Razonable, Raymund R.

Abstract In this cohort of 51 patients managed with retained “destination spacers” after the resection of infected joint prostheses, the presence of preoperative sinus drainage was significantly associated with reinfection. Chronic antimicrobial suppression after destination-spacer retention did not significantly prevent reinfections.

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015.

Abstract Background Current guidelines preferentially recommend valganciclovir (VGCV) prophylaxis over PET in most D+R− organ transplant populations, but adequately powered direct comparative clinical trials are lacking. Methods D+R− LTR were randomly assigned (1:1, stratified by site and T-cell depleting induction) to receive either PET (weekly plasma CMV DNAemia at central laboratory for 100 days, with VGCV 900 mg bid for DNAemia at any level, until two consecutive negative weekly tests) or prophy (VGCV 900 mg qd for 100 days). The primary outcome was CMV disease by 12 months as adjudicated by an independent, blinded, endpoint committee in ITT population. Secondary outcomes were opportunistic infections (OIs) (invasive fungal and bacterial), neutropenia (ANC < 1000/µL), acute rejection, graft loss, and mortality assessed at12 months. Results From October 2012 to June 2017, 205 patients were randomized at six centers; 100 to PET, 105 to prophy. The incidence of CMV disease was 9% (9/100) in PET and 19% (20/105) in prophy (P = 0.039) with majority of difference due to post-prophylaxis disease: 6% in PET vs. 17% in prophy (P = 0.027). CMV disease included syndrome in 55% (16/29) and end-organ in 45% (13/29), with similar proportions in two groups. Secondary outcomes were not different for PET and prophy groups: OIs (19% vs. 21%), neutropenia (34% vs.. 28%), acute rejection (27% vs. 27%), graft loss (2% vs. 2%), and mortality (10% vs. 6%), respectively, P > 0.05 for all comparisons. Mortality at last follow-up (median 3.2 years) was not different for PET vs. prophy (14% vs. 18%, P = 0.43). Conclusions PET significantly reduced the incidence of CMV disease compared with prophy in D+R- LTR, and was associated with similar other clinical outcomes. Current guidelines should be revised to recommend PET over prophylaxis in this setting, and similar trials conducted in other D+R− transplant populations. (Funded by NIAID; ClinicalTrials.gov# NCT01552369.) Disclosures D. Winston, Merck: Investigator, Research support. Chimerix: Investigator, Research support. Shire: Investigator, Research support. Gilead: Investigator, Research support. Oxford Immunotech: Investigator, Research support. G. M. Lyon III, Shire: Investigator, institutional research support. Hookipa: Investigator, institutional research support. Merck: Investigator, institutional research support. F. P. Silveira, Shire: contracted clinical research, site investigator. A. P. Limaye, Merk: Consultant and Investigator, Consulting fee and Research grant. Astellas Pharma Inc.: Consultant and Investigator, Consulting fee. Helocyte Inc.: Consultant, Consulting fee.

AbstractBackgroundMycobacterium tuberculosis (TB) is common worldwide, but is rarely reported after hematopoietic transplantation (HSCT). We reviewed all TB cases among HSCT since 2010 to provide an update on its epidemiology, clinical presentation, management and outcome.MethodsSeveral databases were reviewed from January 1, 2010 to June 30, 2018 using key words tuberculosis and hematopoietic transplantation.ResultsThe 47 cases of TB were reported during the study period. The highest TB frequency was reported from India (2.9%), with a median frequency of 2% (range, 0.18%‐2.9%). The majority were recipients of allogeneic transplants (45/47, 95.7%). Pulmonary TB was the most common clinical presentation (20/47, 42.6%). The median time to clinical presentation was 4.6 (range, 3‐12.9) and 2.4 (range, 0.6‐5) months, based on cohort data and case reports, respectively. Fever was reported in 87.5% (14/16) of patients. First‐line quadruple drug therapy was frequently used (29/35, 82.9%), with a median length of 12 and 9 months for cohorts and case reports, respectively. All‐cause and attributable mortality was 27.6% (13/47), and 8.5% (4/47), respectively.ConclusionsMycobacterium tuberculosis presents early after HSCT, most commonly as fever. A high index of suspicion is needed for early diagnosis and treatment, to prevent TB‐attributable mortality.