ABSTRACT
OBJECTIVES: Among carbapenem-sparing therapies, ceftolozane/tazobactam has been proposed for the treatment of infections due to CTX-M-15-producing Escherichia coli. However, few data exist on its in vivo activity in infections associated with a high bacterial inoculum. METHODS: We analysed ceftolozane/tazobactam activity against susceptible E. coli CFT073-RR and its CTX-M-15-producing transconjugant E. coli CFT073-RR Tc blaCTX-M-15, in vitro at low and high inocula, and in a high-inoculum murine model of peritonitis. RESULTS: Against E. coli CFT073-RR Tc blaCTX-M-15, ceftolozane/tazobactam bactericidal effect was impaired in vitro with only a minor inoculum effect; this translated into reduced activity compared with imipenem in the mouse peritonitis model. CONCLUSIONS: Combination of extended spectrum ß-lactamase expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Escherichia coli/drug effects , Imipenem/pharmacology , Peritonitis/drug therapy , Tazobactam/pharmacology , beta-Lactamases/metabolism , Animals , Bacterial Load , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/metabolism , Disease Models, Animal , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Infections/drug therapy , Mice , Mice, Inbred ICR , Microbial Sensitivity Tests , Peritonitis/microbiology , beta-Lactamase Inhibitors/pharmacologyABSTRACT
OBJECTIVES: Cefepime is a fourth-generation cephalosporin active against Pseudomonas aeruginosa and most Enterobacteriaceae. Intravenous (IV) administration is the standard route of prescription. However, subcutaneous administration (SC) may represent an interesting alternative. We aimed to evaluate SC administration of cefepime versus the IV route in geriatric patients. PATIENTS AND METHODS: Multicenter retrospective analysis in patients treated with cefepime by SC route who underwent plasma concentration monitoring. RESULTS: Twelve patients were included in the SC group and matched to 12 patients in the IV group. The median and mean Cmin levels were 29.05mg/L [14.2-48.2]; 33.4mg/L (±21.8) in the SC group and 31.9mg/L [26.5-51.7]; 39.6mg/L (±27) (P=NS) in the IV group. No local SC administration-related complications were reported. No relapse was observed over six months of follow up. CONCLUSION: Subcutaneous use of cefepime seems to have the same clinical and microbiological effectiveness as parenteral administration.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cefepime/administration & dosage , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Cefepime/pharmacokinetics , Cefepime/therapeutic use , Female , Humans , Injections, Subcutaneous , Male , Retrospective Studies , Treatment OutcomeABSTRACT
Vertebral osteomyelitis caused by non-tuberculous mycobacteria is a rare disease, with only 31 cases and one nosocomial outbreak reported in the literature (MedLine review between 1965 and December 2003). The clinical features are often indistinguishable from those of pyogenic osteomyelitis. Early diagnosis of such infections is a major challenge because of the slow growth of these microorganisms. No consensus guidelines for the treatment of these infections exist. Prolonged anti-mycobacterial therapy in combination with surgical debridement is recommended.
