Richard A. Jacobs

Lipid Formulations of Amphotericin B: Clinical Efficacy and Toxicities

Commercially available lipid formulations of amphotericin B (Abelcet, Amphotec, and AmBisome) represent a significant advance in drug delivery technology. Differences in biochemical, pharmacokinetic, and pharmacodynamic properties among the lipid products have been shown in in vitro and in vivo models. Clinical experience with these products has been primarily in patients either refractory to or intolerant of conventional amphotericin B deoxycholate (AmBd). None of the lipid-based products demonstrates superior efficacy when prospectively compared with AmBd in the treatment of documented infections. When used for the empirical treatment of febrile neutropenia, AmBisome significantly reduced the incidence of proven emergent fungal infections but did not improve short-term survival rates, in comparison with AmBd. Acute infusion-related adverse events vary, whereas nephrotoxicity is reduced with all three lipid formulations. Until superior efficacy is clearly shown (for documented infections) or pharmacoeconomic analyses document the value of these drugs, use of such expensive agents should be highly restricted to those who are intolerant of or refractory to AmBd.

Fungal infections in patients with acute leukemia

We reviewed the records of 32 patients with acute leukemia and proved invasive fungal infections to determine the clinical and pathologic characteristics of systemic mycosis in patients undergoing intensive induction chemotherapy. The incidence of invasive fungal infections among our patients was at least 27 percent, and Candida and Aspergillus accounted for the majority of these infections. Patients with systemic candidiasis generally had prolonged severe neutropenia, fever refractory to antibiotics, and evidence of mucosal colonization by fungi. At autopsy, Candida was always widely disseminated. Patients with aspergillosis generally had neutropenia, fever, and pulmonary infiltrates at the time of admission to the hospital and, at autopsy, their infections were primarily confined to the lungs. Patients infected with both Candida and Aspergillus had clinical and pathologic findings that were a combination of the features of each type of infection. A diagnosis of invasive fungal infection was established before death in only nine of the patients, all of whom had systemic candidiasis. Four of these patients were successfully treated and survived their hospitalization. The reasons for frequently misdiagnosing and unsuccessfully treating systemic mycosis in patients with acute leukemia are examined, and suggestions are made for improved management of patients at high risk for these infections. These suggestions are based upon recognition of the clinical settings in which fungal infections occur, the aggressive use of invasive diagnostic procedures, and the early empiric use of amphotericin B.

Epidemic Postsurgical Candida Parapsilosis Endophthalmitis: Clinical Findings and Management of 15 Consecutive Cases

Fifteen cases of postoperative Candida parapsilosis endophthalmitis occurring secondary to a contaminated lot of an irrigating solution were studied. All patients underwent a vitreous tap or diagnostic and therapeutic vitrectomy. Eleven of the 15 specimens were positive for the organism. Fourteen patients were treated with pars plana vitrectomy surgery. All patients were treated with intravitreal amphotericin B and systemic amphotericin B and 5-fluorocytosine. Two clinical recurrences were successfully treated with intravitreal amphotericin B, removal of the pseudophakos, and oral ketoconazole. The intraocular lens was retained in 11 of the 14 pseudophakic patients. Final visual acuities ranged from 20/25 to no light perception with eight of 15 patients having 20/60 or better visual acuities. Measurable levels of intraocular amphotericin B were found after systemic amphotericin B administration. Two patients with totals of 20 and 30 micrograms of intravitreal amphotericin B over 48 and 96 hours, respectively, had near normal ERGs one year later. Posterior capsulotomy and vitrectomy appear to decrease amphotericin B toxicity and allow sequential intraocular injection of this drug within a short time period.

Ceftriaxone Therapy for Staphylococcal Osteomyelitis: A Review

Ceftriaxone, although less active than standard antistaphylococcal agents, is potentially useful in the treatment of osteomyelitis. Thirty-one patients with osteomyelitis due to Staphylococcus aureus were identified, 22 of whom were treated with ceftriaxone and 9 with other agents. Of those patients treated with ceftriaxone, 17 were cured; all treatment failures were associated with chronic osteomyelitis and continued presence of necrotic bone or infected hardware. It is concluded that ceftriaxone is effective in the ambulatory treatment of S. aureus osteomyelitis.

Impact of a Piperacillin‐Tazobactam Shortage on Antimicrobial Prescribing and the Rate of Vancomycin‐Resistant Enterococci and Clostridium difficile Infections

Study Objective. To evaluate the impact of a shortage of piperacillintazobactam in the United States in 2002 on antimicrobial prescribing and associated rates of vancomycin‐resistant enterococci (VRE) and Clostridium difficile infections.

Antimicrobial therapy of gram-negative bacteremia at two university-affiliated medical centers

PURPOSE To describe antimicrobial prescribing practices and patient outcomes associated with the treatment of aerobic gram-negative rod bacteremia at two university-affiliated medical centers. SUBJECTS AND METHODS All adult patients with gram-negative bacteremia (N = 326) who were at Stanford and University of California, San Francisco (UCSF) Hospitals from September 1, 1996 through August 31, 1997 were evaluated via retrospective review of medical records. RESULTS Most patient characteristics were similar between institutions; however, patients at Stanford were more likely to have had a diagnosis of bone marrow transplantation, liver failure, or poor nutritional status, while more patients at UCSF had solid organ transplant, diabetes, pulmonary disease, or hypotension. The bacteriology was similar at both sites, with Escherichia coli the predominant pathogen (139 [43%] of 326). The majority of episodes were community acquired (67% [218/326]). Patients at Stanford were more likely to have been treated empirically with aminoglycosides (28% vs. 7%, P <0.001) and noncephalosporin beta-lactams (31% vs. 11%, P <0.001), while patients at UCSF were more likely to have received cephalosporins (62% vs. 29%, P <0.001) and fluoroquinolones (21% vs. 11%, P = 0.02). These patterns continued for definitive therapy. Overall mortality was 60 (19%) of 326. Several risk factors were associated with 14-day mortality, including severity of illness, neutropenia, diabetes mellitus, use of vasopressors, and empiric use of a noncephalosporin beta-lactam. CONCLUSION Prescribing practices for the treatment of gram-negative bacteremia differed significantly in the two institutions despite similar patients and pathogens.

Immune Reconstitution Reactions in Human Immunodeficiency Virus–Negative Patients: Report of a Case and Review of the Literature

BACKGROUND Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon initially described in patients with human immunodeficiency virus. Upon initiation of combination antiretroviral therapy, recovery of cellular immunity triggers inflammation to a preexisting infection or antigen that causes paradoxical worsening of clinical disease. A similar phenomenon can occur in human immunodeficiency virus-negative patients, including pregnant women, neutropenic hosts, solid-organ or stem cell transplant recipients, and patients receiving tumor necrosis factor inhibitors. OBSERVATIONS We report a case of leprosy unmasking and downgrading reaction after stem cell transplantation that highlights some of the challenges inherent to the diagnosis of IRIS, especially in patients without human immunodeficiency virus infection, as well as review the spectrum of previously reported cases of IRIS reactions in this population. CONCLUSIONS The mechanism of immune reconstitution reactions is complex and variable, depending on the underlying antigen and the mechanism of immunosuppression or shift in immune status. Use of the term IRIS can aid our recognition of an important phenomenon that occurs in the setting of immunosuppression or shifts in immunity but should not deter us from thinking critically about the distinct processes that underlie this heterogeneous group of conditions.

Case Report: Nocardia Osteomyelitis

Osteomyelitis is an unusual manifestation of infection with Nocardia spp, and most cases result from direct extension from a primary lung or cutaneous lesion. The authors report what they believe to be the first case of Nocardia vertebral osteomyelitis occurring postoperatively, and review the literature on the 19 previously reported cases of Nocardia osteomyelitis due to hematogenous dissemination or direct inoculation, excluding those occurring from direct extension of a mycetoma or primary lung infection.

Impact of an Intravenous Fluconazole Restriction Policy on Patient Outcomes

OBJECTIVE: To evaluate both the economic and clinical impact of an intravenous fluconazole restriction policy in a university teaching hospital. METHODS: Intravenous fluconazole was restricted to patients unable to take oral medications due to significant nausea or to patients whose oral intake was restricted. A retrospective chart review and computerized record review was conducted in patients receiving intravenous or oral fluconazole from January 1 to June 30, 1997, and again from January 1 to June 30, 1998, after implementation of the policy. RESULTS: Six-month institutional expenditures for intravenous fluconazole decreased following policy implementation, from

A therapeutic trial of antituberculous therapy for suspected lupus vulgaris: How long does it take to see clinical improvement?

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