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Background: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration. Methods: Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics. Results: Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10-3). A normal CRP-value at 1 month was protective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and tolerance compared to the intravenous route. Conclusions: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible subcutaneous administration in outpatients. The loading dose might be increase to 9-12 mg/kg to quickly reach the therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the subcutaneous route. [ABSTRACT FROM AUTHOR]

Background: The experience of clinicians in charge of the in-hospital management of peritonsillar abscesses supports the association between severe forms and anti-inflammatory drug (AID) consumption. However, this observation is based on a limited number of clinical studies. Our objective was to assess the prevalence and impact of AID consumption in patients with peritonsillar abscesses.Methods: All patients referred to the ear, nose and throat surgery department for a peritonsillar abscess were included in a retrospective cohort study (2012-2014).Results: Among the 216 included patients (male, 55 %; median age, 32 years [IQR, 26-40]), 127 had received AID (59 %), including corticosteroids (n = 67, 31 %) and/or non-steroidal AIDs (NSAIDs, n = 76, 35 %). 199 patients (92 %) benefit from a puncture and 5 (2 %) from a surgery under general anesthesia, associated with ceftriaxone/metronidazole (51 %) or amoxicillin/clavulanic acid (46 %). An iterative surgical procedure was required in 93 cases (43 %), including 19 % under general anesthesia. Bacteriological analysis (79 %) mainly disclosed streptococci (66 %) of A (18 %) and/or milleri (33 %) groups. The prevalence of anaerobes was higher in patients using AIDs (46 % versus 29 %, p = 0.034), regardless of prior antibiotic therapy. 65 patients benefited from a CT-scan; AID consumption was associated with larger abscesses (6.8 [IQR, 3.7-12.7] versus 2.9 [IQR, 0.9-7.8] cm(3); p = 0.005). AID consumption was not a risk factor of iterative surgical procedure.Conclusions: In comparison to the prescribing habits in uncomplicated upper respiratory tract infection, the high prevalence of AID consumption in patients with peritonsillar suppuration suggests a role of AIDs in promoting these complications. [ABSTRACT FROM AUTHOR]

Background: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients.Methods: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves.Results: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE.Conclusions: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded. [ABSTRACT FROM AUTHOR]

Introduction: Patients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA.Methods: This matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed.Results: Fifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p < 0.001 for all variables). PIPA was a strong independent risk factor for mortality in the ICU (odds ratio 7.44, 95 % confidence interval 2.93-18.93, p < 0.001) before vasopressor therapy, renal replacement therapy, and duration of mechanical ventilation. Before ICU admission, the use of corticosteroids and antibiotics significantly increased the risk of PIPA (p = 0.004 and p < 0.001, respectively). No significant difference in bacterial etiologic agents responsible for colonization and/or infection was found between the groups. Antifungal treatment was started in 64 % of PIPA cases, with a poor impact on the overall outcome.Conclusions: PIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 50-year-old woman who was diagnosed with nontuberculous mycobacteria (NTM) infection and treated due to the detection of the interferon-y (IFN-y) autoantibodies. Topics discussed include her pathological examination that revealed a nonnecrotizing granuloma, the continued use of the antimycobacterial treatment and changed to azithromycin suppressive therapy and a reviewed literature for the other cases of IFN-y antibody-related NTM infection.

Objective: Pneumonia is a frequent cause of acute respiratory distress syndrome (ARDS), and Pseudomonas aeruginosa is a leading pathogen in nosocomial pneumonia. The management of ARDS remains a major problem, and only a limited number of options can improve the oxygenation. Inhaled nitric oxide (iNO) has been widely used, although this molecule is a free radical potentially harmful through the generation of toxic radical derivatives. The goal of our study was to assess the consequences of iNO (10 ppm) in a rat model of P. aeruginosa-induced lung injury.Design: The animals were exposed for 24 h to iNO after instillation of the pathogen. Distal alveolar fluid clearance (DAFC) and epithelial and endothelial permeability were measured with a double flux of radio-labeled albumin.Results: DAFC and epithelial permeability were increased in pneumonia but not influenced by iNO. In contrast, endothelial permeability was statistically significantly higher in the pneumonic animals exposed to iNO than in the pneumonic group without iNO (0.24+/-0.03 vs 0.47+/-0.1, p<0.05). This increase was not related to the production of nitrate/nitrite, nor to the increase of the inflammatory response evaluated by cytokine levels in the bronchoalveolar lavage fluid (TNF-alpha, IL-6, IL-10). The alveolar recruitment of polymorphonuclear neutrophils was comparable in the pneumonic group exposed to iNO and the pneumonic group without iNO.Conclusion: iNO increases the endothelial permeability in P. aeruginosa pneumonia. The mechanism is not related to the production of nitrate/nitrite or to a greater inflammatory response. [ABSTRACT FROM AUTHOR]

Introduction The incomplete immune recovery upon effective long-term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients []. Immune cellular activation, Tregs or very low-level viraemia has been alternatively suspected, but never investigated simultaneously []. Materials and Methods We performed a cross-sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm3, mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm3 were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one-step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA-, and CD4+CD25+FoxP3+CD45RA-HLADR+phenotypes as recently described []. Activated T cells were identified using (i) elevated HLA-DR expression for CD4+T cells, and (ii) increased expressions of HLA-DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low-level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR. Results Thirty-nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low-level viraemia were found to be associated with iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively). Conclusions We present here the largest study investigating simultaneously immune response to long-term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low-level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients. [ABSTRACT FROM AUTHOR]

After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus–associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs were observed independently of cidofovir dose or administration route. Cidofovir is an effective therapy for BKV-HC but requires very precise renal function management to avoid toxicity. Cidofovir treatment modalities (high dose, intravesical instillation, or low dose [≤1 mg/kg]) needs to be investigated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

The article analyzes the virulence of 56 nonclonal Pseudomonas aeruginosa strains taken from patients with ventilator-acquired pneumonia in an effort to determine which among these factors is the most important. The authors report that they used a murine model of pneumonia to avoid human immune response variation. They reveal that their experiment showed that type three secretion system and elastase are the most important virulence factors among strains of Pseudomonas aeruginosa.