Safety and efficacy of transcatheter embolization with Glubran®2 cyanoacrylate glue for acute arterial bleeding: a single-center experience with 104 patients.

PURPOSE: To assess the efficacy and the safety of Glubran®2 n-butyl cyanoacrylate metacryloxysulfolane (NBCA-MS) transcatheter arterial embolization (TAE) for acute arterial bleeding from varied anatomic sites and to evaluate the predictive factors associated with clinical success and 30-day mortality. METHODS: A retrospective review of consecutive patients who underwent emergent NBCA-MS Glubran®2 TAE between July 2014 and August 2016 was conducted. Variables including age, sex, underlying malignancy, cardiovascular comorbidities, coagulation data, systolic blood pressure, and number of red blood cells units (RBC) transfused before TAE were collected. Clinical success, 30-day mortality, and complication rates were evaluated. Prognostic factors were evaluated by uni- and multivariate logistic regression analyses for clinical success, and by uni- and bivariate analyses after adjustment by bleeding sites for 30-day mortality. RESULTS: 104 patients underwent technically successful embolization with bleeding located in muscles (n = 34, 32.7%), digestive tract (n = 28, 26.9%), and viscera (n = 42, 40.4%). Clinical success rate was 76% (n = 79) and 30-day mortality rate was 21.2% (n = 22). Clinical failure was significantly associated with mortality (p < 0.0001). A number of RBC units transfused greater than or equal to 3 were associated with poorer clinical success (p = 0.025) and higher mortality (p = 0.03). Complications (n = 4, 3.8%) requiring surgery occurred only at puncture site. No ischemic complications requiring further invasive treatment occurred. Mean TAE treatment time was 4.55 min. CONCLUSIONS: NBCA-MS Glubran®2 TAE is a fast, effective, and safe treatment for acute arterial bleeding whatever the bleeding site.

Ceftaroline versus ceftriaxone in a highly penicillin-resistant pneumococcal pneumonia rabbit model using simulated human dosing.

Ceftaroline (CPT) is a new cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), as well as common Gram-negative pathogens. This study investigated the in vivo efficacy of a 48-hour simulated human dose regimen of CPT compared with ceftriaxone (CRO) against isolates of S. pneumoniae with different susceptibilities to penicillin in a rabbit pneumonia model. Three S. pneumoniae strains were used: CRO-susceptible penicillin-susceptible S. pneumoniae (CRO-S PSSP), CRO-susceptible penicillin-intermediate S. pneumoniae (CRO-S PISP), and CRO-resistant penicillin-resistant S. pneumoniae (CRO-R PRSP). Animals were randomized to the control group (no treatment) (n = 22) or to a group given intravenous (IV) CPT human equivalent (HE) dosage (600 mg/12 h; n = 19) or IV CRO HE dosage (1 g/24 h; n = 19). The total doses needed to achieve the HE dosage were 71 and 82 mg/kg of body weight/24 h for CRO and CPT, respectively. One group of rabbits infected with the CRO-R PRSP strain received intramuscular (IM) administration of CPT (5 or 20 mg/kg twice daily; n = 5 for each). Evaluation of efficacy was based on bacterial counts in the lungs and spleen. For IV CPT and IV CRO, the mean areas under the concentration-time curves from 0 to 24 h (AUC(0-24)s) were 155 and 938 mg · h/liter, respectively, the maximum concentrations in serum (C(max)s) were 20 and 158 mg/liter, respectively, and the minimum concentrations in serum (C(min)s) were 1.3 and 6 mg/liter, respectively. Both agents effectively treated pulmonary infections caused by CRO-S PSSP or CRO-S PISP with complete bacterial eradication in the lungs and spleen after 2 days of treatment. Against PRSP, CPT demonstrated excellent bactericidal activity, reducing bacterial counts in the lungs and spleen by approximately 8 and 4 log units, respectively (P < 0.001); CRO treatment resulted in a 2-log-unit reduction in the bacterial counts in lungs that did not reach statistical significance. Twice-daily IM CPT (5 mg/kg) reduced the bacterial burden by approximately 6 log units in the lungs and 3 log units in the spleen, and the 20-mg/kg dosage effectively eradicated PRSP infection. These findings further validate the in vivo bactericidal activity of CPT against pneumococci.

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. DESIGN: Prospective experimental study. SETTING: University hospital laboratory. SUBJECTS: Male New Zealand White rabbits (n = 75). INTERVENTIONS: S. pneumoniae (16089 strain; minimal inhibitory concentration for moxifloxacin = 0.125 mg/L) was instilled intrabronchially. Four hours later, a human-like moxifloxacin treatment was initiated in spontaneously breathing (SB) and mechanically ventilated (MV) animals. Untreated rabbits were used as controls. Survivors were killed 48 hrs later. Pneumonia was assessed and moxifloxacin pharmacokinetics were analyzed. MEASUREMENTS AND MAIN RESULTS: Moxifloxacin treatment was associated with an improvement in survival in the SB animals (13 of 13 [100%] vs. eight of 37 [21.6%] controls). The survival rate was less influenced by treatment in MV rabbits (seven of 15 [46.1%] vs. one of eight [12.5%] controls). The lung bacterial burden was greater in MV compared with SB rabbits (5.1 +/- 2.4 vs. 1.6 +/- 1.4 log10 colony-forming units/g, respectively). Nearly all the untreated animals presented bacteremia as reflected by a positive spleen culture. No bacteremia was found in SB animals treated with moxifloxacin. In contrast, three of 13 (23.1%) moxifloxacin-treated and MV animals had positive spleen cultures. The apparent volume of distribution of moxifloxacin was lower in MV compared with SB rabbits. CONCLUSIONS: In our model of moxifloxacin-treated S. pneumoniae pneumonia, mechanical ventilation was associated with a higher mortality rate and seemed to promote bacterial growth as well as systemic spread of the infection. In addition, the volume of distribution of moxifloxacin was reduced in the presence of mechanical ventilation. Although the roles of factors such as anesthesia, paralysis, and endotracheal tube insertion could not be established, these results suggest that mechanical ventilation may impair host lung defense, rendering antibiotic therapy less effective.

Mutant selection window in levofloxacin and moxifloxacin treatments of experimental pneumococcal pneumonia in a rabbit model of human therapy.

For some pneumococci the fluoroquinolone MICs are low but the mutant prevention concentrations (MPCs) are high; this difference defines in vitro the mutant selection window (MSW). We investigated in vivo the bacterial reduction and the occurrence of resistant mutants with moxifloxacin (MFX; 400 mg once daily) or levofloxacin (LVX; 500 mg twice daily) in treatments similar to those in humans with experimental pneumonia due to pneumococci (expPP) exhibiting various MICs and MPCs. The MIC/MPC for MFX and LVX and genotypes were as follows: strain 16089, 0.125/0.125 and 0.5/0.5 (wild type); strain MS1A, 0.25/0.25 and 1/2 (efflux); strain MS2A, 0.25/4 and 1.75/28 (parC79); strain MR3B4, 0.25/4 and 2/32 (parC79); strain M16, 0.5/2 and 8/32 (parC83); strain Gyr-1207, 1.5/3 and 8/16 (gyrA); and strain MQ3A, 4/4 and 16/64 (parC and gyrA). Both drugs were efficient with wild type-expPP, but only MFX was efficient with efflux-expPP. No bacterial reduction was observed for parC-expPPs due to mutants observed in 18 to 100% of animals, depending on the strain and the drug tested. These mutants showed unbound area under the concentration-time curve and MICs of from 50 to 164 for MFX. The in vivo pharmacodynamic boundaries of the MSW were different for MFX and LVX. We conclude that, after LVX or MFX treatment, mutants occur in vivo if there is a preexisting parC mutation, since the drug concentrations fall below the MPCs of these strains. Since the MPC determination cannot be routinely determined, these phenotypes or genotypes should be detected by simple tests to guide the therapeutic options.