Imipenem and cilastatin in acute osteomyelitis and suppurative arthritis. Therapy in infants and children

Twenty-five infants and children with acute osteomyelitis (n = 7), suppurative arthritis (n = 11), or both (n = 7) were treated with imipenem and cilastatin sodium. Patients ranged in age from 5 months to 11.3 years. Needle aspiration of infected sites was performed in all patients, and 11 (44%) required further surgical drainage. Imipenem and cilastatin sodium in a dosage of 100 mg/kg/d was used for children 3 years of age or younger, while older ones received 60 mg/kg/d intravenously, divided in four equal doses. Bacterial pathogens were identified in 15 patients (60%): Staphylococcus aureus in five, Haemophilus influenzae b in four, Pseudomonas aeruginosa in two, Streptococcus pneumoniae in one, group A Streptococcus in one, Kingella kingae in one, and Citrobacter amalonaticus in one. All isolates were susceptible to imipenem in vitro. Imipenem and cilastatin therapy was continued for a median of six days followed by treatment with appropriate orally administered antibiotics. Median peak serum bactericidal titers after imipenem and cilastatin infusions were 1:512 for S aureus, 1:32 for H influenzae b, 1:512 for streptococci, and 1:16 for gram-negative rods. All but one patient with P aeruginosa osteomyelitis responded favorably to imipenem and cilastatin. The median duration until resolution of symptoms was six days. Imipenem and cilastatin infusions were well tolerated, and side effects included maculopapular rash in one patient, watery diarrhea in one, and mild transient elevation of alanine aminotransferase levels in three. Because of imipenem and cilastatin's unusually broad spectrum of activity and its relative safety, this drug combination can be used for the initial, empiric therapy of acute bone and joint infections in pediatric patients.     

Simplified treatment of acute staphylococcal osteomyelitis of childhood. The Finnish Study Group

OBJECTIVE: Recommendations on treatment of acute staphylococcal osteomyelitis of children, based mostly on retrospective analyses, comprise surgical drainage, up to 6 weeks fo antimicrobials guided by the erythrocyte sedimentation rate, and the possibility of switching to the oral route only if monitoring of serum bactericidal titer is guaranteed. A prospective study was conducted to test whether the treatment could be simplified. DESIGN: Fifty pediatric cases of acute Staphylococcus aureus osteomyelitis were randomized to receive 150 mg/kg/day of cephradine divided in four doses, or 40 mg/kg/day in four doses of clindamycin. The treatment was initiated intravenously, but switched to oral administration mostly within 4 days, using the same doses. The peak antimicrobial serum inhibitory titer or bactericidal titer was not measured. The course of illness was monitored by blood leukocytes, erythrocyte sedimentation rate, and serum C-reactive protein. The follow-up was extended to 1 year posthospitalization. SETTING: Eight tertiary pediatric-orthopedic hospitals in Finland. MAIN OUTCOME MEASURE: Full recovery and remaining healthy at least 12 months from hospital discharge. RESULTS: The lower and upper extremities were affected in 72% and 8% of patients, respectively. No surgery at all or needle aspiration only was performed in 62% and drilling in 38%. C-reactive protein and the sedimentation rate normalized within 9 days and 29 days, respectively. X-ray changes developed in 68% but had no prognostic significance. The mean hospitalization time was 11 days, and the total duration of antimicrobials was 23 days. No failure has occurred nor have long-term sequelae been observed in any patient. CONCLUSIONS: Treatment of pediatric acute staphylococcal osteomyelitis can be simplified and costs reduced by keeping surgery at a minimum, shortening hospitalization and the course of antimicrobials, switching quickly to the oral route, and not monitoring serum bactericidal activity.     

Pelvic osteomyelitis in children.

Six children (7 to 16 years of age) with pelvic osteomyelitis are described. Sites of involvement included the pubis in three patients, the ilium in two patients, and the ischium in one patient. All were right-sided. Each patient presented with a history of fever and an abnormal gait. In four, the point tenderness indicated the site of bony involvement. All patients had pain on abduction but free passive range of motion of the hip. Soft tissue swelling was present on admission pelvic roentgenograms in five patients. Intravenous pyelogram revealed deviation of the bladder toward the midline in each of four patients studied. Roentgenographic changes typical of osteomyelitis developed in four patients ten days to ten weeks after onset of symptoms. In four patients in whom an organism was identified, Staphylococcus aureus was isolated from blood and/or bone. All isolates were methicillin-sensitive and two were penicillin-sensitive. Purulent material was drained from three of the five patients who underwent surgical exploration of the pelvis. All patients received parenteral antistaphylococcal therapy for 3 to 5 1/2 weeks (mean, 4 weeks). Oral antibiotics were given to five patients for an additional 3 to 14 weeks. All patients recovered completely.     

Use of the serum bactericidal titer to assess the adequacy of oral antibiotic therapy in the treatment of acute hematogenous osteomyelitis.

Serum bactericidal titers against Staphylococcus aureus were measured in 63 children who were receiving mafcillin or methicillin intravenously, or dicloxacillin, penicillin, or cephalexin orally. The SBTs obtained following unit does of 25 mg/kg of dicloxacillin, 35 mg/kg of penicillin, or 25 mg/kg of cephalexin with probenecid were comparable to those seen following intravenous doses of 40 mg/kg nafcillin or methicillin. Twenty-two children with acute hematogenous osteomyelitis proven or presumed to be due to S. aureus were treated intravenously until point tenderness and fever had resolved, and then with oral therapy. The mean duration of intravenous therapy was 14 days. Oral doses were adjusted so that a peak SBT of greater than or equal to 1:16 and a trough SBT of greater than or equal to 1:2 were obtained in most children. No recurrences occurred. The SBT proved to be a practical means of assessing the adequacy of oral therapy in children with infections due to S. aureus.     

Acute osteomyelitis in the child with sickle cell disease in a tropical zone: value of oral fluoroquinolones]

AIM: This study was designed to assess the efficacy and the safety of fluoroquinolones in their compassionate use for acute osteomyelitis in children with sickle cell disease in a tropical country. PATIENTS AND METHODS: This study was non comparative, including twelve children (eight SS, three SC and one SEzerothalassemia) treated for acute osteomyelitis with oral ciprofloxacin or ofloxacin because of the following reasons: financial inability to afford conventional parenteral beta-lactams therapy (nine patients), refusal of hospitalization (two patients), and failure of conventional treatment (one patient). RESULTS: The mean age of patients was 9.5 +/- 2.6 years. The long bones were the predominantly site. Salmonella species were present in 75% of cases, followed by other enterobacteriaceae (16.7%), and Staphylococcus aureus (8.3%). Successful outcome occurred in all cases after three to four-weeks of treatment and 45 days of plaster immobilization. Transient bilateral Achilles tendon tendinitis was noted in a five-year-old patient. CONCLUSION: In economically developing countries, oral fluoroquinolones may be a therapeutic alternative for acute osteomyelitis in patients with sickle cell disease particularly in cases of financial hardship or failure with conventional therapy.     

Osteomyelitis in infants and children. A review of 163 cases.

One hundred sixty-three cases of osteomyelitis in infants and children were seen at our hospital during the past 15 years. There were twice as many boys as girls. Staphylococcus aureus was the major etiologic agent, being identified in 61% of the cases. Gram-negative bacteria were responsible for only 14 cases (9%). The femur, the tibia, or the humerus were affected in 103 of the 152 patients with single bone involvement. Ostoemyelitis of more than one bone was seen in 11 cases (7%). Associated joint infectin was confirmed in 29 patients. There were no deaths. Surgical drainage was carried out in 81 cases (50%). Ten patients had recurrent or persistent drainage and one developed a Brodie abscess. Of the patients with S aureus osteomyelitis, chronic disease occurred in 19% of those receiving parenterally administered antibiotics for three weeks or less, but in only one patient (2%) of those who received parenteral antibiotics longer than three weeks.     

Course and treatment of osteomyelitis in childhood (author's transl)]

In the years 1955-1972 132 children with osteomyelitis were treated in the Pediatric, Surgical and Orthopedic Department of the university of Kiel. There was no increase in the incidence of osteomyelitis during this period. Acute hematogenous osteomyelitis was diagnosed in 111 children, chronic hematogenous osteomyelitis in 11 children, traumatic and postoperative osteomyelitis in 10 children. Secondary chronic osteomyelitis occurred in 1 patient. Mainly staphylococci (in 90%) were the pathogenic bacteria, whereas haemophilus, pseudomonas, streptococci group A, E. coli and mixed infections occurred less frequently. In 17 of 111 patients with acute hematogenous osteomyelitis there were no roentgenological changes. Bacteriological investigations of blood and pus, and the antistaphylolysin reaction (repeated in the course of the disease) were helpful to establish the diagnosis in many cases. 107 of 111 patients with acute hematogenous osteomyelitis were cured (8 patients with defects). 4 children died in septic shock or because of complications (meningitis, pleural empyema, pneumonia). Bactericidal antibiotics in high dosage (penicillins, gentamicin) were superior to bacteriostatic antibiotics. Additional surgical treatment was necessary in 49 of 111 patients with acute hematogenous osteomyelitis. Recommendations for antibiotic therapy of osteomyelitis are given.     

NON-SPECIFIC IMMUNITY IN NEPHROTIC SYNDROME

Abstract. Yetgin, S., Gur, A. and Saatci, U. (Department of Paediatrics, Children's Medical Center, Hacettepe University, Ankara, Turkey). Non-specific immunity in nephrotic syndrome. Acta Paediatr Scand, 69:21, 1980.—In order to explain susceptibility to bacterial infection in patients with nephrotic syndrome, bactericidal capacity of polymorphonuclear neutrophils (PMN) and serum opsonic activity were studied. The groups consisted of 29 patients and 29 controls. Bactericidal capacity was found to be statistically significant defective in the patient group when compared with controls for Staphylococcus aureus and Escherichia coli . Serum opsinic activity was found to be defective in up to 50% of the patients, but it was not statistically significant for either bacteria. There is no correlation between the impairment of bactericidal capacity and serum total protein, albumin, globulin, total lipid, cholesterol, age of patients and the duration of the illness. When bactericidal capacity was examined in five patients in remission it had returned to the normal level. The results of this study suggest that bactericidal capacity and possibly serum opsonic activity are influenced by the nephrotic syndrome     

Oral graft vs. host disease in children – Treatment with topical tacrolimus ointment

Abstract:  Oral chronic graft vs. host disease (GVHD) frequently presents in patients with sclerotic features of skin GVHD and is often associated with considerable limitations of oral food intake and decreased quality of life. Systemic tacrolimus is efficacious for prophylaxis and treatment of acute and chronic GVHD and topical tacrolimus has shown activity in chronic GVHD skin lesions. We therefore initiated a pilot study to investigate the safety and efficacy of topical tacrolimus ointment in children with oral GVHD. Six patients suffering from oral GVHD (five chronic and one acute) were included in the study. Tacrolimus ointment 0.1% was applied twice daily using sterile gauze. The only side-effects observed were a slight burning discomfort after the first application in one patient and after food intake in another patient. Tacrolimus was absorbed systemically in four of six patients. Of six patients, we observed a complete response in two, a very good partial response (VGPR) in two, and a PR in two patients, respectively. We conclude that topical application of tacrolimus ointment holds promise as a safe and efficacious treatment for oral GVHD in children. The Food and Drug Administration has recently issued a health advisory about a potential cancer risk associated with topical tacrolimus treatment of the skin; therefore, its benefits should be weighed against its potential risks and diligent long-term follow-up should be carried out especially in children.     

Clinical presentation and management of Pseudomonas osteomyelitis

To determine the incidence and clinical characteristics of Pseudomonas aeruginosa osteomyelitis in children, the records of 144 hospitalized patients under 19 years of age were reviewed; 104 fulfilled the study criteria for the diagnosis of acute or chronic osteomyelitis. Pseudomonas aeruginosa was recovered from 10.6 percent of the children and was the second most common pathogen isolated. In comparison to children with staphylococcal infections, patients with pseudomonal osteomyelitis were significantly older, gave an antecedent history of penetrating trauma, and lacked clinical and laboratory evidence of systemic illness. The data collected in this study suggest that osteomyelitis due to Pseudomonas aeruginosa is a distinct entity with clinical features differing from those of Staphylococcus aureus. Management should be directed at adequate surgical debridement followed by 10 to 21 days of antimicrobial therapy.     

Development of serum bactericidal activity following nontypable Haemophilus influenzae acute otitis media

We monitored the development of serum bactericidal antibody in eight children with acute nontypable Haemophilus influenzae otitis media and correlated its development with the appearance of antibody against lipooligosaccharide and surface-exposed outer membrane proteins of the infecting strains. Complement-dependent bactericidal activity was absent in acute sera but increased to titers of 1:4 to 1:32 in sera obtained 4 to 6 weeks later. Absorption of anti-lipooligosaccharide antibodies from convalescent sera had no effect on bactericidal titers of five patients and resulted in small decreases in titer in three patients. Lipooligosaccharide-absorbed samples had persisting bactericidal titers of 1:4 to 1:16. Four of eight acute samples lacked antibodies to surface-exposed outer membrane proteins whereas four had low concentrations of antibody directed against one or more Mr 100,000 to 250,000 outer membrane proteins. Convalescent samples from all eight children showed substantial increases in antibodies directed primarily against Mr 100,000 to 250,000 proteins. Thus, both surface-exposed Mr 100,000 to 250,000 outer membrane proteins and lipooligosaccharide are immunogenic during Haemophilus otitis media and are potential targets of bactericidal antibody.     

Scintigraphic differentiation of bone infarction from osteomyelitis in children with sickle cell disease

Bone scans or bone marrow scans or both were obtained during 42 episodes of bone pain in 40 children with sickle cell disease, and the usefulness of these procedures was compared. On the basis of the subsequent clinical course, a diagnosis of bone infarction was made in 34 episodes, and osteomyelitis in eight. Among 22 patients with bone infarction, uptake on bone scan was increased in 14, decreased in three, and normal in five. Seven of eight patients with osteomyelitis had increased uptake on bone scan; one had normal uptake. In contrast, marrow scan uptake was markedly decreased in 15 of 16 patients with bone infarction, and was normal in five of five patients with osteomyelitis. Thus, decreased uptake on bone marrow scan in a patient with sickle cell disease and bone pain almost invariably indicates infarction, whereas normal uptake strongly suggests the diagnosis of osteomyelitis. We found marrow scans more useful than bone scans for this differential diagnosis.     

Serial determination of serum ferritin in children with acute lymphoblastic leukemia. Evaluation of its usefulness as a prognostic index.

Thirty children with acute lymphoblastic leukemia were monitored with serial serum ferritin determinations for up to 17 months. In children with acute lymphoblastic leukemia before initiation of therapy, or in relapse, the mean serum ferritin concentration was 636 microgram/l. In children who went into primary remission. the mean serum ferritin concentration fell from 265 microgram/l prior to start of treatment, to 161 microgram/l after 3 months of treatment. Five patients relapsed. Their serum ferritin levels prior to the relapses ranged from 7 to 135 microgram/l. At the time of relapse a further increase in serum ferritin was found in only 2 of the children. Thus, whereas high serum ferritin levels may signal disease activity in acute lymphoblastic leukemia, a normal serum ferritin level does not exlude disease activity or impending relapse.     

Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process

We report seven patients with chronic recurrent multifocal osteomyelitis, an uncommon childhood disease of unknown etiology. These patients presented with insidious onset of bone pain at one or more sites associated with erythema, swelling and tenderness. Scintigraphy and radiography were consistent with osteomyelitis at multiple sites. Bone biopsies confirmed osteomyelitis but no organisms were consistently isolated. During a 1- to 3-year follow-up, most patients developed new symptomatic lesions. The disease was unaffected by antimicrobial therapy. Two of our patients had psoriasis and all were rheumatoid factor-, antinuclear factor- and HLA-B27-negative. We speculate that chronic recurrent osteomyelitis is a noninfectious inflammatory condition, a seronegative spondyloarthropathy. Chronic recurrent osteomyelitis is a clinical entity that should be recognized so that invasive diagnostic procedures and antimicrobial therapy are appropriately used. The patient may be reassured that this is not a malignant condition although there may be exacerbations over many years.     

Success of short-course parenteral antibiotic therapy for acute osteomyelitis of childhood

The outcome of acute osteomyelitis treated with sequential therapy consisting of a short course of parenteral antibiotics, followed by oral antibiotics, was studied. To be considered acute osteomyelitis, related symptoms must have been present for less than 2 weeks before diagnosis. Short-course parenteral antibiotics (therapy for 7 days or less) and then oral antibiotics were used to treat 29 patients (median age, 6.3 years). Pathogens were identified from blood cultures and bone aspirates. Staphylococcus aureus was isolated in 59%. Median duration of parenteral antibiotics and oral antibiotics was 4 days (range, 0-7 days) and 28 days (range, 14-42 days), respectively. Median duration of combined (parenteral and oral) therapy was 32 days (range, 20-49 days). No failures or complications were noted at the 6-month follow-up, which was available for 27 patients. Short-course parenteral antibiotic therapy followed by oral therapy appears to be effective for treatment of acute, uncomplicated osteomyelitis.     

Oral graft vs. host disease in children--treatment with topical tacrolimus ointment

Oral chronic graft vs. host disease (GVHD) frequently presents in patients with sclerotic features of skin GVHD and is often associated with considerable limitations of oral food intake and decreased quality of life. Systemic tacrolimus is efficacious for prophylaxis and treatment of acute and chronic GVHD and topical tacrolimus has shown activity in chronic GVHD skin lesions. We therefore initiated a pilot study to investigate the safety and efficacy of topical tacrolimus ointment in children with oral GVHD. Six patients suffering from oral GVHD (five chronic and one acute) were included in the study. Tacrolimus ointment 0.1% was applied twice daily using sterile gauze. The only side-effects observed were a slight burning discomfort after the first application in one patient and after food intake in another patient. Tacrolimus was absorbed systemically in four of six patients. Of six patients, we observed a complete response in two, a very good partial response (VGPR) in two, and a PR in two patients, respectively. We conclude that topical application of tacrolimus ointment holds promise as a safe and efficacious treatment for oral GVHD in children. The Food and Drug Administration has recently issued a health advisory about a potential cancer risk associated with topical tacrolimus treatment of the skin; therefore, its benefits should be weighed against its potential risks and diligent long-term follow-up should be carried out especially in children.     

Osteoarticular infections in children with sickle cell disease

Thirteen children with sickle cell disease were identified as having 14 episodes of osteoarticular infection in a review of 27 years' experience. There were eight episodes of osteomyelitis or osteoarthritis and six of suppurative arthritis alone. The etiologic agents in osteomyelitis or osteoarthritis were Salmonella sp in four cases, Escherichia coli in one, Enterobacter aerogenes in one, Staphylococcus aureus in one, and Haemophilus influenzae type b in one. Five of the cases with infection limited to the joint were caused by Streptococcus pneumoniae; the sixth was caused by H influenzae type b. Fever (greater than or equal to 38.3 degrees C) was present in all children and the temperature was in excess of 39 degrees C in 62%. The mean duration of pain before admission was 4.5 days. The initial total white blood cell count ranged from 5,200 to 29,700/microL (mean 19,436/microL) and the total band neutrophil count ranged from 0 to 5,103/microL (mean 1,660/microL). The ESR was greater than 20 mm/h in eight of the ten patients who were tested. Management consisted of antibiotic therapy in all. Needle aspiration was performed in two patients with osteomyelitis and in three with suppurative arthritis. Incision and drainage was performed in two cases of osteomyelitis and in four with suppurative arthritis. The outcome was satisfactory in all except one patient who had several complications as a consequence of femoral neck osteomyelitis. Recurrence was reported in only one patient.     

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??Abstract??Objective To expore the clinical features of acute osteomyelitis of neonate. Methods A retrospective study was done about clinical symptoms??radiologic features and treatments in 13 neonates who were diagnosed with osteomyelitis in Children’s Hospital Affliated to Chongqing University of Medical Sciences from 2004 to 2012. Results There were eleven male and two female infants??10 babies were related to bacteraemia and 3 cases were due to infection nearby.Limb bones were most commonly compromised. Six babies had joint involvement. Local swelling and disorder of limb’s activity were the most common clinical symptoms. Twelve patients got positve culture results from blood??pus or joint fluid samples. The most common pathogens were Staphylococcus aureus and Gram-negative bacteria. All of the babies accepted antibiotic treatment while 4 cases also underwent surgeries. All osteomyelitis patients had good outcomes. None had any sequelae among the 7 cases during the following 2 months to 2 years. Conclusion Neonatal osteomyelitis is not a rare disease with atypical clinical features. Radiologic and bacteriologic examination should be carried out once osteomyelitis is suspected. Appropriate antibiotics and necessary surgery are important to avoid further damage as well as long-term sequelae.     

Prosthetic valve endocarditis due to Haemophilus parainfluenzae biotype II.

Haemophilus parainfluenzae endocarditis is characterized by great variation in the acuteness of presentation, difficulty in isolation of the pathogen, a 50% to 60% incidence of major arterial emboli, and variability of response to therapy. Prosthetic valve endocarditis (PVE) due to H parainfluenzae biotype II occurred in a 14-year-old girl with congenital heart disease and a Starr-Edwards mitral valve prosthesis. Management was complicated by a prolonged culture-negative period (eight days), intermittent bacteremia (only five of 15 positive blood cultures), an embolus to the right femoral artery, progressive congestive heart failure, and urgent prosthestic valve replacement. Cure was achieved with 44 days of ampicillin sodium-gentamicin sulfate therapy monitored by serum bactericidal titers.     

Studies on Phagocytosis and Microbicidal Activity of Monocytes in Children with Acute Leukemia.

Phagocytosis and microbicidal activity of monocytes in children with acute leukemia were studied in relation to the stages of the disease and severe fungalinfections. Phagocytosis and microbicidal activity of monocytes were defective in the active phase (before therapy, during relapse), and normalized during complete remission. Monocyte candidacidal activity in 11 of the 15 patients with severe infections was also defective. Extracellular factors such as serum from the patient, leukemic blast cells in the active phase and antileukemic drugs (prednisolone, vincristine, methotrexate) did not alter the monocyte functions at the concentrations tested. In seven patients with severe fungal infections, monocyte phagocytosis of Candidu albicans was defective in some patients, Candidacidal activity of monocytes was defective in all patients. The present study indicates that phagocytosis and microbicidal activity of monocytes are defective in the active phase of childhood acute leukemia and microbicidal activity is closely associated with the occurrence of severe fungal infections.