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Trimethoprim-sulfamethoxazole in cyst fluid from autosomal dominant polycystic kidneys
L W Elzinga1, T A Golper, A L Rashad
1Department of Medicine, Oregon Health Sciences University, Portland.
Abstract:
Cyst infection in patients with autosomal-dominant polycystic kidney disease (ADPKD) is often refractory to therapy, in part because of the limited entry of commonly used antibiotics into cyst fluid. To study the efficacy of trimethoprim-sulfamethoxazole in cyst infection, cyst fluid was obtained by percutaneous aspiration or at surgery from eight patients with ADPKD receiving trimethoprim-sulfamethoxazole. Cysts were categorized as nongradient or gradient by cyst-fluid sodium concentration. Trimethoprim-sulfamethoxazole concentrations within cysts were determined and cyst fluid inhibitory and bactericidal titers were assessed in vitro against Escherichia coli, Proteus mirabilis and Streptococcus fecalis. The mean cyst fluid trimethoprim and sulfamethoxazole concentrations were 15.2 micrograms/ml and 42.5 micrograms/ml, respectively. Preferential accumulation of trimethoprim was observed in gradient cysts, exceeding serum levels more than eightfold. Sulfamethoxazole penetrated cysts to a lesser extent, with concentrations ranging from 10 to 70 percent of the serum level. Cyst fluid sampled prior to trimethoprim-sulfamethoxazole administration (control) demonstrated no antibacterial activity, while cyst fluid inhibitory and bactericidal titers following antibiotic administration were 1:32 or greater in most instances. These studies indicate that trimethoprim-sulfamethoxazole is likely to be efficacious in the treatment of cyst infection in polycystic kidneys.
Insights
Trimethoprim-sulfamethoxazole effectively penetrates cysts in autosomal-dominant polycystic kidney disease (ADPKD) patients. This antibiotic combination shows significant antibacterial activity in cyst fluid, suggesting efficacy for treating ADPKD cyst infections.
Area of Science:
- Nephrology
- Pharmacology
- Infectious Diseases
Background:
- Cyst infections in autosomal-dominant polycystic kidney disease (ADPKD) are challenging due to poor antibiotic penetration into cyst fluid.
- Limited antibiotic entry into cysts hinders effective treatment of ADPKD complications.
Purpose of the Study:
- To evaluate the efficacy of trimethoprim-sulfamethoxazole in treating cyst infections in ADPKD patients.
- To determine antibiotic concentrations and antibacterial activity within ADPKD cyst fluid.
Main Methods:
- Collected cyst fluid from eight ADPKD patients undergoing treatment with trimethoprim-sulfamethoxazole.
- Categorized cysts based on fluid sodium concentration (gradient vs. nongradient).
- Measured trimethoprim-sulfamethoxazole concentrations and assessed in vitro antibacterial activity (inhibitory and bactericidal titers) against common bacterial pathogens.
Main Results:
- Mean cyst fluid concentrations of trimethoprim and sulfamethoxazole were 15.2 and 42.5 µg/ml, respectively.
- Trimethoprim showed preferential accumulation in gradient cysts, exceeding serum levels eightfold.
- Cyst fluid demonstrated significant antibacterial activity (titer ≥ 1:32) post-antibiotic administration.
Conclusions:
- Trimethoprim-sulfamethoxazole demonstrates favorable penetration and potent antibacterial activity within ADPKD cysts.
- The findings suggest trimethoprim-sulfamethoxazole is a promising therapeutic option for ADPKD cyst infections.