Bioterrorism alleging use of anthrax and interim guidelines for management--United States, 1998.
From October 30 through December 23, 1998, CDC received reports of a series of bioterroristic threats of anthrax exposure. Letters alleged to contain anthrax were sent to health clinics on October 30, 1998, in Indiana, Kentucky, and Tennessee. During December 17-23 in California, a letter alleged to contain anthrax was sent to a private business, and three telephone threats of anthrax contamination of ventilation systems were made to private and public buildings. All threats were hoaxes and are under investigation by the Federal Bureau of Investigation (FBI) and local law enforcement officials. The public health implications of these threats were investigated to assist in developing national public health guidelines for responding to bioterrorism. This report summarizes the findings of these investigations and provides interim guidance for public health authorities on bioterrorism related to anthrax. (+info)
Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells.
8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection. (+info)
Prediction of the effects of inoculum size on the antimicrobial action of trovafloxacin and ciprofloxacin against Staphylococcus aureus and Escherichia coli in an in vitro dynamic model.
The effect of inoculum size (N0) on antimicrobial action has not been extensively studied in in vitro dynamic models. To investigate this effect and its predictability, killing and regrowth kinetics of Staphylococcus aureus and Escherichia coli exposed to monoexponentially decreasing concentrations of trovafloxacin (as a single dose) and ciprofloxacin (two doses at a 12-h interval) were compared at N0 = 10(6) and 10(9) CFU/ml (S. aureus) and at N0 = 10(6), 10(7), and 10(9) CFU/ml (E. coli). A series of pharmacokinetic profiles of trovafloxacin and ciprofloxacin with respective half-lives of 9.2 and 4 h were simulated at different ratios of area under the concentration-time curve (AUC) to MIC (in [micrograms x hours/milliliter]/[micrograms/milliliter]): 58 to 466 with trovafloxacin and 116 to 932 with ciprofloxacin for S. aureus and 58 to 233 and 116 to 466 for E. coli, respectively. Although the effect of N0 was more pronounced for E. coli than for S. aureus, only a minor increase in minimum numbers of surviving bacteria and an almost negligible delay in their regrowth were associated with an increase of the N0 for both organisms. The N0-induced reductions of the intensity of the antimicrobial effect (IE, area between control growth and the killing-regrowth curves) were also relatively small. However, the N0 effect could not be eliminated either by simple shifting of the time-kill curves obtained at higher N0s by the difference between the higher and lowest N0 or by operating with IEs determined within the N0-adopted upper limits of bacterial numbers (IE's). By using multivariate correlation and regression analyses, linear relationships between IE and log AUC/MIC and log N0 related to the respective mean values [(log AUC/MIC)average and (log N0)average] were established for both trovafloxacin and ciprofloxacin against each of the strains (r2 = 0.97 to 0.99). The antimicrobial effect may be accurately predicted at a given AUC/MIC of trovafloxacin or ciprofloxacin and at a given N0 based on the relationship IE = a + b [(log AUC/MIC)/(log AUC/MIC)average] - c [(log N0)/(log N0)average]. Moreover, the relative impacts of AUC/MIC and N0 on IE may be evaluated. Since the c/b ratios for trovafloxacin and ciprofloxacin against E. coli were much lower (0.3 to 0.4) than that for ampicillin-sulbactam as examined previously (1.9), the inoculum effect with the quinolones may be much less pronounced than with the beta-lactams. The described approach to the analysis of the inoculum effect in in vitro dynamic models might be useful in studies with other antibiotic classes. (+info)
Influences of urinary pH on ciprofloxacin pharmacokinetics in humans and antimicrobial activity in vitro versus those of sparfloxacin.
The impact of acidification and alkalinization of urine on the pharmacokinetics of ciprofloxacin was investigated after single 200-mg oral doses were administered to nine healthy male volunteers. In addition, the effect of human urine on the MICs of ciprofloxacin and sparfloxacin against some common urinary tract pathogens such as Escherichia coli and Pseudomonas aeruginosa was investigated. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride or sodium bicarbonate, respectively. Plasma ciprofloxacin levels in all subjects were adequately described in terms of two-compartment model kinetics with first-order absorption. Acidification and alkalinization treatments had no effect on ciprofloxacin absorption, distribution, or elimination. The total amount of unchanged ciprofloxacin excreted over 24 h under acidic conditions was 88.4 +/- 14.5 mg (mean +/- standard deviation) (44.2% of the oral dose) and 82.4 +/- 16.5 mg (41.2% of the oral dose) under alkaline conditions, while the total amount of unchanged drug excreted over 24 h in volunteers receiving neither sodium bicarbonate nor ammonium chloride was 90.53 +/- 9.8 mg (45.2% of the oral dose). The mean renal clearance of ciprofloxacin was 16.78 +/- 2.67, 16.08 +/- 3.2, and 16.31 +/- 2.67 liters/h with acidification, alkalinization, and control, respectively. Renal clearance and concentrations of ciprofloxacin in urine were not correlated with urinary pH. The antibacterial activity of ciprofloxacin and sparfloxacin against E. coli NIHJ JC-2 and P. aeruginosa ATCC 27853 was affected by human urine and in particular by its pH. The activities of both quinolones against E. coli NIHJ JC-2 were lower at lower urinary pH and rather uniform, while in the case of P. aeruginosa ATCC 27853 ciprofloxacin was more active than sparfloxacin. (+info)
Evaluation of bactericidal activities of LY333328, vancomycin, teicoplanin, ampicillin-sulbactam, trovafloxacin, and RP59500 alone or in combination with rifampin or gentamicin against different strains of vancomycin-intermediate Staphylococcus aureus by time-kill curve methods.
This in vitro study evaluated the activities of vancomycin, LY333328, and teicoplanin alone and in combination with gentamicin, rifampin, and RP59500 against Staphylococcus aureus isolates with intermediate susceptibilities to vancomycin. Ampicillin-sulbactam and trovafloxacin were also evaluated. LY333328 and ampicillin-sulbactam resulted in bactericidal activity against all isolates. The combination of gentamicin with glycopeptides showed synergistic activity, while rifampin had no added benefit. (+info)
Moxifloxacin: a comparison with other antimicrobial agents of in-vitro activity against Streptococcus pneumoniae.
Two hundred representative isolates, including 26 strains of Streptococcus pneumoniae with intermediate resistance to penicillin, were selected from a collection obtained from blood cultures of patients with bacteraemic pneumococcal pneumonia. The MICs of moxifloxacin (BAY 12-8039), grepafloxacin, sparfloxacin, levofloxacin, ofloxacin, ciprofloxacin, erythromycin, tetracycline and penicillin G were determined by a standard agar dilution technique. Moxifloxacin had the highest in-vitro activity against S. pneumoniae (MIC90 = 0.25 mg/L; MIC range 0.06-0.25 mg/L). The MIC90 values were one dilution lower than those obtained with sparfloxacin and grepafloxacin, three dilutions lower than those obtained with levofloxacin, and four dilutions lower than those of ofloxacin and ciprofloxacin. (+info)
The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus.
In Staphylococcus aureus, in addition to mutations in the grl and gyr gene loci, multidrug efflux pumps like NorA contribute to decreased fluoroquinolone susceptibility. Efflux pumps can be inhibited by the plant alkaloid reserpine, which, at 20 mg/L, reduced sparfloxacin, moxifloxacin and ciprofloxacin IC50s and MICs by up to four-fold in 11, 21 and 48 of the 102 unrelated clinical isolates tested, respectively. The effect was less pronounced with the hydrophobic drugs sparfloxacin and moxifloxacin than with the hydrophilic drug ciprofloxacin and was stable in all 25 clonally related isolates tested. (+info)
Fluoroquinolone toxicity profiles: a review focusing on newer agents.
For 2 decades fluoroquinolones have been found to be generally well-tolerated and safe. Adverse events may be inherent to the class or influenced by structural modifications. The commonest adverse events are gastrointestinal tract (GI) and central nervous system (CNS) reactions; nephrotoxicity and tendinitis are infrequent, but agents differ greatly in phototoxic potential. Fluoroquinolones are safe in elderly, human immunodeficiency virus-infected, and neutropenic patients, but because of possible effects on articular cartilage, they are not currently recommended for children or pregnant women. Four new agents have recently been licensed. Levofloxacin causes few GI or CNS adverse events and is minimally phototoxic. Sparfloxacin infrequently causes GI or CNS effects but is associated with relatively high rates of phototoxicity and prolongation of the electrocardiographic QTc interval (Q-T interval, corrected for heart rate). Grepafloxacin causes relatively high rates of GI effects, taste perversion, and QTc interval prolongation, but it is minimally phototoxic. Trovafloxacin is associated with a moderate rate of GI effects and a relatively high incidence of dizziness but has low phototoxic potential. (+info)