Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: a meta-analysis.

PURPOSE: To assess the relationship between high vancomycin minimum inhibitory concentrations (MIC), in patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), and both mortality and complicated bacteremia. METHODS: Embase, Medline, EBM, Scopus and Web of Science were searched for studies published from January 1st 2014 to February 29th 2020. "High" vancomycin MIC cut off was defined as ≥ 1.5 mg/L. Three referees independently reviewed studies that compared outcomes in patients with MRSAB stratified by vancomycin MIC. Subgroup analyses were performed for rates of mortality and complicated bacteremia. RESULTS: A total of 13 studies with 2089 patients were included. Overall, mortality was 27.7% and 23.3% in the high and low vancomycin MIC group, respectively. No significant difference was found between vancomycin MIC groups for overall mortality, in-hospital mortality, late mortality, persistent bacteremia, severe sepsis or septic shock, acute renal failure, septic emboli or endocarditis, and osteomyelitis or septic arthritis. Early mortality was significantly associated with low vancomycin MIC. Mortality in studies using broth microdilution method (BMD) and need for mechanical ventilation were significantly associated with high vancomycin MIC. CONCLUSION: Overall mortality and complicated bacteremia were not significantly associated with high vancomycin MICs in a patient with MRSAB. Randomized controlled trials to assess the utility of vancomycin MIC values in predicting mortality and other adverse clinical outcomes are warranted.

Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective endocarditis.

BACKGROUND: The current diagnosis of infective endocarditis (IE) is based on the modified Duke criteria, which has approximately 80% sensitivity for the diagnosis of native valve endocarditis (NVE), with lower sensitivity for the diagnosis of prosthetic valve endocarditis (PVE) and culture-negative endocarditis. There is preliminary evidence that 18F-FDG PET/CT is an adjunctive diagnostic test with high accuracy reported in small studies to date. We therefore performed a meta-analysis of studies evaluating the use of PET/CT in the diagnosis of IE to establish a more precise estimate of accuracy. METHODS: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov were searched from January 1990 to April 2017 for studies evaluating the accuracy of PET/CT for the evaluation of possible IE. RESULTS: We identified 13 studies involving 537 patients that were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of IE was 76.8% (95% CI 71.8-81.4%; Q = 39.9, P < 0.01; I2 = 69.9%) and the pooled specificity was 77.9% (95% CI 71.9-83.2%; Q = 44.42, P < 0.01; I2 = 73.0%). Diagnostic accuracy was improved for PVE with sensitivity of 80.5% (95% CI 74.1-86.0%; Q = 25.5, P < 0.01; I2 = 72.5%) and specificity of 73.1% (95% CI 63.8-81.2%; Q = 32.1, P < 0.01; I2 = 78.2%). Additional extracardiac foci of infection were found on 17% of patients on whole body PET/CT. CONCLUSION: PET/CT is a useful adjunctive diagnostic tool in the evaluation of diagnostically challenging cases of IE, particularly in prosthetic valve endocarditis. It also has the potential to detect clinically relevant extracardiac foci of infection, malignancy, and other sources of inflammation leading to more appropriate treatment regimens and surgical intervention.

Role of 18F-FDG PET/CT in the diagnosis of cardiovascular implantable electronic device infections: A meta-analysis.

OBJECTIVE: We performed a meta-analysis evaluating the use of fluorine-18-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in the diagnosis of cardiovascular implantable electronic device (CIED) infections. BACKGROUND: PET/CT may be helpful in the diagnosis of CIED infection, particularly in patients with the absence of localizing signs or definitive echocardiographic findings. METHODS: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov from January 1990 to April 2017 were searched for studies evaluating the accuracy of PET/CT in the diagnosis of CIED infections. RESULTS: Overall, 14 studies involving 492 patients were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of CIED infection was 83% (95% CI 78%-86%) and the pooled specificity was 89% (95% CI 84%-94%). PET/CT demonstrated a higher sensitivity of 96% (95% CI 86%-99%) and specificity of 97% (95% CI 86%-99%) for diagnosis of pocket infections. Diagnostic accuracy for lead infections or CIED-IE was lower with pooled sensitivity of 76% (95% CI 65%-85%) and specificity of 83% (95% CI 72%-90%). CONCLUSION: Use of PET/CT in the evaluation of CIED infection has both a high sensitivity (83%) and specificity (89%) and deserves consideration in the management of selected patients with suspected CIED infections.

Invasive fungal infections associated with prior respiratory viral infections in immunocompromised hosts.

BACKGROUND: Increased risk of invasive pulmonary aspergillosis after influenza infection has been reported; however data are limited. PURPOSE: To describe Invasive fungal infections (IFI) associated with preceding respiratory viral infection at a large referral center. METHODS: We reviewed all IFI cases among patients with positive influenza and/or RSV nasopharyngeal/lower respiratory tract PCR from October 2015 to December 2016. Cases of pulmonary IFI were classified as possible, probable, and definite based on EORTC-MSG definitions. RESULTS: We identified 8 cases (4 influenza, 4 RSV); 3 with probable Aspergillosis, 1 possible Aspergillosis, 1 probable Histoplasmosis, 1 probable Mucormycosis, and 2 possible IFI (consistent clinical and imaging findings). Half of our patients were men with a mean age of 64 years (SD 8) and median Charlson Comorbidity Score of 3.5 (IQR 3-7). Most common risk factors were stem cell transplant (75%) and neutropenia (62.5%). Four patients were on antifungal prophylaxis at presentation. All patients received anti-viral therapy with oseltamivir/ribavirin and 50% received empiric antibiotics. Median duration from onset of viral infection to diagnosis of IFI was 8.5 days (IQR 2.5-14) and 75% were diagnosed during the same admission. All received antifungal therapy; 62.5% required ICU care, and 37.5% died during index hospitalization. CONCLUSIONS: Our study supports earlier observations describing IFI following respiratory viral infection in immunocompromised hosts. Secondary IFI occurred in 1.4% of our cohort and most occurred during the index admission. IFI following viral illness is associated with high mortality and early detection and therapy may improve outcomes.

Unrecognized pre-transplant disseminated Coxiella burnetti infection diagnosed in a post-transplant heart-kidney recipient.

To the best of our knowledge, we report the first case of pre-transplant unrecognized disseminated Coxiella burnetii infection, unmasked in the post-transplant period leading to both heart and kidney allograft dysfunction. A 59 year old man with a history of simultaneous heart-kidney transplantation due to end stage heart failure from severe aortic regurgitation (AR) and cryoglobulinemic immune complex mediated concentric necrotizing glomerulonephritis (GN), presents with a history of intermittent fevers and fatigue. Prior to transplantation he was treated for multiple episodes of culture negative endocarditis requiring bio-prosthetic valve replacement. Evaluation of fever included a transesophageal echocardiogram (TEE) that revealed a large hyperechoic mass on the anterior mitral leaflet with perforation, severe mitral regurgitation and moderate AR. Blood cultures were negative at that time. Owing to development of allograft mitral and aortic valve insufficiency, he underwent allograft bio-prosthetic mitral valve (MV) replacement and aortic valvuloplasty 2 years following his transplantation. Pathologic examination of the allograft mitral valve demonstrated fibrinopurulent exudate with degenerating bacterial organisms, consistent with vegetation and myxoid degenerative changes. Due to a high suspicion for native heart C. burnetii prosthetic valve endocarditis prior to transplantation, we re-evaluated the native explanted heart histopathology, as well as the explanted allograft MV. Cardiac allograft and native MV were positive for C. burnetii by real-time PCR. C. burnetii serology was consistent with persistent infection as well.

Diagnostic evaluation and management of culture-negative cardiovascular implantable electronic device infections.

BACKGROUND: Culture-negative (CN) cardiovascular implantable electronic device (CIED) infections represent a significant management challenge for clinicians with no specific guidelines addressing this subgroup of patients. The aim of the current investigation is to report our institutional experience of CN CIED infections and propose a systematic approach to diagnostic evaluation and management of these complicated cases based on our observations. METHODS: We retrospectively screened all CIED infection cases at Mayo Clinic from 2005 through 2017. Using standardized criteria to define significant microbial growth, all patients with positive blood or pocket/device cultures were excluded. RESULTS: A total of 835 cases of CIED infection were screened, and of these, 47 (6%) met CN-CIED infection criteria. Majority of patients (77%) in this cohort had received antimicrobial therapy prior to device cultures with a median duration of 8 days. The most common presentation was device pocket infection (81%). All patients underwent device removal. Route of antibiotics was switched from oral to parenteral and spectrum of activity expanded from initial therapy in 23% of patients despite negative cultures. Majority of patients (80%) were dismissed on parenteral therapy. Adverse events attributed to intravenous antibiotic therapy were documented in 63% of the cases. No recurrence was reported and 6-month survival was 94.8%. CONCLUSIONS: Pocket and device cultures in suspected CIED infections may be negative due to preextraction oral antibiotics. However, frequently these patients are managed with broad-spectrum parenteral therapy postextraction.

Dual versus single antiplatelet therapy in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: Although dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve replacement (TAVR), this approach is not evidence based. We therefore sought to systematically review the current evidence for this practice in terms of 30-day outcome looking at stroke, MI, bleeding, and death. METHODS: Relevant studies were identified through electronic literature search. Studies involving single antiplatelet therapy (SAPT) and DAPT in patients undergoing TAVR were included. Study specific risk ratios were calculated and combined using random-effects model meta-analysis. RESULTS: Analysis of data from 410 patients, stroke occurred in seven (3.16%) of SAPT and six (3.17%) of DAPT RR=1.03 (95% CI, 0.36-2.96, P=0.96). In analysis of 530 patients, MI occurred in three (1.07%) of SAPT and one (0.40%) of DAPT RR=1.97 (95% CI, 0.29-13.29, P=0.49), significant bleeding (major, life threatening and bleeding requiring transfusion) occurred in 20 (7.11%) of SAPT and 43 (17.27%) of DAPT RR=0.41 (95% CI, 0.25-0.69, P=0.0006). Number needed to harm for major or life threatening bleeding was 10. Death occurred in 15 (6.78%) of SAPT and 15 (7.94%) of DAPT (RR 0.91; 95% CI 0.46-1.79, P=0.78). CONCLUSION: Our meta-analysis suggests that at 30 days following TAVR there is no difference between post-procedural SAPT versus DAPT for the risk of stroke or MI and DAPT may have a higher bleeding risk. Adequately powered RCTs are warranted to clarify the optimal antiplatelet treatment strategy following TAVR.

The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection.

Background: Solid organ transplant (SOT) candidates should be screened and treated for latent tuberculosis infection (LTBI) to prevent tuberculosis (TB) reactivation after transplantation. We aimed to assess the steps from positive QuantiFERON (QFT) through LTBI treatment (cascade of care) in the SOT population. Methods: We conducted a retrospective study of SOT recipients older than 18 y with a positive QFT during pretransplant evaluation at the Mayo Clinic from January 2010 to June 2023. We analyzed each cascade step to determine associated drop-out factors for LTBI management. Results: Of 629 patients who had positive QFT results, 587 (93%) were evaluated by an infectious disease (ID) specialist, 478 (76%) were recommended to start LTBI treatment, 473 (75%) initiated LTBI treatment, and 457 (73%) completed LTBI treatment. LTBI treatment was not recommended in 109 patients evaluated by infectious disease, most of whom had previously received either LTBI (n = 72) or TB (n = 14) treatment. LTBI treatment was initiated before or after transplantation for 45% and 55% of patients, respectively. Isoniazid monotherapy was the most common regimen (92%), and adverse events were rare (7%). Seven patients developed active TB infection posttransplantation under various circumstances (3 without LTBI treatment, 1 during LTBI treatment, and 3 after completing LTBI treatment). Conclusions: Our findings demonstrate the variability of LTBI management in SOT recipients with positive QFT. When recommended, most patients completed LTBI treatment successfully. Nonetheless, active TB was noted regardless of whether patients received LTBI treatment. This study highlights the importance of optimizing LTBI management in this population.

Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.

BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. STUDY ELIGIBILITY CRITERIA: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Rural-urban Differences in Long-term Mortality and Readmission Following COVID-19 Hospitalization, 2020 to 2023.

Background: We compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. Methods: The study comprised adults hospitalized for COVID-19 at 17 hospitals in 4 US states between March 2020 and July 2022, followed until May 2023. The main analysis included all patients, whereas a sensitivity analysis focused on residents from 4 states containing 17 hospitals. Additional analyses compared the pre- and postvaccination periods. Results: The main analysis involved 9325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; the mean age was 65 years (rural, 66 years; urban, 64 years); 3894 women (rural, 41%; urban, 42%); 8007 Whites (rural, 87%; urban, 83%); 1738 deaths (rural, 21%; urban, 17%); and 2729 readmissions (rural, 30%; urban, 29%). During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (log-rank, P < .001; hazard ratio, 1.22; 95% confidence interval, 1.10-1.34, P < .001), and a trend toward a higher readmission rate (log-rank, P = .038; hazard ratio, 1.06; 95% confidence interval, .98-1.15; P = .130). The results remained consistent in the sensitivity analysis and in both pre- and postvaccination time periods. Conclusions and Relevance: Patients from rural counties experienced higher mortality and tended to be readmitted more frequently following COVID-19 hospitalization over the long term compared with those from urban counties, a difference that remained even after the introduction of COVID-19 vaccines.

"Let the Cat Out of the Heart": Clinical Characteristics of Patients Presenting With Blood Culture-Negative Endocarditis Due to Bartonella Species.

Patients with blood culture-negative endocarditis due to Bartonella infection frequently presented with fever, cytopenias, kidney failure, and positive PR3-ANCA. Bartonella IgG titers were variable. Patients commonly underwent surgery with overall low mortality.

Risk factors and outcomes of non-tuberculous mycobacteria infection in lung transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Patients with structural lung disease and immunocompromised status are at increased risk of pulmonary non-tuberculous mycobacteria (NTM) infection. However, literature on NTM in lung transplant recipients (LTR) is limited. We sought to systematically review the literature and perform a meta-analysis to examine associations with NTM disease and isolation in LTRs and their influence on mortality and chronic lung allograft dysfunction (CLAD). METHODS: A literature search of MEDLINE and Embase was performed on February 23, 2022. NTM disease was defined according to international guidelines. Isolation was defined as any growth of NTM in culture. Odds ratios (OR) were pooled for risk factors of NTM disease or isolation, and hazard ratios (HR) were pooled for mortality or CLAD. RESULTS: Eleven studies totaling 3,371 patients were eligible for inclusion, 10 of which underwent meta-analysis. Cystic fibrosis (OR 1.84, 95% confidence interval [CI] 1.03-3.30; I2 = 0%) and pre-transplant NTM isolation (OR 2.40, 95% CI 1.20-4.83; I2 = 0%) were associated with NTM disease. Only male sex was associated with NTM isolation (OR 1.45, 95% CI 1.01-2.10; I2 = 0%). NTM disease was associated with increased mortality (HR 2.69, 95% CI 1.70-4.26; I2 = 0%) and CLAD (HR 2.11, 95% CI 1.03-4.35; I2 = 44%). NTM isolation was not associated with mortality in pooled analysis or CLAD in 1 included study. CONCLUSIONS: NTM disease, but not isolation, is associated with worse outcomes. Several factors were associated with development of NTM disease, including cystic fibrosis and pretransplant NTM isolation. Strategies to optimize prevention and treatment of NTM disease in lung transplant recipients are needed.

Risk Factors for Surgical-Site Infections After Liver Transplant: Does Perioperative Antibiotic Regimen Matter?

BACKGROUND: Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. METHODS: Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. RESULTS: Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin-tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ-space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10-20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. CONCLUSIONS: The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

Deep Brain Stimulator Device Infection: The Mayo Clinic Rochester Experience.

Background: Deep brain stimulator (DBS)-related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods: This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results: There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9-6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions: Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Pharmacogenomic panel testing provides insight and enhances medication management in people with HIV.

OBJECTIVE: Our study aimed to assess the impact of pharmacogenomic panel testing in people with HIV (PWH). DESIGN: Prospective, observational intervention assessment. METHODS: One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants' current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. RESULTS: Ninety-six participants (median age 53 years, 74% white, 84% men, 89% viral load <50 copies/ml) completed panel testing, yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in one participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. CONCLUSION: Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.