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The effects of 5-day courses of orally administered cephalexin, clindamycin and erythromycin on the Gram-negative, aerobic faecal flora of healthy adults were examined. The concentration of cephalexin reached in the intestine was high enough to cause the emergence of resistant Gram-negative bacteria; organisms belonging to the genera Enterobacter, Citrobacter and Pseudomonas increased to easily detectable levels. The faecal concentration of erythromycin was high and caused a severe reduction of the coliform flora. Clindamycin administration resulted in a considerable increase in the coliform count; the increase in the proportion of klebsiellae was especially marked.

Uptake of amino beta-lactam antibiotics into rat intestinal brush border membrane vesicles has been examined for characterization of the transport of the antibiotics through the gut wall of the rat. The uptake of cephradine, cephalexin and ampicillin into membrane vesicles was similar, and there were no significant changes in the uptake in the presence of a NaCl or a KCl gradient. These results suggested that the carrier-mediated transport systems relating to amino acids and glucose were not concerned with the intestinal absorption mechanism of amino beta-lactam antibiotics.

The pivaloxymethyl ester of 7-(D-2-amino-2-phenylacetamido)-desacetoxicephalosporanic acid hydrochloride (ST-21) and cephalexin possess the same bacteridal activity. In fact, in the animal body ST-21 releases cephalexin. The acute toxicity study shows the good tolerance of both substances, whereas the tissue distribution is different, both after oral and i.v. administration. Cephalexin concentrations in some tissues of rats and rabbits, particularly in the lungs and kidneys, are higher and longer-lasting in the animals treated with ST-21 than in those receiving cephalexin, thus showing a different pattern of distribution in the body. For this reason ST-21 might be more suited for the treatment of lung and kidney infections.

Cephalexin has an antimicrobial spectrum that includes those pathogens most frequently encountered in clinical practice. It is useful in the treatment of infections of the upper and lower respiratory tract, skin and soft tissue, and the genitourinary tract. It can be administered in relatively high oral doses without gastrointestinal irritation, and because it is absorbed high in the intestinal tract, it does not disturb the lower bowel flora. Because of its stability and chemical configuration, it causes a very low incidence of allergy. Cephalexin is not absorbed from the stomach but is totally and rapidly absorbed in the upper intestine. Children, because of their greater body water turnover, may need higher doses per kilogram than those used in treating adults. Distribution to the tissues, other than the spinal fluid and aqueous humour, is rapidly achieved. Cephalexin does not penetrate into the host tissue cells, which probably accounts for its low incidence of side effects. Binding to human serum proteins is low, and there is no measurable destruction or metabolism of cephalexin during its sojourn in the body fluids. Cephalexin is rapidly cleared from the body by the kidneys. Seventy to 100% of the dose is found in the urine 6-8 hr after each dose. Concentrations of 500-1000 micrograms/ml of urine follow 250 to 500 mg oral doses of cephalexin, many times greater than the minimum inhibitory concentration for the usual urinary tract pathogens. Patients with creatinine clearances less than 30 ml/min require a reduction in cephalexin dosage. This reduction should be proportional to the reduced function which may be established by determination of creatinine clearance or serum creatinine.

Optimal therapy of infections caused by bacteria able to survive within phagocytes requires the use of antibiotics which inactivate these intracellular organisms. To define characteristics that determine entry of antimicrobial agents into phagocytes, we studied the uptake of 14 radiolabeled antibiotics by rabbit AM. Cell-antibiotic mixtures were incubated for 2 hr, and at intervals antibiotic uptake was determined by velocity-gradient centrifugation (separation of cells from extracellular antibiotic). Many drugs failed to penetrate AM readily. Cellular concentrations of penicillin G and three cephalosporin antibiotics were much lower than extracellular levels (C/E = less than 0.1 to 0.4). Gentamicin, isoniazid, and tetracycline attained C/E values of 0.5 to 0.8. The more lipid-soluble antibiotics, refampin, lincomycin, and chloramphenicol, were concentrated approximately twofold (C/E = 2) in AM. Ethambutol (C/E = 7) and two erythromycin preparations (C/E = greater than 20) were markedly accumulated by macrophages. In comparison with other antibiotics tested, the uptake of clindamycin was both massive and rapid (C/E = 50 by 30 min). Ethambutol, erythromycin and clindamycin uptakes by AM are dependent upon oxidative metabolic processes. Detailed characterization of clindamycin uptake confirmed that the drug is accumulated by an active transport system. These findings, in association with studies of antibiotic-mediated influence on phagocytes, should provide information useful in establishing guidelines for optimal antibiotic usage.

Susceptibility testing of clinical isolates of several gram-negative and gram-positive species showed LY163892 to be more active than cefaclor and cephalexin. OXA-2, TEM-1, TEM-2, PSE-1, CEP-1, CARB-3 and SHV-1 beta-lactamases showed similar activity against LY163892 and cefaclor, whereas OXA-1 hydrolyzed the latter more rapidly. Organisms producing these beta-lactamases, but not TEM-2 and CEP-1, appeared to be more susceptible to LY163892 than cephalexin, although cephalexin proved to be more resistant to beta-lactamase activity. Strains producing TEM-2 and CEP-1 were resistant to LY163892, cefaclor and cephalexin.

Oral cephalexin, 1 to 2 g daily for 3 days, was given to six stable, noninfected patients receiving maintenance continuous ambulatory peritoneal dialysis (CAPD). The peak serum concentration after a 2 g initial dose was between 73 and 123 mg/L. On the second and third day in five patients who received a 2 g daily oral dose, the serum concentrations were between 35 and 118 mg/L in serum obtained 1 to 1.5 hours after the dosing. Similar serum concentrations were seen in one patient who only received a 1 g oral dose on the second and third day. Cephalexin concentrations in the peritoneal dialysate reached a peak on the first day between 4 to 14 hours after the dose and were between 31 to 78 mg/L. During the second and third day, the highest cephalexin concentration was 118 mg/L and the lowest was 12 mg/L. The data are consistent with the feasibility of oral cephalexin for treatment of CAPD-associated peritonitis with microorganisms that are sensitive to these levels of cephalexin.

A comparative study to determine the transfer of cefroxadine (CXD), an oral cephem antibiotic, to the human tears was undertaken using cephalexin (CEX) as the control drug. The mean tear levels of 250 mg each of CXD and CEX after oral administration in 6 volunteers were equally peaked at 0.26 micrograms/ml with CXD after 1 to 2 hours and with CEX after 2 hours. The changes of tear levels were also equal for both drugs. The ratios between the tear and the blood levels at 2 hours after oral administration were almost equal with 4.1% for CXD and 3.7% for CEX. From the above evidence it has been confirmed that the both drugs were equivalent with regard to the concentration profiles in human tears after oral medication.

In a cross-over study, 10 healthy adult volunteers received 1 g cefaclor and 1 g cephalexin orally 1 hour after a standard breakfast. Serum levels of cefaclor rose somewhat faster and were higher than those of cephalexin in the first 60 minutes. At the end of the second hour the serum concentration of cephalexin was 50--100% higher. The area under the serum level curve averaged 45 hr-micrograms/ml for cefaclor and 60 hr-micrograms/ml for cephalexin. Calculated pharmacokinetic constants indicate that the absorption rate of cefaclor was nearly the same as that of cephalexin. The serum half-life of cefaclor was 1 hr. The urine recovery of cefaclor for 9 hours averaged 65%, whereas cephalexin resulted in a urine recovery of 85%. To evaluate sputum levels, 15 adult patients with bronchial carcinoma and secondary bronchitis or pneumonia were treated with 0.5 g of cefaclor orally 4 times daily. The mean individual sputum levels were 0.44 micrograms/ml (after the first dose) and 0.54 micrograms/ml (after repeated administration). In 10 other patients, after a single 1 g dose of cefaclor mean sputum levels after 1 hour and 3 hours doubled, whereas peak concentrations in sputum after 2 hours did not differ significantly. These results suggest that cefaclor will be useful in respiratory tract infections caused by sensitive bacteria.

1. Human serum protein binding of cefadroxil and some other cephalosporins were determined by centrifugal ultrafiltration (U.F.) method and equilibrium dialysis (E.D.) method. The binding rates of cefadroxil were 28.1% by U.F. method and 3.8% (beta 1*), 11.6% (beta 2*) by E.D. method. 2. Protein binding of cefadroxil with sera of various animal species were also determined by E.D. method. The binding rates were low as well as that with human serum. 3. With two popular calculation formula for E.D. method, binding rate was considered on the alteration of the ratio of V2/V1.

The general pharmacological properties of cefadroxil which is a new semisynthetized cephalosporin were examined and following results were obtained. 1) Cefadroxil had no appreciable influences on the central nervous system in mice and the EEG in cats. 2) Cefadroxil had no effects on the isolated smooth muscle organs. 3) Cefadroxil had no effects on the passage of charcoal meal in mice and the motility of the stomach in situ in rabbits. 4) Cefadroxil inhibited the gastric secretion in pylorus-ligated rats. 5) Cefadroxil induced no marked changes in the respiration, blood pressure, heart rate, electrocardiogram and femoral blood flow in anesthetized dogs. Cefadroxil had no effects on the isolated hearts and ear vessles of rabbits. 6) Cefadroxil decreased the urine volume and the excretion of electrolytes (Na+, K+ and Cl-) in first three hours in rats. 7) Cefadroxil increased the biliary secretion in rats. No significant effects of cefadroxil were found in the other pharmacological experiments.

In 20 patients with acute pulmonary infections, sputum purulence, sputum volume, and concentration and excretion of cephalexin in the sputum significantly decreased concurrently during therapy. The concentration of cephalexin in the serum remained unchanged. Significant correlations were observed between drug concentrations in sputum and serum and between drug excretion in sputum and concentration in serum. These observations may be explained by decreased integrity of the "blood-bronchus barrier" during inflammation, with diffusion of serum into bronchial mucus, without the necessity of postulating active transport.

Cephalexin was given to 24 patients before and after operation on the bile ducts and gall bladder. Two patients had obstructive jaundice. Samples of the bile were taken either directly from the gall bladder at operation or via the T-tube. Cephalexin was excreted in the bile, peak levels being obtained after two to three hours. These levels could be raised if probenecid was given concurrently. Higher levels were found in patients with functioning gall-bladders. A trial of cephalexin seems justified for the treatment of typhoid carriers.