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C A Kauffman

Publications and source records attributed to C A Kauffman.

At least 37 records · Page 2Linked to original sources

Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.

Amphotericin B↗

Practice guidelines for the management of patients with sporotrichosis. For the Mycoses Study Group. Infectious Diseases Society of America.

UNLABELLED: The recommendations for the treatment of sporotrichosis were derived primarily from multicenter, nonrandomized treatment trials, small retrospective series, and case reports; no randomized, comparative treatment trials have been reported. Most cases of sporotrichosis are non life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. The treatment of choice for fixed cutaneous or lymphocutaneous sporotrichosis is itraconazole for 36 months. The preferred treatment for osteoarticular sporotrichosis also is itraconazole, but therapy must be continued for at least 12 months. Pulmonary sporotrichosis responds poorly to treatment. Severe infection requires treatment with amphotericin B; mild to moderate infection can be treated with itraconazole. Meningeal and disseminated forms of sporotrichosis are rare and usually require treatment with amphotericin B. AIDS patients most often have disseminated infection and require life-long suppressive therapy with itraconazole after initial use of amphotericin B. OVERVIEW: Sporotrichosis is caused by the dimorphic fungus Sporothrix schenckii, which is found throughout the world in decaying vegetation, sphagnum moss, and soil. The usual mode of infection is by cutaneous inoculation of the organism. Pulmonary and disseminated forms of infection, although uncommon, can occur when S. schenckii conidia are inhaled. Infections are most often sporadic and usually associated with trauma during the course of outdoor work. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos. Outbreaks have been well-described and often are traced back to activities that involved contaminated sphagnum moss, hay, or wood. Most cases of sporotrichosis are localized to the skin and subcutaneous tissues. Dissemination to osteoarticular structures and viscera is uncommon and appears to occur more often in patients who have a history of alcohol abuse or immunosuppression, especially AIDS. Spontaneous resolution of sporotrichosis is rare, and treatment is required for most patients. Although sporotrichosis localized to skin and subcutaneous tissues is readily treated, management of osteoarticular, other localized visceral, and disseminated forms of sporotrichosis is difficult. OBJECTIVE: The objective of these guidelines is to provide recommendations for the treatment of various forms of sporotrichosis. OUTCOMES: The desired outcomes of treatment include eradication of S. schenckii from tissues, resolution of symptoms and signs of active infection, and return of function of involved organs. In persons with AIDS, eradication of the organism may not be possible, but clinical resolution should be attained and subsequently maintained with suppressive antifungal therapy. EVIDENCE: The English-language literature on the treatment of sporotrichosis was reviewed. Although randomized, blinded, controlled treatment trials were sought, none were found to have been performed for the treatment of sporotrichosis. Therefore, most weight was placed on those reports that were derived from multicenter trials of specific treatment modalities for sporotrichosis. Small series from a single institution and individual case reports were accorded less importance. VALUES: The highest value was placed on clinical efficacy and the ability of the antifungal regimen to eradicate the organism, but safety, tolerability, and cost of therapy were also valued. BENEFITS AND COSTS: The benefits of successfully treating sporotrichosis accrue primarily for the patient. Because this infection is not spread from person-to-person, public health aspects of treatment are of minor importance. Most forms of sporotrichosis are not life-threatening; thus, therapy is aimed at decreasing morbidity, improving quality of life, and allowing the patient to return to occupational and familial pursuits. (ABSTRACT TRUNCATED)

AIDS-Related Opportunistic Infections↗

Epidemiology of yeast colonization in the intensive care unit.

In order to investigate the epidemiology of colonization and possible transmission of yeasts among patients and healthcare workers in adult intensive care units (ICUs), 194 patients were followed for a mean of 9 +/- 11 days and 63 healthcare workers were followed for a mean of 132 +/- 52 days. Among the patients, 142 (73%) were colonized by yeast, with Candida albicans being the species most commonly recovered. Most patients (65%) were already colonized with yeast upon admission to the intensive care unit; only 17% became colonized after admission. Persistent colonization occurred in 51 (55%) of 92 patients who had more than three cultures performed; in 75% of them, colonization persisted with the same strain of Candida albicans or Candida glabrata. Bacterial infection in the month preceding entry into the ICU was the only risk factor significantly associated with yeast colonization. Among the healthcare workers, yeasts were isolated from 42 (67%). Candida albicans was most frequently recovered from the oropharynx (19% of occasions), and Candida parapsilosis was most frequently found on hands (8% of occasions). Persistent colonization of the oropharynx occurred in only six healthcare workers, and none had persistence of yeasts on hands. In this non-outbreak setting, 5 (4%) of 123 patient/healthcare worker interactions that were linked epidemiologically yielded the same strain of Candida albicans, providing evidence for possible cross-transmission. No similar link was found between healthcare worker-patient interactions and colonization with Candida glabrata or Candida parapsilosis.

Adult↗

Prevention and prophylaxis of invasive fungal sinusitis in the immunocompromised patient.

Fungal infections are a leading cause of morbidity and mortality among immunocompromised patients. Invasive fungal sinusitis is a devastating complication of immunosuppression. Treatment options are limited and often ineffective, making prevention important. Measures to decrease environmental exposure, indications for antifungal prophylaxis, and limitations of current regimens are discussed.

Antifungal Agents↗

Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.001), with higher eradication rates among patients completing 14 days of therapy (P<.0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients. Pretreatment serum creatinine levels were inversely related to candiduria eradication. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.

Aged↗

Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Although fungal urinary tract infections are an increasing nosocomial problem, the significance of funguria is still not clear. This multicenter prospective surveillance study of 861 patients was undertaken to define the epidemiology, management, and outcomes of funguria. Diabetes mellitus was present in 39% of patients, urinary tract abnormalities in 37.7%, and malignancy in 22.2%; only 10.9% had no underlying illnesses. Concomitant nonfungal infections were present in 85%, 90% had received antimicrobial agents, and 83.2% had urinary tract drainage devices. Candida albicans was found in 51.8% of patients and Candida glabrata in 15.6%. Microbiological and clinical outcomes were documented for 530 (61.6%) of the 861 patients. No specific therapy for funguria was given to 155 patients, and the yeast cleared from the urine of 117 (75.5%) of them. Of the 116 patients who had a catheter removed as the only treatment, the funguria cleared in 41 (35.3%). Antifungal therapy was given to 259 patients, eradicating funguria in 130 (50.2%). The rate of eradication with fluconazole was 45.5%, and with amphotericin B bladder irrigation it was 54.4%. Only 7 patients (1.3%) had documented candidemia. The mortality rate was 19.8%, reflecting the multiple serious underlying illnesses found in these patients with funguria.

Aged↗

Pathogenic organisms associated with artificial fingernails worn by healthcare workers.

OBJECTIVE: To determine differences in the identity and quantity of microbial flora from healthcare workers (HCWs) wearing artificial nails compared with control HCWs with native nails. DESIGN: Two separate studies were undertaken. In study 1, 12 HCWs who did not normally wear artificial nails wore polished artificial nails on their nondominant hand for 15 days. Identity and quantity of microflora were compared between the artificial nails and the polished native nails of the other hand. In study 2, the microbial flora of the nails of 30 HCWs who wore permanent acrylic artificial nails were compared with that of control HCWs who had native nails. In both studies, nail surfaces were swabbed and subungual debris was collected to obtain material for culture. Staphylococcus aureus, gram-negative bacilli, enterococci, and yeasts were considered to be potential pathogens. All organisms were identified and quantified. RESULTS: In study 1, potential pathogens were isolated from more samples obtained from artificial nails than native nails (92% vs. 62%; P<.001). Colonization of artificial nails increased over time; by day 15, 71% of cultures yielded a pathogen compared with 21% on day 1 (P=.004). A significantly greater quantity of organisms (expressed as mean log10 colony-forming units +/- standard deviation) was isolated from the subungual area than the nail surface; this was noted for both artificial (5.0+/-1.4 vs. 4.1+/-1.0; P<.001) and native nails (4.9+/-1.3 vs. 3.7+/-0.8; P<.001). More organisms were found on the surface of artificial nails than native nails (P=.008), but there were no differences noted in the quantities of organisms isolated from the subungual areas. In study 2, HCWs wearing artificial nails were more likely to have a pathogen isolated than controls (87% vs. 43%; P=.001). More HCWs with artificial nails had gram-negative bacilli (47% vs. 17%; P=.03) and yeasts (50% vs. 13%; P=.006) than control HCWs. However, the quantities of organisms isolated from HCWs wearing artificial nails and controls did not differ. CONCLUSIONS: Artificial fingernails were more likely to harbor pathogens, especially gram-negative bacilli and yeasts, than native nails. The longer artificial nails were worn, the more likely that a pathogen was isolated. Current recommendations restricting artificial fingernails in certain healthcare settings appear justified.

Adult↗

Effectiveness of a vancomycin restriction policy in changing the prescribing patterns of house staff.

After noting a rise in vancomycin-resistant enterococci (VRE) infections, we initiated a program to decrease inappropriate vancomycin use that focused on improvement of house staff prescribing practices. The initial intervention in June, 1995, encouraging house staff to follow hospital guidelines for vancomycin use and eliciting support from service chiefs in this effort, had little impact. A more intensive educational intervention, beginning in January, 1996, involved concurrent review of all vancomycin orders and one-on-one discussion with the house staff regarding the rationale for the order by an infectious diseases clinical pharmacist. When usage was deemed inappropriate, the pharmacist asked that vancomycin be discontinued, but no automatic stop orders were issued. During the next two and one-half years, this second intervention proved effective at decreasing inappropriate use from 39% to 16.8% +/- 2.4% (p = 0.005). This change was primarily due to a decrease in appropriate vancomycin prophylaxis by cardiothoracic surgery. VRE infections decreased from 0.29/100 patients discharged prior to initiating the program to 0.13/100 patients discharged after the second intervention (p = 0.01). This educational program, although labor-intensive, preserved house staff decision-making skills related to antibiotic prescribing at the same time that it decreased inappropriate vancomycin use.

Antibiotic Prophylaxis↗

Does long-term itraconazole prophylaxis result in in vitro azole resistance in mucosal Candida albicans isolates from persons with advanced human immunodeficiency virus infection? The National Institute of Allergy and Infectious Diseases Mycoses study group.

The effects of prolonged itraconazole exposure on the susceptibility of Candida albicans isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal Candida sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (P = 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group. C. albicans accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC(50)) for last-episode isolates from the itraconazole group was 0.125 microg/ml compared to 0.015 microg/ml for the placebo group subjects, P = 0.0001. The MIC(50) of fluconazole for the last isolates from the itraconazole group was 1.5 microg/ml compared to 0.5 microg/ml for the placebo subjects (P = 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (P = 0.001). Similarly, a lower proportion of C. albicans isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (P = 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (P = 0.001); fluconazole susceptibility, 23 and 4%, respectively (P = 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole.

AIDS-Related Opportunistic Infections↗

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium.

A symposium was held on May 8, 2000 to discuss the management of deep infections with Candida species. Among the findings discussed were the following. Candiduria is most often benign, though it occurs in patients with serious underlying diseases. Candida species are now the fourth most common cause of nosocomial bloodstream infections, usually arising from an intravenous catheter. Candida albicans represents only 50-60% of the isolates. There has been no change in the frequency of fluconazole resistance in C. albicans but some of the other species now being isolated from blood are constitutively more resistant to this drug. Nevertheless, for most non-neutropenic patients with candidemia, fluconazole is a reasonable choice for initial therapy. In the neutropenic patient, candidemia is now uncommon. Deep candida infections in neutropenic patients are usually being treated empirically with an amphotericin B formulation. Hepatosplenic candidiasis is usually detected only after recovery from neutropenia but can be suspected by imaging techniques. Improved diagnostic techniques for deep candidiasis in the neutropenic patient remain a critical requirement.

Antifungal Agents↗

Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients.

BACKGROUND: Staphylococcus aureus is a common cause of serious infection in patients infected with HIV. OBJECTIVES: To evaluate risk factors for and quantitative effect of S. aureus infection in HIV-infected patients, with special attention to nasal carriage. DESIGN: Prospective, multihospital cohort study. SETTING: Three tertiary care Veterans Affairs Medical Centers. PARTICIPANTS: 231 ambulatory HIV-infected patients. RESULTS: Thirty-four percent of patients were nasal carriers of S. aureus. Of these patients, 38% were persistent carriers and 62% were intermittent carriers. Twenty-one episodes of infection occurred in 13 patients: Ten were bacteremias (including 2 cases of endocarditis), 1 was pneumonia, and 10 were cutaneous or subcutaneous infections. Seventeen (85%) of these episodes occurred in patients with CD4 counts less than 100 cells/mm3. Recurrent infections occurred in 3 of 7 patients who survived an initial S. aureus infection. The mortality rate was higher among patients with S. aureus infection than among those without infection (P = 0.03). Factors significantly associated with S. aureus infection were nasal carriage, presence of a vascular catheter, low CD4 count, and neutropenia. Molecular strain typing indicated that for 6 of 7 infected patients, the strain of S. aureus isolated from the infected sites was the same as that previously cultured from the nares. CONCLUSION: Nasal carriage is an important risk factor for S. aureus infection in HIV-infected patients. Controlled studies are indicated to determine whether eradication of nasal carriage in a selected subset of patients (for example, those with a low CD4 cell count) might prevent invasive S. aureus infection in patients with HIV infection.

AIDS-Related Opportunistic Infections↗

Colorimetric method for susceptibility testing of voriconazole and other triazoles against Candida species.

A microdilution assay using Alamar Blue, a colorimetric indicator, was compared with the NCCLS macrodilution broth assay for voriconazole, fluconazole, and itraconazole against Candida albicans, Candida glabrata, and Candida krusei. Concordance (+/- 2 dilutions) between the two methods was highest for voriconazole (98.3%), and for fluconazole and itraconazole it was 94.3 and 95.4%, respectively. Twenty-six of 32 (81.2%) discordant readings (> or = 3 dilutions different) were noted in C. glabrata isolates, and all but two isolates showing discordance had higher minimum inhibitory concentration readings with the colorimetric method.

Antifungal Agents↗

Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection.

AIDS-Related Opportunistic Infections↗

Sporotrichosis.

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Humans↗

Systemic antifungal agents. What is in the pipeline?

With the increase in serious and often life-threatening fungal infections over the last 2 decades, there has been an enhanced effort to bring new antifungal agents into the therapeutic armamentarium. The introduction of new agents into the clinical setting has been slow, in part because several drugs which appeared promising in vitro and in short term animal studies later proved to be toxic. Toxicity has been a major hurdle in the development of antifungal agents because mammalian cells, in contrast to bacterial cells, share with fungal cells many structures and metabolic pathways. For example, the 2 most common classes of antifungal agents, polyenes and azoles, target the synthesis of the cell membrane, a structure shared by both mammalian and fungal cells, and thus these drugs have inherent toxicity. Antifungal agents that act on protein synthesis are also inherently toxic to mammalian as well as fungal cells. New agents that target the fungal cell wall, a structure with no homology in mammalian cells, may prove to be less toxic and are currently of great interest.

Antifungal Agents↗

In vitro activity of voriconazole against Candida species.

The in vitro activity of voriconazole was compared with that of itraconazole and fluconazole against 181 isolates of Candida albicans, 124 isolates of Candida glabrata, and 20 isolates of Candida krusei obtained from the early 1980s through the mid-1990s. Voriconazole had greater intrinsic activity than fluconazole or itraconazole against all three Candida species. For C. glabrata, C. krusei, and C. albicans, the MIC50 values for voriconazole were 1 microgram/mL, 0.5 microgram/mL, and 0.01 microgram/mL, respectively compared with fluconazole MIC50 values of 8 micrograms/mL, 64 micrograms/mL, and 0.25 microgram/mL, respectively. If isolates from AIDS patients were excluded, MIC values for isolates from the 1990s were no higher than those noted for isolates from the 1980s. Voriconazole, a new triazole antifungal agent, appears to have enhanced activity against these three species of Candida; the clinical relevance of these findings should be studied in treatment trials.

Antifungal Agents↗