Do dietary interventions exert clinically important effects on the bioavailability of ß-lactam antibiotics? A systematic review with meta-analyses.

BACKGROUND: Managing drug-food interactions may help to achieve the optimal action and safety profile of ß-lactam antibiotics. METHODS: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 ß-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. RESULTS: Eighteen of 25 ß-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed ß-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). CONCLUSIONS: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

Evaluation of 5-day therapy with telithromycin, a novel ketolide antibacterial, for the treatment of tonsillopharyngitis.

A pooled analysis of two double-blind, multicentre, Phase III studies compared oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus; GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS tonsillopharyngitis were randomised to receive telithromycin (n = 430), penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S. pyogenes (n = 590) obtained from throat swab samples on study entry were tested for their in-vitro susceptibility to telithromycin, clarithromycin and azithromycin. Telithromycin demonstrated in-vitro activity against the clinical isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively), including erythromycin-resistant strains. At the post-therapy/test of cure (TOC) visit (days 16-23), satisfactory bacteriological outcome was demonstrated for 88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated patients, respectively (per-protocol population). Overall, GABHS eradication rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6% (248/265) and 90.9% (220/242) for telithromycin and pooled comparators, respectively. Telithromycin was generally well-tolerated. Most adverse events considered to be possibly related to study medication were gastrointestinal and of mild intensity. Discontinuations as a result of adverse events were few in both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days was as effective as penicillin V or clarithromycin for 10 days in the treatment of GABHS tonsillopharyngitis.

Failure to eradicate Group A beta-haemolytic streptococci (GABHS) from the upper respiratory tract after antibiotic treatment.

The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue.

A novel microphysiometer based on MLAPS for drugs screening.

This paper presents a novel microphysiometer for simultaneous measurements of several extracellular ions concentrations in living cells based on MLAPS (multi-light addressable potentiometric sensor). In the microphysiometer, different sensitive membranes are illuminated in parallel with n light sources at different frequencies, the response amplitudes of each frequency component can be measured on-line by parallel processing algorithm. By the experiments, we can analyze the relations of the extracellular environmental H(+), Na(+), K(+), Ca(2+) under the effects of western medicines (dilantin, phenobarbital sodium, penicillin sodium) and Chinese drugs (scutellaria, medlar, hemlock parsley), and estimate the effects of several drugs. As the novel microphysiometer works under regular cell culture conditions, cells can be repeatedly simulated with drugs to complete dose-response curve within a few hours. With the detection of a general parameter (extruded protons and ions), the system can be used to monitor the real-time process of the cells' metabolism, observe the functional responses of different kinds of membrane-bound receptors, evaluate the drugs.

Are penicillin treatment failures in Arcanobacterium haemolyticum pharyngotonsillitis caused by intracellularly residing bacteria?

Arcanobacterium haemolyticum is an infrequent agent of pharyngotonsillitis in children and young adults. Despite the fact that A. haemolyticum is fully sensitive to penicillin in vitro, penicillin treatment failures are frequent. The ability of A. haemolyticum to invade HEp-2 cells and survive intracellulary was investigated. All 12 strains tested, of which 10 were isolated from patients with pharyngotonsillitis, and 2 were reference strains, were internalized by the HEp-2 cells. Four strains tested further, one of the reference strains and 3 of the clinical isolates, proved able to survive intracellularly for 4 days, thus creating intracellular reservoirs of bacteria. It was also shown that erythromycin, an antibiotic known to penetrate well intracellularly, efficiently killed these bacteria.

Use of gamma-linolenic acid in the treatment of schizophrenia and tardive dyskinesia.

There is good background evidence to suggest that essential fatty acids and their eicosanoid derivatives may play a role in schizophrenia and in with tardive dyskinesia. Trials involving treatment with essential fatty acids, or eicosanoids or drugs which stimulate eicosanoid synthesis have shown modestly promising results. Particularly favourable outcomes in both schizophrenia and tardive dyskinesia were associated with combined treatment using essential fatty acids and nutritional supplements.

[Changes in the sensitivity of pneumococci to antibiotics. Therapeutic consequences]. / Evolution de la sensibilité des pneumocoques aux antibiotiques. Conséquences thérapeutiques.

Streptococcus pneumoniae has a prominent role in infectious bronchopulmonary diseases. This organism is normally sensitive to a vast number of antibiotics. However, in recent years, acquired resistance against tetracyclines, macrolides, and, more recently, penicillins, has emerged. Since 1987, there is indeed a regular increase in the frequency of strains that have a lower sensitivity to penicillin G (less than 1% before 1986; 12% in 1990). However, this percentage of strains with a lower sensitivity is much more important among non-invasive as opposed to invasive organisms that are isolated from blood, pleural and spinal fluid cultures (3.3% in 1990). Among strains with abnormal sensitivity to penicillin G, there are very selective serotypes or serogroups: 4 types or groups (23, 19, 6 and 14) represent 80% of these strains. More than 80% of the strains of MIC greater than 2 mg/l are among only one stereotype, 23F. This abnormal sensitivity to penicillin G implies a modification of sensitivity to all beta-lactams, but MIC increase to a variable extent depending on the antiinfectious agent. The most efficient agents against strains of lower sensitivity are amoxicillin, imipenem and parenteral third generation cephalosporins. On the other hand, for all oral first, second and third generation cephalosporins, MIC increase to levels for which seric levels that are reached hardly demonstrate convincing efficiency. Even if resistance levels are less marked as shown by strains isolated from pulmonary infections as compared to what is seen in ENT, the trend in the development of abnormal sensitivity of pneumococci to beta-lactam agents urges the clinician to take into account these data in the therapeutic coverage of bronchopulmonary infections.

Efficacy of orally administered penicillin V for prophylaxis of experimentally induced streptococcal endocarditis.

Four oral penicillin V regimens were compared for the ability to prevent Streptococcus sanguis infection of experimentally induced valvular heart lesions in rabbits. Challenge doses of 10(4), 10(6), and 10(8) CFU of a penicillin-susceptible strain of S. sanguis were used in this study. Measured by recovery of test organisms from endocardial lesions, the lowest-concentration inoculum was infective for 53% of the recipients; the higher-concentration inocula were infective for all recipients. A single-oral-dose penicillin V regimen (36 mg/kg of body weight) prevented endocarditis when rabbits were challenged with 10(4) CFU, but protection diminished with increasing inoculum concentrations. In contrast, addition of a second penicillin V dose (18 mg/kg of body weight) administered with a 7-h interval between doses achieved fully effective prophylaxis against even the highest inoculum tested (10(8) CFU). A repeated set of experiments in which half the dose of penicillin V was administered showed significantly reduced protection against S. sanguis endocarditis.

Penicillin treatment in oral surgery in patients with coagulation disorders.

There are clinical observations indicating that the frequency of postoperative bleeding after oral surgery in patients with coagulation disorders is reduced by prophylactic antibiotic treatment. To assess this effect, the concentrations of phenoxymethylpenicillin in plasma and saliva were determined during treatment and compared with the MIC values for penicillin of the oral bacteria of four patients with coagulation disorders. The concentration of penicillin in plasma of the patients considerably exceeded the MIC values of all isolated bacteria. In mixed saliva and saliva of the parotid and submandibular glands no penicillin activity could be detected. The bacteria isolated from the oral cavity of the patients did not in vitro exhibit either fibrinolytic or plasminogen activator activity. Thus, the oral bacteria of patients with coagulopathies probably do not cause an increased bleeding tendency by their intra- or extracellular enzymes.