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A 44-year-old woman undergoing therapy for acute promyelocytic leukemia (APL) developed disseminated tuberculosis. Mycobacterium tuberculosis (TB) was isolated from the blood and sputum. Initial drug susceptibility testing (DST) of the blood isolate revealed resistance to isoniazid and ethambutol but the sputum isolate showed no resistance. Due to drug resistance concerns, the patient was treated with multiple second and third-line drugs, and suffered from drug side effects. To further investigate the DST discrepancies, whole genome sequencing (WGS) was performed on both isolates. No known resistance mutations to first line or second line drugs were identified in either isolate, which was confirmed by additional susceptibility testing performed by a different reference laboratory and the California Department of Public Health (CDPH) laboratory. Treatment was reduced to a simpler and less toxic regimen due to these investigations. WGS is shown to be a valuable tool for resolving discordant phenotypic DST results of TB isolates and has the potential to provide accurate and timely results guiding appropriate therapy in the clinical setting.

Nocardial infections have been rare after allogeneic hematopoietic stem cell transplantation (HSCT). We report 10 recent cases of late-onset nocardiosis (median time of onset of 508 days after transplantation) primarily in patients on high doses of corticosteroids for graft-versus-host disease. All 10 patients had pulmonary infection caused by Nocardia species susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). At time of diagnosis 8 of 10 patients were not receiving TMP-SMX for prophylaxis of Pneumocystis jiroveci pneumonia (PJP; 7 on atovaquone, 1 on i.v. pentamidine). After the initiation of atovaquone prophylaxis for PJP in place of TMP-SMX for many UCLA allogeneic HSCT patients in 2012, 9 cases of nocardiosis occurred in 411 patients (2.2%) over the next 6 years (2012 to 2017) compared with only 1 case in 575 patients (0.17%) during the previous 12 years (2000 to 2011). Although there were no deaths directly related to nocardial infection treated primarily with TMP-SMX, overall mortality in this group of patients was 40%. Based on this experience, the use of atovaquone for PJP prophylaxis in place of TMP-SMX may be associated with an increased risk for previously rare nocardial infections after allogeneic HSCT.

BackgroundThe utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain.MethodsAs part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs.ResultsOverall, 46.4% of the patients at baseline had positive GM (index ≥ 0.5) and 89.6% had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100% (12/12) of the patients with IFI had positive baseline BG and as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P < 0.001).ConclusionsThe GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.