Enhanced detection of hydrogen sulfide generated in cell culture using an agar trap method.

Lack of reliable methods to accurately measure hydrogen sulfide (H(2)S) produced in vitro has impeded research on the physiology of this gaseous mediator. Current in vitro methods involve measurement of H(2)S in cell culture media following incubation with H(2)S-releasing compounds. However, this method is inaccurate because H(2)S gas has a short life and thus evades detection.

Frequency of 1st- and 2nd-step topoisomerase mutations in Streptococcus pneumoniae following levofloxacin and moxifloxacin exposure.

Seven Streptococcus pneumoniae isolates were exposed to inhibitory concentrations of levofloxacin and moxifloxacin in antibiotic-containing agar dilution plates. Colony counts were used to calculate the frequency of mutation. DNA was sequenced to detect mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes.

In vitro pharmacodynamics of moxifloxacin versus levofloxacin against 4 strains of Streptococcus pneumoniae: 1 wild type, 2 first-step parC mutants, and 1 pump mutant.

Levofloxacin binds topoisomerase IV, whereas moxifloxacin preferentially binds DNA gyrase. Most 1st-step pneumococcal mutants have alterations in the parC gene of topoisomerase IV. Because of differential binding affinity, moxifloxacin may have superior activity against 1st-step mutants compared with levofloxacin.

In vitro evaluation of the activities of telavancin, cefazolin, and vancomycin against methicillin-susceptible and methicillin-resistant Staphylococcus aureus in peritoneal dialysate.

This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

Colistin methanesulfonate against multidrug-resistant Acinetobacter baumannii in an in vitro pharmacodynamic model.

Using an in vitro pharmacodynamic model, a multidrug-resistant strain of Acinetobacter baumannii was exposed to colistin methanesulfonate alone and in combination with ceftazidime. Pre- and postexposure colistin sulfate MICs were determined. A single daily dose of colistin methanesulfonate combined with continuous-infusion ceftazidime prevented regrowth and postexposure MIC increases.

Consistent rates of kill of Staphylococcus aureus by gentamicin over a 6-fold clinical concentration range in an in vitro pharmacodynamic model (IVPDM).

Objectives: To compare the effect of a 6-fold range in gentamicin concentration on the bacterial killing of Staphylococcus aureus.

Methods: Six 24 h duplicate experiments were performed using an in vitro pharmacodynamic model (IVPDM) which was inoculated with 10(6) cfu/mL S. aureus (ATCC 29213) and subjected to desired initial gentamicin concentrations of 0, 5, 10, 15 and 20 mg/L.

Mutant prevention concentrations of ABT-492, levofloxacin, moxifloxacin, and gatifloxacin against three common respiratory pathogens.

The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates.

Levofloxacin plus metronidazole administered once daily versus moxifloxacin monotherapy against a mixed infection of Escherichia coli and Bacteroides fragilis in an in vitro pharmacodynamic model.

Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model.

Dynamic analysis of peritoneal dialysis associated peritonitis.

Peritoneal dialysis associated peritonitis (PDAP) has a historical incidence of approximately 0.3 to 0.5 episodes per patient per year; it represents the leading cause for hospitalization in patients on peritoneal dialysis (PD) and imposes a significant burden of morbidity.

Pharmacodynamics of pulse dosing versus standard dosing: in vitro metronidazole activity against Bacteroides fragilis and Bacteroides thetaiotaomicron.

Pulse dosing is a novel approach to dosing that produces escalating antibiotic levels early in the dosing interval followed by a prolonged dose-free period. Antibiotic is frontloaded by means of four sequential bolus injections, after which antibiotic levels are allowed to diminish until the next dose. This study compares standard thrice-daily dosing and pulse dosing of metronidazole against Bacteroides spp.

Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an in vitro peritoneal dialysate model.

Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the antibacterial activity of cell wall-active agents. By use of an in vitro static model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of 10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25 mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S.

Mutation prevention concentration of ceftriaxone, meropenem, imipenem, and ertapenem against three strains of Streptococcus pneumoniae.

This investigation tested the mutation prevention concentration (MPC) concept using imipenem, meropenem, ceftriaxone, and ertapenem against three strains of Streptococcus pneumoniae (PCN MIC = 0.012, 1, 8 mg/L, respectively). MIC, MBC, and MPC values for each of the beta-lactams did not differ by more than one tube dilution.

Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model.

Despite the marketing of a series of new antibiotics for antibiotic-resistant gram-positive bacteria, no new agents for multiple-antibiotic-resistant gram-negative infections will be available for quite some time. Clinicians will need to find more effective ways to utilize available agents. Colistin is an older but novel antibiotic that fell into disfavor with clinicians some time ago yet still retains a very favorable antibacterial spectrum, especially for Pseudomonas and Acinetobacter spp.

Comparison of linezolid activities under aerobic and anaerobic conditions against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium.

Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium were exposed to linezolid (MIC of 2 mg/liter) under aerobic or anaerobic conditions in an in vitro pharmacodynamic model. Drug concentration and half-life were adjusted to simulate clinical dosing (600 mg twice daily) of linezolid. Linezolid produced a 2-log(10) killing at 24 h, and rates of killing against each of these facultative organisms as measured by mean survival time appeared similar under aerobic and anaerobic conditions.

Microbiologic effectiveness of time- or concentration-based dosing strategies in Streptococcus pneumoniae.

This in vitro study evaluated the pharmacodynamic performance of levofloxacin using different dosing strategies against both a levofloxacin-sensitive (MIC = 1 mg/liter) and -resistant (MIC = 16 mg/liter) strain of Streptococcus pneumoniae. The strain was genotypically characterized by a mutation in gyrA and two mutations in parE; resistance was shown not to be efflux-mediated. The purpose of this study was to determine if simulated levofloxacin dosing strategies focused either on time or concentration would affect microbiologic outcome.

Comparative pharmacodynamics of three newer fluoroquinolones versus six strains of staphylococci in an in vitro model under aerobic and anaerobic conditions.

Six strains of staphylococci were exposed to levofloxacin, moxifloxacin, or trovafloxacin in an in vitro pharmacodynamic model under both aerobic and anaerobic conditions. Each agent demonstrated a rapid 3-log(10) kill versus susceptible isolates regardless of condition. Against clinical isolates with reduced susceptibility, regrowth occurred by 24 h and was frequently associated with further increases in MICs.