RESUMEN
BACKGROUND: High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. METHODS: All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. RESULTS: From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. CONCLUSIONS: We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.
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Daptomicina , Eosinofilia Pulmonar , Humanos , Daptomicina/uso terapéutico , Antibacterianos/uso terapéutico , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/tratamiento farmacológico , Miotoxicidad/tratamiento farmacológico , Estudios Prospectivos , Teorema de Bayes , Proteína C-Reactiva , Factores de RiesgoRESUMEN
This article highlights four recent updates in infectious disease in the management of bone and joint infections (BJI). During the first six weeks of treatment of a BJI, with or without orthopedic implant, oral antimicrobial therapy is as effective as intravenous therapy. For periprosthetic joint infections, a randomized control study failed to demonstrate non-inferiority of 6 versus 12 weeks of antibiotic therapy. In diabetic foot osteomyelitis, a 3-week course of antibiotics appears to be non-inferior to a 6-week course. Phage therapy seems promising in adjunctive therapy of complex BJI.
Cet article expose quatre nouveautés thérapeutiques significatives en orthopédie septique. Durant les six premières semaines de traitement d'une infection ostéoarticulaire, avec ou sans matériel, une antibiothérapie per os est aussi efficace qu'une antibiothérapie intraveineuse. Concernant les arthroplasties infectées, il n'y a pas de preuve suffisante à raccourcir le traitement antibiotique à moins de douze semaines. Dans les ostéomyélites de pied diabétique, une antibiothérapie de trois semaines semble non inférieure à une thérapie de six semaines. Finalement, la phagothérapie est prometteuse dans les infections ostéoarticulaires, particulièrement dans les situations d'échec des traitements conventionnels.
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Artritis Infecciosa , Enfermedades Transmisibles , Pie Diabético , Osteomielitis , Humanos , Enfermedades Transmisibles/tratamiento farmacológico , Artritis Infecciosa/tratamiento farmacológico , Osteomielitis/terapia , Antibacterianos/uso terapéutico , Pie Diabético/tratamiento farmacológicoRESUMEN
Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.
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Trasplante de Órganos , Osteomielitis , Humanos , Masculino , Trasplante de Órganos/efectos adversos , Estudios de Casos y Controles , Estudios de Cohortes , Receptores de Trasplantes , Osteomielitis/epidemiología , Osteomielitis/etiologíaRESUMEN
BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.
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Diabetes Mellitus , Pie Diabético , Osteomielitis , Infecciones de los Tejidos Blandos , Anciano , Antibacterianos , Desbridamiento , Diabetes Mellitus/tratamiento farmacológico , Pie Diabético/complicaciones , Pie Diabético/tratamiento farmacológico , Femenino , Humanos , Masculino , Osteomielitis/inducido químicamente , Osteomielitis/etiología , Proyectos Piloto , Infecciones de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
Wound healing issues are not rare after total knee arthroplasty. While most patients heal with local wound care, a minority is susceptible to develop serious complications such as peri-prosthetic joint infection. If direct closure is not feasible, we recommend a multidisciplinary approach based on the ortho-plastic model to determine the optimal wound closure strategy. Negative pressure wound therapy can be used while waiting for definitive coverage to optimise wound environment. Medial gastrocnemius flap is considered as the gold standard procedure for peri-prosthetic substance loss around the knee.
Les problèmes de cicatrisation ne sont pas rares après l'implantation d'une prothèse totale de genou. La plupart des patients guérissent avec des soins locaux mais une minorité d'entre eux peut développer des complications redoutables allant jusqu'à l'infection périprothétique. Hormis les situations pour lesquelles une fermeture directe de la cicatrice chirurgicale peut être réalisée, nous recommandons une approche multidisciplinaire basée sur le modèle de l'ortho-plastique afin de déterminer la stratégie de reconstruction la plus adaptée. La thérapie par pression négative peut être utilisée pour conditionner la plaie en vue d'un geste de couverture définitive. Le lambeau gastrocnémien médial est considéré comme la procédure de référence pour les pertes de substance périprothétique du genou.
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Artroplastia de Reemplazo de Rodilla , Procedimientos de Cirugía Plástica , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Colgajos Quirúrgicos/cirugía , Articulación de la Rodilla/cirugía , Cicatrización de Heridas , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks) duration compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with noninferior results for clinical remission and adverse events (AEs). METHODS: In this prospective, randomized, noninferiority pilot trial, we randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after the end of therapy was 2 months. We compared outcomes using Cox regression and noninferiority analyses (25% margin, power 80%). RESULTS: Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridements was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared with 36 (73%) in the 6-week arm (Pâ =â .21). The number of AEs was similar in the 2 study arms (17/44 vs 16/49; Pâ =â .51), as were the remission incidences in the per-protocol (PP) population (33/39 vs 32/43; Pâ =â .26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (ITT population: hazard ratio [HR], 1.1 [95% confidence interval {CI}, .6-1.7]; PP population: HR, 0.8 [95% CI: .5-1.4]). CONCLUSIONS: In this randomized controlled pilot trial, a postdebridement systemic antibiotic therapy course for DFO of 3 weeks gave similar (and statistically noninferior) incidences of remission and AE to a course of 6 weeks. CLINICAL TRIALS REGISTRATION: NCT03615807; BASEC 2016-01008 (Switzerland).
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Diabetes Mellitus , Pie Diabético , Osteomielitis , Anciano , Antibacterianos/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Pie Diabético/tratamiento farmacológico , Pie Diabético/cirugía , Femenino , Humanos , Masculino , Osteomielitis/tratamiento farmacológico , Proyectos Piloto , Estudios ProspectivosRESUMEN
Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures.
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Diabetes Mellitus , Pie Diabético , Antibacterianos/uso terapéutico , Proteína C-Reactiva/análisis , Diabetes Mellitus/tratamiento farmacológico , Pie Diabético/tratamiento farmacológico , Humanos , Estudios Prospectivos , RecurrenciaRESUMEN
What's new in infectious diseases in 2020â ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «â PIRATEâ ¼ indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.
Que dire des nouveautés en maladies infectieuses en 2020â ? L'année a été marquée évidemment par la pandémie du Covid-19, motivant une revue dans cet article, des connaissances actuelles sur le SARS-CoV-2 et de sa prise en charge. Les résultats du projet suisse PIRATE ont montré une non-infériorité pour les bactériémies Gram négatif entre une antibiothérapie de 7 jours ou guidée par la CRP face à une durée de 14 jours. Une étude mongolienne n'a pas permis de montrer le bénéfice d'une substitution en vitamine D chez les enfants sur l'incidence de la tuberculose. Le baloxavir, un nouvel antiviral contre la grippe, a été approuvé par Swissmedic. Et enfin, des nouvelles recommandations américaines sur le monitoring thérapeutique de la vancomycine et sur le dépistage universel de l'hépatite C ont été publiées.
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Infectología/tendencias , Antibacterianos/administración & dosificación , Antivirales/uso terapéutico , Proteína C-Reactiva/análisis , COVID-19 , Niño , Enfermedades Transmisibles/tratamiento farmacológico , Humanos , Gripe Humana/tratamiento farmacológico , Pandemias , Tuberculosis/prevención & control , Vitamina D/administración & dosificaciónRESUMEN
Xpert MTB/RIF assay, a real-time PCR assay designed to detect Mycobacterium tuberculosis, has proven sensitive and specific when performed on respiratory samples in a high prevalence setting. However, it was suggested as less accurate in a low-incidence environment. We evaluated the accuracy of the Xpert for the diagnosis of tuberculosis (TB) on pulmonary and extrapulmonary samples in Geneva (Switzerland), where the prevalence of active TB is very low. From March 2009 to February 2013, the Xpert was performed on clinical samples. All specimens were also processed using auramine, AFB staining, and mycobacterial culture with both solid and liquid media. The accuracy of both microscopy and Xpert was determined retrospectively using cultures as the reference method. A total of 732 clinical specimens were processed with the Xpert. The Xpert had a high specificity (97.5%; 95% confidence interval (CI), 95.8-98.5%) and revealed much more sensitive (82.7%; 95% CI, 74.1-89.0%) than microscopy (55.5%; 95% CI, 45.7-64.8%) for the diagnosis of TB, with a high negative predictive value (96.8%; 95% CI, 95.0-98.0%). The advantage of PCR over microscopy was even more pronounced for extrapulmonary specimens (sensitivity of 70% (95% CI, 50.4-84.6%) compared with 23.3% (95% CI, 10.6-42.7%)). Despite the low prevalence of TB in Switzerland, results performance for respiratory samples was similar to that reported in high prevalence countries. The high negative predictive value is clinically helpful in our setting, where pulmonary TB needs to be reasonably ruled out. When considering extrapulmonary samples, microscopy performed poorly compared with Xpert. This study shows that the Xpert remains accurate and useful in a low-incidence setting.
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Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Tuberculosis Pulmonar/diagnóstico , Líquido del Lavado Bronquioalveolar/microbiología , Pruebas Diagnósticas de Rutina , Humanos , Incidencia , Mycobacterium tuberculosis/genética , Prevalencia , Sensibilidad y Especificidad , Suiza , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
Despite a benign appearance, any foot injury occurring in a patient with diabetes requires multidisciplinary management if dreaded complications such as amputation are to be avoided. From a pathophysiological point of view, foot ulcer generally results from the combination of lower extremity neuropathy, mechanical overload, immunopathy and vascular insufficiency. The treatment associates in all cases an offloading and one or more debridements. Depending on the grade of the ulcer, adjuvant treatments, such as antibiotic therapy, revascularization, and hyperbaric oxygen therapy may be indicated.
En dépit d'un aspect bénin, toute plaie au niveau d'un pied survenant chez un patient avec un diabète nécessite une prise en charge multidisciplinaire si l'on veut éviter des complications redoutables comme une amputation. D'un point de vue physiopathologique, l'ulcère du pied résulte généralement de la combinaison entre une neuropathie des membres inférieurs, une surcharge mécanique, une immunopathie et une insuffisance vasculaire. La prise en charge associe dans tous les cas une décharge et un ou plusieurs débridements. Selon la gravité de l'ulcère, des traitements adjuvants sont indiqués, tels qu'une antibiothérapie, une revascularisation et une oxygénothérapie hyperbare.
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Complicaciones de la Diabetes , Pie Diabético/complicaciones , Pie Diabético/terapia , Amputación Quirúrgica , Humanos , Oxigenoterapia Hiperbárica , Procedimientos Quirúrgicos VascularesRESUMEN
Skin infections are a frequent cause of consultation, yet the diagnosis can be challenging for physicians. Microbiological documentation is rare, and empiric antibiotic regimens should cover the most commonly identified bacteria, i.e. streptococci Staphylococcus aureus. Other pathogens should be considered in case of immunosuppression or certain exposures. Necrotizing fasciitis (NF) is a severe but rare infection. Early surgical management in parallel with antibiotics is the cornerstone of treatment. Despite the high incidence of these infections, little progress has been made in their management and some areas of uncertainty exist, especially regarding the optimal duration of treatment, the prevention of recurrences and the use of polyclonal immunoglobulins for NF. This article reviews the main aspects of diagnosis and treatment of these infections.
Les infections de la peau sont fréquentes mais leur diagnostic peut représenter un défi pour le clinicien. La documentation de l'étiologie microbiologique est rare et le traitement empirique doit couvrir les germes fréquents, notamment Streptococcus spp. et Staphylococcus aureus. Des bactéries inhabituelles peuvent être retrouvées lors d'immunosuppression ou exposition spéciale. La fasciite nécrosante (FN) est une infection sévère mais rare, dont le traitement repose sur la chirurgie rapide et l'antibiothérapie. Malgré leur fréquence, peu de progrès ont été réalisés dans la prise en charge de ces infections et des incertitudes persistent par rapport à la durée optimale de traitement, la prophylaxie pour les récurrences ou l'utilité des immunoglobulines polyclonales intraveineuses pour la FN. Cet article aborde les aspects diagnostiques et thérapeutiques de ces infections.
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Enfermedades Cutáneas Infecciosas/diagnóstico , Enfermedades Cutáneas Infecciosas/terapia , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/terapia , Antibacterianos/uso terapéutico , Fascitis Necrotizante/tratamiento farmacológico , Fascitis Necrotizante/microbiología , Humanos , Inmunoglobulinas/uso terapéutico , Enfermedades Cutáneas Infecciosas/microbiología , Enfermedades Cutáneas Infecciosas/cirugía , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/cirugía , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacosRESUMEN
Animal and human bites are a common cause of admission to the emergency room and the infections are common, although they are often trivialized. Complications can range from simple cellulitis to septic shock especially in asplenic patients with Capnoyctophaga canimorsus infection. Other less common infections are possible such as rat-bite fever, leptospirosis, tularemia, and evaluation of post-exposure prophylaxis (anti-tetanus, anti-rabies, HIV, HBV) is essential. Antibiotic prophylaxis remains controversial but is recommended for certain groups of patients and must cover common bite pathogens.
Les morsures animales et humaines sont un motif fréquent d'admission aux urgences et leur infection est fréquente, alors qu'elles sont souvent banalisées. Les complications peuvent aller d'une simple dermohypodermite au choc septique, notamment chez les patients aspléniques lors d'infection à Capnocytophaga canimorsus. D'autres infections moins communes sont possibles comme la «â rat-bite feverâ ¼, la leptospirose, la tularémie, et l'évaluation des prophylaxies postexpositionnelles (antitétanique, antirabiqueâ ; VIH, VHB en cas de morsures humaines) est primordiale. L'antibioprophylaxie reste controversée, mais est recommandée pour certains groupes de patients, et se doit de couvrir les germes retrouvés fréquemment lors de morsures.
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Mordeduras y Picaduras , Mordeduras Humanas , Rabia , Tétanos , Animales , Humanos , Profilaxis Posexposición , Rabia/prevención & control , Tétanos/prevención & controlRESUMEN
Total hip and knee arthroplasties are associated with a risk of infection ranging between 0.5 and 2 %, and pose a difficult diagnosis and prolonged treatment for the infected patient. The treatment must be multidisciplinary, consisting of orthopaedic surgeons, infectious diseases specialists, and radiologists, aiming at an accurate diagnosis and appropriate decisions, adapted to the clinical situation of the patient. We review the latest consensus on the diagnosis and management of these infections.
Les arthroplasties prothétiques de la hanche (PTH) et du genou (PTG) sont associées à un taux d'infection compris entre 0,5 et 2 %. En dépit d'un risque faible, cette complication est redoutable, car elle peut être difficile à diagnostiquer, et son traitement implique une ou plusieurs révisions chirurgicales associées à une antibiothérapie prolongée. La prise en charge des patients nécessite une collaboration entre chirurgiens orthopédistes, infectiologues et radiologues, afin de garantir le traitement le plus approprié. Dans ce contexte, cet article propose une synthèse des méthodes récentes de diagnostic et de traitement médico-chirurgical de l'infection périprothétique.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Artroplastia de Reemplazo de Cadera/tendencias , Artroplastia de Reemplazo de Rodilla/tendencias , HumanosRESUMEN
Background: Daptomycin is increasingly used in the treatment of bone and joint infections (BJIs) and may be responsible for daptomycin-induced eosinophilic pneumonia (DIEP), a potentially severe adverse drug reaction. The aim of this study was to describe DIEP in patients treated at a referral center for the management of BJI, and to revisit current definitions of this disease. Methods: Patients treated from 1 January 2012 to 31 March 2021 were included in a prospective cohort (NCT02817711), in which all potential serious adverse events are prospectively recorded. Patients diagnosed with DIEP were retrospectively analyzed using different definitions. Results: In a total of 4664 patients included in the cohort during the study period, 1021 patients (21.9%) received daptomycin, of whom 17 (1.7%) were diagnosed with DIEP. Most patients were male (n = 11 [64.7%]), and periprosthetic joint infection was the commonest BJI (n = 12 [70.6%]). Only 1 patient had bronchoalveolar lavage (BAL) eosinophil count ≥25%, while most patients had peripheral blood eosinophilia (n = 15 [88.2%]). Chest computed tomography (CT) was compatible with eosinophilic pneumonia in 13 of 14 cases (92.9%). All patients recovered upon discontinuation of daptomycin. Using the different definitions available, only a minority of cases fulfilled existing criteria for DIEP. We propose a new algorithm that includes specific CT scan signs, and systemic instead of BAL eosinophilia. Conclusions: DIEP is a rare event that requires prompt discontinuation of the causative antibiotic. Current criteria to diagnose definite DIEP are too restrictive and not easily applicable in clinical practice. A new algorithm is proposed here (Lyon algorithm) to facilitate the early identification of DIEP.
RESUMEN
Bone and joint infections are difficult to treat, and increasing antibiotic resistance has only made them more challenging. This has led to renewed interest in phage therapy (PT). The aim of this systematic review was to determine success rate, current treatment modalities and safety of PT in bone and joint infections.A systematic search of PubMed, EMBASE and Cochrane databases as well as the journal PHAGE for literature published between January 2000 and April 2021 was conducted according to PRISMA guidelines to identify all human studies assessing bacteriophages as therapy for bone and joint infections. All study designs and patient populations were eligible. The review's primary outcome was success rate.Twenty records describing a total of 51 patients and 52 treatment episodes were included. No randomized controlled studies were identified. The overall success rate was 71% (n = 37/52). Topical administration alone was the most frequent administration route (85%, n = 44/52). Antibiotics were administered concomitantly with PT in the majority of treatments (79%, n = 41/52), and surgery was performed for 87% (n = 45/52) of treatment episodes. Four minor adverse events related to PT were reported, representing 8% (n = 4/52) of treatment episodes.PT for bone and joint infections has not been evaluated in any randomized controlled clinical study, and current administration modalities are highly variable between case reports and case series. While publications included here show potential benefit and few adverse effects, clinical trials are warranted to assess the efficacy of PT for bone and joint infections and determine optimal treatment modalities. Cite this article: EFORT Open Rev 2021;6:1148-1156. DOI: 10.1302/2058-5241.6.210073.
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A prospective cohort study was conducted to evaluate long-term safety of tedizolid as suppressive antimicrobial treatment in patients with implant-associated bone and joint infection caused by multidrug-resistant gram-positive pathogens. Seventeen patients received tedizolid with a median duration of treatment of 6 months. No patients developed a serious adverse event.
RESUMEN
Introduction: Costs related to bone and joint infection (BJI) management are increasing worldwide, particularly due to the growing use of off-label antibiotics that are expensive treatments (ETs), in conjunction with increasing incidence of multi-drug-resistant pathogens. The aim of this study was to evaluate the whole costs related to these treatments during the patient route, including those attributed to the rehabilitation centre (RC) stay in one regional referral centre in France. The total annual cost of ETs for managing complex BJIs in France was then estimated. Material and methods: A prospective monocentric observational study was conducted from 2014 to 2019 in a referral centre for BJI management (CRIOAc - Centre de Référence des Infections OstéoArticulaires complexes). Costs related to expensive treatments ("old" ETs, i.e. ceftaroline, ertapenem, daptomycin, colistin, tigecycline, and linezolid and "new" ETs, defined as those used since 2017, including ceftobiprole, ceftazidime-avibactam, ceftolozane-tazobactam, tedizolid, and dalbavancin) were prospectively recorded. In all cases, the use of these ETs was validated during multidisciplinary meetings. Results: Of the 3219 patients treated, 1682 (52.3â¯%) received at least one ET, and 21.5â¯% of patients who received ET were managed in RCs. The overall cost of ETs remained high but stable (EURâ¯1â¯033â¯610 in 2014; EURâ¯1â¯129â¯862 in 2019), despite the increase of patients treated by ETs (from 182 in 2014 to 512 in 2019) and in the cumulative days of treatment (9739 to 16â¯191â¯d). Daptomycin was the most prescribed molecule (46.2â¯% of patients in 2014 and 56.8â¯% in 2019, with 53.8â¯% overall), but its cost has decreased since this molecule was genericized in 2018; the same trend was observed for linezolid. Thus, costs for old ETs decreased overall, from EURâ¯1â¯033â¯610 in 2014 to EURâ¯604â¯997 in 2019, but global costs remained stable due to new ET utilization accounting for 46.5â¯% of overall costs in 2019. Tedizolid, used as suppressive antimicrobial therapy, represented 77.5â¯% of total new ET costs. In our centre, dalbavancin was never used. The cost paid by RCs for ETs and the duration of ET remained stable overall between 2016 and 2019. Conclusions: A high consumption of off-label ET is required to treat patients with BJIs in a CRIOAc, and the consequence is a high cost of antimicrobial therapy for these patients, estimated to be almost EURâ¯10â¯million in France annually. Costs associated with ET utilization remained stable over the years. On the one hand, the introduction of the generic drugs of daptomycin and linezolid has significantly decreased the share of old ETs, but, on the other hand, the need for new ETs to treat infections associated with more resistant pathogens has not led to decrease in the overall costs. A drastic price reduction of generic drugs is essential to limit the costs associated with more complex BJIs.
RESUMEN
Primary and revision arthroplasties are increasing worldwide, as are periprosthetic joint infections (PJI). The management of PJI requires surgery, the strategy of which is dictated by the acute or chronic nature of the infection, with an exchange of the implant in the event of a chronic PJI or in the case of recurrence with the same pathogen. We report the case of a 63-year-old man with two episodes of Streptococcus dysgalactiae subsp. equisimilis PJI within 9 months. Based on clinical suspicion of an haematogenous PJI, the patient was treated by DAIR (debridement, antibiotics, implant retention), while genomic sequencing revealed two different strains, confirming our hypothesis that no additional surgery was needed. Hence, we report a case where genomic analysis was decisive for the decision of the best therapeutic strategy.