Diana F Florescu

University of Nebraska at Omaha, Omaha, Nebraska, United States

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Publications (47)161.98 Total impact

  • Uriel Sandkovsky, Luciano Vargas, Diana F Florescu
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    ABSTRACT: Infections caused by adenoviruses are associated with significant morbidity and mortality in both hematopoietic stem cell and solid organ transplant recipients. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung and small-bowel transplant recipients. Management of these infections may be difficult and includes reduction of immunosuppression whenever possible combined sometimes with antiviral therapy (mainly cidofovir). The currently available antiviral therapy is limited by the need for intravenous administration, potentially significant renal and hematologic toxicities. New emerging therapies such as brincidofovir and transfusion of adenovirus-specific T-lymphocytes may increase the available armamentarium for these potentially life-threatening infections.
    Current Infectious Disease Reports 08/2014; 16(8):416.
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    ABSTRACT: Clinical experience with cidofovir in pediatric solid organ transplantation is limited. We assessed the effect of cidofovir use on renal function.
    The Pediatric Infectious Disease Journal 07/2014; · 3.57 Impact Factor
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    ABSTRACT: Background: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. Methods: PRISMA guidelines were followed and random-effects models were performed. Results: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34-2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00-2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts.Conclusion The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.
    Expert Review of Anti-infective Therapy 05/2014; · 2.07 Impact Factor
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    ABSTRACT: Background. Prophylactic and preemptive strategies are used to prevent cytomegalovirus infections after solid organ transplantation. We assessed the safety and efficacy of both strategies for CMV prevention. Methods. DerSimonian and Laird random-effects model was used for pooling the data and Q statistic and I-squared methods were used to assess statistical heterogeneity. Results. Twenty studies (2744 patients) were selected for the direct analysis and 20 studies (2544 patients) for the indirect analysis. The odds of CMV syndrome (OR=1.10;95%CI:0.60-2.03;p=0.757;Q=18.55;I(2)=51.49%) and disease (OR=0.77;95%CI:0.41-1.47;p=0.432;Q=32.71;I(2)=44.97%.) were not significantly different between strategies. The odds of developing late-onset CMV infections were higher for the prophylactic compared to the preemptive strategy (OR=6.21;95%CI:2.55-15.20;p<0.0001;Q=9.66;I(2)=37.9%). The odds of CMV viremia were lower for prophylaxis (OR=0.42;95%CI:0.24-0.74;p=0.003;Q=48.10;I(2)=75.1%) than preemptive therapy. No differences between strategies were noted for: graft loss (OR=0.88;95%CI:0.37-2.13;p=0.779;Q=13.03,I(2)=38.62%), graft loss censored for death (OR=0.73;95%CI:0.17-3.21;p=0.679;Q=4.48;I(2)=55.32%), acute rejection (OR=0.93;95%CI:0.70-1.24;p=0.637;Q=12.99;I(2)=7.61%) and mortality (OR=0.80;95%CI:0.56-1.14;p=0.220;Q=8.76;I(2)=0%). Other infections (HSV, VZV, bacterial and fungal infections) were not significantly different between strategies. Leukopenia (OR=1.97;95%CI:1.39-2.79;p=0.0001;Q=7.10;I(2)=0%) and neutropenia (OR=2.07;95%CI:1.13-3.78;p=0.018;Q=6.77;I(2)=11.40%) were more frequent with prophylaxis than preemptive strategy. The results of direct and indirect comparisons were consistent. Conclusions. Prophylaxis was associated with less early post-transplant viremia, but with significantly more late-onset CMV infections and side effects - leukopenia and neutropenia, than the preemptive strategy. Both preventive strategies showed similar efficacy in preventing CMV syndrome and disease, with no differences regarding rejection, graft loss, death and opportunistic infections.
    Clinical Infectious Diseases 01/2014; · 9.37 Impact Factor
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    Diana F Florescu, Andre C Kalil
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    ABSTRACT: Severe sepsis is traditionally associated with bacterial diseases. While fungi and parasites can also cause sepsis, they are significantly less common than bacterial causes. However, viruses are becoming a growing cause of severe sepsis worldwide. Among these viruses, influenza is crossing all geographic boundaries and is causing larger epidemics and pandemics. As a consequence, more critically ill patients with severe sepsis caused directly by influenza viruses, or indirectly by influenza-induced secondary bacterial infections are being admitted to hospitals worldwide. This manuscript aims to provide a pathophysiological and clinical update on the link between influenza and severe sepsis.
    Virulence 11/2013; 5(1). · 2.79 Impact Factor
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    ABSTRACT: Practice variation regarding cytomegalovirus (CMV) prevention and treatment across intestinal transplantation (IT) programs is unknown. An electronic survey was sent to IT programs registered with the Intestinal Transplant Association. Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. Seventy-seven percent of IT programs responded to the survey. For CMV D+/R- recipients, 39.1% programs used universal prophylaxis (UP), 8.7% preemptive strategy (PE), and 52.2% hybrid strategy. For CMV R+ recipients, 45.8% programs used UP, 12.5% PE, 37.1% hybrid strategy, and 4.2% none. For CMV D-/R- recipients, 39.1% programs used UP, 21.7% PE, 26.1% hybrid strategy, and 13% none. Frequency of monitoring for PE was weekly 71.4% of programs, every 2 weeks 21.4%, and monthly 7.1%. For CMV viremia, syndrome and disease, the most common first-line agents used were ganciclovir (100% and 96.2%) and valganciclovir (23.1%) and the second-line agent was foscarnet (73.1% and 84.6%). Immunoglobulins were administered in 65.4% of the programs for pneumonia (69.2%), meningoencephalitis (50%), enteritis (46.2%), colitis (38.5%), syndrome (42.3%), viremia (30.8%), and resistant/refractory infections (11.5%). Prophylaxis and hybrid strategy were the most commonly used. Treatment practices were consistent and mainly involved ganciclovir as first-line agent and foscarnet as second-line agent. The use of immunoglobulins appeared to be more common than in other allografts.
    Transplantation 10/2013; · 3.78 Impact Factor
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    ABSTRACT: Hypogammaglobulinemia has been described after solid organ transplantation and has been associated with increased risk of infections. The aim of the study was to evaluate the rate of severe hypogammaglobulinemia and its relationship with the risk of infections during the first year posttransplantation. Eighteen studies (1756 patients) that evaluated hypogammaglobulinemia and posttransplant infections were included. The data were pooled using the DerSimonian and Laird random-effects model. Q statistic method was used to assess statistical heterogeneity. Within the first year posttransplantation, the rate of hypogammaglobulinemia (IgG < 700 mg/dL) was 45% (95% CI: 0.34-0.55; Q = 330.1, p < 0.0001), the rate of mild hypogammaglobulinemia (IgG = 400-700 mg/dL) was 39% (95% CI: 0.22-0.56; Q = 210.09, p < 0.0001) and the rate of severe hypogammaglobulinemia (IgG < 400 mg/dL) was 15% (95% CI: 0.08-0.22; Q = 50.15, p < 0.0001). The rate of hypogammaglobulinemia by allograft type: heart 49% (21%-78%; Q = 131.16, p < 0.0001); kidney 40% (30%-49%; Q = 24.55, p = 0.0002); liver 16% (0.001%-35%; Q = 14.31, p = 0.0002) and lung 63% (53%-74%; Q = 6.85, p = 0.08). The odds of respiratory infection (OR = 4.83; 95% CI: 1.66-14.05; p = 0.004; I(2) = 0%), CMV (OR = 2.40; 95% CI: 1.16-4.96; p = 0.02; I(2) = 26.66%), Aspergillus (OR = 8.19; 95% CI: 2.38-28.21; p = 0.0009; I(2) = 17.02%) and other fungal infections (OR = 3.69; 95% CI: 1.11-12.33; p = 0.03; I(2) = 0%) for patients with IgG <400 mg/dL were higher than the odds for patients with IgG >400 mg/dL. The odds for 1-year all-cause mortality for severe hypogammaglobulinemia group was 21.91 times higher than those for IgG >400 mg/dL group (95% CI: 2.49-192.55; p = 0.005; I(2) = 0%). Severe hypogammaglobulinemia during the first year posttransplantation significantly increased the risk of CMV, fungal and respiratory infections, and was associated with higher 1-year all-cause mortality.
    American Journal of Transplantation 08/2013; · 6.19 Impact Factor
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    Andre C Kalil, Diana F Florescu
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    ABSTRACT: Despite the same manufacturer, the same drotrecogin alfa activated dose, and the same placebo-controlled design, the negative result from the PROWESS-SHOCK trial contradicted the survival benefit observed in the PROWESS trial. We hypothesize that the different results were due to factors other than the experimental therapy and performed an analysis of the clinical heterogeneity (differences related to the trials' clinical aspects) and the statistical heterogeneity (differences related to the trials' statistical aspects) between these trials. Baseline characteristics and co-interventions were analyzed by chi-square testing and mortality was analyzed by random-effects modeling and I2. Our findings show that clinical variables presented significant heterogeneity, and that up to 90% of the mortality differences between both trials were not due to chance. These results demonstrate that PROWESS and PROWESS-SHOCK are not comparable trials due to the highly significant clinical and statistical heterogeneity. We propose a new and pragmatic solution.
    Critical care (London, England) 07/2013; 17(4):167. · 4.72 Impact Factor
  • Diana F Florescu, Alan N Langnas, Uriel Sandkovsky
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    ABSTRACT: Intestinal transplantation (IT) has become a standard treatment for patients with intestinal failure and complications of parenteral nutrition. The pool of intestinal transplant recipients has been slowly growing over the last two decades. Of the 2191 ITs performed between 1 January 1990 and 31 March 2012, 50.5% were children less than 10 years of age. Survival rates at 1, 5 and 10 years have been reported to be 78.5, 58.2 and 47%, respectively. IT restores organ functions, but it is associated with complications, with infections representing the major cause of morbidity and mortality in this population.
    Expert Review of Anticancer Therapy 04/2013; 11(4):367-81. · 3.22 Impact Factor
  • Diana F Florescu, Joong Y Kwon, Ioana Dumitru
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    ABSTRACT: Adenovirus infections have been associated with significant morbidity and mortality in immunocompromised hosts. The clinical significance of adenoviral disease in heart transplantation is not well defined; in particular, the significance of adenovirus identification in myocardium remains unclear. Although severe adenovirus disease has been described in heart transplant recipients, adenovirus infections seem to be more frequently associated with increased risk of adverse cardiac events such as rejection, ventricular dysfunction, coronary vasculopathy, need for re-transplantation and graft loss because of death. Cidofovir is currently considered the standard of treatment for adenovirus disease not responding to reduction of immunosuppression.
    Cardiology in review 03/2013;
  • Marius C Florescu, Clifford D Miles, Diana F Florescu
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    ABSTRACT: Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus infections in renal transplant recipients have typically manifested as hemorrhagic cystitis and tubulointerstitial nephritis, less severe diseases than often seen in other solid organ transplant recipients (i.e. pneumonia, hepatitis and enteritis). The prevalent adenovirus subgroups associated with cystitis and nephritis are B1 and B2 with the serotypes 7, 11, 34, 35. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring of and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus disease not responding to reduction of immunosuppression.
    Nephrology Dialysis Transplantation 03/2013; · 3.37 Impact Factor
  • D F Florescu, J A Hoffman
    American Journal of Transplantation 03/2013; 13(s4):206-211. · 6.19 Impact Factor
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    ABSTRACT: We describe two patients who developed gastrointestinal bleeding due to cytomegalovirus (CMV) colitis after placement of a HeartMate II left ventricular assist device (LVAD). We aim to raise awareness of CMV colitis as a possible cause of gastrointestinal bleeding after LVAD placement and discuss potential mechanisms for CMV reactivation and areas for future research.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 01/2013; · 2.17 Impact Factor
  • Diana F Florescu, Andre C Kalil
    Critical care medicine 12/2012; 40(12):3313-4. · 6.37 Impact Factor
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    ABSTRACT: BACKGROUND: Valganciclovir was approved by the FDA in 2004 for cytomegalovirus (CMV) prophylaxis except for liver recipients because of their high incidence of CMV disease with this drug. However, surveys show its common off-label use for CMV prophylaxis in liver recipients. We aimed to evaluate the risk of CMV disease with valganciclovir prophylaxis in liver transplant recipients. METHODS: All studies that evaluated liver transplant recipients and used valganciclovir (900mg or 450mg daily) for the prevention of CMV disease were included. RESULTS: Controlled studies (5 studies, N=483) were pooled by the random-effects model; single-arm studies (5 studies, N=380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with valganciclovir compared to ganciclovir was 1.81 (95%CI 1.00,3.29);P=0.05;I(2) =0%. For high-risk (D+/R-) patients, the risk of CMV disease was 1.96 (95%CI 1.05,3.67);P=0.035;I2=0%. The risk of CMV disease remained significant with valganciclovir 900mg daily (P=0.04), but not with valganciclovir 450mg daily (P=0.76). The risk of leucopenia with valganciclovir was 1.87 (1.03,3.37);P=0.039;I(2) =0%.For single-arm trials, the overall CMV disease rate was 12% (95%CI 9%,16%;P<0.0001), and for high risk was 20% (95%CI 10%,38%;P=0.002). CONCLUSIONS: Valganciclovir 900mg daily may not be safe for CMV prophylaxis in high-risk liver transplant recipients due to its significant 2-fold increase in the risk of CMV disease and 1.9-fold increase in leucopenia. Alternative CMV prophylaxis should be used for liver recipients. Liver Transpl, 2012. © 2012 AASLD.
    Liver Transplantation 08/2012; · 3.94 Impact Factor
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    ABSTRACT: Keck M, Mindru C, Kalil AC, Mercer DF, Florescu DF. Respiratory syncytial virus lower respiratory tract infection in a pediatric liver transplant recipient treated with oral ribavirin. Abstract:  The mainstay of therapy for RSV disease is supportive care, although aerosolized ribavirin has been used to treat infants and young children with severe lower respiratory tract infections. Aerosolized ribavirin has adverse effects, high cost and teratogenic potential. We report the case of a pediatric liver transplant recipient diagnosed with lower respiratory RSV infection, who was successfully treated with oral ribavirin.
    Pediatric Transplantation 04/2012; · 1.50 Impact Factor
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    ABSTRACT: Scopulariopsis species and their Microascus teleomorphs are cosmopolitan fungi that are uncommonly associated with invasive disease. This report describes a case of fatal disseminated Scopulariopsis brevicaulis disease in a patient with diffuse large B cell lymphoma who underwent high-dose chemotherapy followed by a matched unrelated donor stem cell transplant. This case is compared with 32 prior cases of proven invasive Scopulariopsis (Microascus) infections reported in the literature. A focus of this report is the diagnostic methods utilized which included histopathology and culture with both micromorphologic and genotypic procedures employed to confirm the species identification.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 04/2012; 50(6):561-9. · 2.13 Impact Factor
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    ABSTRACT: Cystic fibrosis (CF) patients have numerous infectious exacerbations requiring prolonged antibiotic treatments, some of which are nephrotoxic. Inhaled antibiotics can reach detectable serum levels. We studied the impact of chronic nephrotoxic antibiotic exposure on kidney function in CF population. We collected data retrospectively for 113 adult CF patients followed for 8.5 years. Fifty-seven (50.4%) were males and 56 (49.5%) females (mean age 31.7 years [SD 9.9]), of which 31% had diabetes and 9.7% had hypertension. Over 8.5 years follow up, there were no significant changes in blood urea nitrogen (BUN; P = 0.92) or creatinine (P = 0.2) in the whole group. 22% of patients had ≥1 episodes of acute kidney injury (AKI). The presence of AKI was associated with increased BUN (P = 0.002) and creatinine (P = 0.056) at the end of follow up. Use of intravenous colistin, gentamicin, tobramycin, or vancomycin did not correlate with increased BUN (P = 0.64; P = 0.49; P = 0.51; P = 0.47) or creatinine (P = 0.43; P = 0.49; P = 0.17; P = 0.2) after 8.5 years. Elevated tobramycin peak and trough levels did not correlate with increased BUN or creatinine. Inhaled colistin and gentamicin correlated with increased BUN (P = 0.009; P = 0.02) but not creatinine (P = 0.45; P = 0.46). Inhaled tobramycin did not correlate with increased BUN (P = 0.17) or creatinine (P = 0.58). Only inhaled colistin correlated with AKI episodes (P = 0.03). Chronic inhaled colistin and gentamicin are associated with an increase in BUN but not creatinine at the end of follow up. Inhaled colistin was associated with episodes of AKI. Well-managed intravenous use of nephrotoxic antibiotics in CF population is associated with no major long-term renal toxicity.
    Hemodialysis International 04/2012; 16(3):414-9. · 1.44 Impact Factor
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    ABSTRACT: Little information regarding bloodstream infections (BSIs) in small bowel transplantation has been published. We reviewed the medical records of 98 pediatric patients who underwent small bowel transplantation. Patients' characteristics were analyzed with Wilcoxon rank-sum, χ or Fisher's exact tests. We estimated the overall survival by the Kaplan-Meier method and compared survival distributions between groups with the log-rank test. Sixty-eight patients developed ≥1episode of BSIs (total of 146 episodes), and 69.1% of the first infections were diagnosed in the 3 months post-transplantation. The most common sources of infection were as follows: central venous catheters (49.3%) and intra-abdominal infections (32.9%). Central venous catheters were present in 86.3%, and total parenteral nutrition within 7 days before infection was administered in 72.6% of episodes. Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulase-negative Staphylococcus (40 isolates). Patients with infections were younger than those without (median 1.4 versus 2.1 years, P=0.02). Four grafts were lost after transplantation in patients with BSIs and 2 in patients without BSIs (P = 0.99). One-year survival rate for patients without BSIs was 86.7% (95% confidence interval: 68.3%-94.8%) versus 72.1% in patients with BSIs (95% confidence interval: 59.8%-81.2%). Overall time to death was shorter in patients with BSIs than in patients without BSIs (P=0.056). Almost 70% of small bowel transplantation recipients developed BSIs, mainly in the early months after transplantation. BSIs were mainly from a central venous catheter or intra-abdominal source. Enterococcus spp were the most frequently isolated organisms. Patients with BSIs had worse survival than patients with BSIs.
    The Pediatric Infectious Disease Journal 03/2012; 31(7):700-4. · 3.57 Impact Factor
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    ABSTRACT: Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP. We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I(2) method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates. Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI], .74-1.77; P = .56; I(2) = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI, .48-1.66; P = .71; I(2) = 0%]; retrospective OR, 1.45 [95% CI, .79-2.68; P = .23; I(2) = 0%]); randomized trials OR, 0.86 [95% CI, .43-1.74; P = .68; I(2) = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P = .95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). Fourteen single-arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies. Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP.
    Clinical Infectious Diseases 03/2012; 54(5):670-80. · 9.37 Impact Factor

Publication Stats

254 Citations
161.98 Total Impact Points


  • 2008–2013
    • University of Nebraska at Omaha
      • • Department of Biostatistics
      • • Department of Internal Medicine
      Omaha, Nebraska, United States
    • University of Nebraska Medical Center
      • Division of Infectious Diseases
      Omaha, Nebraska, United States
  • 2011–2012
    • The Nebraska Medical Center
      Omaha, Nebraska, United States