Background:Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma. Methods:A retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009-July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data. Results:Twenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection). Conclusions:M bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

Ureaplasma spp. are small and fastidious bacteria that may cause urogenital infections in healthy adults and, in rare cases, invasive disease. These bacteria have been increasingly recognized in immunocompromised patients and have been associated with hyperammonemia syndrome, particularly in lung transplant recipients. In this context, we present a unique clinical case of Ureaplasma parvum prostate abscess, a condition rarely observed in heart transplant recipients, diagnosed using next-generation sequencing (NGS).

PURPOSE OF REVIEW:This article aims to provide an intuitive framework for diagnosing and managing healthcare-associated diarrhea (HCAD) in the immunocompromised (IC) host. RECENT FINDINGS:Our understanding of diarrhea in hospitalized IC patients has significantly evolved. However, the challenge lies in distinguishing between these patients' numerous causes of diarrhea. The incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels has led to a paradigm shift in our approach to diarrhea. However, using these panels judiciously is of utmost importance, as their misuse can lead to over-testing, overtreatment, and increased hospital costs. We propose a stepwise diagnostic algorithm that ensures diagnostic stewardship, optimal patient care, and resource utilization. SUMMARY:Diarrhea is a common complication in hospitalized IC patients and is associated with significant morbidity and rare mortality. The advent of new diagnostics, such as GI multiplex PCR panels, holds promise in facilitating the detection of recognized pathogens and may allow for improved outcomes using pathogen-targeted therapy.

We report the case of a 71-year-old man who presented 2 years following renal transplantation with diffuse, unilateral cytomegalovirus retinitis five weeks after receiving an intravitreal dexamethasone implant device for the management of central retinal vein occlusion. Examination of the left eye showed diffuse retinal hemorrhages, attenuated and tortuous retinal vessels, and superior retinal whitening. The patient was successfully treated with serial intravitreal foscarnet injections and oral valganciclovir with disease regression observed by 12 weeks after presentation. The patient’s visual acuity and examination remained stable at 9-months follow-up.

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.

A left-handed 51-year-old previously healthy man presented with progressively decreased motor skills (primarily writing) and mild right frontal headache. On physical examination, he was alert with no meningismus. Cranial nerve testing and fundoscopy were normal. Minimal left-sided weakness in an upper motor neuron distribution affecting deltoid, triceps, finger extensor, and iliopsoas was observed. Tone and gait were normal. Magnetic resonance imaging (MRI) of the brain revealed a 2.1-cm ring-enhancing lesion in the right aspect of the pons, with involvement of the proximal right cerebellar peduncle (Figure 1). Cerebrospinal fluid (CSF) analysis showed a white blood cell count of 2 cells/mm3. The patient’s CSF protein level was 107.3 mg/dL and his CSF glucose level was 52 mg/dL. Subsequent computed tomography of the chest, abdomen, and pelvis showed no evidence of metastatic disease. Blastomyces antigen enzyme immunoassay (EIA) in urine was 3.62 ng/mL (reference range: none detected), and...

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.

Infections of the urinary system may involve the lower urinary tract (confined to the bladder) or the upper urinary tract (pyelonephritis). The spectrum of urinary conditions ranges from asymptomatic bacteriuria, symptomatic urinary tract infection (UTI), and sepsis associated with UTI that requires hospital admission. The treatment of UTIs include antibiotics that can result in long-term alteration of the normal microbiota of the gastrointestinal tract and in the development of multidrug-resistant microorganisms. For this reason, a urine sample should be cultured to identify causative organisms and their antimicrobial susceptibilities.

Waldenstrom 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. MYD88(L265P) and CXCR4 genetic status are pivotal for tailoring treatment options. Ibrutinib is a suitable treatment option for both treatment-naive 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.

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.

Despite advances in culture and molecular diagnostic methods and availability of transesophageal echocardiography at most centers, diagnosis of infective endocarditis (IE) remains challenging. Complications and mortality associated with IE have CONFERENCE COVERAGE Karen Giuliano, PhD: Oral Care to Reduce Hospital Infections (continued on page 29) CONFERENCE COVERAGE Invasive Pulmonary Aspergillosis Rates in ICU Patients With Influenza Are Surprisingly Low

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, ...

BACKGROUND:Bloodstream infections (BSI) with rapidly growing mycobacteria (RGM) resulted in recent nosocomial outbreaks predominantly in immunocompromised patients. A little is known about the clinical implications of RGM BSI with different species. METHODS:We conducted a multicenter retrospective cohort study of patients with RGM BSI from November 2011 to December 2020. Demographic data, clinical presentation, laboratory and radiographic findings and microbiological characteristics were used to tabulate descriptive statistics. We performed a comparative analysis of patients with BSI due to Mycobacterium abscessus complex (MABC) vs. other RGM. RESULTS:We identified 32 patients with positive blood cultures for RGM, 4/32 (12.5%) were considered to have unclear significance. The most common source for RGM BSI was intravascular catheters (14/28, 50%). Compared to other sources, patients with catheter-related bloodstream infection (CRBSI) received a shorter course of antimicrobial therapy (median [IQR]: one month [0.37-2.25] vs. six months [2-12]), (P = 0.01). The most common species isolated were MABC (12/28, 42.9%), followed by Mycobacterium fortuitum group (6/28, 21.4%) and Mycobacterium chelonae (6/28, 21.4%). Compared to other RGM, MABC BSI was more likely to be secondary to skin and soft tissue infection, associated with longer hospital stay (P = 0.04) and higher death rates despite a higher number of antimicrobial agents used for empirical and directed therapy per patient. CONCLUSION:MABC BSI is associated with an overall more resistant profile, longer hospital stay, and higher death rate despite a more aggressive therapy approach.

Tuberculosis transmission has been documented in health care settings where health care providers and patients encounter persons with unsuspected, infectious tuberculosis disease who have not been isolated in a timely manner or have not received appropriate treatment. Initial risk assessment for tuberculosis is crucial for determining administrative, environmental, and respiratory protective measures. Preventing the spread of aerosol-transmissible pathogens requires the use of airborne infection isolation rooms. In addition, respiratory protection with an N95 or higher-level respirator is recommended. Patients with suspected or confirmed respiratory tuberculosis disease should not share rooms.

Abstract Background Elizabethkingia spp. are non-enteric, gram-negative bacilli that are ubiquitous in environment. It has recently been identified as a causative pathogen in hospital outbreaks of life-threatening bloodstream infections in the Midwestern United States. Methods Retrospective electronic medical record review was performed for patients with Elizabethkingia spp. isolated from any site between November 2011 and September 2020 at our tertiary academic medical center. Antimicrobial susceptibilities are performed using Wadsworth agar dilution method. Results Fifteen cases with Elizabethkingia spp. were included. Ten patients (66.7%) were male and fourteen (93.3%) were Caucasian. The median age was 58 years (IQR 42-67). Four patients had diabetes mellitus, with two of these having end-organ damage (nephropathy, neuropathy, or retinopathy). Five patients had a tracheostomy, two patients had a history of lung transplantation, and four patients had active malignancy at the time of diagnosis (table 1). The most common clinical syndrome was respiratory infection (n=6), followed by catheter-related bloodstream infection (CRBSI) (n=4). Three patients were considered to be asymptomatically colonized. Five patients (33.3%) died, one of which was attributable to Elizabethkingia infection. A total of 55 isolates from all sites were available from the fifteen patients. The most common site of isolation was respiratory tract (23/55, 41.8%). In total, 33 of 55 isolates had polymicrobial growth, with the highest rate occurring in respiratory tract specimens (Table 2). A total of 23 clinical isolates were included in tabulation of antimicrobial susceptibility profiles; except for aztreonam (n=13). 95.7% of Elizabethkingia isolates were susceptible to trimethoprim-sulfamethoxazole, followed by levofloxacin and piperacillin-tazobactam (87% and 73.9%, respectively). All isolates were uniformly resistant to amikacin, aztreonam, and tobramycin (Table 3). Conclusion Elizabethkingia spp. can result in respiratory, bloodstream, and sinus infections especially in patients with active malignancy and tracheostomy. Amongst tested antimicrobials, trimethoprim-sulfamethoxazole showed the most favorable susceptibility profile (Figure 1). Figure 1. AN, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; FEP, cefepime; GM, gentamicin; LVX, levofloxacin; MEM, meropenem; NN, tobramycin; SXT, sulfamethoxazole/trimethoprim; TZP, piperacillin/tazobactam. Disclosures All Authors: No reported disclosures

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel treatment for various types of hematologic malignancy. We presented a case of refractory diffuse large B cell lymphoma patient who developed acute invasive fungal rhinosinusitis (AIFR) from Fusarium species after CAR-T therapy. Our photos illustrated the classic clinical, endoscopic, and histopathologic findings of AIFR.

PURPOSETo identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy.SUMMARYAn 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."CONCLUSIONRifampin-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 β-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.

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.

Question: A 42-year-old man with a history of advanced HIV/AIDS presented with epigastric pain, nausea, and fever. He has no history of alcohol intake. Physical examination showed exquisite tenderness in the epigastric area. Laboratory examination revealed normal white blood cell count (5.7 × 109/L) and platelet count (156 × 109/L); elevated amylase (163 U/L; reference range, 26–102 U/L) and lipase (84 U/L, reference range, 12–61 U/L); HIV-1 RNA of 16,200 copies/mL; and CD4 T lymphocyte cell counts of 6 cells/μL. He denies hypertriglyceridemia. A computed tomography scan of the abdomen demonstrated a nonspecific sausage-like appearance of the pancreas with increased mesenteric edema and stranding (Figure A). Endoscopic ultrasound examination revealed diffuse hypoechoic pancreatic enlargement (Figure B), and fine needle aspirate was performed (Figures C–E). What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Diffuse parenchymal enlargement giving a sausage-shaped appearance is a characteristic computed tomography finding in autoimmune pancreatitis. However, diffuse involvement of the pancreas can occur with various inflammatory, infectious, infiltrative, or neoplastic disorders. Imaging can demonstrate the pattern and extent of pancreatic involvement, but clinical and laboratory parameters are often required to elucidate and confirm the diagnosis.1Tenner S. Baillie J. DeWitt J. et al.American College of Gastroenterology guideline: management of acute pancreatitis.Am J Gastroenterol. 2013; 108 (1416): 1400-1415Crossref PubMed Scopus (1194) Google Scholar In some instances, histologic diagnosis is crucial before appropriate medical or surgical therapy is instituted. The etiologies of pancreatitis in HIV/AIDS patients include antiretroviral drugs (primarily didanosine), antibiotic prophylaxis (pentamidine and trimethoprim-sulfamethoxazole), pancreatic malignancies (Kaposi sarcoma and lymphoma), and opportunistic infections.2Barshak M.B. Pancreatic Infection.Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Elsevier, New York2020Google Scholar However, Mycobacterium avium Complex Infection (MAC)-associated pancreatitis is rare, with only a few documented case reports. It has been hypothesized that pancreatic enzymes (lipase and deoxyribonuclease) inhibit the growth of mycobacteria, which may account for the relatively low incidence of this disease.3Cho S.B. Pancreatic tuberculosis presenting with pancreatic cystic tumor: a case report and review of the literature.Korean J Gastroenterol. 2009; 53: 324-328Crossref Scopus (14) Google Scholar Histopathologic findings on endoscopic ultrasound examination with fine needle aspirate from peripancreatic soft tissue showed diffuse infiltration by histiocytes (Figure C). The lesional cells are positive for CD68 (Figure D) and negative for S100, HMB45, keratin AE1/AE3 by immunohistochemistry. A special stain for acid-fast bacilli showed clusters of rod-shaped bacilli within macrophages, consistent with MAC infection (Figure E). Fungal and tuberculosis blood cultures were also positive for MAC. MAC-specific treatment with rifabutin, moxifloxacin, ethambutol, and amikacin was started. Antiretroviral therapy was reinitiated, but the patient was lost to follow-up. In patients with HIV/AIDS, opportunistic infections including cytomegalovirus, herpes simplex virus, tuberculosis, and MAC should be considered in the initial evaluation of pancreatitis. Although uncommon, opportunistic infections are considered treatable and curable causes of pancreatitis.

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.