Pharmacokinetics of once daily intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients.
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This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 +/- 3.1%, volume of distribution 0.20 +/- 0.05 L/kg, and plasma half-life 39.9 +/- 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 +/- 2.3, 1. 4 +/- 1.1, and 3.5 +/- 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 +/- 14.3 and 31.8 +/- 11. 7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis. (+info)
Pharmacokinetics of intermittent intravenous cefazolin and tobramycin in patients treated with automated peritoneal dialysis.
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There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler : 10.67 +/- 4.66 h; cefazolin off cycler : 23.09 +/- 5.6 h; P = 0.001; tobramycin on cycler : 14.27 +/- 4.53 h; tobramycin off cycler : 68. 5 +/- 26.47 h; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg); however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients. (+info)
A survey of CAPD peritonitis management and outcomes in North and South Thames NHS regions (U.K.): support for the ISPD guidelines. International Society for Peritoneal Dialysis.
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OBJECTIVE: This survey examined the current management of continuous ambulatory peritoneal dialysis (CAPD) peritonitis and the effectiveness of the various antibiotic protocols in use. DESIGN: The information required was elicited via a postal questionnaire. SETTING: The questionnaire was posted to each renal dialysis unit offering CAPD throughout the North and South Thames National Health Service regions. PATIENTS: All patients using CAPD at each responding unit were eligible for inclusion. MAIN OUTCOME MEASURES: Each unit provided details of their CAPD peritonitis episodes for 1997. Each unit's empirical treatment regimen for CAPD peritonitis was sought in addition to response rates. Also requested were numbers for peritonitis episodes, recurrences, and negative cultures, plus the peritonitis rate per patient-month. RESULTS: Thirteen units returned the questionnaire (87% of the survey population). Nine of the 13 units were using vancomycin regimens, with the remainder using cephalosporin regimens. The results were compared to the audit standards of the British Renal Association. Seventy percent of units reached the 80% mark for response rate; similar results were achieved with both the vancomycin and cephalosporin regimens. Ninety-two percent achieved the suggested peritonitis rate of 1 episode every 18 patient-months; 30% achieved the culture-negative rate of 10%. The average recurrence rate was 19%. CONCLUSION: The units contacted achieved most of the standards suggested by the British Renal Association; however, wide variations did exist. Recent guidelines have suggested avoiding vancomycin-based regimens in order to reduce the incidence of vancomycin resistance. The suggested regimen of a cephalosporin with an aminoglycoside seems to represent a suitable alternative. (+info)
Infection related to intracranial pressure monitors in adults: analysis of risk factors and antibiotic prophylaxis.
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OBJECTIVE: Infection is a complication related to intracranial pressure monitoring devices. The timing, duration, and role of prophylactic antimicrobial agents against intracranial pressure monitor (ICPM) related infection have not previously been well defined. Risk factors and selection, duration, and timing of antibiotic prophylaxis in patients with ICPMs were evaluated. METHODS: Records of all consecutive patients who underwent ICPM insertion between 1993 and 1996 were reviewed. Patients included were older than 12 years with an ICPM placed for at least 24 hours. Exclusion criteria consisted of ICPM placed before admission or documented CSF infection before or at the time of insertion. Standard criteria were applied to all patients for diagnosis of CSF infection. RESULTS: A total of 215 patients were included, 16 (7.4%) of whom developed CSF infection. Antibiotic prophylaxis for ICPM placement was administered to 63% of infected and 59% of non-infected patients. Vancomycin (60%) and cefazolin (34%) were used most often. Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of those without CSF infection received their first antibiotic dose within the 2 hours before ICPM insertion. Risk factors for CSF infection included duration of monitoring greater than 5 days (RR 4.0 (1.3-11.9)); presence of ventriculostomy (RR 3.4 (1.0-10.7)); CSF leak (RR 6.3 (1.5-27.4)); concurrent systemic infection (RR 3.4 (1.2-9.5)); or serial ICPM (RR 4.9 (1. 7-13.8)). CONCLUSIONS: Administration of antibiotics to patients before or at the time of ICPM placement did not decrease the incidence of CSF infection. Patients found to be at greater risk for infection at our institution included duration of ICPM greater than 5 days, use of ventricular catheter, CSF leak, concurrent systemic infection, or serial ICPM. (+info)
Effect of protein concentration and binding on antibiotic assays.
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ASSAY CURVES, USING A DISK DIFFUSION METHOD FOR THE ANTIBIOTICS GENTAMICIN AND CEFAZOLIN, WERE PREPARED WITH: saline, saline plus 10% serum, and ascitic, synovial, cerebrospinal, and pleural fluids. The curves were compared with a standard curve prepared with pooled human serum. The pH, total protein, glucose, blood urea nitrogen, sodium, potassium, calcium, phosphorus, chloride, CO(2) content, uric acid, cholesterol, bilirubin, serum glutamic oxalacetic transaminase, CPK, LDH, and alkaline phosphatase were determined and compared for all fluids. Measurements for cefazolin levels were falsely elevated in those fluids with low protein content when serum was used as a reference standard. There was a linear inverse relationship between the protein content of the fluids and the cefazolin level with serum as the standard for the assay of this highly protein-bound antibiotic. No discrepancies were observed in the assay curves for gentamicin, an antibiotic known not to be bound by serum proteins. (+info)
Correlation of intraperitoneal antibiotic pharmacokinetics and peritoneal membrane transport characteristics.
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OBJECTIVE: To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy. DESIGN AND METHODS: This retrospective study re-evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients. Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient (r). RESULTS: Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin (r values ranged from 0.698 to 0.986; p < 0.05). CONCLUSION: These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration. (+info)
Nocardia Asteroides keratitis: report of seven patients and literature review.
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PURPOSE: To describe clinical features and treatment outcomes in patients with advanced Nocardia asteroides keratitis. METHODS: Retrospective review of case records of 7 patients with culture-proven Nocardia keratitis. RESULTS: Corneal infection occurred after corneal trauma in two patients, cataract surgery in three patients, penetrating keratoplasty in one patient and was associated with a silicone buckle element infection in one patient. Mean duration of infection at presentation was 33.4 days (7-75 days), and five patients had received prior treatment with corticosteroids. Six of seven patients had deep corneal suppuration at the time of presentation, clinically suggestive of mycotic keratitis. In two patients who had received prolonged corticosteroid therapy (> or = 45 days), the eyes could not be salvaged. Complete resolution of infection was achieved in all 4 eyes treated with topical fortified cefazolin eye drops (50 mg/ml). (+info)
Activity of cefazolin against dense populations of enterobacteria.
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The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible and -resistant strains of Escherichia coli at a lower concentration than any other beta-lactam agent tested; its stability to beta-lactamase, as judged by regrowth studies, was generally considerably greater than that of other antibiotics of this group. Tested against 103 ampicillin-resistant enterobacteria, cefazolin was found to be more active than cephalothin against E. coli, but no systematic increase in susceptibility to cefazolin was seen with other species. A study of cefazolin in an in vitro model which simulates the hydrokinetic features of the urinary bladder showed it to be as active as ampicillin against ampicillin-susceptible E. coli and as active as cephalothin against ampicillin-resistant E. coli. (+info)