Graeme N. Forrest

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

Background. The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. Methods. Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. Results. Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30–1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12–0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16–0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. Conclusions. Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Infections Due to Scedosporium apiospermum and Scedosporium prolificans in Transplant Recipients: Clinical Characteristics and Impact of Antifungal Agent Therapy on Outcome

BACKGROUND Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients. METHODS The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Maranon [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non-transplant recipients with scedosporiosis who were described in the literature. RESULTS Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P=.045), to have an earlier onset of infection (P=.007), to be neutropenic (P<.0001), and to have fungemia (P=.04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P=.002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P=.08). Presence of disseminated infection (OR, 0.20; P=.03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P=.02) independently predicted a better survival in this model. CONCLUSIONS Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

Peptide Nucleic Acid Fluorescence In Situ Hybridization-Based Identification of Candida albicans and Its Impact on Mortality and Antifungal Therapy Costs

ABSTRACT The impact of rapid identification of Candida albicans blood isolates by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) on the selection and expenditure of antifungal therapy was evaluated. PNA FISH was 100% sensitive and specific in the rapid identification of 31 out of 72 candidemias as C. albicans and resulted in a significant reduction of caspofungin usage, with an overall cost savings of

Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case-Control Study to Assess Risks for Disease and Outcome

1,729 per patient.

Peptide Nucleic Acid Fluorescent In Situ Hybridization for Hospital-Acquired Enterococcal Bacteremia: Delivering Earlier Effective Antimicrobial Therapy

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Impact of a Computerized Clinical Decision Support System on Reducing Inappropriate Antimicrobial Use: A Randomized Controlled Trial

ABSTRACT Hospital-acquired vancomycin-resistant enterococcal bacteremia has been associated with increased hospital costs, length of stay, and mortality. The peptide nucleic acid fluorescent in situ hybridization (PNA FISH) test for Enterococcus faecalis and other enterococci (EFOE) is a multicolor probe that differentiates E. faecalis from other enterococcal species within 3 h directly from blood cultures demonstrating gram-positive cocci in pairs and chains (GPCPC). A quasiexperimental study was performed over two consecutive years beginning in 2005 that identified GPCPC by conventional microbiological methods, and in 2006 PNA FISH was added with a treatment algorithm developed by the antimicrobial team (AMT). The primary outcome assessed was the time from blood culture draw to the implementation of effective antimicrobial therapy before and after PNA FISH. The severity of illness, patient location, and empirical antimicrobial therapy were measured. A total of 224 patients with hospital-acquired enterococcal bacteremia were evaluated, with 129 in the preintervention period and 95 in the PNA FISH period. PNA FISH identified E. faecalis 3 days earlier than conventional cultures (1.1 versus 4.1 days; P < 0.001). PNA FISH identified Enterococcus faecium a median 2.3 days earlier (1.1 versus 3.4 days; P < 0.001) and was associated with statistically significant reductions in the time to initiating effective therapy (1.3 versus 3.1 days; P < 0.001) and decreased 30-day mortality (26% versus 45%; P = 0.04). The EFOE PNA FISH test in conjunction with an AMT treatment algorithm resulted in earlier initiation of appropriate empirical antimicrobial therapy for patients with hospital-acquired E. faecium bacteremia.

Rifampin Combination Therapy for Nonmycobacterial Infections

OBJECTIVE Many hospitals utilize antimicrobial management teams (AMTs) to improve patient care. However, most function with minimal computer support. We evaluated the effectiveness and cost-effectiveness of a computerized clinical decision support system for the management of antimicrobial utilization. DESIGN A randomized controlled trial in adult inpatients between May 10 and August 3, 2004. Antimicrobial utilization was managed by an existing AMT using the system in the intervention arm and without the system in the control arm. The system was developed to alert the AMT of potentially inadequate antimicrobial therapy. MEASUREMENTS Outcomes assessed were hospital antimicrobial expenditures, mortality, length of hospitalization, and time spent managing antimicrobial utilization. RESULTS The AMT intervened on 359 (16%) of 2,237 patients in the intervention arm and 180 (8%) of 2,270 in the control arm, while spending approximately one hour less each day on the intervention arm. Hospital antimicrobial expenditures were

Antimicrobial stewardship at a large tertiary care academic medical center: cost analysis before, during, and after a 7-year program.

285,812 in the intervention arm and

Addition of Rifampin to Standard Therapy for Treatment of Native Valve Infective Endocarditis Caused by Staphylococcus aureus

370,006 in the control arm, for a savings of

Prevalence of Candida dubliniensis Fungemia at a Large Teaching Hospital

84,194 (23%), or