Pseudomonas aeruginosa is the nosocomial bacterial pathogen most commonly isolated from the respiratory tract. Animal models of this infection are extremely valuable for studies of virulence and immunity. We thus evaluated the utility of a simple model of acute pneumonia for analyzing P. aeruginosa virulence by characterizing the course of bacterial infection in BALB/c mice following application of bacteria to the nares of anesthetized animals. Bacterial aspiration into the lungs was rapid, and 67 to 100% of the inoculum could be recovered within minutes from the lungs, with 0.1 to 1% of the inoculum found intracellularly shortly after infection. At later time points up to 10% of the bacteria were intracellular, as revealed by gentamicin exclusion assays on single-cell suspensions of infected lungs. Expression of exoenzyme U (ExoU) by P. aeruginosa is associated with a cytotoxic effect on epithelial cells in vitro and virulence in animal models. Insertional mutations in the exoU gene confer a noncytotoxic phenotype on mutant strains and decrease virulence for animals. We used the model of acute pneumonia to determine whether introduction of the exoU gene into noncytotoxic strains of P. aeruginosa lacking this gene affected virulence. Seven phenotypically noncytotoxic P. aeruginosa strains were transformed with pUCP19exoUspcU which carries the exoU gene and its associated chaperone. Three of these strains became cytotoxic to cultured epithelial cells in vitro. These strains all secreted ExoU, as confirmed by detection of the ExoU protein with specific antisera. The 50% lethal dose of exoU-expressing strains was significantly lower for all three P. aeruginosa isolates carrying plasmid pUCP19exoUspcU than for the isogenic exoU-negative strains. mRNA specific for ExoU was readily detected in the lungs of animals infected with the transformed P. aeruginosa strains. Introduction of the exoU gene confers a cytotoxic phenotype on some, but not all, otherwise-noncytotoxic P. aeruginosa strains and, for recombinant strains that could express ExoU, there was markedly increased virulence in a murine model of acute pneumonia and systemic spread.Pseudomonas aeruginosa infection occurs when normal defense mechanisms are impaired or in cases of extensive tissue damage. Extracellular virulence factors including proteases, cytotoxins, phospholipases, pili, flagella, and smooth lipopolysaccharides have been shown to contribute to virulence in various animal models (18,25,26). Proteins exported by the type III secretion system, notably, exoenzyme S (ExoS), ExoT, and ExoU, have toxic effects on cells in culture (3,7,14,24,27,28) and are thought to be important virulence factors of P. aeruginosa. Disruption of the pscC gene (a member of the secretin family of proteins needed for secretion of the exoenzyme proteins) by insertion of Tn1 (29) reduced the virulence of cytotoxic strain PA 388 in burn wound infections in mice (18). This disruption did not affect levels of the mutant strain in a rat model of chronic lung infection, although...

Aspiration pneumonia, necrotising pneumonia and primary lung abscess are complications arising from the aspiration of infectious material from the oral cavity or stomach. There is limited information on optimal antibacterial therapeutic regimens. Patients with pulmonary infection following aspiration (n = 95) were included in a prospective, open, randomised, comparative multicentre trial to compare the safety, clinical and bacteriological efficacy of ampicillin + sulbactam vs. clindamycin +/- cephalosporin. Treated patients (n = 70) received sequential antibiotic therapy with either ampicillin + sulbactam (n = 37) or clindamycin (n = 33), with or without a second- or third-generation cephalosporin, administered until the complete resolution of clinical and radiological abnormalities. Definite or presumptive pathogens were isolated from 58 patients. Mean duration of therapy was 22.7 days for ampicillin + sulbactam and 24.1 days for clindamycin. In patients treated with ampicillin + sulbactam, the clinical response was 73.0% at the end of therapy and 67.5% 7-14 days after therapy. For clindamycin, the rates were 66.7% and 63.5%, respectively. Bacteriological response was similar in both treatment arms. Nine patients died (12.9%), with a Simplified Acute Physiology Score of > 30 points being the only significant predictive factor for therapeutic failure. Ampicillin + sulbactam and clindamycin +/- cephalosporin were both well-tolerated and proved equally effective in the treatment of aspiration pneumonia and lung abscess.

In the treatment of aspiration-associated pulmonary infections moxifloxacin appears to be clinically as effective and as safe as ampicillin/sulbactam; but, however, having the additional benefit of a more convenient (400 mg qd) treatment.

A simple prediction model based on three factors may identify COPD patients at low risk for exacerbations with gram-negative enteric bacilli and P. aeruginosa. Bacterial Etiology in COPD Exacerbations.