The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.
Objectives Intact urethral support and normal sphincter function are deemed important for urinary continence. We aimed to test whether the location of urethral kinking (as the probable anatomical correlate of maximal pressure transmission) is associated with stress urinary incontinence and/or urodynamic stress incontinence. Methods This was a retrospective study of women seen at a tertiary urogynecological center in 2017. Patients had undergone an interview, multichannel urodynamic testing and four‐dimensional translabial ultrasound examination. Those with a history of anti‐incontinence surgery, absence of urethral kinking on ultrasound and/or missing or inadequate ultrasound volume data were excluded. Volume data were used to assess urethral mobility using a semi‐automated Excel® urethral motion profile program. Mobility vectors were calculated using the formula √((x valsalva − x rest)2 + (y valsalva − y rest)2), where x and y are the coordinates of six equidistant points along the length of the urethra from the bladder neck to the external urethral meatus. The location of urethral kinking was identified as a concave contour of the urethra on the vaginal side in the midsagittal plane on maximum Valsalva maneuver. The distance between the center of the kink and the bladder neck was measured and expressed as a centile in relation to the total length of the urethra, using the formula: (distance from bladder neck/total length of urethra) × 100. Univariate and multivariate analyses were performed to test the associations of stress urinary incontinence and urodynamic stress incontinence with age, maximum urethral pressure, urethral mobility vectors and location of urethral kinking. Results Of 450 women seen during the study period, 61 were excluded owing to previous incontinence surgery and 82 owing to absence of urethral kinking, inadequate volume data or missing data, leaving 307 women included, of whom 227 (74%) complained of stress urinary incontinence and 211 (69%) complained of urgency urinary incontinence. 190 (62%) of the women were diagnosed with urodynamic stress incontinence. On multivariate analysis, maximum urethral pressure (36 vs 50 cmH2O; P < 0.001), mid‐urethral mobility (2.27 vs 2.03 cm; P = 0.003) and location of urethral kinking (63.1st vs 59.7th centile; P = 0.002) were associated significantly with urodynamic stress incontinence. The location of urethral kinking was associated with stress urinary incontinence on univariate analysis (P = 0.026) but not on multivariate analysis (P = 0.21). Conclusions The location of urethral kinking is associated with urodynamic stress incontinence. The further urethral kinking is from the mid urethra, the more likely is urodynamic stress incontinence. This provides circumstantial evidence for the pressure‐transmission theory of stress urinary continence. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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