Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial.

PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

Pilot study to evaluate the need and implementation of a multifaceted nurse-led antimicrobial stewardship intervention in residential aged care.

Objectives: To evaluate the need and feasibility of a nurse-led antimicrobial stewardship (AMS) programme in two Australian residential aged care homes (RACHs) to inform a stepped-wedged, cluster randomized controlled trial (SW-cRCT). Methods: A mixed-methods pilot study of a nurse-led AMS programme was performed in two RACHs in Victoria, Australia (July-December 2019). The AMS programme comprised education, infection assessment and management guidelines, and documentation to support appropriate antimicrobial use in urinary, lower respiratory and skin/soft tissue infections. The programme was implemented over three phases: (i) pre-implementation education and integration (1 month); (ii) implementation of the intervention (3 months); and (iii) post-intervention evaluation (1 month). Baseline RACH and resident data and weekly infection and antimicrobial usage were collected and analysed descriptively to evaluate the need for AMS strategies. Feedback on intervention resources and implementation barriers were identified from semi-structured interviews, an online staff questionnaire and researcher field notes. Results: Six key barriers to implementation of the intervention were identified and used to refine the intervention: aged care staffing and capacity; access to education; resistance to practice change; role of staff in AMS; leadership and ownership of the intervention at the RACH and organization level; and family expectations. A total of 61 antimicrobials were prescribed for 40 residents over the 3 month intervention. Overall, 48% of antibiotics did not meet minimum criteria for appropriate initiation (respiratory: 73%; urinary: 54%; skin/soft tissue: 0%). Conclusions: Several barriers and opportunities to improve implementation of AMS in RACHs were identified. Findings were used to inform a revised intervention to be evaluated in a larger SW-cRCT.

Imaging in osteoarticular infection in adults.

BACKGROUND: Osteoarticular infections are uncommon and required a multimodal approach for diagnosis. Imaging forms an important component of this multimodal approach. OBJECTIVES: In this narrative review, we describe the different imaging modalities, features of osteoarticular infections present on these imaging approaches and recommendations for which imaging modality should be considered in different types of osteoarticular infections. SOURCES: This narrative review was based on literature review from PubMed and was limited to bacterial infections in adult patients. CONTENT: Imaging modalities include modalities that provide information on the anatomy or radionuclide imaging that provides information about the metabolic activity of the area of interest. Anatomical imaging includes plain radiographs (X-ray), computed tomography, and magnetic resonance imaging. Radionuclide approaches include three-phase bone scintigraphy, gallium scans, white blood cell scintigraphy, and 18F-fluorodeoxy-glucose positron emission tomography. The optimal radiological modality for diagnosis is influenced by multiple factors, including infection location, presence of metalware, timing of infection from any preceding surgery or fracture, antibiotic use, and patient comorbidities. Local availability of scanning modality, tracer supply, technical expertise, and patient access also influences choice. IMPLICATIONS: A collaborative approach with imaging, pathology and clinical input in a multidisciplinary setting is paramount for the diagnosis of osteoarticular infections. Increasing research and improvements in technology will further improve the utility and accuracy of imaging approaches for imaging in osteoarticular infections.

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.).

The clinical application of beta-lactam antibiotic therapeutic drug monitoring in the critical care setting.

Critically ill patients have increased variability in beta-lactam antibiotic (beta-lactam) exposure due to alterations in their volume of distribution and elimination. Therapeutic drug monitoring (TDM) of beta-lactams, as a dose optimization and individualization tool, has been recommended to overcome this variability in exposure. Despite its potential benefit, only a few centres worldwide perform beta-lactam TDM. An important reason for the low uptake is that the evidence for clinical benefits of beta-lactam TDM is not well established. TDM also requires the availability of specific infrastructure, knowledge and expertise. Observational studies and systematic reviews have demonstrated that TDM leads to an improvement in achieving target concentrations, a reduction in potentially toxic concentrations and improvement of clinical and microbiological outcomes. However, a small number of randomized controlled trials have not shown a mortality benefit. Opportunities for improved study design are apparent, as existing studies are limited by their inclusion of heterogeneous patient populations, including patients that may not even have infection, small sample size, variability in the types of beta-lactams included, infections caused by highly susceptible bacteria, and varied sampling, analytical and dosing algorithm methods. Here we review the fundamentals of beta-lactam TDM in critically ill patients, the existing clinical evidence and the practical aspects involved in beta-lactam TDM implementation.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Accuracy of antibacterial indication documentation in an electronic medicines management system.

Introduction: Electronic medicines management (EMM) systems are relatively new in the Australian healthcare system. This tertiary hospital network implemented an EMM in 2018, with mandatory documentation of antimicrobial indication when prescribing. Free-text (unrestricted) and pre-defined dropdown (restricted) indications are utilized according to antimicrobial restriction. Objectives: To determine accuracy of antibacterial indication documentation on the medication administration record (MAR) when prescribing and to evaluate factors influencing accuracy of documentation. Methods: A random sample of 400 inpatient admissions of ≥24 h, between March and September 2019, with the first antibacterial prescription per encounter reviewed retrospectively. Demographic and prescription details were extracted. Indication accuracy was assessed by comparing MAR documentation with the medical notes (gold standard). Statistical analysis compared factors associated with accuracy of indication using chi-squared and Fisher's exact tests. Results: Antibacterials were prescribed in 9708 admissions. Of the 400 patients included (60% male; median age 60 years, IQR 40-73), 225 prescriptions were unrestricted and 175 were restricted. Patients were managed by emergency (118), surgical (178) and medical (104) teams. Overall accuracy of antibacterial indication documentation on the MAR was 86%. A higher accuracy rate was found for the unrestricted proportion compared with the restricted proportion (94.2% versus 75.2%; P < 0.0001). Surgical teams had higher accuracy compared with medical and emergency teams (94.4% versus 78.8% versus 79.7%; P < 0.0001). Discussion: Antibacterial indication documentation on the MAR when prescribing demonstrated a high rate of accuracy. Multiple factors influenced this accuracy, which requires further study to determine the impact on accuracy, with a view to improve future EMM builds.

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review.

AIM: Daptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections. METHODS: A systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no discrimination on study type or time of publication. STUDY SELECTION: Adults (age ≥18 years) with a Gram-positive infection requiring treatment with daptomycin who received TDM, with subsequent reporting of serum concentrations and dose adjustment where necessary, were included. RESULTS: In total, 2869 studies were identified, of which nine met the inclusion criteria. No studies of daptomycin TDM including a relevant control arm have been published to date. All of the included studies were single-arm observational cohort studies. Broad heterogeneity was observed between the studies in terms of included pathogens, infection types, daptomycin TDM practices, reported clinical outcomes, and reporting of potential confounders. CONCLUSIONS: No studies exploring the efficacy of routine daptomycin TDM on patient-centred outcomes in comparison with fixed dosing regimens have been published to date. This represents a key knowledge gap as opposed to an inherent lack of efficacy. Further well-designed, comparative studies are required to determine the role of daptomycin TDM in patients with Gram-positive infections.

Penetration of Vancomycin into Noninfected Bone in Patients Undergoing Total Joint Arthroplasty Evaluated by a Minimal Physiologically Based Population Pharmacokinetic Modeling Approach.

Arthroplasty is a healthcare priority and represents high volume, high cost surgery. Periprosthetic joint infection (PJI) results in significant mortality, thus it is vital that the risk for PJI is minimized. Vancomycin is recommended for surgical prophylaxis in total joint arthroplasty (TJA) by current clinical practice guidelines endorsed by the Infectious Diseases Society of America. This study aimed to develop a new assay to determine vancomycin concentrations in serum and bone, and a minimal physiologically based population PK (mPBPK) model to evaluate vancomycin bone penetration in noninfected patients. Eleven patients undergoing TJA received 0.5-2.0 g intravenous vancomycin over 12-150 min before surgery. Excised bone specimens and four blood samples were collected per patient. Bone samples were pulverized under liquid nitrogen using a cryogenic mill. Vancomycin concentrations in serum and bone were analyzed by liquid chromatography-tandem mass spectrometry and subjected to mPBPK modeling. Vancomycin serum and bone concentrations ranged from 9.30 to 86.6 mg/L, and 1.94-37.0 mg/L, respectively. Average bone to serum concentration ratio was 0.41 (0.16-1.0) based on the collected samples. The population mean total body clearance was 2.12L/h/kg0.75. Inclusion of total body weight as a covariate substantially decreased interindividual variability in clearance. The bone/blood partition coefficient (Kpbone) was estimated at 0.635, reflecting the average bone/blood concentration ratio at steady-state. The model predicted median ratio of vancomycin area under the curve (AUC) for bone/AUC for serum was 44%. Observed vancomycin concentrations in bone were overall consistent with perfusion-limited distribution from blood to bone. An mPBPK model overall well described vancomycin concentrations in serum and bone.

Antibiotic management of urinary tract infections in the post-antibiotic era: a narrative review highlighting diagnostic and antimicrobial stewardship.

BACKGROUND: As one of the most common indications for antimicrobial prescription in the community, the management of urinary tract infections (UTIs) is both complicated by, and a driver of, antimicrobial resistance. OBJECTIVES: To highlight the key clinical decisions involved in the diagnosis and treatment of UTIs in adult women, focusing on clinical effectiveness and both diagnostic and antimicrobial stewardship as we approach the post-antimicrobial era. SOURCES: Literature reviewed via directed PubMed searches and manual searching of the reference list for included studies to identify key references to respond to the objectives. A strict time limit was not applied. We prioritised recent publications, randomised trials, and systematic reviews (with or without meta-analyses) where available. Searches were limited to English language articles. A formal quality assessment was not performed; however, the strengths and limitations of each paper were reviewed by the authors throughout the preparation of this manuscript. CONTENT: We discuss the management of UTIs in ambulatory adult women, with particular focus on uncomplicated infections. We address the diagnosis of UTIs, including the following: definition and categorisation; bedside assessments and point-of-care tests; and the indications for, and use of, laboratory tests. We then discuss the treatment of UTIs, including the following: indications for treatment, antimicrobial sparing approaches, key considerations when selecting a specific antimicrobial agent, specific treatment scenarios, and duration of treatment. We finally outline emerging areas of interest in this field. IMPLICATIONS: The steady increase in antimicrobial resistance among common uropathogens has had a substantial affect on the management of UTIs. Regarding both diagnosis and treatment, the clinician must consider both the patient (clinical effectiveness and adverse effects, including collateral damage) and the community more broadly (population-level antimicrobial selection pressure).

Beta-Lactam Antibiotic Therapeutic Drug Monitoring in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.

Early antimicrobial stewardship team intervention on appropriateness of antimicrobial therapy in suspected sepsis: a randomized controlled trial.

OBJECTIVES: There has been concern that the imperative to administer rapid antimicrobials in septic patients may result in inappropriate antimicrobial use. We aimed to determine the impact of early antimicrobial stewardship (AMS) team intervention in patients with Medical Emergency Team (MET) calls for suspected sepsis. METHODS: We performed a randomized controlled trial of non-ICU inpatients who had a MET call for suspected sepsis. Patients were randomized to standard care (management of antimicrobial therapy by the treating team) or early targeted intervention (AMS review 48 h post-MET call). The primary outcome was appropriateness of antimicrobial therapy 72 h post-MET call, as determined by a panel of blinded infectious diseases physicians. RESULTS: In total, 90 patients were enrolled; 45 were randomly allocated to the intervention group, and 45 to the control group. More patients in the AMS intervention group were receiving appropriate antimicrobials 72 h following the MET call (67% versus 44%, P = 0.03). In the intervention group, 27 recommendations were made by the AMS team; 74% of recommendations were accepted, including 30% of cases where antimicrobials were discontinued or de-escalated. There were non-significant differences in total duration of antimicrobial therapy (8.7 versus 10.7 days, P = 0.39), sepsis-related ICU-admission rates (13% versus 18%, P = 0.56) and sepsis-related in-hospital mortality (7% versus 9%, P = 0.71) between intervention and control groups, respectively. CONCLUSIONS: AMS team intervention resulted in significant improvement in appropriateness of antimicrobial therapy following MET calls due to suspected sepsis. Targeted AMS review should be implemented to support early antimicrobial de-escalation and optimization in patients with suspected sepsis.

Multicentre stepped-wedge cluster randomised controlled trial of an antimicrobial stewardship programme in residential aged care: protocol for the START trial.

INTRODUCTION: Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs. METHODS AND ANALYSIS: The START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms, Clostridioides difficile infection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs. TRIAL REGISTRATION NUMBER: NCT03941509.

Randomised Controlled Trials of Alcohol-Based Surgical Site Skin Preparation for the Prevention of Surgical Site Infections: Systematic Review and Meta-Analysis.

(1) Background: Surgical site skin preparation is an important approach to prevent postoperative wound infections. International guidelines recommend that alcohol-based combinations be used, however, the optimal combination remains uncertain. This study compares the effectiveness of alcohol-based chlorhexidine and alcohol-based iodophor for surgical site skin preparation for prevention of surgical site infections (SSIs). (2) Methods: Randomised controlled trials comparing alcohol-based interventions for surgical site skin preparation were included. The proportion of SSIs was compared using risk ratios (RR) with 95% confidence intervals (95% CI). The meta-analysis was performed with a fixed effect model using Mantel-Haenszel methods. As an a priori subgroup analysis SSI risk was examined according to different surgical procedural groups. (3) Results: Thirteen studies were included (n = 6023 participants). The use of chlorhexidine-alcohol was associated with a reduction in risk of SSIs compared with iodophor-alcohol (RR 0.790; 95% CI 0.669, 0.932). On sub-group analysis, chlorhexidine-alcohol was associated with a reduction in SSIs in caesarean surgery (RR 0.614; 95% CI 0.453, 0.831) however, chlorhexidine-alcohol was associated with an increased risk of SSI in bone and joint surgery (RR 2.667; 95% CI 1.051, 6.765). When excluding studies at high risk of bias on sensitivity analysis, this difference in alcohol-based combinations for bone and joint surgery was no longer observed (RR 2.636; 95% CI 0.995, 6.983). (4) Conclusions: The use of chlorhexidine-alcohol skin preparations was associated with a reduced risk of SSI compared to iodophor-alcohol agents. However, the efficacy of alcohol-based preparation agents may differ according to the surgical procedure group. This difference must be interpreted with caution given the low number of studies and potential for bias, however, it warrants further investigation into the potential biological and clinical validity of these findings.

Perioperative antimicrobial decision making: Focused ethnography study in orthopedic and cardiothoracic surgeries in an Australian hospital.

OBJECTIVE: Antimicrobial use in the surgical setting is common and frequently inappropriate. Understanding the behavioral context of antimicrobial use is a critical step to developing stewardship programs. DESIGN: In this study, we employed qualitative methodologies to describe the phenomenon of antimicrobial use in 2 surgical units: orthopedic surgery and cardiothoracic surgery. SETTING: This study was conducted at a public, quaternary, university-affiliated hospital. PARTICIPANTS: Healthcare professionals from the 2 surgical unit teams participated in the study. METHODS: We used focused ethnographic and face-to-face semi-structured interviews to observe antimicrobial decision-making behaviors across the patient's journey from the preadmission clinic to the operating room to the postoperative ward. RESULTS: We identified 4 key themes influencing decision making in the surgical setting. Compartmentalized communication (theme 1) was observed with demarcated roles and defined pathways for communication (theme 2). Antimicrobial decisions in the operating room were driven by the most senior members of the team. These decisions, however, were delegated to more junior members of staff in the ward and clinic environment (theme 3). Throughout the patient's journey, communication with the patient about antimicrobial use was limited (theme 4). CONCLUSIONS: Approaches to decision making in surgery are highly structured. Although this structure appears to facilitate smooth flow of responsibility, more junior members of the staff may be disempowered. In addition, opportunities for shared decision making with patients were limited. Antimicrobial stewardship programs need to recognize the hierarchal structure as well as opportunities to engage the patient in shared decision making.

Studying Biofilm and Clinical Issues in Orthopedics.

The association between biofilm-forming microorganisms and prosthetic joint infection influences all aspect of management including approaches to diagnosis, management and prevention. This article will provide an overview of new anti-biofilm strategies for management of prosthetic joint infection.

Laboratory Workflow Analysis of Culture of Periprosthetic Tissues in Blood Culture Bottles.

Culture of periprosthetic tissue specimens in blood culture bottles is more sensitive than conventional techniques, but the impact on laboratory workflow has yet to be addressed. Herein, we examined the impact of culture of periprosthetic tissues in blood culture bottles on laboratory workflow and cost. The workflow was process mapped, decision tree models were constructed using probabilities of positive and negative cultures drawn from our published study (T. N. Peel, B. L. Dylla, J. G. Hughes, D. T. Lynch, K. E. Greenwood-Quaintance, A. C. Cheng, J. N. Mandrekar, and R. Patel, mBio 7:e01776-15, 2016, https://doi.org/10.1128/mBio.01776-15), and the processing times and resource costs from the laboratory staff time viewpoint were used to compare periprosthetic tissues culture processes using conventional techniques with culture in blood culture bottles. Sensitivity analysis was performed using various rates of positive cultures. Annualized labor savings were estimated based on salary costs from the U.S. Labor Bureau for Laboratory staff. The model demonstrated a 60.1% reduction in mean total staff time with the adoption of tissue inoculation into blood culture bottles compared to conventional techniques (mean ± standard deviation, 30.7 ± 27.6 versus 77.0 ± 35.3 h per month, respectively; P < 0.001). The estimated annualized labor cost savings of culture using blood culture bottles was $10,876.83 (±$337.16). Sensitivity analysis was performed using various rates of culture positivity (5 to 50%). Culture in blood culture bottles was cost-effective, based on the estimated labor cost savings of $2,132.71 for each percent increase in test accuracy. In conclusion, culture of periprosthetic tissue in blood culture bottles is not only more accurate than but is also cost-saving compared to conventional culture methods.

The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention: The Results of a Large Multicenter Study.

BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.

What is the role of catheter antibiotic prophylaxis for patients undergoing joint arthroplasty?

BACKGROUND: Antimicrobial prophylaxis at the time of urinary catheter insertion and removal is commonly administered in patients undergoing joint arthroplasty, despite the lack of evidence to support this practice. The rationale is the theoretical risk of prosthetic joint infection arising from bacterial seeding from the urinary tract at the time of catheterization. In an era of antimicrobial stewardship, further assessment is warranted. METHODS: This study aimed to investigate the incidence of catheter-associated (CA) bacteriuria and bacteraemia in patients undergoing total joint arthroplasty and to assess the antimicrobial susceptibility of any isolated microorganisms. This prospective observational study undertaken over a 6-month period (May to October 2014) included 99 patients undergoing elective primary hip and knee arthroplasty at St Vincent's Hospital, Melbourne. Urine specimens were collected at insertion and removal of urinary catheters along with blood cultures upon urinary catheter removal. RESULTS: Overall 98% of the cohort received catheter antimicrobial prophylaxis for urinary catheter insertion and removal; the majority of patients received gentamicin (94%). Bacteriuria on catheter insertion had an incidence of 4.4%. The incidence of CA bacteriuria was 1.3%. All cultured organisms were sensitive to commonly used antibiotics including cephazolin. There were no cases of bacteraemia with urinary catheter removal. Increasing age, American Society of Anesthesiologists status and female gender were associated with the development of bacteriuria. CONCLUSION: The incidence of CA bacteriuria and bacteraemia with antimicrobial prophylaxis is low. This study provokes discussion about the requirement of catheter prophylaxis in this surgical context and the utility of preoperative urine screening.