Development of a new pneumonia rabbit model for the preclinical evaluation of future anti-infective strategies.

Carbapenem-resistant (CRAB) is an emerging cause of hospital-acquired pneumonia (HAP). Preclinical large models are warranted to predict the efficacy and the resistance profile of anti-infectives and mimic how they will be used in the human treatment of CRAB-HAP. Here we reported on the development of an experimental pneumonia model in immunocompromised rabbits, receiving a 48-h human-simulated regimen.

Efficacy of ceftaroline and rifampin, alone or combined, in a rat model of methicillin-resistant osteomyelitis without implant.

Methicillin-resistant (MRSE) contributes to a high percentage of orthopedic infections, and their treatment represents a huge challenge. The present study aimed to evaluate the efficacy of ceftaroline alone or combined with rifampin in a rat MRSE osteomyelitis model and the bone penetration of ceftaroline. A ceftaroline monotherapy showed a significant bacterial reduction in infected bones after a 7-day period of treatment.

Complex Regulation of Gamma-Hemolysin Expression Impacts Staphylococcus aureus Virulence.

Staphylococcus aureus gamma-hemolysin CB (HlgCB) is a core-genome-encoded pore-forming toxin that targets the C5a receptor, similar to the phage-encoded Panton-Valentine leucocidin (PVL). Absolute quantification by mass spectrometry of HlgCB in 39 community-acquired pneumonia (CAP) isolates showed considerable variations in the HlgC and HlgB yields between isolates. Moreover, although HlgC and HlgB are encoded on a single operon, their levels were dissociated in 10% of the clinical strains studied.

A novel antibacterial compound decreases MRSA biofilm formation without the use of antibiotics in a murine model.

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21.

Adverse Mechanical Ventilation and Pneumococcal Pneumonia Induce Immune and Mitochondrial Dysfunctions Mitigated by Mesenchymal Stem Cells in Rabbits.

Background: Mechanical ventilation for pneumonia may contribute to lung injury due to factors that include mitochondrial dysfunction, and mesenchymal stem cells may attenuate injury. This study hypothesized that mechanical ventilation induces immune and mitochondrial dysfunction, with or without pneumococcal pneumonia, that could be mitigated by mesenchymal stem cells alone or combined with antibiotics.

Methods: Male rabbits underwent protective mechanical ventilation (8 ml/kg tidal volume, 5 cm H2O end-expiratory pressure) or adverse mechanical ventilation (20 ml/kg tidal-volume, zero end-expiratory pressure) or were allowed to breathe spontaneously.

In vitro antimicrobial activity of daptomycin alone and in adjunction with either amoxicillin, cefotaxime or rifampicin against the main pathogens responsible for bacterial meningitis in adults.

Objectives: As daptomycin adjunction is currently under clinical evaluation in the multicentre phase II AddaMAP study to improve the prognosis of pneumococcal meningitis, the present work aimed at evaluating the in vitro antimicrobial activity of daptomycin-based combinations against some of the most frequent species responsible for bacterial meningitis.

Methods: Clinically relevant strains of Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Neisseria meningitidis were obtained from National Reference Centers. The antimicrobial activity of amoxicillin, cefotaxime and rifampicin, either alone or in association with daptomycin, was explored through the determination of minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) as well as time-kill assay (TKA) using the broth microdilution method.

Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant.

We developed a rat model of methicillin-resistant (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen.

Efficacy of Bacteriophages in a Staphylococcus aureus Nondiabetic or Diabetic Foot Infection Murine Model.

This study investigated the efficacy of three bacteriophages combined compared with linezolid in two mouse models (nondiabetic and diabetic) of foot infection. In both models, a single injection of bacteriophages in the hindpaw showed significant antibacterial efficacy. Linezolid was as effective as bacteriophages in nondiabetic animals but ineffective in diabetic animals.

Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid.

Staphylococcus aureus pneumonia is associated with high mortality irrespective of antibiotic susceptibility. Both MRSA and MSSA strains produce powerful cytotoxins: alpha-hemolysin(Hla) and up to five leukocidins - LukSF-PV, HlgAB, HlgCB, LukED and LukGH (LukAB) - to evade host innate defense mechanisms. Neutralizing cytotoxins has been shown to provide survival benefit in rabbit S.

Mechanical ventilation and Streptococcus pneumoniae pneumonia alter mitochondrial homeostasis.

Required mechanical ventilation (MV) may contribute to bacterial dissemination in patients with Streptococcus pneumoniae pneumonia. Significant variations in plasma mitochondrial DNA (mtDNA) have been reported in sepsis according to the outcome. The impact of lung stretch during MV was addressed in a model of pneumonia.

Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation.

Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group).

Effectiveness of and obstacles to antibiotic streamlining to amoxicillin monotherapy in bacteremic pneumococcal pneumonia.

Background: Antibiotic streamlining is pivotal to reduce the emergence of resistant bacteria. However, whether streamlining is frequently performed and safe in difficult situations, such as bacteremic pneumococcal pneumonia (BPP), has still to be assessed.

Methods: All adult patients admitted to Dijon Hospital (France) from 2005 to 2013 who had BPP without complications, and were alive on the third day were enrolled.

Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit.

Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP.

Preliminary results of a new antibiotic susceptibility test against biofilm installation in device-associated infections: the Antibiofilmogram®.

Biofilms are complex communities of microorganisms embedded in an extracellular matrix and adherent to a surface. The development was described as a four-stage process leading to the formation of a mature biofilm which was resistant to immune system and antibiotic actions. In bone and joint infections (BJIs), the formation of biofilms is a leading cause of treatment failure.

A leukocyte score to improve clinical outcome predictions in bacteremic pneumococcal pneumonia in adults.

Background: Bacteremic pneumococcal pneumonia (BPP) is associated with high and early mortality. A simple procedure to predict mortality is crucial.

Methods: All adult patients with BPP admitted from 2005 through 2013 to the University Hospital of Dijon, France, were enrolled to study 30-day mortality and associated factors, particularly leukocyte counts.

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients.

Background: Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients.

Methods: A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected.

Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide.

Introduction: Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response.

Factors associated with mucoid transition of Pseudomonas aeruginosa in cystic fibrosis patients.

Although the mucoid form of Pseudomonas aeruginosa (Pa) is largely responsible for the progression of lung disease in cystic fibrosis (CF), the relationship between factors relating daily-care regimes to mucoidy acquisition are as yet poorly investigated. Fifty-two CF patients registered at the CF centre of Dijon, France, were retrospectively evaluated from the date of Pa colonization either to the first positive sputum culture for mucoid Pa (n = 26) or to the last culture in which the Pa remained non-mucoid (n = 26). All clinical, pathological and therapeutic events were recorded.

In vivo efficacy of humanised intermittent versus continuous ceftazidime in combination with tobramycin in an experimental model of pseudomonal pneumonia.

In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus continuous infusion with or without tobramycin (TOB) for the treatment of pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively.

Efficacy of humanlike Augmentin SR (2000/125 mg) twice daily treatment on Haemophilus influenzae experimental pneumonia in rabbits.

We investigated the efficacy of 2 formulations of Augmentin on experimental pneumonia due to Haemophilus influenzae (HI) in rabbits. Two strains were used (H128 and 401285) with amoxicillin/clavulanic acid MICs of 1/0.5 mg/l and 4/2 mg/l.

[Mutation window for the "pneumococcus-fluoroquinolone" couple. Contribution of experimental models].

Low-level resistance to fluoroquinolones (in vitro susceptible but with topoisomerase mutation, parC) is currently rare among pneumococci in France. However, this resistance is more frequently observed in previously exposed patients and therapeutic failure has been reported. These issues were investigated by using a humanized model of experimental pneumonia induced by pneumococci exhibiting this low-level resistance profile.

In-vivo impact of the MexXY efflux system on aminoglycoside efficacy in an experimental model of Pseudomonas aeruginosa pneumonia treated with tobramycin.

Aminoglycosides are of major importance in treating Pseudomonas aeruginosa pneumonia (PAP). However, their efficacy may be compromised by low-level resistance caused by the inducible MexXY multidrug efflux pump. In the present study, the impact of the MexXY efflux pump was investigated in vivo in an experimental model of PAP in rabbits treated with intravenous tobramycin.

The impact of mechanical ventilation on the moxifloxacin treatment of experimental pneumonia caused by Streptococcus pneumoniae.

Objective: Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and is responsible for early-onset ventilator-associated pneumonia as well. In intensive care units, community-acquired pneumonia is still associated with a mortality rate of up to 30%, especially when mechanical ventilation is required. Our objective was to study to what extent MV could influence the efficacy of moxifloxacin in a rabbit model of pneumonia.

Influence of positive end-expiratory pressure (PEEP) on histopathological and bacteriological aspects of pneumonia during low tidal volume mechanical ventilation.

Objective: Ventilatory strategies combining low tidal volume (V(T)) with positive end-expiratory pressure (PEEP) are considered to be lung protective. The influence of the PEEP level was investigated on bacteriology and histology in a model of ventilator-associated pneumonia.

Subjects: Nineteen New Zealand rabbits.