Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

OBJECTIVES: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. METHODS: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. RESULTS: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). CONCLUSIONS: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Effect of prophylactic use of cefazolin in caesarean section on postoperative infection: A meta-analysis.

Caesarean section rate is increasing and postoperative wound infection is a major health-threatening complication after caesarean section (CS). The aim of this study was to evaluate the efficacy of Cefazolin at different time for post-caesarean delivery. The aim of this study was to compare the use of Cefazolin at different times on infections after CS. The time of antibiotic use in CS can be divided into two groups: before skin incision (SI) and after cord clamping (CC). In this study, 268 relevant articles were found in the database, and finally, 10 articles were analysed. This study included a total of 5256 cases of caesarean section. The data on wound infections, endometritis, urinary tract infections and fever were analysed. Perform an analysis of the data using RevMan 5.3. The results showed that cefazolin before SI reduced wound infection compared to after CC (odds ratio [OR], 0.51; 95% CI: 0.37-0.69; p < 0.0001). Cefazolin prophylactically used before SI reduce endometritis after CS compared to after CC (OR, 0.52; 95% CI: 0.35-0.77; p = 0.001). There was no significant difference in urinary tract infections after CS between cefazolin prophylactically used before SI and after CC (OR, 0.80; 95% CI: 0.50-11.28; p = 0.35). There was no significant difference in fever after CS between the prophylactic use of cefazolin before SI and after CC (OR, 0.60; 95% CI: 0.26-11.43; p = 0.225). Cefazolin before SI reduces wound infection and endometritis after CS.

Cefazolin as a predictor of urinary cephalosporin activity in indicated Enterobacterales.

Traditionally, cephalothin susceptibility results were used to predict the susceptibility of additional cephalosporins; however, in 2013-2014, the Clinical and Laboratory Standards Institute (CLSI) revisited this practice and determined that cefazolin is a more accurate proxy than cephalothin for uncomplicated urinary tract infections (uUTIs). Therefore, a cefazolin surrogacy breakpoint was established to predict the susceptibility of seven oral cephalosporins for Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in the context of uUTIs. Clinical microbiology laboratories face several operational challenges when implementing the cefazolin surrogacy breakpoint, which may lead to confusion for the best path forward. Here, we review the historical context and data behind the surrogacy breakpoints, review PK/PD profiles for oral cephalosporins, discuss challenges in deploying the breakpoint, and highlight the limited clinical outcome data in this space.

Effect of Antibiotic Prophylaxis on Infection Rates in Pediatric Supracondylar Humerus Fractures Treated with Closed Reduction and Percutaneous Pinning: A Prospective Double-Blinded Randomized Controlled Trial.

BACKGROUND: Supracondylar humerus fractures (SCHFs) are the most common elbow fracture in the pediatric population. In the case of displaced fractures, closed reduction and percutaneous Kirschner wire pinning (CRPP) is commonly performed. Infection rates are between 0 and 7%; however, retrospective studies have shown no benefit of preoperative antibiotics. There continues to be notable variability in antibiotic usage based on surgeon preference and local institutional policy. We conducted a double-blinded, randomized controlled trial to evaluate whether antibiotic prophylaxis reduces the risk of infection in pediatric SCHF patients treated with CRPP. METHODS: Pediatric patients with displaced SCHF who presented to a pediatric hospital were enrolled and randomized into two groups. Group I received one dose of prophylactic antibiotics (25 mg/kg cefazolin IV up to 1g or clindamycin 10 mg/kg up to 600 mg/kg IV in the case of cefazolin allergy). Group II received placebo (10-mL prefilled syringe of normal saline). All patients underwent CRPP and casting followed by pin removal 3 to 6 weeks after the initial procedure. The presence of pin-site infection, erythema, drainage, septic arthritis, and osteomyelitis was recorded. RESULTS: One hundred sixty patients were enrolled in the study. Eighty-two patients were randomized to receive antibiotics, and 78 patients were randomized to placebo. No difference was seen in the rate of infection between the treatment groups (1.2% in the antibiotic group versus 1.3% in the placebo group; P = 1.00). Presence of purulent drainage (0.0% versus 1.3%; P = 0.49), septic arthritis (0.0% versus 0.0%; P = 1.00), and osteomyelitis (1.2% versus 0.0%; P = 1.00) was similar in both groups. No difference in the need for additional antibiotics (1.2% versus 1.3%; P = 1.00) or additional surgery (1.2% versus 0.0%; P = 1.00) was found between groups. DISCUSSION: The use of antibiotic prophylaxis did not affect the risk of infection in pediatric patients who underwent CRPP for displaced SCHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03261830. LEVEL OF EVIDENCE: Therapeutic Level I.

Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime.

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.

Prolonged efficacy of cefazolin in intraosseous regional prophylaxis for total knee arthroplasty: a rabbit model study.

BACKGROUND: A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. METHODS: Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. RESULTS: The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. CONCLUSIONS: Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Comparison of the effect between cefazolin/cefuroxime and broad-spectrum antibiotics in preventing post-operative pulmonary infections for smoking patients receiving video-assisted thoracoscopic lung surgery: a propensity score-matched retrospective cohort study.

BACKGROUND: The selection of prophylactic antibiotics for preventing post-operative pulmonary infections in smoking patients undergoing video-assisted thoracoscopic lung surgery (VATLS) is not clear. METHODS: In this retrospective cohort study, the outcomes of 572 smoking patients undergoing VATLS with prophylactic cefazolin/cefuroxime or other antibiotics were analyzed. Patients were classified as cefazolin/cefuroxime group and the control group. A 1:1 propensity score matching was also performed. RESULTS: The primary outcome of the incidence of post-operative pulmonary infection did not differ significantly between the two groups (23.7% vs 30.5%, RR = 0.777, 95%CI 0.564 ~ 1.070 p = 0.113). Similarly, secondary outcomes including the incidence of post-operative fever, the white blood cell count and neutrophils on the 3rd day after the surgery, and time for blood routine test recovery were all found without significant difference between the two groups. In the multivariate logistic regression model, no association was found between prophylactic use of cefazolin/cefuroxime and post-operative pulmonary infections after controlling other possible confounding factors (OR = 0.685, 95%CI 0.441 ~ 1.065, p = 0.093). CONCLUSIONS: Prophylactic use of cefazolin/cefuroxime was not associated with more adverse clinical outcomes among smoking populations undergoing VATLS when compared with broad-spectrum antibiotics and the two drugs are still feasible for peri-operative prophylactic use for smoking population before the surgery.

Can Perioperative Antibiotic Choice Impact Rates of Infectious Complications After Percutaneous Nephrolithotomy? A Single-Blind, Prospective Randomized Trial.

Objective: National guidelines recommend periprocedural antibiotics before percutaneous nephrolithotomy (PCNL), yet it is not clear which is superior. We conducted a randomized trial to compare two guideline-recommended antibiotics: ciprofloxacin (cipro) vs cefazolin, on PCNL outcomes, focusing on the development of systemic inflammatory response syndrome (SIRS) criteria. Methods: Adult patients who were not considered high risk for surgical or infectious complications and undergoing PCNL were randomized to receive either cipro or cefazolin perioperatively. All had negative preoperative urine cultures. Demographic and perioperative data were collected, including SIRS criteria, intraoperative urine culture, duration of hospitalization, and need for intensive care. SIRS is defined by ≥2 of the following: body temperature <96.8°F or >100.4°F, heart rate >90 bpm, respiratory rate >20 per minute, and white blood cell count <4000 or >12,000 cells/mm3. Results: One hundred forty-seven patients were enrolled and randomized (79 cefazolin and 68 cipro). All preoperative characteristics were similar (p > 0.05), except for mean age, which was higher in the cipro group (64 vs 57 years, p = 0.03). Intra- and postoperative findings were similar, with no difference between groups (p > 0.05), except a longer mean hospital stay in the cefazolin group (2 hours longer, p = 0.02). There was no difference between SIRS episodes in both univariate and multivariate analyses. Conclusions: Despite the relatively broader coverage for urinary tract pathogens with ciprofloxacin, this prospective randomized trial did not show superiority over cefazolin. Our findings therefore support two appropriate options for perioperative antibiotic prophylaxis in patients undergoing PCNL who are nonhigh risk for infectious complications.

Antibiotic Prophylaxis for Grade 3 Open Fractures: A Retrospective Comparison of Ceftriaxone Plus Vancomycin Versus Cefazolin Plus Gentamicin.

Background: Because of the established path of bacterial entry and contamination-associated mechanisms, grade 3 open orthopedic fractures represent a substantial infection risk. The Eastern Association for the Surgery of Trauma (EAST) guidelines recommended covering Staphylococcus aureus and adding aminoglycoside gram-negative coverage. Local institutional guidelines rely on ceftriaxone for gram negative coverage and add methicillin-resistant Staphylococcus aureus coverage with vancomycin. Patients and Methods: The electronic health records of adults admitted for a grade 3 open fracture between January 1, 2016, and October 31, 2021, were retrospectively reviewed. Patients who received cefazolin and gentamicin (CZ+GM) or ceftriaxone and vancomycin (CRO+VA) as prophylaxis were included. We recorded the rate of a composite treatment failure outcome of receipt of antibiotic agents, infection-related hospitalization, or subsequent debridement for injury-site skin and soft tissue infection or osteomyelitis. The presence of acute kidney injury (AKI) was also evaluated. Results: There were 65 patients included in the CZ+GM group and 53 patients in the CRO+VA group. Patients in the CZ+GM group were younger (mean 42.6 compared with 50.6 years; p = 0.02). Otherwise, there were no significant differences between groups' demographics, mechanism and site of injury, timeline of care, or surgical interventions. More patients in the CZ+GM arm met the composite treatment failure outcome, but it was not statistically significant (45% vs. 32%; p = 0.2). There were similar rates of treatment failure at 30 days (21% vs. 26%; p = 0.5) and for only osteomyelitis (8% vs. 9%; p = 1). Conclusions: The trend in numerically lower treatment failure rates in the CRO+VA group across outcomes provides sufficient evidence to continue the current local recommendations. Given our sample size, type 2 error may have occurred, and studies with greater power should analyze this question.

Antimicrobial Prophylaxis With Ampicillin-sulbactam Compared With Cefazolin for Esophagectomy: Nationwide Inpatient Database Study in Japan.

OBJECTIVE: To assess the effect of antimicrobial prophylaxis with ampicillin-sulbactam (ABPC/SBT) compared with cefazolin (CEZ) on the short-term outcomes after esophagectomy. BACKGROUND: CEZ is widely used for antimicrobial prophylaxis in esophagectomy without procedure-specific evidence, whereas ABPC/SBT is preferred in some hospitals to target both aerobic and anaerobic oral bacteria. METHODS: Data of patients who underwent esophagectomy for cancer between July 2010 and March 2019 were extracted from a nationwide Japanese inpatient database. Overlap propensity score weighting was conducted to compare the short-term outcomes [including surgical site infection (SSI), anastomotic leakage, and respiratory failure] between antimicrobial prophylaxis with CEZ and ABPC/SBT after adjusting for potential confounders. Sensitivity analyses were also performed using propensity score matching and instrumental variable analyses. RESULTS: Among 17,772 eligible patients, 16,077 (90.5%) and 1695 (9.5%) patients were administered CEZ and ABPC/SBT, respectively. SSI, anastomotic leakage, and respiratory failure occurred in 2971 (16.7%), 2604 (14.7%), and 2754 patients (15.5%), respectively. After overlap weighting, ABPC/SBT was significantly associated with a reduction in SSI [odds ratio 0.51 (95% CI: 0.43-0.60)], anastomotic leakage [0.51 (0.43-0.61)], and respiratory failure [0.66 (0.57-0.77)]. ABPC/SBT was also associated with reduced respiratory complications, postoperative length of stay, and total hospitalization costs. The proportion of Clostridioides difficile colitis and noninfectious complications did not differ between the groups. Propensity score matching and instrumental variable analyses demonstrated equivalent results. CONCLUSIONS: The administration of ABPC/SBT as antimicrobial prophylaxis for esophagectomy was associated with better short-term postoperative outcomes compared with CEZ.

Non-cefazolin antibiotic prophylaxis is associated with higher rates of elbow periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a common source of failure following elbow arthroplasty. Perioperative prophylactic antibiotics are considered standard of care. However, there are no data regarding the comparative efficacy of various antibiotics in the prevention of PJI for elbow arthroplasty. Previous studies in shoulder, hip, and knee arthroplasty have demonstrated higher rates of PJI with administration of non-cefazolin antibiotics. The elbow has higher rates of PJI than other joints. Therefore, this study evaluated whether perioperative antibiotic choice affects rates of PJI in elbow arthroplasty. MATERIALS AND METHODS: A single-institution, prospectively collected total joint registry database was queried to identify patients who underwent primary elbow arthroplasty between 2003 and 2021. Elbows with known infection prior to arthroplasty (25) and procedures with incomplete perioperative antibiotic data (7) were excluded, for a final sample size of 603 total elbow arthroplasties and 19 distal humerus hemiarthroplasties. Cefazolin was administered in 561 elbows (90%) and non-cefazolin antibiotics including vancomycin (32 elbows, 5%), clindamycin (27 elbows, 4%), and piperacillin/tazobactam (2 elbows, 0.3%) were administered in the remaining 61 elbows (10%). Univariate and multivariate analyses were conducted to determine the association between the antibiotic administered and the development of PJI. Infection-free survivorship was estimated using the Kaplan-Meier method. RESULTS: Deep infection occurred in 47 elbows (7.5%), and 16 elbows (2.5%) were diagnosed with superficial infections. Univariate analysis demonstrated that patients receiving non-cefazolin alternatives were at significantly higher risk for any infection (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.4-5.0; P < .01) and deep infection (HR 2.7, 95% CI 1.3-5.5; P < .01) compared with cefazolin administration. Multivariable analysis, controlling for several independent predictors of PJI (tobacco use, male sex, surgical indication other than osteoarthritis, and American Society of Anesthesiologists score), showed that non-cefazolin administration had a higher risk for any infection (HR 2.8, 95% CI 1.4-5.3; P < .01) and deep infection (HR 2.9, 95% CI 1.3-6.3; P < .01). Survivorship free of infection was significantly higher at all time points for the cefazolin cohort. DISCUSSION: In primary elbow arthroplasty, cefazolin administration was associated with significantly lower rates of PJI compared to non-cefazolin antibiotics, even in patients with a greater number of prior surgeries, which is known to increase the risk of PJI. For patients with penicillin or cephalosporin allergies, preoperative allergy testing or a cefazolin test dose should be considered before administering non-cefazolin alternatives.

Impact of Blast Overpressure on the Pharmacokinetics of Various Antibiotics in Sprague Dawley Rats.

INTRODUCTION: Combat injuries are complex and multimodal. Most injuries to the extremities occur because of explosive devices such as improvised explosive devices. Blast exposure dramatically increases the risk of infection in combat wounds, and there is limited available information on the best antibiotic treatments for these injuries. We previously demonstrated that mice exposed to blast displayed a delayed clearance of cefazolin from the plasma and liver; further semi-mechanistic modeling determined that cefazolin concentrations in the skin of these mice were reduced. Our objective was to investigate the effects of blast on the pharmacokinetics of antibiotics of different types used for the treatment of combat wounds in the rat model. MATERIALS AND METHODS: Male Sprague Dawley rats were exposed to blast overpressure followed by injection of a bolus of animal equivalent doses of an antibiotic (cefazolin, cefepime, ertapenem, or clindamycin) into the tail vein at 1-hour post-blast exposure. Blood was collected at predetermined time points via repeated sampling from the tail vein. Animals were also euthanized at predetermined time points, at which time liver, kidney, skin, and blood via cardiac puncture were collected. Antibiotic concentrations were determined by ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Blast-exposed rats exhibited a similar rate of clearance compared to non-blasted rats in the blood, liver, kidney, and skin, which is inconsistent with the data regarding cefazolin in blast-exposed mice. CONCLUSIONS: Our results in rats do not recapitulate our previous observation of delayed cefazolin clearance in mice following the blast overpressure exposure. Although using rats permitted us to collect multiple blood samples from the same animals, rats may not be a suitable model for measuring the pharmacokinetics of antibiotics following blast. The interpretation of the results may be challenging because of variation in data among rat subjects in the same sample groups.

Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Comparison of Cefazolin and Ceftriaxone as Antimicrobial Prophylaxis in Pancreatoduodenectomy with Preoperative Drainage: Incidence of Surgical Site Infection and Susceptibility of Bacteria in Bile.

BACKGROUND: The optimal perioperative antimicrobial agent for preventing surgical site infection (SSI) in pancreatoduodenectomy (PD) with preoperative biliary drainage (PBD) remains unclear. METHODS: We retrospectively reviewed 288 patients who underwent PD after PBD between 2010 and 2020 at our institution. Patients were classified into two groups according to the perioperative antimicrobial agent used (cefazoline [CEZ] group [n = 108] and ceftriaxone [CTRX] group [n = 180]). The incidence of SSI, type of bacteria in intraoperative bile culture (IBC), and antimicrobial susceptibility to prophylactic antimicrobial agents were analyzed. RESULTS: The incidence of incisional SSI was significantly lower in the CTRX group than in the CEZ group (18% vs. 31%, P = 0.021), whereas the incidence of organ/space SSI in the two groups did not differ to a statistically significant extent (35% vs. 44%, P = 0.133). Gram-negative rod (GNR) bacteria in the IBC showed better antimicrobial susceptibility in the CTRX group than in the CEZ group. In multivariate analysis, antimicrobial resistance due to GNR was a significant risk factor for incisional SSI (odds ratio, 3.50; P < 0.001). CONCLUSIONS: CTRX had better antimicrobial coverage than CEZ for GNR cultured from intraoperative bile samples. In addition, CTRX provides better antimicrobial prophylaxis than CEZ against superficial SSI in patients with PD after PBD. TRIAL REGISTRATION NUMBER: This study was not a clinical trial and had no registration numbers.