Comparison of piperacillin exposure in the lungs of critically ill patients and healthy volunteers.

Background: Severe infections of the respiratory tracts of critically ill patients are common and associated with excess morbidity and mortality. Piperacillin is commonly used to treat pulmonary infections in critically ill patients. Adequate antibiotic concentration in the epithelial lining fluid (ELF) of the lung is essential for successful treatment of pulmonary infection. Objectives: To compare piperacillin pharmacokinetics/pharmacodynamics in the serum and ELF of healthy volunteers and critically ill patients. Methods: Piperacillin concentrations in the serum and ELF of healthy volunteers and critically ill patients were compared using population methodologies. Results: Median piperacillin exposure was significantly higher in the serum and the ELF of critically ill patients compared with healthy volunteers. The IQR for serum piperacillin exposure in critically ill patients was six times greater than for healthy volunteers. The IQR for piperacillin exposure in the ELF of critically ill patients was four times greater than for healthy volunteers. The median pulmonary piperacillin penetration ratio was 0.31 in healthy volunteers and 0.54 in critically ill patients. Conclusions: Greater variability in serum and ELF piperacillin concentrations is observed in critically ill patients compared with healthy adult subjects and must be considered in the development of dosage regimens. Pulmonary penetration of antimicrobial agents should be studied in critically ill patients, as well as healthy volunteers, during drug development to ensure appropriate dosing of patients with pneumonia.

Tools for the Individualized Therapy of Teicoplanin for Neonates and Children.

The aim of this study was to develop a population pharmacokinetic (PK) model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the software constructed for individualized therapy. We developed a nonparametric population model fitted to PK data from neonates, infants, and older children. We then implemented this model in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility. It was used to predict the dosages required to achieve optimal teicoplanin predose targets (15 mg/liter) from day 3 of therapy. We performed individual simulations for an infant and a child from the original population, who provided early first dosing interval concentration-time data. An allometric model that used weight as a measure of size and that also incorporated renal function using the estimated glomerular filtration rate (eGFR), or the ratio of postnatal age (PNA) to serum creatinine concentration (SCr) for infants <3 months old, best described the data. The median population PK parameters were as follows: elimination rate constant (Ke) = 0.03 · (wt/70)-0.25 · Renal (h-1); V = 19.5 · (wt/70) (liters); Renal = eGFR0.07 (ml/min/1.73 m2), or Renal = PNA/SCr (µmol/liter). Increased teicoplanin dosages and alternative administration techniques (extended infusions and fractionated multiple dosing) were required in order to achieve the targets safely by day 3 in simulated cases. The software was able to predict individual measured concentrations and the dosages and administration techniques required to achieve the desired target concentrations early in therapy. Prospective evaluation is now needed in order to ensure that this individualized teicoplanin therapy approach is applicable in the clinical setting. (This study has been registered in the European Union Clinical Trials Register under EudraCT no. 2012-005738-12.).

Pharmacodynamics of teicoplanin against MRSA.

OBJECTIVES: The overall study aim was to identify the relevant preclinical teicoplanin pharmacokinetic (PK)/pharmacodynamic (PD) indices to predict efficacy and suppression of resistance in MRSA infection. METHODS: A hollow-fibre infection model and a neutropenic murine thigh infection model were developed. The PK/PD data generated were modelled using a non-parametric population modelling approach with Pmetrics. The posterior Bayesian estimates derived were used to study the exposure-effect relationships. Monte Carlo simulations from previously developed population PK models in adults and children were conducted to explore the probability of target attainment (PTA) for teicoplanin dosage regimens against the current EUCAST WT susceptibility range. RESULTS: There was a concentration-dependent activity of teicoplanin in both the in vitro and in vivo models. A total in vivo AUC/MIC of 610.4 (total AUC of 305.2 mg·h/L) for an MRSA strain with an MIC of 0.5 mg/L was needed for efficacy (2 log10 cell kill) against a total bacterial population. A total AUC/MIC ratio of ∼1500 (total AUC of ∼750 mg·h/L) was needed to suppress the emergence of resistance. The PTA analyses showed that adult and paediatric patients receiving a standard regimen were only successfully treated for the in vivo bactericidal target if the MIC was ≤0.125 mg/L in adults and ≤0.064 mg/L in children. CONCLUSIONS: This study improves our understanding of teicoplanin PD against MRSA and defines an in vivo AUC/MIC target for efficacy and suppression of resistance. Additional studies are needed to further corroborate the PK/PD index in a variety of infection models and in patients.

Population pharmacokinetics and pharmacodynamics of teicoplanin in neonates: making better use of C-reactive protein to deliver individualized therapy.

OBJECTIVES: There is uncertainty about the optimal teicoplanin regimens for neonates. The study aim was to determine the population pharmacokinetics (PK) of teicoplanin in neonates, evaluate currently recommended regimens and explore the exposure-effect relationships. METHODS: An open-label PK study was conducted. Neonates from 26 to 44 weeks post-menstrual age were recruited (n = 18). The teicoplanin regimen was a 16 mg/kg loading dose, followed by 8 mg/kg once daily. Therapeutic drug monitoring and dose adjustment were not conducted. A standard two-compartment PK model was developed, followed by models that incorporated weight. A PK/pharmacodynamic (PD) model with C-reactive protein serial measurements as the PD input was fitted to the data. Monte Carlo simulations (n = 5000) were performed using Pmetrics. The AUCs at steady state and the proportion of patients achieving the recommended drug exposures (i.e. Cmin >15 mg/L) were determined. The study was registered in the European Clinical Trials Database Registry (EudraCT: 2012-005738-12). RESULTS: The PK allometric model best accounted for the observed data. The PK parameters medians were: clearance = 0.435 × (weight/70)0.75 (L/h); volume = 0.765 (L); Kcp = 1.3 (h-1); and Kpc = 0.629 (h-1). The individual time-course of C-reactive protein was well described using the Bayesian posterior estimates for each patient. The simulated median AUC96-120 was 302.3 mg·h/L and the median Cmin at 120 h was 12.9 mg/L; 38.8% of patients attained a Cmin >15 mg/L by 120 h. CONCLUSIONS: Teicoplanin population PK is highly variable in neonates, weight being the best descriptor of PK variability. A low percentage of neonates were able to achieve Cmin >15 mg/L. The routine use of therapeutic drug monitoring and improved knowledge on the PD of teicoplanin is required.

Pharmacodynamics of vancomycin for CoNS infection: experimental basis for optimal use of vancomycin in neonates.

OBJECTIVES: CoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage regimens. METHODS: A hollow fibre and a novel rabbit model of neonatal central line-associated bloodstream CoNS infections were developed. The results were then bridged to neonates by use of population pharmacokinetic techniques and Monte Carlo simulations. RESULTS: There was a dose-dependent reduction in the total bacterial population and C-reactive protein levels. The AUC/MIC and Cmax/MIC ratios were strongly linked with total and mutant resistant cell kill. Maximal amplification of resistance was observed in vitro at an fAUC/MIC of 200 mg ·â€Šh/L. Simulations predicted that neonates <29 weeks post-menstrual age are underdosed with standard regimens with respect to older age groups. CONCLUSIONS: The AUC/MIC and Cmax/MIC ratios are the pharmacodynamic indices that best explain total and resistant cell kill in CoNS infection. This suggests that less-fractionated regimens are appropriate for clinical use and continuous infusions may be associated with increased risk of emergence of antimicrobial resistance. This study has provided the pharmacodynamic evidence to inform an optimized neonatal dosage regimen to take into a randomized controlled trial.

Pharmacodynamics of fosfomycin: insights into clinical use for antimicrobial resistance.

The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing E. coli strains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycin-resistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [for E. coli urinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (fAUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically against E. coli strains in preventing the emergence of fosfomycin resistance.

Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis.

OBJECTIVES: Limited information about the pharmacokinetics of micafungin in the peritoneal cavity is available. The aim of this study was to explore the pharmacokinetics/pharmacodynamics of micafungin in plasma and peritoneal fluid in post-surgical critically ill patients with proven or suspected intra-abdominal fungal infection. METHODS: Patients were administered 100 mg/day micafungin. Serial blood and peritoneal fluid samples were collected on day 1 and day 3 (steady-state) of treatment. Concentrations were determined by validated chromatography and were subject to a population pharmacokinetic analysis with Pmetrics(®). Monte Carlo simulations were performed for AUC0-24/MIC ratios in plasma. The PTA was calculated using AUC0-24/MIC cut-offs: 285 for Candida parapsilosis and 3000 for non-parapsilosis Candida spp. RESULTS: Ten patients were included; six were male. The median (range) age, APACHE II score and Mannheim peritonitis index were 72 (43-85) years, 15 (11-36) and 26 (8-37), respectively. On day 1, median (SD) penetration of micafungin into the peritoneal cavity was 30% (30%-40%). A three-compartment model adequately described the data. The mean (SD) estimates for clearance and volume of distribution of the central compartment were 1.27 (0.75) L/h and 9.26 (1.11) L, respectively. In most patients, the PTA in plasma was ≥ 90% for MICs of 0.008-0.016 mg/L for Candida spp. and 0.125-0.25 mg/L for C. parapsilosis. CONCLUSIONS: After the first dose, micafungin at 100 mg/day achieves pharmacokinetic/pharmacodynamic targets in plasma for Candida spp. and C. parapsilosis MICs of 0.008-0.016 and 0.125-0.25 mg/L, respectively.

Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy.

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r(2) of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

Population pharmacokinetics of teicoplanin in children.

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment (Kcp), 0.474/3.876 h(-1) (8.16 h(-1)); and first-order rate constant from peripheral to central compartment (Kpc), 0.292/3.994 h(-1) (8.93 h(-1)). The percentage of patients with a minimum concentration of drug in serum (Cmin) of <10 mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of >10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.).

An invertebrate model to evaluate virulence in Aspergillus fumigatus: the role of azole resistance.

The impact of different mutations in the Aspergillus fumigatus ergosterol biosynthesis pathway on pathogenesis has been evaluated using a simple invertebrate mini host, the caterpillar Galleria mellonella. A set of strains that includes clinical isolates and isogenic mutants with mutations at the cyp51A gene conferring azole resistance were studied. All strains demonstrated a similar in vitro growth pattern and are equally virulent against the insect larvae. These results suggest that in A. fumigatus acquisition of this particular azole-resistance mechanism would not imply any significant change in virulence. G. mellonella may provide a convenient and inexpensive model for the in vivo prescreening of mutants of A. fumigatus, contributing to the generation of a hypotheses that can be further tested in refined experiments in mammalian models.

Pharmacokinetics and pharmacodynamics of anidulafungin for experimental Candida endophthalmitis: insights into the utility of echinocandins for treatment of a potentially sight-threatening infection.

Candida chorioretinitis and endophthalmitis are relatively common manifestations of disseminated candidiasis. Anidulafungin is increasingly used for the treatment of disseminated candidiasis, but its efficacy for Candida endophthalmitis is not known. A nonneutropenic model of hematogenous Candida endophthalmitis was used. Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The fungal densities in the kidney and vitreous humor were determined. Anidulafungin concentrations in the plasma and vitreous humor were measured using high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model was used to link anidulafungin concentrations with the observed antifungal effect. The area under the concentration-time curve (AUC) associated with stasis was determined in the both the kidney and the vitreous humor. The results were bridged to humans to identify likely dosages that are associated with significant antifungal activity within the eye. Inoculation of Candida albicans resulted in logarithmic growth in both the vitreous humor and the kidney. The pharmacokinetics of anidulafungin were linear. There was dose-dependent penetration of the anidulafungin into the vitreous humor. The exposure-response relationships in the kidney and vitreous were completely discordant. AUCs of 270 and 100 were required for stasis in the eye and kidney, respectively. The currently licensed regimen results in an AUC for an average patient that is associated with stasis in the kidney but minimal antifungal activity in the eye. We conclude that anidulafungin penetrates the eye in a dose-dependent manner and that dosages higher than those currently licensed are required to achieve significant antifungal activity in the eye.

Impact of Bolus dosing versus continuous infusion of Piperacillin and Tazobactam on the development of antimicrobial resistance in Pseudomonas aeruginosa.

Management of nosocomial pneumonia is frequently complicated by bacterial resistance. Extended infusions of beta-lactams are increasingly being used to improve clinical outcomes. However, the impact of this strategy on the emergence of antimicrobial resistance is not known. A hollow-fiber infection model with Pseudomonas aeruginosa (PAO1) was used. Pharmacokinetic (PK) profiles of piperacillin-tazobactam similar to those in humans were simulated over 5 days. Three dosages of piperacillin-tazobactam were administered over 0.5 h or 4 h, with redosing every 8 h. Two initial bacterial densities were investigated (∼10(4) CFU/ml and ∼10(7) CFU/ml). The time courses of the total bacterial population and the resistant subpopulation were determined. All data were described using a mathematical model, which was then used to define the relationship between drug concentrations, bacterial killing, and emergence of piperacillin resistance. There was logarithmic growth in controls in the initial 24 h, reaching a plateau of ∼9 log10 CFU/ml. Bacterial killing following administration of piperacillin via bolus dosing and that after extended infusions were similar. For the lower initial bacterial density, trough total plasma piperacillin concentration/MIC ratios of 3.4 and 10.4 for bolus and extended-infusion regimens, respectively, were able to suppress the emergence of piperacillin resistance. For the higher initial bacterial density, all regimens were associated with progressive growth of a resistant subpopulation. A stratified approach, according to bacterial density, is required to treat patients with nosocomial pneumonia. Antimicrobial monotherapy may be sufficient for some patients. However, for patients with a high bacterial burden, alternative therapeutic strategies are required to maximize bacterial killing and prevent antimicrobial resistance.

Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections.

While extended infusions of piperacillin-tazobactam (TZP) are increasingly used in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP has not been widely assessed. To assess its effect on the pharmacokinetic profile of TZP, seven serum samples were collected from 11 hospitalized patients who received 3.375 g TZP intravenously for 4 h every 8 h. Population pharmacokinetic models were fit to the PK data utilizing first-order, Michaelis-Menten (MM), and parallel first-order/MM clearance. A population PK model with first-order clearance was fit to the tazobactam PK data. Monte Carlo simulations (MCSs) were used to determine the most effective administration schedule to ensure that free piperacillin concentrations were above the MIC for at least 50% of the dosing interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance. The model incorporating parallel linear/MM clearance best fit the piperacillin PK data. The MCSs demonstrated that approximately 50% of the administered piperacillin is cleared by the nonlinear clearance mechanism. The results of the MCSs also revealed that more intensive TZP extended infusion dosing schemes (3.375 to 4.5 g intravenously [3-h infusion] every 6 h) than those commonly used in clinical practice were needed to maximize the 50% fT>MIC for MICs of ≥8 mg/liter. This study suggests that extended infusion of TZP is the most effective method of administration for patients with nosocomial infections. Due to the hyperclearance nature of the hospitalized patient populations studied, more intensive TZP dosing regimens may be needed to maximize fT>MIC in certain hospitalized populations.

Disseminated Candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin.

The clinical utility of the echinocandins is potentially compromised by the emergence of drug resistance. We investigated whether Candida albicans with amino acid substitutions at position Ser645 in Fks1 can be treated with either a conventional or an elevated dosage of micafungin. We studied Candida albicans (wild-type SC5314; MIC, 0.06 mg/liter) and four fks1 mutants (one FKS1/fks1 heterozygote mutant [MIC, 0.5 mg/liter] and three fks1/fks1 homozygous mutants [MICs for all, 2 mg/liter]) with a variety of amino acid substitutions at Ser645. The pharmacokinetic and pharmacodynamic relationships were characterized in a persistently neutropenic murine model of disseminated candidiasis. A mathematical model was fitted to all pharmacokinetic and pharmacodynamic data. This mathematical model was then used to "humanize" the murine pharmacokinetics, and the predicted antifungal effect was determined. The estimated maximal rate of growth and ultimate fungal densities in the kidney for each of the strains were similar. The administration of micafungin at 1 mg/kg of body weight to the wild type resulted in moderate antifungal activity, whereas the administration of 5 and 20 mg/kg resulted in rapid fungicidal activity. In contrast, the FKS1/fks heterozygote was killed only with 20 mg/kg, and the homozygous fks1 mutants failed to respond to any dosage. The bridging study revealed that human dosages of 100 and 400 mg/day were active only against the wild type, with no activity against either the heterozygote or the homozygote mutants. Ser645 Fks1 Candida albicans mutants cannot be treated with either conventional or elevated dosages of micafungin and should be deemed resistant.

Comparing the outcomes of external oblique and transversus abdominus release using the AHSQC database.

PURPOSE: Myofascial release techniques at the time of complex hernia repair allow for tension-free closure of the midline fascia. Two common techniques are the open external oblique release (EOR) and the transversus abdominis release (TAR). Each technique has its reported advantages and disadvantages, but there have been few comparative studies. The purpose of this project was to compare the outcomes of these two myofascial release techniques. METHODS: The Americas Hernia Society Quality Collaborative (AHSQC) database was queried and produced a data set on 24 May 2018. All patients undergoing open incision hernia repair with an open EOR or TAR were evaluated, and outcomes were compared including hernia recurrence, quality of life, and 30-day wound-related complications. RESULTS: 3610 patients met the inclusion criteria of undergoing open incisional hernia repair (501 undergoing EOR and 3109 undergoing TAR). Seventy surgeons from 50 institutions contributed EOR patients, and 124 surgeons from 89 institutions contributed TAR patients with no differences between the two groups in surgeons' affiliation. Comparing open EOR and TAR showed no significant differences in hernia recurrence, quality of life, or 30-day surgical site infection rate. EOR had a significantly higher rate of surgical site occurrences compared with TAR (p < 0.05); however, this did not result in an increase in surgical site occurrences requiring procedural interventions. CONCLUSIONS: Equivalent outcomes were achieved using the EOR or TAR techniques in the open repair of incisional hernias. Both techniques offer consistently good outcomes and are important adjuncts in the repair of complex incisional hernias.

Primary non-complicated midline ventral hernia: overview of approaches and controversies.

Umbilical hernias and epigastric hernias are some of the most common hernias in the world. Umbilical and epigastric hernia defects can range from small (<1 cm) to very large/complex hernias, and treatment options should be tailored to the clinical situation. Repair techniques include open, laparoscopic, and robotics options, each with advantages and disadvantages. A mesh-based repair is indicated in most cases due to having fewer associated recurrences. Overall outcomes are favorable following umbilical and epigastric hernia repairs; however, some patients have chronic complaints mostly related to recurrences. This report is an overview of available techniques for repair of umbilical and epigastric hernias. It also discusses ongoing controversies related to umbilical and epigastric hernia repairs, the limitations of available literature, and the need for future research.

Hernia prevention: practice patterns and surgeons' attitudes about abdominal wall closure and the use of prophylactic mesh.

PURPOSE: The penetration of hernia prevention techniques into surgical practice remains unknown. METHODS: A survey about knowledge/attitudes on hernia prevention was sent to the members of hernia societies. RESULTS: The 497 respondents were mostly from the US (47%) or Europe (40%). Most reported practicing, but not measuring their suture-to-wound length closure of > 4:1 (63%) and practicing but not measuring the number of stitches (58%). Reasons for not using short stitch closure were: does not apply to patient population (19%), not familiar enough with methods to correctly execute (25%), takes too long (13%), not reimbursed (4%), concerned about closure-related complications (27%), and other (22%). Regarding prophylactic mesh, respondents stated they were not familiar with literature (11%), familiar with literature but would not use (24%), familiar with literature and interested in use (45%), familiar with literature and using (15%), and other (5%). CONCLUSIONS: There appears to be some application of hernia prevention principles related to fascial closure; however, the use of prophylactic mesh still appears to be controversial.

Prophylactic mesh used in ileal conduit formation following radical cystectomy: a retrospective cohort.

PURPOSE: Given the difficulty of durable repairs, there is continued interest in hernia prevention. One emerging prevention technique for parastomal hernias is prophylactic mesh placement, whereby mesh is inserted during the index procedure as hernia prophylaxis. We evaluated our experience using prophylactic mesh when creating an ileal conduit. METHODS: We retrospectively reviewed patients undergoing robotic cystectomy with ileal conduit from 6/2010 to 8/2017. Patient demographics and operative/perioperative outcomes were documented. We evaluated hernia recurrence using postoperative computed tomography scanning or physical exam. Prophylactic mesh was inserted at the operating surgeon's discretion using a synthetic resorbable or biologic mesh. RESULTS: During the study period, 38 patients underwent robotic-assisted cystectomy with ileal conduit formation. Average patient age was 68 years, with 28 (74%) male and 35 (92%) Caucasian patients. Three patients (8%) required conversion to open, and one patient (3%) had a concomitant colorectal resection. Thirty-one (88%) patients had postoperative computed tomography scanning. Prophylactic mesh was used in 18 patients (47%) in a retrorectus position. Of these, 15 (83%) patients had synthetic resorbable mesh and 3 (17%) patients had biologic mesh. At average follow-up of 21 months, one hernia recurred (5%) in a patient without mesh placement at the time of ileal conduit. At an average follow-up of 11 months, there have been no recurrences and no mesh-related complications in the prophylactic mesh group. CONCLUSIONS: Using prophylactic mesh in ileal conduit, creation is feasible and may decrease the parastomal hernia formation rate. Further study of using synthetic resorbable and biologic meshes for hernia prophylaxis is warranted.

Suture to wound length ratio in abdominal wall closure: how well are we doing?

PURPOSE: Research has established that a ≥4:1 suture to wound (S:W) length ratio decreases incisional hernias. We evaluated our ability to obtain a 4:1 S:W length ratio in a surgery residency program. METHODS: Consecutive abdominal wall closures from 12/1/2013 through 4/9/2015 were reviewed. The length of the incisions and amount of suture used were measured. Patient demographics and operative variables were documented and compared related to inability to obtain a 4:1 ratio. RESULTS: One hundred patients underwent abdominal closure with S:W length measurements. Average wound length was 18.3 cm; average suture length used was 84.5 cm; and average S:W length ratio was 4.6:1. An S:W length ratio of ≥4:1 was achieved in 76% of cases. There was no difference in race, age, gender, BMI, type of procedure, or resident level in obtaining a 4:1 S:W length ratio. There was a significantly higher rate of not achieving a 4:1 ratio when two residents closed. Postoperative infection rate and hernia rate increased when a 4:1 S:W length ratio was not achieved compared with an adequate S:W length ratio. CONCLUSIONS: Despite the known importance of achieving a 4:1 S:W length ratio for abdominal closure, it was only achieved in 76% of study patients. Improved education on the importance of fascial closure is needed.

An evaluation of abdominal wall closure in general surgical and gynecological residents.

PURPOSE: To evaluate abdominal wall closure knowledge base and technical skills in surgical and OB/GYN residents. METHODS: Residents consented to participate in a skills laboratory and quiz. The skills portion involved closure of a 10-cm incision on a simulated abdominal wall. Participants were timed, filmed, and graded using a standardized grading system. RESULTS: Thirty surgical and OB/GYN residents participated. All residents reported closing the abdominal wall continuously, 97% preferred slowly absorbing sutures (28/29), 97% preferred taking 1-cm bites (29/30), and 93% spaced bites 1 cm apart (27/29). However, 77% (10/13) of surgery residents identified 4:1 as the ideal suture to wound length ratio; 47% (7/15) of OB/GYN residents believed it to be 2:1, and another 40% (6/15) indicated 3:1 (p < 0.0001). In the simulation, OB/GYN residents used significantly fewer stitches (p = 0.0028), significantly more distance between bites (p < 0.0001), and significantly larger bite size (p < 0.0001) than surgery residents. When graded, there was no significant difference between programs. CONCLUSIONS: Despite some knowledge regarding the principles of abdominal wall closure among surgical and OB/GYN residents, more instruction is needed. We identified some differences in knowledge base and techniques for abdominal wall closure among general surgery and OB/GYN residents, which are likely due to differences in educational curriculums.