An observational study on the epidemiology of respiratory tract bacterial pathogens and their susceptibility to four injectable beta-lactam antibiotics: piperacillin, piperacillin/tazobactam, ceftazidime and ceftriaxone.

Bacterial infections of the respiratory tract account for a large proportion of total medical consultations in general practice. In recent years, antibiotic resistance has increased alarmingly in a number of bacterial species that are common causes of these infections. The aim of this observational study was to determine the antibiotic resistance of microbial agents isolated from patients with acute or acutely exacerbated respiratory infections. Subjects recruited as potential sources of bacteria were either outpatients seen in a number of specialized clinics and hospital practices, or hospitalized patients. Overall, 648 consecutive patients (67% male, mean age 48.1+/-27.0 years) with infection of the upper or lower respiratory tract were observed during a 13-month period. A total of 551 pathogenic microbial strains were isolated and tested for their in vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and ceftriaxone. Among all isolates, the four most frequent pathogens were Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates, 18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46 isolates, 8%). The susceptibility of gram-positive isolates ranged from 97.5% to 95.1%, and no remarkable difference was found in the antibacterial activity of tested b-lactam antibiotics. The susceptibility of gram-negative isolates to piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%, respectively. In contrast, differences were found between piperacillin (or piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone (p<0.0003) in gram-negative isolates. We conclude that, despite the extensive use of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in medical practice during the past three decades, the susceptibility of the most common pathogens involved in the etiology of upper and lower respiratory tract infections to these antibiotics is still high. In particular, bacterial resistance developed by gram-positive organisms against piperacillin is negligible and not alarming.

Chemotherapy and immunomodulation in the elderly.

Ageing brings about an impairment of all body functions. Any antimicrobial and oncological treatment must take into account the senescent condition of the patient. Aged people are considered an immunodepressed population and oncotherapy has envisaged the use of components of the immune system. Our hope is to dispose shortly such neuroimmunomodulators as to be able to activate the impaired immune system which is present in the elderly.

Pathogen-host interaction.

Host defense, as it generally applies to humans, refers to the individual's ability to withstand infections. Human host defense mechanisms are numerous, diversified, complex, and often interdependent. The administration of drugs may influence some phases of immunocompetence mechanisms. The effect of several antimicrobial agents on organic defenses has been studied. The parameters considered were chemotaxis, phagocytosis, intracellular killing, superoxide-anion production, antibody production, lymphocyte subset behavior, and natural killer cell activity. Some antibacterial agents inhibit these parameters, whereas others can enhance some of these immune parameters to differing extents. Some antibacterial agents have a neutral effect on these parameters.

Cortical and medullary kidney tissue levels of cefonicid in human beings.

Cefonicid concentration has been determined microbiologically in cortical and medullary tissue in 30 patient undergoing surgery because of neoplastic disease localized within the kidney. Each subject received 1 g of cefonicid intramuscularly in a single administration. The patients were divided into six groups, from which samples of blood and tissue were collected 2, 4, 6, 8, 12, 24 h respectively after treatment with the drug. The mean peak serum levels appeared at the second hour (74.96 +/- 8.14 mcg/ml) and the decay shows a monoexponential behaviour, reaching a minimum value of 5.4 +/- 2.33 mcg/ml at the 24th hour. In the cortical tissue of the kidney the peak levels appeared at the fourth hour (26.22 +/- 8.87 mcg/g), while at the 24th hour levels were about 3.08 +/- 0.81 mcg/g. A very similar behaviour could also be observed in the medullary tissue of the kidney with peak levels at the fourth hour (25.82 +/- 10.06 mcg/g) and levels of 3.48 +/- 0.85 mcg/g at the 24th hour. A delay in the decay of tissue levels in comparison with the decay of blood levels could be observed from the eighth hour.

Prostatic tissue concentrations and serum levels of Myocamicin in human subjects.

The diffusion of Myocamicin in the prostatic tissue of patients undergoing prostatectomy after a single oral dose of 600 mg has been studied. The maximum concentration of antibiotic in the prostatic tissue and the serum peak are reached at the first hour with mean values respectively of 3.8 micrograms/g and 2.6 micrograms/ml. The concentrations of Myocamicin remain more elevated in the prostatic tissue compared with the serum levels, at the second, fourth and sixth hours. Myocamicin has shown itself to be an antibiotic with optimal capabilities of diffusion in the prostatic tissue, where it rapidly reaches good therapeutic concentrations.

Non-interference of xibornol on the theophylline blood levels.

The authors have proposed the evaluation of the possible pharmacokinetic interactions between xibornol and theophylline. This study has been carried out on eight healthy volunteers of both sexes between 19 and 27 years of age. On the first day each subject was treated with 600 mg oral sustained-release formulation of aminophylline at 08h00 and at 20h00. From the 2nd day an oral administration of 500 mg of xibornol every 8 h was added to the treatment of aminophylline. On the 1st, 2nd and 5th day blood samples were taken after 30, 90, 180 and 300 min following drug administration. After serum separation an analysis was performed on them. The results have shown that theophylline levels at the programmed times during the three days tested are just overlapping. In conclusion the administration of xibornol does not introduce any interference with theophylline clearance or lengthening of its plasma half-life.

Ribavirin influence on theophylline plasma levels in adult and children.

The pharmacokinetics of ribavirin and aminophylline (theophylline ethylenediamine) after oral administration in healthy adults and in children suffering from viral infections of the respiratory tract, with superimposition of bronchial asthma or asthmatic syndrome, was studied. By the prompt-release formulation of aminophylline the hematic peak is reached within the first 30 min (9.03 micrograms/ml) from intake, whereas by the sustained-release formulation the peak is reached only within the 5th hour (8.5 micrograms/ml). After administration of ribavirin no interferences with the clearance of theophylline both in adults and children were noted.