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Biomedical subjects

J E Conte

Publications and source records attributed to J E Conte.

At least 37 records · Page 2Linked to original sources
PubMed1990

Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial.

OBJECTIVE: To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS: The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS: The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prevention of Pneumocystis carinii pneumonia by inhaled pentamidine.

The efficacy and toxicity of pentamidine inhaled once a month to prevent Pneumocystis carinii pneumonia (PCP) was investigated in 102 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The cohort was compared with historical controls after a mean duration of prophylaxis of 6.38 months. 86% and 15% of the patients had AIDS or ARC, respectively. 50% of patients had had one previous episode of PCP, 9% had had two episodes, and 3% had had three. 11 patients acquired PCP. Among these 51 patients with one prior episode of PCP, the PCP-free survival after 3.03, 4.7, and 6.38 months of prophylaxis was 98%, 92%, and 82%, respectively. Compared with those for historical controls, the data suggest that inhaled pentamidine can delay relapse by 6 months and reduce the rate of relapse by 50%. PCP acquired while patients were inhaling pentamidine prophylactically was mild and had a case-fatality rate of only 9%. Further investigation of the prophylactic value of inhaled pentamidine is warranted.

AIDS-Related Complex↗
PubMed1988

Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion.

Pentamidine pulmonary pharmacokinetics were studied in 13 patients receiving once-daily inhaled therapy and 4 patients receiving low-dose intravenous treatment for Pneumocystis carinii pneumonia. Twenty-four hours after inhaled or intravenous therapy, the mean (+/- standard deviation) concentrations of pentamidine in serial bronchoalveolar specimen fluid ranged from 28.6 +/- 10 to 177.5 +/- 28 ng/ml and 6.05 +/- 2.29 to 21.4 +/- 15.7 ng/ml, respectively. Pentamidine concentrations in brochoalveolar fluid were generally higher after 2 weeks than after day 1 of therapy; however, the differences were not statistically different (P greater than 0.05). The pulmonary half-life after inhaled therapy is long; pentamidine was detectable in bronchoalveolar fluid at 33 (one patient), 69 (one patient), and 115 (one patient) days following the completion of 2 weeks of therapy. Systemic absorption of pentamidine was minimal; the mean (+/- standard deviation) plasma concentration at the completion of inhalation was 13.84 +/- 11.8 ng/ml, or 5% of the mean peak plasma concentration achieved after intravenous administration. Accumulation in the plasma did not occur with repeated inhalation as has been described with multiple intravenous dosing. Cumulative urinary excretion 24 h after the first dose was 5% of that observed with intravenous administration. These data may have importance in designing dosage regimens for the further investigation of inhaled pentamidine for treatment or prophylaxis of P. carinii pneumonia.

Absorption↗
PubMed1987

Ceftriaxone treatment of multidrug-resistant Salmonella osteomyelitis.

Empiric treatment of serious Salmonella infections has been complicated by the emergence of strains resistant to multiple antimicrobial agents, including ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. Recent reports suggest that the third-generation cephalosporins may be effective therapy for Salmonella infections. This report describes a case of antibiotic-resistant Salmonella heidelberg prosthetic hip infection successfully treated with prosthesis removal and once-daily ceftriaxone. Tube dilution sensitivity testing of the organism demonstrated minimal inhibitory and minimal bactericidal concentrations of 0.12 microgram/ml. Serum bactericidal activity, 30 minutes after infusion, was inhibitory and bactericidal at 1:512. It is concluded that the favorable preliminary results reported in the literature and the outcome in this patient suggest that the third-generation cephalosporins may be effective therapy for Salmonella infections and should undergo clinical trials.

Adult↗
PubMed1987

Pentamidine pharmacokinetics in patients with AIDS with impaired renal function.

In patients with normal renal function, pentamidine elimination half-life and plasma clearance (mean +/- SD) were 6.22 +/- 1.17 hr and 411 +/- 55 liters/hr, respectively. With creatinine clearances from 35 to 145 ml/min, neither the elimination half-life (P = .47) nor the plasma clearance (P = .40) was correlated with renal function. Plasma concentrations in patients receiving dialysis ranged between 5.9 and 582 ng/ml and appeared not to be significantly affected by dialysis. The number of prior doses and the elimination half-life estimated from the terminal slope were correlated (r = .81, P = .025), and the results suggested that the current assay technology is still not sensitive enough to detect true elimination half-life. Trough plasma concentrations ranged between 4.3 and 67.5 ng/ml (28.4 +/- 26.6 ng/ml) in patients who had received prior doses of pentamidine, a result suggesting that drug accumulation occurs with multiple dosing. The data suggest that dosage adjustments are not necessary with creatinine clearances of greater than 35 ml/min. Because multiple dosing leads to increased trough concentrations and drug accumulation, lower dose regimens may still be efficacious, yet associated with reduced toxicity.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Pharmacokinetics of cefpiramide in volunteers with normal or impaired renal function.

The pharmacokinetics of a single 2.0-g intravenous dose of cefpiramide in patients with normal or impaired renal function were studied. Serial concentrations in serum and urine were measured by using high-performance liquid chromatography, and the effect of the concentration in serum on protein binding was assessed. Thirty patients (ten with creatinine clearances of greater than 80 ml/min, ten with creatinine clearances between 10 and 80 ml/min, and ten on dialysis) were studied. The concentration-time curve of cefpiramide was best described by an open two-compartment model. The elimination half-lives in patients with normal or impaired renal function or those on dialysis were 5.41 +/- 1.44, 8.3 +/- 2.82, and 8.38 +/- 4.06 h, respectively, and the serum clearances in the same groups were 2.0 +/- 0.84, 1.29 +/- 0.45, and 2.04 +/- 1.10 liters/h, respectively. There were no significant differences in any of the parameters among the three groups of patients. In patients with normal or impaired renal function, protein binding varied between 93.0 +/- 1.3% at 304.4 micrograms/ml and 99.3 +/- 0.8% at 41.1 micrograms/ml and was linearly and inversely related to the cefpiramide concentration in serum. In patients on dialysis, protein binding was significantly lower (P less than 0.05) and varied between 88.5 +/- 7.1% at 173.4 micrograms/ml to 94.9 +/- 4.8% at 46.8 micrograms/ml. In patients with normal or abnormal renal function, renal cefpiramide clearance decreased linearly with declining renal function, whereas plasma clearance was maintained. Therefore, nonrenal elimination becomes more important as renal impairment progresses.

Adolescent↗
PubMed1987

Comparative antibacterial activity of Vancocin and generic vancomycin.

The in vitro antibacterial activity of generic vancomycin was compared with that of Vancocin (vancomycin hydrochloride; Eli Lilly & Co.) using macrotube dilution testing and subculture. There were no significant differences in MICs or MBCs of the two drugs when tested against a variety of recently isolated hospital pathogens.

Enterobacteriaceae↗
PubMed1987

Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study.

STUDY OBJECTIVE: To evaluate inhaled or reduced-dose intravenous pentamidine for the treatment of patients with mild Pneumocystis carinii pneumonia. DESIGN: Open, nonrandomized pilot study; measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: Of 22 men with mild P. carinii pneumonia (PO2 greater than or equal to 55 mm Hg), 15 (9 in the inhaled group and 6 in the intravenous group) received treatment for their first episode and 7 for a repeat episode. INTERVENTIONS: Pentamidine isethionate, 4 mg/kg body weight by inhalation, or 3 mg/kg intravenously, was given once daily, as long as clinically indicated. MEASUREMENTS AND MAIN RESULTS: Of the 13 patients in the inhaled group, 9 has a satisfactory response; and of the 10 in the reduced-dose intravenous group, 9 had a satisfactory response. Major adverse reactions occurred in two patients in each group. Three patients in the inhaled group appeared to have had early relapses. Bronchoalveolar lavage fluid concentrations of pentamidine ranged between 16.8 +/- 7.3 ng/mL and 149.7 +/- 38.2 ng/mL in the inhaled group and 3.4 +/- 0.2 ng/mL and 10.9 ng/mL in the intravenous group. CONCLUSIONS: Inhaled or reduced-dose intravenous pentamidine may be an effective and less toxic therapy for mild P. carinii pneumonia. These regimens are not recommended for general use until larger controlled trials are conducted.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Use of a specific and sensitive assay to determine pentamidine pharmacokinetics in patients with AIDS.

The first-dose pharmacokinetics of pentamidine were studied in patients with AIDS. Pentamidine isethionate (4 mg/kg) was administered intramuscularly or intravenously to two groups of six patients each. Serial plasma and urine concentrations were measured by high-performance liquid chromatography, which is accurate and precise (sensitivity limits, 2.29 ng/ml in plasma and 229 ng/ml in urine). The mean peak concentrations in plasma after intramuscular and intravenous administration were 209 ng/ml and 612 ng/ml, respectively. Plasma concentrations, which declined biexponentially, were detectable throughout the 24-hr dosing interval and fell to less than 25 ng/ml after 8 hr. The mean plasma clearance, elimination half-life, apparent volume of distribution, and apparent volume at steady state for intramuscularly treated patients were 305 liters/hr, 9.36 hr, 924 liters, and 2,724 liters, respectively; these parameters for intravenously treated patients were 248 liters/hr, 6.40 hr, 140 liters, and 821 liters, respectively. Renal clearance of pentamidine was 5.0% of the plasma clearance for intramuscularly treated patients and 2.5% for intravenously treated patients. We found significant differences in the pharmacokinetic parameters between intramuscularly and intravenously treated patients.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Multiple-dose pharmacokinetics of cefonicid in patients with impaired renal function.

The pharmacokinetics of multiple-dose administration of cefonicid to patients with normal and impaired renal function were studied by using high-performance liquid chromatography to measure serial serum and urine concentrations. Eighteen patients received an initial dose of 15 mg/kg intravenously over 12 min plus two or three subsequent modified doses at intervals of 24 to 72 h, depending upon the degree of renal impairment. Six patients chronically requiring hemodialysis and 12 nondialysis subjects (creatinine clearance, 10 to 80 ml/min per 1.73 m2) were studied. The concentrations of cefonicid in serum after the initial dose were best described by an open two-compartment model. The elimination half-life of cefonicid ranged between 5.5 and 84.9 h. Mean peak and trough concentrations in serum for all patients were 178.2 +/- 29.3 micrograms/ml (plus or minus standard deviation) and 39.0 +/- 17.5 micrograms/ml, respectively. Trough concentrations were higher in patients requiring hemodialysis than in nondialysis subjects, but the difference was clinically insignificant. The renal clearance/plasma clearance ratio of cefonicid was linearly related to creatinine clearance and decreased with impaired renal function. Therefore, nonrenal mechanisms of elimination become more important as renal function declines. Since cefonicid concentrations were within the therapeutic range for nearly all dosing intervals, we conclude that the guidelines used for dosage reduction and interval prolongation in this study result in therapeutically adequate concentrations in serum and, at the same time, result in no significant drug accumulation.

Adult↗
PubMed1986

Infection with human immunodeficiency virus in the hospital. Epidemiology, infection control, and biosafety considerations.

Infection with the human immunodeficiency virus (HIV) (formerly HTLV-III/LAV) is transmitted by sexual contact, by blood and blood products, and perinatally. There is no evidence for casual transmission. The risk to health care workers is low but appropriate infection control precautions should be taken. Specimens should be transported to the laboratory in plastic bags labeled with an easily recognized biohazard warning. Placing patients in private rooms is unnecessary unless a patient has an additional illness that requires such an arrangement. Disinfection, sterilization, housekeeping, and waste management must be done according to recommended guidelines. Asymptomatic hospital personnel with HIV antibody can safely engage in direct patient care. Routine HIV serologic screening of personnel or patients is not recommended. Counseling and HIV antibody testing should be offered to pregnant high-risk women. Laboratories that process specimens potentially containing HIV virus should adhere to maximum containment procedures. An intensive and continuing educational program on the epidemiology of HIV infection and appropriate infection control practice is recommended.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Vancomycin treatment for enterococcal meningitis.

Although clinical disease due to enterococcus is common, there has been only limited experience in the treatment of central nervous system infections by this pathogen. In particular, there have been few reports regarding the treatment of such infections in the penicillin-allergic individual. We present two cases of meningitis due to enterococci, including one case with a brain abscess, in patients with strong histories of penicillin sensitivity. We treated these patients with vancomycin hydrochloride and an aminoglycoside. Vancomycin with an aminoglycoside seems to be a reasonable treatment for enterococcal central nervous system infections.

Adult↗
PubMed1983

Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal fluid penetration.

In the treatment of serious infections, combinations of beta-lactam antibiotics are being utilized in order to avoid aminoglycoside toxicity and to achieve antibacterial synergy. The pharmacokinetic disposition of amdinocillin and cephalothin was determined, when administered alone or in combination to healthy volunteers, as well as the penetration of amdinocillin into human cerebrospinal fluid. Six subjects received, on separate occasions, single intravenous doses of amdinocillin 10 mg/kg, cephalothin 15 mg/kg, or a combination of the two in the same doses. The elimination half-lives of amdinocillin and cephalothin are increased when these drugs are given simultaneously, compared with when they are administered alone. However, no significant differences were observed. When they were given in combination, no significant changes in plasma clearance, renal clearance, or steady-state volume of distribution were found. Eight patients undergoing lumbar puncture for various neurologic disorders without inflamed meninges received a single dose of 10 mg/kg amdinocillin intravenously. One to two hours later, simultaneous plasma and cerebrospinal fluid samples were obtained. The concentration of amdinocillin in the cerebrospinal fluid ranged from approximately 1 to 10 percent of concomitant plasma concentrations. Thus, amdinocillin penetrates in the cerebrospinal fluid in marginal amounts in the absence of meningeal inflammation.

Adult↗