Antimicrobial formulary control: is the glass half empty or half full?
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Anti-Bacterial Agents↗
Biomedical subjects
C Pomeroy
Publications and source records attributed to C Pomeroy.
T-lymphocyte subsets in patients with abnormal body weight: longitudinal studies. in anorexia nervosa and obesity.
OBJECTIVE: In contrast to other types of starvation which are characterized by low CD4+ counts and increased susceptibility to infection, anorexia nervosa is not associated with an increase in infectious complications. To determine why infection risk of anorectics differs from that of other starving populations, we studied T-lymphocytes, including CD4+ and CD8+ phenotypes, in patients with anorexia nervosa, and for comparison, in dieting obese subjects. METHODS: T-lymphocyte phenotypes were determined by flow cytometric analysis of monoclonal antibody-labeled cells obtained from patients with anorexia nervosa before and after successful therapy and weight gain, and in obese subjects before and after weight loss on a very-low-calorie diet. RESULTS: Weight loss in anorectics and obese dieters was associated with normal CD4+ counts. Unexpectedly, CD8+ counts were low in anorectics, both before and after weight gain, and in obese subjects after (but not before) dieting. DISCUSSION: Normal CD4+ counts in anorectics and obese dieters, despite marked weight loss, may explain the lack of increased infection risk in these eating-disordered patients, in contrast to other starving populations. The observation that CD8+ counts are low in anorectics with low and restored body weight and in obese patients after dieting has not been previously reported. The persistence of low CD8+ counts in anorectics even after weight gain suggests that some factors other than weight loss per se may be involved, possibly including effects due to stress, comorbid psychiatric conditions, or unidentified aspects of dysregulated pathophysiology secondary to disordered eating.
Adolescent↗
Prophylactic antibiotics for the prevention of early infection in multiple myeloma.
PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.
Aged↗
Impact of prophylactic ganciclovir on bronchoalveolar lavage lymphocyte numbers and phenotypes in murine cytomegalovirus-induced reactivation of Toxoplasma pneumonia.
In a mouse model of cytomegalovirus (CMV)-induced immunosuppression, murine CMV (MCMV) infection results in reactivation of Toxoplasma pneumonia, and prophylactic but not delayed administration of ganciclovir attenuates the severity of this pneumonia. We now report that the protection observed with ganciclovir is associated with blunting of the alterations in bronchoalveolar lavage (BAL) lymphocyte numbers and phenotypes observed in untreated mice. Specifically, prophylactic ganciclovir prevents the usual drop in BAL CD4+ lymphocytes observed in the first week after MCMV injection--that is, the period of MCMV-associated immunosuppression. Furthermore, prophylactic ganciclovir markedly blunts the usual rise in BAL T lymphocytes (CD8+ > CD4+) seen later during the peak of reactivated Toxoplasma pneumonia. These findings suggest that prophylactic ganciclovir can protect animals from virus-associated opportunistic pneumonia by attenuating virus-induced changes in BAL lymphocytes and the attendant suppression of lung immunity.
Animals↗
Upper respiratory tract infections in the immunocompromised host.
Infections of the upper respiratory tract are a major source of morbidity and mortality in the immunocompromised host. The risks and types of infections are dictated by the specific immune defects present in the patient. Infections may involve virtually any of the structures in the upper respiratory tract, including the oral cavity, pharynx, larynx, trachea, ear, and sinuses. Infections may be complicated by abscess formation or invasion of critical central nervous system or neck space structures. Physicians must maintain a high index of clinical suspicion for upper respiratory tract infections, especially because they may present in an atypical fashion or be caused by unusual organisms in immunocompromised patients. For many of these infections, prompt initiation of appropriate antimicrobial therapy may be life saving. Prophylactic use of antibiotics, antifungal drugs, or antiviral agents is indicated in specific groups of immunocompromised patients.
AIDS-Related Opportunistic Infections↗
Electrocardiographic findings associated with very low calorie dieting.
OBJECTIVE: To determine the safety of very low calorie diets (VLCD) in regard to their effects on cardiac function. DESIGN: EKG changes were analyzed for 126 women on a VLCD of 3349 kJ/d (800 kcal/d). EKGs were done when the diet was begun, after 3 months of dieting, and at a 6 month follow up after being off the diet for 3 months. SETTING: Subjects were solicited through advertisements and charged $1,000 for participating after being screened for age, weight, and health status. MAIN OUTCOME MEASURES: EKG QTc intervals, PR interval, QRS interval, ST-T wave changes, and heart rate. RESULTS: Over one-fourth (27.0%) of subjects had normal EKGs at all three time points studied. Sinus bradycardia was the most common abnormality, observed in 60 subjects (47.6%) on at least one of the three EKGs. Fifty-eight (46%) patients had EKGs with ST-T wave abnormalities observed on at least one of the EKGs. Eight subjects (6.4%) had prolonged QTc (more than one standard deviation beyond the average for women) intervals on at least one EKG. None of these eight persons had significant untoward medical consequences. CONCLUSION: A VLCD diet of 3349 kJ/d (800 kcal/d) for up to 3 months is not associated with significant electrocardiographic abnormalities or clinical cardiac complications, provided the patients have low cardiovascular risk at baseline.
Adult↗
Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa.
Anorexia nervosa is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. To determine the potential role of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in anorexia nervosa, serum concentrations of these cytokines were measured in patients with anorexia nervosa during starvation and after weight gain. Serum IL-6 and TGF-beta concentrations were both significantly elevated during starvation and returned to levels comparable to those of normal-weight controls by the end of therapy. In contrast, serum TNF-alpha levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.
Adolescent↗
Cytomegalovirus replication in murine microglial cell cultures: suppression of permissive infection by interferon-gamma.
The pathogenesis of encephalitis due to cytomegalovirus (CMV), particularly the role of microglial cells in the spread or control of infection, remains incompletely defined. In this study, microglial cells were isolated from the brains of newborn mice and infected in vitro with murine CMV (MCMV). Microglial cells supported productive MCMV replication, and the MCMV-infected microglia manifested a cytopathic effect (CPE) characteristic of CMV infection. Exposure of microglia to interferon-gamma (IFN-gamma) 24 h before infection markedly suppressed virus production and resultant CPE in a dose-dependent fashion. Furthermore, the addition of IFN-gamma 2 h after infection demonstrated an antiviral effect equivalent to that achieved when IFN-gamma was administered 2 h before infection. These results demonstrate that murine microglial cells are fully permissive to MCMV replication and that IFN-gamma markedly suppresses virus expression in these cells.
Animals↗
HIV antibody testing: the gap between policy and practice.
In response to recent laws regulating human immunodeficiency virus (HIV) antibody testing practices in all federal hospitals, our university-affiliated Veterans Affairs Hospital instituted several interventions designed to increase appropriate testing. Specific hospital policy requiring restriction of testing to high-risk individuals, provision of pre- and posttest counseling, and documentation of written consent was instituted. In addition, an education campaign to inform physicians of hospital policy and training of counselors as physician extenders was undertaken. To determine the efficacy of these interventions, we reviewed all HIV antibody tests performed during a subsequent six-month period (n = 221). Only 14% of tests met all hospital policy requirements. The decision to test was prompted by identification of a risk factor or other acceptable reason for testing for only 31% of patients. Risk reduction counseling was provided for only 28% of patients. Written consent was documented for 62% of patients. Health care providers on surgical services were less likely than others to comply with hospital policy (p < 0.0001). We conclude that an interventional program including specific hospital policy mandates, physician education, and provision of trained counselors was not adequate to ensure optimal HIV antibody testing practices. If this gap between policy and practice is to be closed, additional interventions, or alternatively modification of policy guidelines, will be needed.
AIDS Serodiagnosis↗
Cognitive-behavioral group psychotherapy of bulimia nervosa: importance of logistical variables.
Although much of the psychotherapy for psychiatric disorders is conducted on a weekly basis, several researchers in the field of bulimia nervosa have utilized a more intensive approach as a means to strengthen treatment effects. A second issue concerns the amount of emphasis that should be placed on encouraging the interruption of bulimic symptoms early in treatment. In the current study we systematically studied these two issues. Subjects were randomly assigned to one of four forms of cognitive-behavioral group psychotherapy, the four cells differing on the variables of intensity and emphasis on abstinence. The results indicate that a high intensity approach, an early abstinence approach, or a combination of these two approaches are all significantly more effective in inducing remission in patients with bulimia nervosa compared with a weekly psychotherapy that uses the same manual-based cognitive-behavioral therapy approach.
Adolescent↗
Cytomegalovirus disease of the gastrointestinal tract in patients without AIDS.
Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can cause serious disease in immunocompromised patients. Recipients of solid organ and bone marrow transplants, persons with malignancies, and those receiving immunosuppressive medications are at risk. When CMV infection of the GI tract causes disease, symptoms include pain, ulceration, bleeding, diarrhea, and perforation. All levels of the GI tract, from the oropharynx to the anus, may be involved. Pathological examination of involved gut typically reveals diffuse ulcerations and necrosis with scattered CMV inclusions, although a variety of other abnormalities have been described. Before the introduction of antiviral therapy effective against CMV, mortality was high. However, the use of ganciclovir or foscarnet has improved the prognosis of CMV disease of the GI tract dramatically. CMV infection should be included in the differential diagnosis of GI disease in immunocompromised patients, and the clinician should pursue appropriate diagnostic and therapeutic interventions aggressively.
Aged↗
Detection of latent cytomegalovirus DNA in diverse organs of mice.
Latency is essential to the pathogenesis of cytomegalovirus (CMV) infection and disease. A survey of mouse organs that might contain latent murine CMV (MCMV) DNA was conducted using nested enzymatic amplification of a 200-bp region of exon 4 of the major immediate early gene 1. MCMV DNA was detected in diverse organs including the heart, kidney, liver, lung, spleen, brain, and salivary glands. The total number of organs in which latent MCMV DNA was detected was significantly greater in mice infected at 4 weeks of age (64/70) than in mice infected at 7 weeks of age (40/69). This phenomenon was associated with greater viral replication in the same organs during acute infection. These results indicate that latent MCMV infection is distributed much more widely than previously suspected and is directly correlated with the extent of viral replication during acute infection.
Age Factors↗
Effect of ganciclovir on murine cytomegalovirus-induced reactivation of toxoplasma pneumonia.
Active cytomegalovirus (CMV) infection induces immunosuppression and predisposes to the development of life-threatening superinfections in immunocompromised patients. We have described a mouse model in which acute murine CMV (MCMV) infection reactivates previously dormant Toxoplasma gondii infection, manifested as pneumonia. To determine whether therapy with ganciclovir might prevent MCMV-induced reactivation of T. gondii pneumonia, we administered ganciclovir to mice starting 1 day before to 2 days after MCMV infection and continuing for 14 days. When ganciclovir was begun early (before, on the day of, or 1 day after MCMV infection), the severity of T. gondii pneumonia reactivated by MCMV was significantly reduced. However, when therapy was delayed, no beneficial effect of ganciclovir was observed and the severity of MCMV-induced reactivation of T. gondii pneumonia was comparable to that seen in untreated animals. We conclude that ganciclovir therapy can attenuate but not eliminate MCMV-induced reactivation of T. gondii pneumonia and that prophylactic or very early administration of the drug is necessary to achieve protection.
Animals↗
Zidovudine therapy of HIV-associated thrombocytopenia: from MAIDS to AIDS.
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Acquired Immunodeficiency Syndrome↗
Cryptococcal disease presenting as cellulitis.
Three immunocompromised patients presented with cellulitis as the primary manifestation of cryptococcal disease. Two were recipients of cadaveric renal transplants who were receiving immunosuppressive drug therapy. The other patient had profound lymphopenia and severe hypoalbuminemia due to intestinal lymphangiectasia. All had failed to respond to empiric therapy for presumed bacterial cellulitis before results of skin biopsy or aspiration were available for the correct diagnosis to be made. With administration of systemic antifungal therapy, two patients survived. Although other forms of cryptococcal involvement of the skin are not rare, cellulitis is seldom considered to be a cutaneous manifestation of the disease. Our cases and a review of the English-language literature indicate that Cryptococcus neoformans must be included in the differential diagnosis of cellulitis in immunocompromised patients and that the presence of cryptococcal cellulitis suggests disseminated cryptococcal disease. Prompt diagnosis and treatment may dramatically reduce mortality.
Adult↗
Pulmonary toxoplasmosis: a review.
Toxoplasma pneumonia is being recognized with increased frequency, especially in patients with AIDS. We reviewed the English-, French-, and Spanish-language literature from January 1966 through February 1991 to identify cases of postnatally acquired pneumonia associated with Toxoplasma gondii. We identified two distinct clinical syndromes, one in immunocompetent patients and one in patients with defects in cell-mediated immunity. Shortness of breath and cough were the most common symptoms and fever and rales the most common signs in both groups of patients. Lymphadenopathy and hepatosplenomegaly were reported more frequently for immunocompetent patients. Chest roentgenographs usually revealed bilateral interstitial infiltrates, but a variety of other roentgenographic findings were reported. Serological findings were suggestive of active toxoplasmosis in immunocompetent but not in immunosuppressed patients. In early reports, identification of T. gondii as the etiologic agent of pneumonia was based on serology or autopsy findings. In more recent reports, open lung biopsy and especially bronchoalveolar lavage were used for diagnosis. Mortality among patients with toxoplasma pneumonia was 55%. However, in cases of T. gondii pneumonia diagnosed during life, mortality was 0 for immunocompetent patients and 40% for immunosuppressed patients. In immunosuppressed patients, improvement was associated with specific antitoxoplasma drug therapy. Unfortunately, relapses were common. We also reviewed data on series of patients with disseminated toxoplasmosis manifested predominantly in extrapulmonary sites and found that 33% of these patients had evidence of subclinical pulmonary involvement even though pneumonia had not been diagnosed clinically.
Acquired Immunodeficiency Syndrome↗
Cytomegalovirus-induced reactivation of Toxoplasma gondii pneumonia in mice: lung lymphocyte phenotypes and suppressor function.
Active cytomegalovirus (CMV) infection is associated with immunosuppression and predisposes to the development of life-threatening superinfections in immunocompromised patients. In a mouse model of virus-induced immunosuppression, acute murine CMV (MCMV) infection induced reactivation of dormant Toxoplasma gondii infection, producing Toxoplasma pneumonia. Changes in lung lymphocyte numbers and phenotypes appeared to be integral to the pathogenesis of MCMV-induced reactivation of T. gondii pneumonia. Numbers of lung CD4+ cells decreased during acute MCMV infection in mice with dormant T. gondii infection as well as in previously uninfected mice. Dually infected mice subsequently developed reactivation of Toxoplasma pneumonia. The pneumonia was characterized by a large influx of T lymphocytes, predominantly CD8+ cells, into the lungs. These lung lymphocytes markedly suppressed the ability of immune splenocytes to proliferate in response to T. gondii antigens and concanavalin A in vitro. These results suggested that the initial fall in the numbers of lung CD4+ cells observed after MCMV infection may have induced reactivation of T. gondii infection in the lungs. The subsequent pneumonia appeared to be a manifestation of a massive influx of T lymphocytes, especially CD8+ cells, into the lungs.
Animals↗
Effects of morphine addiction on the pathogenesis of murine toxoplasmosis.
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Animals↗