Oral antibiotic therapy for skeletal infections of children. II. Therapy of osteomyelitis and suppurative arthritis

Antimicrobial regimens consisting of a brief initial period of parenteral therapy followed by oral therapy were investigated in infants and children with suppurative bone and joint disease. There were 30 patients with acute hematogenous disease (19 osteomyelitis; three osteoarthritis; eight arthritis) and five with subacute or chronic osteomyelitis. Disease was due to Staphylococcus aureus in 26, Hemophilus influenzae in five, streptococci in three, and S. aureus plus Streptococcus pyogenes in one patient. Pus was removed by surgical drainage or needle aspiration. Oral therapy was monitored by assay of antibiotic concentration and bactericidal activity in serum. Adjustments in dosage were made when necessary to assure a peak serum bactericidal titer of at least 1:8. One patient progressed to chronic osteomyelitis but all other patients with acute disease responded well. Oral therapy provides increased patient comfort and decreases the risk of nosocomial infection associated with prolonged intravenous therapy. It should be carried out only under carefully monitored conditions in hospital to assure compliance and adequacy of serum bactericidal activity.     

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.     

Relapse of Hemophilus influenzae type b meningitis after combined antibiotic therapy: report of a case.

Antibiotic therapy of bacterial meningitis is being reevaluated due to reports of ampicillin-resistant strains of Hemophilus influenzae type b. The infant reported had a relapse of H. influenzae type b meningitis after an excellent clinical and bacteriologic response to an initial course of combined antibiotic therapy including chloramphenicol. This relapse is postulated to be due to localized cerebral vasculitis which was not treated for a sufficient period of time during the initial course of therapy. The patient responded well to a second course of penicillin and chloramphenicol. Since the use of pencillin and chloramphenicol will be increasing, the clinician should be aware that bacteriologic relapse of H. influenzae type b meningitis may occur with chloramphenicol therapy.     

Onset of Hemophilus influenzae type-b meningitis during cefaclor therapy for preseptal cellulitis

Second generation cephalosporins are frequently used for the treatment of bacteremic Hemophilus influenzae type b infections. "Breakthrough" meningitis during cefamandole therapy has documented the need for adequate cerebrospinal fluid penetration by these antibiotics if they are to be used in the therapy of Hemophilus infections. A child with H. influenzae type b preseptal cellulitis is reported who initially responded to treatment with intravenous cefuroxime and oral cefaclor. However, while still receiving cefaclor, the child was readmitted with H. influenzae meningitis. Microtiter broth dilution susceptibility testing performed during the second admission showed the isolate to be relatively resistant to cefuroxime (minimum bactericidal concentration [MBC] = 4 micrograms/ml) and resistant to cefaclor (MBC greater than 16 micrograms/ml). This experience documents the need to monitor the clinical response closely during therapy of H. influenzae bacteremic infections with these second generation cephalosporin treatment regimens. In addition, attention should be paid to minimum inhibitory concentrations of these cephalosporins, since variations in H. influenzae type b susceptibility to these agents may limit their efficacy.     

Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy

A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.     

Hemophilus influenzae type f meningitis in an adolescent

A 17-year-old male with Hemophilus influenzae type f meningitis is reported. Recent studies which suggest that the incidence of H. influenzae meningitis in older individuals is increasing are reviewed. Therefore, we recommend that antimicrobial therapy directed against H. influenzae be included in the initial management of older children, adolescents, and adults with acute bacterial meningitis.     

Pneumococcal osteomyelitis and arthritis in children. A hospital series and literature review

Twenty-nine children with pneumococcal osteomyelitis and/or arthritis, 11 of whom had osteomyelitis, were treated at Cook County Hospital, Chicago, Ill, in the past 20 years. They were mostly normal children with a single focus of infection. They represented more than 5% of the hospitalized children with a systemic pneumococcal infection. Most of the pneumococcal isolates were serotyped; serotype 19, in particular, seemed to be unusually common in these children. Twenty-three of the 29 children with pneumococcal osteomyelitis and/or arthritis had been hospitalized in the past 15 years. These 23 children were compared with 161 hospitalized children who had bone and joint infections with other isolated bacteria. The children with pneumococcal osteomyelitis and/or arthritis were indistinguishable from most of the other children, except by age. All but three of the children with pneumococcal osteomyelitis and/or arthritis were between the ages of 3 and 24 months. In this age group, Pneumococcus was the common isolate from children with osteomyelitis, and second only to Haemophilus influenzae from children with bacterial arthritis. Pneumococcal osteomyelitis and/or arthritis has never been rare; the medical literature describes at least 245 other children, most of whom were younger than 2 years.     

Arthritis associated with Haemophilus influenzae meningitis: septic or reactive?

We reviewed 165 pediatric cases of Haemophilus influenzae type b meningitis and found 11 (6.7%) with associated arthritis. Synovial fluid culture and Gram stain suggested that only three of these 11 cases were caused by a septic process. In all three children with septic arthritis, joint symptoms were present on admission or within 24 hours. In contrast, of the eight who had reactive arthritis, arthritis did not appear in six until after 1 week of antibiotic therapy. Patients with septic arthritis were older than patients with reactive arthritis (mean 31 months vs 17 months), had a longer duration of symptoms before the start of antibiotic therapy (mean 6.0 days vs 2.5 days), and were more likely to have a positive blood culture (67% vs 18%). It is probable that the majority of episodes of synovitis occurring after H. influenzae meningitis occur as a result of a reactive rather than a septic process. Treatment of reactive arthritis should be with anti-inflammatory agents rather than with multiple joint aspirations and prolonged antibiotic therapy.     

Detection and quantitation of bacteremia in childhood.

Quantitative blood cultures were sought in 383 children, from whom routine blood cultures were obtained because of fever, by direct plating of 10 and 100 microliter blood onto solidified media. There were 14 positive cultures from 12 patients. These were 7 Hemophilus influenzae type b, 5 Streptococcus penumoniae, and 2 Staphylococcus aureus. The direct-plating technique permitted more rapid identification of positive cultures, and detected three episodes not identified by routine broth culture. Bacterial counts ranged from 20 to greater than 10(4) bacteria/ml blood. In the three cases of H. influenzae type b meningitis, bacteremia exceeded 10(3)/ml. Among nine patients in whom bacteremia was unassociated with meningitis, (bacteremia without evident localized disease 5, pneumonia 2, epiglottitis 1, peritonitis 1), bacteremia was less than 10(3)/ml. This technique may aid detection of bacteremia and help identify those children at highest risk for developing septic complications, such as meningitis.     

Cerebral infarction in Hemophilus influenzae type B meningitis

Over a 5-year period, 8 (4.7%) of the 170 children diagnosed at Milwaukee Children's Hospital as having Hemophilus influenzae type b (HITB) meningitis developed cerebral infarction. Compared with children who did not develop infarcts or with children who developed other neurologic complications, such as subdural effusion, empyema, or meningoencephalitis, these children had significantly higher cerebrospinal fluid (CSF) leukocyte counts on initial lumbar puncture and had a greater likelihood of seizure activity. In seven of eight patients with cerebral infarction, a focal or generalized seizure heralded neurologic findings associated with abnormal radiographic studies. Two of the eight patients died, and two were permanently severely damaged. In the other four patients, there was eventual recovery from gross neurologic deficits. The mortality in patients with HITB meningitis complicated by cerebral infarction (25%) was significantly greater than that in other patients with HITB meningitis (0.6%). The pathophysiology of infarction in patients with bacterial meningitis is uncertain but may in part relate to arteriospasm. Cerebral infarction is a serious, and in the present experience, not uncommon complication of H. influenzae meningitis.     

Meningitis due to Haemophilus influenzae other than type b: case report and review.

A 4-month-old female infant with meningitis caused by Haemophilus influenzae type f had a hospital course complicated by sterile subdural effusions and persistent neurologic abnormalities. One year later she was normal in all respects. The infant's mother had serum bactericidal antibodies to H. influenzae type b but not to type f. During recovery the patient had no bactericidal antibodies to type b, and the type f organism could not be maintained in her serum. Review of the literature identified 40 cases of meningitis reported as caused by H. influenzae other than type b. An evaluation of the ten cases described as due to encapsulated strains (a, e, and f) shows that the age distribution and clinical features are similar to those of meningitis caused by type b. Only five cases of meningitis caused by unencapsulated H. influenzae have been described. Four of the patients were older than the usual age range for type b meningitis and two had prior head trauma. A large clinical trial in Finland with a two-year observation period has demonstrated no untoward increase in non-b H. influenzae meningitis in recipients of a type b vaccine. Serious infections caused by other H. influenzae types will continue to occur sporadically and may increase in frequency when an effective vaccine against type b is widely used in infants.     

Acute osteomyelitis in children. Reassessment of etiologic agents and their clinical characteristics

One hundred thirty-five children with acute osteomyelitis were identified by chart review during a 7-year period, January 1, 1980, through December 31, 1986. Bacteriologic causes were detected in 75 (55%) of the patients. Staphylococcus aureus, Haemophilus influenzae type b, and Pseudomonas aeruginosa were identified in 34 (25%), 16 (12%), and eight (6%) children, respectively. Staphylococcus aureus occurred in all age groups, H influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group. Pseudomonas aeruginosa occurred exclusively in children older than 9 years. Children with H influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria, although children with H influenzae type b tended to have more joint effusions (63% vs 27%), less lower extremity disease (22% vs 70%), and fewer positive cultures from bone or joint aspirates (41% vs 89%). Unlike most pediatric cases of osteomyelitis, the ones due to P aeruginosa did not represent the hematogenous route of infection; penetrating injury to the foot was present in every case. Children with P aeruginosa infections were older than 9 years (100%), predominantly male (88%), often afebrile (83%), and never bacteremic. These data provide guidelines for the initial work-up and management of osteomyelitis in children.     

The diagnostic significance of countercurrent immunoelectrophoresis (CIE) in bacterial meningitis in children (author's transl)

In 52 children with meningitis caused by Hemophilus influenzae, pneumococci, meningococci and group B streptococci the organism responsible could be identified in 41 cases (79%) within one hour with specific antisera by means of countercurrent immunoelectrophoresis (CIE). False positive results were not observed in meningitis caused by other organisms, aseptic meningitis, septicemia, etc. In 4 cases the organism could only be identified by CIE since the children had received antibiotics and the culture was negative. Group B meningococci are often missed in CIE. CIE proved to be a valuable tool in diagnostic procedures of bacterial meningitis.     

Incidence of ampicillin-resistant Hemophilus influenzae in otitis media.

Ampicillin resistance in Hemophilus influenzae type b causing serious infections is appreciated, but little is known about ampicillin resistance in nonencapsulated strains causing otitis media. The ampicillin sensitivity of 984 middle-ear isolates of H. influenzae from children in Huntsville, Ala. obtained from 1970-1976, was examined: Nine AmpR isolates were found: one in 1973, two in 1974, three in 1975, and three in the first five months of 1976. Seven strains were nonencapsulated; two were type b. All nine produced beta-lactomase. The incidence of ampicillin resistance in strains causing otitis media increased from 0.6% in 1973 to 2.4% in 1976. AmpR H. influenzae infection should be suspected in situations where ampicillin therapy of otitis media is unsuccessful.     

化脓性脑膜炎合并硬膜下积液80例分析

目的 探讨更合理的化脓性脑膜炎合并硬膜下积液的诊断与治疗方法。方法 收集1992年1月至1999年12月确认为化脓性脑膜炎的病例291例，男188例，女103例，年龄10d至13岁。结果 291例化脓性脑膜炎中并发硬膜下积液者80例，发病率为27．5％，年龄在15d－16个月，均为前囟门未闭的儿童。在并发硬膜下积液的80例中以肺炎双球菌脑膜炎为多，占37例（46．3％），其次为嗜血流感杆菌脑膜炎，21例（26．3％）。不同细菌脑膜炎硬膜下积液的发生率不同。硬膜下积液多出现在病程的4－10d。80例合并硬膜下积液的病人中，单纯性积液7例；硬膜下感染45例；积脓28例，2例死亡。结论 硬膜下积液、感染或积脓的病因尚不明确，可能与化脓性脑膜炎时，脑血管通透性增强，脑血管表浅静脉发生炎性栓塞，细菌随血液循环进入硬膜下腔等因素有关。诊断明确者经过积极合理的治疗，成活者，积液均于6个月内吸收。     

Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants. Correlation with a scoring system for severity of sequelae.

OBJECTIVES--To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population. DESIGN--A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years. Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated. Data obtained on admission to the hospital were used to calculate HTPS. SETTING--Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska. STUDY SUBJECTS--51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988. One child was infected with both organisms, producing a total of 64 cases for study. SELECTION PROCEDURES--Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control. MEASUREMENTS AND RESULTS--Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States. After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States. Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype. Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis. The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae. Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission. CONCLUSIONS--Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts. The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center.     

Persistent pleocytosis in bacterial meningitis.

Persistent pleocytosis of greater than 60 white blood cells/mm3 was commonly seen in children adequately treated for bacterial meningitis. It occurred in 13 of 21 (62%) children with Hemophilus influenzae meningitis and in 2 of 9 (22%) with pneumococcal meningitis. Pleocytosis alone cannot be used as an indication of prolonging therapy; significance of persistent pleocytosis is not known.     

Joint and bone infections due to anaerobic bacteria in children

The current review describes the microbiology, diagnosis and management of septic arthritis and osteomyelitis due to anaerobic bacteria in children. Staphylococcus aureus, Haemophilus influenzae type-b, and Group A streptococcus, Streptococcus pneumoniae, Kingela kingae, Neisseria meningiditis and Salmonella spp are the predominant aerobic bacteria that cause arthritis in children. Gonococcal arthritis can occur in sexually active adolescents. The predominant aerobes causing osteomyelitis in children are S. aureus, H. influenzae type-b, Gram-negative enteric bacteria, beta-hemolytic streptococci, S. pneumoniae, K. kingae, Bartonella henselae and Borrelia burgdorferi. Anaerobes have rarely been reported as a cause of these infections in children. The main anaerobes in arthritis include anaerobic Gram negative bacilli including Bacteroides fragilis group, Fusobacterium spp., Clostridium spp. and Peptostreptococcus spp. Most of the cases of anaerobic arthritis, in contrast to anaerobic osteomyelitis, involved a single isolate. Most of the cases of anaerobic arthritis are secondary to hematogenous spread. Many patients with osteomyelitis due to anaerobic bacteria have evidence of anaerobic infection elsewhere in the body, which is the source of the organisms involved in osteomyelitis. Treatment of arthritis and osteomyelitis involving anaerobic bacteria includes symptomatic therapy, immobilization in some cases, adequate drainage of purulent material and antibiotic therapy effective to these organisms.     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91)

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.     

Acute epiglottitis: therapeutic consequences of change in the resistance of Haemophilus influenzae serotype B

From July 1977 to May 1987, 27 children with acute epiglottitis were treated in our intensive care unit. Haemophilus influenzae type b was identified by positive blood culture in 14 of 27 cases. Until 1983 the first 11 children were treated with ampicillin (100 mg/kg) for a mean duration of 10 days according to the standard therapeutic regimen and/or proven sensitivity from blood cultures (5 of 11 cases). The first finding of an ampicillin resistant Haemophilus influenza type b strain dates from January 1984. From this date on initial antibiotic therapy consisted of cefotaxime (100 mg/kg). Blood cultures proved good sensitivity to cefotaxime (100%) but an increasing rate of resistance to ampicillin (3 of 9 identified strains). Haemophilus influenzae septicemia in acute epiglottitis is verified by the isolation of Haemophilus influenzae type b from blood cultures (14/27) and the additional pneumonias (14/27). Additional meningitis as seen is a very rare complication. Facing these potentially life-threatening secondary foci of this invasive infection, an effective antibiotic therapy is mandatory. Our experiences confirm recommendations from US, UK, Australia, and Spain, where ampicillin was replaced by third generation cephalosporins as initial antibiotic therapy due to the increasing rate of resistance of Haemophilus influenzae type b.