Immunocompromised State Research Articles

Spontaneous remission of de novo membranous nephropathy in post-allogeneic hematopoietic stem cell transplantation patients: A report of two cases.

Membranous nephropathy (MN) is one of the most common de novo glomerular diseases developing in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Most authors have used immunosuppression for its treatment to target the underlying immune-mediated processes, akin to graft-versus-host disease, but the optimal management is currently unclear. Limited reports in the literature described the use of a conservative approach with success, particularly in cases with lower risks of progression, such as non-nephrotic-range proteinuria or early reduction of proteinuria by 6 months. We report two cases of post-HSCT MN with moderate risk features, namely prolonged durations of nephrotic-range proteinuria, that spontaneously resolved with conservative treatment. Patient 1 was of advanced age and in an immunocompromised state, while patient 2 was in need of a greater graft-versus-disease effect from the donor's immune system, which necessitated a balance between the risk of immunosuppression and the risk of progressive kidney function loss. These cases demonstrated that conservative treatment can be a reasonable approach in selected patients with post-HSCT MN, including those with moderate risk.

COVID-19 throughout pandemic waves and virus variants: a real-life experience in an Italian hospital.

New therapies and vaccines changed the management of COVID-19. The aim of this retrospective study was to describe characteristics, in-hospital mortality and its predictors in patients with moderate/severe COVID-19, considering the 4 different pandemic waves and viral variants' prevalence from February 2020 to January 2022. Among 1135 patients included, 873 (77%) had at least one comorbidity, 177 (16%) were immunocompromised. From waves 1 to 4, patients with severe respiratory failure and ICU admission decreased over time (p < 0.001), like the length of in-hospital stay (p < 0.001). Despite a reduction of in-hospital mortality from 19% to 11%, increased risk of death was related to older age and immunocompromising conditions, especially during the 4th wave (HR = 5.07 and HR = 10.86, p < 0.001 respectively) while remdesivir treatment in the 3rd wave (HR = 0.41, p = 0.010) and positive serology (aHR = 0.66, p = 0.027) were protective for survival. These data support the need for tailoring vaccine campaign for future COVID-19 waves.

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications. We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately. Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death. Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Unveiling the Immunostimulatory Potential of Rhus Toxicodendron in Immunocompromised Balb/C Mice Induced with Cyclophosphamide.

This study investigated how Rhus toxicodendron (RT) (6C, 30C, and 200C) can boost the immune system of BALB/c mice that were given cyclophosphamide (CPM), which is an anticancer drug that weakens the immune system. RT, known for its historical use in traditional homeopathic remedies, has demonstrated immunomodulatory and anti-inflammatory effects in various experimental models. To test the immune-boosting effects of RT, CPM (80 mg/kg) was given intraperitoneally to mice on days 4, 8, and 12 of the study but not to the normal control group. CPM-induced immunosuppression led to significant decreases in red blood cell (RBC), white blood cell (WBC), and hemoglobin (Hb) levels, and reduced spleen and thymus indices. Phagocytic activity, cytokine concentrations, and spleen architecture were also adversely affected. RT treatment, particularly at 200C, significantly ameliorated these effects, improving RBC, WBC, and Hb levels. Furthermore, RT partially prevented CPM-induced atrophy of immune organs. Treatment positively influenced cytokine production at both the protein and mRNA levels, restoring immune balance. Histopathological results confirmed that RT stimulated the immune system. The cells were more stable, and the white pulp in the spleen was arranged in a regular pattern. These findings suggest that RT may serve as an adjunctive immunostimulant therapy for conditions characterized by immunosuppression. However, further investigations in other immunocompromised states must validate these results before considering human clinical trials.

The Impact of Biliary Injury on the Recurrence of Biliary Cancer and Benign Disease after Liver Transplantation: Risk Factors and Mechanisms.

Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.

Bullous Cellulitis Due to Coagulase Negative Staphylococcus in Immunocompromised Patient

Introduction: Bullous Cellulitis is initially characterized by erythema and rapid development of bullae. This disease is most often caused by Beta-hemolytic streptococci and rarely by other bacteria such as Coagulase-Negative Staphylococcus (CoNS) type Staphylococcus haemolyticus. Immunocompromised state and history of malignancy are at high risk of infection with this bacterium. Local complications such as bullae can occur in obesity. Case Presentation: A 48-year-old woman with complaints of tensed and loose-walled blisters with a reddish base on the right thigh. The patient had a medical history of Thyroid Cancer, Acute Renal Failure, and Bulging Mass pelvic femur. On physical examination, the patient was unconscious with a ventilator. Dermatological examination of the dextra inferior extremity showed loose bullae with a positive Nikolsky sign and tensed bullae over the erythematous patches, ill-defined, irregular edges, and warm palpable. Laboratory results of leukocytosis, hypoalbumin, and CoNS bacteria from blood culture. An ALT-70 score obtained a total score of 5. Conclusion: Cases of bullous cellulitis are quite rare; cases like this usually occur in patients with an immunocompromised predisposition and obesity. CoNS is a commensal bacteria but, in some cases, could be a pathogen causing cellulitis. Poor prognosis that ends in death could occur in patients who have various complications.

Acute upper airway obstruction caused by mouth floor cellulitis in a patient of advanced age: a case report and literature review.

Mouth floor cellulitis is a type of diffuse cellulitis involving the submandibular, submental, and sublingual spaces. This condition may cause asphyxia due to elevation and posterior deviation of the tissues of the floor of the mouth. The severity of submandibular gland infection often escalates in the presence of underlying comorbidities. Advanced age, hyperglycemia, and an immunocompromised status often lead to the rapid development of infection, resulting in complications such as acute upper airway obstruction. These complications increase treatment difficulty and the risk of mortality. We herein report a case involving an older adult with diabetes who developed mouth floor cellulitis secondary to a submandibular gland infection. Despite the severity of the submandibular gland infection, a timely, effective, and multidisciplinary approach improved the patient's prognosis.

Tension Pyopneumothorax in an Immunocompetent Adolescent: A Case Report.

Tension pyopneumothorax is a rare, life-threatening condition that occurs as a complication of intrathoracic infection or bronchopleural fistula. In the few cases reported in the literature, the patients typically have multiple comorbidities, underlying lung disease, and/or an immunocompromised state. This case describes tension pyopneumothorax in a previously healthy adolescent male with no existing risk factors for this disease. After emergent stabilization and admission, surgical exploration of the chest revealed no fistulas or pleural defects. Extensive workup did not show any underlying risk factors for development of this condition. This case of pyopneumothorax with progression to tension physiology is exceedingly rare. Uniquely, the patient had no underlying medical or anatomical predisposition to developing this condition. The case also emphasizes pediatric patients' capacity to compensate in the setting of critical illness.

Evaluation of Negative Pressure Dressings for Closed Surgical Incisions in Decreasing Surgical Site Infections After Emergency Laparotomy: A Randomized Controlled Study.

Objectives The aim of this study is to compare the effectiveness of negative pressure dressings (NPDs) versus conventional dressings for closed surgical incisions after emergency midline laparotomy, focusing on their impact on surgical site infection (SSI) rates, wound dehiscence, hospital stay duration, and cosmetic outcomes. Methods The randomized controlled study was conducted over 24 months, involving 80 patients aged 18-65 years who had peritonitis and underwent emergency midline laparotomies. Patients with diabetes mellitus, a BMI >35 kg/m², immunocompromised conditions, or those requiring re-exploration within 30 days of surgery were excluded. The participants were randomly assigned into two groups using a computer-generated randomization table: Group A, the case group, consisted of 40 patients who received NPDs, while Group B, the control group, included 40 patients who received conventional dressings. Data were recorded in Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and analyzed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), with a p-value of <0.05 considered statistically significant. Results The overall occurrence of SSIs within the 30-day follow-up period was significantly lower in the NPD group compared to the conventional dressing group (30% vs. 70%, p < 0.05). The mean duration of hospital stay was 14.85 ± 10.43 days for the NPD group and 15.4 ± 9.75 days for the control group, with no statistically significant difference (p = 0.712). The mean Vancouver Scar Scale score was 5.3 ± 2.47 in the NPD group and 6.5 ± 2.14 in the control group, also showing no statistically significant difference (p = 0.11). Conclusions NPDs significantly reduced the incidence of SSIs compared to conventional dressings, but they did not have a significant impact on scar cosmesis or the duration of hospital stay.

Exploring the Risks of Copulatory Trauma in Immunocompromised NOD SCID Mice

This report documents a sudden and fatal case of copulatory breeding trauma in a 7-month old NOD SCID male breeder mouse. While similar injuries in other mouse strains typically result in recovery, the immunocompromised status of NOD SCID mice significantly impairs their healing abilities and heightens their susceptibility to infections. The mouse exhibited acute lethargy, gastrointestinal distress, and penile discharge, leading to death within a few hours. Postmortem examination revealed a significantly distended bladder with hemorrhagic spots, and urine analysis showed numerous motile sperm-like structures. The findings indicate that copulatory trauma was the primary cause of death, emphasizing the need for careful monitoring and preventive measures in breeding management, particularly for immunocompromised strains.

Obstructive Tracheobronchitis in Influenza-Associated Pulmonary Aspergillosis.

We report a bronchoscopic image of a 36-year-old with significant airway obstruction from obstructive tracheobronchitis secondary to invasive pulmonary aspergillosis. It is rare to see such a severe form of obstructive tracheobronchitis, likely caused by the patient'sp immunocompromised status and rapid progression nature of influenza-associated pulmonary aspergillosis.

Evaluation of Local Prescribing Patterns and Antimicrobial Resistance in Women With Acute Pyelonephritis Caused by E. coli.

Owing to increasing local Escherichia coli resistance and current guidelines for the treatment of acute pyelonephritis (APN) over 14 years old, an evaluation of local prescribing patterns is warranted. The purpose of this study was to evaluate local prescribing patterns and appropriateness of antibiotics in acute uncomplicated APN. This is a retrospective cohort study of female patients aged 18 to 89 years diagnosed with APN and positive urine culture growing E. coli. Exclusion criteria included pregnancy, immunocompromised status, and complicated urinary tract infections. Outcomes included antibiotic appropriateness and its effects on hospital admission, hospital length of stay, and 30-day readmission. Between 2017 and 2022, 308 female patients were diagnosed with APN and had positive urine cultures, with 104 seen only in the emergency department (ED) and 109 admitted to the hospital. Patients seen in the ED had a significant increase in E. coli resistance to discharge antibiotics (12.5% vs 2.8%, P = 0.0070). In those patients discharged on antibiotics resistant to E. coli, significantly more patients returned to the ED in 30 days (31.3% vs 10.7%, P = 0.0155). Patients seen only in the ED were more likely to have resistant organisms to discharge antibiotics compared with those admitted to the hospital. Patients discharged on antibiotics resistant to E. coli had a 3-fold increase in returning to the ED within 30 days regardless of admitted location. Follow-up of all cultures should be performed, and patients resistant to discharge antibiotics should be contacted and antibiotic regimens changed.

Estimating the Health-Related Quality of Life Benefit of Prophylactic Treatment for COVID-19 in Immunocompromised People: A Multimethod Valuation Study.

Background: Pre-exposure prophylaxis (PrEP) for COVID-19 provides additional protection, beyond vaccines alone, for individuals who are immunocompromised (IC). This may reduce the need for preventative behavioral modification, such as shielding-a behavioral restriction limiting an IC individual to minimize face-to-face interactions and/or crowded places. Therefore, PrEP may improve psychosocial well-being and health-related quality of life (HRQoL) for individuals with IC conditions. Objective: To estimate the potential HRQoL and utility benefit of PrEP for prevention of COVID-19 in individuals with IC conditions who may not have an adequate response of full vaccination (and therefore are at "highest risk" of severe COVID-19) that can be used in future economic evaluations of preventative therapies against COVID-19. Methods: Vignettes describing HRQoL associated with 2 pre-PrEP states (shielding and semi-shielding behavioral restrictions) and a post-PrEP state were developed from a literature review and tested through interviews with clinicians (n = 4) and individuals with IC conditions (n = 10). Vignettes were valued by a general population sample (N = 100) using a visual analog scale (VAS), time trade-off (TTO), and EQ-5D-5L. A sample of individuals with IC conditions (n = 48) valued their current HRQoL and a post-PrEP vignette using VAS and EQ-5D-5L. Results: Individuals with IC conditions reported a mean current EQ-5D-5L score of 0.574, and 0.656 for post-PrEP based on the vignette. PrEP would lead to behavior changes for 75% (30/40) of individuals with IC conditions and an emotional benefit for 93% (37/40) of individuals with IC conditions. Mean values from the general population valuation based on EQ-5D-5L ranged from 0.606 ("shielding") to 0.932 ("post-PrEP"). Conclusion: This study quantified the expected health state utility benefit of reduced psychosocial burden and behavioral restriction. PrEP would potentially result in a utility gain between 0.082 and 0.326, dependent on valuation approach and expected change in behavioral restrictions, leading to improvements in daily activities and emotional well-being.

RSV Risk Profile in Hospitalized Adults and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p = < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p = < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjustedOR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38-84%) lower odds of experiencing any severe outcome compared to COVID-19. RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

PRAME Expression in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression pattern of PRAME in Merkel cell carcinoma is unknown. In this study, we examine PRAME expression in Merkel cell carcinoma and explore its prognostic implications. The institutional archives at the University of Virginia were used to search for tumors classified as Merkel cell carcinoma from 2004 to 2022. All potential cases were reviewed to confirm the diagnosis, and electronic medical records were searched for clinical and demographic data. Tumors were subsequently immunostained for PRAME and Merkel cell polyomavirus. Cox proportional hazards regression models were used to estimate relative (all-cause) survival of PRAME positivity and MCPyV positivity in our study as well as MCC-specific survival of PRAME positivity. Univariate and multivariable models were created for each outcome related to all-cause survival. A total of 39 cases were included in the study. Twenty-eight percent (11 cases) demonstrated strong PRAME expression, and 27% of cases were positive for Merkel cell polyomavirus. There was no statistically significant correlation between PRAME expression and virus positivity. With respect to PRAME, the adjusted all-cause mortality hazard ratio was 11.4 (95% CI: 1.8, 70.8). The unadjusted MCC-specific hazard ratio was 4.6 (95% CI: 0.8, 27.5). The adjusted hazard ratio pertaining to Merkel cell polyomavirus infection was 0.25 (95% CI: 0.02, 2.96). In this limited cohort, PRAME expression appears to correlate with worse outcomes in Merkel cell carcinoma.

Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. Apply the authors' classification system within a validation cohort. Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

Chagas disease in the immunocompromised host.

To highlight recent advances in our understanding of Trypanosoma cruzi infection in immunocompromised individuals, a condition that is increasingly recognized as populations shift and use of immunosuppressive medications becomes more commonplace. Chagas disease screening programs should include people at risk for both Chagas disease and immunocompromise, e.g. people who have resided for ≥6 months in endemic Latin America who have an immunocompromising condition such as HIV or who are planned to start an immunosuppressive medication regimen. The goal of identifying such individuals is to allow management strategies that will reduce their risk of T. cruzi reactivation disease. For people with HIV- T. cruzi coinfection, strict adherence to antiretroviral therapy is important and antitrypanosomal treatment is urgent in the setting of symptomatic reactivation. People at risk for T. cruzi reactivation due to immunosuppression caused by advanced hematologic conditions or postsolid organ transplantation should be monitored via T. cruzi qPCR and treated with preemptive antitrypanosomal therapy if rising parasite load on serial specimens indicates reactivation. Reduction of the immunosuppressive regimen, if possible, is important. Chronic Chagas disease can lead to severe disease in immunocompromised individuals, particularly those with advanced HIV (CD4 + < 200 cells/mm 3 ) or peri-transplantation.

Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy

Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.

CRISPR-Cas3 and type I restriction-modification team up against blaKPC-IncF plasmid transfer in Klebsiella pneumoniae

ObjectiveWe explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks.Methods932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and blaKPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems.ResultsWe found a significant inverse correlation between the presence of CRISPR and R-M systems and blaKPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in blaKPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder blaKPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of blaKPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity.ConclusionsOur results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP.

Epidemiology and Duration of Therapy in Patients with Gram-negative Bloodstream Infections: Retrospective Analysis

Background: Longer courses of antibiotics can be associated with antimicrobial resistance and adverse effects. Randomized clinical trials support treating gram-negative bloodstream infections (GN-BSI) for a shorter duration with a consensus that a seven-day course of antibiotics is appropriate for uncomplicated GN-BSI. Prior to the implementation of a GN-BSI treatment guideline at our institution, we aimed to evaluate the characteristics of patients with GN-BSI and the duration of antibiotic therapy (DOT). Method: We retrospectively reviewed adult inpatients who had a blood culture with at least 1 gram-negative organism within 6 months (November 2022 to April 2023). Patients were excluded if they had a concomitant gram-positive bloodstream infection or if they were transitioned to comfort-focused care within 48 hours of their first positive blood culture. Complicated GN-BSI was defined as exhibiting any of the following: involvement of bone, joint, endovascular system, or foreign body, an inability to achieve source control, immunocompromised status, or failure to demonstrate clinical improvement or culture clearance within 72 hours. The primary outcome of this study was the mean DOT in patients with GN-BSI. Result: 100 patients met the inclusion criteria. Escherichia coli, identified in 54 cases, emerged as the most frequent organism. Urine (41) was the predominant source of bacteremia. Cefepime (48) was the most common empiric agent used. Of the 91 patients with available ceftriaxone susceptibility results, 84% had a susceptible organism. Amongst the 51 patients classified as having a complicated GN-BSI, the leading reason was immunosuppression. Table 1 presents a comparative analysis of complicated vs. uncomplicated GN-BSI. The average DOT for complicated GN-BSI was longer than the uncomplicated infections (20 vs. 11 days, P &lt; 0 .005). Additionally, fewer patients transitioned to oral therapy in the complicated group (33% vs. 67%, P &lt; 0 .005). Conclusion: At our institution, patients with uncomplicated GN-BSI have a shorter DOT and are more likely to transition to oral therapy than those with complicated GN-BSI. However, the mean DOT for uncomplicated infections remained longer than seven days and a large number of uncomplicated GN-BSI patients did not transition to oral therapy, indicating room for improvement in local practice through antimicrobial stewardship initiatives.