Chronic Nonspinal Osteomyelitis in Adults: Consensus Recommendations on Percutaneous Bone Biopsies from the Society of Academic Bone Radiologists.

The diagnosis and management of chronic nonspinal osteomyelitis can be challenging, and guidelines regarding the appropriateness of performing percutaneous image-guided biopsies to acquire bone samples for microbiological analysis remain limited. An expert panel convened by the Society of Academic Bone Radiologists developed and endorsed consensus statements on the various indications for percutaneous image-guided biopsies to standardize care and eliminate inconsistencies across institutions. The issued statements pertain to several commonly encountered clinical presentations of chronic osteomyelitis and were supported by a literature review. For most patients, MRI can help guide management and effectively rule out osteomyelitis when performed soon after presentation. Additionally, in the appropriate clinical setting, open wounds such as sinus tracts and ulcers, as well as joint fluid aspirates, can be used for microbiological culture to determine the causative microorganism. If MRI findings are positive, surgery is not needed, and alternative sites for microbiological culture are not available, then percutaneous image-guided biopsies can be performed. The expert panel recommends that antibiotics be avoided or discontinued for an optimal period of 2 weeks prior to a biopsy whenever possible. Patients with extensive necrotic decubitus ulcers or other surgical emergencies should not undergo percutaneous image-guided biopsies but rather should be admitted for surgical debridement and intraoperative cultures. Multidisciplinary discussion and approach are crucial to ensure optimal diagnosis and care of patients diagnosed with chronic osteomyelitis.

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies.

Toll-like receptors (TLRs), as a family of pattern recognition receptors, play an important role in the recognition of HIV-1 molecular structures by various cells of the innate immune system, but also provide a functional association with subsequent mechanisms of adaptive immunity. TLR7 and TLR8 play a particularly important role in the innate immune response to RNA viruses due to their ability to recognise GU-rich single-stranded RNA molecules and subsequently activate intracellular signalling pathways resulting in expression of genes coding for various biological response modifiers (interferons, proinflammatory cytokines, chemokines). The aim of this review is to summarise the most recent knowledge on the role of TLRs in the innate immune response to HIV-1 and the role of TLR gene polymorphisms in the biology and in the clinical aspects of HIV infections. In addition, the role of TLR agonists as latency reversing agents in research to treat HIV infections and as immunomodulators in HIV vaccine research will be discussed.

Periprosthetic Joint Infection: A Review of Antibiotic Treatment.

A team approach among orthopaedic surgeons, infectious disease specialists, and patients is of paramount importance when treating periprosthetic joint infections (PJIs). Treatment usually includes various surgical approaches along with antibiotic treatment. Antibiotic selection requires a multifactorial decision that depends on the organism that is identified, its antibiotic-resistance profile, the extent of the infection, and factors associated with the host. Antibiotic duration is dependent on surgical intervention and the type of organism. Typically, patients are treated for 6 weeks after debridement, antibiotics, and implant retention (DAIR) and for 4 to 6 weeks after single-stage and 2-stage revision arthroplasty. Levofloxacin in combination with rifampin has shown favorable outcomes for Staphylococcus PJI treatment. Quinolones have excellent bioavailability and bone and joint concentrations. Ciprofloxacin can be used for sensitive gram-negative infections. Evidence is emerging that supports the use of oral antibiotics after 7 days of intravenous antibiotics for the treatment of PJI. Although this should be considered carefully, it can potentially alleviate the burden on patients and caregivers, with fewer intravenous lines and the potential for fewer complications.

Isolated septic facet joints: an underdiagnosed distinct clinical entity.

OBJECTIVES: We review a series of isolated septic facet joints (ISFJ) that present as a distinct clinical entity compared with spondylodiscitis. We aim to raise awareness that septic facet joints are not a rare entity in the era of modern imaging. METHODS: We reviewed 353 patients with confirmed spine infections from 2008 to 2017. Of the 353 cases, there were 152 septic facet joints based on MR imaging. Sixty-two presented as ISFJ without evidence of spondylodiscitis and were reviewed. RESULTS: Patients were predominantly male 38/62 (61%). The mean age was 56.7 years. Onset of back pain was more acute compared with spondylodiscitis and usually unilateral. The distribution was as follows: 6 cervical, 12 thoracic, and 44 lumbar facets. The majority of ISFJ, 53/62 (85%), were associated with an epidural abscess (EDA) 53/62. The cervical and thoracic EDA required surgical decompression more frequently than lumbar; 100%, 75%, and 53% respectively. Pathogen was identified in 59/62 (95%) cases. Most cases were associated with bacteremia 50/62 (81%). Seven ISFJ were introduced iatrogenically. All iatrogenic ISFJ required surgical decompression. CONCLUSION: Septic facet joints are not rare, but frequently overlooked as the origin of an epidural abscess. The majority of cases are hematogenously seeded and associated with bacteremia. Surgical decompression is frequently required secondary to the high incidence of associated epidural abscess. Iatrogenic septic facet joints are rare but associated with significant morbidity. From a clinical standpoint, it is helpful to delineate the origin of EDA as either secondary to spondylodiscitis or SFJ.

What Demographic and Clinical Factors Are Associated with In-hospital Mortality in Patients with Necrotizing Fasciitis?

BACKGROUND: Necrotizing fasciitis is a rare infection with rapid deterioration and a high mortality rate. Factors associated with in-hospital mortality have not been thoroughly evaluated. Although predictive models identifying the diagnosis of necrotizing fasciitis have been described (such as the Laboratory Risk Indicator for Necrotizing Fasciitis [LRINEC]), their use in predicting mortality is limited. QUESTIONS/PURPOSES: (1) What demographic factors are associated with in-hospital mortality in patients with necrotizing fasciitis? (2) What clinical factors are associated with in-hospital mortality? (3) What laboratory values are associated with in-hospital mortality? (4) Is the LRINEC score useful in predicting mortality? METHODS: We retrospectively studied all patients with necrotizing fasciitis at our tertiary care institution during a 10-year period. In all, 134 patients were identified; after filtering out patients with missing data (seven) and those without histologically confirmed necrotizing fasciitis (12), 115 patients remained. These patients were treated with early-initiation antibiotic therapy and aggressive surgical intervention once the diagnosis was suspected. Demographic data, clinical features, laboratory results, and treatment variables were identified. The median age was 56 years and 42% of patients were female. Of the 115 patients analyzed, 15% (17) died in the hospital. Univariate and receiver operating characteristic analyses were performed due to the low number of mortality events seen in this cohort. RESULTS: The demographic factors associated with in-hospital mortality were older age (median: 64 years for nonsurvivors [interquartile range (IQR) 57-79] versus 55 years for survivors [IQR 45-63]; p = 0.002), coronary artery disease (odds ratio 4.56 [95% confidence interval (CI) 1.51 to 14]; p = 0.008), chronic kidney disease (OR 4.92 [95% CI 1.62 to 15]; p = 0.006), and transfer from an outside hospital (OR 3.47 [95% CI 1.19 to 10]; p = 0.02). The presenting clinical characteristics associated with in-hospital mortality were positive initial blood culture results (OR 4.76 [95% CI 1.59 to 15]; p = 0.01), lactic acidosis (OR 4.33 [95% CI 1.42 to 16]; p = 0.02), and multiple organ dysfunction syndrome (OR 6.37 [95% CI 2.05 to 20]; p = 0.002). Laboratory values at initial presentation that were associated with in-hospital mortality were platelet count (difference of medians -136 [95% CI -203 to -70]; p < 0.001), serum pH (difference of medians -0.13 [95% CI -0.21 to -0.03]; p = 0.02), serum lactate (difference of medians 0.90 [95% CI 0.40 to 4.80]; p < 0.001), serum creatinine (difference of medians 1.93 [95% CI 0.65 to 3.44]; p < 0.001), partial thromboplastin time (difference of medians 8.30 [95% CI 1.85 to 13]; p = 0.03), and international normalized ratio (difference of medians 0.1 [95% CI 0.0 to 0.5]; p = 0.004). The LRINEC score was a poor predictor of mortality with an area under the receiver operating characteristics curve of 0.56 [95% CI 0.45-0.67]. CONCLUSIONS: Factors aiding clinical recognition of necrotizing fasciitis are not consistently helpful in predicting mortality of this infection. Identifying patients with potentially compromised organ function should lead to aggressive and expedited measures for diagnosis and treatment. Future multicenter studies with larger populations and a standardized algorithm of treatment triggered by high clinical suspicion can be used to validate these findings to better help prognosticate this potentially fatal diagnosis.Level of Evidence Level III, therapeutic study.

Incidence and Characteristics of Osteoarticular Infections in Patients With Infective Endocarditis.

Osteoarticular infections (OAIs) in the setting of infective endocarditis (IE) are uncommon. Although morbidity and mortality have been widely studied, details of the characteristics of patients with concurrent IE and OAI are limited. Therefore, the purpose of this study was to determine the (1) incidence, (2) mortality, (3) clinical features, and (4) microbiological profiles of OAIs in the setting of IE. A retrospective review was conducted of 1280 IE cases at a large academic institution between 2009 and 2015. Patients were categorized according to the following OAI types: spondylodiskitis, large joint septic arthritis, other site infections, or multiple affected joints. Inpatient mortality rates, clinical findings, and microbiological characteristics were compared between OAI types. Overall, the incidence of OAI among IE patients was 6.8% (n=87). The in-hospital mortality rate was 9.2% (n=8) and was not significantly associated with OAI type (P=.801). Eighteen patients had multiple affected joints resulting in a total of 114 infected sites. Of these, 39% (n=44) were spondylodiskitis, 29% (n=33) were large joint septic arthritis, and 32% (n=37) were infections of smaller joints. Back pain was most common among patients with spondylodiskitis (P<.001), whereas fever and general fatigue were most common with septic arthritis (P<.001). Of the available bone/ joint cultures, 69% were positive. Overall, Staphylococcus aureus was the most common IE pathogen in patients with both IE and OAI (63%). Clinicians should maintain a high suspicion for OAI in patients with IE caused by Staphylococcus aureus, particularly spondylodiskitis among those presenting with back pain. [Orthopedics 2020; 43(1):24-29.].

Update on spinal epidural abscess.

PURPOSE OF REVIEW: Spinal epidural abscess (SEA) is still a rare but potentially very morbid infection of the spine. In recent years, the incidence has risen sharply but the condition remains a medical conundrum wrought with unacceptably long diagnostic delays. The outcome depends on timely diagnosis and missed opportunities can be associated with catastrophic consequences. Management and outcomes have improved over the past decade. This review focuses on risk factors and markers that can aid in establishing the diagnosis, the radiological characteristics of SEA on MRI and their clinical implications, as well as the importance of establishing clear indications for surgical decompression. RECENT FINDINGS: This once exclusively surgically managed entity is increasingly treated conservatively with antimicrobial therapy. Patients diagnosed in a timely fashion, prior to cord involvement and the onset of neurologic deficits can safely be managed without decompressive surgery with targeted antimicrobial therapy. Patients with acute cord compression and gross neurologic deficits promptly undergo decompression. The greatest therapeutic dilemma remains the group with mild neurological deficits. As failure rates of delayed surgery approach 40%, recent research is focused on predictive models for failure of conservative SEA management. In addition, protocols are being implemented with some success, to shorten the diagnostic delay of SEA on initial presentation. SUMMARY: SEA is a potentially devastating condition that is frequently missed. Protocols are put in place to facilitate early evaluation of back pain in patients with red flags with appropriate cross-sectional imaging, namely contrast-enhanced MRI. Efforts for establishing clear-cut indications for surgical decompression of SEA are underway.

Treatment Challenges of Prosthetic Hip Infection with Associated Iliacus Muscle Abscess: Report of 5 Cases and Literature Review.

Prosthetic joint infection is an unfortunate though well-recognized complication of total joint arthroplasty. An iliacus and/or iliopsoas muscle abscess is a rarely documented presentation of hip prosthetic joint infection. It is thought an unrecognized retroperitoneal nidus of infection can be a source of continual seeding of the prosthetic hip joint, prolonging attempts to eradicate infection despite aggressive debridement and explant attempts. The current study presents five cases demonstrating this clinical scenario, and discusses various treatment challenges. In each case we report the patient's clinical history, pertinent imaging, management and outcome. Diagnosis of the iliacus muscle abscess was made using computed tomography imaging. In brief, the mean number of total drainage procedures (open and percutaneous) per patient was 4.2, and outcomes consisted of one patient with a hip girdlestone, two patients with delayed revisions, and two patients with retained prosthesis. All patients ended with functional pain and on oral antibiotic suppression with an average follow up of 18 months. This article highlights an iliacus muscle abscess as an unrecognized source of infection to a prosthetic hip. It demonstrates resilience to standard treatment protocols for prosthetic hip infection, and is associated with poor patient outcomes. Aggressive surgical debridement appears to remain critical to treatment success, and early retroperitoneal debridement of the abscess should be considered.

Infections of the Spine.

Pyogenic infections of the bony spinal column and the intervertebral discs are on a steady rise in an aging western population. Despite advanced medical imaging, this clinical entity of devastating consequences if missed, still presents a diagnostic conundrum and is plagued by an unacceptably long diagnostic delay. The aim of this article is to raise awareness of the heterogeneity of spinal infections paralleling the complex structure of the spinal column and neighboring soft tissues. Emphasis is placed on the clinical presentation and management of septic facet joints and psoas muscle abscesses associated with lumbar spondylodiscitis.

Septic Arthritis of an Atlantoaxial Facet Joint with Normal Inflammatory Markers: Case Report and Literature Review.

BACKGROUND: Septic arthritis of the atlantoaxial facet joint is extremely rare. Contiguous spread to the median atlantoaxial joints with subsequent dens erosion can lead to atlantoaxial instability. Misleading normal inflammatory markers can result in delayed diagnosis and catastrophic consequences. CASE DESCRIPTION: A 56-year-old man presented with right-sided neck pain that had lasted for 2 days. He did not have fever or chills, and his serum C-reactive protein and erythrocyte sedimentation rate were normal. The patient was diagnosed with acute neck strain and treated conservatively. The pain continued for the next 3 weeks; cervical spine radiographs demonstrated normal findings with the exception of degenerative changes. The patient was treated with physical rehabilitation for the presumed neck strain and degenerative changes of the cervical vertebrae. Worsening neck pain and stiffness prompted a magnetic resonance imaging study obtained 5 weeks after the initial presentation, which showed an epidural collection with septic arthritis of the right facet and median atlantoaxial joints. Computed tomography demonstrated severe dens erosion. Surgical evacuation of the abscess and occipitocervical fusion were performed. Pathologic evaluation of tissue obtained during surgery demonstrated the presence of an infection, and Streptococcus anginosus grew from cultures. CONCLUSIONS: Infection must be considered in the differential diagnosis for neck pain when imaging findings are suggestive of an infectious process, even in an afebrile patient with normal C-reactive protein and erythrocyte sedimentation rate levels. Magnetic resonance imaging and computed tomography can play a critical role in such cases, potentially leading to a more timely diagnosis.

Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations.

Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and l-ascorbic acid (l-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of l-ascorbic (1-4, 8-10, 13-15) and imino-l-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of l-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 ± 1.8 µM) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 ± 0.1 µM) while the 9-deazahypoxanthine derivative of l-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 ± 1.3 µM) and prominent effect on L1210/0 (IC50 = 4.5 ± 0.5 µM). Furthermore, the 9-deazapurine derivative disubstituted with two imino-l-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 ± 0.3 µM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 ± 0.2 µM). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of l-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells.

Novel 1,2,4-triazole and imidazole derivatives of L-ascorbic and imino-ascorbic acid: synthesis, anti-HCV and antitumor activity evaluations.

Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 ± 4 and 7.3 ± 0.1 µM, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead.

Inhibition of the class C beta-lactamase from Acinetobacter spp.: insights into effective inhibitor design.

The need to develop beta-lactamase inhibitors against class C cephalosporinases of Gram-negative pathogens represents an urgent clinical priority. To respond to this challenge, five boronic acid derivatives, including a new cefoperazone analogue, were synthesized and tested against the class C cephalosporinase of Acinetobacter baumannii [Acinetobacter-derived cephalosporinase (ADC)]. The commercially available carbapenem antibiotics were also assayed. In the boronic acid series, a chiral cephalothin analogue with a meta-carboxyphenyl moiety corresponding to the C(3)/C(4) carboxylate of beta-lactams showed the lowest K(i) (11 +/- 1 nM). In antimicrobial susceptibility tests, this cephalothin analogue lowered the ceftazidime and cefotaxime minimum inhibitory concentrations (MICs) of Escherichia coli DH10B cells carrying bla(ADC) from 16 to 4 microg/mL and from 8 to 1 microg/mL, respectively. On the other hand, each carbapenem exhibited a K(i) of <20 microM, and timed electrospray ionization mass spectrometry (ESI-MS) demonstrated the formation of adducts corresponding to acyl-enzyme intermediates with both intact carbapenem and carbapenem lacking the C(6) hydroxyethyl group. To improve our understanding of the interactions between the beta-lactamase and the inhibitors, we constructed models of ADC as an acyl-enzyme intermediate with (i) the meta-carboxyphenyl cephalothin analogue and (ii) the carbapenems, imipenem and meropenem. Our first model suggests that this chiral cephalothin analogue adopts a novel conformation in the beta-lactamase active site. Further, the addition of the substituent mimicking the cephalosporin dihydrothiazine ring may significantly improve affinity for the ADC beta-lactamase. In contrast, the ADC-carbapenem models offer a novel role for the R(2) side group and also suggest that elimination of the C(6) hydroxyethyl group by retroaldolic reaction leads to a significant conformational change in the acyl-enzyme intermediate. Lessons from the diverse mechanisms and structures of the boronic acid derivatives and carbapenems provide insights for the development of new beta-lactamase inhibitors against these critical drug resistance targets.

What's new in antibiotic resistance? Focus on beta-lactamases.

In gram-negative bacteria, beta-lactamases are the most important mechanism of resistance to beta-lactam antibiotics. Currently, the beta-lactamases receiving the most attention are the extended-spectrum beta-lactamases (ESBLs), inhibitor-resistant beta-lactamases and carbapenemases. When found in Escherichia coli and Klebsiella spp., ESBLs confer resistance to extended-spectrum cephalosporins, such as ceftazidime, cefotaxime and cefepime. Hence, ESBLs limit the choice of beta-lactam therapy to carbapenems. A worrisome trend is the increasing number of pathogens found in isolates from patients in the community that possess ESBLs. It is equally distressing that carbapenemases (serine and metallo-beta-lactamases) are being found in many of the same bacteria that harbor ESBLs, for example Klebsiella pneumoniae. Despite many years studying beta-lactamases, important clinical and scientific questions still remain.