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Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin, Tazobactam, and Vancomycin During Negative Pressure Wound Therapy.

ABSTRACT: Objective: Negative pressure wound therapy (NPWT) uses subatmospheric pressure as a noninvasive adjunct to treat wounds and has demonstrated clinical efficacy by accelerating healing of a variety of acute and chronic wounds. NPWT may also play a role in preventing or treating wound infections, possibly by increasing wound penetration of antibiotics. However, clinical data in patients undergoing antibiotic and NPWT treatment are limited. Approach: To evaluate the wound penetration of antibiotics in NPWT patients, we conducted a prospective, observational study of burn and trauma patients treated with NPWT and systemic antibiotics. We evaluated the plasma pharmacokinetic profile of systemic vancomycin, ciprofloxacin, cefazolin, and piperacillin/tazobactam, as well as total and unbound antibiotic concentrations in wound exudate from the same patients. Results: Data from 32 patients with 37 wounds undergoing NPWT demonstrated that vancomycin, ciprofloxacin, and piperacillin/tazobactam all penetrated wounds with exudate to plasma concentration ratios more than 0.8. Cefazolin did not penetrate wounds in patients undergoing NPWT as effectively, with an average exudate to plasma concentration ratio of 0.51. Innovation: Clinical data on the wound penetration of antibiotics in patients undergoing NPWT are limited, but these data suggest that antibiotics have different capacities for wound penetration during NPWT that should be considered when making clinical decisions. Conclusion: This initial report suggests that (1) vancomycin, ciprofloxacin, and piperacillin/tazobactam effectively penetrate wounds during NPWT and (2) cefazolin as well as other antibiotics may not penetrate wounds during NPWT.

SUBMITTER: Rowan MP

PROVIDER: S-EPMC5286546 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin, Tazobactam, and Vancomycin During Negative Pressure Wound Therapy.

Rowan Matthew P MP Niece Krista L KL Rizzo Julie A JA Akers Kevin S KS

Advances in wound care 20170201 2

<b>Objective:</b> Negative pressure wound therapy (NPWT) uses subatmospheric pressure as a noninvasive adjunct to treat wounds and has demonstrated clinical efficacy by accelerating healing of a variety of acute and chronic wounds. NPWT may also play a role in preventing or treating wound infections, possibly by increasing wound penetration of antibiotics. However, clinical data in patients undergoing antibiotic and NPWT treatment are limited. <b>Approach:</b> To evaluate the wound penetration o ...[more]

PMID: 28224048

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Project description:Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P ⟨ 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74-2.39; aOR, 2.31; 95% CI, 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy. Journal of Hospital Medicine 2017;12:77-82.

Project description:Importanceβ-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.ObjectiveTo assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal β-lactam antibiotic throughout the first week of hospitalization.Design, setting, and participantsThis retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal β-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.).Main outcomes and measuresThe primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal β-lactam antibiotic.ResultsA total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal β-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).Conclusions and relevanceCoadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Project description:Negative pressure wound therapy (NPWT) has been used to promote wound healing in a variety of settings, including as an adjunct to silver-impregnated dressings in the acute management of paediatric burns. Fluid aspirated by the NPWT system represents a potentially insightful research matrix for understanding the burn wound microenvironment and the biochemical mechanisms of action of NPWT. The aim of this study was to characterise the proteome of wound fluid collected using NPWT from children with small-area thermal burns. Samples were obtained as part of a randomised controlled trial investigating the clinical efficacy of adjunctive NPWT. They were compared with blister fluid specimens from paediatric burn patients matched according to demographic and injury characteristics. Protein identification and quantification were performed via liquid chromatography tandem mass spectrometry (LC-MS/MS) and sequential window acquisition of all theoretical mass spectra (SWATH) data-independent acquisition. Proteins and biological pathways which were unique or enriched in negative pressure fluid samples were evaluated using principal components, partial least squares-discriminant, and gene ontology enrichment analyses. Eight viable samples of NPWT fluid were collected and analysed with eight matched blister fluid samples. A total of 502 proteins were quantitatively profiled in the NPWT fluid, of which 444 (88.4%) were shared with blister fluid. Several proteins exhibited significant abundance differences between fluid types, with NPWT fluid showing a higher abundance of proteases matrix metalloprotease-9 and arginase-1, immune cell surface molecule low affinity immunoglobulin gamma Fc region receptor III-A, actin-binding protein filamin-A, plasma protein alpha-2-macroglobulin, and haemoglobin subunit alpha. The results lend support to the hypothesis that NPWT augments wound healing through the modulation of factors involved in the inflammatory response, granulation tissue synthesis, and extracellular matrix maintenance.

Dataset Information

Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin, Tazobactam, and Vancomycin During Negative Pressure Wound Therapy.

Publications

Wound Penetration of Cefazolin, Ciprofloxacin, Piperacillin, Tazobactam, and Vancomycin During Negative Pressure Wound Therapy.

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