Bone and joint infections of the hand.

BACKGROUND: Little guidance is currently available for standardized diagnostic protocols and therapeutic recommendations for bone and joint infections (BJIs) of the hand. OBJECTIVES: To summarize the available data in the scientific English-language literature on the diagnosis and treatment of native BJIs of the hand. To illustrate these concepts from a narrative point of view in areas where there is lack of evidence. SOURCES: We performed a systematic PubMed and Internet search of studies that investigated hand BJIs in adult patients. CONTENT: Few studies have systematically investigated and validated diagnostic concepts, classifications or surgical treatment protocols. Most concepts derive from traditional intra-institutional experience, expert opinions and extrapolations from infections in large joints and long bones. Similarly, there is no uniformly accepted infection definition of BJIs of the hand. The best-documented literature is available for microbiological findings and antibiotic treatment duration in uncomplicated native joint arthritis of the fingers. Retrospective studies and one prospective randomized trial suggest that post-surgical targeted antibiotic therapy of 2 weeks results in a microbiological cure rate of ≥88%. IMPLICATIONS: Studies on diagnostic workup and infection definition and classification are urgently needed to compare inter-institutional outcome results and generate guidelines for the best patient care. For uncomplicated pyogenic arthritis of native joints, current evidence suggests that a 2-week course of antibiotic therapy following surgery cures the infection.

Association between treatment duration and mortality or relapse in adult patients with Staphylococcus aureus bacteraemia: a retrospective cohort study.

OBJECTIVES: The aim was to evaluate the effect of duration of therapy (DOT) on mortality and relapse for patients with Staphylococcus aureus bacteraemia (SAB). METHODS: We performed a retrospective single-centre cohort study including adult patients with SAB. We determined the association between DOT (≤14 days versus >14 days) and mortality by adjusted hazard ratios (aHR) and 95% confidence intervals through Cox regression adjusted for immortal-time bias and confounding by indication, stratified by presence of complicated SAB (any of: endocarditis, implant, duration of SAB >2 days, fever >3 days). The primary outcome was 90-day all-cause mortality, and the secondary outcome was 90-day relapse. RESULTS: Between January 2010 and December 2015, we included 530 patients, of whom 94 out of 530 (17.7%) had methicillin-resistant SAB and 305 out of 530 (57.6%) had complicated SAB. Ninety-day mortality was 27.0% (143/530), with no significant trend across the study period; median time to death was 17 days (interquartile range (IQR) 8-30) after onset of SAB. Median DOT was 20 days (IQR 13-39). Patients with complicated SAB had significantly reduced mortality with DOT >14 days (aHR 0.32, 95% CI 0.16-0.64). DOT was not associated with mortality in patients with uncomplicated SAB (aHR 0.85; 0.41-1.78). Eighteen (18/530) patients (3.4%) relapsed; on univariate analysis, DOT was not associated with relapse (HR 1.01; 0.97-1.06). CONCLUSIONS: DOT >14 days is associated with higher survival in patients with complicated SAB, but not for patients with uncomplicated SAB. No association was found for relapse, but 90-day relapse was very low in this cohort. Importantly, 90-day mortality remained high across the study period.

[The challenges of surgical tourism in the field of aesthetic surgery]. / Les enjeux du tourisme chirurgical dans le domaine de la chirurgie esthétique.

INTRODUCTION: Surgical tourism is a growing phenomenon, causing a surge demand for the management of its complications. In this study, we aimed to evaluate complications that occur after cosmetic breast surgery abroad; and their costs for the public health system. MATERIAL AND METHODS: We reviewed the medical files of patients treated in our department for a complication after cosmetic breast surgery outside Switzerland and assessed all complications requiring hospitalization; and estimated the overall medical costs. RESULTS: Over a two-year period, 26 patients were treated for 39 complications. The main complication was infection (71% of cases), mainly with a multidrug-resistant organism (47%) and atypical mycobacteria. Of the 16 patients with breast prosthesis, 7 implants were removed. The effective average costs incurred for the hospital care of these cases was estimated to 14'724 Swiss Francs (∼12'963 Euros) per patient. CONCLUSION: The high rate of multidrug-resistant and mycobacterial atypical infections are a major public health problem. It is necessary to inform patients much better about the risks of surgical tourism. Furthermore, the danger of transfer of multidrug-resistant or atypical germs from abroad should not be overlooked. Physicians should be informed about this risk and take necessary measures for treatment and diagnosis of these complications.

Non-compliance with IDSA guidelines for patients presenting with methicillin-susceptible Staphylococcus aureus prosthetic joint infection is a risk factor for treatment failure.

OBJECTIVE: The long-term impact of treatment strategies proposed by the IDSA guidelines for patients presenting with methicillin-susceptible S. aureus (MSSA) prosthetic joint infection (PJI) is not well-known. PATIENTS AND METHODS: Retrospective (2000-2010) cohort study including patients presenting with MSSA hip or knee PJI. A univariate Cox analysis was performed to determine if the non-compliance with IDSA surgical guidelines was a risk factor for treatment failure. RESULTS: Eighty-nine patients with a mean follow-up of 2.8 years were included. Non-compliance with IDSA surgical guidelines was associated with treatment failure (hazard ratio 2.157; 95% CI [1.022-4.7]). The American Society of Anesthesiologists score, inadequate antimicrobial therapy, and a rifampicin-based regimen did not significantly influence patient outcome. CONCLUSION: Based on the IDSA guidelines, if a patient presenting with MSSA PJI is not eligible for implant retention, complete implant removal is needed to limit treatment failure.

Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study.

OBJECTIVES: Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomized to it. Therapeutic drug monitoring (TDM) of ß-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold. METHODS: In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection. RESULTS: A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.732 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels >20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8). CONCLUSIONS: Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/L. For those receiving intermittent infusions, trough concentrations >20 mg/L should be avoided until further information is available from prospective studies.

Rapid molecular determination of methicillin resistance in staphylococcal bacteraemia improves early targeted antibiotic prescribing: a randomized clinical trial.

Empiric therapy of methicillin-susceptible Staphylococcus aureus (MSSA) infections with vancomycin is associated with poorer outcome than targeted therapy with ß-lactams. Our objective was to evaluate whether rapid determination of methicillin resistance shortens the time from Gram stain to targeted antimicrobial therapy in staphylococcal bacteraemia, thereby reducing vancomycin overuse. This was a single-centre open parallel RCT. Gram-positive cocci in clusters in positive blood culture underwent real-time PCR for rapid species and methicillin resistance determination parallel to conventional microbiology. Patients were randomized 1:1 so that clinicians would be informed of PCR results (intervention group) or not (control group). Eighty-nine patients (intervention 48, control 41) were analysed. MRSA was identified in seven patients, MSSA in 46, and CoNS in 36. PCR results were highly concordant (87/89) with standard microbiology. Median time (hours) from Gram stain to transmission of methicillin-susceptibility was 3.9 (2.8-4.3) vs. 25.4 (24.4-26-7) in intervention vs. control groups (p <0.001). Median time (hours) from Gram stain to targeted treatment was similar for 'all staphylococci' [6 (3.8-10) vs. 8 (1-36) p 0.13] but shorter in the intervention group when considering S. aureus only [5 (3-7) vs. 25.5 (3.8-54) p <0.001]. When standard susceptibility testing was complete, 41/48 (85.4%) patients in the intervention group were already receiving targeted therapy compared with 23/41 (56.1%) in the control group (p 0.004). There was no significant effect on clinical outcomes. Rapid determination of methicillin resistance in staphylococcal bacteraemia is accurate and reduces significantly the time to targeted antibiotic therapy in the subgroup of S. aureus, thereby avoiding unnecessary exposure to vancomycin.

[Management of an infection associated with a prosthetic arthroplasty: the necessity of collaboration between surgeon and infectiologist]. / Prise en charge des infections d'arthroplasties prothétiques une collaboration entre chirurgiens et infectiologues.

The total number of total knee and hip joint arthroplasties is constinuously rising, due to an increasing population of physically active elderly patients. For primary elective arthroplasties, the infection risk ranges between I and 2%, but equals to a high morbidity, costs and complications for the individual infected patient. Diagnosis and management of prosthetic joint infections are improving. We review the latest consensus on the diagnosis and management of these infections and reveal some insight in still debated issues.

[Community-acquired bacterial septic arthritis in adults: diagnosis and treatment]. / Arthrite septique bactérienne communautaire chez l'adulte: du diagnostic au traitement.

The diagnosis of acute native joint bacterial infection can be difficult, because of its non- specific clinical and biological manifestation. Its management is often an emergency. Following a joint puncture, early joint lavage is performed, either by surgical drainage or by repeated arthrocentesis; and accompanied by systemic antibiotics, of which the ideal duration and route of administration remains unknown. The postoperative care is characterized by joint mobilization to avoid joint stiffening.

Challenges in diagnosing infection in the diabetic foot.

Diagnosing the presence of infection in the foot of a patient with diabetes can sometimes be a difficult task. Because open wounds are always colonized with microorganisms, most agree that infection should be diagnosed by the presence of systemic or local signs of inflammation. Determining whether or not infection is present in bone can be especially difficult. Diagnosis begins with a history and physical examination in which both classic and 'secondary' findings suggesting invasion of microorganisms or a host response are sought. Serological tests may be helpful, especially measurement of the erythrocyte sedimentation rate in osteomyelitis, but all (including bone biomarkers and procalcitonin) are relatively non-specific. Cultures of properly obtained soft tissue and bone specimens can diagnose and define the causative pathogens in diabetic foot infections. Newer molecular microbial techniques, which may not only identify more organisms but also virulence factors and antibiotic resistance, look very promising. Imaging tests generally begin with plain X-rays; when these are inconclusive or when more detail of bone or soft tissue abnormalities is required, more advanced studies are needed. Among these, magnetic resonance imaging is generally superior to standard radionuclide studies, but newer hybrid imaging techniques (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging) look to be useful techniques, and new radiopharmaceuticals are on the horizon. In some cases, ultrasonography, photographic and thermographic methods may also be diagnostically useful. Improved methods developed and tested over the past decade have clearly increased our accuracy in diagnosing diabetic foot infections.

Non-tuberculous mycobacterial infections of the hand.

UNLABELLED: Non-tuberculous mycobacterial infections of the hand are difficult to treat and require a long time before remission. But how long should we wait to see an improvement? To answer this question, the published scientific literature was reviewed in English, French and German. Tuberculosis, arthritis and osteomyelitis cases were excluded. A total of 241 non-tuberculous mycobacterial hand infections in 38 scientific publications were retrieved. Most were case reports or series. The median age of the patients was 58years and one third was female. Patients were immunocompromised in 17 episodes. The most common species were Mycobacterium marinum in 198 episodes (82%), followed by M. chelonae in 13 cases (5%). There were no cases of mixed infection. Most infections were aquatic in origin and community-acquired, and were treated with a combination of surgical debridement and long-duration systemic combination antibiotic therapy (14 different regimens; no local antibiotics) for a median duration of 6months. The median number of surgical procedures was 2.5 (range 1-5). Clinical success was not immediate: a median period of 3months (range 2-6) was necessary before the first signs of improvement were observed. The majority (173 cases; 76%) remained entirely cured after a median follow-up time of 1.7years (range, 1-6). Only two microbiological recurrences occurred (1%). However, 49 patients (21%) had long-term sequelae such as pain, stiffness and swelling. The approach of long-duration antibiotic treatment in combination with repeated surgery for mycobacterial soft tissue infections of the hand leads to few recurrences. However, clinical success is not immediate and may take up to 3months. TYPE OF STUDY: Therapeutic study: systematic review of level III studies. LEVEL OF EVIDENCE: III.

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection.

OBJECTIVES: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. METHODS: We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854). RESULTS: Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group. CONCLUSIONS: Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

[Deep soft tissue infections]. / Infections profondes des tissus mous.

The clinical presentations of deep soft tissue infections can, initially, mimicry superficial skin infections such as erysipelas. However, a rapidly deteriorating health status, the spreading of the lesions and the lack of clear visual limitation of the infection on the skin are hallmarks of a more severe underlying infection, which may endanger patients' life. An immediate adequate multidisciplinary approach to therapy within a few hours is mandatory. The first step is surgical exploration with debridement of all infected tissues, accompanied by antibiotic therapy and additional supportive measures. Despite progress in the understanding of the physiopathology, the delay between suspicion of diagnosis and surgical exploration remains critical. Because of the low incidence of such severe infections, only multicenter studies might reveal deeper insights of optimal therapeutic strategies in the future and for possible improved patients' survival.

Managing diabetic foot infections: a review of the new guidelines.

Foot infections are amongst the most frequent and severe complications linked to diabetes mellitus and are the most common non-traumatic cause of lower limb amputation. Appropriate management of these infections, however, can improve their outcome. The Infectious Diseases Society of America (IDSA) constituted a panel of multidisciplinary experts in 2004 to develop guidelines for the diagnosis and treatment of diabetic foot infections, which have been widely used and validated. Because there have been many new publications in the field, and the IDSA updated the format for all guidelines, they asked the diabetic foot infection committee to revise the 2004 publication. The revised guidelines, based on a thorough and systematic review of the literature, were published in 2012. They are built around 10 key questions concerning diagnosis and treatment; these are answered, with a summary of the evidence provided, and given a GRADE rating for the strength of the recommendation and quality of the evidence. The updated guidelines also include advice on implementing these recommendations, suggestions for regulatory changes to enhance care for diabetic foot infections, recommendations on performance measures and suggested areas for future research. They also include 14 tables, 1 figure, and 345 references, most of which were published after the first guidelines in 2004. Implementing these guidelines should improve outcomes in patients with a DFI.

Is there any benefit in pre-operative urinary analysis before elective total joint replacement?

Whether patients with asymptomatic bacteriuria should be investigated and treated before elective hip and knee replacement is controversial, although it is a widespread practice. We conducted a prospective observational cohort study with urine analyses before surgery and three days post-operatively. Patients with symptomatic urinary infections or an indwelling catheter were excluded. Post-discharge surveillance included questionnaires to patients and general practitioners at three months. Among 510 patients (309 women and 201 men), with a median age of 69 years (16 to 97) undergoing lower limb joint replacements (290 hips and 220 knees), 182 (36%) had pre-operative asymptomatic bacteriuria, mostly due to Escherichia coli, and 181 (35%) had white cells in the urine. Most patients (95%) received a single intravenous peri-operative dose (1.5 g) of cefuroxime as prophylaxis. On the third post-operative day urinary analysis identified white cells in 99 samples (19%) and bacteriuria in 208 (41%). Pathogens in the cultures on the third post-operative day were different from those in the pre-operative samples in 260 patients (51%). Only 25 patients (5%) developed a symptomatic urinary infection during their stay or in a subsequent three-month follow-up period, and two thirds of organisms identified were unrelated to those found during the admission. All symptomatic infections were successfully treated with oral antibiotics with no perceived effect on the joint replacement. We conclude that testing and treating asymptomatic urinary tract colonisation before joint replacement is unnecessary.

Diabetic foot infections: state-of-the-art.

Foot infections are frequent and potentially devastating complications of diabetes. Unchecked, infection can progress contiguously to involve the deeper soft tissues and ultimately the bone. Foot ulcers in people with diabetes are most often the consequence of one or more of the following: peripheral sensory neuropathy, motor neuropathy and gait disorders, peripheral arterial insufficiency or immunological impairments. Infection develops in over half of foot ulcers and is the factor that most often leads to lower extremity amputation. These amputations are associated with substantial morbidity, reduced quality of life and major financial costs. Most infections can be successfully treated with optimal wound care, antibiotic therapy and surgical procedures. Employing evidence-based guidelines, multidisciplinary teams and institution-specific clinical pathways provides the best approach to guide clinicians through this multifaceted problem. All clinicians regularly seeing people with diabetes should have an understanding of how to prevent, diagnose and treat foot infections, which requires familiarity with the pathophysiology of the problem and the literature supporting currently recommended care.

Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection.

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively). Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis.

[Where are we in the treatment of chronic osteomyelitis?]. / Où en est-on dans le traitement médical des ostéomyélites chroniques?

Chronic osteomyelitis is a multifaceted bacterial infection with common features, which requires surgery for remission. The duration and modality of concomitant administration of antibiotic agents for adult patients is still based on expert opinions. The traditional recommendation of 6 to 12 weeks of antibiotic therapy with intravenous administration for at least the first 2 weeks is more and more challenged in favor of an oral antibiotic treatment with selected agents from the start. There is no evidence that the total duration of antibiotic therapy for more than 6-12 weeks improves outcome, when compared with shorter regimens. External advice from an expert team with combined surgeons and infectious disease physicians may help to reduce antibiotic consumption in a cost-effective way.

Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update.

Prevention of surgical site infection in orthopaedic surgery and bone trauma has some hallmarks not shared with other surgical disciplines: low inoculum for implant infections; pathogenicity of coagulase-negative staphylococci and other skin commensals; possible haematogenous origin; and long post-discharge surveillance periods. Only some of the many measures to prevent orthopaedic surgical site infection are based on strong evidence and there is insufficient evidence to show which element is superior over any other. This highlights the need for multimodal approaches involving active post-discharge surveillance, as well as preventive measures at every step of the care process. These range from preoperative care to surgery and postoperative care at the individual patient level, including department-wide interventions targeting all healthcare-associated infections and improving antibiotic stewardship. Although theoretically reducible to zero, the maximum realistic extent to decrease surgical site infection in elective orthopaedic surgery remains unknown.