In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid

Continuous ambulatory peritoneal dialysis is an important modality of therapy for patients with renal disease. However, peritonitis continues to be a major risk factor and is usually treated by intraperitoneal administration of antimicrobial agents. Few data are available concerning the stability of antimicrobial agents in peritoneal dialysis solution beyond 48 h. Our investigation was designed to establish the chemical and biological stability of gentamicin alone and in combination with cefazolin in peritoneal dialysis solution at 6 and 72 h by an immunoassay and by an in vitro bactericidal test against American Type Culture Collection (Rockville, Md.) strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. In addition, uninfected peritoneal dialysis effluent was inoculated with three American Type Culture Collection strains and gentamicin or imipenem. Gentamicin alone or in combination with cefazolin was not altered chemically and was bactericidal for Staphylococcus spp. but not P. aeruginosa. In contrast, imipenem was active against both Staphylococcus spp. and P. aeruginosa. Undefined factors other than inactivation of gentamicin may be responsible for the lack of bactericidal activity and treatment failure of Pseudomonas infections.

Section: Discussionsupporting

confidence: 52%

In vitro bactericidal activities of gentamicin, cefazolin, and imipenem in peritoneal dialysis fluids

Halstead

Guzzo

Giardina

et al. 1989

“…Ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dehydro-4-oxo-7-[1-piperazinyl]-3-quinolinecarboxylic acid hydrochloride), a new carboxyquinoline derivative, is highly effective in vitro against these organisms. Moreover, ciprofloxacin was found to have bactericidal activity in vitro against P. aeruginosa in peritoneal fluid obtained from patients undergoing CAPD (6). Thus, ciprofloxacin may prove to be a useful therapeutic agent in CAPD-related peritonitis, provided that adequate concentrations are achievable in peritoneal fluid.…”

mentioning

confidence: 99%

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis

Shalit¹,

Greenwood²,

Marks³

et al. 1986

Self Cite

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 ,ug/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 ,ug/ml, and

“…Finally, there is evidence in vitro that antibiotic activity is different in dianeal fluid than in standard broth. Significant impairment in the activities of aminoglycosides, fluoroquinolones, cephalosporins, and vancomycin has been shown in the comparison of MICs and minimum bactericidal concentrations in dianeal fluid to standard broth (12,28,30,31,33).…”

Section: Discussionmentioning

confidence: 99%

Peritoneal Fluid Titer Test for Peritoneal Dialysis-Related Peritonitis

Strijack

Harding

Ariano

et al. 2004

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.Peritonitis is a common and potentially serious infection of patients undergoing continuous ambulatory peritoneal dialysis (PD). Significant complications include hospitalization, protracted or recurrent infections, catheter removal, and an attributable mortality approaching 10% (4, 9, 10). Over the past decades, there have been significant reductions in the incidence of PD-related peritonitis (32) but only modest improvements in treatment, which fails in 20 to 30% of cases. Clinical studies are often restricted by relatively small patient numbers and inadequate power to detect significant differences among antibiotic therapies. Furthermore, delays in the identification and susceptibility testing of infecting pathogens lead to most, if not all, patients receiving empirical, broad-spectrum antibiotics before allocation to pathogen-directed treatments (14). Alternative methods to assess and compare antibiotic therapies for PD-related peritonitis are needed.Therapeutic decisions for the management of PD-related peritonitis are often guided by the standard microbiological test of antibiotic susceptibility, MIC. However, MIC interpretations do not account for the unique factors in PD-related peritonitis including (i) much higher intraperit...