Bronchopulmonary penetration of isavuconazole in lung transplant recipients.

Isavuconazole's (ISA) pharmacokinetics was studied among lung transplant recipients to evaluate its bronchopulmonary penetration. This study included 13 patients and showed mean serum concentrations of 3.30 (standard deviation [SD] 0.45), 5.12 (SD 1.36), and 6.31 (SD 0.95) at 2 h, 4 h, and 24 h respectively. Mean concentrations in the epithelial lining fluid were 0.969 (SD 0.895), 2.141 (SD 1.265), and 2.812 (SD 0.693) at the same time points. ISA is a drug with a tolerable safety profile that achieves adequate concentrations in the lung.

Interrupted versus continuous suture for bronchial anastomosis in lung transplantation: does it matter?

OBJECTIVES: Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) by analysing airway complications requiring intervention. METHODS: Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side. RESULTS: A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% [95% confidence interval (CI): 2.8-8.6] per patient (14/245) and 3.7% (95% CI: 2.0-5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 [95% CI: 1.1-12.3], P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients. CONCLUSIONS: In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.

Peripheral blood eosinophilia as a marker of acute cellular rejection in lung transplant recipients.

Previous studies in solid organ transplantation have shown a relationship between circulating eosinophil (EOS) counts and the presence of acute cellular rejection (ACR). However, the relationship between this potential biomarker and ACR in lung transplant (LTx) patients remains unclear. OBJECTIVE: To assess the association between EOS and the presence of acute cellular rejection in lung transplant recipients. MATERIALS AND METHODS: Retrospective study of 583 transbronchial biopsies (TBB) performed in 256 lung transplant patients between 2012 and 2018. We analyzed age, sex, underlying pathology, date of transplant, indications for TBB, presence and degree of ACR, and the simultaneous absolute and relative EOS. RESULTS: ACR were observed in 170 of 583 TBB (29.2%). EOS in patients with ACR were higher than in patients without ACR (203.6 ± 248/mm3 vs 103.1 ± 153/mm3; p < 0.001). High levels of both absolute and relative EOS were associated with the presence of ACR regardless of the underlying disease (odds ratio [OR] 1.003; 95% confidence interval [CI], 1.002-1.004; OR 1.226; 95% CI, 1.120-1.342) and time after transplant (OR 1.003; 95% CI, 1.002-1.004 and OR 1.239; 95% CI, 1.132-1.356). Moreover, both absolute and relative EOS were strongly associated with moderate and severe grades of ACR (OR 3.55; 95% CI, 3.00-4.10 and OR 3.56; 95% CI, 3.00-4.12). CONCLUSIONS: EOS are elevated in ACR, especially in moderate or severe ACR. Increased vigilance for ACR is therefore advisable in lung transplant recipients with elevated EOS.

Cytomegalovirus Immunoglobulin for Prophylaxis and Treatment of Cytomegalovirus Infection in the (Val)Ganciclovir Era: A Single-Center Experience.

BACKGROUND: Evidence concerning the effectiveness of anti-cytomegalovirus immunoglobulin (CMVIg) following lung transplantation in the era of new antiviral agents is limited and controversial. MATERIAL AND METHODS: At-risk patients (donor seropositive/recipient seronegative [D+/R-] and R+) received valganciclovir for 3 months (R+) or 6 months (D+/R). CMVIg (2 mg/kg) was given to D+/R- patients on days 1, 4, 8, 15, and 30 post-transplant, then monthly for a further year. Patients with valganciclovir-induced leukopenia were switched to CMVIg (2 mg/kg) prophylaxis. Tissue-invasive disease was treated with intravenous ganciclovir with CMVIg (2 mg/kg) every other day for 1 week and then weekly until discharge. RESULTS: Of 159 patients analyzed, 26 (17%) were D+/R-. Cytomegalovirus (CMV) viremia was more frequent in D+/R- recipients than in R+ patients (61% vs. 35%; P<0.05), but developed at a similar time (mean 10±6 vs. 11±7 months) and resolved in all cases following treatment. One patient developed clinical and laboratory signs of CMV syndrome (fever >38°C), leukopenia, and detection of CMV in blood. Ten patients developed tissue-invasive disease after completion of prophylaxis (5 pneumonitis and 5 gastrointestinal disease); all were successfully treated with combined intravenous ganciclovir and CMVIg. None of the 18 donor seropositive/recipient seronegative patients who were switched from valganciclovir to CMVIg for persistent leukopenia developed CMV viremia during treatment. No cases of CMV infection or disease were attributable to ganciclovir-resistant strains. During follow-up, 44 patients died (4/26 R+/D- [15%], 40/133 R+ [30%), none directly due to CMV infection. CONCLUSIONS: Combined prophylaxis with valganciclovir and CMVIg delayed CMV viremia and tissue-invasive disease in D+/R- lung transplant recipients, and prevented CMV-related mortality and development of ganciclovir resistance. CMVIg monotherapy prophylaxis was effective in R+ patients with ganciclovir-related toxicity.