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Biomedical subjects

F R Sattler

Publications and source records attributed to F R Sattler.

At least 37 records · Page 2Linked to original sources
PubMed1994

Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

OBJECTIVE: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized, double-blind, dose-ranging study. SETTING: Outpatient clinics. PATIENTS: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. INTERVENTIONS: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. MAIN OUTCOME MEASURE: Median number of colony-forming units of M. avium complex per milliliter of blood. RESULTS: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001). After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08). At 6 weeks, the median number of CFUs of M. avium complex/mL of blood was 0 or 1 for all three groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). CONCLUSIONS: Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

AIDS-Related Opportunistic Infections↗
PubMed1994

Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031.

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

AIDS-Related Opportunistic Infections↗
PubMed1992

New developments in the treatment of Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia and therapies to treat this infection are associated with frequent and severe morbidity in patients with acquired immunodeficiency syndrome (AIDS). Mortality rates remain in the 20 to 40 percent range for severe episodes. Thus, less toxic and more effective therapies are needed. For mild-to-moderately severe episodes (PaO2 greater than 70 mm Hg or [A-a]DO2 less than 35 mm Hg), studies suggest that trimethoprim-dapsone, clindamycin-primaquine, and BW 566C80 may cause less toxicity than conventional therapy with trimethoprim-sulfamethoxazole or parenteral pentamidine. However, prospective, controlled trials are needed to establish whether the newer therapies are as effective as the existing licensed treatments. Aerosolized pentamidine is another new therapy that is better tolerated than trimethoprim-sulfamethoxazole but may not be as effective as parenteral treatment when there is extensive airspace consolidation. For severe episodes (PaO2 less than 70 mm Hg or [A-a]DO2 greater than 35 mm Hg), recent studies have established that adjunctive therapy with corticosteroids reduces mortality approximately twofold. For patients who have failed conventional treatments and are unable to ingest oral medications, trimetrexate may be tried. Other compounds being tested may further expand the therapeutic armamentarium with safer and more effective drugs.

Adrenal Cortex Hormones↗
PubMed1991

Acetaminophen does not impair clearance of zidovudine.

OBJECTIVE: To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity. DESIGN: Dose escalation, drug interaction study. SETTING: University clinical research center. PATIENTS: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. INTERVENTIONS: Acetaminophen and 200 mg of zidovudine simultaneously every 4 hours. For 13 patients, the unit dosage of acetaminophen was 325 mg for 3 days; for 8 patients, the dosage was 650 mg for 3 days; and, for 6 patients, the dosage was 650 mg for 7 days. MEASUREMENTS: Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment. MAIN RESULTS: Neither zidovudine clearance nor production of the glucuronide conjugate of zidovudine was impaired after treatment with acetaminophen. Clearance of zidovudine was actually accelerated by 5%, 11%, and 33% with the three acetaminophen regimens, respectively (P = 0.002 by analysis of variance; P = 0.04 for linear trend when changes in the area-under-the-curve for zidovudine were compared). CONCLUSION: Because serum concentrations of zidovudine decrease after the coadministration of acetaminophen, a pharmacokinetic interaction between zidovudine and acetaminophen is unlikely to increase the risk for hematologic toxicity associated with zidovudine.

AIDS-Related Complex↗
PubMed1991

Ascitic fluid and serum cefotaxime and desacetyl cefotaxime levels in patients treated for bacterial peritonitis.

Forty-one episodes of ascitic fluid infection were treated with cefotaxime 2 g intravenously every 8 hr, and ascitic fluid and serum were sampled 6, 12, 24, 48, and 96 hr after the first dose of antibiotic. Concentrations of cefotaxime and desacetyl cefotaxime were measured in ascitic fluid and serum by high-performance liquid chromatography. There was essentially 100% penetration of cefotaxime and metabolite from serum into ascitic fluid at all time points. Ascitic fluid was sterilized in 94% of episodes after the first dose of antibiotic. The ascitic fluid concentration of cefotaxime 6 hr after the first dose of antibiotic was greater than 20 times the minimal inhibitory concentration of the drug for 90% of the isolated flora. This rapid ascitic fluid penetration of cefotaxime in high concentration explains the rapid sterilization of ascitic fluid by the drug in the setting of bacterial peritonitis and obviates the need to give a loading dose or intraperitoneal injection.

Adult↗
PubMed1991

Clindamycin and primaquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS.

The combination of clindamycin and primaquine was investigated as primary treatment for mild or moderately severe Pneumocystis carinii pneumonia (alveolar-arterial oxygen gradient less than 40 torr) in 36 AIDS patients. All patients were treated with primaquine 30 mg (base) orally for 21 days. The first 22 patients were treated with clindamycin 900 mg i.v. q8h for the first 10 days, followed by clindamycin 450 mg q6h orally for 11 days. Twenty of these 22 patients (91%) showed a marked clinical response by day 7. Four patients were later withdrawn from the study due to toxicity. An additional 14 patients were treated with an entirely oral regimen of clindamycin and primaquine. Thirteen of the 14 patients (93%) showed a marked therapeutic response and 12 (86%) successfully completed treatment. The combination of clindamycin and primaquine appears to be an effective and well-tolerated treatment for mild to moderately severe Pneumocystis carinii pneumonia in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease.

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required.

Adult↗
PubMed1991

Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii pneumonia.

In a prospective, noncomparative study, seven patients with mild Pneumocystis carinii pneumonia, characterized by room air arterial PO2 greater than 60 mm Hg at the time of presentation, were treated with dapsone alone at a dose of 200 mg daily. Two of the seven patients required mechanical ventilation for respiratory failure on day 5 of dapsone therapy; both died. Four patients experienced major side effects during dapsone therapy. None of the seven patients successfully completed a full course of therapy with dapsone. We conclude that high-dose, single-agent dapsone is not suitable for further study as therapy for Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.

BACKGROUND: Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial. METHODS: A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy. RESULTS: Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms. CONCLUSIONS: Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.

To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Mycobacterial disease in patients with human immunodeficiency virus infection.

We compared the clinical features of disease due to tuberculosis and to Mycobacterium avium complex (MAC) in 94 patients with human immunodeficiency virus infection. Tuberculosis preceded the diagnosis of acquired immunodeficiency syndrome in 26 (67%) of 39 cases, compared with none of 55 with MAC infection. Chest roentgenographic findings suggested mycobacterial infection in 24 (83%) of 29 patients with pulmonary tuberculosis, compared with 7 (25%) of 28 with MAC infection. Sputum smears revealed acid-fast bacilli in 19 (83%) of 23 patients with pulmonary tuberculosis, but only 4 (16%) of 25 cases of pulmonary MAC infection. In 39 patients with tuberculosis, lymphadenitis and pleuritis were present in 13 (33%) and 8 (20%), respectively, but occurrence was rare in patients with MAC infection. In contrast, mycobacteremia was more frequent in MAC infection, occurring in 47 (85%) of 55 cases. In 5 patients, tuberculosis was unsuspected and probably contributed to death. These findings suggest that clinical features often distinguish tuberculosis from MAC infection in patients with human immunodeficiency virus infection. In addition, more intensive diagnostic use of sputum acid-fast smears may improve the outcome in patients with tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study.

STUDY OBJECTIVE: To ascertain the efficacy and toxicity of trimethoprim-sulfamethoxazole or pentamidine when either is given alone during the entire treatment period for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective, randomized, noncrossover comparison of trimethoprim-sulfamethoxazole with pentamidine. Trimethoprim-sulfamethoxazole dosage was adjusted to maintain serum trimethoprim at 5 to 8 micrograms/mL. Pentamidine dosage was reduced by 30% to 50% for an absolute rise in serum creatinine of more than 88 mumol/L (1 mg/dL). SETTING: Tertiary care hospital and AIDS clinic. PATIENTS: Thirty-six patients were treated with trimethoprim-sulfamethoxazole and 34 with pentamidine. Pretreatment clinical features and laboratory test results were similar in the two groups. MEASUREMENTS AND MAIN RESULTS: Thirty-six recipients of trimethoprim-sulfamethoxazole and 33 recipients of pentamidine completed therapy without crossover. Trimethoprim-sulfamethoxazole caused a rash (44%) and anemia (39%) more frequently (P less than or equal to 0.03, whereas pentamidine caused nephrotoxicity (64%), hypotension (27%), or hypoglycemia (21%) more frequently (P less than or equal to 0.01). The (A - a)DO2 improved by greater than 1.3 kPa (10 mmHg) 8 days earlier for trimethoprim-sulfamethoxazole recipients (95% CI for the difference in response, -1 to 17; P = 0.04). Thirty-one (86%) patients treated with trimethoprim-sulfamethoxazole and 20 (61%) with pentamidine survived and were without respiratory support at completion of treatment (95% CI for the difference in response, 5% to 45%; P = 0.03). CONCLUSIONS: For most patients with AIDS and P. carinii pneumonia, successful treatment with a single agent is possible. Toxicity associated with the two standard treatments is rarely life-threatening and may be diminished if the trimethoprim-sulfamethoxazole dosage is modified by pharmacokinetic monitoring and the pentamidine dosage is reduced for nephrotoxicity. Oxygenation improved more quickly and survival was better with trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Risk factors for hypoglycemia associated with pentamidine therapy for Pneumocystis pneumonia.

In 1984, three patients died of severe hypoglycemia after receiving pentamidine isethionate to treat Pneumocystis pneumonia. These deaths occurred on days 8, 12, and 19 of treatment, respectively. To assess risk factors associated with pentamidine treatment and hypoglycemia, we reviewed records of patients treated with pentamidine in New York City in 1984; ninety-seven percent of these patients had a diagnosis of acquired immunodeficiency syndrome. Hypoglycemia occurred in 23 (14%) of 164 patients. Hypoglycemia was more likely to occur in patients who received therapy of longer duration and an increasing dosage of pentamidine. Patients at greater risk for hypoglycemia also included those who had received pentamidine previously and those who experienced azotemia during treatment. This serious, potentially fatal, reaction should be considered in all patients who are treated with pentamidine, particularly those receiving prolonged or recurrent therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Impaired hemostasis caused by beta-lactam antibiotics.

Beta-lactam antibiotics can directly impair hemostasis by two separate nonimmune mechanisms. First, the NMTT-substituted cephalosporin drugs may cause hypoprothrombinemia by interfering with the hepatic activation of clotting factors II, VII, IX, and X. Second, the antipseudomonal penicillins may cause the bleeding time to be prolonged by interfering with platelet aggregation to physiologic agonists. In surgical patients who are malnourished, have impaired gastrointestinal function, or have renal failure, the potential for these adverse effects is increased. Serious bleeding requires treatment with fresh frozen plasma when hypoprothrombinemia is caused by NMTT-containing cephalosporins, since the prothrombin time returns to baseline relatively slowly after therapy with vitamin K. Hemorrhage caused by beta-lactam-induced platelet dysfunction must be treated with platelet concentrates, since new platelets sufficient to correct the defect do not enter the circulation for several days after treatment with the offending drug is discontinued. The more desirable approach is to prevent hypoprothrombinemia by giving vitamin K prophylaxis and to avoid beta-lactams that impair platelet function in seriously ill patients at increased risk for bleeding.

Anti-Bacterial Agents↗