In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility.

Objectives: In order to explore the pharmacodynamic need for continuous versus intermittent (three times a day) administration of ceftazidime in critically ill patients, a pharmacokinetic computerized device was used to simulate concentrations of ceftazidime in human serum after 6 g/day. Methods: Efficacy was measured as the capability of simulated concentrations over time to reduce initial inoculum against four strains of Pseudomonas aeruginosa. MICs of the strains matched NCCLS breakpoints: one susceptible strain (MIC=8 mg/L), two intermediate strains (MIC=16 mg/L) and one resistant strain (MIC=32 mg/L). C_max was 119.97±2.53 mg/L for intermittent bolus and C_ss (steady-state concentration) was 40.38±0.16 mg/L for continuous infusion. AUC_0–24 was similar for both regimens (∼950 mg·h/L). Inhibitory quotients were three times higher for the intermittent administration whereas t > MIC was higher for continuous infusion (100%) versus intermittent administration (99.8%, 69% and 47.6% for the susceptible, intermediate and resistant strains, respectively). Results: Against the susceptible and intermediate strains, no differences were found between both regimens with ≥ 3 log₁₀ reduction from 8 to 24 h. Against the resistant strain, only the continuous infusion achieved this bactericidal activity in the same time period, minimizing the differences between resistant and susceptible strains. Significantly higher initial inoculum reduction at 32 h was obtained for the continuous versus the intermittent administration (83.35% versus 38.40%, respectively). Conclusions: These results stress the importance of optimizing t >MIC, even at peri-MIC concentrations, of ceftazidime against resistant strains. Local prevalence of resistance justifies, on a pharmacodynamic basis, electing for continuous infusion versus intermittent administration.

Aims: The aim of this study was to analyse the nucleotide sequences of regions encoding the penicillin-binding domains of pbp1A, pbp2B and pbp2X genes and murM alleles from 14 selected amoxicillin-resistant Streptococcus pneumoniae isolates (MICs 8–16 mg/L) obtained in Spain. Methods: PFGE and dideoxynucleotide chain termination sequencing were used. Results: Analysis of PFGE profiles showed that the amoxicillin-resistant S. pneumoniae strains belonged to six different PFGE patterns including the Spain^23F-1, Spain^6B-2, Spain^9V-3 and Spain¹⁴-5 international clones; however, 8 of the 14 strains belonged to the Spain^9V-3 clone. These strains showed the typical changes in penicillin-binding proteins (PBPs) 1A and 2X and had 10 unique changes in the 590–641 region of PBP2B as described previously. Transformation experiments tried to incorporate the transpeptidase domain of PBP2B including the 590–641 region associated with amoxicillin-resistant pneumococci. Sequencing of the pbp2B genes revealed that part of the 3′ region of the pbp2B sequence encoding a region of the domain (around amino acid 514–538 to the C terminus of PBP2B) did not recombine with the R6 pbp2B gene. The murM sequence analysis showed that 6, 6 and 2 amoxicillin-resistant S. pneumoniae strains had murMA, murMB5 and murMB6 alleles, respectively. However, strains with murMB5 or murMB6 alleles showed a single mutation (N₅₃₇D) in the 537–581 region of PBP2B, while strains with the murMA allele had 12 unique changes. Conclusions: Ten unique changes in the 590–641 region of PBP2B and no specific murM alleles were found in S. pneumoniae strains isolated in Spain with an amoxicillin MIC ≥8 mg/L (MICs from 6 to 12 mg/L by 1 mg/L step dilution). In addition, the presence of specific mutations in PBP2B seems to play a key role in the presence of different murM alleles in these amoxicillin-resistant pneumococcal strains.

We aimed to evaluate the effects of ultrasound-assisted wound (UAW) debridement on cellular proliferation and dermal repair in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical/sharp wound debridement. A randomized controlled trial was performed involving 51 outpatients with complicated diabetic foot ulcers that either received surgical debridement (n = 24) or UAW debridement (n = 27) every week during a six-week treatment period. Compared to patients receiving surgical debridement, patients treated with UAW debridement exhibited significantly improved cellular proliferation, as determined by CD31 staining, Masson’s trichrome staining, and actin staining. Bacterial loads were significantly reduced in the UAW debridement group compared to the surgical group (UAW group 4.27 ± 0.37 day 0 to 2.11 ± 0.8 versus surgical group 4.66 ± 1.21 day 0 to 4.39 ± 1.24 day 42; p = 0.01). Time to healing was also significantly lower (p = 0.04) in the UAW group (9.7 ± 3.8 weeks) compared to the surgical group (14.8 ± 12.3 weeks), but both groups had similar rates of patients that were healed after six months of follow-up (23 patients (85.1%) in the UAW group vs. 20 patients (83.3%) in the surgical group; p = 0.856). We propose that UAW debridement could be an effective alternative when surgical debridement is not available or is contraindicated for use on patients with complicated diabetic foot ulcers.

Bactericidal activity depends on antibiotic–bacteria couples, resistance phenotype and theoretically on protein binding. This work explores the influence of protein binding on the bactericidal activity of two antibiotics, daptomycin versus vancomycin, that exhibit, respectively, different C_max (56 versus 25.5 mg/L), protein binding (91.7% versus 36.9%) and thus theoretical free-drug fractions (4.7 versus 16.1 mg/L). The effect of the presence of physiological concentrations of human albumin (4 g/dL) or human serum (90%) on the bactericidal activity of daptomycin was studied against Gram-positive isolates with troublesome resistance phenotypes [multidrug-resistant Streptococcus pneumoniae (MDRSP), methicillin-resistant Staphylococcus aureus (MRSA), heterogeneous vancomycin-intermediate MRSA (MRSA-hVI) and vancomycin-resistant Enterococcus faecium]. Killing curves (final inocula of ∼10⁷ cfu/mL) were performed using daptomycin and vancomycin concentrations similar to the C_max obtained in serum. Daptomycin was rapidly bactericidal (≥3 log₁₀ initial inocula reduction) against S. pneumoniae and S. aureus, regardless of the strain tested or the presence of albumin or human serum (that slightly delayed bactericidal activity). Against vancomycin-susceptible or -resistant enterococci, daptomycin exhibited rapid bactericidal activity, delayed to 8 and 24 h, respectively, by human albumin. Vancomycin exhibited much slower bactericidal activity against MDRSP and methicillin-susceptible or -resistant S. aureus, but was never bactericidal against MRSA-hVI and vancomycin-susceptible or -resistant E. faecium. Daptomycin exhibited rapid bactericidal activity against the strains of the three Gram-positive species tested, regardless of resistance phenotype or the presence of physiological concentrations of albumin.