Pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg

PurposeTo investigate the pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg.Material/methods.Plasma concentrations were measured in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3 [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples were drawn at the following time points 0, 0.5, 6, 8 hours after infusion. Ciprofloxacin concentrations were determined by high-performance liquid chromatography. Results. In the cases where ciprofloxacin was applied in targeted antibiotic therapy the minimum inhibitory concentrations (MIC) were ≤0.5 mg/l. The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58-7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic parameters for ciprofloxacin in the analyzed patients were as follows: k_el, 0.21 h^?1; t_1/2kel, 3.37 h; AUC_0-inf, 10.10 mg×h/l; AUMC_0-last, 15.36 mg×h²/l; MRT, 1.71 h; V_d, 214.8 l; Cl, 39.70 l/h. Considering the maximum value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values of the PK/PD indexes AUIC>125 and C_max /MIC>10, respectively.Conclusions.The target plasma concentrations after the first dose of ciprofloxacin were reached only in a few critically ill patients. Considerable inter-subject variability for PK/PD parameters in ICU patients requires systematic monitoring.     

The relationship between CR3 deficiency and neutrophil actin assembly

Polymorphonuclear leukocytes (PMN) with a deficiency of the complement receptor type 3 (CR3) membrane glycoprotein family have impairments in the ability to adhere to surfaces as well as chemotactic and phagocytic defects, processes that require a functional contractile apparatus. PMN from the patient with neutrophil actin dysfunction (NAD) displayed similar functional characteristics to those with CR3 deficiency suggesting the two disorders may be the same disease. In order to evaluate the relationship between CR3 deficiency and actin assembly, actin filament assembly was measured in PMN from six previously reported homozygotes (two severe and four moderate CR3-deficient patients) as well as five heterozygotes for CR3 deficiency. PMN from all patients had normal unstimulated concentrations of F-actin and after exposure to the chemotactic peptide FMLP (5 x 10(-7) mol/L for 5 to 40 seconds at 25 degrees C) assembled actin normally. Pretreatment of normal PMN with concentrations of monoclonal anti-alpha CR3 antibody, capable of blocking PMN adherence, also failed to impair FMLP- induced actin filament assembly. CR3 glycoprotein expression was measured in PMNs from the mother, father, and older sister of the NAD patient (N Engl J Med 291:1093, 1974). Actin filament assembly was recently shown to be defective in PMNs from all three family members. The total concentrations of the alpha and beta CR3 subunits were below normal in PMN detergent extracts from the mother (25% of simultaneous controls) and older sister (56% of control). PMN surface expression of these two subunits was also found to be depressed (mother, 50%; older sister, 63% of control). These findings suggest these two NAD family members are heterozygote carriers for CR3 deficiency as well as NAD. Simultaneous studies of the father, however, demonstrated normal total concentrations of both the alpha and beta CR3 subunits (126% of controls) as well as normal surface expression of both subunits after phorbol myristate acetate stimulation and incubation at 37 degrees C (mean, 112% of controls) but slightly lower than normal levels after FMLP stimulation (mean, 83%). These findings indicate that CR3 deficiency generally is not associated with defective actin filament assembly and support the conclusion that NAD represents a unique kindred in which PMN actin function differs from previously reported genotypes of CR3 deficiency.     

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.     

Private Investment Purchase and Nursing Home Financial Health

Objective

To explore the impact of nursing home acquisition by private investment firms on nursing home costs, revenue, and overall financial health.

Data Sources

Merged data from the Medicare Cost Reports and the Online Survey, Certification, and Reporting system for the period 1998–2010.

Study Design

Regression specification incorporating facility and time fixed effects.

Principal Findings

We found little impact on the financial health of nursing homes following purchase by private investment companies. However, our findings did suggest that private investment firms acquired nursing home chains in good financial health, possibly to derive profit from the company’s real estate holdings.

Conclusions

Private investment acquired facilities are an important feature of today’s nursing home sector. Although we did not observe a negative impact on the financial health of nursing homes, this development raises important issues about ownership oversight and transparency for the entire nursing home sector.