February 2019: Onc and transplant ID
Transplant-and-treat looks like a viable strategy for HCV-infected donor hearts. This was a small (n=10), single arm trial looking at outcomes of orthotopic heart transplant from an HCV-positive donor to an HCV-negative recipient, followed by HCV treatment. Patients using LVADs or with liver disease were excluded from the trial, and only hearts from donors with a genotype 1 HCV infection were eligible. Twenty patients enrolled in the trial and 10 ended up getting an HCV-infected heart; the median wait time from study consent to transplant was 39 days. All ten patients had positive HCV RNA levels following transplantation and all ten experienced a rapid decline in HCV levels after starting treatment with elbasvir/grazoprevir. Nine patients reached SVR12; the one non-success was due to the patient going into antibody-mediated rejection, multi-organ failure and death on posttransplant day 79; this was not deemed related the patient’s HCV or HCV treatment. No serious adverse events attributable to HCV treatment occurred, and the authors concluded that HCV positive-to-negative orthotopic heart transplantation is a viable strategy. 30768838
When Stenotrophomonas maltophilia infection causes hemorrhagic pneumonia in cancer patients, it’s bad news. You tend not to see much steno outside of cancer hospitals, because it usually only shows up in patients who’ve had their normal flora carpet-bombed by repeated courses of broad-spectrum antibiotics. Moreover, when it does show up it’s often as a benign colonizer of urinary catheters that ought to have been taken out already. But, occasionally we see invasive infections due to S. maltophilia, most often line-associated bacteremias, and (in part because of the patient populations in which they occur) these infections can have dire outcomes.
Hemorrhagic pneumonia is a characteristic manifestation of invasive S. maltophilia infection. In this study, the authors retrospectively examined 118 cases of S. maltophilia bacteremia seen at their large academic medical center over a ten-year period. The mean age was 56, most patients had an underlying leukemia (69%), and just over half of the cancers represented either refractory or recurrent disease. Most patients had either a catheter-related infection (43%) or pneumonia (47%), and 20/118 (17%) had hemorrhagic pneumonia. Most of the patients who developed hemorrhagic pneumonia had an acute leukemia (74%), most often AML; most either had gone allogeneic stem cell transplant (40%) or had refractory/recurrent disease (42%); and nearly all were neutropenic (94%).
The 30-day mortality rate was 61% overall, but 95% among the patients with hemorrhagic pneumonia, which of course was associated with death in multivariate analysis (OR 106; p=0.002). Compared with other types of infection, non-hemorrhagic pneumonia was also meaningfully associated with an elevated risk of death (OR 9.8; p=0.002). The only protective factor identified in multivariate analysis was empirical use of trimethoprim-sulfamethoxazole within 72hr of symptom onset (OR 0.07; p=0.007). Ninety-six percent of patients who died did so within a week of infection diagnosis; the median time to death was two days.
So, beware invasive S. maltophilia infections in your sickest-of-the-sick oncology patients, particularly S. maltophilia pneumonia and especially its hemorrhagic form. The prognosis is bad, but thinking about the diagnosis and giving TMP/SMX at the earliest consideration will give your patient their best shot at a good outcome. 30421302
Ciprofloxacin prophylaxis does not prevent BK viremia in renal transplant recipients. Yes, ciprofloxacin has some in vitro activity against BK virus. But the clinical data has consistently shown that, like “fetch,” ciprofloxacin for BK virus isn’t going to happen. This was a double-blind RTC randomizing 200 renal transplant recipients 2:1 to receive either three months of ciprofloxacin prophylaxis or placebo after their transplants to prevent BK viremia. The outcome of interest was the presence of BK viremia six months after transplantation. Believe it or not, ciprofloxacin prophylaxis actually led to higher rates of BK viremia at six months out! (19% vs 8%; p=0.03). More importantly, ciprofloxacin prophylaxis was associated with a higher rate of quinolone-resistant Gram-negative infections (83% vs 50%; p=0.04). Ciprofloxacin for BK virsues isn’t going to happen. Researchers should stop trying to make it happen. 30811872
How common are invasive fungal infections in lung transplant patients? This was a single-center prospective study. The authors collected clinical data on all patients undergoing lung transplantation at the Duke University medical center over a 7-year period. They focused on invasive fungal infections (IFIs) in the 180 days after transplant. Of note, the hospital’s standard antifungal prophylaxis regimen consisted of aerosolized amphotericin B, administered during hospitalization.
A total 156/815 (19%) of lung transplant recipients developed an IFI. The prevalence of invasive candidiasis was 11% and of non-Candida IFI was 8%; the invasive Candida infections occurred earlier than the non-Candida IFIs (median 31 vs 86 days). Seventy-two percent of the IFIs occurred while the patient was not taking antifungal prophylaxis; the remaining cases included breakthrough infections due to both Candida and other fungi, and were mostly associated with micafungin (n=16) and aerosolized amphotericin B (n=24).
Given the high rates of IFI in this cohort, including a non-Candida infection prevalence of nearly 10% and a Candida infection prevalence exceeding 10%, systemic antifungal therapy is clearly indicated after lung transplantation. As most Candida infections occurred in the early postoperative period, the authors suggest that Candida prophylaxis need only be continued for 90 days; antimold prophylaxis, on the other hand, they suggest be continued for at least six months. 30801642