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J Blaser

Publications and source records attributed to J Blaser.

66 records · Page 4Linked to original sources
PubMed1985

Aminoglycoside monitoring: timing of peak levels is critical.

Recommendations for optimal therapeutic peak concentrations of aminoglycosides are often not differentiated with respect to duration of infusion and timing of peak sample thereafter. To document the relevance of the timing, 139 dose intervals were analyzed in 58 patients during administration of gentamicin, amikacin, and netilmicin. Serum concentrations measured immediately after 30-min infusions were compared with concentrations obtained 90 min later (2 h values). The ratio of 30 min/2 h concentrations showed considerable variability. This ratio was less than 1.5 in 15% of the dose intervals analyzed and greater than 3 in 8% of the intervals. The poor correlation between concentrations measured at 30 min and at 2 h was documented by the coefficients of variation of 0.82, 0.30, and 0.67 for gentamicin, amikacin, and netilmicin, respectively. This variability was not explained by interindividual differences, renal function, or drug half-life. However, the initial decrease in concentrations was significantly lower in patients with impaired renal function (p less than 0.001). These data suggest that timing is critical for the sampling of serum to determine peak levels in patients and the definition of optimal therapeutic concentrations.

Aminoglycosides↗
PubMed1983

[Monotherapy of systematic Pseudomonas aeruginosa infections with ceftazidime. The causes of therapeutic failures].

Ceftazidime, a new cephalosporin, is characterized by very good in-vitro action against P. aeruginosa. Nonetheless, clinical and (or) microbiological failure occurred in four patients with severe P. aeruginosa infections being treated with ceftazidime. Main cause infections being treated with ceftazidime. Main cause of the discrepancy between in-vitro and in-vivo results during treatment of three patients was a rapid drop in bacterial sensitivity. Superinfection with resistant microorganisms was excluded by the identity of the isolated bacteria in the different epidemiological markers before and during treatment. This rise in resistance was also demonstrated in-vitro by culturing clinically isolated material in ceftazidime-containing media: a 16-fold decrease in sensitivity was demonstrated within three subcultures. Increased beta-lactamase activity of the resistant strains makes it likely that enzymatic inactivation was part of the resistance mechanism. Good inducibility of beta-lactamases and absent resistance transfer argue for chromosomal localisation of the resistance. Because of the development of resistance, severe infections caused by P. aeruginosa should not be treated by ceftazidime alone. In order early to discover the development of resistance, microbiological samples should be taken periodically and examined for their sensitivity.

Ceftazidime↗
PubMed1983

Increase of amikacin half-life during therapy in patients with renal insufficiency.

Serum kinetics of amikacin were investigated in 17 severely ill patients. During both the first and last dose intervals of therapy, the serum concentration time course of every patient was documented by 17 blood samples. Six of the patients had moderate to severe renal insufficiency (serum creatinine greater than 1.5 mg/100 ml). In this group of patients, a pronounced rise in serum half-life of amikacin was observed, increasing from a mean of 11.2 to 21.5 h for the first and last interval, respectively. In contrast, mean half-life remained stable in the group of 11 patients with normal renal function. No change in mean serum creatinine occurred in either group, when data from the beginning and the end of therapy were compared. Therefore, the increase of amikacin half-life is apparently not due to a reduction of the glomerular filtration rate, but rather to a decrease of the ratio of amikacin to creatinine clearance. Indeed, a significant reduction of this ratio could be shown in the seven patients in which 24-h creatinine clearance was determined during the first and last day of therapy. This phenomenon is discussed in the context of aminoglycoside accumulation in deep compartments. We conclude that the daily dose of amikacin has to be reduced during therapy in patients with impaired, but stable, renal function.

Adult↗
PubMed1981

Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime.

The pharmacokinetics of cefotaxime, moxalactam, and ceftazidime were investigated in six human volunteers who received in a crossover fashion doses of 0.5, 1.0, and 2.0 g of each drug by a 5-min infusion. Doses of 1.0 g were repeated after the administration of probenecid. Serum and urine concentrations were assayed with an agar diffusion method. Serum concentrations of moxalactam exceeded those of ceftazidime at all times and were distinctly higher than those of cefotaxime. The normalized area under the concentration time curve (defined as the ratio of the area under the curve per dose) reflects this relationship: compared with cefotaxime the normalized area under the curve of moxalactam was 3 to 4 times higher, and that of ceftazidime was 2 to 3 times higher. By intra-individual comparisons, the area under the curve of moxalactam was 44% larger than that of ceftazidime. With increasing doses, cefotaxime exhibited a nonlinear increase of the area under the curve. The half-lives of moxalactam, ceftazidime, and cefotaxime were 2.34, 1.95, and 1.16 h, respectively. The volume of distribution averaged 0.20 +/- 0.03, 0.23 +/- 0.02, and 0.25 +/- 0.04 liters per kg, and the mean total body clearance was 84, 131, and 328 ml/min for moxalactam, ceftazidime, and cefotaxime, respectively. The 24-h urinary recovery was highest for moxalactam (75 +/- 4%) followed by ceftazidime (68 +/- 11%) and cefotaxime (53 +/- 6%). The influence of probenecid on serum concentrations, half-life, area under the curve, and clearance was most apparent with cefotaxime, whereas the pharmacokinetics of moxalactam and ceftazidime were only slightly affected. After the 0.5- and 2.0- g doses of cefotaxime, desacetyl-cefotaxime activity (determined by high-pressure liquid chromatography) reached a peak of 2.7 and 9.9 mug/ml and declined with a half-life of 1.9 and 1.4 h. The ratio of the R(-) and S(-) epimers of moxalactam, which could be differentiated by high-pressure liquid chromatography, fell rapidly from 0.81 at 0.17 h to 0.5 at 5 h, indicating the presence of twice as much of the microbiologically less active S(-) epimer. From a pharmacokinetic standpoint it appears reasonable to conclude that moxalactam and possibly ceftazidime could be administered twice daily and that cefotaxime could be administered three or even four times daily.

Cefotaxime↗
PubMed1979

Human pharmacology of cefotaxime (HR 756), a new cephalosporin.

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their beta-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 mug/ml, and mean steady-state serum concentrations were 27, 64, and 138 mug/ml, respectively. The mean terminal half-life was 75 +/- 7 min. The total volume of distribution averaged 0.22 +/- 0.03 liters/kg of body weight. Total body and renal clearances were 232 +/- 30 and 145 +/- 24 ml/min per 1.73 m(2), respectively; 63 +/- 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 +/- 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded.

Cephalosporins↗
PubMedDate not supplied

Side-effects due to the intravenous infusion of erythromycin lactobionate.

A double-blind study was designed to test the hypothesis that local side-effects during i. v. administration of erythromycin lactobionate depend on the drug concentration and that they can therefore be minimized by dissolving erythromycin in a larger infusion volume. Forty healthy students were assigned in a randomized sequence to four 30 min infusions: 120 and 250 ml of erythromycin lactobionate (1 g in 0.9% NaCl) and 120 and 250 ml of placebo (0.9% NaCl). An unexpectedly high incidence (95% and 80% for the infusion volumes of 120 and 250 ml, respectively) of severe systemic side-effects was observed during the first 79 infusions. Because all of these systemic side-effects were associated with the infusion of erythromycin, the study was terminated at this point. Side-effects included abdominal cramps, nausea, vomiting, dizziness and profuse sweating. The postulated positive effect of lower erythromycin concentrations in the infusion on local side-effects (pain at the infusion site, erythema) was marginal (63% vs. 45%). Compared to the systemic side-effects, the problem of local tolerance is less important. In young adults, 30 min infusions of 1 g erythromycin lactobionate are associated with a high incidence of systemic side-effects which may be due to an age-dependent effect of the drug on smooth muscle.

Adult↗
PubMedDate not supplied

Effect of peritoneal fluid pH on outcome of aminoglycoside treatment of intraabdominal infections.

Netilmicin and clindamycin were administered to 47 patients with an intraabdominal infection who underwent emergency laparotomy. Thirty-one patients were cured, seven were improved, and therapy failed in nine patients despite the fact that all aerobic bacteria isolated from these patients were sensitive to netilmicin as determined by standard in vitro susceptibility tests. The pH of peritoneal and drainage fluid collected intraoperatively and during follow-up correlated with clinical outcome. Acidic pH was found in 21 of 33 (64%) specimens sampled from patients with therapeutic failure compared to 17 of 80 (21%) obtained from the categories "cured" and "improved" (p < 0.001). Netilmicin concentrations in serum or peritoneal/drainage fluid did not correlate with clinical outcome. Netilmicin levels were above the minimal inhibitory concentration of the pathogens in 59 of 64 (92%) drainage fluid specimens in which aerobic bacteria were isolated. Aerobic bacteria were isolated in 91% of drainage fluid specimens if the pH was less than 7.0, compared to 37% if pH was more than 7.0 (p < 0.001). Reduction of pH antagonized aminoglycoside activity in vitro against clinical isolates of Escherichia coli. Surgical reexploration should be considered in cases of deterioration following a laparotomy associated with detection of acidic drainage fluid.

Abdomen↗
PubMedDate not supplied

Analysis of pH, pO2 and pCO2 in drainage fluid allows for rapid detection of infectious complications during the follow-up period after abdominal surgery.

Low pH (< 7.1) and pO2 (< 6.5 kPa) and high pCO2 (> 8 kPa) of peritoneal fluid have been previously associated with the presence of intra-abdominal infection. These parameters were monitored in drainage fluid following emergency laparotomy in 40 patients operated on for intra-abdominal infections and also in 15 patients who underwent laparotomy for another reason than infection. Significant differences were observed beginning on the fourth postoperative day between the 48 patients who improved or were cured and the seven patients in whom therapy failed due to anastomotic breakdown or abscess formation. Anastomotic leaks or abscesses were radiologically confirmed. In five of the seven failures, complications were first detected by analysis of pH, pO2 and pCO2 before clinical symptoms became evident. Specificity for each of these parameters in drainage fluid samples obtained after the second postoperative day was > 94%. Assessment of the three parameters allowed for simple, cost-effective, rapid and early detection of infectious complications following abdominal surgery.

Ascitic Fluid↗
PubMedDate not supplied

Variability of serum concentrations of trimethoprim and sulfamethoxazole during high dose therapy.

Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment of Pneumocystis carinii pneumonia. Daily doses of 15-22 mg/kg trimethoprim and 75-110 mg/kg sulfamethoxazole were given every 6 h. Despite administration of a loading dose of twice the regular dose, serum trough concentrations continuously rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamethoxazole. After 4-6 days mean trough concentrations of trimethoprim and sulfamethoxazole were 7.7 +/- 3.0 and 198 +/- 74 mg/l, with individual values of < 4.6 and < 103 mg/l in two patients and > 11.4 and > 307 mg/l in two others. Patients treated orally or i.v. had similar serum levels. However, large interindividual variability was observed despite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxazole over several days of treatment.

AIDS-Related Opportunistic Infections↗