Wendy S. Armstrong

Pneumocystis carinii Mutations Are Associated with Duration of Sulfa or Sulfone Prophylaxis Exposure in AIDS Patients

This study was conducted to determine whether Pneumocystis carinii dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97 AIDS patients with PCP between 1991 and 1999 from 4 medical centers were amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis compared with 23% of isolates from patients not exposed (P=.001). Duration of prophylaxis increased the risk of mutations (relative risk [RR] for each exposure month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone prophylaxis increases the chance of developing a P. carinii mutation. The majority of patients with mutations respond to sulfa or sulfone therapy.

Pneumocystis carinii cytochrome b mutations are associated with atovaquone exposure in patients with AIDS

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.

Human Immunodeficiency Virus—Associated Fever of Unknown Origin: A Study of 70 Patients in the United States and Review

To characterize the clinical features of human immunodeficiency virus (HIV)-associated fever of unknown origin (FUO) in the United States, we performed a retrospective analysis of cases that fulfilled specific criteria (published by Durack and Street in 1991) at two medical centers in the United States between 1992 and 1997. Seventy cases met criteria for HIV-associated FUO; the mean CD4 cell count was 58/mm3, and the mean duration of fever was 42 days. A cause of FUO was found in 56 of the 70 cases; 43 were of a single etiology, and in 13 cases multiple conditions were established. The most common diagnoses were disseminated Mycobacterium avium infection (DMAC; 31%), Pneumocystis carinii pneumonia (13%), cytomegalovirus infection (11%), disseminated histoplasmosis (7%), and lymphoma (7%). In this United States series, FUO occurs most often in the late stage of HIV infection, individual cases often have multiple etiologies, and DMAC is the most common diagnosis.

Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in immunocompromised patients

Recent studies have shown that mutations in two amino acid positions of the Pneumocystis carinii dihydropteroate synthase gene are significantly more common in immunocompromised patients with P. carinii pneumonia who fail sulfa or sulfone prophylaxis. This paper reviews the studies that suggest that these mutations may be responsible for some failures of prophylaxis in P. carinii.

Increase in Prevalence of Pneumocystis carinii Mutations in Patients with AIDS and P. carinii Pneumonia, in the United States and China

This study of Pneumocystis carinii dihydropteroate synthase (DHPS) mutations in patients with AIDS who have P. carinii pneumonia compares the change in the prevalence of such mutations in the United States, where sulfa-drug prophylaxis is widespread, to that in China, where it is infrequent. The DHPS gene from 145 US patients presenting during 1983-2001 and from 15 Chinese patients presenting during 1998-2001 was amplified by polymerase chain reaction and was sequenced. In the United States, 40% of patients had DHPS mutations; 38% received sulfa-drug prophylaxis. Mutation prevalence increased to 70% during 2000-2001, from 25% during 1994-1995 (P<.01). In China, 7% of patients had DHPS mutations; none received sulfa-drug prophylaxis. The prevalence of P. carinii DHPS mutations has markedly increased in the United States but remains low in China.

Epidural abscess: a delayed complication of esophageal stenting for benign stricture

A case of anterior cervical epidural abscess associated with perforation of an endoscopically placed esophageal stent is presented. Although delayed esophageal perforation is a known complication of endoscopic stenting, no cases presenting with epidural abscess have yet been reported. The increasing application of endoscopic stenting for benign esophageal strictures provides greater opportunity for this type of delayed complication.

Case Report. Recurrence of increased intracranial pressure with antiretroviral therapy in an AIDS patient with cryptococcal meningitis

Summary.  We present the case of an AIDS patient with cryptococcal meningitis who, after an excellent clinical and mycological response to antifungal therapy, developed an exacerbation of signs and symptoms, including elevated intracranial pressure and an increase in cerebrospinal fluid cryptococcal antigen and white blood cells, following the initiation of highly active antiretroviral therapy (HAART). Cultures yielded no growth and the patient responded to repeated lumbar punctures without changing or intensifying antifungal therapy. To our knowledge, this is the first report of symptomatic elevated intracranial pressure occurring during HAART‐related immune recovery in a patient with cryptococcal meningitis. Exacerbation of symptoms does not necessarily reflect mycological failure that requires a change in antifungal therapy, but may relate to acutely increased intracranial pressure that will respond to simple measures, such as repeated lumbar punctures.

Use of Cytokines in Human Immunodeficiency Virus-Infected Patients: Colony-Stimulating Factors, Erythropoietin, and Interleukin-2

The recombinant human cytokines granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and interleukin-2 (IL-2) have been manufactured and licensed. Studies have been carried out that investigate the use of G-CSF and GM-CSF to reverse leukopenia, as adjunctive therapy for HIV-associated infections and for novel approaches to treat HIV infection, including stem cell mobilization. In addition, studies that identified the role of erythropoietin in the management of anemia have been performed. Furthermore, the abilities of G-CSF and erythropoietin to permit the continued use of marrow suppressive agents that are key in managing HIV infection have been assessed. The aim of this review is to summarize these studies and to describe the reports that evaluate the use of IL-2 to enhance elevation of CD4 cell counts mediated by highly active antiretroviral therapy. This summary is important to the treating clinician in that it identifies the optimal use of these cytokines in current clinical practice as well as their potential future roles.

Successful Treatment of Vancomycin Resistant Enterococcus faecium Mediastinitis Associated With Left Ventricular Assist Devices

We present 2 cases of vancomycin-resistant Enterococcus faecium mediastinitis associated with left ventricular assist devices in the setting of heart transplantation. Despite complicated operative courses and deep infection secondary to antimicrobial resistant organisms, both patients were successfully treated and have remained infection free in the long term.

A case of fatal West Nile virus meningoencephalitis associated with receipt of blood transfusions after open heart surgery

First identified in the United States in 1999, West Nile virus caused approximately 3,500 infections in the late summer and fall of 2002. The virus is predominantly transmitted by mosquitoes, and the risk of infection through blood product transfusion is believed to be low. We present a case of West Nile virus encephalitis transmitted by red blood cell transfusion at the time of coronary artery bypass grafting that resulted in the patients death. Individuals undergoing procedures with high blood product transfusion requirements, such as cardiac surgery or organ transplantation, may be at higher risk of this nosocomial infection during epidemics.