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People who inject drugs (PWID) presenting with injection drug use-associated infections are an understudied population excluded from most prospective infectious disease (ID) clinical trials. Careful application of the existing ID literature to PWID must consider their unique medical, psychological, and social challenges. Identification and treatment of the underlying substance use disorder are key underpinnings to any successful ID intervention.

Progressive multifocal leukoencephalopathy (PML), presenting as immune reconstitution inflammatory syndrome (IRIS), is a known complication of antiretroviral therapy (ART) in people living with HIV (PLWH). Typically preceded by ART initiation, IRIS may appear simultaneously/unmasked (PML-s-IRIS) or as a delayed/worsening/paradoxical (PML-d-IRIS) presentation of known PML disease. Primary cerebellar tropism continues to be a rare presentation, and paradoxical cerebellar involvement of PML-IRIS syndrome can be a challenge for both diagnosis and management. Steroids have been suggested as a possible therapy in severe cases but the duration of steroid therapy remain elusive. Our case is that of a 34-year-old man with newly diagnosed HIV simultaneously found to have cerebellar PML. His PML lesions however worsened after initiation of ART (PML-d-IRIS) with evidence of increased intracranial pressure. Despite initial favorable response to a short duration of steroids, he had multiple recurrence of his PML lesions after steroids were discontinued. The presence of predominant cerebellar lesions and the question of how long steroids should be provided to prevent or minimize PML recurrence is the highlight of our case. This report emphasizes the need for more controlled studies to assist clinicians in the optimal diagnosis and management of PML-IRIS in PLWH.

Flea-borne typhus (FBT), although usually perceived as a self-resolving febrile illness, actually encompasses a wide spectrum of disease severity, including fulminant sepsis with multi-organ failure. In endemic Texas and California, the incidence of FBT has more than doubled over the last decade. Clinicians remain unfamiliar with severe septic presentations of FBT when considering the etiologies of acute undifferentiated febrile syndromes. The diagnostic challenges of FBT include the nonspecific and variable nature of both history and physical examination and the lack of diagnostic testing that can provide clinically relevant information early in the course of infection. These barriers perpetuate misdiagnoses in critically ill patients and lead to delay in initiating appropriate antibiotics, which may contribute to preventable morbidity and mortality. This case series describes the clinical and diagnostic trajectories of three patients who developed FBT-associated multi-organ dysfunction. These patients achieved resolution of infection after receiving doxycycline in the context of a high clinical suspicion. Patients residing in FBT-endemic areas presenting with a febrile illness of unknown etiology with a suggestive constellation of hyponatremia, elevated transaminase levels, and thrombocytopenia should be suspected of having FBT. Clinicians should proceed to serologic testing with early doxycycline therapy for potential rickettsiosis. Familiarizing clinicians with the presentation of rickettsiosis-associated septic syndromes and its early and appropriate antibiotic treatment can provide lifesaving care and reduce health-care costs through prevention of the morbidity associated with FBT.

Introduction Toxoplasma gondii DNA can be detected by polymerase chain reaction (PCR) in up to 16% of hematopoietic cell transplant (HCT) patients post-transplant with attributable mortality of 44-66%. The majority (73-87%) of cases result from reactivation in previously exposed (i.e., Toxoplasma seropositive) recipients and most (67-87%) occur in patients not receiving effective prophylaxis. Clinical data on the efficacy of atovaquone for primary prophylaxis of toxoplasmosis following HCT is scarce. Reports of breakthrough toxoplasmosis in patients receiving atovaquone have raised concerns about its efficacy in high-risk patients such as donor positive (D+)/recipient negative (R-) heart transplant and R+ allogeneic HCT recipients. Objectives We describe three HCT patients with breakthrough toxoplasmosis while receiving atovaquone prophylaxis. Methods & Results We identified 126 (94 allogeneic and 23 autologous) HCT patients (August 2016-June 2019) who received atovaquone for Pneumocystis jirovecii pneumonia (PJP) prophylaxis. Seroprevalence among allogeneic HCT recipients with known Toxoplasmaserostatus (n=84) was 37%. Among 31 Toxoplasma seropositive allogeneic HCT recipients, 14 received atovaquone as initial prophylaxis and 17 received only after developing intolerance to trimethoprim-sulfamethoxazole (TMP-SMX). Three (10%) patients had breakthrough Toxoplasma reactivation, two of them with central nervous system (CNS) disease. Median time to reactivation was 66 (range, 52-67) days post-transplant. In the two cases with positive PCR in blood, Toxoplasma DNA became undetectable at 8 and 20 days of therapy, suggesting that parasitemia can be successfully managed with preemptive treatment. All three patients died. Death of patient #2 was suspected to be due to disseminated toxoplasmosis as PCR blood was positive at time of death. Median time to death from diagnosis of Toxoplasma reactivation was 83 (range, 57-311) days. CMV viremia preceded Toxoplasmareactivation in all cases; CMV may have impacted infection risk . All three patients underwent T cell depletion during conditioning. Absolute and CD4 lymphopenia at the time of diagnosis were a shared feature in these cases (median ALC: 176/mm3). Conclusion Breakthrough toxoplasmosis is a potentially fatal complication in HCT patients receiving atovaquone prophylaxis. TMP-SMX should remain the prophylactic agent of choice and PCR-based pre-emptive therapy should be considered in the pre-engraftment period and in patients at risk not receiving TMP-SMX. Such preventive strategies could improve outcomes in vulnerable Toxoplasma seropositive HCT recipients.

Lyme disease remains the most common vector-borne disease in North America. This academic teaching case highlights a full diagnostic workup fueled by anchoring bias, resulting in a presumptive diagnosis of early disseminated Lyme meningitis. Patient report of direct tick exposure, neurocranial defects, and equivocal serologies, despite geographic region of low pretest probability, confounded the clinical picture. Infectious workup confirmed the true diagnosis to be aseptic meningitis due to enterovirus. This clinical vignette acknowledges the habitual anchoring biases in the daily decision-making among internists and trainees contributing to misdiagnoses and subsequently, overtreatment.

Background The opportunistic parasite Toxoplasma causes life-threatening complications in immunocompromised hosts such as hematopoietic cell transplantation (HCT) recipients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the agent of choice in preventing Pneumocystis jirovecii pneumonia and Toxoplasma, but bone marrow suppression often precludes its use. Broad-spectrum atovaquone also targets protozoan tachyzoite and cyst forms, but few studies examine its efficacy in prophylaxis among this vulnerable population. We present two HCT patients experiencing breakthrough toxoplasmosis despite compliance with atovaquone prophylaxis. Methods Review of literature and electronic medical records. Results Case 1. A 68-year-oldToxoplasma seropositive woman with myelodysplastic syndrome underwent Flu-Mel-ATG-matched unrelated donor HCT. On day +68 post HCT, she presented with encephalopathy. MRI brain revealed solid and ring-enhancing lesions correlating with positive CSF T. gondii PCR. Serum DNA PCR was negative. She received 12 weeks of sulfadiazine, pyrimethamine, and leucovorin with clinical and radiological improvement. Atovaquone prophylaxis was restarted given pancytopenia intolerance of TMP-SMX. Despite compliance, she experienced recurrent central nervous system toxoplasmosis. Her demise followed an unrelated ischemic cerebrovascular accident. Case 2. A 53-year-old Toxoplasma seropositive woman with CMV viremia and severe aplastic anemia limiting TMP-SMX use presented with pancytopenia on day +46 after HCT. Diagnosed with graft failure, routine screening revealed positive Toxoplasma PCR while on atovaquone prophylaxis. Toxoplasma PCR became negative after preemptive therapy. She underwent a second Flu-Cy-ATG-TBI-matched related donor HCT. 2 months later, medication noncompliance led to readmission with CMV viremia and culture-negative sepsis. Blood Toxoplasma PCR was positive at the time of death. Conclusion Toxoplasmosis prophylaxis failure can occur in allogeneic HCT recipients receiving atovaquone. When possible, TMP-SMX should remain first-line agent for this indication. In those unable to tolerate TMP-SMX, close clinical and Toxoplasma PCR monitoring may help identify reactivation and facilitate early initiation of therapy. Disclosures All authors: No reported disclosures.