Intravenous metronidazole for treatment of infections involving anaerobic bacteria.

Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.     

In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and gram-positive cutaneous infections

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.     

Simulated leg-length discrepancy: its effect on mean center-of-pressure position and postural sway

We hypothesized that leg-length discrepancies of as little as 1cm would induce a significant postural shift and increase the extent of postural sway. We had 14 normal volunteers stand on a force platform with their feet in a standard position. Center-of-pressure data were recorded at 100Hz for 20 seconds while the subjects stood barefoot with no lifts or (in random order) with lifts of 1, 2, 3, and 4cm under their left and right feet. From these data we derived the mean center-of-pressure position and the extent of postural sway. Lifts of as little as 1cm shifted the mean center-of-pressure toward the longer leg to a statistically significant extent (p less than 0.001), the mean difference compared with the barefoot condition being 6.1% of the distance between the feet; increasing the discrepancy did not proportionately increase the effect. The postural sway (total travel of the center-of-pressure) in a mediolateral direction increased significantly with a 1cm discrepancy (p less than 0.01), and continued to increase in proportion to the magnitude of the discrepancy. There were no effects on anteroposterior position or sway and no influence of left-right dominance. These results support our hypothesis that a leg-length discrepancy of as little as 1cm may be biomechanically important.     

QUANTITATIVE STUDIES OF SULFONAMIDE RESISTANCE

1. In vitro experiments were performed with E. coli, using a method designed for the quantitative study of various aspects of sulfonamide resistance. 2. Resistance was found to be a gradually developing process, and was demonstrated for all four drugs tested, sulfanilamide, sulfapyridine, sulfathiazole, and sulfadiazine. 3. It was shown that the degree of resistance developed was correlated with the bacteriostatic potency of the sulfonamides, and that organisms resistant to certain bacteriostatic concentrations of one sulfonamide were equally resistant to similar bacteriostatic concentrations of the other sulfonamides. 4. These observations were interpreted as indicating that the development of sulfonamide resistance represents an interaction between the organisms and the one common structural unit of all the sulfonamides, namely, the p-amino nucleus. It is also suggested that this interaction may involve the same enzyme system (or systems) as those concerned in the antagonism of the sulfonamides by para-aminobenzoic acid. 5. The relation of these findings to the broader aspects of sulfonamide resistance is discussed, and it is postulated that, despite reports to the contrary, all organisms susceptible to the bacteriostatic action of the sulfonamides are capable of becoming resistant to all of the sulfonamides.