Are Antibiotics of Value for a Whipple Procedure?

Pancreatoduodenectomy is a complex surgical procedure with a high rate of morbidity, of which surgical-site infections (SSIs) make a large portion. Reduction of SSI rates is critical to decrease hospital lengths of stay, readmissions, delays in adjuvant therapies, and financial health care burden. Current clinical guidelines recommend the administration of cefoxitin as surgical prophylaxis prior to pancreatoduodenectomy. In April 2023, a randomized controlled trial was published in JAMA which showed that piperacillin-tazobactam as perioperative surgical prophylaxis prior to pancreatoduodenectomy decreased 30 day SSI rates (primary outcome), clinically relevant postoperative pancreatic fistula, postoperative sepsis, and Clostridium difficile infection rates.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

Surgical Site Infections in Trauma Exploratory Laparotomies Preoperative Ceftriaxone and Metronidazole Versus Cefoxitin.

Surgical site infections (SSIs) remain a significant cause of morbidity and mortality in patients undergoing traumatic exploratory laparotomy. The goal of this study was to compare antibiotic usage and subsequent outcomes in patients undergoing traumatic exploratory laparotomy. A retrospective chart analysis and a chi-square test of independence were performed to examine the relation between preoperative cefoxitin versus ceftriaxone and metronidazole and the rate of SSI development. 323 patients were analyzed, 111 patients receiving cefoxitin and 212 patients receiving ceftriaxone and metronidazole. The proportion of patients who developed SSI was 16.2% for the cefoxitin group and 9.9% for the ceftriaxone and metronidazole group, X2 (1, N = 323) = 2.7, P = .098, thus displaying no statistical difference in the development of SSIs between patients in the cefoxitin group when compared to the ceftriaxone and metronidazole group.

Population pharmacokinetics of prophylactic cefoxitin in elective bariatric surgery patients: a prospective monocentric study.

BACKGROUND: This study describes the population pharmacokinetics of cefoxitin in obese patients undergoing elective bariatric surgery and evaluates different dosing regimens for achievement of pre-defined target exposures. METHODS: Serial blood samples were collected during surgery with relevant clinical data. Total serum cefoxitin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. The cefoxitin unbound fraction (fu) was estimated. Dosing simulations were performed to ascertain the probability of target attainment (PTA) to achieve cefoxitin fu above minimum inhibitory concentrations (MIC) from surgical incision to wound closure. Fractional target attainment (FTA) was calculated against MIC distributions of common pathogens. RESULTS: A total of 123 obese patients (median BMI 44.3 kg/m2) were included with 381 cefoxitin concentration values. Cefoxitin was best described by a one-compartment model, with a mean clearance and volume of distribution of 10.9 ± 6.1 L/h and 23.4 ± 10.5 L, respectively. In surgery <2 h, a 2 and a 4 g doses were sufficient for an MIC up to 4 and 8 mg/L (fu 50%), respectively. In prolonged surgery (2-4 h), only continuous infusion enabled optimal PTA for an MIC up to 16 mg/L. Optimal FTAs were obtained against Staphylococcus aureus and Escherichia Coli only when simulating with 50% cefoxitin protein binding (intermittent regimen) and regardless of the protein binding for the continuous infusion. CONCLUSION: Intermittent dosing regimens resulted in optimal FTAs against susceptible MIC distributions of S. aureus and E. coli when simulating with 50% cefoxitin protein binding. Continuous infusion of cefoxitin may improve FTA regardless of protein binding. STUDY REGISTRATION: Registration on ClinicalTrials.gov, NCT03306290.

Cefoxitin for Intra-amniotic Infections and Endometritis: A Retrospective Comparison to Traditional Antimicrobial Therapy Regimens Within a Healthcare System.

BACKGROUND: Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change. METHODS: This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling. RESULTS: A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010). CONCLUSIONS: Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI.

Radiographic severity and treatment outcome of Mycobacterium abscessus complex pulmonary disease.

INTRODUCTION: The lack of reliable predictors for the treatment response complicates decisions to initiate treatment in patients with Mycobacterium abscessus complex pulmonary disease (MABC-PD). We aimed to investigate whether baseline radiographic disease severity is associated with treatment outcome in MABC-PD. METHOD: We retrospectively analyzed 101 patients with MABC-PD (54 with M. abscessus-PD and 47 with M. massiliense-PD) treated in a tertiary referral hospital between January 2006 and December 2019. Using chest computed tomography images, baseline radiographic disease severity was quantitatively scored according to five categories of radiographic lesions (bronchiectasis, bronchiolitis, cavities, nodules, and consolidation). RESULTS: Treatment success was achieved in 53.7% of patients with M. abscessus-PD and 85.1% of patients with M. massiliense-PD. Higher overall scores for baseline radiographic disease severity were associated with treatment failure in patients with M. massiliense-PD (aOR 1.35, 95% CI 1.02-1.79 for each 1-point increase in severity score), as well as in patients with M. abscessus-PD (aOR 1.15, 95% CI 1.00-1.33). This was particularly prominent in patients with overall severity score of ≥14 (aOR 31.16, 95% CI 1.12-868.95 for M. massiliense-PD and aOR 3.55, 95% CI 1.01-12.45 for M. abscessus-PD). Among variable radiographic abnormalities, the score for cavitary lesion severity was associated with treatment failure in patients with M. abscessus-PD (aOR 1.26, 95% CI 1.01-1.56), but not in patients with M. massiliense-PD. CONCLUSIONS: Given the association between baseline radiographic disease severity and treatment outcome, initiating treatment should be actively considered before significant progression of radiographic lesions in patients with MABC-PD.

Influence of the Obesity Phenotype on the Adequacy of Antibiotic Prophylaxis with Cefoxitin for Obese Patients Undergoing Bariatric Surgery: Lessons Learnt and Future Considerations.

BACKGROUND AND OBJECTIVES: A high inter-individual variability in pharmacokinetic parameters in obese patients is observed. The objective of this study was to evaluate the effect of obesity parameters on the pharmacokinetics of cefoxitin administered for antibiotic prophylaxis during bariatric surgery. METHODS: This a secondary analysis of a pharmacokinetic study involving 174 obese patients scheduled for bariatric surgery and receiving a 4-g dose of cefoxitin. Blood samples were collected at incision and wound closure. The total plasma concentrations were assessed utilising a validated high-performance liquid chromatography-tandem mass spectrometry method. The pharmacokinetic and pharmacodynamic target was defined as an estimated free concentration of cefoxitin at the time of wound closure >8 mg/L. Specific evaluated obesity parameters were fat body mass, fat body mass/height2, lean body mass, lean body mass/height2, visceral adipose tissue and presence of a metabolic syndrome. RESULTS: A total of 174 patients (median age 47 years) with a majority of women (75.3%) and a median BMI of 44 kg/m2 were analysed. The percentage of patients who met the pharmacokinetic and pharmacodynamic target was 85.1%. In the whole population, a tendency to fail to reach the target was observed with a higher lean mass over height2 [OR = 0.79; 95% CI (0.62-1.01); P = 0.060]. In the female subgroup, higher lean mass over height2 [OR = 0.63; 95% CI (0.41-0.97); P = 0.037] and the presence of a metabolic syndrome [OR = 0.17; 95% CI (0.03-0.83); P = 0.030] were associated with failure to reach the pharmacokinetic and pharmacodynamic target. CONCLUSION: Obese patients with a higher lean mass and a metabolic syndrome could constitute a subgroup at risk for cefoxitin under-dosage.

A NSQIP-based randomized clinical trial evaluating choice of prophylactic antibiotics for pancreaticoduodenectomy.

Surgical site infection after pancreaticoduodenectomy is often caused by pathogens resistant to standard prophylactic antibiotics, suggesting that broad-spectrum antibiotics may be more effective prophylactic agents. This article describes the rationale and methodology underlying a multicenter randomized trial evaluating piperacillin-tazobactam compared with cefoxitin for surgical site infection prevention following pancreaticoduodenectomy. As the first US randomized surgical trial to utilize a clinical registry for data collection, this study serves as proof of concept for registry-based clinical trials.

Reassessing the dosing of cefoxitin prophylaxis during major abdominal surgery: insights from microdialysis and population pharmacokinetic modelling.

OBJECTIVES: Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. METHODS: Data from eight patients undergoing major abdominal surgery were analysed using population pharmacokinetic modelling, and Monte Carlo simulations were conducted to determine the PTA for aerobic and anaerobic pathogens. ClinicalTrials.gov: NCT02703857. RESULTS: Only 2.3% and 47.4% of the simulated patients maintained cefoxitin subcutaneous concentrations above the MIC breakpoint for anaerobic (MIC = 16 mg/L) and aerobic (MIC = 8 mg/L) pathogens, respectively. New simulations with administration of a loading dose followed by a constant infusion of cefoxitin were conducted and demonstrate that, notwithstanding using the same total dose per unit of time, continuous infusion of cefoxitin can cover aerobes in 96.6% of the simulated patients, but remains insufficient for anaerobic bacteria. CONCLUSIONS: The recommended dosing regimen of cefoxitin is insufficient for covering the usual bacteria during abdominal surgery. Administration of a loading dose followed by a constant infusion should be considered for aerobic bacteria and cefoxitin should be avoided as SAP for anaerobic bacteria.

Cefoxitin Prophylaxis During Pediatric Cardiac Surgery: Retrospective Exploration of Postoperative Trough Levels.

BACKGROUND: This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery. METHODS: Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery. RESULTS: Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6-4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62-0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18-36; P = 0.004) showed a significant relationship with the PD targets. CONCLUSIONS: Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.

Mycobacterium abscessus Infection During Ustekinumab Treatment in Crohn's Disease: A Case Report and Review of the Literature.

The introduction of ustekinumab, an interleukin [IL]12/23 p40 inhibitor, to the therapeutic armamentarium of Crohn's disease has provided a much needed treatment option for patients who have failed conventional biologics with anti-tumour necrosis factor [TNF] and anti-integrin agents. Despite targeting two major cytokine pathways, the side effect profile of ustekinumab appears to be favourable in clinical trials. In particular, the risk of tuberculosis infection was observed to be lower than in patients who have received anti-TNF agents. The risk of non-tuberculosis mycobacterium infection, however, remains unknown. Here, we report the first case of a patient with Crohn's disease who developed Mycobacterium abscessus infection while on ustekinumab treatment.

Higher versus Lower Dose of Cefotetan or Cefoxitin for Surgical Prophylaxis in Patients Weighing One Hundred Twenty Kilograms or More.

BACKGROUND: Clinical practice guidelines recommend a 2-g dose of cefotetan and cefoxitin for surgical prophylaxis. Pharmacokinetic data suggest benefit from higher cefotetan and cefoxitin dosing in obese patients. However, clinical studies examining higher dosing strategies in this at-risk population are lacking. The purpose of this study was to determine whether 3 g of cefotetan or cefoxitin administered pre-operatively for patients who weigh 120 kg or more is associated with a lower proportion of surgical site infection (SSI) compared with 2 g. PATIENTS AND METHODS: Medical records of patients weighing 120 kg or more who had received cefotetan or cefoxitin (2 or 3 g) as surgical prophylaxis for intra-abdominal procedures between July 2012 and August 2015 were reviewed for the development of an SSI (primary outcome), study drug-related adverse events, and re-admissions attributed to SSIs (secondary outcomes). Relative risk calculations were performed for analysis of the primary and secondary outcomes. RESULTS: One-hundred seventy-five procedures in 169 patients were included in the study. Cefotetan was used in 81% (141/175) of procedures. Three grams of cefotetan or cefoxitin was used in 20% (35/175) of procedures. The median body mass index (BMI) in both dosing groups was 42 kg/m2 and patients who received 3 g more often weighed more than 130 kg (relative risk [RR] 1.36, 1.01-1.76; p = 0.04). Surgical site infections occurred in 20.7% within the 2-g group and 22.9% in the 3-g group (RR 1.10, 0.55-2.20; p = 0.78). There was no difference in the number of study drug-related adverse effects in the 3-g compared with the 2-g group. Thirty-day re-admissions because of SSI also did not differ between the 2-g and 3-g groups (7.9% vs. 17.1%, respectively; p = 0.11). CONCLUSION: This small retrospective study did not find a difference in SSI rates between 3-g and 2-g surgical prophylaxis dosing for patients 120 kg or more with a median BMI >40 kg/m2.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial.

INTRODUCTION: Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. METHODS AND ANALYSIS: Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine-alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION: COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: EudraCT 2015-002559-84; NCT02618720.

[Effects of the combined therapy of heat sensitive moxibustion and acupoint injection on endometrial receptivity of hypdrosalphinx infertility in the patients after hysteroscopy and laparoscopy].

OBJECTIVE: To explore the effects of the combined therapy of heat sensitive moxibustion and acupoint injection on endometrial receptivity of hypdrosalphinx infertility in the patients after hysteroscopy and laparoscopy on the base of routine post-operative anti-inflammation. METHODS: A total of 210 patients of hypdrosalphinx infertility after hysteroscopy and laparoscopy were divided into a combined therapy group, a heat sensitive moxibustion group and a control group, 70 cases in each one according to the random number table. In the control group, the intravenous drip of cefoxitin sodium was adopted, and the anti-inflammation treatment was given for 1 week after operation. In the heat sensitive moxibustion group, on the basis of the treatment as the control group, the heat sensitive moxibustion was applied after vaginal bleeding stopped. The acupoints were Yaoyangguan (GV 3), Guanyuan (CV 4), Qihai (CV 6), Shenshu (BL 23), Sanyinjiao (SP 6), Yinlingquan (SP 9) and Zigong (EX-CA1). The acupoints were modified according to the different syndromes. In the combined therapy group, on the basis of the regimen as the heat sensitive moxibustion group, after vaginal bleeding stopped, the acupoint injection was given alternatively at bilateral Tiangong (extra, 1.0 cm inferior and bilateral to the cervix) with lidocaine 1 mL, amikacin 2 mL and salvia injection 2 mL. The treatment was given once every day, the treatment for 10 times as one course and a total of 3 courses were required. The endometrial type, thickness, uterine arterial plusatility index (PI) and resistance index (RI) were observed in the patients of each group. RESULTS: After treatment, the numbers of A-type endometrial type in the combined therapy group and the heat sensitive moxibustion group were remarkably higher than those of the control group [57.1% (40/7) vs 31.4% (22/70), 50.0% (35/70) vs 31.4% (22/70), both P<0.05]. The endometrial thickness after treatment was all increased as compared with that before treatment in each group (all P<0.05). The increasing degree in the combined therapy group was better than either the heat sensitive moxibustion group or the control group (both P<0.05). The improvement in the heat sensitive moxibustion group was superior to the control group (P<0.05). PI and RI in the combination group and PI in the control group were decreased after treatment (all P<0.05). The improvements of PI and RI in the combination group were better than those in the heat moxibustion group (both P<0.05), which were superior to those in the control group (all P<0.05). CONCLUSION: In the patients of hypdrosalphinx infertility after hysteroscopy and laparoscopy, the combined therapy of heat sensitive moxibustion and acupoint injection increases endometrial thickness, reduces uterine arterial resistance and improves endometrial receptivity.

Antibiotic Powder Reduces Surgical Site Infections in Children After Single-Incision Laparoscopic Appendectomy for Acute Appendicitis.

BACKGROUND: Single-incision laparoscopic appendectomy (SILA) has a higher rate of wound infection than the multiport technique. The purpose of this project was to determine whether the use of topical antibiotic powder reduces surgical site infections (SSIs) in pediatric patients who undergo SILA. METHODS: Patients aged 0-21 years who underwent SILA for acute appendicitis from April 2015 to November 2016 were included in this quality improvement initiative. Cefoxitin powder was placed in the umbilical wound before skin closure. Data were prospectively collected and outcome measures were compared with a historical cohort who underwent SILA before the implementation of antibiotic powder. RESULTS: There were 108 patients in the historical group (HIST) and 126 in the powder group (POWD). The groups were similar in age (HIST: 11.5 ± 3.6 versus POWD: 12.2 ± 3.7 years, P = .15) and body mass index percentile (HIST: 57.6 ± 30.7 versus POWD: 58.8 ± 27.8, P = .84). Operative time was longer in the powder group (HIST: 26.5 ± 7.5 versus POWD: 29.7 ± 8.9 minutes, P = .004). Length of stay (HIST: 0.2 ± 0.4 versus POWD: 0.1 ± 0.4 days, P = .06), 30-day return to emergency department (HIST: 7% versus POWD: 8%, P = 1.0), and hospital readmissions (HIST: 5% versus POWD: 2%, P = .8) were similar. There was a significantly lower rate of superficial SSIs in the powder group (HIST: 4.6% versus POWD: 0%, P = .02). CONCLUSIONS: In pediatric patients undergoing SILA for acute appendicitis, the use of cefoxitin powder in the umbilical wound is a simple intervention to reduce the incidence of superficial SSIs.

Observation on Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section.

This paper aims to observe the effect of Shenqi Fuzheng Injection combined with cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were retrospectively analyzed. They randomized into control group and treatment group, and there were 63 cases in each group. Patients in control group were given Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi Fuzheng Injection on the basis of control group. After 7 days of treatment, the clinical curative effect of the two groups was observed and compared. The body temperature of the patients in treatment group was significantly decreased when compared with control group on the 2nd and 3rd day after operation (P<0.05); the first exhaust time and defecation time of patients in treatment group were significantly shortened when compared with control group (P<0.05); the postoperative hemoglobin and red blood cell count in both groups were all significantly increased when compared with before treatment (P<0.05), and the treatment group were evidently higher than control group (P<0.05); the postoperative neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in both groups were all significantly lowered when compared with before treatment (P<0.05), and the neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in treatment group were significantly lowered when compared with control group (P<0.05). Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section can effectively reduce the postoperative maternal body temperature and promote the recovery of maternal gastrointestinal function, which is conducive to the repair of uterus, further correct anemia after cesarean section and prevent postpartum infection. Its clinical curative effect is ideal, with certain clinical application value.

Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients.

The objective of this study was to determine the pharmacokinetics and pharmacodynamics (PK/PD) of a weight-based cefoxitin dosing regimen for surgical prophylaxis in obese patients. Patients received a single dose of cefoxitin at 40 mg/kg based on total body weight. Cefoxitin samples were obtained over 3 h from serum and adipose tissue, and concentrations were determined by validated high-performance liquid chromatography. Noncompartmental pharmacokinetic analysis was performed, followed by Monte Carlo simulations to estimate probability of target attainment (PTA) for Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis over 4-h periods postdose. Thirty patients undergoing bariatric procedures were enrolled. The body mass index (mean ± standard deviation [SD])was 45.9 ± 8.0 kg/m(2) (range, 35.0 to 76.7 kg/m(2)); the median cefoxitin dose was 5 g (range, 4.0 to 7.5 g). The mean maximum concentrations were 216.15 ± 41.80 µg/ml in serum and 12.62 ± 5.89 in tissue; the mean tissue/serum ratio was 8% ± 3%. In serum, weight-based regimens achieved ≥90% PTA (goal time during which free [unbound] drug concentrations exceed pathogen MICs [fT>MIC] of 100%) for E. coli and S. aureus over 2 h and for B. fragilis over 1 h; in tissue this regimen failed to achieve goal PTA at any time point. The 40-mg/kg regimens achieved higher PTAs over longer periods in both serum and tissue than did the standard 2-g doses. However, although weight-based cefoxitin regimens were better than fixed doses, achievement of desired pharmacodynamic targets was suboptimal in both serum and tissue. Alternative dosing regimens and agents should be explored in order to achieve more favorable antibiotic performance during surgical prophylaxis in obese patients.

Integrated pharmacokinetic-pharmacodynamic modelling to evaluate antimicrobial prophylaxis in abdominal surgery.

OBJECTIVES: To use Monte Carlo simulation with an integrated pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery. METHODS: AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens. RESULTS: Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg. CONCLUSIONS: This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin.

Oral Macrolide Therapy Following Short-term Combination Antibiotic Treatment of Mycobacterium massiliense Lung Disease.

BACKGROUND: Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease. METHODS: Seventy-one patients received oral macrolides, along with an initial 4-week (n = 28) or 2-week (n = 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24 months (4-week IV group) or for at least 12 months after negative sputum culture conversion (2-week IV group). RESULTS: Total treatment duration was longer in the 4-week IV group (median, 23.9 months) than in the 2-week IV group (15.2 months; P < .001). The response rates after 12 months of treatment were 89% for symptoms, 79% for CT scanning, and 100% for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100% (P = .057), 91% (P = .177), and 91% (P = .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense. CONCLUSIONS: Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.

Cefoxitin Plasma and Subcutaneous Adipose Tissue Concentration in Patients Undergoing Sleeve Gastrectomy.

PURPOSE: Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of this study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy. METHODS: A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of the surgical procedure, venous blood samples (5 mL) were collected just before cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition, subcutaneous adipose tissue was collected from the surgical site at the time of surgical incision and at closure. Cefoxitin concentrations in the collected samples were quantified by using an HPLC-ultraviolet method. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration-time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. FINDINGS: Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. The mean age and BMI were 48.7 (6.2) years and 42.8 (7.1) kg/m(2), respectively. At the time of surgical closure, subcutaneous adipose tissue concentrations of cefoxitin were subtherapeutic (<8 µg/mL) in all evaluated patients. IMPLICATIONS: Current dosing strategies for cefoxitin in obese surgical patients may be inadequate, and there is an urgent need to define the appropriate dosage.