Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with a debridement, antibiotics and implant retention (DAIR): a retrospective multicenter study in France.

Introduction: In patients undergoing a « debridement, antibiotics, and implant retention ¼ (DAIR) procedure for acute staphylococcal prosthetic joint infection (PJI), post-operative treatment with rifampin has been associated with a higher probability of success.(1,2) However, it is not known whether it is the total dose, delay of introduction or length of therapy with rifampin that is most strongly associated with the observed improved outcomes. Methods: A multicentric, retrospective cohort study of patients with acute staphylococcal hip and knee PJI treated with DAIR between January 2011 and December 2016. Failure of the DAIR procedure was defined as persistent infection, need for another surgery or death. We fitted logistic and Cox regression multivariate models to identify predictors of DAIR failure. We compared Kaplan-Meier estimates of failure probability in different levels of the 3 variables of interest - total dose, delay of introduction or length of therapy with rifampin - with the log-rank test. Results: 79 patients included (median age 71 years [63.5-81]; 55 men [70%]), including 54 (68%) DAIR successes and 25 (32%) DAIR failures. Patients observed for a median of 435 days [IQR 107.5-834]. Median ASA score significantly lower in DAIR successes than in DAIR failures (2 vs. 3, respectively p = 0.011). Bacterial cultures revealed 65 (82.3%) S. aureus and 16 (20.3%) coagulase negative staphylococci, with 2 patients being infected simultaneously with S. aureus and CNS. Among S. aureus isolates, 7 (10.8%) resistant to methicillin; 2 (3.1 %) resistant to rifampin. Median duration of antimicrobial therapy was 85 days [IQR 28.5-97.8]. Fifty-eight patients (73.4%) received rifampin at a median dose of 14.6 mg/kg/day |IQR 13-16.7], started at a median delay of 8.5 days [IQR, 4-7.5] after debridement surgery. Twenty-one patients (26.6%) developed a drug-related adverse event, leading to rifampin interruption in 6 of them (7.6% of total cohort). Determinants of DAIR failure were rifampin use (HR 0.17, IC [0.06, 0.45], p-value <0.001), association of rifampin with a fluoroquinolone (HR 0.19, IC [0.07, 0.53], p-value = 0.002) and duration of rifampin therapy (HR 0.97, IC [0.95, 1], p-value = 0.022). We did not observe a significant difference between DAIR successes and failures in rifampin use, dose and delay of introduction. In a multivariate Cox model, only duration of rifampin therapy was significantly associated with DAIR failure. Kaplan Meier estimate of DAIR failure probability was significantly higher in patients receiving less than 14 days of rifampin in comparison with those receiving more than 14 days of rifampin (p = 0.0017). Conclusion: Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with DAIR.

Cerebral empyema and abscesses due to Cutibacterium acnes.

INTRODUCTION: Cutibacterium acnes is a commensal bacterium of the skin, frequently reported in prosthetic shoulder or spinal implant infections, but rarely in cranial and intracranial infections. METHODS: We retrospectively reviewed patients with intracranial samples positive to Cutibacterium acnes managed in the neurosurgical units of our hospital of Lyon, France, between 2008-2016. RESULTS: We included 29 patients, of whom 23 had empyema (with or without abscess), 17 had cranial osteomyelitis, and six only had abscess. Prior neurosurgery was reported in 28 patients, and the remaining patient had four spontaneous abscesses. Twelve patients had polymicrobial infections, including methicillin-susceptible Staphylococcus in 11 cases. The clinical diagnosis was difficult because of indolent and delayed symptoms: a CT scan or MRI was required. Thirteen patients (52%) had material at the infection site. All patients with bone flap implant or bones from biological banks had a bone flap-associated infection. Drainage was surgically performed in 25 cases or by CT scan-guided aspiration in four cases. All patients received an adapted antibiotic therapy (from three weeks to six months). The outcome was favorable in 28 patients. Three patients relapsed during the antibiotic therapy, requiring further surgery. CONCLUSION: Cutibacterium acnes can be responsible for postoperative empyema and cerebral abscesses, with particular indolent forms, which make their diagnosis difficult. They are often polymicrobial and associated with bone flap osteomyelitis. Their outcome is favorable after drainage and adapted antibiotic therapy.

Pubic osteomyelitis: Epidemiology and factors associated with treatment failure.

OBJECTIVE: To describe the epidemiology of pubic osteomyelitis (PO) and to look for factors associated with treatment failure. METHOD: Retrospective study describing PO according to outcome: success or failure of initial management. Factors associated with failure determined by univariate Cox analysis. Kaplan-Meier curve compared between groups by log-rank test. RESULTS: Twenty-five patients were included over a 13-year period; 24% of PO had blood-borne infection. Failure (44%) was always observed in chronic postoperative presentations (76%). Fistula (32%) was only observed in postoperative presentations and was significantly associated with failure (HR 5.1; P=0.011). Other risk factors were pelvic malignant tumor history, abscess, infection due to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and polymicrobial infection. CONCLUSION: PO is most often a chronic postoperative polymicrobial infection in patients with comorbidities at high risk of relapse. Studies in larger cohorts could assess the efficacy of more aggressive surgical strategies in patients at high risk of failure.

A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area.

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.

A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.

Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

Combined medico-surgical strategy for invasive sino-orbito-cerebral breakthrough fungal infection with Hormographiella aspergillata in an acute leukaemia patient.

Hormographiella aspergillata is a rare causative agent of invasive filamentous breakthrough infection, mostly arising after echinocandin exposure. We report a neutropenic patient who developed a severe sino-orbito-cerebral H. aspergillata infection while receiving empirical caspofungin, successfully controlled by an aggressive strategy associating surgical debridement and combined high-dose regimen of antifungal drugs.

Management of emerging multidrug-resistant tuberculosis in a low-prevalence setting.

Multidrug-resistant (MDR) tuberculosis (TB) is an emerging concern in communities with a low TB prevalence and a high standard of public health. Twenty-three consecutive adult MDR TB patients who were treated at our institution between 2007 and 2013 were reviewed for demographic characteristics and anti-TB treatment management, which included surgical procedures and long-term patient follow-up. This report of our experience emphasizes the need for an individualized approach as MDR TB brings mycobacterial disease management to a higher level of expertise, and for a balance to be found between international current guidelines and patient-tailored treatment strategies.

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

[Infectious thoracic aortic aneurysms: 7 cases and literature review]. / Anévrismes infectieux de l'aorte thoracique : présentation de 7 cas et revue de la littérature.

PURPOSE: Infectious aortic aneurysms are rare conditions, being responsible of 2% of aortic aneurysms. Most published results are surgical case series concerning infected abdominal aorta. In this retrospective study, we assessed clinical features and outcome of patients presenting infectious thoracic aortic aneurysms. PATIENTS AND METHODS: Diagnosis was based upon a combination of imaging evidence for thoracic aorta aneurysm and evidence for an infective aetiology including a culture of a causative pathogen, or a favourable outcome with anti-infective therapy. Retrospective case series. RESULTS: Six men and one woman were included, with a mean age of 66 years. All the patient presented at least one cardiovascular risk factor or atherosclerosis localisation. Fever (71%) and chest pain (42%) were the most common clinical presenting manifestations. The causative pathogens were: Staphylococcus aureus (N=1), Salmonella enteritidis (N=3) and Candida albicans (N=1). The contrast-enhanced computed-tomography disclosed an aneurysm whose diameter reached more than 50 mm (N=5), that increased rapidly in size (N=5), or presented an inflammatory aspect of the aortic wall (N=4). Management was both medical and interventional: surgery (N=3) or endoluminal repair (N=4). Outcome was favourable in six patients; one patient died from aneurysm-related complications. CONCLUSION: Clinical manifestations revealing an infectious thoracic aneurysm are variable. Diagnosis should be considered in patients presenting a rapidly-growing aneurysm, especially in the presence of elevated acute phase reactants. Endoluminal repair constitutes a treatment option. The role of FDG-PET for diagnosis and follow-up remains to be defined.

[Staphylococcus aureus broncho-pulmonary infections]. / Infections broncho-pulmonaires à Staphylococcus aureus.

Staphylococcus aureus accounts for 2-5% of the etiologies of community-acquired pneumonia. These infections occur mainly in elderly patients with comorbidity, after a respiratory viral infection. S. aureus could also be responsible for necrotizing pneumonia, which occurs in young subjects, also after flu. Necrotizing pneumonia are associated with the production of a particular staphylococcal toxin called Panton-Valentine leukocidin, responsible for pulmonary focal necrosis, occurrence haemoptysis, leucopenia, and death. In Europe, these strains are still predominantly sensitive to anti-staphylococcal penicillin, which must be used at high dosage intravenously in combination with an antibiotic that reduces toxin production such as clindamycin, and intravenous immunoglobulin in severe cases. The mortality rate is estimated at 50%. In addition, S. aureus is one of the pathogens involved in early respiratory infections in cystic fibrosis patients, in whom methicillin resistance plays an important prognostic role. However, the involvement of S. aureus in COPD exacerbations is rare. Finally, S. aureus represents 20 to 30% of cases of hospital-acquired pneumonia, including ventilator-associated pneumonia. In these cases, methicillin-resistance is common and requires the use of glycopeptides or linezolid. The place of new anti-staphylococcal antibiotics such as new generation cephalosporins or tigecyclin remains to be defined.

The follow-up of patients with postoperative infection of the spine.

The follow-up of patients with postoperative infection of the spine required a multidisciplinary teamwork under the guidance of the spine surgeon and the infectious disease (ID) specialist. During follow-up, the spine surgeon has to ensure the absence of neurological, mechanical and implant-related complications using clinical parameters and different imaging modalities. The ID physician has to give particular attention to antimicrobial efficacy and toxicity, especially during the first weeks when patients necessitate high-dose intravenous treatment.

The challenge of infection prevention in spine surgery: an update.

Prevention is particularly challenging in implant-associated bone and joint infection, as it could reduce the following: (1) the risk of infection in particular patient populations; (2) the risk associated with particular surgical procedures; and/or (3) the risk of infection with particular pathogen that has the ability to produce biofilm, such as staphylococci. As a consequence, it is crucial to identify: (1) host-related risk factors that may be involved in the acquisition of infection; (2) surgical procedures particularly at risk of infection; and (3) the different ways to target the most frequent pathogens involved in implant-associated spinal infection. In this article, we reviewed the data of the literature on the infection prevention in spine surgery.

Vaccination in adults with auto-immune disease and/or drug related immune deficiency: results of the GEVACCIM Delphi survey.

INTRODUCTION: There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. METHODS: A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts' opinion and level of agreement were evaluated. RESULTS: The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3-6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was "very good" for eleven, and "good" for the remaining three. CONCLUSION: Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.

Disseminated nontuberculous infections with Mycobacterium genavense during sarcoidosis.

Sarcoidosis is a chronic disease characterised by the development and accumulation of granulomas in multiple organs. We report two observations of disseminated Mycobacterium genavense infection in patients with proven sarcoidosis. High fever and abdominal pain appeared at 8 and 18 months following the initiation of immunosuppressive therapy. Abdominal computed tomography scans of the patients showed diffuse mesenteric lymphadenitis and splenomegaly. The diagnosis was obtained on bone marrow specimens for both patients with numerous acid-fast bacteria at direct examination and positive specific mycobacterial identification by nucleic acid amplification test. Despite prompt antimycobacterial therapy, occurrence of complications (peritonitis post-splenectomy surgery and lung carcinoma) resulted in a fatal outcome for both patients. These cases highlight that opportunistic infections like M. genavense or other nontuberculous mycobacterial infections should be considered for long-standing immunocompromised patients with sarcoidosis.

A recent increase in AIDS at Lyon University Hospitals: patient characteristics and comparisons with previous years.

BACKGROUND: A 36% increase in the incidence of AIDS was observed in 2002/2003 compared with 2000/2001 at Lyon University Hospitals. OBJECTIVES: We compared the characteristics of these patients with the characteristics of those diagnosed previously with AIDS. METHODS: Data for all patients with AIDS diagnosed at Lyon University Hospitals were analyzed. The data were collected prospectively. Multiple logistic regression was used for analysis. RESULTS: The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1985-1989 period were: homosexual exposure [odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.8]; heterosexual exposure in an endemic area (OR 22.5; 95% CI 6.8-74.8), compared with other exposure to HIV; lymphoma as initial AIDS event (OR 10.3; 95% CI 2.7-39.1) compared with Pneumocystis carinii pneumonia; and age at first AIDS event aged 34-38 years (OR 2.5; 95% CI 1.0-6.4), aged 39-46 years (OR 5.1; 95% CI 2.2-11.8), and aged 47-84 years (OR 10.6; 95% CI 4.5-25.1) compared with aged <30 years. The variables independently associated with an AIDS diagnosis in 2002/2003 compared with the 1997/2001 period were age at first AIDS event aged 34-38 years (OR 0.4; 95% CI 0.2-0.9) compared with aged <30 years. CONCLUSION: Recently diagnosed AIDS patients differed from those diagnosed previously, showing an epidemic switch in different populations. The characteristics of the AIDS population in 2002/2003 might reflect public health messages disseminated around 10 years ago or more for the prevention of HIV transmission. Anticipation of populations affected by the AIDS epidemic is difficult.

Characteristics of patients diagnosed with AIDS shortly after first detection of HIV antibodies in Lyon University hospitals from 1985 to 2001.

A diagnosis of AIDS shortly after the detection of HIV antibodies suggests a long-lasting course of the disease without care. The factors associated with a short delay between the initial HIV-1-positive test and the first AIDS-defining event were identified in 1901 patients from 1985 to 2001 in Lyon University hospitals. A total of 576 individuals (30.3%) had an interval of /=60 years (OR 4.5; 95% CI 2.5-8.1), compared to those<30 years old; heterosexuality (OR 2.4; 95% CI 1.6-3.4); injection drug use (OR 2.1; 95% CI 1.5-2.7); and other exposures (OR 2.4; 95% CI 1.6-3.4), compared to homosexual exposure; two opportunistic infections at AIDS (OR 1.8; 95% CI 1.4-2.4) compared to one; and Pneumocystis carinii pneumonia as initial AIDS event (OR 2.6; 95% CI 1.8-3.7), compared to Kaposi's sarcoma. These results provide opportunities to refocus local public health interventions to reduce delayed access to care.

The AIDS epidemic in Lyon: patient characteristics and defining illnesses between 1985 and 2000.

OBJECTIVES: To define the characteristics of 1899 patients diagnosed with AIDS at Lyon University Hospitals (LUH) across four time periods corresponding to different antiretroviral eras, and to analyse the evolution of specific AIDS-defining illnesses (ADIs) with time. METHODS: All AIDS patients at LUH between 1 January 1985 and 31 December 2000 were included in the study. The data were compared using the chi(2) test and one-way analysis of variance. RESULTS: The absolute number of new AIDS cases increased by 30.3% between 1985 and 1995 but decreased by 26.5% between 1996 and 2000. The proportion of women with AIDS increased significantly (P<0.001) and mean age at diagnosis also increased significantly over time (P<0.001). The proportion of infection through heterosexual contact increased dramatically, while that through homo/bisexual intercourse or injection drug use (IDU) decreased significantly (P<0.001). The absolute number of ADIs declined with the introduction of highly active antiretroviral therapies (HAART) (P<10(-6)). Pneumocystis carinii pneumonia remained the leading ADI in 1996-2000 (23.3%). A significant increase in the proportion of non-Hodgkin's lymphoma (NHL) was observed over time (P<10(-5)) but the number of new NHL cases decreased during HIV infection after 1996. CONCLUSIONS: The decline in the incidence of AIDS with the advent of HAART was confirmed in our hospital cohort. The gradual increase in the proportion of NHL among ADIs underscores the long latency period between infection with HIV and the achievement of an effect of HAART on HIV-associated lymphomagenesis.

Prevalence of tobacco use among the adult Lebanese population.

To determine the prevalence of smoking in Lebanon, 727 individuals aged > or = 19 years were randomly selected for study using Emile Roux and Fagerstrom questionnaires. Smokers were defined as those answering "yes" to the question, "Do you currently smoke?" A Fagerstrom score > or = 6 indicated strong nicotine addiction. The prevalence of smoking was 53.6%. The male/female ratio was 1.23, with 67.0% of smokers categorized as addicted. Failure to quit was related to withdrawal symptoms, mostly irritability (57%) and weight gain (20%). Recommendations are given for combating this high prevalence of tobacco use.

[Evaluation of allergic-type reactions to antibiotics and rapid immunotherapy]. / Bilan des réactions de type allergique aux antibiotiques et accoutumance rapide.

Adverse effects of medications, most notably antimicrobials, are becoming increasingly common and raise difficult challenges in the area of clinical pattern definition (wide variety of symptoms, polypharmacy in many cases), diagnosis, and methodology (need for a rapid diagnosis, frequent obscurity of causative mechanisms, and less than ideal reliability of laboratory techniques). Sixty patients were treated by rush immunotherapy to one or more antimicrobials. The pretreatment evaluation included oriented history taking, skin tests, blood cell counts, IgE assays, and cell activation tests (basophils and lymphocytes). The results of this study confirm the usefulness of skin tests (intradermal, prick, or patch tests), which provided etiological orientation in 54 of the 60 cases. They also provide additional evidence of the lack of reliability of currently available in vitro tests (only 29 of the 60 tests were positive).