Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab.

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Ankle fracture and necrotizing fasciitis: a common fracture and a dreadful complication.

Necrotizing fasciitis is a dreadful complication of the soft tissue. This pathology could be triggered by many factors, such as a fracture. We present a case of case of a necrotizing fasciitis in ankle fracture.

A 72-h intervention for improvement of the rate of optimal antibiotic therapy in patients with bloodstream infections.

Antimicrobial stewardship programs are implemented to optimize the use of antibiotics and control the spread of antibiotic resistance. Many antimicrobial stewardship interventions have demonstrated significant efficacy in reducing unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy, and mortality. We evaluated the benefits of a combination of rapid diagnostic tests and an active re-evaluation of antibiotic therapy 72 h after the onset of bloodstream infection (BSI). All patients with BSI from November 2015 to November 2016 in a 1100-bed university hospital in Rome, where an Infectious Disease Consultancy Unit (Unità di Consulenza Infettivologica, UDCI) is available, were re-evaluated at the bedside 72 h after starting antimicrobial therapy and compared to two pre-intervention periods: the UDCI was called by the ward physician for patients with BSI and the UDCI was called directly by the microbiologist immediately after a pathogen was isolated from blood cultures. Recommendations for antibiotic de-escalation or discontinuation significantly increased (54%) from the two pre-intervention periods (32% and 27.2%, p < 0.0001). Appropriate escalation also significantly increased (22.5%) from the pre-intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of antibiotic therapy decreased with intervention (from 21.9 days [standard deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2 to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention periods. Mortality was similar among the study periods (31 patients died in period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90). Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI significantly correlated with an improved rate of optimal antibiotic therapy and decreased duration of antibiotic therapy and length of stay.

Single dose cefazolin is safe and effective for pre-operative prophylaxis in orthopaedic oncology.

Surgical site infections (SSI) are a common potentially preventable complication after surgical procedures. A standardized antibiotic prophylaxis in elective orthopaedic surgery plays a major role in lowering SSI. At present, there is little published evidence regarding standardized antibiotic prophylaxis in orthopaedic oncological surgery. We introduced a prophylactic antibiotic protocol for orthopaedic oncological surgery in our hospital. The proposed protocol consists in "one-shot" intravenous administration of Cefazolin 2g, 30 min before surgery. In our setting, this preoperative antibiotic prophylaxis regimen was associated with a markedly lower rate of SSI's. There is no current evidence in favour of greater effectiveness of prophylaxis beyond 24/48 h after surgery compared to our pre-surgical "one-shot" administration; by contrast, prolonged post-surgical prophylaxis is likely to undermine the patient's bacterial flora and select resistant pathogens. These results are preliminary and should be used to start planning a standardised prophylactic protocol to prevent SSI's after orthopaedic oncological surgery.

Multidisciplinary management of pyogenic spondylodiscitis: epidemiological and clinical features, prognostic factors and long-term outcomes in 207 patients.

PURPOSE: Pyogenic spondylodiscitis (PS) is a potentially life-threatening infection burdened by high morbidity rates. Despite the rising incidence, the proper management of PS is still controversial. Aim of this study was to describe the clinical features of PS and to evaluate the prognostic factors and the long-term outcomes of a large population of patients. METHODS: 207 cases of PS treated from 2008 to 2016 with a 2-year follow-up were enrolled. Clinical data from each patient were recorded. The primary outcome was the rate of healing without residual disability. Secondary outcomes included length of stay, healing from infection, death, relapse, and residual disability. Binomial logistic regression and multivariate analysis were used to evaluate prognostic factors. RESULTS: Median diagnostic delay was 30 days and the rate of onset neurological impairment was 23.6%. Microbiological diagnosis was established in 155 patients (74.3%) and the median duration of total antibiotic therapy was 148 days. Orthopedic treatment was conservative for 124 patients and surgical in 47 cases. Complete healing without disability was achieved in 142 patients (77.6%). Statistically confirmed negative prognostic factors were: negative microbiological culture, neurologic impairment at diagnosis and underlying endocarditis (p ≤ 0.05). Healing from infection rate was 90.9%, while residual disabilities occurred in 23.5%. Observed mortality rate was 7.8%. CONCLUSION: The microbiological diagnosis is the main predictive factor for successful treatment. Early diagnosis and multidisciplinary management are also needed to identify underlying aggressive conditions and to avoid neurological complications associated with poorer long-term outcomes. Despite high healing rates, PS may lead to major disabilities still representing a difficult challenge. These slides can be retrieved under Electronic Supplementary material.

New classification for the treatment of pyogenic spondylodiscitis: validation study on a population of 250 patients with a follow-up of 2 years.

PURPOSE: Pyogenic spondylodiscitis (PS) is still burdened by a high rate of orthopedic and neurological complications. Despite the rising incidence, the choice of a proper orthopedic treatment is often delayed by the lack of clinical data. The aim of this study was to propose a clinical-radiological classification of pyogenic spondylodiscitis to define a standard treatment algorithm. METHODS: Based on data from 250 patients treated from 2008 to 2015, a clinical-radiological classification of pyogenic spondylodiscitis was developed. According to primary classification criteria (bone destruction or segmental instability, epidural abscesses and neurological impairment), three main classes were identified. Subclasses were defined according to secondary criteria. PS without segmental instability or neurological impairment was treated conservatively. When significant bone loss or neurological impairment occurred, surgical stabilization and/or decompression were performed. All patients underwent clinical and radiological 2-year follow-up. RESULTS: Type A PS occurred in 84 patients, while 46 cases were classified as type B and 120 as type C. Average time of hospitalization was 51.94 days and overall healing rate was 92.80%. 140 patients (56.00%) were treated conservatively with average time of immobilization of 218.17 ± 9.89 days. Both VAS and SF-12 scores improved across time points in all classes. Residual chronic back pain occurred in 27 patients (10.80%). Overall observed mortality was 4.80%. CONCLUSIONS: Standardized treatment of PS is highly recommended to ensure patients a good quality of life. The proposed scheme includes all available orthopedic treatments and helps spine surgeons to significantly reduce complications and costs and to avoid overtreatment.

Initial antifungal strategy does not correlate with mortality in patients with candidemia.

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.

Post-operative spondylodiscitis.

Postoperative spine infections (PSIs) are a frequent and dreaded complication of spine surgery. Although different studies have been published, the prevalence of PSIs is thought to be about 5% for most spine surgical procedures. Different risk factors have been identified for PSIs. Among the others, extensive soft tissue dissection, longer operative time, soft tissue devitalization, and use of surgical instrumentation have been associated with higher risks of infection. Direct inoculation during surgery is the common infection route for PSIs. Gram-positive cocci (such as Staphylococcus aureus, Staphylococcus epidermidis and beta-hemolytic streptococci) are the most common pathogens. Gram-negative bacteria also play a role in PSIs and may be associated with systemic illness and multisystem organ failure. A high level of suspicion is of paramount importance in early diagnosis of PSIs. Clinical symptoms of PSIs may be subtle and the infection may become apparent only in its late stages. Early diagnosis is the most important prognostic factor for PSIs. Although blood tests (i.e. ESR, CRP, and white blood cell count) and imaging studies (most commonly MRI) can be useful, it must be clear to the clinician that diagnostic modalities, either tissue biopsy or blood cultures, are of the utmost importance for diagnosing PSIs and devising a correct antibiotic therapy. Antibiotic therapy with early bracing (or bed rest) is the most commonly used treatment method for PSIs. Nevertheless, a more aggressive surgical treatment may be required in some patients. The goals of surgical treatment are to help the eradication of the infection, provide an adequate wound closure, and maintain spine column mechanical stability.

Tuberculous spondylodiscitis: epidemiology, clinical features, treatment, and outcome.

BACKGROUND: Tuberculous spondylodiscitis (TS) is a rare but serious clinical condition which may lead to severe deformity and early or late neurological complications. AIM: To discuss certain aspects of the approach to TSs, focusing upon epidemiology, diagnosis, and treatment outcome. MATERIALS AND METHODS: For the purpose of this review, a literature search was performed using the Pubmed database through to 19th October 2011 to identify studies published in the last 20 years, concerned in epidemiological, clinical, diagnostic, and therapeutical aspects of TS in adults. Only studies drafted in English language and reporting case series of more than 20 patients have been included. RESULTS: TS has been reported to accounts for 1-5% of all TB cases, and for about 50% of the cases of articulo-skeletal TB infections. Despite the actual availability of more effective diagnostic tools, early recognition of TS remains difficult and a high index of suspicion is needed due to the chronic nature of the disease and its insidious and variable clinical presentation. A prompt diagnosis is required to improve long term outcome, and a microbiological confirmation is recommended to enable appropriate choice of anti-mycobacterial agents. Surgery has an important role in alleviating pain, correcting deformities and neurological impairment, and restoring function. CONCLUSIONS: Further studies are required to assess the appropriate duration of anti-microbial treatment, also in regarding of a combined surgical approach.

Medical and surgical treatment of pyogenic spondylodiscitis.

BACKGROUND: Pyogenic vertebral osteomyelitis (PVO) represents approximately 2-7% of all cases of osteomyelitis. The approach to the treatment of PVO may be conservative, which includes antibiotic therapy and orthopaedic treatment, or surgical. AIM: To overview conservative and surigical approaches to PVO. METHODS: A literature review was performed using the Pubmed database to identify studies published in the last 20 years, addressing the treatment of PVO. RESULTS: Empirical antibiotic treatment of PVO, while waiting for the results of cultures or in culture-negative cases, should include broad spectrum agents in association with agents active on Staphylococcus (S.) aureus. Based on local epidemiological data, antibiotics active on methicillin resistant S. aureus (MRSA) should be included. Once an organism has been identified, antibiotics should be initially administered intravenously but the optimal duration of antimicrobial therapy is unclear. Studies have reported that the incidence of treatment failure was higher when i.v. therapy was administered for less than 4 weeks. Rifampin is widely used in the combination therapy of PVO, but no controlled trials are available to define weather this approach is beneficial. Many PVO need a surgical treatment and can represent a real challenge for the orthopaedic surgeon. Anterior and posterior cervical, thoracic, lumbar approaches and the relatives surgical strategies are reported in this review. Moreover, recently the mininvasive posterior stabilization have been proposed as a efficient alternative to open surgery in elderly with severe comorbidities. Possible advantages and limitations of this technique are also reported. CONCLUSIONS: Further research is needed in order to define the optimal duration of antibiotic therapy, and the benefits and limitations of open or mini-invasive surgical techniques.

Epidemiological and clinical features of pyogenic spondylodiscitis.

Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at age less than 20 years and in the group aged 50-70 years. The incidence of PS seems to be increasing in the last years as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of immunosuppressed patients, intravenous drug abuse, and the increase in spinal instrumentation and surgery. PS is in most cases a hematogenous infection. Staphylococcus aureus is the most frequent causative microorganism, accounting for about one half of the cases of PS. Gram-negative rods are causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS) have been reported in 5-16% of cases. Staphylococcus epidermidis is often related to post-operative infections and intracardiac device-related bacteremia. Unremitting back pain, characteristically worsening during the night, is the most common presenting symptom, followed by fever that is present in about one half of the cases. The mortality of PS ranges from 0 to 11%. In a significant number of cases, recrudescence, residual neurological defects or persistent pain may occur.

Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Delayed Auditory Brainstem Responses (ABR) in children after sight-recovery.

Studies in non-human animal models have revealed that in early development, the onset of visual input gates the critical period closure of some auditory functions. The study of rare individuals whose sight was restored after a period of congenital blindness offers the rare opportunity to assess whether early visual input is a prerequisite for the full development of auditory functions in humans as well. Here, we investigated whether a few months of delayed visual onset would affect the development of Auditory Brainstem Responses (ABRs). ABRs are widely used in the clinical practice to assess both functionality and development of the subcortical auditory pathway and, provide reliable data at the individual level. We collected Auditory Brainstem Responses from two case studies, young children (both having less than 5 years of age) who experienced a transient visual deprivation since birth due to congenital bilateral dense cataracts (BC), and who acquired sight at about two months of age. As controls, we tested 41 children (sighted controls, SC) with typical development, as well as two children who were treated (at about two months of age) for congenital monocular cataracts (MC). The SC group data served to predict, at the individual level, wave latencies of each BC and MC participant. Statistics were performed both at the single subject as well as at the group levels on latencies of main ABR waves (I, III, V and SN10). Results revealed delayed response latencies for both BC children compared with the SC group starting from the wave III. Conversely, no difference emerged between MC children and the SC group. These findings suggest that in case the onset of patterned visual input is delayed, the functional development of the subcortical auditory pathway lags behind typical developmental trajectories. Ultimately results are in favor of the presence of a crossmodal sensitive period in the human subcortical auditory system.

"Say Ninetynine": It's Never too Late to Recover from COVID-19.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, showed higher severity and lethality in male older adults . There are currently no specific treatments. Studies are evaluating the efficacy of monoclonal antibodies against interleukin-6 receptor. Here we present the case of a 98-years old man admitted to our COVID-Hospital with acute respiratory failure. Comprehensive geriatric assessment showed no signs of frailty. First-line therapy with hydroxychloroquine and anticoagulants was not effective. Patient was administered intravenous monoclonal antibodies, and he showed remarkable clinical improvement. This case suggests that age alone should not preclude access to new therapeutic approaches. Comprehensive, multisciplinary, multidomain approaches are needed to develop patient-tailored treatments against COVID-19.

Italian young doctors' knowledge, attitudes and practices on antibiotic use and resistance: A national cross-sectional survey.

OBJECTIVES: Antimicrobial resistance (AMR) is one of the major health issues worldwide. Clinicians should play a central role to fight AMR, and medical training is a pivotal issue to combat it; therefore, assessing levels of knowledge, attitudes and practices among young doctors is essential for future antimicrobial stewardship (AMS) programmes. METHODS: A nationwide, cross-sectional, multicentre survey was conducted in Italy. A descriptive analysis of knowledge and attitudes was performed, along with a univariate and multivariate analysis of their determinants. RESULTS: Overall, 1179 young doctors accessed the survey and 1055 (89.5%) completed all sections. Regarding the knowledge section of the questionnaire, almost all participants declared to know the different species of bacteria proposed, however the percentage of participants who correctly responded to clinical quizzes was 23% for the question on vancomycin-resistant enterococci (VRE), 42% on carbapenem-resistant Enterobacteriaceae (CRE), 32% on extended-spectrum ß-lactamase-producing enterobacteria (ESBL) and 27% on methicillin-resistantStaphylococcus aureus (MRSA). Similarly, 81% of participants disagreed in stating that AMR was adequately addressed during their medical training and 71% disagreed that they received the right example from their tutors. Finally, a high rate of agreement with the proposed actions to combat AMR was documented; in particular, the percentage agreement was 76% for respondents who agreed to be part of an active surveillance system or AMS programme. CONCLUSIONS: Tackling AMR should be a priority for politicians and for all health workers. Inclusion of competencies in antibiotic use in all specialty curricula is urgently needed.

Systemic antibiotic treatment of chronic osteomyelitis in adults.

Chronic osteomyelitis is a difficult to treat infection of the bone, which requires a combined medical and surgical approach and often persists intermittently for years, with relapses and failures. The optimal type, route of administration, and duration of antibiotic treatment remain controversial, and the emergence of multi-drug resistant organisms poses major therapeutic challenges. Identification of the causative agent and subsequent targeted antibiotic treatment has a major impact on patients' outcome. In this review, we summarize which intravenous and oral antibiotics are the best options available for the treatment of chronic osteomyelitis, according to specific aetiologies.

Minimally invasive surgery for the treatment of thoraco lumbar pyogenic spondylodiscitis: indications and outcomes.

OBJECTIVE: Pyogenic spondylodiscitis (PS) is a non-specific infection affecting intervertebral disks and adjacent vertebral bodies. Once considered a rare condition in developed countries, the incidence of PS has been increasing alarmingly and still represents a challenge for clinicians and orthopedic surgeons. New minimally invasive techniques have been proposed but the proper indications for these different approaches remain controversial. The aim of this study was to describe the available minimally invasive surgical techniques and to evaluate their proper indications through a review of recent literature. MATERIALS AND METHODS: Over 30 articles of recent scientific literature have been reviewed and analyzed. Studies were searched through the PubMed database using the key words: spondylodiscitis, minimally invasive, and surgical treatment. The most interesting and valid techniques and results have been reported. Despite the exclusion of case reports, all the available studies have been conducted on small groups of patients. Indications for each technique have been reported according to a clinical-radiological classification of PS. RESULTS: Six of the most widely used minimally invasive surgical techniques have been described.  High success rates have been reported in terms of preventing the progression of spondylodiscitis into more destructive forms, reduction of time and operative hospitalization, faster pain relief, early mobilization, and achievement of microbiological diagnosis. CONCLUSIONS: The role of minimally invasive surgery in the treatment of PS is rapidly expanding. Reducing surgery-related morbidity in these frail patients is possible and often necessary. However, while more and more new techniques are being proposed, still few clinical data are available. Clinical comparison studies with open traditional surgery should be encouraged, and more attention should be paid to long-term outcomes. For the present, the indications for minimally invasive procedures should, therefore, be evaluated on a case by case basis and on clinical and radiological findings.

The use of custom-made antibiotic-loaded spacer in periprosthetic knee infection caused by XDR organism: case report and review of literature.

Periprosthetic knee infection (PKI) remains one of the most challenging complications after total knee replacement, especially if caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) organisms. Multiple treatment options are available, such as long-term antibiotic suppression, surgical debridement with retention of the prosthesis, definitive resection arthroplasty, arthrodesis, one-stage or two-stage revision procedures, amputation. We present a rare case of a PKI caused by a XDR Klebsiella pneumoniae in a young patient who underwent a prosthetic reconstruction due to an osteosarcoma of the tibia. In this patient, the PKI has been treated using intravenous administration of Amikacin and an Amikacin-impregnated PMMA custom-made spacer. To our knowledge, only two cases that successfully used hand-mixed antibiotic-loaded spacer based on antibiotic sensitivity for the treatment of PKI caused by MDR and XDR microorganisms have been reported in the literature.

Clinical and prognostic features of prosthetic joint infections caused by Enterococcus spp.

OBJECTIVE: Pathogens colonizing the intestinal or urinary tract such as enterococci or Gram-negative bacilli can cause prosthetic joint infection (PJI). PATIENTS AND METHODS: PJI undergoing 2-stage exchange, referred to the Department of Infectious Diseases of the Cotugno Hospital of Naples and the Fondazione Policlinico Gemelli of Rome over a 7-year period (2009-2015) for Infectious Diseases (ID) consultation were included. Demographic data, detailed information about previous or underlying diseases, findings of the clinical examination, and results of laboratory investigations were analyzed. The cure was defined by the disappearance of clinical, laboratory, and radiological evidence of PJI 96 week after the discontinuation of antibiotic treatment. RESULTS: Thirty-one cases of PJI sustained by Enterococci were included (16 early infections, 13 delayed infections, and 2 late infections). Median age was 73 years (range 39-83), 39% were males. Comorbidities related to an increased risk of infection were reported in 17 (55%) cases. Joint pain interfering with daily living was reported in 27 (87%) cases, fever in 7 with early infection and in no case with delayed or late infection (7/17 vs. 0/14, Odds ratio undefined, p=0.01). Local inflammation and joint effusion were reported in 29 (93%) cases, sinus tract in 25 (81%). Enterococcus faecalis was the etiologic agent in 28 (90%) cases, E. faecium in 2 (6%), E. casseliflavus in 1 (3%). Eleven cases were polymicrobial. Favourable outcome was reported in 20 (65%) cases. Patients with comorbidities reported more frequently an unfavourable outcome (9/17 vs. 2/14, Odds ratio 6.7, 95% CI 1.1-39.8; p=0.06). CONCLUSIONS: Comorbidities should arise the suspect of infection by enterococci. Associative protocols, considering drugs active against biofilm should be considered in the cases with enterococcal infection.