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Biomedical subjects

K Alestig

Publications and source records attributed to K Alestig.

At least 55 records · Page 3Linked to original sources

Clinical evaluation of lysis-centrifugation technique and a biphasic bottle system for blood culture.

The lysis centrifugation technique (Isolator, DuPont) for blood culture was compared with a system with biphasic medium in bottles. The Isolator was filled with 10 ml of blood once. One aerobic and one anaerobic bottle were injected 3 times with 2.5 ml of blood each. Organisms were detected in 90/748 blood cultures; 26 of which were contaminants. 34 pathogens were detected by both methods, 12 with the Isolator only and 18 with the 3 bottle pairs only. The first pair of bottles revealed 45/52 isolates, the second and third pairs gave an additional 6 and 1 isolate respectively. The contamination rate was 2.3% for the Isolator, which is lower than earlier reported, and 1.3% for the bottles. The most common pathogens were Escherichia coli, Pseudomonas aeruginosa and Streptococcus pneumoniae. The Isolator gave a faster diagnosis in 23 of the 34 cases. No decrease in the recovery rate was seen after 8 h, the longest recommended transport time for the Isolator tubes. One Isolator gave the same yield as the first pair of bottles and combining the methods increased the yield 25% compared to either method alone.

Adolescent↗

Tobramycin therapy--two or three doses per day?

11 patients with moderate infections were treated with bolus injections of tobramycin in a fixed dose of 4.5 mg/kg and day for 8 days. The patients were randomized to injections every 8 h (TID) for 4 days followed by injection every 12 h (BID) or vice versa. Serum concentrations were measured on day 2 of each regimen. The TID regimen gave peak levels less than 4 micrograms/ml in 5/11 patients, mean value 4.2 micrograms/ml. With the BID regimen 2 patients had peaks less than 4 micrograms/ml, mean value 5.9 micrograms/ml. The BID regimen seems preferable when treating patients with normal renal function. The bolus injections were well tolerated.

Adult↗

High doses of corticosteroids in the treatment of septic shock.

High doses of corticosteroids are reported to be beneficial in the treatment of septic shock in many animal species, e.g. dog, rat and rabbit. Recent findings in baboons subjected to E. coli shock indicate that early treatment with a combination of antibiotics and steroids strongly enhance survival rate. In clinical studies the protective effects of steroids are more ambiguous, however. In part this may be explained by variations in the amount of steroids used or by the fact that in some studies the steroid is administered late in shock. The dose recommended, 30 mg/kg bw of methylprednisolone or an equivalent amount of another glucocorticoid given once or twice, is based on animal as well as clinical documentation.

Adrenal Cortex Hormones↗

Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients.

127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.

Acyclovir↗

Ceftazidime and renal function.

Glomerular filtration rate (GFR) as measured by 51Chrome-EDTA clearance, decreased with a mean of 10 ml/min during therapy with ceftazidime 2 g bid in 16 patients with initial GFR of 30 to 110 ml/min. A significant increase in the excretion of urinary alanine aminopeptidase was also found. In another three patients with initial GFR of 17-22 ml/min increases in serum creatinine during therapy were noted. These observations indicate that ceftazidime should be used with caution in patients with impaired renal function and not be combined with nephrotoxic drugs until the safety of such combinations has been studied.

Adult↗

Severe acute encephalitis--improved outcome after barbiturate treatment?

Six cases of severe encephalitis due to measles, varicellae, mononucleosis, influenza, rubella and pertussis were treated with high doses of barbiturates in combination with steroids and artificial hyperventilation. Four of the patients also received antiviral therapy. They all survived without neurological sequelae. The use of barbiturates in high doses may be of importance for an improved outcome in patients with severe encephalitis.

Acyclovir↗

Effect of cefoperazone on faecal flora.

The effect of cefoperazone on the intestinal flora was investigated in 29 patients receiving the drug for 7 to 14 days. Faecal specimens were cultured quantitatively for aerobic and anaerobic micro-organisms before, during and after therapy. The cefoperazone treatment was associated with major changes in the faecal flora. There was marked suppression of enterobacteria, staphylococci, streptococci, anaerobic cocci, bacteroides, fusobacteria, bifidobacteria, eubacteria and lactobacilli. The number of enterococci increased in most patients and the number of clostridia remained constant. Eight patients had cultures positive for Clostridium difficile during or after treatment. The marked changes in the intestinal flora can have important clinical consequences.

Adolescent↗

Renal function in patients treated with tobramycin-cefuroxime or tobramycin-penicillin G.

In order to evaluate the potentiating effect of cefuroxime on tobramycin nephrotoxicity 21 immunocompromised patients with suspected septicaemia were randomized to treatment with either tobramycin + cefuroxime or tobramycin + penicillin G. 51Chromium-EDTA clearance, serum creatinine, serum beta 2-microglobulin, urinary, alanine aminopeptidase, urinary N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured during a nine day course of the antibiotic combinations. Enzymuria and a small but significant decrease of 51Chromium-EDTA clearance of equal magnitude in both treatment groups occurred. However the results cannot be extrapolated to other doses and treatment times than used in the study.

Cefuroxime↗

Ceftazidime in clinical practice.

In an open trial, the efficacy of intravenously administered ceftazidime was evaluated in 106 adult patients with urinary or respiratory tract infections, soft tissue infections, osteitis and septicaemia. The most commonly isolated pathogens were Escherichia coli, Pseudomonas spp. and Staphylococcus aureus. Of 85 organisms isolated before treatment, 79% were cleared and 15% were cleared but later relapsed often because of the underlying conditions. Clinical cure was achieved in 70%, improvement occurred in 25% of the patients and 6% failed to respond. Marked increases in serum creatinine occurred in three patients with pre-existing renal impairment treated with ceftazidime in unmodified dosage. Exanthema, diarrhoea or local thrombophlebitis was noted in 13 patients.

Adult↗

Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans.

The pharmacokinetics of intravenously administered N-formimidoyl thienamycin (MK0787) were studied in 14 healthy male subjects in a single-dose study, in which the volunteers received N-formimidoyl thienamycin with and without probenecid, and in a multiple-dose study, in which the subjects were given 250 or 500 mg every 8 h for 10 doses. High dose-related plasma concentrations of N-formimidoyl thienamycin were achieved; co-administration with probenecid resulted in only minor increases in these concentrations. No accumulation in plasma was seen after multiple doses. The plasma half-life of N-formimidoyl thienamycin was slightly less than 1 h and did not increase significantly with the coadministration of probenecid. The urinary recovery of N-formimidoyl thienamycin varied between 6.0 and 38.4% of the dose with a marked intersubject variability. Variations in individual subjects were small, however, when the urinary recoveries after repeated doses were compared. These results were in agreement with previous animal studies showing a renal metabolism of N-formimidoyl thienamycin. Probenecid administration resulted in a marked decrease in N-formimidoyl thienamycin urinary recovery. In vitro experiments showed that the decay of N-formimidoyl thienamycin in spiked pretreatment urine samples was 2 to 5%/h with more rapid degradation at acidic than at basic pH.

Adult↗

Urinary recovery of N-formimidoyl thienamycin (MK0787) as affected by coadministration of N-formimidoyl thienamycin dehydropeptidase inhibitors.

N-Formimidoyl thienamycin (MK0787) undergoes renal metabolism by a dipeptidase, dehydropeptidase I, located on the brush border of the proximal tubular cells. The effects of two inhibitors (MK-789 and MK-791) of dehydropeptidase I on the pharmacokinetics of N-formimidoyl thienamycin were studied in 41 healthy subjects receiving various combinations of N-formimidoyl thienamycin and MK-789 or MK-791. Both inhibitors affected the plasma kinetics of N-formimidoyl thienamycin only to a small extent. Plasma concentrations and the area under the plasma concentration curve increased about 20% with a proportional decrease in plasma clearance. Plasma half-life was not altered significantly. Coadministration of MK-789 or MK-791 resulted in uniform and marked increases in urinary recovery and renal clearance of N-formimidoyl thienamycin. Thus, at an N-formimidoyl thienamycin/MK-791 ratio of 1:0.25 or higher, the urinary recovery was about 72% in all subjects, whereas it varied between 7.7 and 43% when N-formimidoyl thienamycin was given alone. The ratio of the N-formimidoyl thienamycin and MK-791 doses affected response. At relatively higher doses of MK-791, significant increases of N-formimidoyl thienamycin urinary recovery, renal clearance, and urine concentrations occurred during the later part of the 10-h observation period after each administration. At a 1:1 ratio of the two drugs, the inhibition of renal metabolism of N-formimidoyl thienamycin was maintained for at least 8 h, whereas renal clearance declined as soon as 4 h after the administration of a 1:0.25 ratio. The results indicated that MK-789 and MK-791 alter the renal excretion of N-formimidoyl thienamycin from glomerular filtration plus tubular secretion to glomerular filtration only, possibly by competitively inhibiting the penetration of N-formimidoyl thienamycin into the proximal tubular cells.

Adult↗

Intensive care treatment in septic shock.

Deaths in septic shock continue to occur at a high frequency despite current treatment programs. However, the mortality can be substantially decreased with a close bedside attendance of patients at risk and if the patient is transferred to an intensive care unit for intensive treatment and monitoring as soon as shock is suspected or established. The treatment program consists of adequate antibiotic administration in combination with massive doses of steroids and aggressive infusion therapy supplemented with cardiovascular drugs according to the hemodynamic response to the initial treatment.

Anti-Bacterial Agents↗