Should Pseudomonas aeruginosa isolates resistant to one of the fluorinated quinolones be tested for the others? Studies with an experimental model of pneumonia

Abstract

A clinical isolate of Pseudomonas aeruginosa resistant to pefloxacin (Pef) but susceptible to ciprofloxacin (Cip) was studied to compare the in vitro and in vivo activities of Pef, ofloxacin (Ofl), and Cip. The time-kill curve method showed no bactericidal activity for Pef and Ofl, but a reduction of 4 log 10 CFU/ml was achieved with Cip at 1 h. A model of experimental P. aeruginosa pneumonia was used to evaluate in vivo the relevance of the difference in susceptibility observed in vitro. At 36 h, a 100% cumulative survival rate was observed in Cip-treated rats, which was far higher than the survival rate obtained with Pef (53%) or Ofl (46%) (P < 0.001). At 4 h, no bacteremia was observed in Cip-treated rats, whereas 93% of the Pef-treated rats and 80% of the Ofl-treated rats were bacteremic (P < 0.001). The best pulmonary bacterial clearance was observed with Cip. Interestingly, Pef and Ofl, to which the strain was resistant in vitro, showed a fairly good in vivo activity despite sub-MIC concentrations. Cip was more effective than Pef and Ofl in terms of pulmonary and systemic bactericidal activity and provided the best survival rate in animals. We conclude that differences between the different quinolones in terms of the organism's sensitivity assessed in vitro may be relevant and that it might be useful to reconsider the use of a quinolone to which P. aeruginosa shows resistance if the organism shows sensitivity to no other agent.

Keratinocyte growth factor protects againstPseudomonas aeruginosa-induced lung injury

“…A clinical isolate of P. aeruginosa was used for this study as previously described (5). P. aeruginosa was incubated in 125 ml of tryptic soy broth at 37°C in a rotating shaking water bath for 8 h. The culture was then centrifuged (3,000 g for 10 min), washed twice with PBS (pH 7.4), and resuspended in PBS.…”

Bactericidal activity of three β-lactams alone or in combination with a β-lactamase inhibitor and two aminoglycosides against Klebsiella pneumoniae harboring extended-spectrum β-lactamases

“…The addition of a P-lactamase inhibitor such as SUL k aminoglycoside is advisable to avoid failure of treatment. These results are expected to be confirmed with the experimental model of pneumonia [26].…”

In vivo oral efficacy of levofloxacin for treatment of systemic Pseudomonas aeruginosa infections in a murine model of septicemia

“…Pseudomonas aeruginosa is an opportunistic pathogen responsible for a significant number of nosocomial infections (of the lungs, eyes, and intestinal and urinary tracts), especially in patients with cystic fibrosis or with severe burns or in those individuals whose immune systems are severely compromised (1,2,6,9,13,18,19). Pseudomonas species have been shown to develop resistance quickly to new classes of antibiotics (7,14).…”

“…Infections with P. aeruginosa remain some of the most difficult to treat because of their intrinsic resistance to many antimicrobial agents, including the ␤-lactams. As a result, pseudomonal infections continue to be a significant cause of morbidity and mortality (2,13,16).…”

“…Treatment of pseudomonal infections with fluorinated quinolones has increased steadily in parallel with observed increases in ␤-lactam resistance. Ofloxacin, pefloxacin, and ciprofloxacin have been used widely to treat nosocomial pneumonia caused by P. aeruginosa (2). All three of these fluoroquinolones exhibit activity against even multiple-drug-resistant strains of P. aeruginosa.…”