The findings of this study demonstrate tumor depth > or =4 mm moderately differentiated squamous cell carcinoma of the tongue have a substantially higher rate of late cervical metastases. In the basis of these data, it is our recommendation that this be used in the decision to electively treat the neck.

FR264205 is a novel parenteral 3-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against Pseudomonas aeruginosa. The MIC of FR264205 at which 90% of 193 clinical isolates of P. aeruginosa were inhibited was 1 g/ml, 8-to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level of activity against CAZ-, IPM-, and CIP-resistant P. aeruginosa. The reduction in the susceptibility of FR264205 by AmpC ␤-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC ␤-lactamase, the main resistance mechanism for cephalosporins. Neither expression of efflux pumps nor deficiency of OprD decreased the activity of FR264205. No spontaneous resistance mutants were selected in the presence of FR264205, and the reduction in susceptibility to FR264205 was lower than that to CAZ, IPM, and CIP after serial passage, suggesting that FR264205 has a low propensity for selecting resistance. In murine pulmonary, urinary tract, and burn wound models of infection caused by P. aeruginosa, the efficacy of FR264205 was superior or comparable to those of CAZ and IPM. These results indicate that FR264205 should have good potential as an antibacterial agent for P. aeruginosa.Nosocomial infections with gram-negative bacteria are a major problem for immunocompromised patients. Pseudomonas aeruginosa exhibits considerable inherent resistance, caused by low outer membrane permeability, multiple efflux pumps, and chromosomal AmpC ␤-lactamase (12). P. aeruginosa can also acquire additional resistance mechanisms, such as constitutive production of AmpC ␤-lactamase, OprD loss, and overproduction of efflux pumps. Although ceftazidime (CAZ) has been used as a first-line drug for P. aeruginosa infection, resistant mutants showing constitutive AmpC ␤-lactamase production can be selected in clinical settings, leading to therapeutic failure (2). P. aeruginosa has developed resistance not only to cephalosporins but also to carbapenems and quinolones. In 2003, the National Nosocomial Infections Surveillance System reported that resistance rates of P. aeruginosa to imipenem, quinolone, and broad-spectrum cephalosporins were 21.1, 29.5, and 31.9%, respectively. Compared to rates in the period between 1998 and 2002, these rates were increased by 15, 9, and 20%, respectively (15). Therefore, there is a critical need for new anti-P. aeruginosa agents that have no cross-resistance to currently marketed antibacterial agents and low propensities for inducing resistance.In order to generate promising anti-P. aeruginosa agents, research by our group has been directed toward the development of novel cephalosporins. As a result of exploration of structure-activity relationships of 3-(2,4-disubstituted 3-aminopyrazolio)methyl cephalosporins, FR264205 was discovered (Fig. 1). The antibacterial spectrum of FR264205 was similar to that of CAZ, and the MICs of FR264205 for Staphylococcus aureus ATCC 29213, Streptococcus pn...

No abstract

No abstract

No abstract