Markku J. T. Kallio

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.

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.

C-reactive protein is useful in distinguishing Gram stain-negative bacterial meningitis from viral meningitis in children.

OBJECTIVE To clarify to what extent Gram stain-negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. DESIGN Common CSF indices, blood leukocyte counts, and serum CRP values were compared between patients with bacterial meningitis who had a positive CSF bacterial culture but a negative Gram stain and patients with viral meningitis. POPULATION Three hundred twenty-five consecutive patients with CSF culture-proven bacterial meningitis, for whom Gram stain was negative in 55 cases, and 182 children with proven or presumed viral meningitis. RESULTS Significant differences between patients with bacterial and viral meningitis were found in all indices with large overlap in all except serum CRP. In patients with bacterial meningitis, the mean CSF glucose concentration, protein concentration, leukocyte count, blood leukocyte count, and serum CRP were 2.9 mmol/L (52 mg/dL), 1.88 g/L, 4540 x 10(6)/L, 18.0 x 10(9)/L, and 115 mg/L; and in those with viral meningitis, mean values were 3.3 mmol/L (59 mg/dL), 0.52 g/L, 240 x 10(6)/L, 10.6 x 10(9)/L, and <20 mg/L, respectively. Of the tests investigated in this study, only serum CRP was capable of distinguishing Gram stain-negative bacterial meningitis from viral meningitis on admission with high sensitivity (96%), high specificity (93%), and high negative predictive value (99%). CONCLUSION Exclusion of bacterial meningitis with only the conventional tests is difficult. Combined with careful physical examination and CSF analyses, serum CRP measurement affords substantial aid.

Severity of childhood bacterial meningitis and duration of illness before diagnosis

Rapid diagnosis of childhood bacterial meningitis (BM) is generally believed to be essential to avoid poor outcome. To see whether duration of illness before admission to hospital was related to the severity of illness, data from children with BM diagnosed in 18 paediatric hospitals in Finland from 1984 to 1989 were collected prospectively. We divided 286 cases with culture-positive cerebrospinal fluid (CSF) into three groups: BM with a history of up to 24 h (short-history group, n = 141), of more than 24 h and up to 48 h (intermediate-history group, n = 75), and of more than 48 h (long-history group, n = 70). The longer the history, the better the clinical condition of the child. If symptoms or signs of BM lasted 48 h or less, the child did significantly worse, as judged by seven variables, than if the history was longer than 48 h (level of consciousness, p less than 0.001; seizures, p less than 0.01; CSF protein concentration, p less than 0.001; positive CSF gram-stain, p less than 0.01; positive blood culture, p less than 0.05 in Haemophilus influenzae meningitis; serum C-reactive protein, p less than 0.01 between intermediate-history and long-history groups; and urine sodium concentration, p less than 0.001). The differences were not affected by causative organism, sex, age, or preadmission oral antimicrobial agents. The findings show that if BM follows an insidious pattern of disease, diagnostic delay may be unavoidable, which may have medicolegal implications.

Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis

To assess the value of adjunctive intravenous dexamethasone (DXM) and oral glycerol (GLY) for the treatment of bacteriologically proved bacterial meningitis, 122 infants and children with bacterial meningitis were randomly assigned to receive DXM intravenously (n = 32), GLY orally (n = 30), DXM plus GLY (n = 34) or neither (n = 26) of these drugs. All patients were treated with the same antimicrobial agent, ceftriaxone. The patients were followed neurologically for as long as 6 months. A thorough hearing evaluation was performed routinely 2 months or more after discharge from hospital. Overall 4 (7%) of the GLY-treated patients, compared with 11 (19%) of those not given GLY, developed audiologic or neurologic sequelae (P = 0.052), the relative risk of sequelae being 2.94 (95% confidence interval, 0.99 to 8.72). The patients who had received GLY showed less severe or profound bilateral hearing impairment than those not given GLY (0 vs. 7%, P = 0.049), and none of them had other neurologic abnormalities 3 or 6 months after discharge, compared with 5 (9%) of those not treated with GLY (P = 0.024). The DXM recipients showed only a tendency to less severe hearing impairment than those not given DXM. In conclusion oral GLY prevented neurologic sequelae in infants and children with bacterial meningitis more effectively than intravenous DXM.

The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis. A comparison with the usefulness of the erythrocyte sedimentation rate and the white blood-cell count.

Thirty-six children who had bacteriologically confirmed acute hematogenous osteomyelitis but did not have concurrent septic arthritis, and ten children who had confirmed acute hematogenous osteomyelitis and concurrent septic arthritis, were followed for one year to compare the changes in the C-reactive protein level in the blood, the erythrocyte sedimentation rate, and the white blood-cell count. In both groups, the mean C-reactive-protein values were high (eighty-four milligrams per liter in the children who had septic arthritis and osteomyelitis and sixty-five milligrams per liter in those who had osteomyelitis only) at the time of admission to the hospital. However, in the group that had septic arthritis, the increase was significantly higher (p < 0.01) as early as the second day and a normal level (less than twenty milligrams per liter) was reached significantly later (p < 0.001) than in the group that had osteomyelitis only (11 +/- 7 days compared with 6 +/- 3 days [mean and standard deviation]). The erythrocyte sedimentation rate showed the same tendency, but the difference in the rates between the groups did not become evident until the fifth to fourteenth days after admission. A normal erythrocyte sedimentation rate (less than twenty millimeters per hour) was reached in 25 +/- 12 days in the children who had septic arthritis and in 17 +/- 10 days in those who did not (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Low colostral IgA associated with cow's milk allergy.

ABSTRACT. During a nutritional study of 198 infants, seven became allergic to cows milk. The seven infants showed acute cutaneous manifestations during cows milk challenge tests in hospital and six had increased levels of IgE cows milk‐specific antibodies. Neither in the development of the levels of immunoglobulins G, A and M, nor in that of the cows milk‐specific antibodies of these isotypes did these seven patients differ from the remaining infants. Beta‐lactoglobulin content and levels of cows milk‐, and beta‐lactoglobulin‐specific antibodies and of immunoglobulins A, G and M were measured in samples of colostrum and milk from the mothers of the seven infants with cows milk allergy and from a comparison group (non‐atopic mothers of non‐atopic infants). The milk of the mothers whose infants became allergic to cows milk contained less IgA through the lactation: 95% confidence intervals of the groups did not overlap. The difference was most marked in the colostrum. All other measurements were similar in the two groups. This suggests that an infant is more likely to develop cows milk allergy if the mothers colostrum had a low total IgA content.

Prolonged exclusive breastfeeding is associated with increased atopic dermatitis: a prospective follow‐up study of unselected healthy newborns from birth to age 20 years

Background Exclusive breastfeeding for the first 6 months is recommended by the World Health Organization and considered allergy preventive. However, it is not known whether prolonging exclusive breastfeeding for over 6 months provides further benefit in allergy prevention.

Etiology of Pneumonia and Other Common Childhood Infections Requiring Hospitalization and Parenteral Antimicrobial Therapy

The etiology of acute lower respiratory tract infections (mostly pneumonia) in children is well characterized, but these are only some of the community-acquired infections warranting parenteral antimicrobial therapy. We prospectively evaluated all such infections among children aged 3 months to 15 years by use of blood cultures, examination of nasopharyngeal aspirates, and serologies for 15 viral, 7 bacterial, and 1 protozoal agent. Immunocompromised patients and those with urinary tract infection, meningitis, or osteoarticular infection were excluded. In all, 170 children were included. The pathogenic agent was identified in 62% of the cases. Bacteria were detected in 54%, and a pneumococcus was found in 59% of the cases identified. Viruses were found in 15% overall. Sole bacterial or viral infections were detected in 47.1% and 8.1%, respectively. Since thorough screening established the etiology in less than two-thirds of patients ill enough to be hospitalized and treated parenterally, better diagnostics are needed, especially to identify those who would truly benefit from antimicrobial therapy.

Streptococcus mutans Infection Level and Caries in a Group of 5-Year-Old Children

The level of Streptococcus mutans in stimulated saliva and its association with caries experience was evaluated in 149 5-year-old children. In general, salivary S. mutans levels were low, and it was detected only in 46% of saliva samples. There was, however, a clear association between salivary levels of S. mutans and caries experience (chi 2 = 53.65, p less than 0.001). Salivary examination was supplemented with plaque samples in 47 children. The number of S. mutans positive surfaces increased with increasing salivary levels. S. mutans was most often isolated and comprised the highest proportion in the approximal samples. The number of children with high salivary S. mutans levels was very low (6%) when taken into account that 13% of the children were fairly caries active (dmfs greater than or equal to 5). This most probably means that in evaluation of caries risk, the salivary S. mutans screening level is different in preschool children and in older children. The level should be determined in longitudinal studies before applying to preschool children.