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In a 3-year cohort study of adult patients with proven or probable IA, fewer patients initially treated with isavuconazole experienced adverse events compared with voriconazole, but more patients required a change in therapy due to lack of clinical efficacy.

BackgroundAntimicrobial resistance (AMR) is a major challenge in the treatment of infections caused by Pseudomonas aeruginosa. Highly drug-resistant infections are disproportionally caused by a small subset of globally distributed P. aeruginosa sequence types (STs), termed “high-risk clones.” We noted that clonal complex (CC) 446 (which includes STs 298 and 446) isolates were repeatedly cultured at 1 medical center and asked whether this lineage might constitute an emerging high-risk clone.MethodsWe searched P. aeruginosa genomes from collections available from several institutions and from a public database for the presence of CC446 isolates. We determined antibacterial susceptibility using microbroth dilution and examined genome sequences to characterize the population structure of CC446 and investigate the genetic basis of AMR.ResultsCC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR, with 51.9% (28/54) being multidrug-resistant (MDR) and 53.6% of these (15/28) being extensively drug-resistant (XDR). Phylogenetic analysis revealed that most MDR/XDR isolates belonged to a subclade of ST298 (designated ST298*) of which 100% (21/21) were MDR and 61.9% (13/21) were XDR. XDR ST298* was identified repeatedly and consistently at a single academic medical center from 2001 through 2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron.ConclusionsCC446 isolates are globally distributed with multiple occurrences of high AMR. The subclade ST298* is responsible for a prolonged epidemic (≥16 years) of XDR infections at an academic medical center. These findings indicate that CC446 is an emerging high-risk clone deserving further surveillance.

Background Experimental human immunodeficiency virus (HIV)-1 vaccines frequently elicit antibodies against HIV-1 that may react with commonly used HIV diagnostic tests, a phenomenon known as vaccine-induced seropositivity/seroreactivity (VISP/VISR). We sought to determine, under clinic conditions, whether a patient-controlled HIV test, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, detected HIV-1 vaccine-induced antibodies. Methods Plasma assessment of HIV-1 cross-reactivity was examined in end-of-study samples from 57 healthy, HIV-uninfected participants who received a candidate vaccine that has entered Phase 2B and 3 testing. We also screened 120 healthy, HIV-uninfected, unblinded HIV-1 vaccine participants with VISP/VISR for an assessment using saliva. These participants came from 21 different parent vaccine protocols representing 17 different vaccine regimens, all of which contained an HIV-1 envelope immunogen. OraQuick ADVANCE was compared with results from concurrent blood samples using a series of commercial HIV screening immunoassays. Results Fifty-seven unique participant plasma samples were assayed in vitro, and only 1 (1.8%) was reactive by OraQuick ADVANCE. None of the 120 clinic participants (0%; 95% confidence interval, 0% to 3.7%) tested positive by OraQuick ADVANCE, and all were confirmed to be uninfected by HIV-1 viral ribonucleic acid testing. One hundred eighteen of the 120 (98.3%) participants had a reactive HIV test for VISP/VISR: 77 (64%) had at least 1 reactive fourth-generation HIV-1 diagnostic test (P, Experimental HIV-1 vaccines frequently elicit antibodies which cross-react with common HIV diagnostic tests. Vaccine-induced seropositivity/seroreactivity (VISP/VISR) can be problematic for clinical trial volunteers. We tested a point-of-care HIV test, OraQuick ADVANCE, to determine if it could detect VISP/VISR.

Immunization with the conjugated quadrivalent (serogroups A, C, Y, and W-135) meningococcal vaccine (MCV4) after hematopoietic cell transplantation (HCT) is recommended. However, immune responses to MCV4 have not been prospectively studied after HCT. We conducted a vaccine response study among 67 adults who received 1 MCV4 dose a year after autologous or allogeneic HCT from January to September 2014. Pre- and postvaccination serogroup serum bactericidal antibody (SBA) titers were measured a median of 57 days after vaccination. Serogroup-specific responses were defined as a fourfold increase in SBA titer with postvaccination titers ≥1:8. Prior to vaccination, 44 (65.7%) patients had no protective titers (

Attenuated live virus vaccinations are generally recommended 24 months following hematopoietic cell transplantation (HCT) in patients not receiving immunosuppressive therapy. To date, there are no data regarding the safety of live-attenuated herpes zoster or measles-mumps-rubella (MMR) vaccinations in multiple myeloma patients on maintenance lenalidomide or bortezomib following autologous HCT. One hundred thirty-seven multiple myeloma patients on maintenance lenalidomide or bortezomib post-auto-HCT who received either MMR or herpes zoster vaccine were analyzed and any adverse events documented in the medical record in the 42 days following vaccination were recorded. Patients were vaccinated a median of 25 months (range, 18-62) post transplant. The most common post-vaccination adverse event was upper respiratory tract infection (18/137 patients); no rash attributed to vaccine strains or other adverse outcomes potentially related to the vaccines were identified. MMR and herpes zoster vaccination were safe and well-tolerated in this cohort.

TO THE EDITOR: Certain therapies for hematologic malignancies, including anti-CD20 monoclonal antibodies and allogeneic hematopoietic cell transplantation (allo-HCT), are associated with increased risk of hepatitis B virus (HBV) reactivation in patients previously infected with HBV.[1][1],[2][2]

The Gram-negative bacterium Pseudomonas aeruginosa is often multidrug resistant, associated with global epidemic outbreaks, and responsible for significant morbidity and mortality in hospitalized patients. Here, we present the draft genome sequence of BWH047, a multidrug-resistant P. aeruginosa clinical isolate belonging to the epidemic sequence type 235 and demonstrating high levels of colistin resistance.

Key Points Graft-versus-host effects may lead to HIV-1 reactivation and cell death of infected pre-HCT CD4+ T cells. Natural killer cell activation correlates with in vitro HIV-1 transcriptional activity in the setting of HCT.

Background HSV reactivation is a challenging complication of HM and HCT. ACV prophylaxis effectively decreases the incidence of symptomatic HSV episodes, but may contribute to development of ACV-R HSV disease in this population. Outcomes in patients with ACV-R HSV disease remain poorly characterized. Methods We identified adult HM patients and HCT recipients treated at Dana-Farber Cancer Institute who developed clinically significant ACV-R HSV disease between January 1, 2006 and March 1, 2018. HCT recipients typically receive 1 year of ACV prophylaxis after HCT, or longer in those with graft-vs. host disease. Clinical, microbiological and treatment details were collected. Results Nineteen patients had 27 episodes of ACV-R HSV disease during the study. Median age was 50 years (range 31–77); 15 (79%) were men. Fifteen (79%) were allogeneic HCT recipients and 4 (21%) had HM (3 CLL, 1 NHL). Thirteen (68%) had oral ulcers (HSV1), four (21%) had perineal ulcers (3 HSV2, 1 HSV1), one had HSV1 vesicles on the trunk and one had concurrent oral HSV1 and perineal HSV2 ulcers. Three patients had recurrent ACV-R HSV: two had one recurrence each and one had six recurrences. Of 19 first episodes of ACV-R HSV, 15 (79%) were confirmed by culture-based phenotypic resistance testing. Most episodes (20/27, 74%) were treated with foscarnet at clinical diagnosis or after failure of high-dose val-ACV; four of these episodes were also treated with topical cidofovir without success before foscarnet. Three episodes resolved on high-dose val-ACV or IV ACV alone and three were treated with cidofovir or brincidofovir initially. Coinfection was present in 19 episodes (70%), most often bacterial pneumonia or blood stream infection. Twenty-two episodes (81%) resolved completely after a median of 36 days (range 10–88) of treatment. No patient died of HSV disease but five (26%) died before resolution of ACV-R HSV, a median of 25 days (range 1–117) after treatment started. Eight patients died after ACV-R HSV resolved, a median of 111 days (range 27–382) after treatment started. Among HCT recipients, six (37%) died within 12 weeks of diagnosis. Conclusion ACV-R HSV disease is an uncommon complication of HM and allogeneic HCT. While ACV-resistant HSV did not cause death in this cohort, death within 12 weeks of infection was common. Disclosures N. C. Issa, GSK: Investigator, Research grant; Merck: Investigator, Research grant; Akros Pharma: Consultant, Consulting fee. F. M. Marty, Chimerix: Consultant and Investigator, Consulting fee and Research support. S. P. Hammond, Merck: Investigator, Research support.