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Summary Ninety-five group D streptococcal isolates from the feces of 95 healthy persons were compared with 157 group D streptococcal isolates from 38 patients of the surgical intensive care unit (sICU). The typing systems consisted of phage typing, enterococcinotyping and species differentiation. Strains isolated from fecal specimens showed high individuality (66 combination types) whereas strains from the sICU revealed strongly uniform types (32 combination types, three types comprised 83 isolates, i.e. 52.8%). Endogenous colonization was demonstrated by isolation of strains from different locations (throat, trachea, wounds, blood, urine, drains, catheters, and vaginal swabs) from the same patient, and. routes of transmission of the same strains to several patients were traced. The combination of three systems revealed a good discrimination between isolates of fecal and extrafecal specimens. The investigation detected highly preferred types in strains of extrafecal origin which were rarely isolated from fecal specimens. This may indicate that only strains with special characters preferably were able to colonize extraintestinal sites.

The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis.

The pharmacokinetics of high-dose i.v. diazepam were studied in two patients in an intensive care unit. The first patient received up to 240 mg of diazepam daily for 21 days while the second received 60 mg daily for 30 days. Plasma concentrations of diazepam and its major metabolite, desmethyldiazepam, were very large but, despite severe underlying disease and simultaneous administration of several other drugs, the half-lives of diazepam and desmethyldiazepam washout were consistent with those found in healthy persons. Washout half-lives in the first patient were, if anything, shorter than expected, possibly caused by simultaneous administration of phenobarbitone. Thus the kinetics of diazepam are apparently not altered by administration of large doses.