Onc and transplant ID: October 2018

Pretransplant CMV-specific T-cell function predicts who will develop CMV disease after solid organ transplantation. This was a prospective study including 135 solid organ transplant recipients with prior CMV infection. The patients had their CMV-specific cellular immunities quantified by an intracellular cytokine staining assay before transplantation, and their CMV viral loads measured by PCR afterward. Patients without pretransplant T-cell immunity trended toward having more CMV infection (53% vs 36%; p=0.07), and CMV-specific immunity was found to be protective against developing a viremia >2,000 IU/ml (OR 0.28; p<0.01) and against developing CMV disease (0% vs 9%; p = 0.05).

So, cellular immunity-based assays might be another way to risk-stratify patients undergoing SOT and safely make more judicious use of CMV prophylaxis. But honestly, that’s kind of a boring conclusion. The real reason I mention this article is because it demonstrates the correlation between CMV-specific T-cell function and protection from CMV disease. Makes you wonder – could you infuse third party, off-the-shelf CAR-T cells into SOT recipients before or after transplantation in order to prevent CMV disease? This isn’t economically feasible now, but if it became so perhaps we could make CMV a transplant complication of the past. 30292792

Well that didn’t take long: first report of letermovir resistance emerging in a lung transplant recipient with ganciclovir-resistant CMV. A lung transplant recipient developed ganciclovir-resistant CMV harboring UL97 mutation as well as a new UL54 mutation conferring resistance to both ganciclovir and cidofovir. The patient was treated with foscarnet, but failed valganciclovir secondary prophylaxis afterward, so he started therapy with letermovir. The patient’s viral load slowly dropped below the limit of quantitation over 5 weeks, but then began increasing again - at that point a new CMV genotype was done and showed the UL56 mutation C325Y, conferring high-grade resistance to letermovir. Resistance isn’t futile; it’s inevitable. 30286286

Hospital linens carry Mucorales (AKA the world is not sterile: cancer center edition). The context for this study is that three outbreaks of hospital-associated mucormycosis in highly immunocompromised patients have been traced back to either linens or laundry carts, that standards for linen hygiene are not proscribed/enforced by health organizations or particularly well rooted in clinical data, and that mucormycosis in the immunocompromised carries a mortality rate >50%. The investigators met linen delivery trucks at fifteen cancer and transplant centers and performed fungal contact cultures on freshly-laundered linens (i.e., the linens were pressed against a plate of fungal media and then the plate was incubated).

The authors found that 33% of “fresh” linens were visibly soiled with dirt, hair, or insects; supplementary figures A-D are, quite literally, an airing of these hospitals’ dirty laundry.  Mucorales was isolated from linens at 47% of the hospitals, and the prevalence of contamination ranged from 0-24%. Investigators at one facility worked with their laundry staff to have the laundry carts cleaned and “lint control measures” instituted (whatever that means). After these steps, just 1/49 samples from 1/6 sampling dates grew Mucorales.

Using visibly soiled linens in your cancer and/or transplant center is probably a bad idea, if for no other reason than the preservation of your institution’s reputation. But is surveillance and remediation of linen hygiene the best use of infection control funds? I wonder. It’d be nice to see this research group do a before-after study where they clean up the laundry room’s act at each hospital and then see if rates of healthcare-associated mucormycosis change. My bet is that even if you get rid of the Mucorales on the bedsheets, it’s still everywhere else in the hospital, and that anything short of autoclaving the whole building and everyone in it is unlikely to meaningfully reduce the incidence of what is already one of the rarer nosocomial infections. But maybe I’m just a pessimist. 30299481

Speaking of bedsheets (didn’t think I was gonna be able to segue from that one, did you?), an article in this month’s ICHE reports that C. difficile spores on linens survive commercial washing and may be a vector for nosocomial outbreaks of CDI. The authors inoculated the organism onto sheets and then performed “simulated laundering” using an industrial bleach detergent containing sodium hypochlorite, acetic acid and hydrogen peroxide; they also took sheets from patients with CDI, sent the sheets to a commercial launderer, and then cultured the remaining spores. Lo and behold, two of the C. difficile strains tested survived the simulated laundering with bleach, and commercial washing of the naturally contaminated bedsheets reduced the viable spore count by less than 40%! OK, so maybe the laundry rooms need autoclaves after all. 30322417

Patients receiving chemotherapy carry an excess risk of mortality for up to six months after an episode of febrile neutropenia. This paper from OFID followed adults receiving first-line chemotherapy from 6 months after initiation of the chemotherapy until either their first infection, next chemotherapy, or death. A total 7190 patients were followed for a median 7 months, during which 1370 patients developed an infection. Both a single and multiple febrile neutropenia episodes were associated with increased risk of subsequent infection (aIRR 1.9, 95% CI 1.6-2.2 and aIRR 2.2, 95% CI 1.5-3). Mortality rates were statistically significantly elevated in the first 30 days (aIRR 7.5), 1-3 months (aIRR 4.2), and 3-6 months (aIRR 2.3) after an episode of febrile neutropenia; after six months the difference in mortality was no longer significant.

Part of me wonders if this finding represents survival bias – that is, maybe febrile neutropenia isn’t associated with increased risk after six months because by six months all the people who were going to get an infection and/or die have already gotten an infection or died. Still, it’s interesting that an increased risk for death remains in the 1-3 months following chemotherapy, at which point the patient’s neutropenia presumably would have resolved. 30377628