Short-course therapy of gemifloxacin effective against pneumococcal pneumonia in mice.

Standard 7-14 day (d) courses of antimicrobial therapy for community-acquired pneumonia (CAP) are thought to have contributed to the emergence of resistant pneumoccoci. Consequently, short-course fluoroquinolone regimens have been proposed to minimize resistance. To test this, we examined 2-day versus 5-day regimens of gemifloxacin and levofloxacin for treatment of pneumonia in a murine model. In doing so, we also investigated whether the enhanced potency of gemifloxacin would influence outcomes. CD1 Swiss mice were infected intratracheally with 10(5)-CFU of a virulent Streptococcus pneumoniae strain. Drugs were administered every 8 h for 2 d and 5 d, starting at 24 h postinfection. Temperature was used to assess disease progression. Gemifloxacin remained effective for 2 d and 5 d, with survival rates of 100%-83% compared with 40%-58% for levofloxacin. Eighty-nine to 100% of gemifloxacin-treated mice were clear of pulmonary bacteria compared with only 0%-20% for levofloxacin. For levofloxacin-treated mice, 2 of 7 (29%) isolates with a levofloxacin minimum inhibitory concentration (MIC) 4 times that of the infecting parent strain had ParC mutations. By contrast, no isolates recovered from gemifloxacin-treated mice were reduced in susceptibility. Gemifloxacin could be effective in shortening duration of therapy for CAP treatment as well as minimize resistance development.

Phase 1 human trial of adenosine-potassium cardioplegia.

BACKGROUND: The cardioprotective role of adenosine in various models of ischemia-reperfusion, including adenosine supplementation to cardioplegic formulations, has been studied extensively. The appropriate dose of adenosine in humans is uncertain and could be limited by systemic hypotension or AV block. METHODS AND RESULTS: An open-label, nonrandomized phase 1 adenosine dose-ranging study was performed. Patients scheduled for primary isolated coronary bypass surgery were eligible for the study. Antegrade warm blood potassium cardioplegia (ratio, 4:1, blood to crystalloid) was administered in the routine fashion, with adenosine added to the initial 1000-mL dose and final 500-mL dose. Patients were studied in blocks of 4 per concentration. An escalating adenosine dosage schedule was planned to produce blood cardioplegia concentrations from 0 to 250 mumol/L, and the blocks were tested sequentially. Stopping rules were defined for systemic hypotension (phenylephrine dose during cardiopulmonary bypass > or = 5.0 mg; phenylephrine dose during cardioplegic induction > or = 800 micrograms) and AV block (permanent pacemaker insertion; temporary pacing dependency for > 90 minutes after cardiopulmonary bypass). Doses of 1, 2.5, 5, 10, and 25 mumol/L were well tolerated. With 50 mumol/L, systemic hypotension occurred during cardioplegic induction in 3 of 4 patients versus 1 of 24 (P < .005) at all lower concentrations (880 +/- 217 versus 297 +/- 286 micrograms phenylephrine per patient). The studies were repeated with an 8:1 blood-to-crystalloid cardioplegia delivery system. Adenosine concentrations of 0 (n = 4), 15 (n = 12), 20 (n = 8), and 25 mumol/L (n = 4) were tested. Hypotension during cardioplegic induction was more prevalent (P = .05) with the higher doses (15 mumol/L, 394 +/- 189 micrograms, 1 of 12 patients; 20 mumol/L, 360 +/- 355 micrograms, 2 of 8 patients; 25 mumol/L, 600 +/- 478 micrograms, 2 of 4 patients). There were no differences with respect to systemic hypotension during cardiopulmonary bypass or for pacing > 90 minutes after discontinuation of cardiopulmonary bypass, and no patient required permanent pacing. There have been no deaths, Q-wave myocardial infarctions, intra-aortic balloon pump insertions, or cerebral infarctions in the total sample of 56 patients. CONCLUSIONS: Our initial investigations have shown that adenosine can be safely administered during cardiopulmonary bypass. The authors recommend that further studies are warranted using adenosine 15 to 25 mumol/L, depending on the delivery system.

Psychological factors, immunologic activation, and disease activity in rheumatoid arthritis.

The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.