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Biomedical subjects

Barbara D Alexander

Publications and source records attributed to Barbara D Alexander.

At least 19 recordsLinked to original sources
PubMed2007

Comparative evaluation of Etest and sensititre yeastone panels against the Clinical and Laboratory Standards Institute M27-A2 reference broth microdilution method for testing Candida susceptibility to seven antifungal agents.

To assess their utility for antifungal susceptibility testing in our clinical laboratory, the Etest and Sensititre methods were compared with the Clinical and Laboratory Standards Institute (CLSI) M27-A2 reference broth microdilution method. Fluconazole (FL), itraconazole (I), voriconazole (V), posaconazole (P), flucytosine (FC), caspofungin (C), and amphotericin B (A) were tested with 212 Candida isolates. Reference MICs were determined after 48 h of incubation, and Etest and Sensititre MICs were determined after 24 h and 48 h of incubation. Overall, excellent essential agreement (EA) between the reference and test methods was observed for Etest (95%) and Sensititre (91%). Etest showed an >or=92% EA for MICs for all drugs tested; Sensititre showed a >or=92% EA for MICs for I, FC, A, and C but 82% for FL and 85% for V. The overall categorical agreement (CA) was 90% for Etest and 88% for Sensititre; minor errors accounted for the majority of all categorical errors for both systems. Categorical agreement was lowest for Candida glabrata and Candida tropicalis with both test systems. Etest and Sensititre provided better CA at 24 h compared to 48 h for C. glabrata; however, CA for C. glabrata was <80% for FL with both test systems despite MIC determination at 24 h. Agreement between technologists for both methods was >or=98% for each agent against all organisms tested. Overall, Etest and Sensititre methods compared favorably with the CLSI reference method for determining the susceptibility of Candida. However, further evaluation of their performance for determining the MICs of azoles, particularly for C. glabrata, is warranted.

Antifungal Agents↗
PubMed2007

Validation of laboratory screening criteria for herpes simplex virus testing of cerebrospinal fluid.

Most patients with herpes simplex virus (HSV) central nervous system (CNS) infection have abnormal cerebrospinal fluid (CSF) indices. Therefore, we implemented screening criteria based on CSF values and host immune status to guide testing. All CSF samples submitted for HSV PCR analysis from January 1999 through December 2004 were included in the study. Specimens from patients with human immunodeficiency virus, a history of transplants, an age of <2 years, a CSF white blood cell count of >5 cells/mm(3), or a protein level of >50 mg/dl were tested upon request. All other samples were rejected and frozen. To validate our screening criteria, rejected specimens were pooled and tested retrospectively. Electronic medical records were also reviewed. A total of 1,659 HSV PCR requests from 1,458 patients were screened. Of the 1,296 specimens (78.1%) accepted for testing, 1,213 were negative, 7 were positive for HSV type 1 (HSV-1), 26 were positive for HSV-2, and 50 had unavailable results. Sixteen requests were rejected because an alternative microbiologic diagnosis had been established. Of the 347 samples rejected based on criteria, 222 (64.0%) remained available for pooled testing. No HSV-1-positive samples were identified in the rejected specimens. Two rejected specimens tested positive for HSV-2 DNA, but both met acceptance criteria which had not been communicated to the laboratory. Few patients (7.8%) with rejected specimens were treated with acyclovir, which suggests a low clinical concern for HSV encephalitis. Acceptance criteria based on CSF parameters and host immune status saved time and cost and did not miss patients with HSV CNS infection. Communication between the clinician and the laboratory is imperative for a successful screening program.

Adult↗
PubMed2006

Burkholderia glumae infection in an infant with chronic granulomatous disease.

An 8-month-old boy developed a necrotic lung mass from which Burkholderia glumae was recovered, leading to the diagnosis of chronic granulomatous disease (CGD). While other Burkholderia species have been identified as important pathogens in persons with CGD, B. glumae has not been previously reported to cause human infection.

Burkholderia↗
PubMed2006

Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures.

Antifungal expenditures are substantial for many hospitals. Using caspofungin for the treatment of candidemia accounts for a sizable proportion of the costs. A cost minimization study that used a decision analytic model was done to compare in-hospital diagnosis and treatment costs using the Candida albicans peptide nucleic acid fluorescence in situ hybridization (PNA FISH) test versus the C. albicans screen test for differentiating C. albicans from non-albicans Candida species bloodstream infections. Assuming physician notification of yeast identity concurrent with blood culture positivity, potential savings resulting from use of the C. albicans PNA FISH test compared with the C. albicans screen test averaged $1837 per patient treated, although laboratory costs for doing the C. albicans PNA FISH test ($82.72) exceeded those for the C. albicans screen test ($2.83). Savings were realized through a decrease in antifungal drug costs, particularly caspofungin. Incorporating the C. albicans PNA FISH test as part of the initial identification algorithm for yeasts recovered from blood can result in substantial savings for hospitals.

Antifungal Agents↗
PubMed2006

Caspofungin for invasive candidiasis at a tertiary care medical center.

BACKGROUND: Caspofungin is emerging as first-line therapy for invasive candidiasis. Data on the use of caspofungin for treatment for invasive candidiasis are limited to clinical trials and case reports. We report a single-center experience with 104 consecutive courses of caspofungin for the treatment of invasive candidiasis to evaluate a real-world performance of this drug. METHODS: A retrospective chart review of patients receiving caspofungin at a tertiary care medical center was performed. Patient information and microbiologic data were abstracted from patient charts and electronic medical records. RESULTS: Of 241 patients receiving caspofungin for all indications, 122 (51%) had proven invasive candidiasis. There were 104 treatment courses for candidiasis in 99 patients available for review. Bloodstream (66%) and abdominal infections (25%) were the most common sites of infection. Most infections were non-albicans (80/104, 77%; including patients infected with more than one species). Clinical cure rates at the end of therapy were 83% (57/69) for bloodstream infections and 84% (22/26) for abdominal infections. Caspofungin did not clear candidiasis in 14 episodes (microbiologic cure rate 75%, 42/56). CONCLUSIONS: The clinical use of caspofungin has been successful in the treatment of invasive candidiasis, even in patients with prior antifungal exposure. In this unselected review, caspofungin performed similarly as in clinical trials, and clinicians should consider caspofungin as first-line therapy for invasive candidiasis, particularly non-albicans species.

Antifungal Agents↗
PubMed2005

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.

BACKGROUND: Therapeutic practices for Cryptococcus neoformans infection in transplant recipients vary, particularly with regards to antifungal agent employed, and duration of therapy. The risk of relapse and time to recurrence is not known. We assessed antifungal treatment practices for cryptococcosis in a cohort of prospectively followed organ transplant recipients. METHODS: The patients comprised 83 transplant recipients with cryptococcosis followed for a median of 2.1 and up to 5.2 years. RESULTS: Patients with central nervous system infection (69% vs. 16%, P = 0.00001), disseminated infection (82.7% vs. 20%, P = 0.00001), and fungemia (29% vs. 8%, P = 0.046) were more likely to receive regimens containing amphotericin B than fluconazole as primary therapy. The use of fluconazole, on the other hand, was more likely for infection limited to the lungs (64% vs. 14%, P = 0.00002). Survival at 6 months tended to be lower in patients whose CSF cultures at 2 weeks were positive compared to those whose CSF cultures were negative (50% vs. 91%, P = 0.06). Maintenance therapy was employed in 68% (54/79) of the patients who survived >3 weeks. The median duration of maintenance therapy was 183 days; 55% received maintenance for > or = 6 months and 25% for >1 year. Relapse was documented in 1.3% (1/79) of the patients. CONCLUSIONS: A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.

Adult↗
PubMed2005

Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome.

This study describes the association of allograft loss and immune reconstitution syndrome (IRS) in the course of Cryptococcosis neoformans infection in renal transplant recipients. Patients comprised 54 renal allograft recipients with cryptococcosis in a prospective, multicenter study. IRS developed in 5.5% (3/54) of the renal transplant recipient with C. neoformans infection. The renal allograft was lost to chronic rejection in 66% (2/3) of the patients with cryptococcosis who developed IRS compared to 5.9% (3/51) of those who did not (P=0.012). Kaplan-Meier survival analysis showed that subsequent to cryptococcal infection the probability of allograft survival was significantly lower in patients who developed IRS compared to those who did not develop IRS (P=0.0004). Temporal association of graft loss with IRS suggests a common pathophysiologic basis for these entities with implications relevant for the optimal management of renal transplant recipients with cryptococcosis.

Cryptococcosis↗
PubMed2005

Candida glabrata fungemia in transplant patients receiving voriconazole after fluconazole.

The clinical impact of voriconazole resistance in Candida glabrata is not well described. Five hematopoietic stem cell transplant recipients that developed breakthrough Candida glabrata bloodstream infections while receiving voriconazole are described and the clinical management and susceptibility profiles of their isolates are reported. All patients were markedly immunosuppressed, and in all cases, voriconazole use was preceded by prolonged fluconazole exposure (median 60 days); median voriconazole exposure prior to candidemia was 48 days. Isolates from 4 patients were shown to be resistant to fluconazole and itraconazole when tested in vitro; these same isolates had MICs to voriconazole and posaconazole > or = 2 microg/ml. Clinical failure to voriconazole may result from deficits in host defense, retained infected foci, and adaptation of the organism to environmental pressures, the specific sequence and mechanisms of which warrant further study. Clinicians must maintain a high index of suspicion for these infections in highly susceptible hosts despite voriconazole therapy, particularly when voriconazole use is preceded by prolonged fluconazole exposure.

Adolescent↗
PubMed2005

Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans.

BACKGROUND: Measurement of (1-->3)-beta-D-Glucan (BG) has emerged as an adjunct diagnostic strategy for invasive fungal infections (IFI). METHODS: Subjects at 6 clinical sites in the United States were enrolled as either fungal infection-negative subjects (n = 170) or subjects with proven or probable IFI according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria (n = 163). A central laboratory and 4 sites performed assays. A single sample was obtained per patient and was evaluated using an assay to detect serum BG derived from fungal cell walls (range, 0 to > 7000 pg/mL). RESULTS: At a cutoff of 60 pg/mL, the sensitivity and specificity of the assay were 69.9% and 87.1%, respectively, with a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 75.1%. At a cutoff value of 80 pg/mL, the sensitivity and specificity were 64.4% and 92.4%, respectively, with a PPV of 89% and an NPV of 73%. Of the 107 patients with proven candidiasis, 81.3% had positive results at a cutoff value of 60 pg/mL, and 77.6% had positive results at a cutoff value of 80 pg/mL. Of the 10 patients with aspergillosis, 80% had positive results at cutoff values of 60 and 80 pg/mL. The 3 subjects diagnosed with Fusarium species had positive results at a cutoff value of 60 pg/mL. Patients infected with Mucor or Rhizopus species (both of which lack BG) had negative results at both cutoff values, and of the 12 patients with Cryptococcus infection, 3 had positive results at a cutoff value of 60 pg/mL, and 2 had positive results at a cutoff value of 80 pg/mL. Of the subjects with proven positive results who were receiving antifungal therapy (n = 118), 72.9% had results positive for BG at a cutoff value of 60 pg/mL, and 69.5% had results positive for BG at a cutoff value of 80 pg/mL. The interlaboratory sample test r2 was 0.93. CONCLUSION: Reproducible assay results with high specificity and high PPV in a multicenter setting demonstrate that use of an assay to detect serum BG derived from fungal cell walls is a useful diagnostic adjunct for IFI.

Adult↗
PubMed2005

Study of renal safety in amphotericin B lipid complex-treated patients.

To investigate the renal safety of amphotericin B lipid complex (ABLC), records from 3514 ABLC-treated patients with fungal infections were reviewed. The median change in predicted creatinine clearance (CCr) from baseline to the end of therapy was -3 mL/min (range, -119 to 118 mL/min); doubling of serum creatinine (S-Cr) level occurred in 13% of patients, and new dialysis was needed for 3% of patients. Patients with underlying renal disease who had received prior antifungal therapy demonstrated a median CCr of 0.5 mL/min (range, -107 to 52 mL/min). Despite increased risk for renal impairment in allogeneic hematopoietic stem-cell transplant recipients, only 17% of patients demonstrated end-of-therapy doubling of S-Cr levels, and the median change in CCr was -10 mL/min (range, -107 to 108 mL/min). In ABLC-treated patients, concomitant treatment with potentially nephrotoxic agents and a baseline S-Cr level of <2 mg/dL were factors predisposing for the development of nephrotoxicity. These data provide evidence that ABLC may be used safely to treat patients who are at increased risk for renal impairment.

Adolescent↗
PubMed2005

An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.

BACKGROUND: We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. METHODS: The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. RESULTS: In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. CONCLUSIONS: This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

Adult↗
PubMed2005

Non-Aspergillus fungal pneumonia in transplant recipients.

Although species of Aspergillus and Candida account for most deeply invasive and life-threatening fungal infections, the past decades have seen a rise in the immunocompromised population. With this increase, additional fungi have emerged as important agents of morbidity and mortality. These opportunistic fungi are characterized by their ubiquitous presence in the environment, their ability to cause disease in immunosuppressed patients, and their diminished susceptibility to the currently available antifungal agents. Pneumonia, one aspect of a myriad of clinical manifestations caused by these fungal pathogens, is discussed in this article.

Hematopoietic Stem Cell Transplantation↗
PubMed2005

Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens.

The immunosuppressants tacrolimus (FK506) and cyclosporine A inhibit calcineurin and have potent antifungal activity. In this study, 24% of Cryptococcus neoformans isolates from solid-organ transplant patients exhibited altered sensitivity to these drugs, which may have an impact on the infectious course but does not appear to be the consequence of immunosuppressive therapy.

Calcineurin↗
PubMed2005

Posaconazole.

Invasive fungal infections are occurring with increasing frequency secondary to medical advances in the areas of transplantation, cancer management and autoimmune diseases. Unfortunately, the currently available antifungal armamentarium does not meet the increasing needs of managing infection in these complex patient populations. Posaconazole, a new triazole antifungal agent, is being investigated for its role in treating serious infections due to yeasts and molds. This new drug offers an expanded spectrum of activity over other members of its class. In addition to potent activity against fluconazole-resistant Candida and refractory cases of aspergillosis, posaconazole demonstrates activity against Zygomycetes. Posaconazole is a well-tolerated agent that offers a diminished toxicity profile compared with other currently marketed systemic antifungal agents. Clinical success rates thus far have been promising, although the exact role of this agent in treating and preventing invasive fungal infections is yet to be determined.

Antifungal Agents↗
PubMed2005

Echinocandins: role in antifungal therapy, 2005.

Novel therapies to treat invasive fungal infections have revolutionised the care of patients with candidiasis, aspergillosis and other less common fungal infections. Physicians in the twenty first century have access to safer versions of conventional drugs (i.e., lipid amphotericin B products), extended-spectrum versions of established drugs (i.e., voriconazole), as well as a new class of antifungal agents; the echinocandins. The increased number of options in the antifungal armamentarium is well timed, as the incidence of both invasive candidiasis and invasive aspergillosis, and the financial burden associated with these infections, have increased significantly in the past several decades. The increasing incidence of fungal infections has risen in parallel with the increase in critically ill and immunocompromised patients. Candida is the fourth most common bloodstream isolate, approximately 50% of which are non-albicans species. Estimates suggest there to be 9.8 episodes of invasive candidiasis per 1000 admissions to surgical intensive care units, with attributable mortality at 30% and cost per episode of US44,000 dollars. The burden of candidiasis is even higher in the paediatric population, with Candida being the second most common bloodstream infection. The increase in non-albicans candidiasis mandates the introduction of new antifungal agents capable of treating these often azole-resistant isolates. In addition, there has been a rise in the incidence of invasive aspergillosis, the most common invasive mould infection following haematopoietic stem cell transplantation, with an estimated incidence of 10 - 20%. The mortality associated with invasive aspergillosis has increased by 357% since 1980. Unfortunately, the overall survival rate among patients treated with amphotericin B, and even voriconazole, remains suboptimal, as evidenced by the failure of treatment in 47% of patients in the landmark voriconazole versus amphotericin B trial. Given the increasing incidence and suboptimal outcomes of these serious fungal infections, novel therapies represent an opportunity for significant advancement in clinical care. The current challenge is to discover the optimal place for the echinocandins in the treatment of invasive fungal infections.

Anidulafungin↗
PubMed2004

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.

Adolescent↗