The effects of delayed appropriate antimicrobial therapy on children with Staphylococcus aureus blood infection.

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702-0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227-5.144, P = 0.012) for sepsis, 3.109 (1.166-8.290, P = 0.023) for septic shock.    Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality.

Clinical outcomes of subcutaneous implantable cardiac defibrillator implantation - Iran SICD registry.

BACKGROUND: The subcutaneous implantable-defibrillator (S-ICD) is a relatively new alternative to the transvenous ICD system to minimize intravascular lead-related complications. This paper presents outcome of SICD implantation in patients enrolled in Iran S-ICD registry. METHODS: Between October 2015 and June 2022, this prospective multicenter national registry included 223 patients with a standard indication for an ICD, who neither required bradycardia pacing nor needed cardiac resynchronization to evaluate the early post-implant complications and long-term follow-up results of the S-ICD system. RESULTS: The mean age of the patients was 45 ± 17 years. The majority (79.4%) were male. Ischemic cardiomyopathy (39.5%) was the most common underlying disorder among patients selected for S-ICD implant. Most study patients (68.6%) had ICD for primary prevention of sudden cardiac death. Seven patients (3.1%) were found to have suboptimal lead positions. Six patients (2.7%) developed a pocket hematoma; all were managed medically. During a mean follow-up of 2 years, the appropriate therapy was recorded in 13% of the patients and inappropriate ICD intervention mainly due to supraventricular tachycardia in 8.9%. Pocket infection was observed in four patients (1.8%) and five patients (2.2%) died mainly due to heart failure. CONCLUSION: S-ICDs were effective at detecting and treating both induced and spontaneous ventricular arrhythmias. Major clinical complications were rare.

Implantable cardioverter defibrillators in patients with orthotopic heart transplant: A multicenter case series.

BACKGROUND: Sudden cardiac death (SCD) is common after orthotopic heart transplant (OHT). No clear guidelines for implantable cardioverter defibrillator (ICD) implantation in OHT patients at high risk for SCD currently exist. OBJECTIVES: To assess the safety, efficacy, and benefit of ICDs and resynchronization therapy post-OHT. We also provide a systematic review of previous reports. METHODS: A retrospective multicenter cohort study within the United States. Patients with ICD post-OHT between 2000 and 2020 were identified. RESULTS: We analyzed 16 patients from 4 centers. The mean standard-deviation (SD) age was 43 (18) years at OHT and 51 (20) years at ICD implantation. The mean (SD) duration from OHT to ICD implantation was 9 (5) years. The mean (SD) left ventricular ejection fraction (LVEF) was 35% (17%). There were 2 (13%) postprocedural complications: 1 hematoma and 1 death. Mean (SD) follow-up was 24 (23) months. Survival rate was 63% (10/16) at 1 year and 56% (9/16) at 2 years, with 6/7 of those who died having LVEF < 35% at the time of the ICD implantation. Patients were more likely to receive appropriate therapy if their ICD was implanted for secondary (5/8) rather than primary (0/8) prevention (p = .007). Of those who did, 4 patients survived to 30 days post-ICD therapy. Severe CAV was not associated with the rate of appropriate therapy. CONCLUSIONS: Beneficial outcomes were observed when ICDs were implanted for secondary prevention only, and in patients with higher baseline LVEF. We also observed benefits with resynchronization therapy.

Time to appropriate antimicrobial therapy serves an independent prognostic indicator in children with nosocomial Klebsiella pneumoniae bloodstream infection.

We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children's Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46-66.59, P = 0.019; OR 9.69, 95% CI 1.15-81.39, P = 0.036; OR 8.28, 95% CI 1.37-50.10, P = 0.021; OR 6.52, 95% CI 1.08-39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25-393.94, P = 0.035; OR 40.06, 95% CI 2.32-691.35, P = 0.011; OR 22.60, 95% CI 1.78-287.27, P = 0.016; OR 12.21, 95% CI 1.06-140.67, P = 0.045; respectively).Conclusions: TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.

Cycle length of nonsustanied ventricular tachycardias among ICD patients: implications on subsequent appropriate therapies.

BACKGROUND: ICD patients with episodes of nonsustained ventricular tachycardias (NSVT) are at risk of appropriate therapies. However, the relationship between the cycle length (CL) of such NSVTs and the subsequent incidence of appropriate interventions is unknown. METHODS: 416 ICD patients with LVEF < 45% were studied. ICD programming was standardized. NSVT was defined as any VT of 5 or more beats at ≥ 150 bpm occurred in the first 6 months after implantation that terminated spontaneously and was not preceded by any appropriate therapy. The mean follow-up was 41 ± 27 months. RESULTS: We analyzed 2201 NSVTs (mean CL = 323 ms) that occurred in 250 patients; 111 of such episodes were fast (CL ≤ 300 ms). Secondary prevention (HR = 1.7; p < 0.001), number of NSVT episodes (HR = 1.05; 95% CI 1.04-1.07; p < 0.001) and beta-blocker treatment (HR = 0.7; p = 0.04) were independent predictors of appropriate interventions; however, the mean CL of NSVTs was not (p = 0.6). There was a correlation between the mean CL of NSVTs and the CL of the first monomorphic VT: r = 0.88; p < 0.001. This correlation was especially robust in individuals with > 5 NSVTs (r = 0.97; p < 0.001), with an agreement between both values greater than 95%. Patients with any fast NSVT experienced a higher incidence of VF episodes (26%) compared to those without NVSTs (3%) or with only slow NSVTs (7%); p < 0.001. CONCLUSIONS: Unlike the burden, the CL of NSVTs is not a predictor of subsequent appropriate interventions. However, there is a close relationship between the CL of NSVTs and that of arrhythmias that will later lead to appropriate therapies.

Appropriate and inappropriate therapies of implantable cardioverterdefibrillators.

Implantable cardioverter-defibrillators (ICD) reduce mortality of patients with risk of sudden cardiac death in primary and secondary prevention. Patients with implanted ICD can receive appropriate and inappropriate therapies with different incidence in both indication groups. There are some factors which can predict the incidence of ICD therapies. In some cases higher incidence of ICD therapies could negatively impact quality of patients lives. As predictive factors for higher incidence of appropriate therapies are discussed: reduced left venctricular ejection fraction, body mass index, chronic renal failure and frequent hospitalization for acute decompensation of chronic heart failure. As predictive factors for higher incidence of inappropriate therapies are discussed supraventricular tachycardia in patients history and single-chamber implantable kardioverter- defibrillator. The article summarizes indication criteria, incidence, predictive factors and treatment of appropriate and inappropriate therapies.

Effects of Delayed Antibiotic Therapy on Outcomes in Children with Streptococcus pneumoniae Sepsis.

Delayed antimicrobial therapy is associated with poor outcomes in sepsis, but the optimal antibiotic administration time remains unclear. We aimed to investigate the effects of the time of antimicrobial administration on outcomes and evaluate an optimal empirical antibiotic administration time window for children with Streptococcus pneumoniae sepsis. This retrospective study enrolled children with S. pneumoniae sepsis who presented to the Children's Hospital of Chongqing Medical University from May 2011 to December 2018. Classification and regression tree (CART) analysis was used to determine the time-to-appropriate-therapy (TTAT) breakpoint. Outcomes were compared between patients receiving early or delayed therapy, defined by CART-derived TTAT breakpoint. During the study period, 172 patients were included. The CART-derived TTAT breakpoint was 13.6 h. After adjustment for confounding factors, a TTAT of ≥13.6 hours was found to be an independent predictor of sepsis-related in-hospital mortality (odds ratio [OR] = 39.26; 95% confidence interval [CI] = 6.10 to 252.60), septic shock (OR = 4.58; 95% CI = 1.89 to 11.14), and requiring mechanical ventilation (OR = 2.70; 95% CI = 1.01 to 7.35). A Pediatric Risk of Mortality (PRISM) III score of ≥10 was independently associated with delayed therapy. Delayed antibiotic therapy was associated with poor outcomes in children with S. pneumoniae sepsis. The optimal empirical antibiotic administration time window in children with S. pneumoniae sepsis was within 13.6 h. Efforts should be made to ensure timely and appropriate therapy.

Incidence of appropriate implantable cardioverter-defibrillator therapy and mortality after implantable cardioverter-defibrillator generator replacement: results from a real-world nationwide cohort.

AIMS: The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement. METHODS AND RESULTS: We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13-1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57-6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy. CONCLUSION: A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events.

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

AIMS: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce. METHODS AND RESULTS: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics. Multivariate logistic regression models were utilized to identify which parameters predicted time to arrhythmia ≤5 years. The median time-to-first appropriate ICD therapy was 24.8 ± 2.8 months. A shorter time was observed in patients from Asian ethnicity (P < 0.05), those with syncope (P = 0.001), and those with Class IIa indication for ICD (P = 0.001). A longer time was associated with a positive family history of sudden cardiac death (P < 0.05). Multivariate Cox regression revealed shorter time-to-ICD therapy in patients with syncope [odds ratio (OR) 1.65, P = 0.001]. In 193 patients (76.6%), therapy was delivered during the first 5 years. Factors associated with this time were syncope (OR 0.36, P = 0.001), spontaneous Type 1 Brugada electrocardiogram (ECG) (OR 0.5, P < 0.05), and Class IIa indication (OR 0.38, P < 0.01) as opposed to Class IIb (OR 2.41, P < 0.01). A near-significant trend for female gender was also noted (OR 0.13, P = 0.052). Two score models for prediction of <5 years to shock were built. CONCLUSION: First appropriate therapy in BrS patients with prophylactic ICD's occurred during the first 5 years in 76.6% of patients. Syncope and spontaneous Type 1 Brugada ECG correlated with a shorter time to ICD therapy.

Postimplantation ventricular ectopic burden and clinical outcomes in cardiac resynchronization therapy-defibrillator patients: a MADIT-CRT substudy.

BACKGROUND: Frequent ventricular ectopy on preimplantation Holter has been associated with attenuated benefit from cardiac resynchronization therapy (CRT). However, it is unclear whether ectopic burden measured post-CRT implantation can be utilized to evaluate long-term prognosis. We aimed to describe the association between post-CRT implantation ectopic burden and subsequent risk of clinical outcomes. METHODS: At the 12-month follow-up visit, 24-hour Holter recordings were performed in 698 CRT-D patients from the MADIT-CRT study. The mean number of ventricular premature complexes (VPCs/hour) was calculated. High ectopic burden was defined as >10 VPCs/hour and low burden as ≤10 VPCs/hour. Multivariate Cox proportional hazards models were utilized to assess the association between 12-month ectopic burden and the risk of the end points of heart failure (HF) or death and ventricular tachyarrhythmias (VT/VF). RESULTS: At 12 months, 282 (40%) patients presented with low ectopic burden and 416 (60%) patients presented with high ectopic burden. The 3-year risk of HF/death and VT/VF was lower in patients with a low burden (7% and 8%) and significantly higher (25% and 24%) in patients with high burden. In multivariate analyses, patients with a high ectopic burden had approximately threefold increased risk of both HF/death (HR=2.76 [1.62-4.70], p < .001) and VT/VF (HR=2.79 [1.69-4.58], p < .001). CONCLUSION: In CRT-D patients with mild heart failure, high ectopic burden at 12-month follow-up was associated with a high 3-year risk of HF/death and VT/VF and threefold increased risk as compared to patients with low burden. Ectopic burden at 12 months may be a valuable approach for evaluating long-term prognosis.

Appropriateness of Acid Suppression Therapy.

BACKGROUND: The inappropriate startup of long-term acid suppressive therapy (AST) can have clinical and pharmacoeconomic impacts on ambulatory care. OBJECTIVE: To assess the proportion of patients with appropriate initiation of long-term AST in non-critically ill patients. To describe possible risk factors for nonappropriate AST. To calculate the potential savings when eliminating the nonappropriate startup of AST. METHOD: This observational, retrospective study evaluated the appropriateness of startup of long-term AST in medical records using a broad variety of international criteria and guidelines and using a validated screening instrument. RESULTS: A sample of 597 patients was included in the analysis. In 57% of them, AST was appropriately initiated. No specific risk profile could be defined. There was some indication that the availability of a clinical pharmacist and the use of standing orders were correlated to the outcome. Extrapolation to the total population (ie, 2836 patients) led to a total cost of €8880 during hospital stay plus an extra €40 391 per month after discharge. Avoiding inappropriate initiation of AST could lead to a saving of €3805 plus €17 441 per month. CONCLUSION: In all, 43% of initiation of long-term AST in the hospital was inappropriate. The potential savings from avoiding this could be substantial from a health care payer perspective. No patient characteristics that could predict for inappropriate initiation of AST were identified. A correlation between inappropriate initiation and medical disciplines using standing orders that include AST was seen.

Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection.

BACKGROUND: Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS: We conducted a retrospective quasi-experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS: We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS: An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients.

Efficacy of primary preventive ICD therapy in an unselected population of patients with reduced left ventricular ejection fraction.

AIMS: International guidelines advocate an implantable cardioverter and defibrillator (ICD) in patients with reduced left ventricular ejection fraction (LVEF) to prevent sudden death (SCD). Previous data suggest that the benefit of ICD therapy in real life may be lower than expected from the results of controlled studies and side-effects are not negligible. It is also unclear whether women benefit from treatment to the same extent as men. The aim of this study was to investigate the balance between benefits and complications of ICD therapy in a real-life population of patients with heart failure. METHODS AND RESULTS: We studied 865 consecutive patients with reduced LVEF treated with ICDs for primary prevention of SCD in 2006-11 in four tertiary care hospitals in Sweden (age 64 ± 11 years, 82% men, 62% ischaemic). The patients' medical records were scrutinized as regards appropriate therapies, complications related to the defibrillator, all-cause mortality, and gender differences. Mean follow-up was 35 ± 18 months. During follow-up 155 patients (18%) received appropriate ICD therapy, 61 patients (7%) had inappropriate shocks, 110 patients (13%) had at least one complication that required reoperation and 213 patients (25%) died. Men were twice as likely to receive ICD treatment compared with women (20 vs. 9%, P < 0.01), but neither total mortality nor complication rates differed. CONCLUSIONS: Ventricular arrhythmias necessitating ICD therapy are common (6% annually). Women are less likely to have correct ICD treatment, but have the same degree of treatment complications, thus reducing the net benefit of their treatment.

Increasing Rate of Fatal Streptococcus pyogenes Bacteriemia-A Challenge for Prompt Diagnosis and Appropriate Therapy in Real Praxis.

Streptococcus pyogenes, group A streptococci (GAS) bacteriaemia, is a life-threatening infection with high mortality, requiring fast diagnosis together with the use of appropriate antibiotic therapy as soon as possible. Our study analysed data from 93 patients with GAS bacteraemia at the General University Hospital in Prague between January 2006 and March 2024. In the years 2016-2019 there was an increase in GAS bacteraemia. Mortality in the period 2006-2019 was 21.9%; in the period 2020-2024, the mortality increased to 41.4%, p = 0.08. At the same time, in the post-2020 period, the time from hospital admission to death was reduced from 9.5 days to 3 days. A significant predictor of worse outcome in this period was high levels of procalcitonin, >35.1 µg/L (100% sensitivity and 82.35% specificity), and lactate, >5 mmol/L (90.91% sensitivity and 91.67% specificity). Myoglobin was a significant predictor in both compared periods, the AUC was 0.771, p = 0.044, and the AUC was an even 0.889, p ≤ 0.001, respectively. All isolates of S. pyogenes were susceptible to penicillin, and resistance to clindamycin was 20.3% from 2006-2019 and 10.3% in 2020-2024. Appropriate therapy was initiated in 89.1%. and 96.6%, respectively. We hypothesise that the increase in mortality after 2020 might be due to a decrease in the immune status of the population.

A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy.

BACKGROUND: Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. METHODS: We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). RESULTS: MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0-1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). CONCLUSIONS: Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. CLINICAL TRIALS REGISTRATION: Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

Implantable cardioverter-defibrillator in patients with inherited arrhythmia syndromes: A systematic review.

BACKGROUND: The potential benefit of implantable cardioverter-defibrillator (ICD) therapy in individuals with inherited arrhythmia syndromes is well known. However, it is not deprived of morbidity, in the form of inappropriate therapies and other ICD-related complications. OBJECTIVE: The aim of this systematic review is to estimate the rate of appropriate and inappropriate therapy, as well as other ICD-related complications, in individuals with inherited arrhythmia syndromes. METHODS: A systematic review was performed, regarding appropriate and inappropriate therapy, and other ICD-related complications, in individuals with inherited arrhythmia syndromes (Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Early Repolarization Syndrome, Long QT Syndrome and Short QT syndrome). Studies were identified by searching published papers in PubMed and Embase up to August 23rd, 2022. RESULTS: From data gathered of 36 studies, with a total of 2750 individuals, during a mean follow-up time of 69 months, appropriate therapies occurred in 21% of the individuals and inappropriate therapies in 20% of the individuals. Concerning the other ICD-related complications, 456 complications were observed, amongst 2084 individuals (22%), with the most frequent being lead malfunction (46%), followed by infectious complications (13%). CONCLUSIONS: ICD-related complications are not uncommon, especially when one considers the exposure time of young individuals. The incidence of inappropriate therapies was 20%, although lower rates were reported in recent publications. S-ICD is an effective alternative to transvenous ICD for sudden death prevention. The decision to implant an ICD should be individualized, taking into account the risk profile of each patient, as well as the possibility of complications.

Predictors of ventricular tachyarrhythmia in patients with implantable cardioverter-defibrillator and non-ischemic systolic heart failure.

BACKGROUND: The benefit derived from implantable cardioverter-defibrillators (ICD) in subjects with non-ischemic systolic HF (NICM) is less well-established. AIM: The study aimed to determine the incidence, predictors, and prognostic impact of ventricular arrhythmias in patients with ICD and NICM. METHODS: The study sample included 377 consecutive patients with ICD or cardiac resynchronization cardioverter-defibrillators (CRT-D, 74% of patients) and NICM implanted and monitored remotely in a university hospital. RESULTS: During the median (interquartile range [IQR]) follow-up of 1645 (960-2675) days, sustained ventricular arrhythmia occurred in 92 patients (24.4%). Of those, ventricular fibrillation (VF), ventricular tachycardia (VT), and both VT and VF occurred in 10 (10.9%), 72 (78.3%), and 10 (10.9%) patients, respectively. Patients with vs. those without ventricular arrhythmia differed concerning sex, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), post-inflammatory etiology, atrial fibrillation/flutter occurrence, and supraventricular arrhythmia (SVT) other than AF/AFL during follow-up. In multivariable Cox regression, LVEDD (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.003-1.09; P = 0.03), AF/AFL (HR, 1.86; 95% CI, 1.21-2.85; P = 0.004), and SVT (HR, 1.77; 95% CI, 1.10-2.87; P = 0.02) were independent predictors of sustained VT, while AF/AFL (HR, 1.65; 95% CI, 1.07-2.56; P = 0.02) was independent predictor of VF. All-cause mortality in patients with VT/VF was significantly higher than in subjects without sustained ventricular arrhythmias (35.9% vs. 22.4%; P = 0.01). CONCLUSIONS: Ventricular arrhythmia occurred in every fourth patient with NICM and ICD during 4.5 years of observation and was associated with significantly worse prognosis than in subjects free of VT/VF. Higher LVEDD, atrial fibrillation/atrial flutter, and supraventricular tachycardia flag patients at risk of ventricular arrhythmia.

Association of QTc Interval and V4-S Wave With Appropriate ICD Therapy in Hypertrophic Cardiomyopathy.

Background: Ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) may lead to sudden cardiac death (SCD). We aimed to investigate the relationship between electrocardiogram (ECG) indicators and the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy in HCM. Methods: The HCM patients receiving ICD implantation were enrolled consecutively. QT interval correction (QTc) was calculated using Bazett's formula. Long or deep S wave in V4 lead was defined as duration time >50 ms and/or voltage amplitude >0.6 mV. The endpoint in our study was at least one ICD appropriate therapy triggered by ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF), including anti-tachyarrhythmia pacing (ATP) and electrical shock. Results: A total of 149 patients with HCM (mean age 53 ± 14 years, male 69.8%) were studied. Appropriate ICD therapies occurred in 47 patients (31.5%) during a median follow-up of 2.9 years. Cox regression analysis showed that long or deep S wave in V4 lead [hazard ratio (HR) 1.955, 95% confidence interval (CI) 1.017-3.759, P = 0.045] and QTc interval (HR 1.014, 95% CI 1.008-1.021, P < 0.001) were independent risk factors for appropriate ICD therapy. The ROC showed that the optimal cut-off point value for the QTc interval to predict the appropriate ICD therapy was 464 ms, and the AUC was 0.658 (95% CI 0.544-0.762, P = 0.002). The AUC for S wave anomalies in V4 lead was 0.608 (95% CI 0.511-0.706, P = 0.034). We developed a new model that combined the QTc interval and S wave anomalies in V4 lead based on four patient groups. Patients with QTc ≥464 ms and long or deep V4-S wave had the highest risk of developing appropriate ICD therapy (log-rank P < 0.0001). After adding QTc interval and V4-S wave anomalies into the HCM-risk-SCD model, the prediction effect of the new model was significantly improved, and the NRI was 0.302. Conclusions: In this HCM cohort, QTc and S wave anomalies in V4 lead were found to be significant and strong predictors of the risk of appropriate ICD therapy. Patients with QTc ≥464 ms and long or deep S wave had the highest risk. After QTc interval and V4-S wave anomalies adding to the HCM-risk-SCD model, the prediction effect is significantly improved.

Minireview on Novel Anti-infectious Treatment Options and Optimized Drug Regimens for Sepsis.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection is a major public health concern, as it is a leading cause of mortality and critical illness worldwide. Antibiotics are one of the cornerstones of the treatment of sepsis; administering appropriate antibiotics in a rapid fashion to obtain adequate drug concentrations at the site of the infection can improve survival of patients. Nevertheless, it is a challenge for clinicians to do so. Indeed, clinicians today are regularly confronted with infections due to very resistant pathogens, and standard dosage regimens of antibiotics often do not provide adequate antibiotic concentrations at the site of the infection. We provide a narrative minireview of different anti-infectious treatments currently available and suggestions on how to deliver optimized dosage regimens to septic patients. Particular emphasis will be made on newly available anti-infectious therapies.

Subcutaneous versus transvenous implantable defibrillator: An updated meta-analysis.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) placement is a well-established therapy for prevention of sudden cardiac death. The subcutaneous implantable cardioverter-defibrillator (S-ICD) was specifically designed to overcome some of the complications related to the transvenous implantable cardioverter-defibrillator (TV-ICD), such as lead complications and systemic infections. Evidence on the comparison of S-ICD vs TV-ICD are limited. OBJECTIVE: The purpose of this study was to conduct an updated meta-analysis comparing S-ICD vs TV-ICD. METHODS: Electronic databases were searched for studies directly comparing clinical outcomes and complications between S-ICD and TV-ICD. The primary outcome was the composite of clinically relevant complications (lead, pocket, major procedural complications; device-related infections) and inappropriate shocks. Secondary outcomes included death and the individual components of the primary outcome. RESULTS: Thirteen studies comprising 9073 patients were included in the analysis. Mean left ventricular ejection fraction was 40% ± 10%; 30% of patients were female; and 73% had an ICD implanted for primary prevention. There was no statistically significant difference in the risk of the primary outcome between S-ICD and TV-ICD (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.53-1.19). Patients with S-ICD had lower risk of lead complications (OR 0.14; 95% CI 0.06-0.29; P <.00001) and major procedural complications (OR 0.18; 95% CI 0.06-0.57; P = .003) but higher risk of pocket complications (OR 2.18; 95% CI 1.30-3.66; P = .003) compared to those with TV-ICD. No significant differences were found for the other outcomes. CONCLUSION: In patients with an indication for ICD without the need for pacing, TV-ICD and S-ICD are overall comparable in terms of the composite of clinically relevant device-related complications and inappropriate shock.