Multiple-Dose-Kinetics of Ofloxacin after Intraperitoneal Application in CAPD Patients

1991 ◽  
Vol 11 (4) ◽  
pp. 317-321 ◽  
Author(s):  
Dieter Kampf ◽  
Klaus Borner ◽  
Hannelore Hain ◽  
Wolfgang Conrad
Keyword(s):  
Peritoneal Dialysis ◽  
Staphylococcus Epidermidis ◽  
Peritoneal Fluid ◽  
Multiple Dose ◽  
Plasma Concentrations ◽  
Drug Application ◽  
E Coli ◽  
Acute Peritonitis ◽  
The Mean ◽  
Kinetics Of

Pharmacokinetics of ofloxacin in plasma and peritoneal fluid were studied in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Seven patients without peritonitis received 20 mg ofloxacin added to 2L dialysate i.p. every 6 h for one day only, while 4 patients with acute peritonitis were treated with this same dosage every 4 h for 3 days, then every 6 h for the next 7 days. Ofloxacin concentrations in plasma and dialysate were determined by HPLC. After i.p. drug application there was a rapid elimination of ofloxacin from dialysate, this being significantly faster in patients with peritonitis as compared to those without. Likewise, the total amount lost from the first bag after a 3 h dwell was higher in the peritonitis group (84.7±1.5%; mean±SEM) than in the non-peritonitis group (75.6±2.1 %). Twenty-four h after start of ofloxacin treatment, the mean peritoneal fluid concentrations at the end of each exchange studied were all above 3 mg/L. In patients with peritonitis, plasma concentrations of ofloxacin rose to 0.94±0.05 mg/L after 24 h reaching a Cmax of 1.8±0.2 mg/L after a tmax of 84±23 h.lntraperitoneal administration of ofloxacin was well tolerated, and no local or systemic adverse events were observed. Peritonitis episodes that were caused by Staphylococcus epidermidis (3) and by E. coli (1) were cured in all patients.

scholarly journals Peritoneal Fluid Titer Test for Peritoneal Dialysis-Related Peritonitis

2004 ◽  
Vol 48 (5) ◽  
pp. 1719-1726 ◽  
Author(s):  
Christine Strijack ◽  
Godfrey K. M. Harding ◽  
Robert E. Ariano ◽  
Sheryl A. Zelenitsky
Keyword(s):  
Escherichia Coli ◽  
Peritoneal Dialysis ◽  
Pilot Study ◽  
Clinical Outcome ◽  
Staphylococcus Epidermidis ◽  
Peritoneal Fluid ◽  
Enterobacter Cloacae ◽  
Gram Positive Bacteria ◽  
Spent Dialysate ◽  
Preliminary Support

ABSTRACT Standard microbiological tests (i.e., MIC) do not account for the unique factors of peritoneal dialysis (PD)-related peritonitis which can significantly influence treatment response. Our goals were to develop a peritoneal fluid titer (PFT) test and to conduct a pilot study of its association with clinical outcome. The methodology was developed by using spent dialysate collected from patients with bacterial PD-related peritonitis prior to the initiation of antibiotics. Dialysate was processed and spiked with antibiotic to simulate two standard intraperitoneal regimens: cefazolin plus tobramycin and cefazolin alone. Thirty-six clinical isolates, including Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa, were tested. In the pilot study, dialysate was collected from 14 patients with bacterial PD-related peritonitis. Titers were determined by using each patient's dialysate and infecting pathogen. Titers were highly reproducible, with discrepancies in only 1% of cases. Overall, PFTs were notably higher against gram-positive bacteria (P < 0.0001). The addition of tobramycin increased titers significantly from zero to values of 1/16 to 1/64 against E. cloacae and P. aeruginosa (P < 0.0001). In the pilot study, peritoneal fluid inhibitory titers were significantly associated with clinical outcome, with a median value of 1/96 for patients who were cured compared to 1/32 for those who failed treatment (P = 0.036). In conclusion, this study provides preliminary support for the PFT as a pharmacodynamic index specific to the treatment of PD-related peritonitis. With further characterization and validation in patients, the PFT test may advance the study of antibiotic therapies for PD-related peritonitis.

Concentration of Adipokines in Peritoneal Effluent: A New Marker of Acute Peritonitis in Peritoneal Dialysis Patients?

2008 ◽  
Vol 28 (5) ◽  
pp. 527-632 ◽  
Author(s):  
Aureliusz Kolonko ◽  
Jerzy Chudek ◽  
Andrzej Więcek
Keyword(s):  
Peritoneal Dialysis ◽  
Membrane Permeability ◽  
Clinical Symptoms ◽  
Plasma Concentrations ◽  
Signs And Symptoms ◽  
Control Group ◽  
Peritoneal Membrane ◽  
Reactive Protein ◽  
Acute Peritonitis ◽  
Important Challenge

Background An early and reliable diagnostic procedure for acute peritonitis in patients on peritoneal dialysis (PD) without typical clinical symptoms remains an important challenge in modern nephrology. During the first days of peritonitis, establishing the diagnosis based on peritoneal effluent pleocytosis and inflammatory markers [C-reactive protein (CRP) or interleukin-6] is not efficient in all cases. Increased peritoneal membrane permeability is a well-known consequence of peritonitis. Therefore, we evaluated the concentrations of selected circulating adipose tissue-derived proteins in the peritoneal effluent of PD patients with episodes of acute peritonitis. Material and Methods Concentrations of adiponectin and leptin, in both plasma and peritoneal effluent, were assessed in 24 adult PD patients with peritonitis episodes confirmed by clinical symptoms and/or microbiological tests, and in 23 PD patients without signs and symptoms of inflammation (control group). Results In peritoneal effluent collected from patients with acute peritonitis (also without pleocytosis or increased CRP), both adiponectin and leptin concentrations were markedly elevated: adiponectin 744.1 (344.2 – 1144.1) ng/mL vs 4.8 (3.1 – 6.5) ng/mL; leptin 16.3 (9.4 – 23.1) ng/mL vs 5.1 (0.5 – 9.6) ng/mL. Receiver operating characteristic analyses revealed that peritoneal effluent adiponectin concentration >180 ng/mL has 100% sensitivity and 100% specificity, while peritoneal effluent leptin concentration >11.0 ng/mL has 58.3% sensitivity and 95.5% specificity for the diagnosis of acute peritonitis. The increases in adiponectin and leptin concentrations in peritoneal effluent were not consequences of changes in their plasma levels. A positive correlation between peritoneal effluent and plasma concentrations of adiponectin and leptin in patients with peritonitis was found. Conclusion Increased concentration of leptin and especially adiponectin in peritoneal effluent seems to be a valuable and new early marker of high peritoneal membrane permeability due to acute peritonitis.

Pharmacokinetics of intraperitoneal docetaxel and S-1 in patients with gastric cancer with peritoneal carcinomatosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15672-e15672
Author(s):  
K. Hayashi ◽  
H. Kamikozuru
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Carcinomatosis ◽  
Advanced Gastric Cancer ◽  
Peritoneal Fluid ◽  
Causes Of Death ◽  
Plasma Concentrations ◽  
Isotonic Saline ◽  
New Strategy ◽  
The Mean ◽  
High Concentrations

e15672 Background: One of the most causes of death from gastric cancer is peritoneal cartinomatosis. Intraperitoneal docetaxel infusion is expected to be a new strategy for a treatment of peritoneal carcinomatosis. The purpose of this study is to evaluate the plasma and peritoneal pharmacokinetic of intraperitoneal docetaxel infusion in combination with oral administration of S-1. Methods: Eight patients with peritoneal carcinomatosis of advanced gastric cancer were enrolled. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and administered in 2 hour via an implanted intraperitoneal catheter at dosage of 40mg/m2. Five of eight patients were administered S-1 orally at dosage of 80mg/m2. Blood and peritoneal fluid were collected before administration, on completion of the docetaxel infusion(hour 0) and at hours 1,2,4,6,12,24,48,and 72 after completion of the infusion of the docetaxel. Plasma and peritoneal fluid concentrations of docetaxel and 5FU were evaluated. Results: The mean peak peritoneal and plasma concentrations of docetaxel were 18.6×103 ng/ml (at hour 0) and 45 ng/ml (at hour 0 to 2), respectively. The peritoneal concentrations of docetaxel were remained even after 24 and 72 hours (24 hours: 1150ng/ml, 72 hours: 74ng/ml). In seven out of eight patients, plasma concentrations of docetaxel were disappeared after 24 hours, but in only one patient with severe ascites, concentration of plasma docetaxel at hour 24 could be obtained (20 ng/ml). The mean peritoneal and plasma areas under the curves (AUC) of doceta×el were 141x103 ng/ml×hr and 480 ng/ml×hr, respectively. The mean peritoneal concentrations of 5FU kept over 60% of plasma concentrations (plasma: 164.3ng/ml, peritoneal: 105ng/ml). Conclusions: Intaperitoneal docetaxel kept relatively high concentrations even after 72hours. 5FU concentrations were well transfered in peritoneal fluid from plasma via oral S-1 administration. Intraperitoneal docetaxel in combination with S-1 orally may be a useful regimen to the patients with carcinomatosis of advanced gastric cancer. No significant financial relationships to disclose.

Population pharmacokinetics of intra-peritoneal gentamicin and the impact of varying dwell times on pharmacodynamic target attainment in patients with acute peritonitis undergoing peritoneal dialysis

2021 ◽  
Author(s):  
Andras Farkas ◽  
Katerina Oikonomou ◽  
Mohammad Ghanbar ◽  
Phillip Villasurda ◽  
Julie Varghese ◽  
...  
Keyword(s):  
Body Weight ◽  
Peritoneal Dialysis ◽  
Population Pharmacokinetics ◽  
Multiple Dose ◽  
Treatment Success ◽  
Systemic Exposure ◽  
Break Point ◽  
Target Attainment ◽  
Acute Peritonitis ◽  
The Impact

While the use of intraperitoneal (i.p.) gentamicin is common in the treatment of peritoneal dialysis (PD)-related infections, the ability of these regimens to attain pharmacodynamic target indices of interest in blood and dialysate has not been widely reported. Pharmacokinetic (PK) data was obtained and analyzed from a multiple-dose PK study of i.p. gentamicin with 24 patients who received the drug at 0.6 mg/kg dose of body weight. The probability of target attainment (PTA) for indices of treatment success (i.p. peak/MIC ratio >10) and toxicity (plasma AUC < 120 mg*h/L) was determined for 0.3 to 1.2 mg/kg i.p. regimens every 24 h for dwell times of 2 to 6 hours and for the duration of 2-week course. In the peritoneum, successful PTA was achieved by all of the simulated regimens up to an MIC of 1 mg/L, and by doses equal to or greater than 0.6 mg/kg up to the MIC of 2 mg/L. At the susceptibility break point of 4 mg/L only the highest dose of 1.2 mg/kg is likely to provide adequate PTA. Probability of achieving exposure below the threshold of 120 mg*h/L in the daily AUC in plasma seems acceptable for all regimens at or below 0.6 mg/kg. Based on the model we developed, a gentamicin dose of 0.6 mg/kg is sufficient to treat organisms with an MIC of ≤2 mg/L without the risk of significant systemic exposure. The 1.2 mg/kg dose necessary to reach the pharmacodynamic target for efficacy at the clinical break point of 4 mg/L is likely to produce early toxic levels of exposure that is expected to be detrimental to the renal system.

Bactericidal Activity of 0.5% Bupivacaine With Preservatives on Microorganisms in the Human Skin Flora

1997 ◽  
Vol 22 (2) ◽  
pp. 178-184
Author(s):  
Tadakazu Sakuragi ◽  
Hiroyuki Ishino ◽  
Kenjiro Dan
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Body Temperature ◽  
Bactericidal Activity ◽  
Staphylococcus Epidermidis ◽  
Room Temperature ◽  
Physiological Saline ◽  
E Coli ◽  
Skin Flora ◽  
The Mean

Background and ObjectivesThe bactericidal activity of 0.5% bupivacaine with preservatives at body temperature and at room temperature is not known. We studied the bactericidal activity of 0.5% bupivacaine with 0.08% methyl para-oxybenzoate and 0.02% propyl para-aminobenzoate as preservatives and of the preservatives alone at 37°C and at room temperature on two strains of methicillin-resistant Staphylococcus aureus, two strains of methicillin-susceptible S. aureus, and one strain each of Staphylococcus epidermidis and Escherichia coli. Methods. The pathogen was exposed to 0.5% bupivacaine with preservatives or to the preservatives alone for 1, 3, 6, 12, and 24 hours at 37°C and at room temperature. The inocula from these suspensions were cultured for 48 hours at 37°C after the antimicrobial activity of bupivacaine was inactivated by 1:1,000 dilution with physiological saline.ResultsThe 1- through 12-hour exposures of four strains of S. aureus to 0.5% bupivacaine with preservatives at room temperature reduced the mean colony count by 24.2%, 49.2%, 71.3%, and 89.6%, respectively, and the exposure at 37°C reduced the count by 74.1%, 95.2%, 99.9%, and 99.8%, respectively. The differences for 1- through 12-hour exposures were significant (P < .001). The percentage kill in the strains of E. coli and S. epidermidis was significantly higher than that in the strains of S. aureus at all exposure times at room temperature (E. coli, P < .001; S. epidermidis, P < .0001) and at 1- and 3-hour exposures at 37°C (E. coli, P < .001; S. epidermidis, P < .0001). The bactericidal activity of the preservatives was markedly lower that that of 0.5% bupivacaine with preservatives (P < .0001).ConclusionsThe bactericidal activity of 0.5% bupivacaine with preservatives is stronger at body temperature than at room temperature; the bactericidal activity may be due, to a large extent, to bupivacaine rather than to the preservatives; and S. aureus is more resistant to the bactericidal activity of bupivacaine than are S. epidermidis and E. coli.

scholarly journals Intraperitoneal Activity of Heparin During Peritoneal Dialysis

1977 ◽  
Author(s):  
E.D. Gomperts ◽  
K.I. Furman ◽  
J. Hockley
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Antithrombin Iii ◽  
Systemic Blood ◽  
Slow Decay ◽  
Low Concentrations ◽  
Heparin Activity ◽  
The Mean ◽  
Control Plasma ◽  
Intraperitoneal Haemorrhage

Heparin is frequently added to peritoneal dialysate to prevent the formation of thrombi with the resulting obstruction of peritoneal catheters. As a guide for such therapy the pharmacokinetics of intraperitoneal heparin was studied in 11 patients undergoing maintenance peritoneal dialysis. The heparin activity was assessed by adding dialysate to control plasma and measuring the prolongation effect on the activated partial thromboplastin time (A-PTT). It was observed that the A-PTT was prolonged in proportion to the amount of heparin in the peritoneal fluid. The decay of this activity was relatively slow with the mean T½ in the peritoneal cavity being 10.78 ± 0.93h. Systemic blood coagulation was unaffected by single 10,000 U intraperitoneal doses of heparin in that plasma A-PTT's were not lengthened over the ensuing 6 hours. Antithrombin III assessed by immunochemical and functional procedures was present in low concentrations in residual peritoneal fluid aspirated prior to commencing dialysis. Generally this was less than 1/3 of normal plasma values, and with the repeated dilution and outflow sequences of dialysis, the cofactor concentrations fell to negligible levels, usually below 1% by the end of the second cycle. These results indicate therefore that despite the persistence and slow decay of heparin within the peritoneal activity, therapeutic efficacy is unlikely to be achieved except in those cases where adequate cofactor might be introduced as a result of massive intraperitoneal haemorrhage.

scholarly journals Predicting plasma concentrations of common biochemical values from residual peritoneal fluid in patients on peritoneal dialysis.

BMJ ◽  
1978 ◽  
Vol 1 (6128) ◽  
pp. 1670-1670
Author(s):  
M K Chan ◽  
Y C Huang ◽  
Z Varghese ◽  
R A Baillod ◽  
J F Moorhead
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Plasma Concentrations

The Relationship of P1 and Lewis Antigens with Peritoneal Dialysis–Related Escherichia Coli Peritonitis

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 172-178
Author(s):  
I-Wen Ting ◽  
Tze-Wah Kao ◽  
Yen-Ling Chiu ◽  
Shyh-Chyi Lo ◽  
Fu-Chang Hu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Peritoneal Dialysis ◽  
Recurrent Events ◽  
Cox Proportional Hazards ◽  
Blood Type ◽  
Lewis Antigens ◽  
Right Censored Data ◽  
E Coli ◽  
The Mean ◽  
Lewis A

It has been known that the P1 and Lewis antigens on red blood cells (RBCs) affect the risk of Escherichia coli–related urinary tract infection. In the present study, we investigated the associations between those antigens and peritoneal dialysis (PD)–related peritonitis and E. coli peritonitis. We recruited 155 patients (66 men, 89 women) who were under PD treatment in July 2005, checked the P1 and Lewis antigen status of their RBCs, reviewed their medical charts, and recorded the dates and the causative pathogens of peritonitis episodes. The relationships between peritonitis and the antigens were analyzed. The mean age of these PD patients was 52.5 ± 14.9 years, and the mean PD duration was 39.8 ± 38.2 months. A total of 66 peritonitis episodes occurred (over 93.4 patient– months) in 41 patients, with 8 patients having more than 1 episode. In particular, E. coli peritonitis accounted for 16 of the 66 peritonitis episodes. We fitted two multiple Cox proportional hazards models (with the robust variance method) for predicting the hazard rates of peritonitis-free and E. coli peritonitis-free survival times to our right-censored data with recurrent events. We found that patients on PD treatment for less than 4 years with (A) lower serum albumin, (B) one or more previous peritonitis episodes, or (C) negative Lewis a and positive Lewis b antigens (secretor) would be at higher risk of peritonitis. And, conditioning on blood type, the PD patients with one or more previous peritonitis episodes and (A) positive P1 antigen, (B) negative Lewis a and positive Lewis b antigens (secretor), or (C) positive Lewis a and negative Lewis b antigens (non-secretor) would be at higher risk of E. coli peritonitis.

Effect of Peritoneal Dialysis on Plasma and Peritoneal Fluid Concentrations of Isoniazid, Pyrazinamide, and Rifampin

2003 ◽  
Vol 23 (4) ◽  
pp. 362-367
Author(s):  
Curie Ahn ◽  
Kook-Hwan Oh ◽  
Kiwon Kim ◽  
Kyung Yi Lee ◽  
Jung Geon Lee ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
High Performance ◽  
Inhibitory Concentration ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Analysis ◽  
Dialysis Patients ◽  
Pharmacokinetic Profiles ◽  
Fluid Concentration

♦ Objective This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients. ♦ Patients Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study. ♦ Methods After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis. ♦ Results Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time. ♦ Conclusion For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.

Azithromycin: An Assessment of Its Pharmacokinetics and Therapeutic Potential in CAPD

2001 ◽  
Vol 21 (4) ◽  
pp. 372-377 ◽  
Author(s):  
James R. Kent ◽  
Michael K. Almond ◽  
Soraya Dhillon
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Future Research ◽  
Renal Unit ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

Background Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Objective This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. Design The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. Setting The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Patients Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Results Peak plasma concentrations occurred at 2 -3 hours with 0.35 - 1.35 mg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 mg/mL; PD clearance was 0.06 L/hr. Conclusion Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

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