Intraoperative Redosing Research Articles

Intraoperative redosing of antibiotics for prevention of surgical site infections: A systematic review and meta‐analysis

AbstractBackgroundAppropriate antibiotic prophylaxis is essential for preventing surgical site infections (SSI); however, the clinical benefit of intraoperative redosing remains unclear and controversial owing to insufficient reliable evidence. Therefore, we performed a systematic review and meta‐analysis to assess the effectiveness of prophylactic antibiotic redosing in lengthy surgical procedures.MethodsWe systematically searched the PubMed, Cochrane Library, Web of Science, and Ichushi‐Web databases for articles published until 31 December, 2023. We compared the incidence of SSI between patients receiving and not receiving intraoperative redosing of antibiotics in surgeries lasting ≥3 h. Subgroup analyses were conducted across study characteristics. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel random effects model. The risk of bias was assessed using the ROBINS‐I.ResultsOverall, seven observational studies involving 4,671 patients were included. Intraoperative antibiotic redosing significantly reduced the risk of SSI compared with non‐redosing (OR = 0.65, 95% CI = 0.45–0.94, p = 0.02). Subgroup analyses showed that intraoperative redosing decreased SSI risk in studies with a minimum 4‐h operative time, no postoperative antibiotic continuation, and a moderate risk of bias. However, the statistical heterogeneity of the analyses was high among the studies.ConclusionsIntraoperative redosing with prophylactic antibiotics during lengthy surgeries may be associated with a lower risk of SSI than non‐redosing. Therefore, we recommend intraoperative redosing for surgeries lasting beyond 3–4 h to reduce the risk of infection. Further research is required to clarify the optimal redosing interval, which should be prioritized in future studies.

Association of adherence to individual components of Society of Thoracic Surgeons cardiac surgery antibiotic guidelines and postoperative infections

ObjectivesThe study objectives were to measure the association among the 4 components of Society of Thoracic Surgeons antibiotic guidelines and postoperative complications in a cohort of patients undergoing valve or coronary artery bypass grafting requiring cardiopulmonary bypass. MethodsIn this retrospective observational study, adult patients undergoing coronary revascularization or valvular surgery who received a Surgical Care Improvement Project–compliant antibiotic from January 1, 2016, to April 1, 2021, at a single, tertiary care hospital were included. The primary exposures were adherence to the 4 individual components of Society of Thoracic Surgeons antibiotic best practice guidelines. The association of each component and a combined metric was tested in its association with the primary outcome of postoperative infection as determined by Society of Thoracic Surgeons data abstractors, controlling for several known confounders. ResultsOf the 2829 included patients, 1084 (38.3%) received care that was nonadherent to at least 1 aspect of Society of Thoracic Surgeons antibiotic guidelines. The incidence of nonadherence to the 4 individual components was 223 (7.9%) for timing of first dose, 639 (22.6%) for antibiotic choice, 164 (5.8%) for weight-based dose adjustment, and 192 (6.8%) for intraoperative redosing. In adjusted analyses, failure to adhere to first dose timing guidelines was directly associated with Society of Thoracic Surgeons–adjudicated postoperative infection (odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P = .02). Failure of weight-adjusted dosing was associated with both postoperative sepsis (odds ratio, 6.9; 95% confidence interval, 2.5-8.5; P < .01) and 30-day mortality (odds ratio, 4.3; 95% confidence interval, 1.7-11.4; P < .01). No other significant associations among the 4 Society of Thoracic Surgeons metrics individually or as a combination were observed with postoperative infection, sepsis, or 30-day mortality. ConclusionsNonadherence to Society of Thoracic Surgeons antibiotic best practices is common. Failure of antibiotic timing and weight-adjusted dosing is associated with odds of postoperative infection, sepsis, and mortality after cardiac surgery.

Study protocol of REpeat versus SIngle ShoT Antibiotic prophylaxis in major Abdominal Surgery (RESISTAAS I): a prospective observational study of antibiotic prophylaxis practice for patients undergoing major abdominal surgery

IntroductionSurgical site infections (SSIs) are among the most common complications after abdominal surgery and develop in approximately 20% of patients. These patients suffer a 12% increase in mortality, underlying the...

Impact of individualized feedback letters on adherence to surgical antibiotic prophylaxis guidelines: an interrupted time series study (FEEDBACK-ASAP)

Surgical antibiotic prophylaxis (SAP) has been proved to decrease the rate of surgical site infections (SSI), but compliance to SAP guidelines remains suboptimal. This study evaluated the impact of periodically sending individualized feedback letters to surgeons and anesthesiologists on their compliance rate to SAP guidelines. A total of 1491 surgeries were evaluated by retrospective chart review during the pre-intervention period and 668 surgeries were evaluated by prospective chart review during the per-intervention period. Finally, 295 letters were sent to 64 surgeons and 45 anesthesiologists. Compliance rate was assessed as an outcome composed of: indication for SAP, choice of antibiotic agent, antibiotic dose, postoperative duration, timing of the preoperative dose and intraoperative redosing. An interrupted time series design was used to assess a difference on compliance rates before and during the intervention period. Sending individualized feedback letters to surgeons and anesthesiologists did not significantly improve the overall compliance to local SAP guidelines. Individualized feedback letters could be part of future interventions directed at improving compliance to SAP guidelines, but are likely insufficient by themselves to provide significant results.

Intraoperative Redosing of Surgical Antibiotic Prophylaxis in Addition to Preoperative Prophylaxis Versus Single-dose Prophylaxis for the Prevention of Surgical Site Infection: A Meta-analysis and GRADE Recommendation.

The aim of this study was to determine the effect of preoperative surgical antibiotic prophylaxis (SAP) with additional intraoperative redosing compared to single-dose preoperative surgical antibiotic prophylaxis on the incidence of surgical site infections (SSI). Preoperative SAP is standard care for the prevention of SSI. During long surgical procedures, additional intraoperative redosing of SAP is advised, but there is great variability in redosing strategies and compliance rates. We performed a systematic search of MEDLINE (PubMed), Embase, CINAHL and CENTRAL on June 25th, 2021 according to PROSPERO registration CRD42021229035. We included studies that compared the effect of preoperative SAP with additional intraoperative redosing to single dose preoperative SAP (no redosing) on SSI incidence in patients undergoing any type of surgery. Two researchers performed data appraisal and extraction of summary data independently. Meta-analyses were stratified per study type. We used a generic inverse variance random-effects model to estimate a pooled odds ratio with corresponding 95% confidence intervals (CIs). We included 2 randomized controlled trials (RCT) and 8 cohort studies comprising of 9470 patients. Pooled odds ratios for SSI in patients receiving intraoperative redosing compared to those without redosing were 0.47 (95% CI: 0.19-1.16. I2 = 36%) for RCTs and 0.55 (95% CI: 0.38-0.79, I2 = 56%) for observational cohorts. There was considerable clinical heterogeneity among antibiotics used and redosing protocols. GRADE-assessment showed overall low certainty of evidence. Intraoperative redosing of SAP may reduce incidence of SSI compared to a single dose preoperative SAP in any type of surgery, based on studies with considerable heterogeneity of antibiotic regimens and redosing protocols.

PIN3 Impact of Antimicrobial Stewardship Interventions on Compliance with Surgical Antibiotic Prophylaxis: A Systematic Review

There is paucity of data describing the effectiveness of antimicrobial stewardship in improving compliance with surgical antibiotic prophylaxis. This review evaluated the impact of antimicrobial stewardship interventions on compliance with surgical antibiotic prophylaxis measures, surgical site infection and economic outcome. PubMed, Scopus, Science Direct, and Google Scholar databases were searched to identify eligible studies that reported the impact of antimicrobial stewardship on compliance with surgical antibiotic prophylaxis and/or antibiotic utilization, surgical site infections from 2000 to 2017. Fourteen studies were selected; eight (57%) uncontrolled before-and-after studies, and two each randomized trial, interrupted time series and controlled before-and-after studies. Clinician education, organizational changes and audit and feedback were the most common stewardship interventions. Stewardship interventions improved compliance with antibiotic selection (1% - 90%); timing of first dose (5% - 96%); intra-operative re-dosing (28% - 53%); and total compliance (19% - 44%). Duration of antibiotic prophylaxis had the least improvement (7% - 25%) after stewardship interventions. Generally, studies with low baseline compliance rate showed greater improvements after stewardship interventions. Stewardship interventions reduced antibiotic utilization (20% - 35% Defined Daily Dose/100 procedures), surgical site infections (0.8% - 5.6%), and the costs of antibiotic prophylaxis per procedure ($ 2.5 - $ 345). Participation of stakeholders in antimicrobial stewardship program was vital for the success of the interventions. Low quality evidence shows that stewardship interventions improve compliance with surgical antibiotic prophylaxis measures, and reduced antibiotic utilization, surgical site infections and cost of surgical antibiotic prophylaxis.

Utilization of neurosurgical perioperative antimicrobial prophylaxis in a Chinese teaching hospital

Background Audits of antimicrobial prophylaxis is an essential strategy to identify practice gaps in antimicrobial prescribing in healthcare facilities. There is a lack of studies on the costs, quality, and antimicrobial use density of neurosurgical perioperative antimicrobial prophylaxis in China. Objectives Evaluate the appropriateness of perioperative antimicrobial prophylaxis in neurosurgeries and analyze the costs, quality, and antimicrobial use density of neurosurgical perioperative antimicrobial prophylaxis. Setting Beijing Tsinghua Changgung Hospital, a teaching hospital in Beijing. Methods This retrospective study was conducted among 262 neurosurgical patients without infections during 2017. The appropriateness of perioperative antimicrobial prophylaxis was determined based on relevant international and Chinese perioperative antimicrobial prophylaxis guidelines. Main outcome measures Discrepancy rates in perioperative antimicrobial prophylaxis, including indication, choice of antimicrobials, dose, route of administration, time of administration of the first dose, re-dosing, and duration, were analyzed. Results Discrepancies were observed between current practice and relevant guidelines. A total of 51 (32.1%) procedures failed to administer intraoperative re-dosing as needed, and the perioperative antimicrobial prophylaxis duration of 217 (82.8%) procedures was inappropriately prolonged. The choice of antimicrobial agents was optimal in 249 (95%) procedures, and the timing of perioperative antimicrobial prophylaxis was appropriate in all procedures. If perioperative antimicrobial prophylaxis was implemented according to guidelines, the defined daily dose per 100 procedures would decrease from 31.97 to 16.99, and the total cost would reduce from $2000 to $490. Conclusions Effective antimicrobial stewardship is urgently needed to promote the appropriateness of neurosurgical perioperative antimicrobial prophylaxis in China.

882. Evaluating the Risk Factors in Postoperative Infections Following Hysterectomy Procedures: Is Antibiotic Prophylaxis the Issue?

BackgroundInfectious complications after hysterectomy procedures are associated with an additional financial burden and length of stay for patients. In addition, post-hysterectomy surgical site infection is a metric tied to hospital ranking and financial penalties. The objective of this study was to evaluate the appropriateness of surgical prophylaxis for hysterectomies in patients with postoperative infections.MethodsThis is a 1:1 case-control study, matched based on the year of surgery and surgeon performing the procedure, of women ≥ 18 years who underwent hysterectomies between 2013 and 2019. Cases were diagnosed with infection(s) attributable to the procedure within 90 days post-hysterectomy. Patients who did not receive prophylaxis were excluded. The primary outcome of this study was to determine if postoperative infections following hysterectomies were due to inappropriate antibiotic prophylaxis. Secondary outcomes included hospital readmission and mortality. The primary statistical tests utilized included descriptive statistics and chi-square test.ResultsThe study included 86 patients, 43 in each group. Thirty percent of cases and 7% of controls received inappropriate prophylaxis. For cases, reason for inappropriateness was due to underdosing of cefazolin (38%) and gentamicin (54%), and overdosing of cefotetan (8%). For controls, cefazolin (33%) and gentamicin (67%) were underdosed. Twenty-three percent of the cases and 14% of the controls received inappropriate intraoperative redosing. The most common reason for inappropriateness was timing (40% of cases vs 50% of controls) followed by missed intraoperative redosing (50% of cases vs 33% of controls). No difference was observed in the proportion of cases and proportion of controls who received inappropriate treatment (p=0.21). Eighty-eight percent of cases and 5% of controls were readmitted within 3 months (p< 0.0001). Mortality was not noted in either group.ConclusionIn this study, there was no statistically significant association between inappropriate antibiotic prophylaxis and infection. There was still a high incidence of inappropriate antibiotic prophylaxis in the cases. Therefore, education of providers on antibiotic dosing and criteria for intraoperative redosing is warranted.Disclosures All Authors: No reported disclosures

Surgical Antibiotic Prophylaxis: Incidence and Risk of Surgical Site Infection

Introduction: This prospective cross sectional study assessed surgical antibiotic prophylaxis (SAP) practice, the incidence of surgical site infection (SSI) and its associated risks in Universiti Kebangsaan Malaysia Medical Centre. Methods: Patients for elective colorectal, hepatobiliary, upper gastrointestinal, breast and endocrine surgery, who received SAP were included and followed up until day-30 postoperatively. Types of antibiotic, preoperative–dose timing, intraoperative re-dosing and its duration were recorded. The incidence of SSI was calculated and its associated risks expressed in odds ratio. Results: Out of 166 patients recruited, 121 (72.89%) patients received SAP preoperatively, and 91 (75.21%) of them were prescribed the appropriate antibiotic as per our institutional guideline. Three patients who continued to receive therapeutic antibiotic postoperatively were excluded from statistical analysis. Eleven (9.10%) patients received SAP beyond the preoperative–dose timing of 60 minutes (p=0.001), which was an independent risk factor for SSI (adjusted OR 4.527, 95% CI; 1.058-19.367, p=0.042). The risk of SSI also remained in patients who continued to receive SAP beyond 24 hours (OR 4.667, 95% CI; 1.527-14.259, p=0.007). The overall rate of SSI was 17.18%. Conclusion: We found that the choice of antibiotic prescribed for SAP was in accordance to institutional guideline and the relatively high SSI incidence was similar to a recent local report. Although the number of patients receiving preoperative dose-timing of &gt; 60 minutes was low, it was nonetheless an independent risk factor for SSI. The postoperative continuation of SAP for more than 24 hours showed no benefit in reducing SSI.

Surgical site infection prevention protocol for pediatric spinal deformity surgery: does it make a difference?

Retrospective. Can a standardized, hospital-wide care bundle decrease surgical site infection (SSI) rate in pediatric spinal deformity surgery? SSI is a major concern in pediatric spinal deformity surgery. We performed a retrospective review of our primary scoliosis surgeries between 1999 and 2017. In 2008, we implemented a standardized infection reduction bundle. Interventions included preoperative nares screening for methicillin-resistant staphylococcus aureus or methicillin-sensitive Staphylococcus aureus 2weeks preoperatively, and treatment with intranasal mupirocin when positive, a bath or shower the night before surgery, a preoperative chlorohexidine scrub, timing of standardized antibiotic administration, standardized intraoperative re-dosing of antibiotics, limiting operating room traffic, and standardized postoperative wound care. In 2011, we added intrawound vancomycin powder at wound closure. Our inclusion criteria were patients 21years of age or less with idiopathic, neuromuscular, syndromic, or congenital scoliosis who had a primary spinal fusion or a same day anterior and posterior spine fusion with segmental spinal instrumentation of six levels or more. We compared the incidence of early (within 90days of surgery) and late (> 91days) SSI during the first postoperative year. There were 804 patients who met inclusion criteria: 404 in the non-bundle group (NBG) for cases prior to protocol change and 400 in the bundle group (BG) for cases after the protocol change. Postoperatively, there were 29 infections (7.2% of total cases) in the NBG: 9 early (2.2%) and 20 late (5.0%) while in the BG there were only 10 infection (2.5%): 6 early (1.5%) and 4 late (1.0%). The reduction in overall SSIs was statistically significant (p = 0.01). There was a trend toward decreased early infections in the BG, without reaching statistical significance (p = 0.14). Standardized care bundles appear effective in reducing the incidence of postoperative pediatric spine SSIs. Level III.

Surgical Site Infection Prevention Measures in General Surgery: Position Statement by the Surgical Infections Division of the Spanish Association of Surgery

Surgical site infection is associated with prolonged hospital stay and increased morbidity, mortality and healthcare costs, as well as a poorer patient quality of life. Many hospitals have adopted scientifically-validated guidelines for the prevention of surgical site infection. Most of these protocols have resulted in improved postoperative results. The Surgical Infection Division of the Spanish Association of Surgery conducted a critical review of the scientific evidence and the most recent international guidelines in order to select measures with the highest degree of evidence to be applied in Spanish surgical services. The best measures are: no removal or clipping of hair from the surgical field, skin decontamination with alcohol solutions, adequate systemic antibiotic prophylaxis (administration within 30–60min before the incision in a single preoperative dose; intraoperative re-dosing when indicated), maintenance of normothermia and perioperative maintenance of glucose levels.

Medidas de prevención de la infección de localización quirúrgica en cirugía general. Documento de posicionamiento de la Sección de Infección Quirúrgica de la Asociación Española de Cirujanos

Surgical site infection is associated with prolonged hospital stay and increased morbidity, mortality and healthcare costs, as well as a poorer patient quality of life. Many hospitals have adopted scientifically-validated guidelines for the prevention of surgical site infection. Most of these protocols have resulted in improved postoperative results. The Surgical Infection Division of the Spanish Association of Surgery conducted a critical review of the scientific evidence and the most recent international guidelines in order to select measures with the highest degree of evidence to be applied in Spanish surgical services. The best measures are: no removal or clipping of hair from the surgical field, skin decontamination with alcohol solutions, adequate systemic antibiotic prophylaxis (administration within 30-60minutes before the incision in a single preoperative dose; intraoperative re-dosing when indicated), maintenance of normothermia and perioperative maintenance of glucose levels.

Improving the Compliance of Intraoperative Antibiotic Redosing: A Quality Improvement Initiative.

Introduction:At Children’s Hospital and Medical Center in Omaha, Nebraska, the intraoperative antibiotic redosing guidelines and the time frame considered compliant for redosing were unclear. This lack of clarity plus an ill-defined process for ensuring intraoperative antibiotic redosing resulted in a compliance rate of 11%. The organization’s surgical site infection (SSI) rate was 3.19%, above the national benchmark of 1.87%. The primary project goal was to increase intraoperative antibiotic redosing compliance. The secondary project goal was to decrease SSIs.Methods:With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. Implementation of the new guidelines and processes occurred after providing education to the anesthesiologists, surgeons, and circulating nurses. Monthly evaluation of data allowed for quick recognition of oversights followed by the initiation of process updates.Results:Data showed that the initial compliance rate for the intraoperative redosing of antibiotics was 11%. Following interventions, compliance has reached and sustained an average of 99%. Survey results show that provider knowledge of the guidelines and process has improved. Though not directly related, the National Surgical Quality Improvement Program observed that the SSI rate decreased from 3.19% in 2014 to 2.3% in 2018.Conclusions:This project demonstrates that comprehensive education along with antibiotic-specific electronic medical record alerts significantly increased the compliance of intraoperative antibiotic redosing at Children’s Hospital & Medical Center. Continuous education and monthly updates sustained results for over 40 months.

1103. Improving Perioperative Prophylactic Antimicrobial Guideline Concordance in Liver and Lung Transplant Recipients

BackgroundSurgical site infection (SSI) is a common complication among patients undergoing solid-organ transplantation. Administration of perioperative antimicrobials is one modifiable factor that may reduce the risk of SSIs. We sought to evaluate antimicrobial stewardship efforts to improve concordance of perioperative antimicrobial selection (AS) and dose timing (DT) with the institution’s perioperative antimicrobial guidelines among liver (LVR) and lung transplant recipients (LNG).MethodsThis was a single-center, observational study of LVR and LNG between January 1, 2017 and December 31, 2018. Patients receiving antimicrobials for the treatment of infection immediately prior to transplant were excluded. Throughout the study period, several interventions were performed, including: updating AS and DT protocols (2017 Q2) and preoperative order sets (2017 Q4), improving availability of antibiotics in the operating room (2018 Q1), and most recently developing a guideline and providing education for intraoperative redosing based on renal function (2018 Q3). The primary outcome was overall guideline concordance (GC). This was a composite endpoint including preoperative and intraoperative AS and DT, based on the institution’s guideline. Secondary outcomes included SSI rates based on the CDC National Healthcare Safety Network definition and rate of new C. difficile or vancomycin-resistant Enterococci infection or colonization.ResultsAmong 112 patient screened, 79 patients were included (45 LNG and 34 LVR). The median age was 60 years and BMI was 26.5 kg/m2. The median procedure length was 7.8 hours for LNG and 6.9 hours for LVR. Results are shown in Table 1, Figure 1 and Figure 2. All GC rates demonstrate improvements over time, except for intraoperative DT for LNG.ConclusionLimited by a small sample size, our study demonstrates that noninvasive antimicrobial stewardship strategies can yield improvements in GC. Disclosures All authors: No reported disclosures.

A study to evaluate and assess the antibiotic prescription pattern for the surgical prophylaxis to prevent post-operative wound infection (SSI) in a tertiary care hospital

Surgical site infection is a major complication following surgery affecting up to 50 % of operated patients which can be prevented by appropriate antibiotic prophylaxis. Hence this study aims to investigate the pattern of the prophylactic antibiotic usage in patients undergoing elective surgery and to assess the percentage of drugs included in the National List of Essential Medicines (NLEM). This is a Prospective study conducted at Saveetha Medical College and Hospital from April 2018 to April 2019 included medical records of 1093 Patients above 18yrs of age including both sex (male and female) who has undergone elective surgery in Department of General Surgery. Patient's demographic data and comorbidities was also collected and verified for antibiotic prophylaxis, i.e. choice and duration of antibiotics, time of administration, intra-operative dosing, choice and duration of the postoperative use. Pediatrics, Neonatal Surgeries, Pregnant and lactating women were excluded from this study. The obtained data was analyzed, and conclusions were drawn with the help of SPSS analysis software. The results shows Third-generation cephalosporin's injection Taxim (Cefotaxime) was mainly used preoperatively in 486(44.46%) patients by intravenous route followed by cefixime-191(17.47%),ciprofloxacin-161(14.73%). In addition,458(41.90%) patients received either Inj.TT or Metronidazole along with the 1st pre-operative drug. The antibiotics were administered in 2 doses (i.e.) overnight dose and other dose is given just half an hour prior to surgery. No intraoperative redosing was given. The duration of the postoperative prophylaxis was extended to 3 days to 5 days in all 1093 cases. SSI was identified in 25 cases, and overall incidence in our study is 2% which is quite compatible with other studies and incidence is common among patients with age-related risk factors and comorbidities. This study revealed that third-generation cephalosporin Cefotaxime was considered as the main pre and post-operative drug, which is based on surgeon's experience, type of surgery and local antibiotic resistance pattern. Various measures like the development of local hospital Policy, surveillance on SSIs, hospital antibiotic policy, promoting good surgical techniques and strict asepsis in the operating theatre, usage of single antibiotics, and completion of course of antibiotics can prevent the emergence of multi-resistant organisms.

A multifaceted quality improvement project improves intraoperative redosing of surgical antimicrobial prophylaxis during pediatric surgery.

Accurate intraoperative antibiotic redosing contributes to prevention of surgical site infections in pediatric patients. Ensuring compliance with evolving national guidelines of weight-based, intraoperative redosing of antibiotics is challenging to pediatric anesthesiologists. Our primary aim was to increase compliance of antibiotic redoses at the appropriate time and appropriate weight-based dose to 70%. Secondary aims included a subset analysis of time compliance and dose compliance individually, and compliance based on order entry method of the first dose (verbal or electronic). At a freestanding, academic pediatric hospital, we reviewed surgical cases between May 1, 2014, and October 31, 2017 requiring antibiotic redoses. After an institutional change in cefazolin dosing in May 2015, phased interventions to improve compliance included electronic countermeasures to display previous and next dose timing, an alert 5minutes prior to next dose, and weight-based dose recommendation (September 2015). Physical countermeasures include badge cards, posting of guidelines, and updates to housestaff manual (September 2015). Statistical process control charts were used to assess overall antibiotic redose compliance, time compliance, and dose compliance. The chi-square test was used to analyze group differences. A total of 3015 antibiotic redoses were administered during 2341 operative cases between May 1, 2014, and October 31, 2017. Mean monthly compliance with redosing was 4.3% (May 2014-April 2015) and 73% (November 2015-October 2017) (P<0.001). Dose-only compliance increased from 76% to 89% (P<0.001), and time-only compliance increased from 4.9% to 82% (P<0.001). After implementation of countermeasures, electronic order entry compared with verbal order was associated with higher dose compliance, 90% vs 86% (P=0.015). This quality improvement project, utilizing electronic and physical interventions, was effective in improving overall prophylactic antibiotic redosing compliance in accordance with institutional redosing guidelines.

Lack of Pharmacokinetic Basis of Weight-Based Dosing and Intra-Operative Re-Dosing with Cefazolin Surgical Prophylaxis in Obese Patients: Implications for Antibiotic Stewardship.

Traditionally, there have been uniform antibiotic dosing guidelines for prophylaxis for clean-clean-contaminated surgery in both non-obese and obese adults. All other factors predisposing to surgical site infections (SSIs) being equal, over time, the preferred drug is cefazolin. The usual dose, given immediately pre-procedure, has been 1 g intravenously (IV) in non-penicillin-allergic patients, which has been highly effective, Recently, it has become common practice to use high-dose cefazolin; i.e., 3 g IV, in obese patients. This article reviews the literature on high-dose cefazolin prophylactic regimens in the obese from a pharmacokinetic (PK) point of view. There are no comparative studies to support this approach, which is based largely on the theory "more must be better." Weight-based dosing of cefazolin in the obese is flawed, because it does not take into account PK factors, which are critical in the obese. Cefazolin is a water-soluble (hydrophilic) antibiotic that does not penetrate adipose tissue regardless of IV dose. Importantly, adipose tissue is not a valid target tissue in clean-clean-contaminated SSI prophylaxis, as it does not become infected. Higher doses result in proportionately higher serum/non-adipose tissue concentrations, but adipose tissue concentrations are unaffected. Cefazolin displays time-dependent killing kinetics so that as long as serum/tissue concentrations are above the minimum inhibitory concentration (MIC) of SSI pathogens, there is no enhanced killing with higher concentrations relative to concentration-dependent antibiotics. Taking into account PK principles, a cefazolin 1 g IV bolus results in peak serum concentrations of ∼185 mcg/mL, provides at least six hours of intra-operative protection, aside from any post-antibiotic effects, and eliminates any rationale for intra-operative re-dosing for procedures lasting six hours or less. Some have argued that a cefazolin 3 g IV dose in the obese does not matter, as more must necessarily be better. However, from an antibiotic stewardship program (ASP) perspective, unneeded antibiotics are unnecessary. Moreover, the costs of cefazolin 1 g (IV push) at $0.75 versus 2 g (IV piggyback) at $ 6.83 can be significant in large centers using cefazolin prophylaxis for cardiothoracic, orthopedic, obstetric/gynecology, and bariatric surgery. Excessive antibiotics also expose the patient to potential adverse effects; i.e., Clostridium difficile. There is no dose-dependent or duration of exposure effect on resistance with one or two pre-operative or intra-operative doses. Well-done PK-based studies in obese patients clearly demonstrate the lack of benefit of using a 3-g dose or intra-operative re-dosing and show no incremental increase in adipose tissue concentrations with high doses. From an ASP point of view, antibiotic dosing recommendations should be reviewed and revised on the basis of PK principles that indicate that weight-based dosing has no basis for pre-operative prophylaxis in obese patients.

A study on the antimicrobial usage pattern for the prevention of surgical site infections in a teaching hospital

Background: Wrong antimicrobial selection and usage increase the incidence of drug resistance, drug toxicity and superinfections, thus decreasing the quality of healthcare delivery. Various approaches for rationalizing the antimicrobial usage have been recommended. Understanding the existing antimicrobial usage pattern is suggested as the first step in this approach, which would help to understand the current issues and to find the solution. The aim of the study was to evaluate the usage pattern of antimicrobial prophylaxis in surgical patients, to identify any inappropriateness of the usage.Methods: A retrospective evaluation of the randomly selected 258 medical records of general surgical cases for eight months in a tertiary care teaching hospital were verified for the appropriateness of the antimicrobial prophylaxis. The collected data was studied, and conclusions were drawn with the help of appropriate statistics.Results: All the 262 (100%) patients received a third generation cephalosporin through the intravenous route as a prophylactic dose. Also, 92 (35%) patients received nitroimidazole or aminoglycosides in addition to the cephalosporins. The antimicrobials were administered half an hour to one hour before the surgery. No intraoperative redosing was given.Conclusions: The timing of administration of the preoperative dose was at par with international guidelines and well allotted to the nursing staff. The intraoperative dose was appropriately omitted in the short term surgeries. The main concern was the increasing use of the third generation cephalosporins and the long duration of the postoperative prophylaxis, which required to be addressed.

Implementation of a multifaceted program to sustainably improve appropriate intraoperative antibiotic redosing

National guidelines recommend intraoperative redosing of prophylactic antibiotics at defined intervals to reduce the risk of surgical site infections. Compliance with these guidelines is poor. A quality improvement project-including education, progress reports, and automated redosing reminders in the anesthesia electronic health record-was implemented at a large university-affiliated hospital to increase rates of intraoperative antibiotic redosing for surgeries lasting more than 4 hours. A retrospective, observational study was then conducted. The primary outcome was the compliance rate with intraoperative antibiotic redosing criteria for all surgeries lasting more than 4 hours in the pre- and post-project period. The effect of the intervention was assessed by an interrupted time-series Poisson regression model. A total of 13,695 surgical procedures were evaluated. Time-series analysis demonstrated that the project was associated with significant improvement of compliance rates (incidence rate ratio [IRR]: 1.16; P = .002) with no significant change in underlying improvement trend (IRR: 1.00; P = .22). Few peer-reviewed manuscripts describe effective methods to ensure appropriate antibiotic redosing during prolonged surgeries. We demonstrated that a multipronged approach was very effective at producing immediate and sustained improvements in guideline compliance. Implementation of a multifaceted intervention improved rates of guideline-concordant redosing of intraoperative prophylactic antibiotics.

Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial

BackgroundPerioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probability of target attainment (PTA) and fractional target attainment (FTA) than intermittent dosing. MethodsPatients undergoing major surgery received cefazolin 2 g before surgical incision. They were subsequently randomized to receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500 mg h−1) of cefazolin until skin closure. Blood samples were analysed for total and unbound cefazolin concentrations using a validated chromatographic method. Population pharmacokinetic modelling was performed using Pmetrics® software. Calculations of PTA and FTA were performed for common pathogens. ResultsTen patients were enrolled in each arm. A two-compartment linear model best described the time course of the total plasma cefazolin concentrations. The covariates that improved the model were body weight and creatinine clearance. Protein binding varied with time [mean (range) 69 (44–80)%] with a fixed 21% unbound value of cefazolin used for the simulations (120 min post-initial dosing). Mean (sd) central volume of distribution was 5.73 (2.42) litres, and total cefazolin clearance was 4.72 (1.1) litres h−1. Continuous infusions of cefazolin consistently achieved better drug exposures and FTA for different weight and creatinine clearances, particularly for less susceptible pathogens. ConclusionsOur study demonstrates that intraoperative continuous infusions of cefazolin increase the achievement of target plasma concentrations, even with lower infusion doses. Renal function and body weight are important when considering the need for alternative dosing regimens. Clinical trial registrationNCT02058979.