Variable ventilation ages in the equatorial Indian Ocean thermocline during the LGM.

Variations of atmospheric CO2 during the Pleistocene ice-ages have been associated with changes in the drawdown of carbon into the deep-sea. Modelling studies suggest that about one third of the glacial carbon drawdown may not be associated to the deep ocean, but to the thermocline or intermediate ocean. However, the carbon storage capacity of thermocline waters is still poorly constrained. Here we present paired 230Th/U and 14C measurements on scleractinian cold-water corals retrieved from ~ 450 m water depth off the Maldives in the Indian Ocean. Based on these measurements we calculate ∆14C, ∆∆14C and Benthic-Atmosphere (Batm) ages in order to understand the ventilation dynamics of the equatorial Indian Ocean thermocline during the Last Glacial Maximum (LGM). Our results demonstrate a radiocarbon depleted thermocline as low as -250 to -345‰ (∆∆14C), corresponding to ~ 500-2100 years (Batm) old waters at the LGM compared to ~ 380 years today. More broadly, we show that thermocline ventilation ages are one order of magnitude more variable than previously thought. Such a radiocarbon depleted thermocline can at least partly be explained by variable abyssal upwelling of deep-water masses with elevated respired carbon concentrations. Our results therefore have implications for radiocarbon-only based age models and imply that upper thermocline waters as shallow as 400 m depth can also contribute to some of the glacial carbon drawdown.

Fluoroquinolone resistance in Bacteroides fragilis following sparfloxacin exposure.

In vitro pharmacodynamic studies investigating the antimicrobial properties of five fluoroquinolones, (trovafloxacin, sparfloxacin, clinafloxacin, levofloxacin, and ciprofloxacin) against Bacteroides fragilis ATCC 23745 were conducted. The times required to reduce the viable counts by 3 log units were as follows: clinafloxacin, 2.9 h; levofloxacin, 4.6 h; trovafloxacin, 6 h; and sparfloxacin, 10 h. Exposure to ciprofloxacin did not achieve a 3-log decrease in viable counts. The susceptibility of B. fragilis was determined both prior to exposure and following 24 h of exposure to each of the five fluoroquinolones tested. The MICs of clinafloxacin, levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin, metronidazole, cefoxitin, chloramphenicol, and clindamycin were determined by the broth microdilution method. The MICs for B. fragilis preexposure were as follows: clinafloxacin, 0.25 microg/ml; trovafloxacin, 0.5 microg/ml; sparfloxacin, 2 microg /ml; levofloxacin, 2 microg/ml; and ciprofloxacin, 8 microg/ml. Similar pre- and postexposure MICs were obtained for cultures exposed to trovafloxacin, clinafloxacin, levofloxacin, and ciprofloxacin. However, following 24 h of exposure to sparfloxacin, a fluoroquinolone-resistant strain emerged. The MICs for this strain were as follows: clinafloxacin, 1 microg/ml; trovafloxacin, 4 microg/ml; sparfloxacin, 16 microg/ml; levofloxacin, 16 microg/ml; and ciprofloxacin, 32 microg/ml. No changes in the susceptibility of B. fragilis pre- and postexposure to sparfloxacin were noted for metronidazole (MIC, 1 microg/ml), cefoxitin (MIC, 4 microg /ml), chloramphenicol (MIC, 4 microg/ml), and clindamycin (MIC, 0.06 microg/ml). Resistance remained stable as the organism was passaged on antibiotic-free agar for 10 consecutive days. Mutant B. fragilis strains with decreased susceptibility to clinafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were selected on brucella blood agar containing 8x the MIC of levofloxacin at a frequencies of 6.4 x 10(-9), 4x the MICs of trovafloxacin and sparfloxacin at frequencies of 2.2 x 10(-9) and 3. 3 x 10(-10), respectively, and 2x the MIC of clinafloxacin at a frequency of 5.5 x 10(-11); no mutants were selected with ciprofloxacin. The susceptibilities of strains to trovafloxacin, levofloxacin, clinafloxacin, sparfloxacin, and ciprofloxacin before and after exposure to sparfloxacin were modestly affected by the presence of reserpine (20 microg/ml), an inhibitor of antibiotic efflux. The mechanism of fluoroquinolone resistance is being explored, but it is unlikely to be efflux due to a lack of cross-resistance to unrelated antimicrobial agents and to the fact that the MICs for strains before and after exposure to sparfloxacin are minimally affected by reserpine.

The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of Staphylococcus aureus under aerobic and anaerobic conditions.

An in-vitro pharmacodynamic system was used to generate time-kill curves to demonstrate the concentration-independent pharmacodynamics of vancomycin against Staphylococcus aureus ATCC 29213. Initial vancomycin concentrations of 5, 10, 20 and 40 mg/L were studied monoexponentially while simulating a 6 h half-life. One parallel experiment was performed in duplicate using an initial peak concentration of 40 mg/L where both a distribution alpha-phase half-life of 0.66 h for 1 h and an elimination beta-phase half-life of 6 h for 11 h were simulated to determine if the transient distribution phase concentrations of vancomycin have any impact on bacterial killing beyond that provided by the elimination phase concentrations. Additionally, two monoexponential experiments with peak concentrations of 40 and 20 mg/L and a half-life of 6 h were repeated in an anaerobic chamber to determine if killing of S. aureus was affected. The time to achieve a 3 log10 kill was calculated from the linear portion of the regression line and averaged (mean +/- S.D.) 9.0 +/- 1.4 h for all aerobic monoexponential experiments and was 8.4 and 8.6 h for the aerobic biexponential experiments (P > 0.05). For the anaerobic studies, the times to reach 3 log10 kill were significantly greater averaging 18.9 +/- 1.7 h. The slopes of the bacterial kill curves were virtually identical for both monoexponential and biexponential aerobic experiments averaging -0.34 +/- 0.04, yet significantly different from the anaerobic bacterial kill curve slopes of -0.16 +/- 0.015 (P < 0.05). Time-kill curve analyses suggest that varying the concentration of vancomycin does not affect the rate or extent of bacterial killing aerobically or anaerobically against S. aureus and more efficient killing was achieved under aerobic conditions. The simulated distribution phase concentrations did not contribute to more effective killing of this strain of S. aureus.

Therapeutic options for cefotaxime in the management of bacterial infections.

Clinical studies of cefotaxime administered every 8 and 12 h have demonstrated comparable clinical and microbiologic success when compared to traditional 6-h regimens. This phenomena may be explained, in part, by the pharmacokinetic and pharmacodynamic properties of cefotaxime and the antimicrobially active metabolite desacetyl-cefotaxime. Although cefotaxime levels cannot be maintained above the bacterial minimum inhibitory concentration (MIC) for all infecting pathogens with extended dosing intervals, concentrations of desacetyl-cefotaxime remain above the effective concentration for a variety of organisms throughout the extended interval. Cefotaxime dosage adjustment may be accomplished in nonimmunocompromised patients with infections outside the central nervous system including uncomplicated urinary tract and lower respiratory infections. Infections caused by bacteria with MIC90 values < or = 1 microgram/ml usually respond to 8- or 12-h dosage intervals. Less susceptible organisms with MIC90 values between 2 and 8 micrograms/ml, such as Serratia marcescens, may initially require cefotaxime administered every 6 or 8 h. Extended intervals should be avoided or used cautiously in patients that are neutropenic, immunocompromised, or hypermetabolic. Upon evidence of clinical and microbiologic response, therapy may be continued with alternative stepdown therapy.