Claes Henning

Penetration of Ampicillin and Dicloxacillin into Tissue Cage Fluid in Rabbits: Relation to Serum and Tissue Protein Binding

The pharmacokinetics of ampicillin and dicloxacillin following intravenous injection was studied in a tissue cage model in rabbits. Serum protein binding was 98.6% for dicloxacillin and 46.7% for ampicillin, and there were no major differences between the degree of binding in tissue case fluid. The highly bound dicloxacillin gave lower but more sustained levels in tissue cage fluid than ampicillin, and showed a very long elimination half-life. The findings suggest that the flow of albumin into the interstitial space could be of importance for the tissue penetration of highly protein bound antibiotics. The results also indicate dose-dependent pharmacokinetics for dicloxacillin.

Is Penicillin the Appropriate Treatment for Recurrent Tonsillopharyngitis? Results from a Comparative Randomized Blind Study of Cefuroxime Axetil and Phenoxymethylpenicillin in Children

The efficacy of cefuroxime axetil compared with phenoxymethylpenicillin (PcV) was studied in group A beta-haemolytic streptococci (GAS) culture-proven tonsillitis in children aged 3-12 years with a history of at least 1 episode of tonsillopharyngitis requiring antibiotic therapy during the previous 3 months. This was a comparative, randomized, investigator-blind, multicentre study. A total of 236 children received either cefuroxime axetil suspension or PcV syrup. Inclusion criteria were a positive, rapid, group A strep test verified by bacteriological culture and clinical signs and symptoms of tonsillopharyngitis. Cefuroxime axetil treatment gave a significantly higher bacteriological eradication rate and clinical cure rate than PcV. At day 2-5 post treatment the eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for PcV (p < 0.001). The clinical cure rates were 98/114 (86%) and 73/109 (67%) respectively (p < 0.01). Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime axetil patients and 37/109 (34%) PcV patients were treatment failures or had recurrence/reinfection of GAS tonsillopharyngitis (p < 0.001). More than 90% of the patients who experienced bacteriological treatment failure at either the first or second follow-up had the same serotype isolated pre- and post-treatment. During the study period, 21/114 (18%) patients in the cefuroxime axetil group and 50/109 (46%) patients in the PcV group received additional antibiotics (p < 0.001). No serious adverse events were noted and the mild adverse events were equally distributed among the patients in the 2 study groups: 15% for cefuroxime axetil and 14% for PcV.

Cefadroxil Once Daily for Three or Seven Days Versus Amoxycillin for Seven Days in Uncomplicated Urinary Tract Infections in Women

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.

Antibiotic Resistance in Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes in Respiratory Tract Infections in Outpatients

Sensitivity patterns of Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes were studied prospectively in an outpatient population seeking medical advice for respiratory tract infections (RTI) in the Southern parts of Stockholm. In total, 3,214 nasopharyngeal and 1,907 throat swabs were cultured during January-February 1996. 32% of the patients had received antibiotics during the previous year. Reduced penicillin sensitivity in S. pneumoniae was rare (1.3%) and only seen in patients treated with antibiotics during the previous 4 months. Beta-lactamase production in H. influenzae was found in 13.4% of patients who had been treated with antibiotics during the last 4 months and in 7.9% of the others. No resistance (< 1%) to erythromycin was seen in S. pyogenes. In this population-based surveillance, the levels of resistance in common respiratory tract pathogens were thus low and correlated to previous antibiotic treatment. Strict indications for antibiotic treatment in uncomplicated RTI are advocated to maintain a low resistance rate. Penicillin is still the drug of choice in patients without frequent recurrences of RTI in a setting similar to the one studied.

In Vitro Aminoglycoside Resistance of Gram-negative Bacilli and Staphylococci Isolated from Blood in Sweden 1980–1984

The in vitro susceptibility to gentamicin, tobramycin, amikacin and netilmicin in septicaemia isolates was followed during 1980-1984 in 6-8 Swedish laboratories. The bacterial distribution was similar over the years and was dominated by Escherichia coli and staphylococci. Resistance to gentamicin was found in 2.3-3.6%, to tobramycin in 1.4-3.4%, to amikacin and netilmicin in 0.5-0.9%. Production of aminoglycoside modifying enzymes was observed among resistant strains.

Susceptibility to Beta-lactam Antibiotics and Gentamicin of Gram-negative Bacilli Isolated from Hospitalized Patients: A Swedish Multicenter Study

A total of 952 blood and 1543 urine isolates of gram-negative bacilli from hospitalized patients in 1986-1987 were consecutively collected by 10 Swedish laboratories and tested for susceptibility to 8 beta-lactam antibiotics and to gentamicin. The isolates were mostly Escherichia coli (58% and 44%, respectively) and Klebsiella sp. (17% and 18%). Resistance to ampicillin in blood and urine isolates was found in 35% and 45%, respectively, to piperacillin in 5% and 6%, to cephalothin in 26% and 34%, to cefuroxime in 12% and 22%, to cefotaxime in 3% and 5%, to ceftazidime in 1% and 1%, to imipenem in 0.5% and 0.1%, to aztreonam in 3% and 2%, and to gentamicin in 0.8% and 0%. Resistance of clinically important gram-negative bacilli to new beta-lactam antibiotics and to gentamicin is infrequent in Sweden.

Comparative study of netilmicin/tinidazole versus netilmicin/clindamycin in the treatment of severe abdominal infections.

The efficacy of netilmicin combined with tinidazole (N + T) or clindamycin (N + C) in the treatment of severe abdominal infections was evaluated in a prospective randomized study with 20 patients in the N + T group and 21 patients in the N + C group. Normally the maintaining dose for netilmicin was 2.25 mg/kg every 12 h, for tinidazole 400 mg every 12 h and for clindamycin 300-600 mg every 6-8 h. The mean duration time of treatment was 8 days in the N + T group and 10 days in the N + C group respectively. In the N + T group 18 patients were cured and in the N + C group 17 patients. Among aerobic bacteria Escherichia coli was most frequently isolated and among anaerobes Bacteroides sp. All aerobic bacteria with 2 exceptions were susceptible to netilmicin and all anaerobic bacteria but 2 to tinidazole or clindamycin. Adequate serum levels were obtained for each antibiotic during therapy. In this study with a small number of patients the combination of netilmicin and tinidazole was as effective as netilmicin and clindamycin.

Penetration of Alafosfalin and Ampicillin into Tissue Cage Fluid in Rabbits

The pharmacokinetics of alafosfalin and ampicillin were studied in rabbits. Serum concentrations were compared to levels in subcutaneous tissue fluid obtained from implanted tissue cages. The concentrations of alafosfalin exceeded those of ampicillin and the drugs were eliminated at similar rates from serum and tissue fluid.

Factors influencing the biological inactivation of high protein bound beta‐lactam antibiotics in vitro

Unpredictable inactivation of antimicrobial agents may cause erratic results in pharmacokinetic studies. In this study we followed the inactivation of the high protein bound beta‐lactams flucloxacillin, dicloxacillin and ceftriaxone in vitro. The antibiotics were added to pools of human and rabbit sera, ultrafiltrates of these pools, rabbit interstitial fluid, phosphate buffered saline (PBS), rabbit albumin in PBS and sodium dodecyl sulphate (SDS) treated preparations of human sera. Ceftriaxone was relatively stable but different serum pools varied significantly in their flucloxacillin and dicloxacillin inactivating capacity. The dominating inactivation took place within five minutes after the addition of antibiotics to serum. The inactivating factor was heat stable at 56 °C, 0.5 h, of relatively high molecular weight, and not related to albumin. The inactivating capacity could be diminished by SDS‐treatment of serum suggesting a lipoprotein nature.