Marta Bodro

Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients

Recent changes in the management of patients with haematological malignancies might have influenced the aetiology, characteristics, antimicrobial resistance and outcomes of bloodstream infection (BSI) during neutropenia. We compared 272 episodes of BSI in adult neutropenic patients with cancer prospectively collected from January 1991 to December 1996 (first period), when quinolone prophylaxis was used, with 283 episodes recorded from January 2006 to March 2010 (second period), when antibacterial prophylaxis was stopped. Patients in the second period were significantly older and were more likely to have graft-versus-host disease and a urinary catheter in place, whereas the presence of a central venous catheter, parenteral nutrition, corticosteroids and antifungal and quinolone prophylaxis, were more frequent in the first period. More patients in the first period had mucositis and soft-tissue infection as the origin of BSI, but an endogenous source was more common during the second. Gram-positive BSI was more frequent in the first period (64% versus 41%; p <0.001), mainly due to coagulase-negative staphylococci and viridans group streptococci. In the second period gram-negative BSI increased (28% versus 49%; p <0.001), quinolone susceptibilities were recovered, but multidrug-resistant gram-negative BSI also increased (1% versus 6%; p <0.001). Although patients in the second period were more likely to need admission to the intensive-care unit, overall case-fatality rate was similar in the two periods (19% versus 15%). The aetiology of BSI in neutropenic patients with cancer has shifted from gram-positive to gram-negative organisms. Multidrug resistance among gram-negative bacilli is emerging as a therapeutic challenge. Overall case-fatality rate remains high.

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.

Impact of Antibiotic Resistance on the Development of Recurrent and Relapsing Symptomatic Urinary Tract Infection in Kidney Recipients

We sought to determine the frequency, risk factors, and clinical impact of recurrent urinary tract infections (UTI) in kidney transplant recipients. Of 867 patients who received a kidney transplant between 2003 and 2010, 174 (20%) presented at least one episode of UTI. Fifty‐five patients presented a recurrent UTI (32%) and 78% of them could be also considered relapsing episodes. Recurrent UTI was caused by extended‐spectrum betalactamase (ESBL)–producing Klebsiella pneumoniae (31%), followed by non‐ESBL producing Escherichia coli (15%), multidrug‐resistant (MDR) Pseudomonas aeruginosa (14%), and ESBL‐producing E. coli (13%). The variables associated with a higher risk of recurrent UTI were a first or second episode of infection by MDR bacteria (OR 12; 95%CI 528), age >60 years (OR 2.2; 95%CI 1.15.1), and reoperation (OR 3; 95%CI 1.37.1). In addition, more relapses were recorded in patients with UTI caused by MDR organisms than in those with susceptible microorganisms. There were no differences in acute rejection, graft function, graft loss or 1 year mortality between groups. In conclusion, recurrent UTI is frequent among kidney recipients and associated with MDR organism. Classic risk factors for UTI (female gender and diabetes) are absent in kidney recipients, thus highlighting the relevance of uropathogens in this population.

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.

Increase in Bloodstream Infection Due to Vancomycin-Susceptible Enterococcus faecium in Cancer Patients: Risk Factors, Molecular Epidemiology and Outcomes

We conducted a prospective study to assess the risk factors, molecular epidemiology and outcome of bloodstream infection (BSI) due to Enterococcus faecium in hospitalized cancer patients. Between 2006 and 2012, a significant increase in vancomycin-susceptible E. faecium BSI was observed among cancer patients. Comparison of 54 episodes of BSI due to E. faecium with 38 episodes of BSI due to E. faecalis showed that previous use of carbapenems was the only independent risk factor for E. faecium acquisition (OR 10.24; 95% CI, 1.35-77.66). All E. faecium isolates were susceptible to glycopeptides, whereas 97% showed high-level resistance to ampicillin and ciprofloxacin. All 30 isolates available for genotyping belonged to the hospital-associated E. faecium lineages 17, 18 and 78. After 2009, most of the isolates belonged to ST117 (lineage 78). Patients with E. faecium BSI were more likely to receive inadequate initial empirical antibiotic therapy than patients with E. faecalis BSI, and time to adequate empirical antibiotic therapy was also longer in the former group. No significant differences were found between the two groups regarding early and overall case-fatality rates. Independent risk factors for overall case-fatality were current corticosteroids (OR 4.18; 95% CI, 1.34-13.01) and intensive care unit admission (OR 9.97; 95% CI, 1.96-50.63). The emergence of E. faecium among cancer patients is a concern since there are limited treatment options and it may presage the emergence of vancomycin-resistant enterococci. A rationale approach that combines infection control with antimicrobial stewardship.

Reduced incidence of pneumonia in influenza-vaccinated solid organ transplant recipients with influenza disease

Abstract Whether influenza vaccination influences the severity of illness in cases of clinical failure in solid organ transplant (SOT) recipients receiving influenza vaccine has not been extensively studied. Our goal was to evaluate the frequency of influenza vaccination among SOT recipients with influenza disease and its impact on the illness severity during the 2010–2011 season. Adult SOT recipients with confirmed influenza infection were included from December 2010 to April 2011. Follow-up data were recorded and antibody titres were determined using a microneutralization assay. Sixty-four SOT recipients were included in the study, ten (15.6%) with severe disease, requiring admission to intensive care units, of whom four (6.3%) died. In all, 34 (53.1%) received the 2010–2011 seasonal influenza vaccine and 32 (50.0%) received the 2009-H1N1 pandemic vaccine, and none had detectable antibodies against influenza at the time of diagnosis of influenza infection. Twenty-three (67.6%) of the patients that received the vaccine required hospital admission and presented less dyspnoea (10, 29.4% versus 14 (50.0%), p 0.09) and pneumonia (8, 23.8% versus 15, 50.0%, p 0.03, relative risk 0.3, 95% CI 0.1-0.9) than unvaccinated patients, with relative risk reductions of 60% and 70%, respectively. Although influenza vaccination confers protection on SOT recipients against developing influenza pneumonia, the rate of clinical failure is still high. New strategies to improve influenza immunization are needed for this group of patients.

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.

Impact of urinary tract infections on short-term kidney graft outcome

Urinary tract infections (UTIs) are frequent after renal transplantation, but their impact on short-term graft outcome is not well established. All kidney transplants performed between July 2003 and December 2010 were investigated to evaluate the impact of UTI on graft function at 1 year after transplantation. Of 867 patients who received a kidney transplant, 184 (21%) developed at least one episode of UTI, at a median of 18 days after transplantation. The prevalence of acute graft pyelonephritis (AGP) was 15%. The most frequent pathogens identified were Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa, 37% of which were considered to be multidrug-resistant strains. Thirty-eight patients (4%) lost their grafts, 225 patients (26%) had graft function impairment and the 1-year mortality rate was 3%; however, no patient died as a consequence of a UTI. Surgical re-intervention and the development of at least one episode of AGP were independently associated with 1-year graft function impairment. Moreover, the development of at least one episode of AGP was associated with graft loss at 1 year. Patients with AGP caused by a resistant strain had graft function impairment more frequently, although this difference did not reach statistical significance (53% vs. 36%, p 0.07). Neither asymptomatic bacteriuria nor acute uncomplicated UTI were associated with graft function impairment in multivariate analysis. To conclude, UTIs are frequent in kidney transplant recipients, especially in the early post-transplantation period. Although AGP was significantly associated with kidney graft function impairment and 1-year post-transplantation graft loss, lower UTIs did not affect graft function.

Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high‐risk liver transplantation recipients: A propensity score analysis

Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high‐risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR‐LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005‐2012), we analyzed 195 HR‐LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001‐0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR‐LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR‐LTRs, although bilirubin levels may be increased.