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Intracellular bactericidal activity of ampicillin/sulbactam and erythromycin was determined with a human macrophage-like (U-937) cell line infected with Legionella pneumophila. Cell monolayers inoculated with L. pneumophila were treated with erythromycin, ampicillin, sulbactam, or ampicillin/sulbactam during the logarithmic phase of bacterial growth. Intracellular bacterial counts were determined at 2-h intervals for 8 h from the time that antibiotics were added. The number of viable intracellular bacteria increased during this time by 0.9 x log10 cfu/mL (P < 0.05) in the control culture, did not change significantly in the cultures treated with ampicillin or sulbactam, decreased by 0.8 x log10 cfu/mL (P < 0.05) with erythromycin, and decreased by 1.8 x log10 cfu/mL with ampicillin/sulbactam (P < 0.05). The number of cfu/mL was significantly less after incubation with ampicillin/sulbactam than with erythromycin (P < 0.05). Ampicillin/sulbactam appeared to have greater bactericidal activity against intracellular L. pneumophila than erythromycin in this in-vitro model. The bactericidal action of ampicillin/sulbactam was significantly greater than would be expected from the additive effects of ampicillin plus sulbactam, suggesting synergic bactericidal activity.

Four pairs of virulent/avirulent strains of Legionella pneumophila were examined for their adherence/uptake and activation of human monocytes. Oxidative metabolic responses of monocytes were quantitated by measuring intracellular hydrogen peroxide generation using flow cytometry and by assessment of superoxide dismutase-inhibitable superoxide anion generation. All L. pneumophila strains induced less of a response than did Escherichia coli. Within each pair of isolates, virulent strains of L. pneumophila stimulated the oxidative response of monocytes less than avirulent variants. To determine effects of complement fixation by each strain on their adherence to monocytes, a phagocytic index (PI) was determined under various conditions. In autologous donor serum (AS), all L. pneumophila strains had a PI in the range of 2.1-3.1 bacteria per monocyte, with E. coli having a PI of 9.1. No significant differences were observed between virulent L. pneumophila strains and their avirulent variants. In the presence of heat-inactivated AS, all PI fell to 0.13-0.20 for the L. pneumophila strains, and to 2.16 for E. coli. Using heat-inactivated AS reconstituted with exogenous human complement as a source of opsonization, levels of PI were indistinguishable from their respective levels in AS. This suggests that complement fixation plays an important role in the adherence of virulent and avirulent L. pneumophila to human monocytes.

Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.

Cephalexin has had 12 years of extensive clinical usage in the management of respiratory tract and other infections. It is reliably absorbed from the gastrointestinal tract and reaches therapeutic levels in serum and tissues. Toxicity and adverse side effects are minimal. The antimicrobial spectrum includes a majority of the pathogens usually associated with community-acquired lower respiratory tract infections with the significant exception of Haemophilus influenzae. Resistance of H. influenzae strains reduces the uses of cephalexin in the paediatric population and may limit its effectiveness in some patients with acute exacerbations of chronic bronchitis. In contrast, it is inordinately effective in managing most adult patients with lower respiratory tract infections, either as a primary agent, as a substitute for penicillins or other antimicrobial agents in patients unable to receive these, or for continuation of therapy in individuals who no longer require parenteral compounds. As with other cephalosporins, caution should be exercised to exclude meningitis when treating patients with respiratory tract infections since the majority of these compounds, including cephalexin, produce little or no cerebrospinal fluid levels.