C-reactive protein for discriminating treatment failure from slow responding pneumonia.

BACKGROUND: The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment. METHODS: This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP. We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively. RESULTS: By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p<0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78-0.96). CONCLUSION: Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve.

L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study.

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours (r = 0.85, P<0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume (r = -0.40 and r = -0.35, respectively, P<0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days (P<0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.