Efficacy of ceftazidime-avibactam in various combinations for the treatment of experimental osteomyelitis due to Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae.

BACKGROUND: Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis. METHODS: KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×108 CFU of KPC-99YC. Six groups started treatment 14 days later for 7 days: control, colistin, CAZ-AVI, CAZ-AVI plus gentamicin, CAZ-AVI plus colistin and CAZ-AVI plus fosfomycin. Antibiotic dosages were selected to simulate plasma concentrations obtained in humans. Treatment was evaluated according to bone cultures quantified in log10 CFU. RESULTS: In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination. CONCLUSIONS: CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.

Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus.

Osteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. STATEMENT OF SIGNIFICANCE: In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.

Vertebral osteomyelitis caused by the novel pathogen Cutibacterium modestum: a case report.

BACKGROUND: Cutibacterium modestum is one of the five species of the genus Cutibacterium. While C. acnes has been reported as an important pathogen in bone and joint infections, the clinical characteristics of C. modestum infections remain unclear. Moreover, thus far, there has been no clinical case report regarding C. modestum infections. CASE PRESENTATION: An 82-year-old man with a history of repeated trigger point injections for lumbago at the L4 level presented with fever and an exacerbation of lumbago. Physical examination indicated knocking pain at the L4-L5 levels; magnetic resonance imaging showed irregular bone destruction of the L4 vertebral body, and low T1 and high T2 intensity lesions at the L4-L5 intervertebral disc. Two sets of blood cultures (two aerobic and two anaerobic) were performed. Intravenous cefazolin was administered, considering the common pathogens of vertebral osteomyelitis, such as Staphylococcus aureus. The patient's condition did not improve; thereafter, anaerobic culture bottles revealed Gram-positive rods on day 11 of incubation. There was no evidence of infective endocarditis upon transthoracic echocardiography. Needle aspiration from the L4-L5 intervertebral disc was performed on day 13 that also showed the presence of Gram-positive rods. The patient was diagnosed with vertebral osteomyelitis caused by C. modestum using a combination of characteristic peak analysis with matrix-assisted laser desorption ionization (MALDI), microbial biochemistry examinations, and 16S rRNA gene sequencing from the blood and pus cultures. He was successfully treated with alternative intravenous ampicillin, followed by oral amoxicillin for 10 weeks, according to the tests for ampicillin susceptibility, with a minimum inhibitory concentration of 0.016 µg/mL using E-test® under aerobic conditions. CONCLUSIONS: Cutibacterium modestum is a microorganism that is difficult to identify. A combination of characteristic peaks with MALDI, appropriate microbial biochemical examinations, and 16S rRNA gene sequencing may serve as an efficient guide for the identification of C. modestum.

Usefulness of therapeutic drug monitoring in estimating the duration of dalbavancin optimal target attainment in staphylococcal osteoarticular infections: a proof-of-concept.

Dalbavancin is increasingly used for the treatment of staphylococcal osteoarticular infections (OIs). Some population pharmacokinetic studies suggest that a regimen of two 1500 mg doses 1 week apart could ensure effective treatment for several weeks. Here we aim to provide clinicians with a proof-of-concept of the potential role that therapeutic drug monitoring may have in giving real-time feedback of the estimated duration of optimal treatment of staphylococcal OIs with dalbavancin in each single patient.

Antibiogram profiles and efficacy of antibiotic regimens of bacterial isolates from chronic osteomyelitis of the appendicular skeleton: A developing-world perspective.

BACKGROUND: Empirical antibiotic strategies in the treatment of chronic osteomyelitis should ideally be based on local microbiological antibiograms. OBJECTIVES: To review the antibiogram profiles of bacterial isolates of patients undergoing surgical treatment for chronic osteomyelitis and identify the most appropriate empirical antibiotic strategy. METHODS: A retrospective review of clinical records and microbial culture reports was performed for all patients who underwent treatment for chronic osteomyelitis at two orthopaedic units in Western Cape Province, South Africa, between March 2016 and December 2019. Reported antibiotic susceptibility data were used to predict the potential efficacy of different empirical antibiotic regimens, according to underlying aetiology (fracture related, contiguous, haematogenous). RESULTS: Two hundred patients with chronic osteomyelitis of the appendicular skeleton underwent surgical management. Antibiogram profiles for 218 organisms, isolated from 169 patients, were evaluated. Staphylococcus aureus (41%) and Enterobacterales (30%) were the most common organisms isolated. The combinations of meropenem plus vancomycin, and piperacillin-tazobactam plus amikacin plus vancomycin, as empirical postoperative antibiotics would both effectively treat 78% of chronic osteomyelitis cases overall. The most effective practical oral combinations were co-amoxiclav plus ciprofloxacin (61%) and co-trimoxazole plus ciprofloxacin (61%). CONCLUSIONS: This study reports antibiogram profiles in the developing-world setting that could potentially guide empirical antibiotic choices in the management of chronic osteomyelitis.

Hyperbaric oxygen for refractory osteomyelitis.

Refractory osteomyelitis is defined as a chronic osteomyelitis that persists or recurs after appropriate interventions have been performed or where acute osteomyelitis has not responded to accepted management techniques [1]. To date, no randomized clinical trials examining the effects of hyperbaric oxygen (HBO2) therapy on refractory osteomyelitis exist, and the number of new osteomyelitis clinical trials conducted over the past decade has been limited. However, based on a comprehensive review of the scientific literature, the addition of HBO2 therapy to routine surgical and antibiotic treatment of previously refractory osteomyelitis appears to be both safe and ultimately improves infection resolution rates. In most cases, the best clinical results are obtained when HBO2 treatment is administered in conjunction with culture-directed antibiotics and initiated soon after clinically indicated surgical debridement. Where extensive surgical debridement or removal of fixation hardware is relatively contraindicated (e.g., cranial, spinal, sternal, or pediatric osteomyelitis), a trial of culture-directed antibiotics and HBO2 therapy prior to undertaking more than limited surgical interventions provides a reasonable prospect for osteomyelitis cure. HBO2 therapy is ordinarily delivered on a once daily basis, five-seven days per week, for 90-120 minutes using 2.0-3.0 atmospheres absolute (ATA) pressure. Where prompt clinical improvement is seen, the existing regimen of antibiotics and HBO2 therapy should be continued for approximately four to six weeks. Typically, 20-40 HBO2 sessions are required to achieve sustained therapeutic benefit. In contrast, if prompt clinical response is not noted or osteomyelitis recurs after this initial treatment period, then continuation of the current antibiotic and HBO2 treatment regimen is unlikely to be effective. Instead, clinical management strategies should be reassessed and additional surgical debridement and/or modification of antibiotic therapy considered. Subsequent reinstitution of HBO2 therapy will again help maximize the overall chances for treatment success in these persistently refractory patients.

Clindamycin combination treatment for the treatment of bone and joint infections caused by clindamycin-susceptible, erythromycin-resistant Staphylococcus spp.

The objective of this study was to evaluate the clinical outcomes and safety of clindamycin combination antibiotherapy for the treatment of erythromycin-resistant, lincosamide-susceptible bone and joint infections caused by Staphylococcus spp. Between January 2010 and September 2018, 46 patients with Staphylococcus spp. erythromycin-resistant, lincosamide-susceptible bone and joint infections were treated with clindamycin combination antibiotherapy for 6 to 12 weeks. The type of infection was prosthetic in 20 cases (43.5%), osteosynthetic device in 15 cases (32.6%), chronic osteomyelitis in 7 cases (15.2%), and arthritis in 4 cases (8.7%). The cure rate was 67.4% by intention to treat and 84.6% per protocol, with a median follow-up of 398 days (range 86-843). Only 2 relapses (5.1%) were observed in patients with chronic osteomyelitis; an acquired resistance to lincosamides developed in 1 case. Clindamycin combination therapy appears to be effective for the treatment of bone and joint infection caused by erythromycin-resistant, lincosamide-susceptible Staphylococcus spp.

Sarocladium and Acremonium infections: New faces of an old opportunistic fungus.

The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.

Granulomatous polyarthritis caused by Talaromyces georgiensis in a dog.

A 6-y-old, 3.5-kg, spayed female Toy Poodle was presented with left forelimb lameness of 2-d duration. Two months before the initial presentation, radiography showed osteolysis of the medial epicondyle of the left humerus, and the left forelimb was amputated. Grossly, the articular villi of the elbow joint were markedly thickened, and the articular cartilage surfaces of the distal humerus and proximal radius had partial erosion. Histologically, granulomatous arthritis and osteomyelitis characterized by the presence of abundant macrophages containing numerous fungi were observed. ITS and ß-tubulin sequences amplified from the isolate from the specimen were 100% and 99% identical to type strain UTHSC D16-145T of Talaromyces georgiensis, respectively. Canine osteoarthritis caused by T. georgiensis has not been reported previously, to our knowledge.

Efficacy of generic meropenem products in combination with colistin in carbapenemase-producing Klebsiella pneumoniae experimental osteomyelitis.

Guidelines for the management of carbapenemase-producing Enterobacterales (CPE) infections recommend a combination of two active agents, including meropenem if the minimum inhibitory concentration (MIC) is ≤8 mg/L. The therapeutic equivalence of meropenem generics has been challenged. We compared the bactericidal activity of meropenem innovator (AstraZeneca) and four generic products (Actavis, Kabi, Mylan and Panpharma), both in vitro and in vivo, in association with colistin. In vitro time-kill studies were performed at 4 × MIC. An experimental model of KPC-producing Klebsiella pneumoniae osteomyelitis was induced in rabbits by tibial injection of a sclerosing agent followed by 2 × 108 CFU of K. pneumoniae KPC-99YC (meropenem MIC = 4 mg/L; colistin MIC = 1 mg/L). At 14 days after inoculation, treatment for 7 days started in seven groups of ≥10 rabbits, including a control group, a colistin group, and one group for each meropenem product (i.e. the innovator and four generics), in combination with colistin. In vitro, meropenem + colistin was bactericidal with no viable bacteria after 6 h, and this effect was similar with all meropenem products. In the osteomyelitis model, there was no significant difference between meropenem generics and the innovator when combined with colistin. Colistin-resistant strains were detected after treatment with colistin + meropenem innovator (n = 3) and generics (n = 3). The efficacy of four meropenem generics did not differ from the innovator in vitro and in an experimental rabbit model of KPC-producing K. pneumoniae osteomyelitis in terms of bactericidal activity and the emergence of resistance.

Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing.

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.

Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis.

BACKGROUND: We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO). METHODS: Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1-17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14-42 days total). Primary endpoint: protocol-defined clinical improvement by Day 5 in the modified intention-to-treat (MITT) population (confirmed AHO, ≥1 dose of study treatment); differences between study arms were evaluated using a prespecified 15% noninferiority margin for daptomycin. RESULTS: Seventy-three patients per arm received treatment. Pathogens were isolated from 62% of patients (83% methicillin-susceptible Staphylococcus aureus, 9% methicillin-resistant S. aureus [MRSA]). Clinical improvement by Day 5 was observed in 55/71 (78%) daptomycin- and 58/70 (83%) comparator-treated MITT patients (95% confidence interval [CI]: -19.4, 7.4). This difference was not statistically significant; however, daptomycin did not meet the prespecified 15% noninferiority margin, since the lower bound of the 95% CI extended below 15%. Overall, 82% of daptomycin and 87% of comparator patients achieved clinical cure at the test-of-cure visit (secondary endpoint). More comparator patients had treatment-emergent (63% vs. 46%) and treatment-related (18% vs. 7%) adverse events. CONCLUSIONS: Differences between daptomycin and comparator for the primary endpoint were not statistically significant; however, prespecified noninferiority criteria for daptomycin were not met. With insufficient cases of confirmed MRSA, we could not evaluate daptomycin for MRSA AHO. Our nonvalidated protocol design yields valuable information for implementing future trials in AHO (ClinicalTrials.gov NCT01922011).

Frequency of Dosing of Cephalexin for Oral Step-Down Therapy of Pediatric Osteoarticular Infections Caused by Methicillin-Sensitive Staphylococcus Aureus.

Osteoarticular infections are one of the more common invasive bacterial infections encountered in children. There exist significant practice variations in both the diagnosis and treatment of such infections. However, the practice of transitioning from parenteral therapy to oral antibiotics has been well validated by several studies. For methicillin-sensitive Staphylococcus aureus (MSSA), cephalexin is often recommended. Prospective, controlled data regarding optimal dosing of cephalexin in pediatric osteomyelitis are not available. We sought to review our retrospective, uncontrolled data on four times daily (QID) versus three times daily (TID) dosing of cephalexin for pediatric osteoarticular infections. Children ≥1 month to <18 years of age admitted to Rady Children's Hospital-San Diego with a diagnosis of osteomyelitis or septic arthritis between January 1, 2002, and November 30, 2007, were identified and previously reported. Only patients with culture-positive MSSA infections are included in this report. Demographic and clinical data were manually extracted from the electronic medical record. Fifty-nine patients were treated with cephalexin and had records available for review through our electronic medical record. Thirty-eight patients (64.4%) were treated QID, and 21 patients (35.6%) were treated TID. Clinical cure was achieved in all patients with only one adverse event occurring in the QID group. In this retrospective chart review of children with osteoarticular infections caused by MSSA treated with cephalexin, similar clinical outcomes were found with QID versus TID dosing.

Co-administration of Erythromycin and Leech Salivary Extract Alleviates Osteomyelitis in Rats Induced by Methicillin-Resistant Staphylococcus aureus.

OBJECTIVE: Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA). MATERIALS AND METHODS: Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed. RESULTS: Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats. CLINICAL SIGNIFICANCE: The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics.

Aspergillus necrotizing otitis externa with temporomandibulozygomatic involvement.

INTRODUCTION: Aspergillus necrotizing otitis externa (NOE) is a rare disease, often associated with delayed diagnosis, the management of which is poorly defined. SUMMARY: The authors report a case of Aspergillus flavus necrotizing otitis externa with temporomandibular arthritis and temporozygomatic osteomyelitis with Staphylococcal coinfection in a diabetic patient. The diagnosis and discontinuation of treatment were guided by PET-CT scan. A favourable course without sequelae was observed after repeated surgical curettage and 3 months of antifungal therapy. DISCUSSION: Aspergillus flavus is the agent most commonly incriminated in NOE. Indirect diagnostic tests (serology) may be negative. The diagnosis is based on imaging-guided surgical biopsy with histological examination and standard and fungal microbiological culture. Treatment requires a combination of surgery and antifungal therapy. The duration of antifungal therapy is poorly defined and discontinuation of therapy can be guided by PET-CT scan.

Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

A dual-functional implant with an enzyme-responsive effect for bacterial infection therapy and tissue regeneration.

Biomaterial-associated bacterial infection is one of the major causes of implant failure. The treatment of such an implant infection typically requires the elimination of bacteria and acceleration of tissue regeneration around implants simultaneously. To address this issue, an ideal implanted material should have the dual functions of bacterial infection therapy and tissue regeneration at the same time. Herein, an enzyme-responsive nanoplatform was fabricated in order to treat implant-associated bacterial infection and accelerate tissue regeneration in vivo. Firstly, Ag nanoparticles were pre-encapsulated in mesoporous silica nanoparticles (MSNs) by a one-pot method. Then, poly-l-glutamic acid (PG) and polyallylamine hydrochloride (PAH) were assembled by the layer-by-layer (LBL) assembly technique on MSN-Ag to form LBL@MSN-Ag nanoparticles. Furthermore, the LBL@MSN-Ag nanoparticles were deposited on the surface of polydopamine-modified Ti substrates. PG is a homogeneous polyamide composed of an amide linkage, which can be degraded by glutamyl endonuclease secreted by Staphylococcus aureus. Inductively coupled plasma spectroscopy (ICP) results proved that the LBL@MSN-Ag particles show a significant enzyme responsive release of Ag ions. Furthermore, results of antibacterial experiments in vitro showed that the Ti substrates modified with an LBL@MSN-Ag nanocoating presented an excellent antibacterial effect. As for an animal experiment in vivo, in a bacterium infected femur-defect rat model, the modified Ti implants effectively treated bacterial infection. More importantly, the results of micro-CT, haematoxylin-eosin staining and Masson's trichrome staining demonstrated that the modified Ti implants significantly promoted the formation of new bone tissue after implantation for 4 weeks. The present system paves the way for developing the next generation of implants with the functions of treating bacterial infection and promoting tissue regeneration.

Extensive eggshell-like debridement technique plus antibiotic-loaded calcium sulphate for one-stage treatment of chronic calcaneal osteomyelitis.

BACKGROUND: Management of chronic calcaneal osteomyelitis is challenging. At present, there is still no widely accepted, simple, and effective surgical method to eradicate the infection and prevent osteomyelitis recurrence. The objective of this study was to assess the outcomes of one-stage treatment of chronic calcaneal osteomyelitis with a shape-preserving debridement technique combined with antibiotic-loaded calcium sulphate. METHODS: Between 2012 and 2018, 33 patients (33 limbs) with chronic calcaneal osteomyelitis were treated with a novel debridement technique, named "eggshell-like debridement", plus antibiotic-impregnated calcium sulphate. The infection remission rate, recurrence rate, and amputation rate were analyzed. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to assess postoperative hindfoot function. RESULTS: 26 patients (81.8%) achieved infection remission without recurrence. In the patients with osteomyelitis remission, pain, limitation of movement, sinus tracts, and typical redness and swelling were generally eliminated. Most of the patients could tolerate full weight-bearing without pain. The average AOFAS ankle and hindfoot score was 88 points (range, 67-100 points), implying the foot function was mostly restored. 6 patients (18.2%) had osteomyelitis recurrence but no amputation was required to elimilate the infection. CONCLUSIONS: Eggshell-like debridement combined with antibiotic-loaded calcium sulphate is an effective method for one-stage management of chronic calcaneal osteomyelitis. With the application of this technique, secondary autogenous bone or muscle flap grafts are unnecessary. The surgical procedure can be simplified whlie the hindfoot function is well preserved.

New Alternative Therapeutic Strategy for Gustilo Type IIIB Open Fractures, Using an Intra-Wound Continuous Negative Pressure Irrigation Treatment System.

The treatment of Gustilo type IIIB and IIIC open fractures remains a challenging problem, because the infection rate is 15-45%. Infection can lead to serious complications such as osteomyelitis or amputation. The intra-wound continuous negative pressure and irrigation treatment (IW-CONPIT) was developed for infected wounds and intractable ulcers, and is very effective in suppressing infection and accelerating wound healing. Here the IW-CONPIT was applied to severe open fractures for the purpose of preventing infection. After thorough debridement and lavage of the wound, bony stabilization is performed by external fixation. Dermal matrix is grafted onto any areas where the bone or tendon is exposed. A sponge containing two tubes is placed over the entire surface of the wound including the dermal matrix. Then it is covered with a film dressing to make the wound completely airtight. A bottle of physiologic saline solution is attached to one tube, and a continuous aspirator is attached to the other. This system maintains negative pressure on the wound surface, which is continuously irrigated. Thirty-five patients were treated with this method. A superficial infection developed in two cases but was resolved by additional debridement and continued application of IW-CONPIT. Complete wound healing was obtained with split thickness skin graft in all cases. There were no complications such as osteomyelitis, delayed bone union or amputation. IW-CONPIT was able to definitively prevent wound infection in Gustilo type ⅢB open fractures. We believe this method will become a standard treatment option for this condition.

Long-Term Compassionate Use of Cefiderocol To Treat Chronic Osteomyelitis Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum-ß-Lactamase-Producing Klebsiella pneumoniae in a Pediatric Patient.

We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.