Optimization of appropriate antimicrobial prophylaxis in general surgery: a prospective cohort study.

BACKGROUND: Surgical site infections (SSI) are characterized by infections occurring in the surgical incision site, organ or cavity in the postoperative period. Adherence to surgical antimicrobial prophylaxis (SAP) is paramount in mitigating the occurrence of SSIs. In this study, we aimed to evaluate the appropriateness of SAP use in patients undergoing surgical procedures in the field of general surgery according to the American Society of Health-System Pharmacists (ASHP) guideline and to determine the difference between the pre-training period (pre-TP) and the post-training period (post-TP) organized according to this guideline. METHODS: It is a single-center prospective study conducted in general surgery wards between January 2022 and May 2023, with 404 patients pre-TP and 406 patients post-TP. RESULTS: Cefazolin emerged as the predominant agent for SAP, favored in 86.8% (703/810) of cases. Appropriate cefazolin dosage increased significantly from 41% (129 patients) in pre-TP to 92.6% (276 patients) in post-TP (p < 0.001), along with a rise in adherence to recommended timing of administration from 42.2% (133 patients) to 62.8% (187 patients) (p < 0.001). The proportion of patients receiving antibiotics during hospitalization in the ward postoperatively decreased post-TP (21-14.3%; p = 0.012), as did antibiotic prescription at discharge (16.8-10.3%; p = 0.008). The incidence of SSI showed a slight increase from 9.9% in pre-TP to 13.3% in post-TP (p = 0.131). CONCLUSIONS: Routine training sessions for surgeons emerged as crucial strategies to optimize patient care and enhance SAP compliance rates, particularly given the burden of clinical responsibilities faced by surgical teams.

[Intraosseous vancomycin in total knee arthroplasty]. / Vancomicina intraósea en artroplastía total de rodilla.

INTRODUCTION: intravenous antibiotic prophylaxis has significantly reduced the incidence of periprosthetic joint infection (PJI) in knee surgeries. However, for patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, prophylaxis should include vancomycin. Intraosseous (IO) administration of vancomycin could enhance its effectiveness in total knee arthroplasty (TKA). MATERIAL AND METHODS: a retrospective review was conducted, including 143 patients at risk of PJI scheduled for TKA who received IO vancomycin along with intravenous (IV) cefazolin, referred to as group I (GI), between May 2021 and December 2022. The occurrence of complications in the first three postoperative months was evaluated. Results were compared with 140 patients without risk factors who received standard IV prophylaxis, designated as group II (GII). RESULTS: in GI, 500 mg of IO vancomycin was administered, injected into the proximal tibia, in addition to standard IV prophylaxis. In GII, patients received only IV cefazolin. The incidence of complications was 1.64% in GI and 1.4% in GII. The PJI rate at 90 postoperative days was 0.69% in GI and 0.71% in GII. CONCLUSIONS: IO vancomycin administration, along with standard IV prophylaxis, provides a safe and effective alternative for patients at risk of MRSA colonization. This approach minimizes complications associated with IV vancomycin use and addresses logistical challenges of timely administration.

INTRODUCCIÓN: la profilaxis antibiótica intravenosa ha reducido significativamente la incidencia de infección articular periprotésica (IAP) en cirugías de rodilla. No obstante, para pacientes colonizados con Staphylococcus aureus resistente a meticilina (SARM) o aquellos con riesgo de colonización, la profilaxis debe incluir vancomicina. La administración intraósea de vancomicina podría potenciar su efectividad en la artroplastía total de rodilla. MATERIAL Y MÉTODOS: se realizó una revisión retrospectiva que incluyó a 143 pacientes en riesgo de IAP programados para artroplastía total de rodilla que recibieron vancomicina intraósea junto a cefazolina intravenosa (IV), a quienes denominamos grupo I (GI), entre mayo de 2021 y diciembre de 2022. Se evaluó la aparición de complicaciones en los primeros tres meses postoperatorios. Los resultados se compararon con 140 pacientes sin factores de riesgo que recibieron profilaxis intravenosa estándar, denominados grupo II (GII). RESULTADOS: en el GI, se administraron 500 mg de vancomicina intraósea, inyectados en la tibia proximal, además de la profilaxis intravenosa estándar. En el GII, los pacientes recibieron sólo cefazolina intravenosa. La incidencia de complicaciones fue de 1.64% en el GI y de 1.4% en el GII. La tasa de IAP a los 90 días postoperatorios fue de 0.69% en el GI y de 0.71% en el GII. CONCLUSIONES: la administración de vancomicina intraósea, junto con la profilaxis intravenosa estándar, ofrece una alternativa segura y eficaz para pacientes con riesgo de colonización por SARM. Este enfoque minimiza las complicaciones asociadas con el uso intravenoso de vancomicina y soluciona los desafíos logísticos de la administración oportuna.

Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery.

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included. A maximum of two venous plasma, target-site plasma, and target-site tissue samples were taken during surgery. The primary outcomes were the cefazolin concentrations in venous plasma, target-site plasma, and target-site tissue. A total of 27 patients [median (interquartile range) age, 42 (29-59) years; 17 (63%) male] with 138 samples were included in the study. A minimum of 6 weeks follow-up was available for all patients. The mean (SD) venous plasma, target-site plasma, and target-site tissue concentrations were 36 (13) µg/mL, 29 (13) µg/mL, and 28 (13) µg/g, respectively, and the cefazolin concentrations between the different locations of surgery did not differ significantly in both target-site plasma and target-site tissue (P = 0.822 and P = 0.840). In conclusion, 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee, significantly surpassing the MIC90 required to combat the most prevalent microorganisms. This study represents the first of its kind to assess cefazolin concentrations in the lower extremities by examining both plasma and tissue samples in this magnitude.

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.

The Intraperitoneal Use of Cephazolin: A Novelty in the Prevention of Intra-abdominal Abscess after Laparoscopic Appendectomy in Children.

BACKGROUND: Laparoscopic appendectomy followed by postoperative intravenous (IV) antibiotics is the standard of care for acute appendicitis and postoperative prevention of intra-abdominal abscesses. The aim of or study was to determine if intraperitoneal irrigation with antibiotics could help prevent intra-abdominal abscess formation after laparoscopic appendectomy for complicated appendicitis in pediatric patients. METHODS: A retrospective study was conducted on consecutive pediatric patients with acute appendicitis who had appendectomy in our Pediatric Surgery Department between August 2020 and February 2022. We compared two groups with similar age and symptoms. The first group (A) was treated with the normal standard of care, i.e., laparoscopic appendectomy and postoperative IV antibiotic therapy. For the second group (B) intraperitoneal cefazoline irrigation was added at the end of the laparoscopic procedure. Postoperative intra-abdominal abscess was diagnosed with ultrasound examination, performed after clinical suspicion/abnormal blood test results. RESULTS: One hundred sixty patients (males:females 109:51; median age 10.5 years [range 3-17 years]) who had laparosopic appendectomy for complicated appendicitis were included, 82 in group A and 78 in group B. In the first 7 days after surgery, 18 patients in group and 5 in group B developed an intra-abdominal abscess (p < 0.005). Drains were positioned in 38 patients in group A vs. 9 in group B. One patient in group A had a different complication which was infection of the surgical incision. CONCLUSIONS: Intraperitoneal cefazoline irrigation at the end of the laparoscopic appendectomy in pediatric patients significantly reduces the formation of intra-abdominal abscesses.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

A 17-Year-Old Male With Hypoxemia After Long-Bone Fracture.

CASE PRESENTATION: An otherwise healthy 17-year-old male patient presented to a periphery hospital with a compound fracture of the right distal tibia and fibula after a traumatic accident on a ski trip. He was treated empirically with IV cefazolin before undergoing open reduction with internal fixation with intramedullary nail for surgical fixation. Postoperatively, he became febrile, tachypneic, and hypoxemic, requiring up to 6 L/min supplemental oxygen by nasal prongs. He reported mild chest discomfort but denied productive cough, hemoptysis, or calf tenderness. Because of nonresolving oxygen demands, on postoperative day (POD) 4, he was transferred to a tertiary care center for further management.

Population pharmacokinetic model of cefazolin in total hip arthroplasty.

Cefazolin is an antibiotic recommended for infection prevention in total hip arthroplasty (THA). However, the dosing regimen necessary to achieve therapeutic concentrations in obese patients remains unclear. The aim of this study was to conduct a population analysis of cefazolin pharmacokinetics (PK) and assess whether cefazolin administration should be weight adapted in THA. Adult patients undergoing THA surgery received an injection of 2000 mg of cefazolin, doubled in the case of BMI > 35 kg/m2 and total body weight > 100 kg. A population PK study was conducted to quantify cefazolin exposure over time compared to the therapeutic concentration threshold. A total of 484 cefazolin measurements were acquired in 100 patients, of whom 29% were obese. A 2-compartment model best fitted the data, and creatinine clearance determined interpatient variability in elimination clearance. Our PK simulations using a 2000 mg cefazolin bolus showed that cefazolin concentrations remained above the threshold throughout surgery, regardless of weight or renal function. A 2000 mg cefazolin single injection without adaptation to weight or renal function and without intraoperative reinjection was efficient in maintaining therapeutic concentrations throughout surgery. The optimal target concentration and necessary duration of its maintenance remain unclear.

Evaluation of Antibiotic Allergies in Surgical Patients.

Antibiotic administration in the perioperative period is the foundation of preventing surgical site infections. ß-Lactam antibiotics, notably the first-generation cephalosporin cefazolin, are the drugs of choice for this indication. However, reported antibiotic allergies often result in the use of suboptimal alternative agents that can lead to an increased risk of infection and adverse effects. A comprehensive allergy history and risk stratification should be completed preoperatively to determine whether or not a patient can be rechallenged with a ß-lactam antibiotic and what testing may be necessary prior to administration. Nursing staff can play a critical role in understanding the implications and management of reported antibiotic allergies in surgical patients in order to optimize patient care.

Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study.

Whether cefazolin is as effective and safer than antistaphylococcal penicillins (ASPs) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) is still debated in the absence of a randomized controlled trial. In this quasi-experimental study, we aimed to assess the effectiveness and safety of these two treatments in MSSA-IE, using the ASPs nationwide shortage in April 2016 as a unique opportunity to overcome the indication bias associated with observational studies. In this single-centre study, we compared patients with Duke-Li definite MSSA-IE treated with ASPs from January 2015 to March 2016 versus those treated with cefazolin from April 2016 to December 2018, when ASPs were not available. Effectiveness outcome was 90-day all-cause mortality. Safety outcomes included significant decrease in GFR and significant increase in serum liver enzymes. Logrank test was used to compare survival rates. Of 73 patients with MSSA-IE, 35 and 38 were treated with ASPs and cefazolin, respectively. Baseline patients' characteristics (demography, native or prosthetic valve IE, clinical characteristics, cardiac and septic complications) were similar between groups. Ninety-day all-cause mortality was 28.6% and 21.1%, in patients treated with ASPs and cefazolin, respectively (logrank p = 0.5727). There was no difference between groups for incident renal or liver toxicity events: acute kidney injury 45.7% vs. 44.7% (p = 0.933), increased ALT 5.7% vs. 13.2% (p = 0.432), bilirubin increase 5.7% vs. 10.5% (p = 0.676), in ASPs vs. cefazolin groups, respectively. In this quasi-experimental, effectiveness and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment.

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Kidney in Pregnant Subjects and Fetus.

The purpose of this study was to develop a physiologically based pharmacokinetic (PBPK) model predicting the pharmacokinetics (PK) of different compounds in pregnant subjects. This model considers the differences in tissue sizes, blood flow rates, enzyme expression levels, glomerular filtration rates, plasma protein binding, and other factors affected during pregnancy in both the maternal and fetal models. The PBPKPlus™ module in GastroPlus® was used to model the PK of cefuroxime and cefazolin. For both compounds, the model was first validated against PK data in healthy non-pregnant volunteers and then applied to predict pregnant groups PK. The model accurately described the PK in both non-pregnant and pregnant groups and explained well differences in the plasma concentration due to pregnancy. The fetal plasma and amniotic fluid concentrations were also predicted reasonably well at different stages of pregnancy. This work describes the use of a PBPK approach for drug development and demonstrates the ability to predict differences in PK in pregnant subjects and fetal exposure for compounds excreted renally. The prediction for pregnant groups is also improved when the model is calibrated with postpartum or non-pregnant female group if such data are available.

Estimation of Ontogeny Functions for Renal Transporters Using a Combined Population Pharmacokinetic and Physiology-Based Pharmacokinetic Approach: Application to OAT1,3.

To date, information on the ontogeny of renal transporters is limited. Here, we propose to estimate the in vivo functional ontogeny of transporters using a combined population pharmacokinetic (popPK) and physiology-based pharmacokinetic (PBPK) modeling approach called popPBPK. Clavulanic acid and amoxicillin were used as probes for glomerular filtration, combined glomerular filtration, and active secretion through OAT1,3, respectively. The predictive value of the estimated OAT1,3 ontogeny function was assessed by PBPK predictions of renal clearance (CLR) of other OAT1,3 substrates: cefazolin and piperacillin. Individual CLR post-hoc values, obtained from a published popPK model on the concomitant use of clavulanic acid and amoxicillin in critically ill children between 1 month and 15 years, were used as dependent variables in the popPBPK analysis. CLR was re-parameterized according to PBPK principles, resulting in the estimation of OAT1,3-mediated intrinsic clearance (CLint,OAT1,3,invivo) and its ontogeny. CLint,OAT1,3,invivo ontogeny was described by a sigmoidal function, reaching half of adult level around 7 months of age, comparable to findings based on renal transporter-specific protein expression data. PBPK-based CLR predictions including this ontogeny function were reasonably accurate for piperacillin in a similar age range (2.5 months-15 years) as well as for cefazolin in neonates as compared to published data (%RMSPE of 21.2 and 22.8%, respectively and %PE within ±50%). Using this novel approach, we estimated an in vivo functional ontogeny profile for CLint,OAT1,3,invivo that yields accurate CLR predictions for different OAT1,3 substrates across different ages. This approach deserves further study on functional ontogeny of other transporters.

Prolonged cefazolin course for treatment of methicillin susceptible staphylococcus species infections and the impact on the emergence of multidrug-resistant bacteria during cloxacillin shortage.

OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.

Antibiotic Stewardship Interventions Improve Choice of Antibiotic Prophylaxis in Total Joint Arthroplasty in Patients with Reported Penicillin Allergies.

BACKGROUND: Most patients who report a penicillin allergy can tolerate cefazolin, the preferred prophylaxis in a total joint arthroplasty (TJA). Regardless, patients with a reported penicillin allergy are less likely to receive first-line perioperative antibiotics as a result of inaccurate penicillin allergy documentation and misconceptions regarding cross-reactivity between penicillin and cephalosporins. The over-reporting of penicillin allergies and the safety of cephalosporins in patients with reported penicillin allergies have been well established throughout the evidence [13]. QUESTIONS/PURPOSES: The study sought to answer two questions: (1) Do antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA? (2) What is the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy? METHODS: This was a single-center, retrospective study of orthopaedic patients older than 18 years who underwent a primary elective TJA at a 261-bed community hospital. The study had two periods: the preintervention period ran from March 1, 2017 to August 30, 2017 and the postintervention period was from March 1, 2019 to August 30, 2019. A total of 396 patients with a history of a documented penicillin allergy underwent a THA or TKA during the study periods. After reviewing every fourth patient with a history of a documented penicillin allergy who met study inclusion criteria and excluding those patients who had a codocumented cephalosporin allergy, a total of 180 patients with a documented penicillin allergy were evaluated (90 patients in the preintervention group and 90 patients in the postintervention group). To answer our first study question, regarding whether antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA, we evaluated appropriate antibiotic usage pre- and postintervention. To answer our second study question, concerning the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy, we reviewed signs of allergic reactions in patients who received cefazolin for a primary TJA and had a documented penicillin allergy. RESULTS: Postintervention antibiotic use was more appropriate (91% [82 of 90] versus 54% [49 of 90], risk ratio 1.67 [95% confidence interval 1.37 to 2.04]; p < 0.01), particularly in patients with nonsevere allergy (preintervention: 47% [36 of 76] versus postintervention: 96% [76 of 79]; p < 0.01). No patients had signs of an allergic reaction related to cefazolin, including eight patients with severe penicillin allergy. CONCLUSION: A multifaceted antibiotic stewardship intervention increased the appropriateness of antibiotic prophylaxis in elective primary TJA. Patients with nonsevere penicillin allergies, even those reporting hives or local swelling, tolerated cefazolin. Antibiotic stewardship interventions can be implemented across institutions to expand cephalosporin use in patients with a reported penicillin allergy within orthopaedic TJA patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Cefazolin prophylaxis in minimally invasive gynecologic surgery - are dosage and timing appropriate? Prospective study using resampling simulation.

OBJECTIVE: Cefazolin is a widely used antimicrobial prophylactic agent, however the appropriate dosage, timing, pharmacology and microbial coverage have not been well-established for gynecologic procedures. We aimed to describe serum concentrations and pharmacokinetics of Intravenous cefazolin given to women prior to scheduled minimally invasive gynecologic surgeries, and to determine whether appropriate antimicrobial coverage had been achieved in short time from prophylactic administration to surgical start time. METHODS: A prospective cohort analysis study, using a resampled dataset, of women undergoing scheduled gynecological surgeries in a university affiliated tertiary medical center. IV cefazolin (1 or 2 gr) was administered prior to incision to women weighing <80 kg (Group A) and ≥80 kg (Group B), respectively. Cefazolin serum levels were obtained at the time of skin incision (Time 0) and 30 min later (Time 30), measured by high-pressure liquid chromatography (HPLC). Appropriate antimicrobial coverage was defined when cefazolin serum levels were above minimal inhibitory concentrations (MIC) for Enterobacteriaceae. RESULTS: Overall, 21 women were included. The mean time interval between drug administration and incision did not differ between the two groups (18 ± 10 min vs. 11 ± 10 min, respectively, p = .0.25). A hierarchical mixed linear regression model, using a simulation of multiple random bootstrap resampling (n = 1,000), revealed that cefazolin serum levels exceeded MIC, regardless of the timing of administration in the sampling intervals. Mean cefazolin serum levels in time 0 and time 30 min were not affected by BMI in patients receiving 1 gr. CONCLUSION: A single dose of IV cefazolin given shortly prior to skin incision provides serum concentrations above minimal inhibitory concentrations for susceptible pathogens in most women undergoing scheduled minimally invasive gynecologic surgery.

Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial).

BACKGROUND: Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, especially below the level of the knee. Antibiotic prophylaxis is not routinely prescribed, even though it has proved to lower SSI rates in other (orthopedic) trauma surgical procedures. The primary objective is to study the effectiveness of a single intravenous dose of 2 g of cefazolin on SSIs after IR following fixation of foot, ankle and/or lower leg fractures. METHODS: This is a multicenter, double-blind placebo controlled trial with a superiority design, including adult patients undergoing elective implant removal after fixation of a fracture of foot, ankle, lower leg or patella. Exclusion criteria are: an active infection, current antibiotic treatment, or a medical condition contraindicating prophylaxis with cefazolin including allergy. Patients are randomized to receive a single preoperative intravenous dose of either 2 g of cefazolin or a placebo (NaCl). The primary analysis will be an intention-to-treat comparison of the proportion of patients with a SSI at 90 days after IR in both groups. DISCUSSION: If 2 g of prophylactic cefazolin proves to be both effective and cost-effective in preventing SSI, this would have implications for current guidelines. Combined with the high infection rate of IR which previous studies have shown, it would be sufficiently substantiated for guidelines to suggest protocolled use of prophylactic antibiotics in IR of foot, ankle, lower leg or patella. Trial registration Nederlands Trial Register (NTR): NL8284, registered on 9th of January 2020, https://www.trialregister.nl/trial/8284.

Toxic shock syndrome with a cytokine storm caused by Staphylococcus simulans: a case report.

BACKGROUND: Exotoxins secreted from Staphylococcus aureus or Streptococcus pyogenes act as superantigens that induce systemic release of inflammatory cytokines and are a common cause of toxic shock syndrome (TSS). However, little is known about TSS caused by coagulase-negative staphylococci (CoNS) and the underlying mechanisms. Here, we present a rare case of TSS caused by Staphylococcus simulans (S. simulans). CASE PRESENTATION: We report the case of a 75-year-old woman who developed pneumococcal pneumonia and bacteremia from S. simulans following an influenza infection. The patient met the clinical criteria for probable TSS, and her symptoms included fever of 39.5 °C, diffuse macular erythroderma, conjunctival congestion, vomiting, diarrhea, liver dysfunction, and disorientation. Therefore, the following treatment was initiated for bacterial pneumonia complicating influenza A with suspected TSS: meropenem (1 g every 8 h), vancomycin (1 g every 12 h), and clindamycin (600 mg every 8 h). Blood cultures taken on the day after admission were positive for CoNS, whereas sputum and pharyngeal cultures grew Streptococcus pneumoniae (Geckler group 4) and methicillin-sensitive S. aureus, respectively. However, exotoxins thought to cause TSS, such as TSS toxin-1 and various enterotoxins, were not detected. The patient's therapy was switched to cefazolin (2 g every 8 h) and clindamycin (600 mg every 8 h) for 14 days based on microbiologic test results. She developed desquamation of the fingers on hospital day 8 and was diagnosed with TSS. Conventional exotoxins, such as TSST-1, and S. aureus enterotoxins were not detected in culture samples. The serum levels of inflammatory cytokines, such as neopterin and IL-6, were high. CD8+ T cells were activated in peripheral blood. Vß2+ population activation, which is characteristic for TSST-1, was not observed in the Vß usage of CD8+ T cells in T cell receptor Vß repertoire distribution analysis. CONCLUSIONS: We present a case of S. simulans-induced TSS. Taken together, we speculate that no specific exotoxins are involved in the induction of TSS in this patient. A likely mechanism is uncontrolled cytokine release (i.e., cytokine storm) induced by non-specific immune reactions against CoNS proliferation.