Review

Authors: Margarita González-Martín, Vanessa Silva, Patricia Poeta...

Osteomyelitis is a challenging infectious disease affecting humans and animals. It is difficult to diagnose because, in many cases, symptoms are non-specific and, for example in implant-related cases, can appear long time after surgery. In addition to this, it is also difficult to treat due to the need to find the appropriate antibiotic regime and delivery system to reach the site of infection and to avoid development of bacterial resistance. The central purpose of this review is to compare the microbiological aspects of osteomyelitis in human and veterinary medicine, with the aim of improving the microbiological diagnosis and treatment of this infection in animals. Furthermore, the study of osteomyelitis in animals may help to improve the development of animal models for testing new treatments in humans. Host factors and underlying conditions have been studied mainly in humans, although aspects as immunodeficiency have been described in some veterinary cases. Even when is still considered the most prevalent causing microorganism, this prevalence should be reviewed using molecular diagnostic techniques, and this could affect treatment options. New approaches to treatment include local delivery of antibiotics using different biomaterials, antimicrobial photodynamic therapy, and new antimicrobial compounds. We would like to remark the need of large, high-quality clinical trials and of the development of guides for the diagnosis and treatment of osteomyelitis in different animal species.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Osteomyelitis; Staphylococcal Infections; Staphylococcus aureus

PubMed: 34936853
DOI: 10.1080/01652176.2021.2022244

Authors: Akram Uddin, David Russell, Fran Game...

BACKGROUND

Osteomyelitis of the foot is a major complication of diabetes that can be limb and life threatening. Systemic antibiotic pharmacotherapy is often used first line to eradicate infection and allow restoration of devitalised bone. The aim is to conduct a systematic review of the effectiveness of systemic antibiotics on osteomyelitis of the foot in adults with diabetes mellitus.

METHODS

A systematic review of all interventional studies treating osteomyelitis with systemic antibiotics in participants with diabetes mellitus and an ulcer of the foot below the malleoli will be conducted. Studies not available in English and in people below the age of 18 will be excluded. Study selection will follow the Patient Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA-P guidelines). The quality of the studies will be assessed using the Cochrane risk-of-bias tool (RoB 2) for all randomised controlled trials and the Newcastle-Ottawa Scale (NOS) will be used for non-randomised controlled trials. Electronic databases will be searched with no timeline restrictions.

DATA EXTRACTION

All identified references will be imported to the Rayyan Application. Studies for eligibility will be screened by two reviewers. One reviewer will perform the data extraction and quality appraisal will be conducted by two authors. If sufficient data is available, the quality will be analysed and a meta-analysis will be performed. Data synthesis will be conducted, and meta-analysis undertaken using RevMan 5.4.1 Meta-analysis software. Non-parametric data may be compared between selective intervention and outcomes.

DISCUSSION

The results of this systematic review will identify the effectiveness of systemic antibiotic therapy on osteomyelitis of the foot in people with diabetes based on the set outcome measure criteria. The findings will establish if there are existing consistent standards or variation in practice when treating diabetic foot osteomyelitis (DFO). The study may establish if guidelines are required to standardise practice when treating DFO with systemic antibiotic therapy. This systematic review protocol will synthesise the existing evidence on the effectiveness of systemic antibiotic therapy for treating DFO.

TRIAL REGISTRATION

International Prospective Register for Systematic Reviews (PROSPERO) number CRD42021245424 .

Topics: Adult; Anti-Bacterial Agents; Diabetes Mellitus; Diabetic Foot; Humans; Meta-Analysis as Topic; Osteomyelitis; Systematic Reviews as Topic

PubMed: 35710432
DOI: 10.1186/s13047-022-00554-3

Authors: Jinzhu Fan, Fei Cong, Xiaoyu Ren...

Objective

To investigate the effectiveness of flap combined with induced membrane technique in treatment of post-traumatic tibial osteomyelitis with soft tissue defect.

Methods

A clinical data of 33 patients with post-traumatic tibial osteomyelitis with soft tissue defect who met the selection criteria between August 2015 and October 2018 was retrospectively analyzed. There were 21 males and 12 females. The age ranged from 19 to 70 years, with an average of 39 years. The osteomyelitis located in the upper 1/3 of tibia in 8 cases, in the middle 1/3 of tibia in 14 cases, and in the lower 1/3 of tibia in 11 cases. According to Cierny-Mader classification standard, 19 cases of osteomyelitis were type Ⅲ and 14 cases were type Ⅳ. The duration of osteomyelitis ranged from 2 months to 20 years (median, 3 months). In the first-stage operation, after radical debridement, the length of bone defect was 1.5-12.5 cm (mean, 5.0 cm) and the size of soft tissue defects ranged from 5 cm×4 cm to 15 cm×12 cm. Bone cement containing antibiotics was implanted into the bone defect and the personalized flap was used to repair the wound. After the wound healed at 6-8 weeks and the infection was controlled, bone grafting was performed to repair bone defects in the second-stage operation.

Results

The flaps survived completely after the first-stage operation in 29 cases. Partial necrosis of the flap occurred in 4 cases and healed after surgical dressing change. All the incisions healed by first intention after the second-stage operation. All patients were followed up 24-32 months (mean, 28 months). All the bone grafts healed after operation, and the radiographic healing time was 3-9 months (mean, 5 months). The clinical healing time was 4-14 months (mean, 8 months). There was no recurrence of osteomyelitis during follow-up. At last follow-up, according to Johner-Wruhs evaluation criteria, the limb function was excellent in 27 cases, good in 4 cases, and fair in 2 cases, with an excellent and good rate of 93.9%.

Conclusion

For the post-traumatic tibial osteomyelitis with soft tissue defect, the flap combined with induced membrane technique is a reliable and effective method and can effectively restore the function of lower limbs with satisfactory effectiveness.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Osteomyelitis; Reconstructive Surgical Procedures; Retrospective Studies; Skin Transplantation; Soft Tissue Injuries; Tibia; Treatment Outcome; Young Adult

PubMed: 35570637
DOI: 10.7507/1002-1892.202201031

Authors: Bartłomiej Juszczak, Jerzy Sułko

To evaluate patient-reported effectiveness, safety and social influence of Pamidronate in the therapy of NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis in children. Authors reviewed self-created questionnaires, which asked patients for symptoms alleviation, adverse drug reactions frequency and degree of severity and daily activities self-reliance. Only surveys with complete answers, which were returned to authors by an e-mail from juvenile patients treated for NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis at the University Children's Hospital of Cracow were analyzed. Between 2010 and 2019, 61 children were diagnosed with NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis at our department. Out of 61 requests sent, 42 complete replies (33 females, 9 males) were gathered and analyzed. All patients included in this research were administered with at least one set of Pamidronate intravenously in the dose of 1 mg/kg/day for 3 consecutive days. Our analysis shows remarkable in terms of patient's impressions decrease of pain intensity after 2.5 series of Pamidronate on average, and total pain resolution after 5.9 series on average. Overall number of adverse drug reaction events reported by responders was 105. One patient developed drug-dependent renal insufficiency in the course of therapy. Outcome assessment indicates that nearly 50% of the studied population was more eager to participate in social life just after the first infusion of the drug. 95% of the surveyed unanimously agreed to recommend Pamidronate therapy to cure NSAIDs-refractory CRMO. 39 out of 42 (93%) patients considered Pamidronate effective at the end of the treatment. Onset of Pamidronate's action is gradual and differs in terms of symptoms alleviation between sexes. The therapy can induce considerable number of adverse drug reactions (2.5 per patient). Only 3 out of 42 (7%) patients were free from any ADRs. To demonstrate the impact of the use of Pamidronate on daily activities more precisely, further research with quantification of the quality of life is warranted.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Chronic Disease; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Osteomyelitis; Pamidronate; Patient Reported Outcome Measures; Quality of Life; Retrospective Studies; Treatment Outcome

PubMed: 34018012
DOI: 10.1007/s00296-021-04886-4

Authors: Taiji Koyama, Goh Ohji, Masako Nishida...

BACKGROUND

Cutibacterium modestum was named in 2020. C. modestum was previously called Propionibacterium humerusii. Several implant-associated infections caused by Cutibacterium species have been previously reported, but native vertebral osteomyelitis due to these bacteria has rarely been reported.

CASE PRESENTATION

A 72-year-old man, who had previously received several nerve block injections for low back pain, was referred to our hospital for deterioration in back pain in the last 1 month. MRI findings were suggestive of L5-S1 vertebral osteomyelitis. Blood cultures and bone biopsy culture revealed the presence of Gram-positive bacilli. The isolate was identified as C. modestum by 16SrRNA gene sequencing. A diagnosis of vertebral osteomyelitis caused by C. modestum was made. Minocycline followed by oral amoxicillin was administered for 3 months. His symptom improved and did not recur after treatment completion.

CONCLUSION

A case of vertebral osteomyelitis caused by C. modestum was encountered. Although C. modestum is very similar to C. acnes, it could be accurately identified by 16SrRNA gene sequencing. This case represents the first documented C. modestum infection in humans.

Topics: Aged; Back Pain; Bone and Bones; Humans; Magnetic Resonance Imaging; Male; Osteomyelitis

PubMed: 35410176
DOI: 10.1186/s12879-022-07341-2

Authors: Tina I Bui, Ann Lindley Gill, Robert A Mooney...

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling postinfection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (tumor necrosis factor-α [TNF-α]) and chemokines (interferon-γ-induced protein 10 kDa [IP-10], keratinocyte-derived chemokine [KC], monokine induced by interferon-γ [MIG], monocyte chemoattractant protein-1 [MCP-1], and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice, with notable increases in the anti-inflammatory bacterium Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested that polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting that polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D. Individuals with obesity-related type 2 diabetes (obesity/T2D) are at a five times increased risk for invasive Staphylococcus aureus osteomyelitis (bone infection) following orthopedic surgeries. With increasing antibiotic resistance and limited discoveries of novel antibiotics, it is imperative that we explore other avenues for therapeutics. In this study, we demonstrated that the dietary fiber oligofructose markedly reduced osteomyelitis severity and hyperinflammation following acute prosthetic joint infections in obese/T2D mice. Reduced infection severity was associated with changes in gut microbiota composition and metabolism, as indicated by increased production of natural polyamines in the gut and circulating plasma. This work identifies a novel role for the gut microbiome in mediating control of bacterial infections and polyamines as beneficial metabolites involved in improving the obesity/T2D host response to osteomyelitis. Understanding the impact of polyamines on host immunity and mechanisms behind decreasing susceptibility to severe implant-associated osteomyelitis is crucial to improving treatment strategies for this patient population.

Topics: Animals; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Inflammation; Interferon-gamma; Mice; Obesity; Osteomyelitis; Polyamines; Staphylococcal Infections; Staphylococcus aureus

PubMed: 35315698
DOI: 10.1128/spectrum.00170-22

Authors: Mengzhu Zhao, Di Wu, Keyi Yu...

Objectives

Chronic non-bacterial osteomyelitis (CNO) is a rare polygenic autoinflammatory bone disease. We aimed to characterize the clinical manifestations and gene variants of Chinese adult patients with CNO.

Methods

By reviewing data of all CNO patients being diagnosed and followed up at the Center for Adult Autoinflammation Diseases, Department of Rheumatology, Peking Union Medical College Hospital, clinical and genetic features of these patients were evaluated and concluded.

Results

The median age of disease onset was 19 (6-64) years old, and adult-onset was observed in 6 (60%) patients. The mean time of diagnosis delay was 92 ± 78 months. The common symptoms were bone pain (10, 100%), fever (9, 90%), and arthritis (6, 60%). In total, there were 54 skeletal lesions, and each patient had no less than 2 lesions. The most frequently affected sites included lower limbs (20.5%), mandible, vertebrae and pelvis (17.5%, separately). Variants of 4 genes were detected in our study including , , and . In seven patients who were treated with combination therapy containing tumor necrosis factor (TNF) α inhibitors, five (55.6%) had a complete response and 2 (44.4%) had a partial response.

Conclusion

This is the first and largest case series of CNO in the Chinese adult patients. Four novel genetic mutations potentially associated with CNO were identified. Notably, CNO should be considered in the differential diagnosis of adult patients with long disease course and recurrent multifocal osteomyelitis of unknown cause, and these patients might benefit from combination therapy containing TNFα inhibitors.

Topics: Adult; China; Chloride Channels; Graft vs Host Disease; Humans; Mandible; Middle Aged; Osteomyelitis; Remission Induction; Young Adult

PubMed: 35422809
DOI: 10.3389/fimmu.2022.860646

Expanding the definition beyond surveillance criteria reveals a large burden of osteomyelitis caused by group B Streptococcus in the United States Veterans Health Administration.

Authors: Tayoot Chengsupanimit, Taissa A Bej, Brigid Wilson...

BACKGROUND

Population-based surveillance studies may underestimate osteomyelitis caused by Group B Streptococcus (GBS). We analyzed cases of GBS osteomyelitis, including patients diagnosed using an expanded case definition that incorporates cultures from non-sterile sites, as well as cultures from normally sterile sites.

METHODS

We retrospectively examined a cohort of veterans with the diagnosis of osteomyelitis between 2008 and 2017. Cases of definite GBS osteomyelitis required GBS isolation from normally sterile sites, (e.g., blood or bone). Cases of probable GBS osteomyelitis permitted GBS isolation from non-sterile sites (e.g., surgical sites, wounds). We compared comorbid conditions, lower extremity amputation and mortality rates in these groups.

RESULTS

Among 1281 cases of GBS osteomyelitis, the median age was 63 years, 87% had diabetes mellitus and 37% had peripheral vascular disease. Similar characteristics were found in 768 (60%) cases classified as definite and 513 (40%) classified as probable GBS osteomyelitis. Polymicrobial infection was less frequent in patients with definite than with probable GBS osteomyelitis (45% vs. 85%; P < 0.001). Mortality rates within 1-year were similar for definite and probable GBS osteomyelitis (12% vs. 10%). Amputation within 1-year occurred in 21% of those with definite and 10% of those with probable GBS osteomyelitis of the lower extremity, with comparable rates in the subset with monomicrobial infection.

CONCLUSIONS

Expanding the definition of GBS osteomyelitis to include cases with cultures from non-sterile sites may be warranted, increasing the estimated burden of GBS osteomyelitis. This can help guide preventive efforts to reduce the impact of GBS osteomyelitis.

Topics: Humans; Middle Aged; Osteomyelitis; Retrospective Studies; Streptococcal Infections; Streptococcus agalactiae; United States; Veterans Health

PubMed: 35260097
DOI: 10.1186/s12879-022-07238-0

Randomized Controlled Trial

[Clinical study of calcium phosphate cement loaded with recombinant human bone morphogenetic protein 2 combined with calcium phosphate cement loaded with antibiotic for chronic osteomyelitis with bone defect].

Authors: Yongfu Tian, Jiquan Liu, Youshui Hu...

OBJECTIVE

To compare the effectiveness of calcium phosphate cement (CPC) loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) combined with CPC loaded with antibiotic versus CPC loaded with antibiotic alone in one stage for chronic osteomyelitis with bone defect.

METHODS

A single-blind prospective randomized controlled clinical trial was conducted. Between April 2018 and April 2019, 80 patients of chronic osteomyelitis with bone defect in accordance with the random number table were randomly divided into two groups, 40 in the trial group (CPC loaded with rhBMP-2 combined with CPC loaded with antibiotic) and 40 in the control group (CPC loaded with antibiotic). There was no significant difference in gender, age, disease duration, lesion, and preoperative white blood cells (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) between the two groups ( >0.05). All patients were implanted the corresponding CPC and external fixator after lesion clearance in the two groups. The postoperative WBC count, platelet count, ESR, CRP, hospital stay, cure rate of osteomyelitis, repaired bone defect volume, the time of external fixator removal, and the time of full weight-bearing of the affected limb were compared between the two groups.

RESULTS

All patients were followed up 12-24 months, with an average of 18.4 months. There was no significant difference in WBC count, platelet count, ESR, and CRP between the two groups at 4 weeks after operation ( >0.05). There were significant differences in WBC count, platelet count, and CRP in the two groups between 1 week before operation and 4 weeks after operation ( <0.05). And the ESR showed no significant difference between pre- and post-operation in the two groups ( >0.05). In the trial group, the anaphylactic exudate occurred in 1 patient with tibial osteomyelitis and the incision healed after oral administration of loratadine. The incisions of other patients healed by first intention in the two groups. One case of distal tibial osteomyelitis recurred in each group, and 1 case of humeral osteomyelitis recurred in the control group. The cure rates of osteomyelitis were 97.5% (39/40) in the trial group and 95% (38/40) in the control group, showing no significant difference between the two groups ( =0.000, =1.000). There was no significant difference in the repaired bone defect volume and hospital stay between the two groups ( >0.05). X-ray film and CT showed that the bone defects were repaired in the two groups. The time of external fixator removal and the time of full weight-bearing of the affected limb were significantly shorter in the trial group than in the control group ( <0.05).

CONCLUSION

Application of CPC loaded with rhBMP-2 and antibiotic in one stage is effective for the chronic osteomyelitis with bone defect, which can accelerate the bone regeneration to repair bone defect, reduce the trauma, shorten the course of treatment, and obtain good function of the affected limb.

Topics: Anti-Bacterial Agents; Bone Cements; Bone Morphogenetic Protein 2; Calcium Phosphates; Humans; Osteomyelitis; Prospective Studies; Single-Blind Method

PubMed: 33998210
DOI: 10.7507/1002-1892.202011106

Authors: Noam Bor, Eytan Dujovny, Barak Rinat...

BACKGROUND

Chronic osteomyelitis is a challenge for orthopedic surgeons. Most patients with osteomyelitis receive two-stage management according to Cierny-Mader. The first stage includes radical debridement and insertion of an antibiotic-impregnated cement spacer (ACS) (beads, rods, nails, or blocks) into the bone defect. The second stage is performed 6-8 weeks later, when the spacer is removed and a cancellous autograft is placed within the bone defect. The possibility of ACS as definitive management for osteomyelitis, avoiding the second stage, is presented.

METHODS

Sixteen patients with osteomyelitis received radical debridement and insertion of an ACS in all forms into the bone defect as a definitive management. In 8 patients, the tibia was infected, 4 had femur infection, 2 humerus, 1 fibula, and 1 ankle. The mean age at the time of the first stage of reconstruction was 49 years (range, 13-71 years). According to the Cierny-Mader classification, 1 patient was C-M IA, another was IB, 7 IIIA, 6 IIIB, and 1 was 4A. All B hosts had systemic illnesses. The mean follow-up period was 6 years (1.5-16 years).

RESULTS

No patient exhibited radiographic evidence of excessive bone loss. Signs of recurrence of osteomyelitis were not noted in any of the patients, and no fractures had occurred by the last follow-up.

CONCLUSION

Our study suggests that a proportion of patients with planned retention of ACS appear to function well without requiring further surgical intervention, especially in elderly or vulnerable patients.

Topics: Aged; Anti-Bacterial Agents; Debridement; Humans; Osteomyelitis; Polymethyl Methacrylate; Tibia; Treatment Outcome

PubMed: 34991574
DOI: 10.1186/s12891-021-04979-y