Predictors of Treatment Failure in Patients With Pyogenic Brain Abscess.

Background: Pyogenic brain abscess poses a significant management challenge to clinicians, hence early diagnosis and interventions are critical. Our objective was to assess predictors of failure of therapy among patients with pyogenic brain abscesses according to surgical versus medical treatment. Methods: Retrospectively reviewed adults with pyogenic brain abscesses at our institution between 2009 and 2020. Treatment was classified as early surgical intervention and no early surgical treatment (medical therapy). Propensity score (PS) adjustment and multivariable regression were used to assess risk of treatment failure from surgical intervention and baseline covariates. Results: A total of 224 patients had pyogenic brain abscess, of whom 106 (47.3%) had early surgical treatment and 118 (52.7%) had medical treatment only. Significant predictors of surgical (vs. medical) treatment included essential hypertension (odds ratio [OR] 95% confidence interval [95% CI] = 2.06 [1.01-4.18]), abscesses number (single vs. multiple, OR [95% CI] =4.81 [1.64-14.08]), midline shift (OR [95% CI] = 3.09 [1.22-7.82]). At 6 months, treatment failure cumulative incidence was 27.1% in the medical group (n = 31) and 21.3% in early surgical group (n = 22). PS-adjusted analysis showed beneficial effect of early surgical treatment (hazard ratio [HR] [95% CI] = 0.55 [0.31-0.98]). Multivariable regression showed similar but statistically nonsignificant estimate of surgical benefit (HR [95% CI] =0.59 [0.34-1.01]; P = 0.056), and significant associations of Charlson Comorbidity Index (CCI) (P = 0.019) and pre-existing central nervous system hardware (P = 0.034) with increased risk of treatment failure. Conclusions: Higher CCI and pre-existing CNS hardware were significant risk factors associated with treatment failure. In propensity-adjusted analysis, early surgery was associated with a 45% reduction in risk of 6-month treatment failure.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Native Vertebral Osteomyelitis in Patients with Staphylococcus Aureus Bacteremia.

BACKGROUND: The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. RESULTS: A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. CONCLUSIONS: Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Diagnosis, management, and outcomes of brain abscess due to gram-negative versus gram-positive bacteria.

OBJECTIVES: Differences in management and outcomes of brain abscesses due to gram-positive (GPB) versus gram-negative bacteria (GNB) are not well defined. METHODS: A retrospective review of adult patients with brain abscesses due to monomicrobial infection from 2009 through 2020 was performed. RESULTS: A total 177 patients had a monomicrobial brain abscess; 143 (80.8%) caused by GPB and 34 (19.2%) by GNB. Patients with GNB had more history of head/neck surgery than those with GPB (58.8% vs 36.4%; P = 0.02). Pathogens in the GNB group included Pseudomonas aeruginosa (29.4%), Klebsiella spp (20.6%), and Enterobacter spp (20.6%). Pathogens in the GPB group included Staphylococcus aureus (32.2%) and Streptococcus spp (31.5%). Most patients had combined medical/surgical management (64.7% GNB vs 63.6% GPB). The median duration of antibiotic therapy was 42 days, and there was no significant difference in infection relapse or 3-month survival rate. Patients with GNB were more likely to have therapeutic failure than those with GPB (44.1% vs 22.4%; P = 0.01). CONCLUSIONS: Compared with brain abscesses caused by GPB, those due to GNB were more likely to occur in patients who had undergone prior head and neck surgery . No statistically significant difference in outcomes was observed between the groups; however, patients with GNB had a higher therapeutic failure rate than those with GPB.

Bacterial Brain Abscess: An Outline for Diagnosis and Management.

Despite advances in the diagnosis and management of brain abscess, significant associated morbidity and mortality remain high. We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009, through June 30, 2020. Overall, 247 patients were identified. The median age was 59 years, and 33.6% had a history of head and neck surgery or traumatic brain injury. Diagnostic brain magnetic resonance imaging (MRI) was performed in the bulk (93.1%) of patients. A total of 205 patients (83%) were managed with medical and surgical treatment. The most common definitive antibiotic regimen was monotherapy (48.2%). The median duration of antimicrobial therapy was 42 days. Compared with those who received combined therapy, patients with medical therapy alone had a higher mortality rate (21.4% vs 6%; P =. 003) with more neurologic sequelae (31% vs 27.1%; P = .5). Most patients with brain abscesses are older with multiple underlying comorbidities, and one-third had antecedent head and neck surgery. A prompt combined surgical and medical approach with prolonged antimicrobial therapy may cure the infection with avoidance of permanent residual neurologic deficits.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia - A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Mucormycosis in Hematopoietic Cell Transplant Recipients and in Patients With Hematological Malignancies in the Era of New Antifungal Agents.

BACKGROUND: The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. METHODS: This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. RESULTS: Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). CONCLUSIONS: Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

Prospective Validation of PREDICT and Its Impact on the Transesophageal Echocardiography Use in Management of Staphylococcus aureus Bacteremia.

BACKGROUND: Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, "PREDICT," that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. METHODS: We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. RESULTS: Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke's criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. CONCLUSIONS: We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.

Pathogen influence on epidemiology, diagnostic evaluation and management of infective endocarditis.

Infective endocarditis (IE) is uncommon and has, in the past, been most often caused by viridans group streptococci (VGS). Due to the indolent nature of these organisms, the phrase 'subacute bacterial endocarditis', so-called 'SBE', was routinely used as it characterised the clinical course of most patients that extended for weeks to months. However, in more recent years, there has been a significant shift in the microbiology of IE with the emergence of staphylococci as the most frequent pathogens, and for IE due to Staphylococcus aureus, the clinical course is acute and can be associated with sepsis. Moreover, increases in IE due to enterococci have occurred and have been characterised by treatment-related complications and worse outcomes. These changes in pathogen distribution have been attributed to a diversification in the target population at risk of IE. While prosthetic valve endocarditis and history of IE remain at highest risk of IE, the rise in prevalence of injection drug use, intracardiac device implantations and other healthcare exposures have heavily contributed to the existing pool of at-risk patients. This review focuses on common IE pathogens and their impact on the clinical profile of IE.

Resource utilization associated with hospital and office-based insertion of a miniaturized insertable cardiac monitor: results from the RIO 2 randomized US study.

Background: Previous studies support operational benefits when moving insertable cardiac monitor (ICM) insertions outside the cardiac catheterization/electrophysiology laboratories, but this has not been directly assessed in a randomized trial or when the procedure is specifically moved to the office setting. To gain insight, the RIO 2 US study collected resource utilization and procedure time intervals for ICM insertion in-office and in-hospital and these data were used to calculate costs associated with staff time and supply use in each setting.Methods and results: The Reveal LINQ In-Office 2 US study (randomized [1:1], multicenter, unblinded) included 482 patients to undergo insertion of the ICM in-hospital (in an operating room or CATH/EP laboratory) (n = 251) or in-office (n = 231). Detailed information on resource utilization was collected prospectively by the study and used to compare resource utilization and procedure time intervals during ICM insertion procedures performed in-office vs. in-hospital. In addition, costs associated with staff time and supply use in each setting were calculated retrospectively. Total visit duration (check-in to discharge) was 107 min shorter in-office vs. in-hospital (95% CI = 97-116 min; p < 0.001). Patient preparation and education in-office were more likely to occur in the same room as the procedure, compared with in-hospital (91.6% vs. 34.2%, p < 0.001 and 87.3% vs. 22.1%, p < 0.001, respectively). There was a reduction in registered nurse and cardiovascular/operating room technologist involvement in-office, accompanied by higher physician and medical assistant participation. Overall staff time spent per case was 75% higher in-hospital, leading to 50% higher staffing costs compared to in-office.Conclusions: ICM insertion in a physician's office vs. a hospital setting resulted in reduced patient visit time and reduced overall staff time, with a consequent reduction in staffing costs. Clinical trial registration: ClinicalTrials.gov NCT02395536.

Clinical and Economic Burden of Hospitalizations for Infective Endocarditis in the United States.

OBJECTIVE: To assess contemporary trends in the incidence, characteristics, and outcomes of hospital admissions for infective endocarditis (IE) in the United States. PATIENTS AND METHODS: Patients ≥18 years admitted with IE between January 1, 2003, and December 31, 2016, were identified in the National Inpatient Sample. We assessed the annual incidence, clinical characteristics, morbidity, mortality, and cost of IE-related hospitalizations. RESULTS: The incidence of IE-related hospitalizations increased from 34,488 (15.9; 95% confidence interval [CI], 15.73, 16.06) per 100,000 adults) in 2003 to 54,405 (21.8; 95% CI, 21.60-21.97) per 100,000 adults) in 2016 (P<.001). The prevalence of patients below 30 years of age, and those who inject drugs, increased from 7.3% to 14.5% and from 4.8% to 15.1%, respectively (P<.001). The annual volume of valve surgery for IE increased from 4049 in 2003 to 6460 in 2016 (P<.001), but the ratio of valve surgery to IE-hospitalizations did not decrease (11.7% in 2003; 11.8% in 2016). There was also a temporal increase in risk-adjusted rates of stroke (8.0% to 13.2%), septic shock (5.4% to 16.3%), and mechanical ventilation (7.7% to 16.5%; P<.001). However, risk-adjusted mortality decreased from 14.4% to 9.8% (P<.001). Median length-of-stay and mean inflation-adjusted cost decreased from 11 to 10 days and from $45,810±$61,787 to $43,020±$55,244, respectively, (P<.001). Nonetheless, the expenditure on IE hospitalizations increased ($1.58 billion in 2003 to $2.34 billion in 2016; P<.001). CONCLUSIONS: There is a substantial recent rise in endocarditis hospitalizations in the United States. Although the adjusted in-hospital mortality of endocarditis and the cost of admission decreased over time, the overall expenditure on in-hospital care for endocarditis increased.

Microbiology of Implant-Based Breast Reconstruction Infections: A Systematic Review.

BACKGROUND: Postsurgical complications have been an increasing concern for hospitals, particularly in light of payment reform. The costs to the health care system are increasing in light of Medicare penalties for readmissions for certain conditions. Surgical site infection following implant-based breast reconstruction (IBR) remains challenging. The rates of positive cultures and isolated microorganisms in IBR are unknown. This systematic review summarizes the reported microorganisms and positive culture rates in the existing literature. METHODS: A systematic review was performed using the guidelines outlined in Preferred Reporting Items for Systematic Reviews and Meta-analyses. Articles were included if breast implant infection rates and culture results were reported. Further subgroup analysis of culture positive infections was performed. RESULTS: A total of 25 studies were included, encompassing 25,177 IBR. Implant infections were reported in 1356 reconstructions (5.4%). Cultures were positive in 74.5% of infections. Gram-positive bacteria were the most common (68.6%), of which Staphylococcus species (51%) was the most isolated pathogen, followed by Pseudomonas. A subgroup analysis showed that early infections (63% vs 88%), radiotherapy (82% vs 93%), and acellular dermal matrix use (90% vs 100%) were associated with lower positive culture rates than their respective counterparts. Patients who received chemotherapy had higher positive culture results (94% vs 83%). Isolated microorganisms also varied among the subgroups. CONCLUSIONS: This systematic review outlines reported microorganisms in IBR. Staphylococcus species and Pseudomonas were the most frequently reported microorganism. Negative cultures were reported in up to 25.5% of infections. Patients with early infections, radiotherapy, and acellular dermal matrix demonstrated higher negative culture rates. This review can help guide the use of empirical antimicrobial therapy in IBR.

Infective endocarditis due to Granulicatella elegans presenting with musculoskeletal symptoms.

A 62-year-old man with essential hypertension and right L4-L5 hemilaminectomy was referred to rheumatology for evaluation of severe arthralgia and myalgia for 12 months. Review of symptoms was significant for night sweats and 20 pounds unintentional weight loss. Physical examination was significant for holosystolic murmur best heard at the cardiac apex of unclear chronicity. Laboratory investigations revealed elevated inflammatory markers, white blood cell count and B-type natriuretic peptide. Transoesophageal echocardiogram showed flail posterior mitral leaflet with severe mitral regurgitation and two vegetations (2.5×1 cm and 1.6×0.3 cm). Abdominal CT showed new focal splenic infarcts, and a brain MRI revealed subacute infarcts, consistent with the embolic phenomenon. Blood cultures grew Granulicatella elegans The patient underwent mitral valve replacement surgery followed by 6 weeks of parenteral therapy with vancomycin and gentamicin, with full recovery at a 3-month follow-up.

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study.

BACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.

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.

Diagnosis of Infectious Fluid Collections in Implant-Based Breast Reconstruction: The Role of Ultrasound.

OBJECTIVE: Implant-based breast reconstruction after mastectomy remains the most common reconstructive modality worldwide. Infection is a frequent complication that negatively affects the reconstructive outcome and increases health-care costs. The aim of this study is to evaluate the accuracy of ultrasonography in identifying fluid collections in patients with breast implant infection. METHODS: After receiving institutional review board approval, a retrospective chart review was performed on patients who presented with breast implant infection after breast reconstruction, during the period 2009-2017. To estimate the sensitivity and specificity of ultrasound (US) in detecting fluid collections, only patients with US evaluation and surgery during the same admission were included. RESULTS: In total, 64 patients with 64 infected implants met the inclusion criteria. Infected devices included 44 (69%) tissue expanders, and 20 (31%) implants, of which 40 (62%) were placed in the subpectoral and 24 (38%) prepectoral positions. Periprosthetic fluid was identified by US preoperatively in 45 (70%) of the patients, and a fluid collection was found in 61 (95%) of the patients during surgery. Sensitivity and specificity of US were 74% and 100%, respectively. Inaccurate US results were more likely in patients with silicone implants than patients with saline expander implants. CONCLUSION: Caution should be exercised in interpreting negative US findings in patients with silicone implants in the setting of infection. Other imaging modalities should be explored if US results are negative in cases with high clinical suspicion.

Lyme Disease-An Unusual Cause of a Mitral Valve Endocarditis.

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi. Cardiac manifestations are rare, occurring in 0.5% to 10% of patients. Lyme carditis and atrioventricular block are established manifestations of Lyme disease. Endocarditis caused by Borrelia has been reported only twice previously, and in both cases, these were species (Borrelia afzelii and Borrelia bissettii) not present in North America. We report a unique case of mitral valve endocarditis caused by B burgdorferi.

Cost-effectiveness of TYRX absorbable antibacterial envelope for prevention of cardiovascular implantable electronic device infection.

AIMS: Infection is a major complication of cardiovascular implantable electronic device (CIED) therapy that usually requires device extraction and is associated with increased morbidity and mortality. The TYRX Antibacterial Envelope is a polypropylene mesh that stabilizes the CIED and elutes minocycline and rifampin to reduce the risk of post-operative infection. METHODS: A decision tree was developed to assess the cost-effectiveness of TYRX vs standard of care (SOC) following implantation of four CIED device types. The model was parameterized for a UK National Health Service perspective. Probabilities were derived from the literature. Resource use included drug acquisition and administration, hospitalization, adverse events, device extraction, and replacement. Incremental cost-effectiveness ratios (ICERs) were calculated from costs and quality-adjusted life-years (QALYs). RESULTS: Over a 12-month time horizon, TYRX was less costly and more effective than SOC when utilized in patients with an ICD or CRT-D. TYRX was associated with ICERs of £46,548 and £21,768 per QALY gained in patients with an IPG or CRT-P, respectively. TYRX was cost-effective at a £30,000 threshold at baseline probabilities of infection exceeding 1.65% (CRT-D), 1.95% (CRT-P), 1.87% (IPG), and 1.38% (ICD). LIMITATIONS AND CONCLUSIONS: Device-specific infection rates for high-risk patients were not available in the literature and not used in this analysis, potentially under-estimating the impact of TYRX in certain devices. Nevertheless, TYRX is associated with a reduction in post-operative infection risk relative to SOC, resulting in reduced healthcare resource utilization at an initial cost. The ICERs are below the accepted willingness-to-pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost-effective prevention option for CIED patients at high-risk of post-operative infection.

Clinical Manifestations and Outcomes of Fluoroquinolone-Related Acute Interstitial Nephritis.

OBJECTIVE: To describe the clinical presentation, diagnosis, and outcomes of patients with biopsy-proven acute interstitial nephritis (AIN) related to fluoroquinolone (FQ) therapy. PATIENT AND METHODS: We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic's campus in Rochester, Minnesota, from January 1, 1993, through December 31, 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy-proven AIN that were attributed to FQ use. RESULTS: We identified 24 patients with FQ-related biopsy-proven AIN at our institution. The most commonly prescribed FQ was ciprofloxacin in 17 patients (71%), and the median antibiotic treatment duration was 7 days (interquartile range [IQR], 5-12 days). The median time from the initiation of FQ to the diagnosis of AIN was 8.5 days (IQR, 3.75-20.75 days). Common clinical manifestations included fever (12; 50%), skin rash (5; 21%), and flank pain (2; 8%), and 9 (38%) had peripheral eosinophilia. However, 4 (17%) of the patients were asymptomatic at the time of diagnosis and AIN was suspected on the basis of routine laboratory monitoring. Most patients (17; 71%) recovered after the discontinuation of antibiotic therapy, and renal function returned to baseline at a median of 20.5 days (IQR, 11.75-27.25 days). Six patients (25%) required temporary hemodialysis, and 14 patients (58%) received corticosteroid therapy. CONCLUSION: The onset of FQ-related AIN can be delayed, and a high index of suspicion is needed by physicians evaluating these patients. Overall outcomes are favorable, with recovery to baseline renal function within 3 weeks of discontinuing the offending drug.