Cost-effectiveness and clinical utility of universal pre-admission MRSA screening in total joint arthroplasty patients.

BACKGROUND: For patients undergoing total joint arthroplasty (TJA), pre-admission meticillin-resistant Staphylococcus aureus (MRSA) nasal screening has been widely adopted to prevent postoperative joint infection. However, screening cost-effectiveness and clinical utility have not been adequately evaluated. AIM: To assess the MRSA infection rate, associated costs, and costs of screening at our institution, before and after screening implementation. METHODS: This was a retrospective cohort study examining patients who underwent TJA at a health system in New York State, between 2005 and 2016. Patients were divided into the 'no-screening' group if the operation occurred prior to adoption of the MRSA screening protocol in 2011 and the 'screening' group if afterwards. The number of MRSA joint infections, cost of each infection, and costs associated with preoperative screening were recorded. Fisher's exact test and cost comparison analysis were performed. FINDINGS: The no-screening group had four MRSA infections in 6088 patients over a seven-year period, whereas the screening group had two in 5177 patients over five years. Fisher's exact test showed no significant association between screening and MRSA infection rate (P = 0.694). The cost of postoperative MRSA joint infection treatment was US$40,919.13 per patient, whereas annual nasal screening was US$103,999.97. CONCLUSION: At our institution, MRSA screening had little impact on infection rates and led to increased costs, with 2.5 MRSA infections required annually to meet the costs of screening. Therefore, the screening protocol may be best suited for high-risk populations, rather than the average TJA patient. The authors recommend a similar clinical utility and cost-effectiveness analysis at other institutions implementing MRSA screening programmes.

Epidemiology and management of Staphylococcus Aureus infective endocarditis in adult patients with congenital heart disease: A single tertiary center experience.

BACKGROUND: Infective endocarditis (IE) is a potentially lethal disease for adults with congenital heart disease (ACHD). Staphylococcus aureus (SA) is one of the commonest pathogens, identified in patients with ACHD and IE. This study aims to analyse the epidemiology, clinical characteristics and in-hospital management of IE due to SA (SAIE) in ACHD. METHODS: This is a single center retrospective study on documented episodes of SAIE in ACHD patients, treated at the Royal Brompton Hospital between 1999 and February 2020. RESULTS: Thirty-seven ACHD patients had an episode of SAIE (mean age 35.5 ± 14.9 years). More than half (51.3%), had a cardiac lesion of at least moderate complexity, with left ventricular outflow tract lesions being the most frequent. Twenty-four (64.9%) patients had a history of at least one previous open-heart surgery, and prosthetic material was used in 20 patients. A predisposing event was identified in 11 episodes (29.7%). Surgery was performed during the same admission in 24 (64.9%) patients, with early surgery (≤ 7 days from admission) performed in 12 patients. Early operation was associated with a shorter in-hospital stay compared to a later operation during the same admission or medical management [28.5 (IQR 23) vs. 43.5 (IQR 30) days, P = 0.028]. In-hospital mortality was 8.1%. Renal dysfunction at admission was associated with in-hospital multiorgan complications and/or death (OR 7.50, 95% CI, 1.18-47.67, P = 0.03). CONCLUSION: SAIE remains a life-threatening complication, necessitating cardiac surgery in the majority of ACHD patients. Ongoing educational investment on prevention and timely SAIE detection is warranted.

Epidemiology and Management of Orbital Cellulitis in Children.

BACKGROUND: The epidemiology of orbital cellulitis likely has evolved due to the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and the adoption of pneumococcal conjugate vaccination. In the absence of published guidelines, management is highly variable. We characterized epidemiology and management over an 11-year period. METHODS: A retrospective cohort study of children 0 to 21 years of age with orbital cellulitis +/- subperiosteal orbital abscess hospitalized at a large quaternary children's hospital from January 2008 to June 2018. We reviewed charts for demographic characteristics, clinical features, management, and outcomes. Using multivariable logistic regression, we evaluated predictors of surgical intervention and assessed whether corticosteroid use or antibiotic duration was related to clinical outcomes. RESULTS: Among 220 patients, methicillin-susceptible S. aureus was the most common organism (26.3%), with MRSA found in only 5.0%. Rates of vancomycin use fluctuated annually from 40.9% to 84.6%. Surgery was performed in 39.5% of the patients. Corticosteroids, used in 70 patients (32.1%), were unrelated to treatment failure (n = 9), defined as persistent signs and symptoms or initial clinical improvement followed by worsening (P = .137). The median antibiotic duration was 17 days (interquartile range 14-26). After controlling for age, gender, proptosis, eye pain with movement, eyelid swelling, neutrophil count, and corticosteroid use, treatment failure was not significantly associated with receipt of ≥ 3 weeks of antibiotic therapy (8/84, 9.5%) compared with > 2 but < 3 weeks (0/51, 0.0%) or ≤ 2 weeks (1/85, 1.2%) (adjusted odds ratio = 5.83 for ≥ 3 vs ≤2 weeks; 95% confidence interval: 0.58, 59.0). CONCLUSIONS: Although MRSA was rare, empiric vancomycin use was high. Treatment failure was uncommon in patients who received ≤ 2 weeks of therapy, suggesting that shorter durations are adequate in some patients.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria.

OBJECTIVES: This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. METHODS: The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes "avoided death" and "avoided resistant infections." One-way sensitivity analyses were performed. RESULTS: This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). CONCLUSIONS: MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Is Linezolid or Daptomycin Favored Over Vancomycin?

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality, and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. METHODS: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. RESULTS: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. CONCLUSION: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB.

Global patterns of necrotizing soft tissue infections: A systematic review and meta-analysis.

BACKGROUND: Frequency, microbiology, and outcomes of necrotizing soft tissue infections vary based on locoregional and environmental factors; however, there has been no global survey of these patterns. We performed a systematic review/meta-analysis on published reports of necrotizing soft tissue infections from across the globe. METHODS: Peer-reviewed empirical studies examining rates of polymicrobial and monomicrobial necrotizing soft tissue infections with microbial isolation and overall mortality rate were extracted along with geographic location using PubMed, Scopus, ProQuest, and Web of Science. Random-effects meta-analyses and sensitivity analyses were performed, adjusting for publication bias. Meta-regression analyses examined moderator effects of risk factors. RESULTS: One hundred and five studies (8,718 total patients) were included. Pooled prevalence of polymicrobial and monomicrobial infections were 53% and 37.9%, respectively. Truncal necrotizing soft tissue infections were commonly polymicrobial (P < .001), whereas monomicrobial infections prevailed in extremities (P = .008). Global prevalence of monomicrobial necrotizing soft tissue infections was observed to increase by 1.1% annually (P = .003). Staphylococcus aureus was the most common organism globally and in North America, Asia, the Middle East, and Africa, followed by Streptococcus pyogenes and Escherichia coli. Methicillin-resistant S. aureus accounted for 16% of necrotizing soft tissue infections globally. Overall mortality was 23.1%, observed to decline globally over the last decade (P = .020). No regional differences were noted for mortality. CONCLUSION: Although polymicrobial infections remain predominant worldwide, the incidence of monomicrobial infections is increasing. The observed decline in necrotizing soft tissue infection-related mortality is encouraging and may reflect advances in management, despite major variations in available healthcare resources globally.

Comparison of an Automated Plate Assessment System (APAS Independence) and Artificial Intelligence (AI) to Manual Plate Reading of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus CHROMagar Surveillance Cultures.

The automated plate assessment system (APAS Independence; Clever Culture System, Bäch, Switzerland) is an automated imaging station linked with interpretive software that detects target colonies of interest on chromogenic media and sorts samples as negative or presumptive positive. We evaluated the accuracy of the APAS to triage methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus cultures using chromogenic medium compared to that by human interpretation. Patient samples collected from the nares on ESwabs were plated onto BD BBL CHROMagar MRSA II and BD BBL CHROMagar Staph aureus and allowed to incubate for 20 to 24 h at 37°C in a non-CO2 incubator. Mauve colonies are suggestive of S. aureus and were confirmed with latex agglutination. Following incubation, samples were first interrogated by APAS before being read by a trained technologist blinded to the APAS interpretation. The triaging by both APAS and the technologists was compared for accuracy. Any discordant results required further analysis by a third reader. Over a 5-month period, 5,913 CHROMagar MRSA cultures were evaluated. Of those, 236 were read as concordantly positive, 5,525 were read as concordantly negative, and 152 required discordant analysis. Positive and negative percent agreements (PPA and NPA, respectively) were 100% and 97.3%, respectively. The APAS detected 5 positive cultures that were missed by manual reading and determined to be true positives. In a separate analysis, 744 CHROMagar Staph aureus plates were read in parallel. Of these, 133 were concordantly positive, 585 were concordantly negative, and 26 required discordant analysis. PPA and NPA were 95.7% and 96.7%, respectively. This study confirmed the high sensitivity of digital image analysis by the APAS Independence such that negative cultures can be reliably reported without technologist intervention (negative predictive values [NPVs] of 100% for CHROMagar MRSA and 99.0% for CHROMagar Staph aureus). Triaging using the APAS Independence may provide great efficiency in a laboratory with high throughput of MRSA and S. aureus surveillance cultures.

Identification of Staphylococcus pseudintermedius Isolates from Wound Cultures by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Improves Accuracy of Susceptibility Reporting at an Increase in Cost.

Staphylococcus pseudintermedius can easily be mistaken for Staphylococcus aureus using phenotypic and rapid biochemical methods. We began confirming the identification of all coagulase-positive staphylococci isolated from human wound cultures at our centralized laboratory, servicing both community and inpatients, with matrix-assisted laser desorption ionization-time of flight mass spectrometry instead of using phenotypic and rapid biochemical tests, and determined the prevalence of S. pseudintermedius since the change in identification procedure and at what cost. A retrospective review was performed on all wound swab cultures from which coagulase-positive staphylococci were isolated 7 months before and after the change in identification procedure. A total of 49 S. intermedius/pseudintermedius (SIP) isolates were identified, including 7 isolates from 14,401 wound cultures in the before period and 42 isolates from 14,147 wound cultures in the after period. The number of SIP isolates as a proportion of isolated coagulase-positive staphylococci increased significantly from the before, 7/6,351 (0.1%), to the after, 42/5,435 (0.7%), period (difference, 0.6% [95% confidence interval, 0.037 to 0.83%, P < 0.0001]). Antibiotic susceptibility testing was performed in 42 isolates; none had an oxacillin MIC of 1.0 to 2.0 µg/ml, the range in which, if the isolate was misidentified as S. aureus, a very major error in susceptibility interpretation would occur. The increase in cost of the change in identification procedure was Can$17,558 per year in our laboratory, performing microbiology testing for community and acute-care patients in a zone servicing nearly 1.7 million people. While we will only continue to learn more about this emerging pathogen if we make attempts to properly identify it in clinical cultures, the additional time and cost involved may be unacceptably high in some laboratories. .

SaQuant: a real-time PCR assay for quantitative assessment of Staphylococcus aureus.

BACKGROUND: Molecular assays are important tools for pathogen detection but need to be periodically re-evaluated with the discovery of additional genetic diversity that may cause assays to exclude target taxa or include non-target taxa. A single well-developed assay can find broad application across research, clinical, and industrial settings. Pathogen prevalence within a population is estimated using such assays and accurate results are critical for formulating effective public health policies and guiding future research. A variety of assays for the detection of Staphylococcus aureus are currently available. The utility of commercial assays for research is limited, given proprietary signatures and lack of transparent validation. RESULTS: In silico testing of existing peer-reviewed assays show that most suffer from a lack of sensitivity and specificity. We found no assays that were specifically designed and validated for quantitative use. Here we present a qPCR assay, SaQuant, for the detection and quantification of S. aureus as might be collected on sampling swabs. Sensitivity and specificity of the assay was 95.6 and 99.9 %, respectively, with a limit of detection of between 3 and 5 genome equivalents and a limit of quantification of 8.27 genome equivalents. The presence of DNA from non-target species likely to be found in a swab sample, did not impact qualitative or quantitative abilities of the assay. CONCLUSIONS: This assay has the potential to serve as a valuable tool for the accurate detection and quantification of S. aureus collected from human body sites in order to better understand the dynamics of prevalence and transmission in community settings.

What is the most cost-effective strategy for nasal screening and Staphylococcus aureus decolonization in patients undergoing total hip arthroplasty?

BACKGROUND: To reduce periprosthetic joint infection after total hip arthroplasty (THA), several nasal screening and decolonization strategies for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) have been performed. These include universal decolonization (UD; i.e., no screening and decolonization for all patients), universal screening and target decolonization (US; i.e., screening for all patients and decolonization for bacterial positive patients), and target screening and decolonization (TS; i.e., screening and decolonization for high-risk populations only). Although TS is the most cost-effective strategy, useful risk factors must be identified. The purpose of this study was to evaluate the presence of predictive factors that enable the TS strategy to be successfully implemented and to compare the costs of each strategy. METHODS: A total of 1654 patients scheduled for primary or revision THA (1464 female, 190 male; mean age 64 years) were screened prior to surgery for bacterial colonization of the nasal mucosa. Risk factors for positive MRSA and S. aureus (including both MRSA and MSSA) tests were analyzed according to the following parameters: sex, age ≥ 80 years, body mass index ≥ 30 kg/m2, antibiotic use within 3 years, corticosteroid use, serum albumin < 3.5 g/dL, glomerular filtration rate < 50 mL/min, presence of brain, thyroid, cardiac, or pulmonary disease, diabetes, asthma, smoking status, and whether revision surgery was performed. The average cost of each strategy was calculated. RESULTS: In total, 29 patients (1.8 %) tested positive for MRSA and 445 (26.9 %) tested positive for S. aureus. No parameters were identified as independent risk factors for MRSA and only female sex was identified as a risk factor for S. aureus (p = 0.003; odds ratio: 1.790; 95 % confidence interval: 1.210-2.640). The average cost of each strategy was 1928.3 yen for UD, 717.6 yen for US, and 717.6 yen for TS (for eradicating MRSA), and 1928.3 yen for UD, 1201.6 yen for US, and 1160.4 yen for TS (for eradicating S. aureus). CONCLUSIONS: No useful predictive parameters for implementing the TS strategy were identified. Based on cost implications, US is the most cost-effective strategy for THA patients.

Can the Xpert MRSA/SA BC assay be used as an antimicrobial stewardship tool? A prospective assay validation and descriptive impact assessment study in a South African setting.

BACKGROUND: Positive blood cultures showing Gram positive cocci in clusters signifies either Staphylococcus aureus or the less-virulent coagulase-negative staphylococci. Rapid identification and methicillin susceptibility determination with the Xpert MRSA/SA BC assay can improve management of S. aureus bloodstream infection and reduce inappropriate antibiotic use. METHODS: We prospectively evaluated the Xpert MRSA/SA BC assay in comparison with culture, on samples referred to our laboratory in the Western Cape, South Africa. We interviewed attending clinicians upon culture result availability, to assess antibiotic choices and estimate potential impact of the assay. RESULTS: Of the 231 samples included, there was 100% concordance between the Xpert MRSA/SA BC assay and culture (methicillin-resistant S. aureus 15/15, methicillin-susceptible S. aureus 42/42, coagulase-negative staphylococci 170/170). Time to final result could be reduced by approximately 30 h with the assay. Of the 178 patients with adequate antibiotic history, optimisation of antistaphylococcal therapy could have occurred more than 1 day sooner in 68.9% with S. aureus bloodstream infection (31/45, 95% CI 53.2-81.4%). Six of the 11 patients with methicillin-resistant S. aureus bloodstream infection (54.5%) could have received anti-MRSA cover sooner. Fifty-four days of antibiotic therapy could have been spared, equating to 0.3 days (95% CI, 0.2-0.4) saved per patient, driven by broad-spectrum beta-lactams (32 days, in 18.0% of the cohort). CONCLUSION: This assay has potential as an antimicrobial stewardship tool; costing and impact on clinical outcome in patients with S. aureus bloodstream infection should be assessed.

Low-cost colorimetric diagnostic screening assay for methicillin resistant Staphylococcus aureus.

The timely diagnosis of MRSA in clinical samples helps to reduce the attendant morbidity/mortality associated with infection due to the organism. The early institution of appropriate therapy or deployment of infection control protocols are dependent on a timely report from the microbiology laboratory. Various assays currently used in the identification of MRSA are associated with inherent shortcomings, thus there is a need to explore newer diagnostic frontiers that can eliminate some of these short comings at a relatively cheap, timely, specific and sensitive manner. We present in this study a MRSA specific optical immunosensor to detect the presence of the pathogen on contaminated surface using control and patient strains. Results revealed a detection limits of 103 CFU mL-1 upon visual observation, and 29 CFU mL-1 as determined by the linear regression equation, following the use of ImageJ to quantify activated cotton swab color intensity. The specificity of the sensor was examined by blind testing a panel of non-MRSA bacteria (E. coli, S. aureus and S. epidermis). Negative visual read-out was observed for all tested non-specific bacteria except for MRSA. Assay takes an average of 5 min and presents a powerful point-of-care diagnostic platform for the detection of MRSA.

Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol.

BACKGROUND: Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections. METHODS/DESIGNS: This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings. DISCUSSION: The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.

Rapid antibiotic susceptibility testing using low-cost, commercially available screen-printed electrodes.

Antimicrobial resistance (AMR) is an issue of upmost global importance, with an annually increasing mortality rate and growing economic burden. Poor antimicrobial stewardship has resulted in an abundance and diverse range of antimicrobial resistance mechanisms. To tackle AMR effectively, better diagnostic tests must be developed in order to improve antibiotic stewardship and reduce the emergence of antibiotic resistant organisms. This study employs a low-cost, commercially available screen printed electrode modified with an agarose-based hydrogel deposit to monitor bacterial growth using the techniques of electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) giving rise to a new approach to measuring susceptibility. Susceptible and drug resistant Staphylococcus aureus strains were deposited onto agarose gel modified electrodes which contained clinically important antibiotics to establish growth profiles for each bacterial strain and monitor the influence of the antibiotic on bacterial growth. The results show that S. aureus is able to grow on electrodes modified with gel containing no antibiotic, but is inhibited when the gel modified electrode is seeded with antibiotic. Conversely, methicillin-resistant S. aureus (MRSA; the drug resistant strain) is able to grow on gel modified electrodes containing clinically relevant concentrations of antibiotic. Results show rapid growth profiles, with possible time to results for antibiotic susceptibility <45 min, a significant improvement on the current gold standards of at least 1-2 days.

Comparative assessment of methicillin resistant Staphylococcus aureus diagnostic assays for use in resource-limited settings.

BACKGROUND: The rise of methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern. Paucity of data on MRSA carriage prevalence and diagnostic methods in resource-limited settings hampers efforts to define the problem and plan an appropriate response. Additionally, high variability in cost and logistical characteristics of MRSA screening methods may impede infection control efforts. We compared the performance of locally-available chromogenic agar BD CHROMagar MRSA II and two PCR-based assays (Hain GenoQuick MRSA and Cepheid Xpert SA Complete) for the detection of asymptomatic MRSA carriage in nasal swabs. RESULTS: During 2015, we enrolled 500 patients from five hospital wards at a Ugandan regional referral hospital. We found 30% prevalence of methicillin-sensitive Staphylococcus aureus (MSSA) nasal carriage, and 5.4% MRSA nasal carriage prevalence. Compared to a composite reference standard defined as a positive test result on any one of the three assays, Hain GenoQuick MRSA demonstrated the highest sensitivity (96%) followed by direct plating on CHROMagar at (70%), with the lowest sensitivity observed with Xpert SA Complete (52%). Cepheid Xpert provided the most rapid results (< 1 h) but was the most expensive (US $45-50/test). Substantially more labor was required for the Hain GenoQuick MRSA compared to Xpert SA Complete or CHROMagar tests. CONCLUSION: MRSA nasal carriage prevalence rates were low, and high diagnostic sensitivity was achieved using Hain GenoQuick MRSA. Chromogenic media had significantly lower sensitivity, but may represent a viable local option given its lower cost compared to PCR-based assays.

A laser-induced breakdown spectroscopy-integrated lateral flow strip (LIBS-LFS) sensor for rapid detection of pathogen.

Incorporation of new readout methods with established analytical devices allows methodological innovations in analytical sciences. Herein, we present a new sensing platform by combining an ultrasensitive element analyzer, namely the laser-induced breakdown spectroscopy (LIBS) and a lateral flow strip (LFS). AgxAuy bimetallic nanoparticles (AgxAuyBNPs) are selected as the labels to deliver the optimal quantitative performance by analyzing the Ag (I) signal from the test (T) line of LFS. For prototypical application in pathogen detection, the LIBS-LFS sensor can achieve a detection limit of 1.6 cfu mL-1 of Staphylococcus aureus (S. aureus) within 10 min, which is superior to conventional methods. Importantly, the signals of AgxAuyBNPs for visual and LIBS analysis are stable and still readable after the detection is finished and the test strip is stored for up to 13 days, suggesting a potential for long-term data preservation. This combination of LIBS with LFS provides a new concept toward integrated nano/analytical devices that can benefit various application scenarios.

Detection of antibiotic resistance genes from blood cultures: performance assessment and potential impact on antibiotic therapy management.

Molecular assays may constitute a valid method for timely prediction of antimicrobial resistance and optimization of empirical antibiotic therapies. This study assessed ELITe MGB assays of blood cultures to detect the main carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, Staphylococcus aureus and mec genes in less than 3 h. Excellent agreement was found between the results of genotypic and conventional phenotypic approaches. Retrospective analysis of medical records revealed that approximately 50% of bloodstream infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae or meticillin-resistant S. aureus were initially treated with inactive drugs. Overall, 36.3% of patients could have been treated with appropriate therapy at least 24 h earlier if molecular data had been used.

Methicillin-Resistant Staphylococcus aureus Prosthetic Valve Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.

Staphylococcus aureus prosthetic valve endocarditis (PVE) remains among the most morbid bacterial infections, with mortality estimates ranging from 40% to 80%. The proportion of PVE cases due to methicillin-resistant Staphylococcus aureus (MRSA) has grown in recent decades, to account for more than 15% of cases of S. aureus PVE and 6% of all cases of PVE. Because no large studies or clinical trials for PVE have been published, most guidelines on the diagnosis and management of MRSA PVE rely upon expert opinion and data from animal models or related conditions (e.g., coagulase-negative Staphylococcus infection). We performed a review of the literature on MRSA PVE to summarize data on pathogenic mechanisms and updates in epidemiology and therapeutic management and to inform diagnostic strategies and priority areas where additional clinical and laboratory data will be particularly useful to guide therapy. Major updates discussed in this review include novel diagnostics, indications for surgical management, the utility of aminoglycosides in medical therapy, and a review of newer antistaphylococcal agents used for the management of MRSA PVE.

Xpert MRSA screening in surgical patient flow; time for a rethink for hub-and-spoke laboratory models?

The move towards pathology networks and hub-and-spoke models of medical laboratory service provision has significantly changed the flow of samples, and the impact of results on patients, over recent years. At the same time advances in technology, including rapid, simple to use molecular platforms, are changing the way microbiology results can be utilized. Like many other medical microbiology laboratories, we struggle with this balance for many different sample types and test requests. Work published by Neilson et al. in Journal of Medical Microbiology last year looked at this balance for methicillin-resistant Staphylococcus aureus (MRSA) genotypic diagnostics and suggested significant cost savings when a whole-healthcare economy perspective was adopted. However, as with all changes, implementing MRSA molecular diagnostics in different clinical settings must be considered carefully. We add to this discussion in our accompanying letter, detailing our experience (in a hub-and-spoke medical microbiology laboratory setting) of 'rapid' MRSA molecular diagnostics for day-case surgery where pre-operative assessment had been missed, exploring the impact and costs of these tests. We find no impact on patient care, but at considerable additional cost. We hope this will add a cautionary note to those considering implementing molecular microbiology diagnostics, and reopen the debate on where, in hub-and-spoke laboratory models, such devices should be situated.

Spontaneous spondylodiscitis: review, incidence, management, and clinical outcome in 44 patients.

OBJECTIVESpontaneous spondylodiscitis remains uncommon but is a serious complication of the vertebral column. Risk factors include diabetes, hemodialysis, intravenous drug abuse, and chronic steroid use, and pain is the most common presenting symptom. This study aims to review the literature and report on the incidence, management, and clinical outcome of spontaneous spondylodiscitis in 44 patients.METHODSThis is a prospective study including 44 patients with spontaneous spondylodiscitis managed in the neurosurgery department of Cairo University Hospitals during the period between January 2012 and October 2017. All patients had a full clinical assessment, laboratory tests, radiological studies in the form of MRI with and without contrast, and a postoperative follow-up of up to 12 months.RESULTSTwelve cases underwent conservative treatment in the form of complete bed rest, intravenous antibiotics, and a spinal brace. Ten cases underwent surgical intervention in the form of laminectomy, debridement, and open biopsy. Twenty-two cases underwent laminectomy and surgical stabilization with fusion. There were 15 cases of tuberculous spondylodiscitis, 6 cases of brucellosis, 6 cases of pyogenic infection, and 17 cases in which no organism could be detected.CONCLUSIONSOnce the primary diagnosis is confirmed, early and adequately prolonged antibiotic therapy is recommended for spontaneous spondylodiscitis. Some cases can be successfully treated with conservative treatment alone, whereas surgery may be needed in other cases such as severe destruction of endplates, spinal abscess formation, mechanical instability, neurological deficits, and severe pain that have failed to respond to conservative treatment.