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Carol A Kauffman

Publications and source records attributed to Carol A Kauffman.

At least 19 recordsLinked to original sources

Histoplasmosis: a clinical and laboratory update.

Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

Amphotericin B↗

Clinical efficacy of new antifungal agents.

Several new options are now available for treating serious fungal infections. All three echinocandin agents currently available have been shown in randomized, blinded clinical trials to be efficacious in treating candidemia and invasive candidiasis. By contrast, the demonstrated efficacy of the echinocandins for the treatment of invasive aspergillosis has been based on historically controlled salvage treatment trials in patients failing or intolerant of other therapies. The new triazole agents, voriconazole and posaconazole, have a broad spectrum of antifungal activity. Voriconazole has become the agent of choice for invasive aspergillosis. On the basis of compassionate treatment data, posaconazole appears to be effective for treatment of zygomycosis. These agents have also been shown to be effective in the treatment of non-Aspergillus mould infections, several of the endemic mycoses and serious Candida infections.

Antifungal Agents↗

Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis.

The endemic mycoses are diverse group of fungi that share several characteristics. They are able to cause disease in healthy hosts, they each occupy a specific ecologic niche in the environment, and they exhibit temperature dimorphism, existing as molds in the environment at temperature of 25 degrees C to 30 degrees C, and as yeasts, or spherules in the case of coccidioidomycosis, at body temperatures. This article discusses histoplasmosis and blastomycosis. Sporotrichosis, which differs in that it is usually a localized lymphocutaneous infection, is included because it shares the characteristics of endemic mycoses.

Antifungal Agents↗

Improving the safety of intravenous admixtures: lessons learned from a Pentostam overdose.

CASE STUDY: Weaknesses in the multistep process of admixture preparation and administration resulted in a patient with cutaneous leishmaniasis (CL) receiving a 10-fold intravenous (IV) overdose of Pentostam (sodium stibogluconalte), a rarely used drug. LESSONS LEARNED: A review of this adverse event resulted in five recommendations: (1) Provide staffing continuity among pharmacists and pharmacy technicians preparing and nurses administering the admixture; (2) Take time to ensure thorough and deliberative consideration ofquestions or concerns about admixture preparation; (3) Use due diligence in performing double checks of admixture calculations; (4) Know the drug and seek clarification when appropriate; and (5) Examine label information carefully. PROGRESS UPDATE: Two changes were made to improve patientsafety. First, a form was developed to accompany the preparation of complex IV drugs, including chemoltherapy solutions and nonformulary IV admixtures; the form is consistently used. Second, the pharmacy service developed information sheets for 12 high-risk drugs frequently used in IV admixtures. DISCUSSION: The medical center had processes in place to prevent medication errors, yet an error occurred nonetheless. Weaknesses were identified in staff communication, quality assurance checks, and product labeling. Also, nurses and pharmacists had less than adequate information about new or unusually dosed medications.

Adult↗

Fungal infections.

Over the last decade, there have been changes in the epidemiology of fungal infections as well as dramatic improvements in the antifungal armamentarium. Candida species are an increasingly important cause of infection among patients in intensive care units. Mold infections continue to occur predominantly among highly immunosuppressed patients, such as those who have acute leukemia and those undergoing hematopoietic stem cell or solid organ transplantation. Aspergillus species remain the most common molds to cause invasive infection, but other environmental molds, such as Scedosporium, Fusarium, and various zygomycetes, including Rhizopus and Mucor, appear to be increasing in some medical centers. We now have available a new class of antifungal agents, the echinocandins, that act to damage the cell walls of Candida and Aspergillus species. Although limited in spectrum and only available in intravenous formulations, these agents are very safe and extremely well tolerated. Another new agent is the expanded spectrum triazole voriconazole. This agent has a very broad spectrum of activity, is available in both oral and intravenous formulations, and is approved for treatment of aspergillosis, other molds, and candidiasis. The major drawbacks with voriconazole are the number of drug-drug interactions and side effects, including rash, hepatitis, and visual disturbances. Treatment with amphotericin B, long the mainstay of antifungal therapy despite its inherent toxicity, is required much less often since the introduction of these new antifungal agents.

Antifungal Agents↗

Vancomycin-resistant enterococcal colonization and infection in liver transplant candidates and recipients: a prospective surveillance study.

BACKGROUND: Vancomycin-resistant enterococcal (VRE) infections cause significant morbidity and mortality among patients undergoing liver transplantation. We performed a prospective study among patients awaiting transplantation to assess rates, risk factors, and outcomes associated with VRE colonization before and after transplantation. METHODS: All adults on the transplantation waiting list from 2000-2003 were eligible. Demographic, historical, and laboratory data, as well as stool samples to be analyzed for VRE, were collected at enrollment and every 4-6 months thereafter until transplantation. After transplantation, samples were obtained every 3 days during hospitalization and were analyzed for VRE; outcomes were assessed at 90 days. RESULTS: Overall, 375 patients were enrolled in our study, and 142 received transplants. VRE colonization occurred in 50 (13%) of 375 patients before transplantation and was independently associated with treatment with antianaerobic antimicrobials, third-generation cephalosporins, proton pump inhibitors, or neomycin; having a recent endoscopic retrograde cholangiopancreatogram or paracentesis procedure; and admission to the liver unit. Of these 50 patients, 22 (44%) received a transplant, and 7 (32%) of 22 developed a VRE infection after transplantation. An additional 22 patients (18%) who were not colonized before transplantation acquired VRE after transplantation; VRE infection developed in 5 (23%) of these patients. Patients colonized with VRE either before or after transplantation had longer stays in the intensive care unit and the hospital. Mortality at 90 days was significantly greater among those who acquired VRE after transplantation (5 [23%] of 22), compared with those who had VRE colonization before transplantation (2 [9%] of 22). CONCLUSIONS: Liver transplantation candidates with VRE colonization before transplantation experience greater morbidity but not greater mortality, compared with noncolonized candidates. Transplant recipients who acquire VRE after transplantation have a higher mortality rate than noncolonized recipients. Strategies should be implemented to reduce nosocomial VRE acquisition after transplantation among this vulnerable group.

Adult↗

Candiduria.

Candiduria is a common finding. Yeasts can be detected in urine that is contaminated during collection, in patients who have bladder colonization, and in patients who have upper urinary tract infection that developed either from retrograde spread from the bladder or hematogenous spread from a distant source. Most patients with candiduria are asymptomatic. The rate of development of complications is not known but appears to be low; candidemia rarely results from asymptomatic candiduria unless obstruction is present or instrumentation of the urinary tract is done. Unfortunately, there are no established diagnostic tests that reliably distinguish infection from colonization. Guidelines for the treatment of candiduria, based almost entirely on anecdotal reports and expert opinions, rather than controlled clinical trials, have been suggested by the Infectious Diseases Society of America. Until reliable methods to distinguish infection from colonization are developed, further treatment trials are unlikely to provide information to guide the clinician in the treatment of candiduria.

Antifungal Agents↗

Candida glabrata fungemia: experience in a tertiary care center.

BACKGROUND: During the past decade, Candida glabrata has emerged as an important cause of fungemia. We reviewed demographic data, risk factors, treatment, and outcomes associated with C. glabrata fungemia from 1995-2002 and performed susceptibility testing of isolates. METHODS: Data on all episodes of fungemia were prospectively recorded, and the associated isolates were saved. Medical records were reviewed retrospectively. Susceptibility testing was performed for fluconazole, itraconazole, and voriconazole. RESULTS: C. glabrata caused 103 (17%) of 609 fungemic episodes during the 8-year period that we studied. Medical records and isolates were available for 94 episodes that occurred in 91 patients. The patients included 42 men and 49 women. The mean age was 51 years. Thirty-four episodes (36%) occurred in patients >60 years old; only 3 episodes occurred in patients <1 year old. The most common predisposing factors were use of broad-spectrum antibiotics (in 86% of episodes), use of central venous catheters (77%), stay in an intensive care unit (48%), renal failure (46%), and receipt of parenteral nutrition (45%). Of the 94 episodes, 83 were treated with antifungal agents. The overall mortality rate at day 30 was 29%. For the 11 episodes that were not treated, the mortality rate was 64% (7 of 11 episodes). Outcome appeared to be unrelated to whether fluconazole or amphotericin B was administered. In vitro, 60% of isolates were resistant to fluconazole, 83% to itraconazole, and 44% to voriconazole. Susceptibility to these azoles did not change over the 8 years of the study. CONCLUSION: C. glabrata fungemia was most often seen in older adults and was associated with a mortality rate of 29%. Outcomes appeared to be unrelated to in vitro susceptibility results and to the antifungal agent used.

Adolescent↗

Experience with community-based amphotericin B infusion therapy.

STUDY OBJECTIVES: To identify the types and frequencies of adverse events associated with community-based amphotericin B infusion therapy. A second objective was to validate the effectiveness of a monitoring system, based on guidelines from the Infectious Diseases Society of America (IDSA). DESIGN: Retrospective medical record review. SETTING: Outpatient clinic at a tertiary care center. PATIENTS: One hundred five patients who received amphotericin B therapy from a home care provider between January 1997 and July 2002. MEASUREMENTS AND MAIN RESULTS: A total of 113 courses of amphotericin B formulations were administered: liposomal amphotericin B, 41 courses (36%), amphotericin B deoxycholate, 31 courses (27%), amphotericin B lipid complex, 31 courses (27%), and amphotericin B colloidal dispersion, 3 courses (3%); an additional 7 courses consisted of sequential therapy with two different formulations. Nephrotoxicity was associated with 46 (41%) courses, electrolyte abnormalities with 40 (35%) courses, venous access device complications with 12 (11%) courses, and infusion reactions with 13 (12%) courses. Nephrotoxicity occurred most frequently in adults aged 60 years or older, solid organ transplant recipients, and those receiving concomitant cyclosporine. Only two (12%) of 17 courses in children younger than 13 years were associated with nephrotoxicity. Thirteen of all 113 courses resulted in patients requiring hospital admission due to their adverse events. Monitoring of electrolyte, serum creatinine, and blood urea nitrogen levels 2 or 3 times/week was adequate for identifying these events. CONCLUSION: Significant rates of adverse events occurred in patients who received community-based amphotericin B infusion therapy. A monitoring system based on IDSA guidelines was effective in facilitating the detection and management of these adverse events.

Adolescent↗

New antifungal agents.

Two new antifungal agents, voriconazole and caspofungin, are now available for treatment of systemic fungal infections. Voriconazole is an extended-spectrum triazole that is fungicidal for filamentous fungi, including Aspergillus, Scedosporium, Fusarium, Paecilomyces, and is active against all species of Candida. It has become first-line therapy for invasive aspergillosis. Voriconazole is given either by the oral or the intravenous route. Clinicians must be aware of drug-drug interactions and side effects, including visual disturbances and photosensitivity rash that can occur when voriconazole is used. Caspofungin is the first drug available from a new class of antifungal agents, echinocandins, that act to inhibit fungal cell wall synthesis. Caspofungin is fungicidal for all species of Candida and more slowly kills Aspergillus species. Caspofungin, available only for intravenous administration, has minimal side effects and very few drug interactions. The echinocandins will find most use for Candida infections and as second-line therapy for Aspergillus infections.

Journal Article↗

Fungemia caused by Zygoascus hellenicus in an allogeneic stem cell transplant recipient.

Zygoascus hellenicus (Candida hellenica) was isolated from a blood culture from a patient who had received an allogeneic stem cell transplant. The isolate displayed an antifungal susceptibility pattern of decreased susceptibility to fluconazole and itraconazole, high susceptibility to voriconazole, and low susceptibility to caspofungin. The organism was misidentified by a commercial yeast identification system. This is the first reported case of human infection with this rare ascomycetous yeast.

Base Sequence↗

Magnitude and duration of elevated gastric pH in patients infected with human immunodeficiency virus after administration of chewable, dispersible, buffered didanosine tablets.

STUDY OBJECTIVES: To test the hypothesis that gastric pH would be elevated above pH 3.0 for at least 2 hours after administration of chewable, dispersible, buffered didanosine tablets. Doses tested were 200 mg (two 100-mg tablets) and 400 mg (two 200-mg tablets). We also sought to compare these doses with regard to maximum gastric pH (pHmax), time to pHmax (TpH-max), time that gastric pH exceeds 3.0 (TpH>3), and area under the gastric pH versus time curve for pH greater than 3.0 (AUCT>pH 3). DESIGN: Prospective, parallel-group, dose-comparison, gastric pH study. SETTING: General Clinical Research Center, University of Michigan Hospitals, Ann Arbor, Michigan. PATIENTS: Nineteen patients infected with human immunodeficiency virus, aged 30-62 years, and receiving long-term didanosine therapy. INTERVENTION: Patients underwent continuous gastric pH monitoring, using the Heidelberg capsule radiotelemetric pH monitoring device. After documentation of a fasting baseline gastric pH below 3.0, patients were given 180 ml of water (control phase), and gastric pH was allowed to return to baseline. After administration of a single, oral dose of didanosine 200 mg or 400 mg with 180 ml of water, gastric pH was recorded until pH remained below 3.0 for 10 minutes. MEASUREMENTS AND MAIN RESULTS: A mean pHmax of 8.6 (range 6.3-9.5) was achieved with a TpH-max of 4.1 minutes (range 1-12.0 min). Mean TpH>3 was 24.9 minutes (range 15-55 min), with an AUCT>pH 3 of 2.6 pH x min(-1) (range 1.2-6.9 pH x min(-1)). The two doses of didanosine tested did not differ significantly in mean gastric pH parameters. CONCLUSIONS: After administration of chewable, dispersible, buffered didanosine tablets, 200 or 400 mg, the mean duration of elevated gastric pH (TpH>3) was less than 30 minutes, with a range of 15-55 minutes. Characterization of the magnitude and duration of elevated gastric pH may allow for earlier administration of other pH-sensitive drugs. The short duration of elevated gastric pH may help explain the wide variability in didanosine bioavailability observed clinically.

Administration, Oral↗

Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial.

Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P=.017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents who received placebo remained colonized (P<.001). At day 90 after study entry, 61% of the residents in the mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction in infections was seen with mupirocin treatment.

Aged↗

A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

Adolescent↗

Voriconazole: a new triazole antifungal agent.

Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi.

Antifungal Agents↗

Histoplasmosis.

The diagnosis of histoplasmosis depends on recognition of the different clinical manifestations of infection, accompanied by knowledge of the accuracy and limitations of tests used for diagnosis of fungal infections. Although most infections are asymptomatic, histoplasmosis can be severe, or even fatal, in patients who have experienced a heavy exposure, have underlying immune defects, or develop progressive disease that is not recognized and treated. This article provides an up-to-date clinical review of histoplasmosis, focusing on recognition, diagnosis, and management.

AIDS-Related Opportunistic Infections↗

Introduction of a waterless alcohol-based hand rub in a long-term-care facility.

OBJECTIVE: To examine the impact of introduction of an alcohol-based hand rub on hand hygiene knowledge and compliance and hand colonization of healthcare workers (HCWs) in a long-term-care facility (LTCF). METHODS: Two floors of an LTCF participated. Ward A used the hand rub as an adjunct to soap and water; ward B was the control. HCWs' hands were cultured using the bag-broth technique for Staphylococcus aureus, gram-negative bacilli (GNB), Candida, and vancomycin-resistant enterococci (VRE). HCWs completed a questionnaire at baseline and after an educational intervention and introduction of rub. RESULTS: Hand hygiene practices, knowledge, and opinions did not change after the educational or rub intervention. Ward A HCWs thought that the rub was faster (P = .002) and less drying (P = .04) than soap. Hand hygiene frequency did not differ at baseline between the two floors, but increased on ward A by the end of the study (P = .04). HCWs were colonized frequently with GNB (66%), Candida (41%), S. aureus (20%), and VRE (9%). Although colonization did not change from baseline on either ward, the rub was more effective in clearing GNB P =.03) and S. aureus (P = .003). Nosocomial infection rates did not change. CONCLUSION: The alcohol-based hand rub was a faster, more convenient, less drying method of hand hygiene for HCWs in an LTCF, and it improved compliance. Although microbial colonization did not change, the rub was more efficacious in removing pathogens already present on the hands of HCWs.

Anti-Infective Agents, Local↗