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.).

Prospective assessment of the frequency of and risk factors for bleeding events in patients treated with cefazolin.

PURPOSE: Major bleedings have been described with cefazolin. The objective was to determine the frequency of bleeding events in cefazolin-treated patients and to identify risk factors for these complications. METHODS: Monocenter prospective observational study of all consecutive cefazolin-treated patients. Patients benefited from a daily clinical assessment of bleedings and a twice-a-week blood sampling including hemostasis. Bleedings were classified according to the International Society on Thrombosis and Hemostasis classification: major, clinically relevant non-major bleedings (CRNMB) and minor bleedings. RESULTS: From September 2019 to July 2020, 120 patients were included, with a mean age of 59.4 (± 20.7) years; 70% of them (84/120) were men. At least 1 CRNMB or major bleeding were observed in 10% of the patients (12/120). Compared to patients with no or minor bleeding, patients with CRNMB or major bleeding were, upon start of cefazolin, more frequently hospitalized in an intensive care unit (7/12, 58.3%, vs. 12/108, 11.1%, P < 0.001, respectively) and receiving vitamin K antagonists (4/12, 33.3%, vs. 8/108, 7.4%, P = 0.019, respectively). After multivariate analysis, patients receiving vitamin K antagonists the day prior bleeding and/or treated for endocarditis were factors associated with an increased risk of CRNMB or major bleeding (odd ratio 1.36, confidence interval 95%, 1.06-1.76, P = 0.020 and 1.30, 1.06-1.61, P = 0.015, respectively). CONCLUSIONS: Bleeding events associated with cefazolin treatment are frequent. Close clinical monitoring should be performed for patients treated for endocarditis and/or receiving vitamin K antagonists. Hemostasis work-up could be restricted to these patients.

Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 µg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 µg/mL compared to strains with MIC of oxacillin < 1 µg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 µg/mL and 176 isolates with an MIC < 1 µg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 µg/mL and an MIC < 1 µg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 µg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Antibiotic choice for Group B Streptococcus prophylaxis in mothers with reported penicillin allergy and associated newborn outcomes.

OBJECTIVE: To evaluate the choice of antibiotic used for intrapartum Group B Streptococcus (GBS) prophylaxis in pregnant individuals with reported penicillin allergies compared to those without reported penicillin allergies and investigate whether there are associated differences in neonatal outcomes. STUDY DESIGN: This retrospective cohort study included mother-infant dyads of GBS positive pregnant individuals who labored and delivered newborns ≥ 35 weeks of gestation at a high-volume urban hospital (2005-2018). The type of antibiotic administered to the mothers for GBS prophylaxis (beta-lactam prophylaxis defined as penicillin-class drug or cefazolin; alternative prophylaxis defined as vancomycin or clindamycin) was compared between those with a penicillin allergy documented in their medical record versus those who did not. Neonatal outcomes included number of postnatal blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, bacteremia, and hospital length of stay and were compared between groups. Bivariable and multivariable analyses were performed. RESULTS: Of 11,334 mother-infant pairs, 1170 (10.3%) mothers had a penicillin allergy documented in their medical record. Of them, 49 (4.2%) received a penicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin, and 413 (35.3%) received vancomycin. Patients with a reported penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to those without penicillin allergy (73.7% vs. 0.2%, p < 0.01). Neonates of patients who received alternative GBS prophylaxis were significantly more likely to undergo a postnatal lab draw compared to neonates of patients who received beta-lactam antibiotics (20.8% vs. 17.3%, OR 1.25 (95% CI 1.08-1.46)). This significant association persisted after adjusting for potential confounders (aOR 1.23, 95% CI 1.06-1.43). There were no other significant differences seen in other newborn outcomes. CONCLUSION: Pregnant individuals who report a penicillin allergy were more likely to receive alternative antibiotics for GBS prophylaxis compared to those without a penicillin allergy. This was associated with an increased frequency of postnatal blood draws among neonates of mothers with a reported penicillin allergy. Administration of alternative intrapartum antibiotic prophylaxis with vancomycin or clindamycin is common in individuals with self-reported penicillin allergy, and maternal alternative antibiotic administration may impact neonatal care, particularly via increased lab draws.

The Effect of Beta-lactam Allergy Status on the Rate of Surgical Site Infections: A Retrospective Cohort Study.

OBJECTIVE: To determine if patients with reported BL allergies have increased odds of developing SSI compared to reported NBL allergic patients. SUMMARY OF BACKGROUND DATA: SSI represent a significant risk of morbidity and mortality for patients. Cefazolin-based perioperative antibiotic prophylaxis is the guideline-recommended drug-of-choice for most procedures. Due to over-reporting of BL allergies, many patients may not receive guideline-directed cephalosporin-based prophylaxis, which may result in an increased SSI rate. METHODS: A single-center retrospective cohort design study was performed. Data was collected on all targeted surgical procedures: cesarean section, vaginal, and abdominal hysterectomy, colon, laminectomy, and spinal fusion surgeries. RESULTS: During the study period, 2676 procedures were analyzed with 454 (17%) and 2222 (83%) in reported BL and NBL allergic cohorts, respectively. Significantly more SSI developed in the BL cohort versus NBL cohort (3.1% vs 1.5%, odds ratio 2.015; 95% confidence interval, 1.090-3.724; P = 0.023). Through a multivariate logistic regression, receipt of a NBL antibiotic regimen was the only variable to have a significant effect on SSI rate (adjusted odds ratio, 3.815; 95% confidence interval, 1.142-12.749; P = 0.030). CONCLUSION: Reported BL allergic patients have an increased odds of developing SSI in comparison to NBL allergic patients. The increased risk is likely related to administration of NBL antibiotic regimens in comparison to BL-based regimens. Thorough antibiotic allergy history collection can be a valuable SSI prevention tool to safely increase the proportion of patients receiving BL regimen.

Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study.

BACKGROUND: The observation that patients presenting for bariatric surgery had a high incidence of neuromuscular blocking agent (NMBA) anaphylaxis prompted this restricted case-control study to test the hypothesis that obesity is a risk factor for NMBA anaphylaxis, independent of differences in pholcodine consumption. METHODS: We compared 145 patients diagnosed with intraoperative NMBA anaphylaxis in Western Australia between 2012 and 2020 with 61 patients with cefazolin anaphylaxis with respect to BMI grade, history of pholcodine consumption, sex, age, comorbid disease, and NMBA type and dose. Confounding was assessed by stratification and binomial logistic regression. RESULTS: Obesity (odds ratio [OR]=2.96, χ2=11.7, P=0.001), 'definite' pholcodine consumption (OR=14.0, χ2=2.6, P<0.001), and female sex (OR=2.70, χ2=9.61, P=0.002) were statistically significant risk factors for NMBA anaphylaxis on univariate analysis. The risk of NMBA anaphylaxis increased with BMI grade. Confounding analysis indicated that both obesity and pholcodine consumption remained important risk factors after correction for confounding, but that sex did not. The relative rate of rocuronium anaphylaxis was estimated to be 3.0 times that of vecuronium using controls as an estimate of market share, and the risk of NMBA anaphylaxis in patients presenting for bariatric surgery was 8.8 times the expected rate (74.9 vs 8.5 per 100 000 anaesthetic procedures). CONCLUSIONS: Obesity is a risk factor for NMBA anaphylaxis, the risk increasing with BMI grade. Pholcodine consumption is also a risk factor, and this is consistent with the pholcodine hypothesis. Rocuronium use is associated with an increased risk of anaphylaxis compared with vecuronium in this population.

Antibiotic regimens for late-onset neonatal sepsis.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. OBJECTIVES: To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. SEARCH METHODS: We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. MAIN RESULTS: We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.

ANTECEDENTES: La sepsis neonatal es una causa importante de morbilidad y mortalidad. Es la tercera causa de mortalidad neonatal a nivel mundial y constituye el 13% de la mortalidad neonatal total. A pesar de la elevada carga de la sepsis neonatal, la evidencia de alta calidad en el diagnóstico y el tratamiento es escasa. Debido a las dificultades de diagnóstico de la sepsis y a la relativa inmunosupresión del neonato, muchos reciben antibióticos por sospecha de sepsis. Los antibióticos se han convertido en el tratamiento más utilizado en las unidades de cuidados intensivos neonatales, y los estudios observacionales realizados en países de ingresos altos indican que entre el 83% y el 94% de los neonatos tratados con antibióticos por sospecha de sepsis tienen hemocultivos negativos. La última revisión Cochrane se actualizó en 2005. Se necesita una revisión sistemática actualizada que evalúe los efectos de los diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de diferentes regímenes antibióticos para la sepsis neonatal de inicio tardío. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las siguientes bases de datos electrónicas: CENTRAL (2021, número 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED y Conference Proceedings Citation Index ­ Science el 12 de marzo de 2021. También se buscaron ensayos controlados aleatorizados (ECA) y cuasialeatorizados en las bases de datos de ensayos clínicos y en las listas de referencias de artículos identificados. CRITERIOS DE SELECCIÓN: Se incluyeron ECA que compararon diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. Se incluyeron participantes mayores de 72 horas de vida en el momento de la asignación al azar, con sospecha o diagnóstico de sepsis neonatal, meningitis, osteomielitis, endocarditis o enterocolitis necrosante. Se excluyeron los ensayos que evaluaron el tratamiento de las infecciones micóticas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los estudios para inclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se utilizó el método GRADE para evaluar la certeza de la evidencia. El desenlace principal fue la mortalidad por todas las causas, y los desenlaces secundarios fueron: eventos adversos graves, asistencia respiratoria, apoyo circulatorio, nefrotoxicidad, deterioro del desarrollo neurológico, enterocolitis necrosante y ototoxicidad. El punto temporal principal de interés fue el seguimiento máximo. RESULTADOS PRINCIPALES: Se incluyeron cinco ECA (580 participantes). Todos los ensayos tuvieron alto riesgo de sesgo y evidencia de certeza muy baja. Los cinco ensayos incluidos evaluaron cinco comparaciones diferentes de antibióticos. No se realizó un metanálisis debido a la falta de datos relevantes. De los cinco ensayos incluidos, un ensayo comparó cefazolina más amikacina con vancomicina más amikacina; un ensayo comparó ticarcilina más ácido clavulánico con flucloxacilina más gentamicina; un ensayo comparó cloxacilina más amikacina con cefotaxima más gentamicina; un ensayo comparó meropenem con atención estándar (ampicilina más gentamicina o cefotaxima más gentamicina); y un ensayo comparó vancomicina más gentamicina con vancomicina más aztreonam. Ninguna de las cinco comparaciones encontró evidencia de una diferencia al evaluar la mortalidad por todas las causas, los eventos adversos graves, el apoyo circulatorio, la nefrotoxicidad, el deterioro del desarrollo neurológico o la enterocolitis necrosante; sin embargo, ninguno de los ensayos se acercó a un tamaño de información que pudiera contribuir significativamente a la evidencia de los beneficios y los riesgos comparativos de cualquier régimen antibiótico en particular. Ninguno de los ensayos evaluó la asistencia respiratoria o la ototoxicidad. Los efectos beneficiosos y perjudiciales de los diferentes regímenes de antibióticos aún no están claros debido a la falta de ensayos con un poder estadístico adecuado y al alto riesgo de errores sistemáticos. CONCLUSIONES DE LOS AUTORES: La evidencia actual no es suficiente para apoyar que un régimen de antibióticos sea superior a otro. Se justifica la realización de ECA con bajo riesgo de sesgo que evalúen diferentes regímenes antibióticos en la sepsis neonatal de inicio tardío.

Retrospective Analysis of Adverse Drug Events Between Nafcillin Versus Cefazolin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections.

Background: Nafcillin or cefazolin are drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Prior studies indicate a higher incidence of acute kidney injury (AKI) with nafcillin, although AKI classification and time to occurrence is not well described. Objective: To characterize the incidence and time to adverse drug events for nafcillin versus cefazolin in the inpatient setting. Methods: A retrospective cohort study evaluated hospitalized, adult patients receiving intravenous nafcillin or cefazolin for treatment of MSSA infection. Incidence and time to AKI based on RIFLE criteria were measured. Secondary end points included antibiotic discontinuation and incidence of neutropenia, thrombocytopenia, elevated transaminases, and Clostridioides difficile infection (CDI). Results: Of 324 patients who received nafcillin (n = 119) or cefazolin (n = 205), higher rates of AKI were found for nafcillin versus cefazolin (19% vs 2%, respectively; P < 0.0001). Median time to AKI with nafcillin was 6.5 days (range, 3-14 days). The majority of patients were classified as RIFLE "Risk" stratum. Nafcillin treatment discontinuations were more frequent than for cefazolin (17.6% vs 0.9%, respectively; P < 0.0001). Nafcillin was an independent predictor of AKI (odds ratio = 12.4; 95% CI = 4.14-47.60, P < 0.0001). No differences in neutropenia, thrombocytopenia, elevated transaminases, or CDI were observed. Conclusion and Relevance: Nafcillin displayed higher rates of AKI at a median of 1 week of therapy, which provides a framework for clinician monitoring and consideration of antibiotic modification. Most patients developed "Risk" class AKI (RIFLE classification), which may be reversible with prompt intervention.

Effect of probiotics on gut microbiome in patients with administration of surgical antibiotic prophylaxis: A randomized controlled study.

Surgical antibiotic prophylaxis (SAP) is recommended for the prevention of surgical site infections. However, there is a concern about adverse effects of SAP, such as antibiotic-associated diarrhea (AAD). To prevent AAD, administration of probiotics has been investigated. Although recent advances in next-generation sequencing makes it possible to analyze the gut microbiome, the effect of probiotics on the gut microbiome in the patients with SAP remains unknown. To test a hypothesis that SAP influences the gut microbiome and probiotics prevent the influence, a randomized controlled study was conducted with patients who underwent spinal surgery at Nagasaki University Hospital. After obtaining informed consent, the patients were automatically classified into the non-probiotics group and the probiotics group. In the probiotics group, the patients took 1 g of Enterococcus faecium 129 BIO 3B-R, 3 times a day on postoperative days (PODs) 1-5. The feces of all patients were sampled before administration of SAP and on PODs 5 and 10. We compared alpha and beta diversity and differential abundance analysis of the gut microbiome before and after SAP. During the study period, a total of 33 patients were evaluated, comprising 17 patients in the non-probiotics group and 16 in the probiotics group. There was no significant difference between the groups regarding patient characteristics. In alpha and beta diversity, there were no significant differences among all combinations. In differential abundance analysis at operational taxonomic unit level, Streptococcus gallolyticus and Roseburia were significantly increased in the non-probiotics group and significantly decreased in the probiotics group.

Early Antibiotic Prophylaxis Prior to Bypass Surgery Improves Tissue Penetration.

BACKGROUND: We previously identified preparation of the internal mammary artery as a risk factor significantly impairing antibiotic tissue penetration into the presternal subcutaneous tissue. We, therefore, adapted our dosing schema regarding preoperative timing to overcome this risk factor. METHODS: Eight patients who underwent coronary artery bypass grafting with a left internal mammary artery and vein grafts were included in this clinical trial. Cefazolin (4 g) was administered twice (3 hours and 1 hour) prior to skin incision and once during skin closure (2 g). Antibiotic concentrations were measured with subcutaneous microdialysis probes on both sternal sides. Results were directly compared with the previously published patient cohort receiving the standard schema (4 g cefazolin prior to skin incision and 2 g during closure). RESULTS: All patients (7 male, 1 female, 69 ± 7 years, 26.3 ± 3.9 kg/m2) survived the perioperative period. Mean area under the curve on the right and left sternal side was 117.0 ± 92.5 µg/mL and 114.5 ± 83.2 µg/mL, respectively (p = 0.95). This was well above the previously measured mean peak tissue concentrations without early preoperative antibiotic administration on the side of mammary artery harvesting (52.4 ± 48.5 µg/mL vs. 13.1 ± 5.8 µg/mL; p = 0.039). The %fT > minimal inhibitory concentration (MIC) for Staphylococcus epidermidis and Staphylococcus aureus during the first 10 hours in presternal tissue was ≥ 70% but did not differ compared with standard schema. CONCLUSIONS: Early, additional preoperative administration of cefazolin was able to significantly increase peak tissue concentrations during surgery compared with the standard protocol. No difference, however, could be achieved in the percentage of time during which the concentration exceeded the MIC.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

Intracameral antibiotics for prophylaxis of postoperative endophthalmitis in Australia: a review.

Postoperative endophthalmitis is a severe complication which may result in loss of vision. Intracameral antibiotics have been shown to reduce the risk of this complication and are extensively used worldwide, with vancomycin, cefuroxime and moxifloxacin most commonly used. Choices in Australia are currently limited to vancomycin and cefazolin, since cefuroxime and moxifloxacin are not available. Vancomycin has been safely and effectively used in our department for more than two decades. Recent publications have risen concerns regarding the association of haemorrhagic occlusive retinal vasculitis a potentially blinding complication with intracameral vancomycin. This concern has driven us to review the safety and efficacy of currently available antibiotics in the context of Australian practice.

Results of Intradermal Skin Testing with Cefazolin according to a History of Hypersensitivity to Antibiotics.

BACKGROUND: The relationship between cephalosporin hypersensitivity and a history of ß-lactam hypersensitivity is unclear. We evaluated the usefulness of routine intradermal cefazolin skin testing and its relationship with the history of ß-lactam hypersensitivity. METHODS: The electronic medical records of patients who underwent intradermal cefazolin (0.3 mg/mL) skin testing without negative controls from January 2010 to January 2011 at Seoul National University Bundang Hospital were evaluated. The history of ß-lactam hypersensitivity of the patients was taken. Immediate adverse reactions after cefazolin injection were evaluated by searching the electronic medical records for key words and reviewing consultation documents of allergy specialists or dermatologists. The medical records of the patients were reviewed by an allergist. RESULTS: There were 13,153 cases of cefazolin skin testing over the 13-month study period. Among the 12,969 cases with negative skin test results, 8 had immediate hypersensitivity related to cefazolin (0.06%). The negative predictive value of cefazolin skin testing alone was 99.94%. The overall positivity rate of cefazolin skin tests was 1.4% (184/13,153). Of the cases with a history of allergy to ß-lactams, 15% (6/40) showed a positive cefazolin skin test result compared to only 1.36% (178/13,113) of cases with no such history (P < 0.001) including some false-positive tests. CONCLUSION: The results suggest that routine screening involving cefazolin skin testing without negative controls is not useful for all patients, but could be helpful for those with a history of ß-lactam hypersensitivity, although a large prospective study is needed to confirm this.

Optimal treatment of MSSA bacteraemias: a meta-analysis of cefazolin versus antistaphylococcal penicillins.

Background: Bacteraemias caused by MSSA are associated with significant morbidity and mortality. Controversy exists over the optimal treatment of severe infections caused by MSSA. This systematic review and meta-analysis aims to identify whether differences in clinical outcomes exist between cefazolin and antistaphylococcal penicillins (ASPs). Methods: PubMed, Cochrane Library and Embase were systematically searched for publications reporting clinical outcomes of cefazolin and ASPs for adult patients with MSSA bacteraemias throughout November 2017. Comparative studies reporting 90 day mortality associated with each treatment were included. Random effects models were used to evaluate the impact of directed treatment agent on the odds of 30 and 90 day mortality, clinical failure, discontinuation due to adverse effects and infection recurrence. Results: Five hundred and ninety-nine articles were evaluated for inclusion, of which seven met all inclusion criteria. Across all studies, 1589 patients received cefazolin and 2802 received an ASP. All-cause 90 day mortality was lower in patients who received cefazolin (OR 0.63, 95% CI 0.41-0.99; I2 = 58%). Odds of discontinuation due to adverse events was significantly lower in patients receiving cefazolin (OR 0.25, 95% CI 0.11-0.56; I2 = 13%). No differences in clinical failure were observed (OR 0.85, 95% CI 0.41-1.76; I2 = 74%). Conclusions: This meta-analysis identified a significant decrease in mortality associated with cefazolin therapy for MSSA bacteraemia compared with ASPs, though no differences in clinical failure were observed. Additionally, cefazolin appeared to be better tolerated. These results should be interpreted with caution given the uncontrolled and retrospective nature of the included studies.

Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy.

BACKGROUND: Perioperative use of cefazolin has been associated with severe allergic reactions, and patients are usually labelled as allergic to penicillin afterwards. The aim of our study was to describe a group of patients with immediate reactions to cefazolin, with proven selective hypersensitivity reactions. METHODS: Systematic review of all patients followed at our drug centre with cefazolin-related reactions, between January 2012 and December 2016. All patients were investigated according to the European Network for Drug Allergy (ENDA) recommendations through skin testing (major and minor penicillin determinants, penicillin, amoxicillin, cefazolin, cefuroxime and ceftriaxone) and oral challenges tests. RESULTS: We included 7 patients (median age 40 years) with perioperative anaphylactic reactions immediately after cefazolin injection, 4 with hypotension and 1 with Kounis syndrome (KS) type I. The presence of a selective IgE-mediated hypersensitivity through positive skin tests to cefazoline has been proven in all patients. Two patients experienced systemic reactions during skin testing. All patients were successfully challenged with amoxicillin, and they tolerated cefuroxime. CONCLUSIONS: Cefazolin can be responsible for immediate severe allergic reactions in perioperative setting, including KS. Allergological workup is essential for an accurate diagnosis and to explore cross-reactivity between cefazolin and other beta-lactams. Our experience confirmed that patients with IgE-mediated hypersensitivity reactions to cefazolin can tolerate other beta-lactams. This selective pattern of clinical reactivity may be explained by its particular chemical structure, whose R1 side-chain is different from other beta-lactams.

Meta-analysis of trials comparing cefazolin to antistaphylococcal penicillins in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia.

AIMS: The objective of this study was to determine the effectiveness and safety of cefazolin vs. antistaphylococcal penicillin (ASP) in the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS: The databases of PubMed, Embase and Cochrane Central were used to identify comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of included trials was performed to assess any differences regarding mortality, clinical cure, recurrence and withdrawal from adverse effects between groups. Data were analysed using fixed effect model. Studies were weighted using Mantel-Haenszel methodology. Heterogeneity was calculated using the I2 statistic. RESULTS: Nine retrospective and one prospective trials were identified involving 4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P < 0.0001] with borderline high heterogeneity (I2  = 51%). Clinical cure was noted more often with cefazolin (RR 1.09, 95% CI 1.02-1.17, P = 0.02), although no difference was noted with relapse (RR 1.29, 95% CI 0.96-1.74 P = 0.09). Analysis also showed more withdrawals from adverse events with ASP vs. cefazolin (RR 0.27, 95% CI 0.16-0.47, P < 0.00001). A minority of patients enrolled in these trials were admitted to the intensive care unit or had endocarditis (11.4% with ASP and 9% with cefazolin). CONCLUSION: Our meta-analysis of retrospective data demonstrate that cefazolin is more effective and safer ASP in patients with MSSA bacteraemia from various causes. Low quality of trials, borderline high heterogeneity, and possible publication bias may limit the validity of our findings. Randomized trials are needed to confirm these findings.