Wayne M. Samuelson

Arthropathy Secondary to Ciprofloxacin in an Adult Cystic Fibrosis Patient

OBJECTIVE: To report a case of possible ciprofloxacin-induced arthropathy in an adult patient with cystic fibrosis (CF). CASE SUMMARY: A 25-year-old man with CF received three separate courses of ciprofloxacin therapy at usual doses for acute pulmonary exacerbations of his disease. During the second and third courses, the patient experienced bilateral swelling of his knees between two to three weeks after initiation of each course. Both times symptoms markedly decreased after discontinuation of the drug. The patient had no prior history of arthropathy. Furthermore, during the last two acute exacerbations of his CF, he did not receive ciprofloxacin and did not experience any symptoms of arthropathy. DISCUSSION: Prior cases of quinolone-induced arthropathy involving pediatric CF patients or adult patients without CF have been reported in the literature. We report the first case of such an arthropathy in an adult patient with CF. The findings are supported by a rechallenge with the drug. CONCLUSIONS: It is likely that ciprofloxacin may produce arthropathy in adult as well as pediatric patients with CF. Quinolones should be considered as a possible cause of arthropathy in adult CF patients.

Assessing redox status in human plasma. Experience in critically ill patients

Clinical evaluation of metabolic acidosis has involved measurement of lactate (L), pyruvate (P), beta-hydroxybutyrate (BOHB), and acetoacetate (AcAc). We previously demonstrated that these metabolites are not at equilibrium in plasma. Their degree of disequilibrium is reflected in the ratio of apparent equilibrium constants (KLP/KBA) for the two redox couplets, L-P and BOHB-AcAc. The purpose of the study was to examine how well this ratio reflects disequilibrium in patients with metabolic acidosis. Measurements of the four metabolites were obtained in 23 critically ill patients. Disequilibrium was again observed, as manifested in an inconstant ratio (p < .01). The ratio increased with clinical improvement. Patients were more likely to die during their ICU stay if the estimated ratio was low, particularly if metabolic acidosis was present. Patients with respiratory acidosis had both intermediate probabilities of death and intermediate ratios when compared to inpatient controls (ICU patients without acidosis). Our data indicate that changes in the L-P-BOHB-AcAc cycle reflect the degree of metabolic derangement in critically ill patients.

Nonequilibrium of two redox couplets in human plasma: lactate-pyruvate and beta-hydroxybutyrate-acetoacetate.

We examined the extracellular equilibrium status of two redox couplets normally found in plasma (lactatepyruvate [L-P], beta-hydroxybutyrate, and acetoacetate) during acute metabolic acidosis produced by muscle exertion. Both pre- and postexertion plasma spontaneously underwent loss of acetoacetate and gain of L when compared to the baseline values. Exercise further induced a 332% rise in L (p < .001) and a 102% rise in P (p < .001). The empirically derived ratio of equilibrium constants, KI.P/KBA, fell 50% (p < .001), and the calculated change in free energy (ΔF) fell from 3.6 to 3.1 kcal/mol (p < .001) after exercise. The changes induced by exertion were simulated closely by an in vitro model of a reduced state. Thus, the triad of a) inconstant metabolite concentrations, b) inconstant KI.P/KBA, and c) ΔF both inconstant and non-zero, indicates that there is no state of equilibrium for these metabolite couplets in human plasma. The KI.P/KBA ratio appeared to reflect the degree of deviation from equilibrium and may therefore be useful when investigating altered redox states such as metabolic acidosis.