N. Sabé

Risk Factors and Outcomes of Bacteremia Caused by Drug-Resistant ESKAPE Pathogens in Solid-Organ Transplant Recipients

Background Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients. Methods All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed. Results Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum &bgr;-lactamase–producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal &bgr;-lactam and extended-spectrum &bgr;-lactamase–producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001). Conclusions Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.

Prophylaxis versus preemptive therapy for cytomegalovirus disease in high‐risk liver transplant recipients

Cytomegalovirus (CMV) infection is an opportunistic infection frequently found after solid organ transplantation, and it contributes significantly to mortality and morbidity. CMV‐seronegative recipients of grafts from CMV‐seropositive donors have the highest risk of CMV disease. The most appropriate strategy for preventing CMV disease in this population is a matter of active debate. In this study, we compared prophylaxis and preemptive therapy for the prevention of CMV disease in donor‐seropositive/recipient‐seronegative (D+/R−) liver recipients. To this end, we selected a retrospective cohort of liver recipients (1992‐2009) for analysis. D+/R− patients were identified from the liver transplant program database. Eighty of 878 consecutive liver recipients (9%) were D+/R−. Six of these patients died within 30 days of transplantation and were excluded. Thirty‐five of the remaining D+/R− patients (47%) received prophylaxis, and 39 patients (53%) followed a preemptive strategy based on CMV antigenemia surveillance. Fifty‐four (73%) were men, the median age was 49 years (range = 15‐68 years), and the mean follow‐up was 68 months (range = 8‐214 months). The baseline characteristics and the initial immunosuppressive regimens were similar for the 2 groups. Ganciclovir or valganciclovir was the antiviral drug used initially in both strategy groups. CMV disease occurred more frequently among D+/R− liver recipients receiving preemptive therapy (33.3% versus 8.6% for the prophylaxis group, P = 0.01), whereas late‐onset CMV disease was found only in patients receiving prophylaxis (5.7% versus 0% for the preemptive therapy group, P = 0.22). No significant differences in acute allograft rejection, other opportunistic infections, or case fatality rates were observed. According to our data, prophylaxis was more effective than preemptive therapy in preventing CMV disease in high‐risk liver transplant recipients. Liver Transpl, 2012.

Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1–2, a Randomized Controlled Clinical Trial

Background Influenza vaccine effectiveness is not optimal in solid organ transplant recipients (SOTR). We hypothesized that a booster dose might increase it. Methods TRANSGRIPE 1-2 is a phase 3, randomized, controlled, multicenter, open-label clinical trial. Patients were randomly assigned (1:1 stratified by study site, type of organ, and time since transplantation) to receive 1 dose (control group) or 2 doses (booster group) of the influenza vaccine 5 weeks apart. Results A total of 499 SOTR were enrolled. Although seroconversion at 10 weeks did not meet significance in the modified intention-to-treat population, seroconversion rates were significantly higher in the booster arm for the per-protocol population (53.8% vs 37.6% for influenza A(H1N1)pdm; 48.1% vs 32.3% for influenza A(H3N2); and 90.7% vs 75% for influenza B; P < .05). Furthermore, seroprotection at 10 weeks was higher in the booster group: 54% vs 43.2% for A(H1N1)pdm; 56.9% vs 45.5% for A(H3N2); and 83.4% vs 71.8% for influenza B (P < .05). The number needed to treat to seroprotect 1 patient was <10. The clinical efficacy (99.2% vs 98.8%) and serious adverse events (6.4% vs 7.5%) were similar for both groups. Conclusions In SOTR, a booster strategy 5 weeks after standard influenza vaccination is safe and effective and induces an increased antibody response compared with standard influenza vaccination consisting of a single dose. Clinical Trials Registration EudraCT (2011-003243-21).

Extensively drug-resistant Pseudomonas aeruginosa bacteremia in solid organ transplant recipients.

Background We sought to determine the risk factors, molecular epidemiology, antibiotic therapy, and outcomes of bacteremia because of extensively drug-resistant (XDR) Pseudomonas aeruginosa in solid organ transplant (SOT) recipients. Methods All episodes of bacteremia occurring in SOT recipients were prospectively documented from 2007 to 2013. Results Of 318 episodes of bacteremia, 49 were caused by P. aeruginosa. Thirty-one strains (63%) were XDR defined by nonsusceptibility to at least one agent in all but two or fewer antipseudomonal antimicrobial categories. Time from transplantation to bacteremia was shorter in XDR P. aeruginosa group comparing to other etiologies (median days 66 vs. 278; P=0.03). Factors independently associated with XDR P. aeruginosa bacteremia were prior transplantation, nosocomial acquisition, and septic shock at onset. XDR P. aeruginosa isolates belonged to a single clone (ST-175). Comparing to other etiologies, patients with bacteremia because of XDR P. aeruginosa more often received inadequate empirical antibiotic therapy. Persistence of bacteremia, shock, respiratory failure and intensive care unit admission were more frequent in patients with XDR P. aeruginosa. The overall case-fatality rate was higher among patients with XDR P. aeruginosa bacteremia than in the others (38% vs. 16%; P=0.009). Conclusion Bacteremia because of XDR P. aeruginosa should be carefully considered when selecting empirical antibiotic therapy for hospitalized SOT recipients with prior transplantation presenting with septic shock.

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.

Ganciclovir‐resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor‐based regimen. This salvage therapy should be considered when other options are not available.

Influenza vaccination during the first 6 months after solid organ transplantation is efficacious and safe

Preventing influenza infection early after transplantation is essential, given the diseases high mortality. A multicentre prospective cohort study in adult solid organ transplant recipients (SOTR) receiving the influenza vaccine during four consecutive influenza seasons (2009-2013) was performed to assess the immunogenicity and safety of influenza vaccination in SOTR before and 6 months after transplantation. A total of 798 SOTR, 130 of them vaccinated within 6 months of transplantation and 668 of them vaccinated more than 6 months since transplantation. Seroprotection was similar in both groups: 73.1% vs. 76.5% for A/(H1N1)pdm (p 0.49), 67.5% vs. 74.1% for A/H3N2 (p 0.17) and 84.2% vs. 85.2% for influenza B (p 0.80), respectively. Geometric mean titres after vaccination did not differ among groups: 117.32 (95% confidence interval (CI) 81.52, 168.83) vs. 87.43 (95% CI 72.87, 104.91) for A/(H1N1)pdm, 120.45 (95% CI 82.17, 176.57) vs. 97.86 (95% CI 81.34, 117.44) for A/H3N2 and 143.32 (95% CI 103.46, 198.53) vs. 145.54 (95% CI 122.35, 174.24) for influenza B, respectively. After adjusting for confounding factors, time since transplantation was not associated with response to vaccination. No cases of rejection or severe adverse events were detected in patients vaccinated within the first 6 months after transplantation. In conclusion, influenza vaccination within the first 6 months after transplantation is as safe and immunogenic as vaccination thereafter. Thus, administration of the influenza vaccine can be recommended as soon as 1 month after transplantation.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long‐term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease.

Donor‐transmitted malaria after heart transplant managed successfully with artesunate

Donor‐transmitted malaria is a rare complication in solid organ transplantation, which causes high mortality. Data concerning the use of artesunate in solid organ transplant recipients are lacking. We report a heart transplant patient who developed donor‐derived severe Plasmodium falciparum malaria, successfully treated with artesunate. Transmission of malaria to 2 of the other transplant recipients from the same donor was also documented.

Management of Ventriculoperitoneal Shunt Infections in Adults: Analysis of Risk Factors Associated With Treatment Failure

Background Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Methods Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.

Daptomycin is safe and effective for the treatment of gram-positive cocci infections in solid organ transplantation.

Infections caused by resistant gram‐positive cocci (GPC), especially to glycopeptides, are difficult to treat in solid organ transplant (SOT) recipients as a result of lower effectiveness and high rates of renal impairment. The aim of this study was to evaluate the use of daptomycin in this population.