Carbapenem-resistant Enterobacterales (CRE) are an important threat to the health of solid organ transplant recipients (SOTr); data comparing outcomes of SOTr with CRE to non-SOTr with CRE are lacking. A matched cohort study was performed within 2 prospective, multicenter, cohort studies (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales and Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales 2). The epidemiology, desirability of outcome rankings outcomes, and mortality of SOTr and non-SOTr hospitalized in the United States (December 2011-August 2017) with clinical isolates with Centers for Disease Control and Prevention-defined CRE were compared. In total, 121 SOTr and 242 matched non-SOTr were included. Fifty-one percent of isolates met infection criteria. SOTr were younger (P < .001), less acutely ill (P = .029), less often had a malignancy history (P = .006), and more often were admitted from home (P < .001) than non-SOTr. SOTr had more favorable adjusted desirability of outcome rankings outcomes; a randomly selected SOTr had a 58% (95% confidence interval, 53%-64%) probability of a better outcome as compared to a randomly selected non-SOTr. All-cause 30-day mortality was 14% (17/121) in SOTr vs 25% (60/242) in non-SOTr, P = .018. After stabilized inverse probability weighted adjustment, SOTr had a 7% lower 30-day mortality risk than non-SOTr (95% confidence interval, -15% to 1%). SOTr with CRE do not have worse outcomes than matched patients without transplant history.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) can increase the susceptibility of individuals to contracting mucormycosis through several mechanisms. Nowadays, coronavirus disease (COVID-19)-associated mucormycosis (CAM) is a serious public health concern, particularly in developing countries. This meta-analysis aims to identify the risk factors that affect the mortality rate of patients with CAM. We systematically searched PubMed, Google Scholar, Scopus, Cochrane library, and preprint databases using pertinent keywords and the reference lists of the included relevant articles from inception till October 27, 2021. In order to reduce the effects of small-scale studies, we only selected cross-sectional, case–control, and cohort studies and case series with at least four patients. We identified 26 articles that included 821 patients with CAM. The effect size (ES) of mortality rate was 28

BACKGROUND:Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). METHODS:We searched PubMed database (last searched 1/6/2022) for English-language reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. RESULTS:We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation. DISCUSSION:We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

Background: Pneumocystis jiroveciii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation.Methods: Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP.Findings: Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7·5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP.Interpretation: Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions.Funding Information: This study was support in part by intramural research funds from the NIH Clinical Center.Declaration of Interests: No conflicts of interest to declare.Ethics Approval Statement: The Yale Institutional Review board approved this study (IRB# 2000023859).

From the Department of Medicine, Division of Infectious Diseases, Yale University School of Medicine, CT. Correspondence to: Carlo Foppiano Palacios, MD, 20 S York St, New Haven, CT 06510. E-mail: [email protected]. The authors have no funding or conflicts of interest to disclose.

OBJECTIVES:To describe the epidemiology of patients with nonintestinal carbapenem-resistant Enterobacterales (CRE) colonization and to compare clinical outcomes of these patients to those with CRE infection. DESIGN:A secondary analysis of Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae 2 (CRACKLE-2), a prospective observational cohort. SETTING:A total of 49 US short-term acute-care hospitals. PATIENTS:Patients hospitalized with CRE isolated from clinical cultures, April, 30, 2016, through August 31, 2017. METHODS:We described characteristics of patients in CRACKLE-2 with nonintestinal CRE colonization and assessed the impact of site of colonization on clinical outcomes. We then compared outcomes of patients defined as having nonintestinal CRE colonization to all those defined as having infection. The primary outcome was a desirability of outcome ranking (DOOR) at 30 days. Secondary outcomes were 30-day mortality and 90-day readmission. RESULTS:Of 547 patients with nonintestinal CRE colonization, 275 (50%) were from the urinary tract, 201 (37%) were from the respiratory tract, and 71 (13%) were from a wound. Patients with urinary tract colonization were more likely to have a more desirable clinical outcome at 30 days than those with respiratory tract colonization, with a DOOR probability of better outcome of 61% (95% confidence interval [CI], 53%-71%). When compared to 255 patients with CRE infection, patients with CRE colonization had a similar overall clinical outcome, as well as 30-day mortality and 90-day readmission rates when analyzed in aggregate or by culture site. Sensitivity analyses demonstrated similar results using different definitions of infection. CONCLUSIONS:Patients with nonintestinal CRE colonization had outcomes similar to those with CRE infection. Clinical outcomes may be influenced more by culture site than classification as "colonized" or "infected."

Background Splenic abscess is a rare infection often resulting from hematogenous spread. Immunocompromised states are commonly comorbid, and the microbiology is heterogeneous. Methods We conducted a retrospective review of 33 cases identified by convenience sampling. Cases were treated in our institution's hospital system between May 2012 and February 2021 and classified as proven or probable based on predetermined criteria. Results The median age was 57 years, and 58% were men. Common underlying diseases included diabetes mellitus (30%), pancreatic disease (30%), and hematological malignancy (15%). The most common mechanism of pathogenesis was hematogenous spread (n = 13). Escherichia coli, enterococcal spp., and anaerobes were frequently implicated. One case was discovered at autopsy and excluded from subsequent analyses. The median duration of antimicrobial therapy (range) was 45 (5-525) days, and the median length of index hospitalization was 20 days. Percutaneous drainage by interventional radiology was common (17 of 32; 53%), and 6 patients underwent splenectomy. Treatment success was achieved in 14 of 32 cases (44%), with clinical stability in 3 of 32 cases (9%). Failures occurred in 13 of 32 (41%) cases, 2 of whom died from splenic abscesses. Two patients (2 of 32) were lost to follow-up. Conclusions To our knowledge, this is the largest North American series since the turn of the century and the first to distinguish between proven and probable cases. As reflected in our series, patients with splenic abscess may require prolonged hospitalizations and courses of antimicrobial therapy. Improvements in management are needed.

BACKGROUND:Bartonellosis is a rare but challenging condition to diagnose with a spectrum of clinical presentations in the immunocompromised host.AIM:To further characterize the presentation of Bartonella henselae (B. henselae) infections in solid organ and hematopoietic stem cell transplant recipients.METHODS:We conducted a single-center retrospective study of all B. henselae testing for 5012 transplant recipients receiving care at a single institution between 2011 and 2018.RESULTS:We identified 38 patients who underwent testing for B. henselae, and three of 38 were found to have bartonellosis. Two of the patients were renal transplant recipients who presented with visceral bartonellosis and symptoms concerning for post-transplant lymphoproliferative disorder. One autologous stem cell transplant recipient presented with cat scratch disease. We detail the clinical courses of these three cases and review the literature concerning the clinical presentations, differential diagnosis, and limitations of diagnostic tests for B. henselae infections in transplant recipients.CONCLUSION:Although the incidence of B. henselae infection in transplant recipients is unknown, it merits inclusion in the differential diagnosis for fever of unknown origin in this population.

Infectious Disease Images (idimages.org) features several hundred with a vast array of diagnoses. The website is organized by cases and images and boasts an atlas with scores of bacteria, viruses, fungi, parasites, and ectoparasites. As a free resource, Infectious Disease Images lends itself nicely to both learners and educators at all levels.

Background. Pyomyositis is a bacterial infection of skeletal muscle that classically leads to abscess formation. A related, but distinct, entity is infectious myositis. The epidemiology of these infections has changed in recent years. Methods. To better characterize both pyomyositis and infectious myositis, we conducted a retrospective study at our tertiary care institution. We identified 43 cases of pyomyositis and 18 cases of infectious myositis treated between January 2012 and May 2020. Results. The mean age of patients was 48 years, and 66% were male. Diabetes mellitus affected one third of patients, and 16% had other immunocompromising comorbidities. Staphylococcal species accounted for 46% of all infections, and common symptoms included muscle pain (95%) and subjective fever (49%). Altered mental status was a presenting symptom in 16% of cases. Approximately half of all patients received >1 class of antibiotic, and the median length of antimicrobial therapy was 18 days. Open and percutaneous drainage procedures figured prominently in the management of these infections, with 28% of patients requiring multiple procedures. Pathology specimens were available for 12 of 61 cases. Overall, the treatment success rate was 84%. Conclusions. Gram-positive bacteria accounted for most infections at our institution, and management commonly involved open or percutaneous drainage procedures. Future studies that prospectively evaluate treatment strategies for pyomyositis and infectious myositis are warranted.

Members of the genus Nocardia are filamentous, Gram-positive, aerobic bacteria and exist ubiquitously in most environments. In 2001, the species Nocardia veterana was first isolated, and it predominantly causes pulmonary infections in immunocompromised hosts. We present the first report of a soft-tissue abscess caused by N. veterana in a 59-year-old woman being treated for chronic cutaneous graft-versus-host disease. After failing to improve with empirical treatment, two incision and drainage procedures were required. She subsequently completed a 1-year course of oral antibiotic therapy consisting of trimethoprim-sulfamethoxazole then azithromycin. No relapse occurred over the next 5 years of follow up. To better characterize N. veterana infections, we performed a systematic literature review and summarized all previously reported cases. Overall, the rising prevalence of immunocompromising conditions warrants increased vigilance for infections caused by atypical or opportunistic pathogens.

Background: Patients with comorbid conditions have a higher risk of mortality with SARS-CoV-2 (COVID-19) infection, but the impact on heart failure patients living near a disease hotspot is unknown. Therefore, we sought to characterize the prevalence and outcomes of COVID-19 in a live registry of heart failure patients across an integrated health care system in Connecticut. Methods: In this retrospective analysis, the Yale Heart Failure Registry (NCT04237701) that includes 26,703 patients with heart failure across a 6-hospital integrated health care system in Connecticut, was queried on April 16th, 2020 for all patients tested for COVID-19. Sociodemographic and geospatial data as well as, clinical management, respiratory failure, and patient mortality were obtained via the real-time registry. Data on COVID-19 specific care was extracted by retrospective chart review. Results: COVID-19 testing was performed on 900 symptomatic patients, comprising 3.4% of the Yale Heart Failure Registry (N=26,703). Overall, 206 (23%) were COVID-19+. As compared to COVID-19-, these patients were more likely to be older, black, have hypertension, coronary artery disease, and were less likely to be on renin angiotensin blockers (P<0.05, all). COVID-19- patients tended to be more diffusely spread across the state whereas COVID-19+ were largely clustered around urban centers. 20% of COVID-19+ patients died, and age was associated with increased risk of death [OR 1.92 95% CI (1.33-2.78); P<0.001]. Among COVID-19+ patients who were [≥]85 years of age rates of hospitalization were 87%, rates of death 36%, and continuing hospitalization 62% at time of manuscript preparation. Conclusions: In this real-world snapshot of COVID-19 infection among a large cohort of heart failure patients, we found that a small proportion had undergone testing. Patients found to be COVID-19+ tended to be black with multiple comorbidities and clustered around lower socioeconomic status communities. Elderly COVID-19+ patients were very likely to be admitted to the hospital and experience high rates of mortality.

Abstract Background Members of the genus Nocardia are filamentous, gram-positive, aerobic bacteria and exist ubiquitously in most environments. In 2001, the species Nocardia veterana was first isolated, and it predominantly causes pulmonary infections in immunocompromised hosts. Methods We present the first report of a soft tissue abscess caused by N. veterana in a 59-year-old woman being treated for chronic cutaneous graft-versus-host disease. Results After failing to improve with empiric treatment, two incision and drainage procedures were required. She subsequently completed a one-year course of oral antibiotic therapy consisting of trimethoprim-sulfamethoxazole then azithromycin. No relapse occurred. To better characterize N. veterana infections, we performed a systematic literature review and summarized all previously reported cases. Nocardia veterana abscess Conclusion The rising prevalence of immunocompromising conditions warrants increased vigilance for N. veterana infections and other atypical or opportunistic pathogens. Disclosures All Authors: No reported disclosures

A 64-year-old man presented to the emergency department in the summer with intermittent fevers that began 7 weeks after he underwent heart transplantation at that hospital. The patient had a history of ischemic cardiomyopathy for which he had received a HeartMate II left ventricular assist device (LVAD) that remained implanted for 2 years. An infection with coagulase-negative staphylococcus had developed in the drive-line of the device, a finding that led to the patient's name being placed higher on the waiting list for transplantation; before transplantation, he had received long-term treatment with doxycycline for suppression. His initial postoperative course was uneventful. After receiving induction therapy with basiliximab, the patient was treated with mycophenolate mofetil, tacrolimus, and prednisone to prevent allograft rejection. He received trimethoprim-sulfamethoxazole and valganciclovir for prophylaxis against pneumocystis and cytomegalovirus (CMV) infections (the patient and donor were both CMV-seropositive). Four weeks after heart transplantation, an endomyocardial biopsy showed grade 2 acute cellular rejection, which prompted administration of pulse therapy with methylprednisolone for 3 days and increased maintenance doses of immunosuppressive therapy. His treatment with tacrolimus was changed to cyclosporine because of tremors. Seven weeks after transplantation, he began to have intermittent high fevers with temperatures of up to 40 degrees C, along with chills, nausea, and headaches.

BACKGROUND:Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short-term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized.METHODS:To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous-flow LVADs placed between August 2007 and July 2019.RESULTS:A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48-2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy.CONCLUSIONS:Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression.

Context.—Direct visualization of Pneumocystis jiroveci organisms, using Gomori methenamine silver (GMS) staining in bronchoalveolar lavage fluid (BAL), is a historical gold standard that has been widely used for the diagnosis of P jiroveci pneumonia (PJP). However, the stain may be less sensitive in human immunodeficiency virus (HIV)–negative immunocompromised patients owing to a lower burden of organisms.Objectives.—To assess the sensitivity of the GMS stain on BAL fluid for the diagnosis of PJP in HIV-negative immunocompromised patients as compared to HIV-positive patients.Design.—We conducted a retrospective review from 2012 to 2018 to identify immunocompromised patients (≥18 years old) who underwent bronchoscopy with BAL GMS staining for the diagnosis of PJP. To assess for sensitivity, we sought to identify BAL GMS-positive cases and BAL GMS-negative cases of PJP. The BAL GMS-negative cases were categorized into proven and probable PJP.Results.—We identified 45 adult immunocompromised patients with proven and probable PJP, including 24 HIV-negative (11 BAL GMS-positive and 13 BAL GMS-negative) and 21 HIV-positive cases (all were BAL GMS-positive). The sensitivity of BAL GMS for the diagnosis of PJP in HIV-negative immunocompromised patients was 11 of 24 (46%) versus 21 of 21 (100%) in HIV-positive patients (CD4: median, 10 cells/mL; range, 3–300 cells/mL). Delayed or missed diagnoses were seen in 3 cases of BAL GMS-negative PJP. Re-examination of BAL GMS slides showed rare P jiroveci cysts in 1 case.Conclusions.—BAL GMS has poor sensitivity for PJP in HIV-negative immunocompromised patients. Using BAL GMS as a sole method for PJP may result in missed or delayed diagnoses in this population.

Left ventricular assist devices (LVADs) are integral for the management of medically refractory heart failure, and LVAD infections are common following device placement. Most infections are caused by Staphylococcal spp. and Gram-negative enteric bacteria but nontuberculous mycobacterial (NTM) infections have been reported. We present the second-ever reported case of a driveline infection caused by Mycobacterium fortuitum in a 75-year-old male with a continuous-flow LVAD. After receiving meropenem, azithromycin, and ciprofloxacin, he underwent device exchange and ultimately died after failing to recover neurologically. Management of NTM infections presents a clinical challenge due to the propensity for rapidly growing mycobacterial species to form biofilms and the possibility of negative cultures delaying diagnosis. To address the literature gap surrounding NTM infections in LVAD patients, we performed a systematic review and present all previously reported cases.

Cutaneous leishmaniasis (CL) is a common disease affecting millions in endemic areas worldwide. We present a case of lupoid leishmaniasis, a rare variant of CL, which clinically mimicked sarcoidosis and/or granulomatous rosacea for 10 years until ultimate diagnosis. An 82-year-old U.S. citizen with an extensive travel history presented with a 10-year history of facial plaques on the cheeks and was previously diagnosed and treated as sarcoidosis. Multiple biopsies (previously and at presentation) revealed tuberculoid granulomas with negative special stains for microorganisms and negative sterile tissue cultures for acid-fast bacilli, bacteria, and fungal organisms. A diagnosis of granulomatous rosacea was rendered and multiple medical therapies were attempted, none with sustained improvement. Repeat biopsy of a new lesion revealed intracellular organisms consistent with leishmaniasis, which was confirmed by polymerase chain reaction (PCR). Lupoid leishmaniasis is a rare presentation of CL including facial plaques that can mimic granulomatous diseases affecting the face including sarcoidosis and granulomatous rosacea. CL can sometimes be challenging to diagnose through standard histopathologic examination; immunohistochemistry for CD1a can be used to augment tissue-based examination and PCR should be sent early in cases with sufficient concern.

Infective endocarditis classically involves non-sterile vegetations on valvular surfaces in the heart. Feared complications include embolization and acute heart failure. Surgical intervention achieves source control and alleviates valvular regurgitation in complicated cases. Vegetations >1 cm are often intervened upon, making massive vegetations uncommon in modern practice. We report the case of a 39-year-old female with history of intravenous drug abuse who presented with a serpiginous vegetation on the native tricuspid valve and methicillin-resistant Staphylococcus aureus bacteremia. The vegetation grew to 5.6 cm by hospital day two, and she successfully underwent a tricuspid valvectomy. Six weeks of intravenous vancomycin therapy were completed without adverse events. To better characterize other dramatic presentations of infective endocarditis, we performed a systematic literature review and summarized all case reports involving ≥4 cm vegetations.

Left ventricular assist devices (LVADs) are used in patients with advanced heart failure. Infections are common complications following device placement; however, the efficacy of chronic antimicrobial suppression therapy for deep-seated infections is not well characterized. We report the case of a 49-year-old male with a HeartMate II LVAD who presented with a methicillin-sensitive Staphylococcus aureus pump pocket infection that was subsequently treated with antibiotics and HeartMate III pump exchange. A vancomycin-resistant Enterococcus faecium (VRE) pump pocket infection then developed and responded to surgical drainage followed by long-term suppression with daptomycin then linezolid for over 870 days. A second pump exchange was not required. To our knowledge, this represents the longest reported use of daptomycin (341 days) without symptomatic adverse events. Managing infections caused by multidrug-resistant pathogens presents a clinical challenge. This case demonstrates the potential for antimicrobial suppression therapy to allow for successful retention of a VRE-infected LVAD.