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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

[A study on experimental pyogenic osteomyelitis. 1. The preferential site of hematogenous osteomyelitis. 2. The role of foreign body in hematogenous infection (author's transl)].

The author undertook the experiments as described below in order to determine the preferential site of hematogenous osteomyelitis and possible effects of foreign bodies in the bone marrow on development of infection. I) In the first experiment, mice were inoculated with 10(7) cells of staphylococcus aureus intravenously into the tail vein and examined for the distribution and proliferation of the organisms in the bones, all over the body. It was found that the orgaisms in the blood stream were distributed to the bones all over the body almost evenly and that after prolonged observation, remarkable proliferation was noted in both femur and tibia. This bacteriological fact was supported by roentgenographic examination of all the bones. II) In the second experiment, inoculation of staphylococcus aureus into the tail vein was made after a foreign body (No. 5 sterile silk thread of 3 mm in lenght) had been inserted into the proximal metaphysis of a tibia of mice. The tibia of both legs was divided into 3 parts: proximal metaphysis, diaphysis and distal metaphysis. Observation were made for the distribution of organisms and state of proliferation in each of these three parts. In order to elucidate how the inserted foreign body promoted the establishment of infection, the group inserted with silk thread was compared with the control group (un-inserted group). The following results were obtained: 1. Although after 2 weeks of inoculation, the foreign body exerted no influences on the distribution and proliferation of organisms, but it was experimentally demonstrated to play a very important role for retention of organisms and maintenance of infection for a long period. 2. When the inoculum size was 10(6) to 10(7), the organisms were distributed evenly throughout the tibia. However, in the diaphysis the organisms tended to disappear, while in the metaphyseal area the organisms were easy to proliferate. It was also shown that at least 10(5) of organisms were needed for the establishment of infection and that the success or failure of establishment of infection is determined usually within 24 hours after inoculation of the organisms. As described above, from this study it was demonstrated that the femur and tibia were the preferential site of hematogenous osteomyelitis and that metaphyseal areas of the long bones were commonly affected. Once hematogenous invasion of organisms occurred, administration of antibiotics should be started as soon as possible, no later than 24 hours. According to our common experience, removal of foreign body is necessary for the complete cure of the injection.

Animals

Pediatric osteomyelitis: II. Arizona hinshawii osteomyelitis.

Two children with sickle cell disease and kwashiorkor developed osteomyelitis caused by an Arizona hinshawii infection. Biologically, this organism is related to the Salmonella species. The infections were successfully treated by surgical drainage and chloramphenicol.

Anemia, Sickle Cell

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

A retrospective study of osteomyelitis in dogs and cats.

Thirty-nine cases of osteomyelitis in dogs and cats were recorded at the Sydney University Veterinary Hospital and Clinic over a three and a half year period. In 36 cases osteomyelitis was established prior to admission. Three cases of osteomyelitis became established from a total of 502 orthopaedic surgery cases seen at the hospital in this period. In the dog the most common source of infection was open reduction of closed fractures, while in the cat, the most common source of infection was an extension from soft tissue infection. More males than females were affected. Ten cases of osteomyelitis were treated successfully, twelve cases required amputation, while euthanasia was performed on thirteen other cases. The problems and principles of treatment of active osteomyelitis as reflected in the treatment of this series of cases have been described.

Amputation, Surgical

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

[Diagnosis and differential diagnosis of acute hematogenous osteomyelitis in infants (author's transl)].

Clinical and laboratory data are frequently unspecific in acute hematogenous osteomyelitis of infants. As prognosis is dependent on early treatment, a timely radiologic diagnosis is mandatory. Because of specialties in the vascular supply, the roentgenmorphologic alterations of acute hematogenous osteomyelitis in infants differ from the appearance of the disease in other age groups. The acute osteomyelitis in infants frequently leads to destruction of the epiphysis and purulent joint effusion. A subtle analysis of soft tissue lesions will already rise suspicion for acute hematogenous osteomyelitis before destructive or reactive osseous alterations prove the diagnosis by roentgenology. Nuclear medicine examinations of the bone have contributed significantly to radiologic diagnosis of acute hematogenous osteomyelitis in infants despite of few negative results. Osseous trauma and other diseases should be included in differential diagnosis. Especially in neonatals and premature infants, variations in the typical course and appearance of the disease may occur.

Acute Disease

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

Pyogenic osteomyelitis of axial bones following civilian gunshot wounds.

A series of forty-five patients with low velocity gunshot wounds to the spine and pelvis were followed up for at least eight weeks to determine the incidence of pyogenic osteomyelitis and the role of debridement and fragment removal in its prevention. Four cases of osteomyelitis were found, and although debridement was not frequently done, the incidence of osteomyelitis was higher following debridement than it was without debridement. The most important cause appeared to be spread of contiguous intraabdominal abscesses into the injured paravertebral muscles and spine. If an intraabdominal abscess did not develop, the presence of gastrointestinal injury did not predispose the patient to osteomyelitis. Based on this study, we can conclude that debridement and fragment removal of the spine and pelvic bones are unnecessary for low velocity missile wounds.

Abscess

The production of prostaglandins in response to experimentally induced osteomyelitis in rabbits.

Osteomyelitis was induced in the tibiae of rabbits by injection of staphylococcus aureus and sodium tetradecylsulphate (STD); additional rabbits were injected with STD alone. Confirmation of osteomyelitis was based on positive culture of the same phage type bacteria from the tibiae and on the characteristic radiographical and histological appearance of osteomyelitis. Only tibiae which proved to be infected by the above criteria showed significantly increased in vitro release and content of Prostaglandin E and Prostaglandin F2 alpha compared with tibiae injected with STD (P less than 0.05). After two weeks infection, infected tibiae released nine times more Prostaglandin E and five times more Prostaglandin F2 alpha than tibiae injected with STD alone. After four weeks infection, infected tibiae released less Prostaglandin E (P less than 0.05) than after two weeks infection but the release of Prostaglandin F2 alpha was similar. The production of large amounts of prostaglandins by bones in response to infection may be the cause of the rapid bone resorption and sequester formation observed in osteomyelitis.

Animals

[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