W. Lance George

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

ÆTIOLOGY OF ANTIMICROBIAL-AGENT-ASSOCIATED COLITIS

Abstract Clostridium difficile was isolated from the faeces of a patient with clindamycin-associated pseudomembranous colitis (P.M.C.). The presence of a preformed faecal toxin and the toxigenicity of both the faecal isolate of C. difficile and a reference strain of C. difficile were demonstrated by tissue-culture assay. The toxin of both strains of C. difficile and that in the patients faeces were neutralised by heating and by incubation with antitoxin to C. sordellii, but not by incubation with antitoxin to C. histolyticum, C. œdematiens (novyi), C. welchii (C. perfringens) or C. septicum. These data implicate the toxin of C. difficile as a major, and perhaps the sole, cause of antimicrobial-agent-associated P.M.C. of man and suggest that the neutralisation of the faecal toxin of P.M.C. by C. sordellii antitoxin, as described by other investigators, may be a non-specific phenomenon.

Constitutional symptoms and health-related quality of life in patients with symptomatic HIV disease

PURPOSE To assess the severity of constitutional symptoms in persons with human immunodeficiency virus (HIV) infection, and their relationship to health-related quality of life (HRQOL). PATIENTS AND METHODS Two hundred five HIV-infected patients (93% male, 26% African American, 28% Latino, 39% white, 7% other ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital and a Veterans Administration hospital in southern California. Consenting subjects were administered a battery that included 11 scales measuring various aspects of health-related quality of life and detailed questions about six constitutional symptoms or symptom complexes (myalgias, exhaustion, anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about other manifestations of HIV disease. RESULTS Constitutional symptoms except weight loss were all strongly related to all measures of quality of life. On 0 (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals having all five symptoms other than weight loss) to 78 (for those with none) for physical function, 43 to 79 for emotional well-being, and 36 to 73 for social function. Adjustment for helper T-lymphocyte counts, duration of illness, and demographic characteristics did not diminish these associations. CONCLUSION The presence, number, and severity of constitutional symptoms in HIV disease is strongly related to health-related quality of life in symptomatic HIV-infected individuals. Identifying and treating these very common symptoms has the potential to improve quality of life in these patients.

Contamination of a hospital environment byClostridium difficile

Clostridium difficile was recovered from a variety of environmental sites in three hospital rooms occupied by a patient who had colitis due to this organism.C. difficile was detected for 40 days after the patient was moved from one of these rooms. These findings suggest that the contaminated hospital environment may be a clinically significant reservoir forC. difficile and that this organism may be a nosocomial pathogen. Isolation of patients and adequate decontamination of rooms may be needed to minimize risk to other patients.

Toxigenicity and antimicrobial susceptibility ofClostridium difficile, a cause of antimicrobial agent-associated colitis

Fourteen of 16 strains ofClostridium difficile, a recently recognized cause of antimicrobial agent-associated ileocolitis in laboratory animals and colitis in man, were found to be toxigenic. The susceptibility of these isolates to a variety of antimicrobial agents provides information that may be of value in assessing the means by whichC. difficile may produce colitis, in developing selective bacteriologic media for diagnosis, and in selecting appropriate antimicrobial therapy for colitis.

Comparison of Clinical Severity Score Indices for Clostridium difficile Infection

OBJECTIVE To compare 8 severity score indices for Clostridium difficile infection (CDI). DESIGN Prospective observational study. METHODS This study was conducted from July through October 2006. All hospitalized patients in 3 university-affiliated hospitals with a positive fecal Clostridium difficile toxin assay result were evaluated. Infection was considered severe if patients had at least 1 of the following clinical events during their hospitalization: (1) death attributed to CDI within 30 days after diagnosis, (2) colectomy necessitated by CDI, or (3) intensive care unit admission for management of complications attributed to CDI. Severity was assessed on the basis of 8 severity score indices, using published criteria for severe CDI as the benchmark. The 8 severity score indices studied were Beth Israel, University of Pittsburgh Medical Center version 1, University of Pittsburgh Medical Center version 2, Hines VA, modified University of Illinois, University of Calgary version 1, University of Calgary version 2, and University of Temple. RESULTS Of 184 patients with CDI evaluated, 19 had severe cases and 165 had nonsevere cases, as assessed on the basis of the defined severe CDI criteria. Sensitivities of the 8 severity score indices studied ranged from 63.2% to 84.2%, and specificities ranged from 59.4% to 93.9%. The Hines VA index had the highest kappa score (0.69 [95% confidence interval, 0.54-0.83]), followed by the University of Pittsburgh Medical Center version 1 index. Independent risk factors for severe CDI determined by multivariate analysis were abdominal distention (P = .007), fever (temperature, 38.0°C or above; P = .042), white blood cell count of at least 20,000 cells/mm(3) (P = .035), and hypoalbuminemia (serum albumin level less than 3 mg/dL; P = .029). CONCLUSION The Hines VA CDI severity score index appeared to display the strongest correlation for predicting more severe forms of CDI.

Intravenous catheter-associated Malassezia furfur fungemia☆

Malassezia furfur, a lipophilic yeast that is the etiologic agent of tinea versicolor, has not been considered as a cause of serious illness in adults in the past. Two adults are described in whom Malassezia furfur fungemia developed while receiving total parenteral nutrition supplemented with lipids. The organism was identified in blood cultures from both patients only after isolation media were supplemented with a source of fatty acids. Because M. furfur will grow only in media supplemented with fatty acids, clinicians should alert the laboratory whenever a lipophilic organism is suspected to be present in blood cultures.

Using the national registry of HIV-infected veterans in research: lessons for the development of disease registries.

Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VAs HIV registry is national in scope, it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VAs national HIV registry, and to test its accuracy and completeness. The VAs national HIV registry contains data that are electronically extracted from VAs computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40,000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem, especially for the pharmacy and laboratory files. In using VAs national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries.

Nontraumatic clostridial myonecrosis: An infectious disease emergency

A 64-year-old man presented with a history of four days of lower abdominal pain and 12 hours of cutaneous discoloration, bullae formation, and swelling of the soft tissues of abdominal wall and right thigh. Myonecrosis of abdominal wall and an adenocarcinoma of the cecum were found at operation. Cultures of blood and fluid from the bullae yielded Clostridium septicum. Nontraumatic clostridial myonecrosis is a fulminant, usually fatal disease that is most often the result of bacteremia from an occult gastrointestinal lesion. Ulceration of the colon or terminal ileum is the most common predisposing condition, and is usually due to gastrointestinal or hematological malignancy. Patients often present with nonspecific complaints, including pain at the affected site and fever. The disease progresses rapidly to include bronze discoloration, edema, and hemorrhagic bullous lesions of the skin, subcutaneous emphysema, and myonecrosis. Presumptive diagnosis often can be made by Gram stain of the bullous fluid that reveals gram-positive bacilli and a paucity of leukocytes. Favorable outcome depends on prompt institution of appropriate antimicrobial therapy and surgical debridement of involved soft tissues, as well as correction of the underlying disorder. This disease should be considered to be a medical-surgical emergency.

Implications for vancomycin-resistant Enterococcus colonization associated with Clostridium difficile infections

BACKGROUND Vancomycin-resistant Enterococcus (VRE) colonization of the gastrointestinal tract shares similar risk factors with Clostridium difficile infection. We sought to elucidate the prevalence and risk factors of VRE colonization associated with C difficile infection. METHODS All adult inpatients with C difficile infection from July 2006 to October 2006 were prospectively evaluated. All C difficile toxin-positive stool samples were screened for detection of VRE. Risk factors for VRE colonization were compared in patients with C difficile infection with and without VRE colonization. RESULTS Of the 158 cases of C difficile infection evaluated, 88 (55.7%) involved VRE colonization. Independent risk factors for VRE colonization were admission from long-term care facilities (P = .013), dementia (P = .017), and hospitalization in the previous 2 months (P = .014). No statistically significant difference between C difficile infection cases with and without VRE colonization in terms of previous receipt (within 1 month) of antibiotics, including metronidazole and vancomycin, was found on multivariate analysis. C difficile infection cases with VRE colonization had a higher prevalence of coinfection with methicillin-resistant Staphylococcus aureus (P = .002) and Acinetobacter spp (P = .006). CONCLUSION VRE colonization was associated with >50% of C difficile infection cases and with a higher rate of coinfection with multidrug-resistant pathogens. Given the high rate of C difficile infection associated with VRE colonization, active surveillance of VRE in patients with C difficile infection is reasonable in high-risk settings.