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Objective: To review the clinical literature focusing on epidemiology, clinical presentation and outcomes of prosthetic joint infections (PJIs) due to gram-negative bacteria (GNB) and to report the experience of a multicentric cohort., Patients and Methods: A retrospective, observational, cohort study was performed in three Italian hospitals. All consecutive PJIs caused by GNB over a 12-year period (from May 2007 to March 2018) were enrolled. Epidemiological, clinical, microbiological and therapeutic features were described. Factors related to treatment failure (defined as the occurrence of death, amputation or starting long-term antimicrobial suppression therapy) were analysed with a Cox regression model., Results: A total of 82 PJIs due to GNB (42.7% men; median age 73 years) were studied. The implants included 65 (79.3%) hip, 16 (19.5%) knee and one (1.2%) shoulder. An early PJI was diagnosed in 16.2% of patients, a delayed PJI in 29.4% and a late PJI in 54.4%. The most common isolated organisms were Escherichia coli (21.7%) and Pseudomonas spp. (20.9%). 13.4% of the isolates were carbapenem-resistant bacteria (CRB). In 53.8% of cases a two-stage exchange arthroplasty was performed and in 32.5% a Girdlestone excision arthroplasty. The average therapeutic failure occurred in 17.7% of cases. The therapeutic failure rate of the two-stage was 10%. PJI due to CRB was identified as a potential risk factor for failure (aHR 4.90; IC 95%, 0.96-25.08; p=0.05). The therapeutic failure rate in the CRB group was 50%., Conclusions: The treatment with the two-stage procedure for PJIs caused by GNB seems to be associated with a low rate of failure, while PJI due to CRB seems to be related to the worst outcome.

Objective: Biochemical markers are commonly used in medicine to guide diagnostic investigation or therapy duration and/or monitor treatment efficacy. Due to the emergence and spread of antimicrobial resistance, markers able to prompt a more rational use of antimicrobial therapy are regarded with the greatest attention. Procalcitonin (PCT) certainly stands out among others, yet its role must be better established especially outside of the critical care area. Data about PCT utilization in non-critical patients, optimal negativity cut-offs as well as a protocol for measurement timing are all lacking., Materials and Methods: To address these issues, a focus group was set up to propose and endorse shared statements regarding the most beneficial use of PCT in real life as infection marker for non-critical patients, based on the authors' experience and a review of recent literature., Results: A group of nine experts in the fields of Infectious Diseases, Internal Medicine, Microbiology, Clinical Chemistry, Surgery and Medical Economics participated in the discussion of nine pre-specified statements., Conclusions: The potential role for PCT in differentiating infectious and non-infectious clinical syndromes and guiding antimicrobial therapy discontinuation was acknowledged. Moreover, a shared measurement protocol and desirable cut-offs for the non-critical area were proposed. Finally, observations were made about a reasonable selection of the patient population to be tested.

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.

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.

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.

Objective: Periprosthetic joint infections (PJI) are one of the most dangerous complications in hip surgery. "Two-stage" revision surgery is the treatment of choice. Nevertheless, 5-10% of failures are reported. The aim of this study is to evaluate which factors determine the failure of the two-stage revision in patients affected by hip PJI., Patients and Methods: We retrospectively enrolled 21 patients treated for hip PJI who had undergone two-stage revision surgery. The diagnosis had been made using criteria established by the Musculoskeletal Infection Society (MSIS) and readapted by the Philadelphia Consensus Conference group. The patients underwent periodic clinical and laboratory controls after the surgical procedure. The two-stage revision treatment was considered unsuccessful in the event of re-infection or in case of severe complications occurring within one year from the treatment., Results: At a mean follow-up of 23.8 months 57% healed with no complications. The reinfection rate was 19% and, after the 3rd stage, the final failure rate was 9.5%. The study has shown, with statistical significance, that a greater number of previous surgical procedures (p<0.05, OR=22) and BMI>25 (p<0.05, OR=4) represent increased risk factors in predicting the failure of two-stage revision surgery. Age, CRP, ESR and a shorter lapse (<60 days) between 1st and 2nd stage were recorded in the failure cases, and have to be considered, even if not statistically significant., Conclusions: Knowing the factors responsible for the increased failure of two-stage revision could lead to closer monitoring and more aggressive management in those patients expected to be at greater risk of reinfection. Obesity and multiple surgeries are risk factors for failure.

Despite adopted precautions, surgical site infection (SSI) rate in orthopaedic surgery and its consequences still remain a major problem. Worldwide, infection prevention and control in perioperative settings are considered of primary importance for every healthcare system. The management of perioperative infections carries a heavy psychological and financial burden, since patients who experience SSI have increased hospital length of stay, morbidity and mortality rates, and higher hospital costs. As the treatment of such infections is particularly difficult in the presence of an implanted biomaterial, the prevention of SSI in orthopaedic surgery represents a challenging key issue, requiring the integration of a range of measures before, during and after surgery. In fact, over the years several aspects of SSI prevention have been studied in order to identify the best SSI prevention strategies and set out appropriate clinical practices. This article will review and summarize the recent international guidelines released on this subject together with other published relevant evidence.

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.

Objective: To evaluate whether PCT levels could be used to distinguish among different bacterial and fungal etiologies in patients with documented bloodstream infection (BSI)., Patients and Methods: Monocentric retrospective cohort study on patients admitted to the Fondazione Policlinico Gemelli Hospital between December 2012 and November 2015 with BSI. Those who had undergone PCT determination within 48 hours of when the first positive blood culture was sampled were included in the study., Results: Four hundred and one patients were included in the study. Both the 24h and 48h PCT values were significantly higher in patients with Gram-negative (GN) BSI than in those with Gram-positive (GP) or candida BSI (p at ANOVA = 0.003). A PCT value of > 1 ng/ml was found in 31.5% of patients with GN BSI. Less than 7% of people with candida BSI had PCT level of > 1 ng/ml. At multivariable regression analysis, GN BSI, septic shock, and plasma creatinine were significantly correlated with PCT values., Conclusions: PCT may be of value in distinguishing GN BSI from GP, and fungal BSI and PCT values of > 1 ng/ml could be used to prevent unnecessary antifungal treatment.

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.

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.

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.

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.