacterial bone and joint infections.

Prospective, Randomized Trial of 10 Days versus 30 Days of Antimicrobial Treatment, Including a Short-Term Course of Parenteral Therapy, for Childhood Septic Arthritis

BACKGROUND The standard treatment for septic arthritis in children is antimicrobials for several weeks (initially administered intravenously) and arthrotomy (at least for the hip and shoulder joints). No sufficiently powered study has examined the true need for these treatments. METHODS In a randomized, multicenter prospective trial in Finland, children aged 3 months to 15 years who had culture-positive septic arthritis were randomized to receive clindamycin or a first-generation cephalosporin for 10 days or 30 days (intravenously for the first 2-4 days). The number of surgical procedures was kept to a minimum. Illness was monitored with preset criteria. Antimicrobial therapy was discontinued when the clinical response was good and the C-reactive protein level decreased to 20 mg/L. The primary end point was full recovery without need for further administration of antimicrobial therapy because of an osteoarticular indication during the 12 months after therapy. RESULTS Of the total 130 cases, 88% were caused by Staphylococcus aureus, Haemophilus influenzae, or Streptococcus pyogenes; 63 patients were in the short-term treatment group, and 67 were in the long-term treatment group. The median durations of antimicrobial treatment were 10 days and 30 days, respectively. Surgical procedures that were more extensive than percutaneous joint aspiration were performed for 12% of patients, with no preponderance to hip or shoulder arthritis. Two late-onset infections occurred in 1 child in the long-term treatment group; however, all patients recovered without sequelae. CONCLUSIONS Large doses of well-absorbed antimicrobials for <2 weeks (initially administered intravenously) and only 1 joint aspiration are sufficient for treatment of most cases of childhood septic arthritis, regardless of the infecting pathogen or anatomical site, if the clinical response is good and the C-reactive protein level normalizes shortly after initiation of treatment.

Clindamycin vs. first-generation cephalosporins for acute osteoarticular infections of childhood-a prospective quasi-randomized controlled trial

No sufficiently powered trial has examined two antimicrobials in acute osteoarticular infections of childhood. We conducted a prospective, multicentre, quasi-randomized trial in Finland, comparing clindamycin with first-generation cephalosporins. The age of patients ranged between 3 months and 15 years, and all cases were culture-positive. We assigned antibiotic treatment intravenously for the first 2-4 days, and continued oral treatment with clindamycin 40 mg/kg/24 h or first-generation cephalosporin 150 mg/kg/24 h in four doses. Surgery was kept to a minimum. Subsiding symptoms and signs and normalization of C-reactive protein (CRP) level were preconditions for the discontinuation of antimicrobials. The main outcome was full recovery without further antimicrobials because of an osteoarticular indication during 12 months after therapy. The intention-to-treat analysis comprised 252 children, 169 of whom were analysed per-protocol: 82 cases of osteomyelitis, 80 of septic arthritis, and seven of osteomyelitis-arthritis. Staphylococcus aureus strains (all methicillin-sensitive) caused 84% of the cases. Except for one non-serious sequela during convalescence in both groups, and two late infections caused by dissimilar agents in one child, all patients recovered. The entire courses (medians) of clindamycin and cephalosporin lasted for 23 and 24 days, respectively. CRP normalized in both groups in 9 days. The patients were discharged, on average, on day 10. Loose stools were reported less often (1%) in the clindamycin group than in the cephalosporin group (7%), but two clindamycin recipients developed rash. Clindamycin or a first-generation cephalosporin, administered mostly orally, perform equally well in childhood osteoarticular infections, provided that high doses and administration four times daily are used. As most methicillin-resistant staphylococci remain clindamycin-sensitive, clindamycin remains an option instead of costly alternatives.

Pediatric septic hip with or without arthrotomy: retrospective analysis of 62 consecutive nonneonatal culture-positive cases.

In our multicenter treatment study on pediatric nonneonatal osteoarticular infections we had 62 septic hip arthritides. All had confirmed joint effusion, were culture-positive, and Staphylococcus aureus was isolated in 71% of the cases. Sixty-one of the 62 had a diagnostic joint aspiration. Following protocol, arthrotomy was to be performed only if the response to antimicrobial treatment was slow. The course of illness was monitored by preset criteria. Analysis of 95% of the patients who attended the last checkup ≥1 year posthospitalization showed that invasive surgery had been avoided in 81% of the patients. All patients recovered completely. Routine arthrotomy in nonneonatal hip arthritis warrants reconsideration.

Management of a child with suspected acute septic arthritis

Acute septic arthritis of childhood is a potentially devastating disease that causes permanent disability and can result in death. Traditional treatment consists of a prolonged course of intravenous antibiotics combined with aggressive surgery. However, this approach is challenged by trials showing satisfactory outcomes with shorter treatment and less invasive surgery. Diagnostic arthrocentesis alone and an antibiotic for a fortnight, including initial intravenous administration for 2–4 days, suffice in most non-neonatal cases. A good penetrating agent, such as clindamycin or a first-generation cephalosporin, exceptionally high doses, and administration four times a day are probably key factors. If the symptoms and signs subside within a few days, and the serum C-reactive protein level drops below 20 mg/l, the antibiotic can usually be safely discontinued. Methicillin-resistant Staphylococcus aureus is a concern, but fortunately, most strains have retained susceptibility to clindamycin. The above guidance is not applicable to neonates and immunocompromised patients who may require a different approach.

Antibiotic treatment for acute haematogenous osteomyelitis of childhood: moving towards shorter courses and oral administration.

Acute haematogenous osteomyelitis (AHOM) of childhood usually affects the long bones of the lower limbs. Although almost any agent may cause AHOM, Staphylococcus aureus is the most common bacterium, followed by Streptococcus pneumoniae and, in some countries, Salmonella spp. and Kingella kingae. Magnetic resonance imaging (MRI) has improved the diagnostic accuracy of traditional radiography and scintigraphy. Except for the pre-treatment diagnostic sample from bone before the institution of antibiotic therapy, no other surgery is usually required. Traditionally, non-neonatal AHOM has been treated with a 1-3-month course of antibiotics, including an intravenous (i.v.) phase for the first weeks, but recent prospective randomised studies challenge this approach. For most uncomplicated cases, a course of 20 days including an i.v. period of 2-4 days suffices, provided large enough doses of a well-absorbed agent (clindamycin or a first-generation cephalosporin, local resistance permitting) are used, administration is four times daily and most symptoms and signs subside within a few days. Serum C-reactive protein (CRP) is a good guide in monitoring the course of illness, and the antimicrobial can usually be discontinued if CRP has decreased to <20 mg/L. Newer and costly agents, such as linezolid, should be reserved for cases due to resistant S. aureus strains. AHOM in neonates and immunocompromised patients probably requires a different approach. Because sequelae may develop slowly, follow-up for at least 1 year post hospitalisation is recommended.

Shortened hospital stay for childhood bone and joint infections: analysis of 265 prospectively collected culture-positive cases in 1983-2005.

Abstract Background: In recent decades the treatment of childhood acute bone and joint infections has shifted towards shorter antibiotic courses and rapid transition to oral therapy. Methods: We prospectively collected 265 culture-positive cases of non-neonatal bone and joint infections in Finnish children during 1983–2005. The duration of antimicrobial treatment and the extent of surgery were defined in the study protocol, but for ethical reasons, the liaison clinician determined the time of discharge using normalization of the serum C-reactive protein (CRP) level as a yardstick. We examined changes during the study in the distribution of causative organisms, severity of disease, and length of hospital stay. Results: Staphylococcus aureus was overwhelmingly the most common causative agent throughout the study, whereas Haemophilus influenzae type b was eliminated soon after the introduction of vaccination. The mean time from initial symptoms to presentation remained the same at 4 days, and no significant change was observed in the severity of disease, CRP, or the rate of sequelae. The mean duration of intravenous antibiotic administration was only 4 days. The average hospital stay shortened significantly from 13 days to 9 days (p = 0.0001). Conclusions: The shortened hospital stay was not due to a change in the anatomical site of these infections, but to simplified treatment. Considerable savings in hospital stay, and thus costs, are feasible in osteoarticular infections of childhood by using CRP in monitoring the disease and shortening intravenous treatment by a swift move to per oral administration.

Management of osteoarticular infections caused by Staphylococcus aureus is similar to that of other etiologies: analysis of 199 staphylococcal bone and joint infections.

Background: Acute hematogenous osteomyelitis, septic arthritis, and their combination are considered to warrant especially aggressive treatment if caused by Staphylococcus aureus. Methods: Our prospective treatment trial of children aged 3 months to 15 years included 199 cases of S. aureus osteomyelitis, septic arthritis, or their combination. These cases were compared with 66 cases caused by other agents, mainly Haemophilus influenzae type b, Streptococcus pneumoniae, or Streptococcus pyogenes. According to protocol, the treatment was initiated intravenously only for 2 to 4 days and completed orally. Nonstaphylococcal and staphylococcal infections were treated similarly. Primary antibiotics were clindamycin or a first-generation cephalosporin. Follow-up lasted ≥12 months posthospitalization. Results: Staphylococcal infections did not significantly differ in the duration of medication, hospital stay, surgery performed, or the number of sequelae when compared with the other etiologic groups. One child with S. aureus arthritis developed 2 late infections by other agents in the same anatomic site. Except 3 mild sequelae (2 caused by S. aureus and 1 by S. pyogenes) 12 months posthospitalization, all patients recovered completely. Conclusions: Osteoarticular infections of childhood caused by methicillin-susceptible S. aureus can be treated according to the same protocol as those used for infections caused by other agents.