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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 73 records · Page 4Linked to original sources

Natural history of disseminated Mycobacterium avium complex infection in AIDS.

This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.

Acquired Immunodeficiency Syndrome↗

The pharmacokinetics of teicoplanin in varying degrees of renal function.

The pharmacokinetics of teicoplanin, a new glycopeptide antibiotic with activity against aerobic gram-positive bacteria, were characterized after intravenous administration of a single 3 mg/kg dose in five healthy volunteers and six patients with various degrees of stable renal insufficiency. Serum and urine samples were collected during a 15-day period and drug concentrations were assayed microbiologically. The mean elimination half-life of teicoplanin was 162.6 +/- 69.8 hours in healthy volunteers and was prolonged with decreased renal function. The mean plasma and renal clearances of teicoplanin in healthy subjects were 11.4 +/- 1.5 ml/min and 10.0 +/- 1.0 ml/min, respectively. Both values decreased in patients with renal failure and correlated significantly with measured creatinine clearances (r2 = 0.938 and 0.884, respectively). A nomogram for dosage adjustment in patients with varying degrees of renal failure is presented.

Adult↗

The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents.

Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.

Acquired Immunodeficiency Syndrome↗

Loss of cerebrovascular autoregulation in experimental meningitis in rabbits.

The present study was designed to determine whether cerebrovascular autoregulation is intact in experimental meningitis and to examine the relationship between fluctuations in cerebral blood flow (CBF) and increased intracranial pressure (ICP). Measurements of CBF were determined by the radionuclide microsphere technique in rabbits with experimental Streptococcus pneumoniae meningitis with simultaneous ICP monitoring via an implanted epidural catheter. CBF and ICP measurements were determined at baseline and when mean arterial blood pressure (MABP) was artificially manipulated by either pharmacologic or mechanical means. CBF was pressure passive with MABP through a range of 30-120 torr, and ICP directly correlated with CBF. These findings indicate that autoregulation of the cerebral circulation is lost during bacterial meningitis, resulting in a critical dependency of cerebral perfusion on systemic blood pressure, and that the parallel changes in ICP and in CBF suggest that fluctuations in CBF may influence intracranial hypertension in this disease.

Animals↗

Pharmacodynamics of antibiotics in experimental bacterial meningitis--two sides to rapid bacterial killing in the cerebrospinal fluid.

In bacterial meningitis, several pharmacodynamic factors determine therapeutic success--when defined as sterilization of the cerebrospinal fluid (CSF); (i) local host defense deficits require the use of bactericidal antibiotics; (ii) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity; (iii) high CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth even during relatively long dosing intervals; (iv) penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier, thus requiring high serum levels to achieve the CSF concentrations necessary for rapid bacterial killing. Beyond these principles, recent data suggest that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active bacterial products. The conflict between the need for rapid CSF sterilization and the harmful consequences of bacterial lysis must be addressed in the therapy of meningitis.

Animals↗

Cryptococcal meningitis in the acquired immunodeficiency syndrome.

Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival.

Acquired Immunodeficiency Syndrome↗

General principles of therapy of pyogenic meningitis.

In bacterial meningitis, several pharmacodynamic factors determine therapeutic success-when defined as sterilization of the CSF: (1) Local host defense deficits in the CNS require the use of bactericidal antibiotics to sterilize the CSF. (2) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity. Protein binding, low pH, and slow bacterial growth rates are among the factors that may explain the high antibiotic concentrations necessary in vivo. (3) High CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth, even during relatively long dosing intervals. (4) Penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier and thus, very high serum levels are necessary to achieve the CSF concentrations required for optimal bactericidal activity. Beyond these principles, recent data suggests that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active products from the lysed bacteria. Since rapid CSF sterilization remains a key therapeutic goal, the harmful consequences of bacterial lysis present a major challenge in the therapy of bacterial meningitis. Currently, dexamethasone represents that only clinically beneficial approach to reduce the harmful effects of bacterial lysis, and novel approaches are required to improve the outcome of this serious infection.

Anti-Bacterial Agents↗

Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome.

We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.

Acquired Immunodeficiency Syndrome↗

Cocaine use and HIV infection in intravenous drug users in San Francisco.

We assessed risk factors for human immunodeficiency virus (HIV) infection in 633 heterosexual intravenous drug users. The HIV seroprevalence was 26% in blacks, 10% in Hispanics, and 6% in whites. Intravenous cocaine use significantly increased the risk of HIV infection, with a seroprevalence of 35% in daily cocaine users (odds ratio, 6.4; 95% confidence interval, 3.0 to 13.3). Black subjects were more likely to use cocaine regularly. Drug use in shooting galleries and sharing of drug injection equipment were also associated with HIV infection and were more common in cocaine users. By multivariate analysis, black race, daily cocaine injection by blacks and Hispanics, all other cocaine injection, heavy use prior to entry into methadone treatment by blacks, and use of drugs in shooting galleries were independent predictors of HIV infection. Methadone therapy was associated with substantial reductions in heroin use and some reduction in cocaine use, but 24% of cocaine users receiving methadone began or increased cocaine injection after entry into treatment.

Black or African American↗

Community-acquired bacteremia in patients with acquired immunodeficiency syndrome: clinical presentation, bacteriology, and outcome.

PURPOSE: Community-acquired bacteremia is an easily treatable infection occurring in patients with acquired immunodeficiency syndrome (AIDS). Although other studies have reported bacterial infections in AIDS patients, none have clearly described the clinical presentation of these patients. In this survey, we sought to define how frequently AIDS patients presented to our institution with community-acquired bacteremia; which organisms and sources of bacteremia were involved; the frequency that these patients presented with abnormal vital signs and white blood cell counts; and the in-hospital outcome of these patients. PATIENTS AND METHODS: We retrospectively identified patients with AIDS hospitalized at San Francisco General Hospital in the 16 months between August 1986 and December 1987 in whom a positive blood culture was drawn within 24 hours of admission. Each of the patient's charts was reviewed for demographic data, relevant past medical history, clinical admission information, laboratory data, and discharge status. RESULTS: We identified 44 episodes of community-acquired bacteremia in 38 patients with AIDS. These episodes represented approximately 5% of the admissions of patients with AIDS. The patients were young (mean age, 38 +/- 7 years), homosexual (43 of 44), and in some cases intravenous drug users (nine of 44). On admission, only 57% of the patients were febrile (temperature greater than 38.3 degrees C) and 23% of the patients presented with normal vital signs. Twenty-seven percent were neutropenic (less than 1,000 neutrophils/mm3). The most common sources of the bacteremia were pneumonia (10), an indwelling central venous line (eight), and cellulitis (seven). A total of 14 patients had no apparent source. Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli were the most common organisms. Only four of the 44 patients died during their hospitalization. CONCLUSION: We conclude that patients with AIDS and community-acquired bacteremia can present to the hospital without abnormal vital signs or white blood cell counts. Clinicians cannot depend on these data to assist them in excluding the possibility of bacteremia in patients with AIDS. In addition, due to the variety of organisms found in our survey, we recommend that broad-spectrum antibiotics should be the empiric therapy in patients with a suspected bacterial infection.

Acquired Immunodeficiency Syndrome↗

Evaluation of FCE 22101 in experimental meningitis caused by Escherichia coli and Streptococcus pneumoniae.

FCE 22101 is a new penem antibiotic with a spectrum of activity suggesting a possible role in the empirical treatment of meningitis. It appears to achieve a mean reduction in bacterial titre in CSF comparable with currently accepted agents for both pneumococcal and Escherichia coli meningitis. Its efficacy may, however, be variable. It does not achieve CSF level/MIC ratios as favourable as imipenem for the pathogens studied. Further studies are necessary to determine its role, if any, in this disease.

Animals↗