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[An experimental study on Pseudomonas osteomyelitis with special reference to the production of experimental osteomyelitis in mice (author's transl)].

I) The author has successfully produced a model of experimental osteomyelitis caused by pseudomonas aeruginosa using the following procedure though such a demonstration has been said to be very difficult. After impregnation in a solution containing about 10(5) pseudomonas aeruginosa, 3 mm silk thread of No. 5 was dried under low-pressure atmosphere and then inserted into the metaphysis of right tibia of a mouse. This method can be produced experimental osteomyelitis in 100% of the animals. In the experimental osteomyelitis generated pathologically by this method, inoculated organisms do not transmigrate into blood, the kidney and the contralateral tibia. This may therefore be regarded as a local infection causing no death, making a long period of observation possible. In view of the X-ray and patho-histological findings, it is similar to human osteomyelitis. Furthermore, its host is a pure-bred mouse with constant elements making a league-scale experiment possible. II) This is an experimental model of osteomyelitis proved quite useful for the quantitative analysis of the effects of antibiotics, and would be a good method for evaluation of antibiotics to be developed in the future.

Animals

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Humans

Osteomyelitis following puncture wounds of the foot in children.

Review of the laboratory and clinical findings and treatment of eight patients with osteomyelitis of the foot after puncture wounds revealed that: 1) osteomyelitis after puncture wounds is a infrequent but potentially serious complication, with significant morbidity; 2) osteomyelitis is frequently preceded by inadequate primary care for simple puncture wounds, and when treatment is appropriate, osteomyelitis usually can be avoided; 3) P. aeruginosa is the most commonly recovered organism; 4) the clinical presentation is characterized by a lack of systemic toxicity, paucity of laboratory abnormalities, and evidence of a localized infection process and the patient may be asymptomatic for a few days to several months after the injury before presentation of the osteomyelitis; and 5) once the infection has become established, treatment must be aggressive, including surgical debridement.

Adolescent

Treatment of chronic osteomyelitis by free grafts of cancellous autologous bone tissue. A preliminary report.

Chronic osteomyelitis was treated by free grafts of autologous bone tissue in 13 consecutive patients aged 18 to 81 to years. In all patients the osteomyelitis was located in the leg, and Staphylococcus aureus was the causative organism. Seven had an infected non-union. The duration of the osteomyelitis varied from less than 1 year to 75 years. Surgical debridement and grafting of cancellous and cortical cancellous bone were performed at the one operation. The osteomyelitis healed after a single operation in all patients but one, who needed three operations before the infection was eradicated. In one patient a second bone grafting operation was necessary before weight-bearing could be allowed. Although the number of patients is small, the results agree well with larger series published recently. Grafting of autologous bone tissue seems to be a very valuable method of treatment for chronic osteomyelitis.

Adolescent

Genomic insights into preantibiotic osteomyelitis pathogens and their link to current resistant hospital strains.

OBJECTIVES: Osteomyelitis is a severe bone infection that was frequently fatal before the introduction of antibiotics and remains a significant healthcare burden today. Staphylococcus aureus is the most common cause, alongside other hospital-acquired pathogens. Despite their clinical importance, the evolutionary history of these bacteria remains poorly understood. We investigated historical osteomyelitis specimens to identify causative pathogens and characterise their genomes, virulence and antimicrobial resistance (AMR). METHODS: Seven osteomyelitis-affected bones from adults dating to 19th-20th century Germany were analysed using ancient DNA (aDNA) approaches. After sequencing and screening, candidate pathogens were prioritised based on authentic aDNA damage patterns, established association with osteomyelitis and exclusion as environmental contaminants. Identified species were characterised by phylogenetics, multilocus sequence typing and virulence/AMR profiling. RESULTS: In four patients, we detected authentic aDNA from Acinetobacter baumannii, S. aureus or Streptococcus pyogenes. Detected taxa in the remaining three patients did not fulfil the criteria for further analysis. Two patients carried A. baumannii genomes clustering closely with modern avian and freshwater isolates. Both harboured virulence genes, alongside intrinsic efflux pumps and β-lactamases. One patient carried an S. aureus strain belonging to the globally disseminated clonal complex 30, responsible for outbreaks since the 1950s. Molecular dating indicated that this strain diverged from the wider lineage around 1800, placing it among the earliest members of this group. It encoded multiple virulence genes, but no methicillin resistance genes. The fourth patient carried an S. pyogenes strain related to modern epidemic lineages from North America, encoding conserved virulence factors, but no AMR genes. CONCLUSIONS: These specimens provide a window into the evolution of osteomyelitis pathogens. Although modern developments such as widespread antibiotic use have intensified the global resistance crisis, our findings indicate that the genetic foundations for pathogenicity and resistance were already present more than 100 years ago.

Ancient DNA

Diagnostic value of sinus-tract cultures in chronic osteomyelitis.

Sinus-tract cultures were compared with cultures of operative specimens from 40 patients with chronic osteomyelitis. Thirty-five patients (87.5%) had a single pathogen isolated from their operative specimens. Only 44% of the sinus-tract cultures contained the operative pathogen. Isolation of Staphyloccus aureus from sinus tracts correlated with the presence of S aureus in the operative specimen. However, less than half of the sinus-tract cultures obtained from patients with S aureus osteomyelitis contained this organism. Isolation of bacteria other than S aureus from sinus tracts had a low likelihood of predicting the pathogen isolated from bone. A presumptive diagnosis of S aureus osteomyelitis is justified if S aureus is isolated from an associated sinus tract. A bacteriologic diagnosis of chronic osteomyelitis based on isolation of common pathogens other than S aureus from sinus tracts must be verified by an appropriate operative culture.

Adolescent

[Sympathetic arthritis. A contribution to plasma cell osteomyelitis (author's transl)].

Sympathetic arthritis is a sterile, non-pyogenic complication due to adjacent bone disease, particularly chronic inflammatory osteomyelitis. Radiologically it is manifested as an arthrosis or serous arthritis (painful effusion), or as a chronic destructive arthitis. In the latter case, there is a lymphatic and plasma cell synovitis which may persist, clinically and radiologically, for a period of months or years before definite radiological signs of a chronic osteomyelitis become apparent. Observations of patients with plasma cell osteomyelitis and chronic destructive sympathetic arthritis indicate a special set of findings due to plasma cell osteomyelitis: metadiaphyseal ossifying periostitis, extreme demineralisation of the adjacent epiphysis with spotty focal sclerosis of the spongiosa and a chronic arthritis.

Adult

Pediatric osteomyelitis: III. anaerobic microorganisms.

Primary osteomyelitis consequent to obligate anaerobic microorganisms represents an infrequently encountered type of infection in pediatric patients. Unlike osteomyelitis caused by more common microorganisms such as Staphylococcus, children with osseous lesions due to anaerobic microorganisms are frequently minimally symptomatic and rarely present the classic signs of fulminant osteomyelitis. Radiographically, the lesions may mimic malignant osseous tumors. Fastidious microbiologic analysis of the material obtained at surgery is necessary to isolate obligate anaerobes. Basic treatment, comprising surgical drainage and appropriate antimicrobial agents, does not differ from that for osteomyelitis caused by aerobic or by facultative anaerobic microorganisms.

Adolescent

[An experimental study on pyogenic osteomyelitis with special reference to the analysis of the therapeutic effects of antibiotics in vivo (author's transl)].

Experimental osteomyelitis was produced in mice by the Ueno's method for the purpose of evaluating therapeutic effects of the antibiotics. The results were as follows: 1) Experimental osteomyelitis produced with penicillin-G sensitive bacteria was completely cured by PC-G 1.8 mg per mouse a day, which provided maintenance of the concentration in serum more than 10 times of MIC for over 12 hours. The dosis of 0.18 mg per mouse per day was insufficient to bring a complete healing. 2) Experimental osteomyelitis produced with penicillin-G resistant bacteria did not heal completely, despite the administration of MPI-PC, a synthetic penicillin designed against penicillin resistant staphylococci, in a dosis of 5 mg twice a day, probably by the following reasons. Since MPI-PC is water-soluble, it is difficult to maintain the concentration in serum more than 10 times of MIC for over 1 hour. In other word, the bacteria was exposed to the effective antibiotic concentration for only one hour twice a day. 3) It was experimentally proved that earlier administration of antibiotics following inoculation provided quicker elimination of bacteria. 4) When bactericidal antibiotics were used, administration twice a day in half dosis gave better results compared with the full dosis once a day. 5) This experimental model of osteomyelitis proved quite useful for quantitative analysis of the effects of antibiotics, which would be applicable as a good method for evaluation of antibiotics to be developed in the future.

Animals

Haemophilus influenzae type b osteomyelitis.

Three children had osteomyelitis due to Haemophilus influenzae type b. They were seen with signs and symptoms indistinguishable from infection caused by other organisms. One child was initially misdiagnosed as having septic arthritis because of failure to appreciate that Hemophilus may also cause bone infection. In the second patient osteomyelitis and arthritis developed during ampicillin sodium therapy for treatment of Hemophilus meningitis. His initial infection was caused by an ampicillin-sensitive isolate but his orthopedic infection subsequently responded to therapy only after changing to a regimen of chloramphenicol. In the third patient, bone scintigraphy was helpful in diagnosis since serial roentgenograms were not diagnostic of osteomyelitis. The anticapsular antibody responses of these patients were measured by radioimmune assay. The levels found were low but comparable to age-matched control children with H influenzae type b meningitis.

Antibodies, Bacterial

Group B streptococcal osteomyelitis and septic arthritis. Its occurrence in infants less than 2 months old.

Nine infants less than 2 months of age with group B streptococcal (GBS) osteomyelitis or septic arthritis, or both, were seen from January 1975 through January 1978. The infants had local joint signs, usually in the absence of systemic signs. The bones and joints involved were equally distributed between proximal humerus and proximal and distal femur. An infant had involvement of the talus. Treatment consisted of two to three weeks of parenteral antibiotics, arthrotomy in infants with arthritis, and bone decompression in infants with osteomyelitis. Clinical follow-up showed normal growth and function of the affected joint. Of the organisms, five were typed: four were type III and one was type Ib. Group B streptococcal osteomyelitis and/or septic arthritis was the second most common late-onset GSB infection, being surpassed only by meningitis.

Arthritis, Infectious

An etiologic shift in infantile osteomyelitis: the emergence of the group B streptococcus.

Twenty-one infants from six to 52 days of age (mean 23.3 days) with osteomyelitis were studied between 1965 and 1977. The etiologic agents were group B streptococcus (8), staphylococcus aureus (6), gramnegative bacilli (4), Streptococcus pneumoniae (1), and unknown (2). Patients with group B streptococcal osteomyelitis were characterized by an uncomplicated neonatal course, single bone involvement with a predilection for involvement of the proximal humerus, and lack of inflammatory signs. In contrast, patients with osteomyelitis due to other organisms frequently had had manipulative procedures predisposing to infection and were more likely to have multiple bone involvement, fever, and leukocytosis at the time of diagnosis. Functional impairment was detected in only one of 17 patients evaluated a mean of 36 months after diagnosis.

Female

Scintigraphy in diagnosis of osteomyelitis of the jaws.

The symptoms of an acute osteomyelitis of the jaws are often uncharacteristic, and typical radiographic changes usually do not appear until after the first weeks of disease. Even when such changes are established it is difficult to distinguish an active infectious disease from lasting changes due to a sterilized osteomyelitis. Scintigraphy with bone-seeking radiopharmaceuticals appears to be a valuable diagnostic technique. A case of osteomyelitis of the mandible is reported.

Female

Choice of antibiotics in management of acute osteomyelitis and acute septic arthritis in children.

A survey of 158 children with acute haematogenous osteomyelitis, and of 94 children with acute septic arthritis over an 8-year period was made to determine which bacteria cause these infections. In the osteomyelitis group the organism most frequently detected was Staphylococcus aureus (74% of cases). In 16% of cases streptococci were found. Staph. aureus was also the most frequently grown organism in cases of acute septic arthritis (55% of cases), but Haemophilus influenzae accounted for 24% of positive cultures. On the basis of the survey it is the current practice of the author to use a combination of methicillin or cloxacillin and penicillin for acute haematogenous osteomyelitis, and methicilline or cloxacillin and ampicillin for acute septic arthritis. The choice of antibiotics is vitally important as treatment must start before the results of culture are known. Repeated evaluation of trends in the pattern of causative organisms is strongly recommended, in order to be aware of changing sensitivity of organisms to antibiotics.

Adolescent

Candida osteomyelitis as a complication of parenteral nutrition in an infant. Successful treatment with flucytosine.

Hematogenous Candida osteomyelitis is described in a two-month-old infant, as a complication of Candida septicemia which occurred during a parenteral hyperalimentation regimen. Treatment with flucytosine led to full recovery. The scarcity of reports on hematogenous Candida osteomyelitis in infants, despite an increased incidence of Candida septicemia, and the non-specific symptomatology which the disease may assume in this age group, indicate the need for greater awareness of this complication. Flucytosine is an antifungal drug which can also be given by mouth and carries relatively low toxicity. We found flucytosine to be extremely effective in the treatment of disseminated infantile Candida osteomyelitis.

Administration, Oral

[Contribution to the treatment of acute haematogenous anc chronic secondary osteomyelitis in children (author's transl)].

The possibility of utilizing antistaphylococcal vaccine and local phage lysate for complex therapy of chronic and acute haematogenous osteomyelitis in children is demonstrated on three clinical cases. The study reassurmes good experience with this therapy in adult patients with chronic osteomyelitis. The results obtained so far in children suggest that the application of antistaphylococcal vaccine and of local phage lysate positively influences the course of the osteomyelitic disease and reduces the number of relpases. In order to specify and intensify the clinical effect of the above mentioned preparations, this method is being employed in other cases of chronic and acute haematogenous osteomyelitis.

Acute Disease