linezolid and Cross-Infection

Enterococci are the leading cause of nosocomial infections worldwide and acquired resistance to a variety of antibiotics. Antimicrobial peptides represent a promising molecule against the antibiotic resistance in bacteria and an indispensable component of the innate immune system. The aim of the study was to develop an antimicrobial peptide against vancomycin-resistant enterococci (VRE). We have designed a series of peptides based on Sapecin B as template. An in vitro antibacterial study of synthetic peptide BF2 against the clinical isolates of vancomycin-resistant and control strains of enterococci showed rapid killing effect on enterococci by killing 99.9% of bacterial cells in 60 min and susceptibility at minimum inhibitory concentration (MIC) range of 6.25-12.5 μg/mL. Synergy of BF2 was observed in combination with vancomycin and teicoplanin. The peptide was bactericidal and nontoxic to mammalian cells. An in vivo study also revealed the antibacterial activity against enterococci-infected Wistar albino rats. BF2 may be used synergistically with antibiotics.

Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cross Infection; Drug Synergism; Enterococcus faecalis; Enterococcus faecium; Erythrocytes; HEK293 Cells; Humans; Oligopeptides; Rats, Wistar; Vancomycin-Resistant Enterococci

Rx-01_423 and Rx-01_667 are two members of the family of oxazolidinones that were designed using a combination of computational and medicinal chemistry and conventional biological techniques. The compounds have a two- to eightfold-improved potency over linezolid against serious gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant streptococci, and vancomycin-resistant enterococci. This enhanced potency extends to the coverage of linezolid-resistant gram-positive microbes, especially multidrug-resistant enterococci and pneumococci. Compounds from this series expand the spectrum compared with linezolid to include fastidious gram-negative organisms like Haemophilus influenzae and Moraxella catarrhalis. Like linezolid, the Rx-01 compounds are bacteriostatic against MRSA and enterococci but are generally bactericidal against S. pneumoniae and H. influenzae.

Topics: Anti-Infective Agents; Bacteria; Community-Acquired Infections; Cross Infection; Enterococcus; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Molecular Structure; Oxazolidinones; Respiratory System; Staphylococcus; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae

Ceftobiprole (BPR) is an investigational cephalosporin with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains. The pharmacodynamic (PD) profile of BPR against S. aureus strains with a variety of susceptibility phenotypes in an immunocompromised murine pneumonia model was characterized. The BPR MICs of the test isolates ranged from 0.25 to 2 mug/ml. Pharmacokinetic (PK) studies were conducted with infected neutropenic BALB/c mice; and the BPR concentrations were measured in plasma, epithelial lining fluid (ELF), and lung tissue. PD studies with these mice were undertaken with eight S. aureus isolates (two methicillin-susceptible S. aureus strains, three hospital-acquired MRSA strains, and three community-acquired MRSA strains). Subcutaneous BPR doses of 2 to 125 mg/kg of body weight/day were administered, and the change in the number of log(10) CFU/ml in lungs was evaluated after 24 h of therapy. The PD profile was characterized by using the free drug exposures (f) determined from the following parameters: the percentage of time that the concentration was greater than the MIC (T > MIC), the maximum concentration in serum/MIC, and the area under the concentration-time curve/MIC. The BPR PK parameters were linear over the dose range studied in plasma, and the ELF concentrations ranged from 60 to 94% of the free plasma concentration. fT > MIC was the parameter that best correlated with efficacy against a diverse array of S. aureus isolates in this murine pneumonia model. The 80% effective dose (ED(80)), ED(50), and stasis exposures appeared to be similar among the isolates studied. BPR exerted maximal antibacterial effects when fT > MIC ranged from 6 to 22%, regardless of the phenotypic profile of resistance to beta-lactam, fluoroquinolone, erythromycin, clindamycin, or tetracycline antibiotics.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Cross Infection; Disease Models, Animal; Drug Resistance, Bacterial; Female; Humans; Methicillin Resistance; Mice; Mice, Inbred BALB C; Phenotype; Pneumonia, Staphylococcal; Staphylococcus aureus

We evaluated the activity of ceftobiprole against 100 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and 100 hospital-associated MRSA (HA-MRSA) isolates. Eight isolates were evaluated by time-kill studies for kill rate and potential for synergy with tobramycin. Ceftobiprole MIC(50) and MIC(90) values were 1 and 2 microg/ml, respectively, against CA-MRSA and HA-MRSA. In time-kill analysis, ceftobiprole was bactericidal at all concentrations tested.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Cross Infection; Daptomycin; Drug Synergism; Humans; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Acetamides; Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Vancomycin Resistance

This study was performed to evaluate the in vitro activity of the amphibian peptide aurein 1.2 and to investigate its interaction with six antibiotics against nosocomial gram-positive cocci. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when aurein 1.2 was combined with clarithromycin and minocycline.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cross Infection; Drug Synergism; Drug Therapy, Combination; Gram-Positive Cocci; Microbial Sensitivity Tests

Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMup(r)) were compared with those of mupirocin-susceptible (Mup(s)) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMup(r) MRSA isolates were identified. The proportion of MRSA strains with HLMup(r) increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMup(r) MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMup(r) MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMup(r) MRSA strains had a plasmid-associated mupA gene, most often associated with a 9-kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMup(r) MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMup(r) is increasing among Canadian strains of MRSA and that HLMup(r) MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mup(s) MRSA strains.

Topics: Aged; Anti-Bacterial Agents; Canada; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Mupirocin; Staphylococcal Infections; Staphylococcus aureus