Antipseudomonal Carbapenems Research Articles

Achromobacter xylosoxidans bacteremia: a 10-year analysis of 54 cases.

Fifty-four cases of Achromobacter xylosoxidans bacteremia diagnosed over a 10-year period in patients from 2 months to 87 years of age were reviewed. Fifty-two episodes were nosocomial. The most frequent underlying condition was neoplasm (solid or hematological). The source of infection was a contaminated intravenous catheter in 35 patients (60%) and pneumonia in 6 patients. Eight (15%) patients died. The only risk factors significantly associated with mortality were age over 65 years and neutropenia. The results of in vitro susceptibility studies of the isolates showed that antibiotic therapy with antipseudomonal penicillins or carbapenems would be a reasonable choice. An epidemiological study conducted in the hemodialysis unit showed Achromobacter xylosoxidans in tap water and on the hands of two healthcare workers but not in the hemodialysis systems. Patients were probably contaminated when healthcare workers manipulated the intravenous catheters without wearing gloves.

In vitro and in vivo antibacterial activity of E1010, a new injectable carbapenem

Background: Preliminary studies indicate that the new antipseudomonal carbapenem E1010 is effective against a broad spectrum of bacteria. Objective: The aim of this study was to examine the in vitro and in vivo activity of E1010 against anaerobes that commonly occur in patients with obstetric and gynecologic bacterial infections. Methods: In the in vitro phase of the study, 234 clinical isolates of 9 aerobic and anaerobic pathogens were collected from patients with obstetric and gynecologic infections. Minimum inhibitory concentrations (MICs) of E1010 were determined by an agar dilution method and compared with those of panipenem, imipenem, meropenem, and ceftazidime. In the in vivo phase, mice were inoculated with a suspension of Bacteroides fragilis isolated from a patient with pelvic peritonitis and were then treated with E1010 20 mg/kg or imipenem/cilastatin 20 mg/kg TID for 5 days. Therapeutic efficacy was assessed based on the incidence of intra-abdominal abscesses and viable bacterial cell counts 5 days after bacterial inoculation. Results: In vitro, E1010 inhibited > 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli, Enterococcus faecalis, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, Peptostreptococcus magnus, B fragilis, and Prevotella bivia. The MIC of E1010 against P aeruginosa was greater than those of panipenem, imipenem, and meropenem. In vivo, E1010 inhibited abscess formation and significantly decreased viable cell counts in abscesses compared with the untreated group ( P < 0.05). In vivo therapeutic efficacy, as measured by decreases in the viable cell count, was equivalent to that of imipenem/cilastatin. Conclusion: These results suggest that E1010 may be useful in the treatment of anaerobic obstetric/gynecologic infections.

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.

In vitro and in vivo evaluation of BO-2727 against imipenem- and/or meropenem-resistant Pseudomonas aeruginosa.

The in vitro and in vivo activity of BO-2727, a carbapenem antibiotic, against resistant clinical isolates of Pseudomonas aeruginosa was studied. The geometric mean MICs against three groups of clinical isolates resistant to imipenem, meropenem and both carbapenems were 4.28, 4.08 and 5.44 micrograms/ml, respectively. BO-2727 also inhibited multiply antibiotic resistant isolates and laboratory mutants including a nalB-type mutant, which showed resistance to antibiotics such as imipenem, meropenem, ceftazidime, and/or ciprofloxacin, at less than 1.56 micrograms/ml. Overall, BO-2727 was 4-fold more active than biapenem, meropenem, panipenem and imipenem with an MIC90 of less than 6.25 micrograms/ml. The presence of basic amino acids in minimal medium less affected the antipseudomonal activity to a minimal extent, suggesting that BO-2727 has diverse penetration routes through the outer membrane other than OprD channel, which facilitates the diffusion of basic amino acids and carbapenems. The in vitro activity of BO-2727 reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results suggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem- and/or meropenem-resistant P. aeruginosa as well as a broad spectrum encompassing Gram-positive and -negative bacteria.