Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

BACKGROUND: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission. METHODS: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center. No prisoners were used in this study, and participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Between June 2021 and January 2023, we transplanted 26 solid organs, including 13 kidneys, 8 livers, 3 hearts, and 1 simultaneous heart and kidney, from 23 SARS-CoV-2-positive donors into 25 SARS-CoV-2 negative recipients. Two of the recipients had a positive SARS-CoV-2 real-time polymerase chain reaction after transplantation, but otherwise, patients had no SARS-CoV-2-related complications, and all patients to date are alive with excellent allograft function. CONCLUSION: Transplantation of non-lung solid organs from SARS-CoV-2-positive donors into uninfected recipients can be safely performed without adverse effects from SARS-CoV-2.

Use of hepatitis B viremic donors in kidney transplant recipients: A single center experience.

Utilization of Hepatitis B virus (HBV)-infected kidney allografts represents an opportunity to bridge the gap between organ supply and demand. Highly efficacious vaccines and antiviral therapies allow these allografts to be transplanted with negligible risk to the recipient. The purpose of this study was to describe the prophylactic strategies and related clinical outcomes of kidney transplant recipients who received a kidney from an HBV viremic donor. Eight patients received an allograft from an HBV viremic deceased kidney donor between January 1, 2017 and December 4, 2020. All recipients were immune to hepatitis B with a surface antibody titer greater than or equal to 10 mIU/ml (range: 12 - > 1000 mIU/ml). After transplant, 62.5% demonstrated HBV core antibody seroconversion at an average of 47.4 ± 28.5 days post-transplant. Anti-viral prophylaxis was initiated in 87.5% of patients; 62.5% preemptively during the transplant admission (range 1-3 days post-transplant) and 25% following HBcAb seroconversion (range 45-304 days post-transplant). Of the four patients who were started on entecavir preemptively, two subsequently core converted. These two patients had an HBV surface antibody less than 100 mIU/ml at the time of transplant. None of the recipients converted to HBV surface antigen positivity. The average estimated glomerular filtration rate was 41 ± 19 ml/min/1.73m2 , and there were no significant elevations in liver enzymes through one year post-transplant. The use of HBV viremic kidney allografts may represent an additional source of transplant organs; however, more studies are needed to better elucidate the optimal protective strategies for these recipients.

Implementing a regional standardized BK polyomavirus screening protocol across eleven transplant centres.

BK polyomavirus (BKPyV) reactivation is regularly monitored after kidney transplant to prevent progression to BK associated nephropathy (BKAN). The New England BK Consortium, made up of 12 transplant centres in the northeastern United States, conducted a quality improvement project to examine adherence to an agreed upon protocol for BKPyV screening for kidney transplants performed in calendar years 2016-2017. In a total of 1047 kidney transplant recipients (KTR) from 11 transplant centres, 204 (19%) had BKPyV infection, defined as detection of BKPyV in plasma, with 41 (4%) KTR progressing to BKAN, defined by either evidence on biopsy tissues or as determined by treating nephrologists. BKPyV infection was treated with reduction of immune suppressants (RIS) in >70% of the patients in all but two centres. There was no graft loss because of BKAN during the two-year follow-up. There were nine cases of post-RIS acute rejection detected during this same period. Adherence to the protocol was low with 54% at 12 months and 38% at 24 months, reflecting challenges of managing transplant patients at all centres. The adherence rate was positively correlated to increased detection of BKPyV infection and was unexpectedly positively correlated to an increase in diagnosis of BKAN.

Initial experience of bamlanivimab monotherapy use in solid organ transplant recipients.

The widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to propagate the coronavirus disease 2019 (COVID-19) pandemic with solid organ transplant (SOT) recipients being an exceptionally vulnerable population for poor outcomes. Treatments for COVID-19 are limited; however, monoclonal antibodies are emerging as a potential therapeutic option to change the trajectory of high-risk patients. This retrospective single center cohort study evaluated the outcomes of SOT recipients with mild to moderate COVID-19 who received bamlanivimab monotherapy. Eighteen SOT recipients (15 kidney, 2 liver, and 1 heart) received the medication between November 9, 2020 and February 10, 2021 with no reported infusion reactions. One patient experienced headache and fatigue following the infusion that resolved within 3 days. Fourteen patients continued their recovery as an outpatient with no further escalation in care. Three patients required hospitalization: two for suspected bacterial pneumonia 9 and 32 days postinfusion, respectively, and one for acute kidney injury 7 days postinfusion. One patient had an emergency room visit for gastrointestinal symptoms 24 days postinfusion. In this small cohort of SOT recipients, bamlanivimab monotherapy appeared to be a well-tolerated option for treatment of mild to moderate COVID-19, but it was not completely effective in preventing hospitalization. One month following the end of this cohort, COVID-19 treatment guidance changed due to the rising prevalence of resistant variants. For this reason, bamlanivimab is now recommended to be used only in combination with etesevimab. Further studies are needed to fully elucidate the role of this therapy in SOT recipients.

Evaluation of cytomegalovirus prophylaxis in low and intermediate risk kidney transplant recipients receiving lymphocyte-depleting induction.

Cytomegalovirus (CMV) is a significant cause of morbidity in kidney transplant recipients (KTR). Historically at our institution, KTR with low and intermediate CMV risk received 6 months of valganciclovir if they received lymphocyte depleting induction therapy. This study evaluates choice and duration of CMV prophylaxis based on donor (D) and recipient (R) CMV serostatus and the incidence of post-transplant CMV viremia in low (D-/R-) and intermediate (R+) risk KTR receiving lymphocyte-depleting induction therapy. A protocol utilizing valacyclovir for 3 months for D-/R- and valganciclovir for 3 months for R+ was evaluated. Adult D-/R- and R+ KTR receiving anti-thymocyte globulin, rabbit or alemtuzumab induction from 8/20/2016 to 9/30/2018 were evaluated through 1 year post-transplant. Patients were excluded if their CMV serostatus was D+/R-, received a multi-organ transplant, or received basiliximab. Seventy-seven subjects met the inclusion criteria: 25 D-/R- (4 historic group, 21 experimental group) and 52 R+ (31 historic, 21 experimental). No D-/R- patients experienced CMV viremia. Among the R+ historic and experimental groups, there was no significant difference in viremia incidence (35.5% vs 52.4%; P = .573). Of these cases, the peak viral load was similar between the groups (median [IQR], 67 [<200-444] vs <50 [<50-217]; P = .711), and there was no difference in the incidence of CMV syndrome (16.1% vs 14.3%; P = 1.000) or CMV related hospitalization (12.9% vs 14.3%; P = 1.000). No patient experienced tissue invasive disease. These results suggest limiting valganciclovir exposure may be possible in low and intermediate risk KTR receiving lymphocyte-depleting induction therapy with no apparent impact on CMV-related outcomes.

CYP51A polymorphisms of Aspergillus fumigatus in lung transplant recipients: Prevalence, correlation with phenotype, and impact on outcomes.

Azole resistance in Aspergillus fumigatus is increasing worldwide and can affect prognosis. It is mostly mediated by cytochrome P51 (CYP51) mutations. In lung transplant recipients (LTR), little is known regarding the prevalence and clinical impact of CYP51 mutations. One hundred thirty-one consecutive A. fumigatus isolates from 103 patients were subjected to CYP51A genotyping through PCR and sequencing. Antifungal susceptibility testing was performed using the Sensititre YeastOne YO-9© broth microdilution technique. Correlations between genotype, phenotype, clinical manifestations of Aspergillus infection, and clinical outcomes were made. Thirty-four (26%) isolates harbored mutations of CYP51A; N248K (n = 14) and A9T (n = 12) were the most frequent. Three isolates displayed multiple point mutations. No significant influences of mutational status were identified regarding azole MICs, the clinical presentation of Aspergillus disease, 1-year all-cause mortality, and clinical outcomes of invasive forms. In the specific context of lung transplant recipients, non-hotspot CYP51A-mutated isolates are regularly encountered; this does not result in major clinical consequences or therapeutic challenges. LAY SUMMARY: In 131 isolates of Aspergillus fumigatus isolates originating from 103 lung transplant recipients, the CYP51A polymorphism rate was 26%, mostly represented by N248K and A9T mutations. These mutations, however, did not significantly impact azoles minimal inhibitory concentrations or clinical outcomes.

Cefiderocol for the Treatment of Adult and Pediatric Patients With Cystic Fibrosis and Achromobacter xylosoxidans Infections.

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance.

Successful management of noncirrhotic hyperammonemia syndrome after kidney transplantation from putative Ureaplasma infection.

Noncirrhotic hyperammonemia (NCH) is a rare but often fatal complication of solid organ transplantation. We present a case wherein an infectious cause of NCH was suspected following kidney transplantation (KT) and the patient was promptly started on empirical antibiotic treatment which proved to be lifesaving. A 56-year-old Chinese woman with a past medical history of end-stage renal disease secondary to ischemic nephropathy and cerebrovascular accident received a kidney from a 52-year-old brain-dead donor with a Kidney Donor Profile Index score of 70%. She experienced immediate graft function and was discharged on post-operative day (POD) 4. On POD 10, she presented with a fever, acute onset of confusion, and abdominal pain. Her mental status deteriorated and required emergent intubation. Empiric broad-spectrum antibiotics were initiated. On hospital day 3, a serum ammonia was 889 µmol/L (normal <53 µmol/L). A urine sample was sent for Ureaplasma polymerase chain reaction (PCR) testing, and moxifloxacin and doxycycline were empirically started. Her ammonia rapidly normalized, and her mental status improved 48 hours after antibiotic initiation. She was extubated 5 days into treatment and was discharged after an 11-day hospitalization. Following discharge, her urine test resulted positive for Ureaplasma parvum or Ureaplasma urealyticum DNA detection with the 16S rRNA gene amplification probe. Mental status changes and hyperammonemia in the first 30 days post-KT should raise suspicion for NCH, and prompt empiric treatment with antimicrobials covering Ureaplasma and Mycoplasma should be considered.

Clostridium paraputrificum septicemia and liver abscess.

We report the first case of a healthy 23-year-old female who underwent an interventional radiology-guided embolization of a hepatic adenoma, which resulted in a gas forming hepatic liver abscess and septicemia by Clostridium paraputrificum. A retrospective review of Clostridial liver abscesses was performed using a PubMed literature search, and we found 57 clostridial hepatic abscess cases. The two most commonly reported clostridial species are C. perfringens and C. septicum (64.9% and 17.5% respectively). C. perfringens cases carried a mortality of 67.6% with median survival of 11 h, and 70.2% of the C. perfringens cases experienced hemolysis. All C. septicum cases were found to have underlying liver malignancy at the time of the presentation with a mortality of only 30%. The remaining cases were caused by various Clostridium species, and this cohort's clinical course was significantly milder when compared to the above C. perfringens and C. septicum cohorts.

Prediction of failure in vancomycin-treated methicillin-resistant Staphylococcus aureus bloodstream infection: a clinically useful risk stratification tool.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of bloodstream infection (BSI) and is often associated with invasive infections and high rates of mortality. Vancomycin has remained the mainstay of therapy for serious Gram-positive infections, particularly MRSA BSI; however, therapeutic failures with vancomycin have been increasingly reported. We conducted a comprehensive evaluation of the factors (patient, strain, infection, and treatment) involved in the etiology and management of MRSA BSI to create a risk stratification tool for clinicians. This study included consecutive patients with MRSA BSI treated with vancomycin over 2 years in an inner-city hospital in Detroit, MI. Classification and regression tree analysis (CART) was used to develop a risk prediction model that characterized vancomycin-treated patients at high risk of clinical failure. Of all factors, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, with a cutoff point of 14, was found to be the strongest predictor of failure and was used to split the population into two groups. Forty-seven percent of the population had an APACHE-II score < 14, a value that was associated with low rates of clinical failure (11%) and mortality (4%). Fifty-four percent of the population had an APACHE-II score ≥ 14, which was associated with high rates of clinical failure (35%) and mortality (23%). The risk stratification model identified the interplay of three other predictors of failure, including the vancomycin MIC as determined by Vitek 2 analysis, the risk level of the source of BSI, and the USA300 strain type. This model can be a useful tool for clinicians to predict the likelihood of success or failure in vancomycin-treated patients with MRSA bloodstream infection.