How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

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.

Molnupiravir: Is It Time to Move In or Move Out?

Molnupiravir: Is It Time to Move In or Move Out?With more than 250 million diagnosed cases and 5 million deaths, Covid-19 is our epoch-defining pandemic - and it is still ongoing. Despite the development of several effective Covid-19 vaccines, there are a limited number of antiviral treatments to reduce disease progression, risk of hospitalization, and death once the infection occurs. In this editorial, we examine the results of the phase 2 randomized, placebo-controlled, double-blind trials evaluating the safety and efficacy of molnupiravir, ...

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.

Cefazolin and rifampin: A coagulopathy-inducing combination.

PURPOSE: To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy. SUMMARY: An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as "definitely avoidable." CONCLUSION: Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the ß-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.

Clinical Presentation, Management, and Outcomes of Patients With Brain Abscess due to Nocardia Species.

BACKGROUND: Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess. METHODS: Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020. RESULTS: Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection. CONCLUSIONS: Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Management of Bloodstream Infections in Left Ventricular Assist Device Recipients: To Suppress, or Not to Suppress?

BACKGROUND: Ascertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources. METHODS: We retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs. RESULTS: A total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse. CONCLUSIONS: Patients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.

Current and Emerging Treatments for Waldenström Macroglobulinemia.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma. The primary goal of therapy is to reduce symptoms related to direct infiltration of the bone marrow and decrease monoclonal IgM-associated complications. Active agents in the management of WM can be broadly classified as rituximab-alkylator combination therapy, proteasome inhibitor-based therapy, and Bruton's tyrosine kinase inhibitor-based therapy. MYD88L265P and CXCR4 genetic status are pivotal for tailoring treatment options. Ibrutinib is a suitable treatment option for both treatment-naïve and relapsing WM patients. Recent advances in the intracellular B cell and cytokine signaling pathways have contributed to the development of novel therapeutic strategies. Current clinical trials are promising and may further advance WM-directed therapy.

Management and Outcome of Left Ventricular Assist Device Infections in Patients Undergoing Cardiac Transplantation.

BACKGROUND: Postoperative management of patients undergoing cardiac transplantation with an infected left ventricular assist device (LVAD) is unclear. METHODS: We retrospectively screened all adults with an LVAD who underwent cardiac transplantation at our institution from 2010 through 2018. We selected all cases of LVAD-specific and LVAD-related infections who were receiving antimicrobial therapy as initial treatment course or chronic suppression at the time of cardiac transplantation. Non-LVAD infections, superficial driveline-infection, or concurrent use of right ventricular assist device or extracorporeal membrane oxygenation device were excluded. RESULTS: A total of 54 cases met study criteria with 18 of 54 (33.6%) classified as LVAD- specific or related infections and 36 of 54 (66.6%) as noninfected. cases of lvad infection had a higher median charlson comorbidity Index score at the time of transplantation compared with noninfected cases (P = .005). Of the 18 cases of infection, 13 of 18 (72.2%) were classified as LVAD-specific and 5 of 18 (27.8%) were classified as LVAD-related. Nine of 13 (69.2%) cases had proven LVAD-specific infections. Antimicrobial therapy was extended posttransplant to treat preceding LVAD-specific infection in all 9 cases (9 of 13, 69.2%) with a median duration of 14 days (interquartile range, 14-28). After LVAD removal, antimicrobial treatment was not continued for preceding LVAD-related infections. CONCLUSIONS: Patients with an LVAD-specific infection were treated with 2 weeks of pathogen-directed therapy postheart transplant without any relapses. For those without LVAD-specific infection or uncomplicated LVAD-related bacteremia who had completed antimicrobial therapy pretransplant, antibiotics were discontinued after standard perioperative prophylaxis and no relapses were observed.

Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof).

The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease 2019 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically available and investigational immunomodulators, such as the interleukin 6 inhibitors tocilizumab and sarilumab and the anti-granulocyte-macrophage colony-stimulating factor lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.

Diagnostic imaging in infective endocarditis: a contemporary perspective.

INTRODUCTION: Infective endocarditis (IE) remains a diagnostic challenge. Prompt diagnosis is essential for accurate risk stratification and appropriate therapeutic decisions and surgical management. In recent years, the use of multimodal imaging has had a transformative effect on the diagnostic approach of IE in selected patients. AREAS COVERED: This review assesses published literature on different imaging modalities for the diagnosis of IE published between 1 January 2009 and 1 February 2020. We illustrate the diagnostic approach to IE with three clinical cases. EXPERT OPINION: Novel approaches to imaging for cardiac and extracardiac complications improve and individualize diagnosis, management, and prognosis in patients with suspected IE. The use of multimodal imaging should be guided by a multidisciplinary group of medical providers that includes infectious disease specialists, radiologists, cardiologists, and cardiothoracic surgeons.