Lithium pharmacokinetics in the obese.

INTRODUCTION: The purpose of this study was to investigate the disposition of lithium in obese subjects compared with the disposition in normal weight volunteers. METHODS: Ten obese volunteers (weight, 110.2 +/- 28.6 kg) were compared with eight evaluable normal weight volunteers (weight, 63.1 +/- 6.6 kg). Oral lithium citrate (31.4 mEq) was administered and blood samples were obtained over a 48-hour period. Creatinine clearance (CLCR) was determined from a 12-hour urine collection. Total body water was determined by the deuterium oxide dilution method. RESULTS: The clearance of lithium (CLLi) for the obese group was significantly greater than that for the control group (33.9 +/- 7.0 ml/min versus 23.0 +/- 6.2 ml/min; p = 0.005). The steady-state volume of distribution (VSS) for the obese group was significantly less than that for the control group (0.42 +/- 0.09 L/kg versus 0.66 +/- 0.16 L/kg; p = 0.001). For the combined group, VSS was significantly correlated with ideal body weight and fat free mass but not with total body weight. The CLLi was significantly correlated with total body weight, but not with CLCR. CONCLUSIONS: The pharmacokinetic properties of lithium were significantly different for the obese subjects compared with those the normal weight control subjects. At steady state there is a direct proportionality between CLLi and the dose required to achieve a given serum lithium concentration, therefore the results of this study suggest that obese patients may require larger lithium maintenance doses than nonobese patients.

Antibiotic susceptibility in the surgical intensive care unit compared with the hospital-wide antibiogram.

OBJECTIVE: To compare the antibiotic susceptibility of bacterial isolates from patients in the surgical intensive care unit (SICU) with hospital-wide bacterial susceptibility. DESIGN: Retrospective cohort analytic study. SETTING: Eight-bed SICU in a university-affiliated teaching hospital. PATIENTS: All hospitalized patients with culture results positive for microorganisms. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Antibiotic susceptibility data were collected retrospectively for all bacterial isolates from SICU patients during July 1, 1994, to June 30, 1995. All duplicate and surveillance cultures were eliminated from the data set. Susceptibility testing was conducted using our standard laboratory methods. Results were compared with the hospital-wide antibiogram (HWA) for the same time period. Comparisons were made using the chi(2) test with Yates correction or the Fisher exact test, as appropriate. Staphylococcus aureus (HWA, n=494; SICU, n=71) was significantly less susceptible to oxacillin (51% vs 28%; P<.001), ciprofloxacin (50% vs 25%; P<.001), erythromycin (46% vs 23%; P<.001), and clindamycin (51% vs 27%; P<.001) in the SICU. Coagulase-negative staphylococci (HWA, n=339; SICU, n=37) were significantly less susceptible to oxacillin (33% vs 16%; P=.04) and clindamycin (57% vs 34%; P=.02). Pseudomonas aeruginosa (HWA, n=513; SICU, n=96) was less susceptible to imipenem (85% vs 74%, P=.01) and more susceptible to ticarcillin-clavulanic acid (88% vs 100%, P<.001) in the SICU. Escherichia coli (HWA, n=474; SICU, n=36) was more susceptible to most penicillin-derivative antibiotics in the SICU (ampicillin [68% vs 83%, P=.06], ticarcillin [65% vs 86%, P=.01], mezlocillin [76% vs 95%, P=.01], and ticarcillin-clavulanic acid [88% vs 100%, P=.02]). CONCLUSIONS: The 2 most commonly isolated bacterial pathogens in the SICU (S aureus and P aeruginosa) had significantly different susceptibility patterns compared with the HWA. Surprisingly, E coli isolated in the SICU tended to be more susceptible to penicillin-derivative antibiotics. These data indicate that empiric antibiotic choices in the SICU may be better guided by unit-specific antibiograms.

Effects of metronidazole on hepatic CYP3A4 activity.

STUDY OBJECTIVE: To evaluate the effect of a short course of oral metronidazole, commonly used for bowel-preparation regimens, on hepatic cytochrome P450 (CYP) 3A4 activity, as measured by the [14C N-methyl]-erythromycin breath test (ERMBT) in healthy volunteers. DESIGN: Prospective, nonrandomized, interventional study SETTING: University-affiliated, community, teaching hospital. SUBJECTS: Five healthy male volunteers. INTERVENTION: Subjects underwent a baseline ERMBT in the morning before receiving three oral doses of metronidazole 500 mg administered at 3 P.M., 7 P.M., and 11 P.M. Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. Changes in ERMBT values were compared with baseline results using Freidman's repeated-measures analysis of variance on ranks. MEASUREMENTS AND MAIN RESULTS: The ERMBT values did not change significantly compared with baseline (p=0.82). Median (range) ERMBT values expressed as a percentage of baseline at 24, 72, and 96 hours were 110.3 (96.2-136.9), 101.3 (99.3-115.0), and 101.8 (95.5-116.3), respectively CONCLUSION: A short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity as measured by the ERMBT.

Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings.

STUDY OBJECTIVE: To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings. DESIGN: Randomized, open-label, single-dose, three-period crossover study. SETTING: University clinical research center. SUBJECTS: Ten healthy volunteers age 23-43 years. INTERVENTIONS: The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a nasogastric feeding tube placed through which PHT acid suspension 400 mg and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collected over 72 hours after each PHT dose, and the serum was analyzed for PHT. MEASUREMENTS AND MAIN RESULTS: The rate and extent of PHT absorption and PHT pharmacokinetics were determined using an empirical quadratic function of time method. Bioavailability, rate of absorption, maximum concentration (Cmax), and time to maximum concentration (Tmax) were compared for the two enteral doses by paired Student's t test. There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0.88 +/- 0.15 vs 0.91 +/- 0.7, p=0.57, 90% CI -0.14-0.071). The Cmax was greater (7.4 +/- 0.9 mg/L vs 5.5 +/- 1.7 mg/L, p=0.019) and Tmax was less (2.5 +/- 3.8 vs.14.8 +/- 11.2 hrs, p=0.004) for the sodium solution. The time to 50% fractional absorption (0.33 +/- 0.08 vs 3.2 +/- 2.4 hrs, p=0.004) and 90% fractional absorption (7.9 +/- 6.2 vs 22.3 +/- 17.2 hrs, p=0.021) was also significantly shorter for the sodium solution. CONCLUSION: The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed.

In vitro selection of resistant Helicobacter pylori.

Four strains of Helicobacter pylori were subjected to an in vitro serial passage technique to compare the propensity of the organisms to develop resistance to seven classes of antibacterial agents. The passages were made on serially doubling concentrations of antibacterial agents incorporated into agar starting at one-half the base-line MIC. The frequency of spontaneous resistance was also determined for each strain at four and eight times the MIC of each antibacterial agent. Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated. The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4- to 16-fold. With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium. Spontaneous resistance rates were generally of a low magnitude and were not predictive of the serial passage results.

[Intrapulmonary solitary round opacities. Diagnosis and therapy]. / Les opacités rondes solitaires intra-pulmonaires. Conduite diagnostique et thérapeutique.

The authors envisage the practical problems brought by unexpected intraparenchymal single round images seen on X ray. Thirty to 40% of these opacities proved to be malignant; the proportion rising over 50% in patients more than 50 years old. The great majority of these malignant tumours are primitive and the earlier the exeresis, the better the prognosis. The criteria of benignity (age under 35, presence of calcification amidst the opacity) are not always absolute. For fear of overlooking a malignant tumour, exploring thoracotomy is recommended.

Clinical response to intravenous nitroglycerin infused through polyethylene or polyvinyl chloride tubing.

The effects of polyethylene and polyvinyl chloride (PVC) administration sets on the clinical response to i.v. nitroglycerin were studied. Patients with ischemic heart disease were randomly assigned to receive nitroglycerin solution through either a polyethylene administration set or a PVC set. The rate of the infusion was 5-10 micrograms/min initially and was adjusted upward by 5-10 micrograms/min every 5-10 minutes until anginal symptoms were relieved or an adverse effect limited further increases. The data collected included patient demographics, the indication for nitroglycerin, nitroglycerin dosages, the initial dosage-adjustment time (the time necessary to reach the initial effective dosage), the number of dosage adjustments and the indications for them, the duration of the infusion, the time of tubing changes, the total dose of nitroglycerin, the amounts of sublingual nitroglycerin and i.v. morphine used, and the occurrence of various clinical events. There were 78 courses of therapy in the PVC group and 62 in the polyethylene group. The two groups were comparable in all respects except gender. There were no significant differences between the two groups in any of the primary study variables. Patients who received i.v. nitroglycerin through a PVC administration set had the same clinical response as patients given the drug through a polyethylene set.