The subcellular distribution of the cell wall-associated protein antigens of Streptococcus salivarius HB, which are involved in specific adhesive properties of the cells, was studied. Mutants which had lost the adhesive properties and lacked the antigens at the cell surface were compared with the parent strain. Immunoelectron microscopy of cryosections of cells labeled with affinity-purified, specific antisera and colloidal gold-protein A complexes was used to locate the antigens. Antigen C (AgC), a glycoprotein involved in attachment to host surfaces, was mainly located in the fibrillar layer outside the cell wall. A smaller amount of label was also found throughout the cytoplasmic area in the form of small clusters of gold particles, which suggests a macromolecular association. Mutant HB-7, which lacks the wall-associated AgC, accumulated AgC reactivity intracellularly. Intracellular AgC was often found associated with isolated areas of increased electron density, but sometimes seemed to fill the entire interior of the cell. Antigen B (AgB), a protein responsible for interbacterial coaggregation, was also located in the fibrillar layer, although its distribution differed from that of the wall-associated AgC since AgB was found predominantly in the peripheral areas. A very small amount of label was also found in the cytoplasmic area as discrete gold particles. Mutant HB-V5, which lacks wall-associated AgB, was not labeled in the fibrillar coat, but showed the same weak intracellular label as the parent strain. Immunolabeling with serum against AgD, another wall-associated protein but of unknown function, demonstrated its presence in the fibrillar layer of strain HB. Negatively stained preparations of whole cells of wild-type S. salivarius and mutants that had lost wall-associated AgB or AgC revealed that two classes of short fibrils are carried on the cell surface at the same time. AgB and AgC are probably located on separate classes of short, protease-sensitive fibrils 91 and 72 nm in length, respectively. A third class of only very sparsely distributed short fibrils (63 nm) was observed on mutant HB-V51, which lacks both wall-associated AgB and AgC antigens. The identity of these fibrils and whether they are present on the wild type are not clear. The function of long, protease-resistant fibrils of 178 nm, which are also present on the wild-type strain, remains unknown.

SUMMARY The pharmacokinetics of ciprofloxacin, a quinoline derivative with marked bactericidal activity against gram-negative bacteria, was studied in calves and pigs following intravenous and oral administration. Ciprofloxacin was rapidly and well distributed in the body, exhibited a short elimination halflife of 2.5 h in both species, and was rapidly absorbed after oral administration (Tnax:2 to 3 h). The oral bioavailability in calves was 53 ± 14% and for 1 pig 37.3%.The renal clearance of the unbound ciprofloxacin for both species was of the same order, indicated a predominantly tubular secretion pattern, and accounted for about 46% of the total drug elimination. No complete drug mass balance could be demonstrated. Small amounts of two metabolites were detected in the urine of calves, but not in pig urine.

Ceftazidime has good antibacterial activity against many Gram-negative micro-organisms including Ps. aeruginosa. The aim of the present study was to calculate a dosage adjustment regimen for renal failure patients and to test it in a second group of patients. A study was made of the pharmacokinetics of ceftazidime 1 g given as a single bolus i.v. injection in 20 patients in an intensive care unit with varying degrees of renal function, including patients on regular haemodialysis. The serum half-life of elimination (t1/2 beta) varied from 1.6 to 45 h depending on renal function. During haemodialysis the mean t1/2 was 4.7 h. A good correlation between the renal clearance of creatinine and ceftazidime was observed. In most patients protein binding was lower than previously observed. From the pharmacokinetic data, a dosage adjustment regimen for patients with renal insufficiency was calculated, which studies in 7 further patients showed to be effective.

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Pharmacokinetic data were obtained from four healthy volunteers after oral administration of a single 400 or 600 mg dose of enoxacin. Enoxacin was absorbed quickly and absorption was increased when enoxacin was ingested after a meal. Renal clearance of enoxacin and 4-oxo-enoxacin decreased after simultaneous administration of probenecid. In addition, pharmacokinetic parameters of enoxacin and its 4-oxo metabolite were determined for plasma and sputum from 19 patients treated with enoxacin, 400 or 600 mg bd, for a respiratory tract infection. The half-life of both enoxacin and 4-oxo-enoxacin was 5-6 h; during treatment with 400 and 600 mg bd, the plasma concentrations exceeded MIC values for most bacteria isolated in respiratory tract infections, including most Pseudomonas aeruginosa strains; Streptococcus pneumoniae was an exception. Diffusion from plasma to sputum was approximately 100%. Of an ingested dose, 60-65% was recovered in the urine in 24 h. In a third study, a single 600 mg dose of enoxacin was given to 15 patients undergoing thoracotomy. Subsequent lung tissue concentrations of enoxacin were significantly higher than plasma concentrations at the same time after ingestion.

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