Biomedical subjects

J A Karlowsky

Publications and source records attributed to J A Karlowsky.

59 records · Page 4Linked to original sources

PubMedDate not supplied

Once versus thrice daily tobramycin alone and in combination with ceftazidime, ciprofloxacin and imipenem in an in vitro pharmacodynamic model.

The purpose of this study was to compare once daily (To24) and thrice daily (To8) tobramycin dosing regimens alone and in combination with ceftazidime, ciprofloxacin and imipenem against a clinical and ATCC strain of Pseudomonas aeruginosa. A one-compartment in vitro pharmacodynamic model was used to simulate bacteremic infection. Pharmacodynamic parameters, including rate of bacterial kill following the first dose or time to achieve a 99.9% reduction in bacterial counts (T99.9%), extent of bacterial kill with subsequent doses and bacterial count at 24 h were characterized for each regimen. Compared to To8 alone, the combination regimens had a shorter T99.9% (p = 0.045) and greater extent of bacterial kill following the first dose (p = 0.045). Compared to To24 alone, the combination regimens demonstrated similar rates (p = 0.067) and extents of bacterial kill following the first dose (p = 0.32), however, produced lower bacterial counts at 24 h (p = 0.045). The various combination regimens appeared equally effective considering rate and extent of bacterial kill following the first dose and residual inocula at 24 h. Ciprofloxacin-containing regimens demonstrated the most bacterial kill with subsequent doses, however, bacterial counts at 24 h were similar to those of other combination regimens.

Anti-Bacterial Agents↗

PubMedDate not supplied

Mecillinam activity compared to ampicillin, trimethoprim/sulfamethoxazole, ciprofloxacin and nitrofurantoin against urinary tract isolates of gram-negative bacilli.

Recent Canadian, American and European studies have reported increased ampicillin and trimethoprim/sulfamethoxazole resistance among urinary tract isolates of Escherichia coli. This trend suggests that a reevaluation of first- and second-line therapies for the treatment of community-acquired urinary tract infections is necessary. Mecillinam, a beta-lactam with preferential activity against gram-negative penicillin binding protein 2 (unlike other beta-lactams which preferentially bind gram-negative penicillin binding proteins 1a, 1b or 3), may offer clinically significant activity against ampicillin-resistant and trimethoprim/sulfamethoxazole-resistant E. coli. To test this assertion, the activity of mecillinam was compared with ampicillin, trimethoprim/sulfamethoxazole, nitrofurantoin and ciprofloxacin against 258 consecutive gram-negative urinary tract isolates collected at a Canadian tertiary care hospital. Mecillinam demonstrated significantly better activity than ampicillin and trimethoprim/sulfamethoxazole and significantly less activity than ciprofloxacin and nitrofurantoin against the 258 isolates tested. Against E. coli isolates specifically, mecillinam was significantly more active than ampicillin and trimethoprim/sulfamethoxazole (p < 0. 001) and as active as ciprofloxacin and nitrofurantoin. Mecillinam was active against 91.9% of ampicillin-resistant E. coli and 95.9% of trimethoprim/sulfamethoxazole-resistant E. coli. We conclude that mecillinam should be reevaluated for potential use in the treatment of community-acquired urinary tract infections.

Amdinocillin↗

PubMedDate not supplied

Comparative activity of cefditoren and other oral beta-lactams against nonpneumococcal streptococci.

BACKGROUND: In vitro studies of cefditoren activity have focused primarily on Streptococcus pneumoniae and other bacterial species isolated from patients with respiratory infections, but relatively few reports have been published describing the activity of cefditoren against clinical isolates of nonpneumococcal streptococci. METHODS: Cefditoren activity was determined by broth microdilution (M7-A5, NCCLS, 2000) for 450 viridans group streptococci, 917 Streptococcus pyogenes and 800 other beta-hemolytic streptococci collected throughout the US during 1999-2000. RESULTS: Against viridans group streptococci, cefditoren (MIC(90), 0.5 microg/ml) was 4- to 32-fold more active than the other beta-lactams tested (penicillin ampicillin, amoxicillin-clavulanate, cefprozil and cefuroxime). The difference in activity between cefditoren and the other beta-lactams was greater for penicillin-nonsusceptible isolates (MIC(90s), 1 microg/ml versus 8-32 microg/ml) than among penicillin-susceptible isolates (MIC(90s), 0.12 versus 0.25- 1 microg/ml). Cefditoren also demonstrated potent activity against S. pyogenes (MIC(90), 0.015 microg/ml) and other beta-hemolytic streptococci (MIC(90), 0.06 microg/ml), comparable to that of the other beta-lactams. CONCLUSIONS: The activity demonstrated by cefditoren against nonpneumococcal streptococci, including beta-lactam- and macrolide-resistant isolates, suggests that this agent holds promise as therapy for infections caused by all clinically significant species of streptococci.

Administration, Oral↗

PubMedDate not supplied

Evolving patterns of resistance to respiratory pathogens in Canada.

Active surveillance of changing resistance patterns is difficult but important for rational therapeutic choices. In Canada, penicillin resistance in Streptococcus pneumoniae has evolved more slowly than in other countries (in Europe and Israel rates exceed 50%). Currently, penicillin resistance is found in roughly 21% of Canadian isolates, and cross-resistance is becoming common. Beta-lactamase production is now found in approximately 28% of Haemophilus influenzae isolates, although more recently, rates over 30% have been found in some areas of Canada. In Moraxella catarrhalis, beta-lactamases are produced by 80% to 90% of bacteria, with resistance to trimethoprim/sulphamethoxazole also found. To date, there have been only a few reports of resistance to the fluoroquinolones. The apparent increase in the rate of development of resistance and cross-resistance will lead to new therapeutic challenges.

Anti-Bacterial Agents↗

PubMedDate not supplied

Aminoglycoside adaptive resistance.

Aminoglycoside adaptive resistance is defined as reduced antimicrobial killing in originally susceptible bacterial populations after initial incubation with aminoglycoside. It is observed in vitro and in vivo, most commonly with Pseudomonas aeruginosa. It appears to correlate with a marked reduction in intracellular aminoglycoside accumulation, although its specific mechanism and the cellular structures responsible remain unknown in P. aeruginosa. Recent work suggests that adaptive resistance develops coincident with cytoplasmic membranes protein changes and regulated expression of genes in the anaerobic respiratory pathway of the organism. It is clinically most relevant in immunocompromised patients and in those with serious infections, especially infections due to gram-negative rods. Treatment of these patients by targeting high peak concentration:minimum inhibitory concentration ratios with once-daily dosing may result in the best outcome. A major unresolved issue concerns the effect of combination therapy on the development of aminoglycoside adaptive resistance.

Aminoglycosides↗