Prognosis of prosthetic valve infective endocarditis due to Streptococcus spp., a retrospective multi-site study to assess the impact of antibiotic treatment duration.

PURPOSE: The duration of antibiotic treatment for prosthetic valve endocarditis caused by Streptococcus spp. is largely based on clinical observations and expert opinion rather than empirical studies. Here we assess the impact of a shorter antibiotic duration. OBJECTIVES: To assess the impact of antibiotic treatment duration for streptococcal prosthetic valve endocarditis on 12-month mortality as well as subsequent morbidity resulting in additional cardiac surgical interventions, and rates of relapse and reinfection. METHODS: This retrospective multisite (N= 3) study examines two decades of data on patients with streptococcal prosthetic valve endocarditis receiving either 4 or 6 weeks of antibiotics. Overall mortality, relapse, and reinfection rates were also assessed for the entire available follow-up period. RESULTS: The sample includes 121 patients (median age 72 years, IQR [53; 81]). The majority (74%, 89/121) received a ß-lactam antibiotic combined with aminoglycoside in 74% (89/121, median bi-therapy 5 days [1; 14]). Twenty-eight patients underwent surgery guided by ESC-guidelines (23%). The 12-month mortality rate was not significantly affected by antibiotic duration (4/40, 10% in the 4-week group vs 3/81, 3.7% in the 6-week group, p=0.34) or aminoglycoside usage (p=0.1). Similarly, there were no significant differences between the 2 treatment groups for secondary surgical procedures (7/40 vs 21/81, p=0.42), relapse or reinfection (1/40 vs 2/81 and 2/40 vs 5/81 respectively). CONCLUSIONS: Our study found no increased adverse outcomes associated with a 4-week antibiotic duration compared to the recommended 6-week regimen. Further randomized trials are needed to ascertain the optimal duration of treatment for streptococcal endocarditis.

Nocardiosis in transplant recipients.

Nocardiosis is a rare opportunistic infection caused by Nocardia spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. Despite recent progress regarding Nocardia identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of Nocardia. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.

Aminoglycosides for infective endocarditis: time to say goodbye?

BACKGROUND: Based on experimental studies showing synergism with ß-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their use is associated with a high risk of renal failure, especially in elderly patients. AIMS: The aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients. SOURCES: PubMed database was searched up to July 2019 to identify relevant studies. CONTENTS: Recent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 µg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 µg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance. IMPLICATIONS: In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.

Post-traumatic Curvularia sp. arthritis in an immunocompetent adult.

A 44-year-old woman, victim of a road accident in Mali was diagnosed with left knee arthritis. Joint effusion aspiration and subcutaneous surgical biopsies were positive for a melanized asexual ascomycete. Using microscopy and molecular biology, the fungus was identified as Curvularia sp. In vitro antifungal susceptibility was determined by the EUCAST broth microdilution reference technique and by E-test. The patient was treated with liposomal amphotericin B before posaconazole relay. Mycological samples obtained 10 days after starting the antifungal therapy by liposomal amphotericin B were negative in culture. Curvularia spp. are environmental fungi which can under certain conditions be pathogenic for humans.

[Improvement of antibiotic therapy adequacy with local guidelines and their reassessment through a multidisciplinary action: Prospective study in an Internal Medicine department]. / Amélioration de l'adéquation des antibiothérapies aux recommandations et de leur réévaluation par une action pluridisciplinaire : étude prospective dans un service de médecine interne.

INTRODUCTION: The implementation of antimicrobial stewardship actions is important in the fight against antimicrobial resistance. The objective of our study was to evaluate the impact of a multidisciplinary program on the adequacy of antibiotic prescriptions with local guidelines in terms of indication, molecule, dosage and treatment duration during the 48-72h reassessment in an internal medicine department. METHOD: This was a before/after monocentric, prospective study. All patients hospitalized in the internal medicine department who were treated with antibiotics for at least 48h were included. The intervention had two components: training of residents about antibiotic treatment and development of a multidisciplinary 48-72h reassessment team. Our primary endpoint was the adequacy of prescriptions with local guidelines, assessed by an independent blinded committee. We also measured antibiotic consumptions. RESULTS: One hundred and twelve patients were included. Adequacy with local recommendations increased from 57.1% to 97.8% (P<0.01), including for the duration of treatment. Traceability of reassessment in medical records increased from 65.3 % to 97.8 % (P<0.01). Finally, the part of consumption of antibiotics with high risk of resistance selection decreased during the period "after" (-10.2 %, P<0.01). CONCLUSION: The set-up of a multimodal (association of pedagogic and incentive actions) and multidisciplinary (internist, clinical pharmacist and antimicrobial stewards) action improved the adequacy of antibiotic prescriptions with local guidelines.

[Legionella spp: An update]. / Actualités sur les infections à Legionella.

Legionella-related disease is caused by an intracellular bacteria mainly living in water. Contamination results from inhalation of Legionella sp containing aerosolized water. Main risk factors are tobacco, immunodeficiency, and advanced age. Antigenuria is the cornerstone of the diagnosis. Immunocompromised patients, more commonly infected with non pneumophilaLegionella, present negative antigenuria, and culture and PCR are essential for the diagnosis. Legionnaires' disease may be severe, especially in elderly and/or immunocompromised patients. Mortality rate varies from 10 % in the general population to 50 % in intensive care. Treatment is based on macrolides or fluoroquinolones. Antibiotic resistance is very rare.

Antibiotic susceptibility testing and species identification of Nocardia isolates: a retrospective analysis of data from a French expert laboratory, 2010-2015.

OBJECTIVES: Nocardia, a Gram-positive bacterium, is responsible for rare and severe infections. Accurate microbiological data are essential to guide antibiotic treatment. Our primary objective was to describe species identification and results of antimicrobial susceptibility testing (AST) for Nocardia isolates analysed over a 6-year period. Secondary objectives were to study temporal trends in species distribution and AST results. METHODS: We retrospectively analysed results from Nocardia isolates sent between January 2010 and December 2015 to a French laboratory dedicated to Nocardia (Observatoire Français des Nocardioses). Species identification was obtained by amplification and sequencing of a 600-bp fragment of the 16S rRNA gene (for all isolates) and of hsp65 (when required). AST was performed using disk diffusion. RESULTS: We included 793 Nocardia isolates, mostly from the lungs (53.8%). The most frequent species were Nocardia farcinica (20.2%), Nocardia abscessus complex (19.9%) and Nocardia nova complex (19.5%). The proportion of N. farcinica increased significantly over time from 13% in 2010 to 27.6% in 2014. Linezolid, amikacin, trimethoprim-sulfamethoxazole, minocycline and imipenem were the most frequently identified active antibiotics with, respectively, 0% (0/734), 2.9% (21/730), 5.4% (40/734), 9.4% (69/734) and 19.5% (143/732) of isolates not susceptible. Nocardia farcinica was frequently not susceptible to cefotaxime (118/148, 79.7% of the isolates), but only about 5% of Nocardia cyriacigeorgica and N. abscessus complex isolates were not susceptible to cefotaxime. CONCLUSIONS: In this first epidemiological study of Nocardia isolated from human samples in France, N. farcinica was the species most frequently identified and its prevalence increased over time.

[Hemophagocytic lymphohistiocytosis with granulomatosis and diffuse T-cell infiltration associated with disseminated Nocardiosis and pulmonary infection due to Streptomyces spp]. / Syndrome d'activation macrophagique associé à une granulomatose et une infiltration lymphocytaire T CD4 diffuse révélant une nocardiose disséminée et une infection pulmonaire à Streptomyces spp.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome frequently secondary to infectious disease, especially in immuno-compromised patients. We report a HLH secondary to disseminated nocardiosis and Streptomyces spp pulmonary infection. CASE REPORT: A 69-years-old women had recent subcutaneous nodules of the forearms and loins associated with peripheral neuropathy and pulmonary nodule of the right upper lobe. Cutaneous biopsy revealed granuloma. Cutaneous lesions worsened and the patient developed a HLH with probable cardiac and neurological involvement, associated with cutaneous granulomatosis and diffuse polyclonal lymphocyte proliferation. Nocardia PCR was positive in cutaneous biopsy. Pulmonary samples revealed Streptomyces in culture and Nocardia in PCR. The evolution under antibiotic treatment was favorable. CONCLUSION: Recent diagnosis of HLH without obvious etiology should lead to etiological investigation, including the search for infections with slow-growing bacteria such as Nocardia or Streptomyces spp.

[Respiratory infections caused by slow-growing bacteria: Nocardia, Actinomyces, Rhodococcus]. / Infections respiratoires à bactéries à croissance lente : Nocardia, Actinomyces, Rhodococcus.

INTRODUCTION: Pneumonia caused by slow-growing bacteria is rare but sometimes severe. STATE OF THE ART: These infections share many similarities such as several differential diagnoses, difficulties to identify the pathogen, the importance of involving the microbiologist in the diagnostic investigation and the need for prolonged antibiotic treatment. However, major differences distinguish them: Nocardia and Rhodococcus infect mainly immunocompromised patients while actinomycosis also concerns immunocompetent patients; the severity of nocardioses is related to their hematogenous spread while locoregional extension by contiguity makes the gravity of actinomycosis. PROSPECTIVE: For these diseases, molecular diagnostic tools are essential, either to obtain a species identification and guide treatment in the case of nocardiosis or to confirm the diagnosis from a biological sample. Treatment of these infections is complex due to: (1) the limited data in the literature; (2) the need for prolonged treatment of several months; (3) the management of toxicities and drug interactions for the treatment of Nocardia and Rhodococcus. CONCLUSION: Close cooperation between pneumonologists, infectious disease specialists and microbiologists is essential for the management of these patients.

Neurological deficit secondary to a pre-sacral abscess with epidural extension up to L3: A case report and literature review.

Isolated epidural abscesses are uncommon lesions. Surgical treatment may be difficult due to the extension of these lesions. We present a case of a pelvic abscess spreading along the path of the sciatic nerve to the gluteus muscles and the lumbar canal, causing neurological compression; requiring surgical treatment with three simultaneous approaches.

ESCMID guideline for the diagnosis and treatment of biofilm infections 2014.

Biofilms cause chronic infections in tissues or by developing on the surfaces of medical devices. Biofilm infections persist despite both antibiotic therapy and the innate and adaptive defence mechanisms of the patient. Biofilm infections are characterized by persisting and progressive pathology due primarily to the inflammatory response surrounding the biofilm. For this reason, many biofilm infections may be difficult to diagnose and treat efficiently. It is the purpose of the guideline to bring the current knowledge of biofilm diagnosis and therapy to the attention of clinical microbiologists and infectious disease specialists. Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with chronic lung infection, patients with chronic wound infections) or associated with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers) are the main focus of the guideline, but experience gained from the biofilm infections included in the guideline may inspire similar work in other biofilm infections. The clinical and laboratory parameters for diagnosing biofilm infections are outlined based on the patient's history, signs and symptoms, microscopic findings, culture-based or culture-independent diagnostic techniques and specific immune responses to identify microorganisms known to cause biofilm infections. First, recommendations are given for the collection of appropriate clinical samples, for reliable methods to specifically detect biofilms, for the evaluation of antibody responses to biofilms, for antibiotic susceptibility testing and for improvement of laboratory reports of biofilm findings in the clinical microbiology laboratory. Second, recommendations are given for the prevention and treatment of biofilm infections and for monitoring treatment effectiveness. Finally, suggestions for future research are given to improve diagnosis and treatment of biofilm infections.

Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge.

BACKGROUND AND PURPOSE: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. EXPERIMENTAL APPROACH: We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. KEY RESULTS: In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg(-1), i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1ß levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1ß levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. CONCLUSIONS AND IMPLICATIONS: Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases.

[Totally implanted access port-related infections: features and management]. / Complications infectieuses liées aux chambres implantables: caractéristiques et prise en charge.

Totally implanted access port-related infections are responsible for their own morbidity and mortality. Main risk factors of totally implanted access port-related infections are total parenteral nutrition, young age, difficulties during insertion, poor general status and neutropenia. Recent guidelines defined intravascular catheter-related infections. This relies on a strict clinical and microbiological work-up including simultaneous culture of blood drawn from the catheter and a peripheral vein. The search for local or general complications is mandatory: clinical and possibly echographic assessments are therefore needed. Depending on the context and the type of microorganism, this evaluation may include transoesophageal echocardiography and search for suppurative thrombosis in case of catheter-related bloodstream infection caused by Staphylococcus aureus. Indeed, intravascular complications in this setting are frequent. Catheter removal is mandatory in case of local complication (tunnel infection or port pocket abscess), septic thrombosis, infective endocarditis, osteomyelitis, septic shock or infection related to specific pathogens (S. aureus, Candida spp., Pseudomonas aeruginosa). Otherwise, retention of the catheter might be proposed given results from recent studies including antibiotic lock therapy associated with systemic antibiotic. Future studies must focus on defining more precisely the factors associated with salvage therapy failure including host, pathogens virulence factors and biofilm formation.