Interspecies recombination occurs frequently in quinolone resistance-determining regions of clinical isolates of Streptococcus pyogenes.

Fluoroquinolone resistance in Streptococcus pyogenes has been reported only anecdotally, but a recent Belgian surveillance study found a rate of nonsusceptibility of 5.4%. From an analysis of these isolates, we show that interspecies horizontal gene transfer within the parC quinolone resistance-determining region is a frequent phenomenon that might contribute to fluoroquinolone resistance.

Prevalence of first-step mutants among levofloxacin-susceptible invasive isolates of Streptococcus pneumoniae in the United States.

By use of a PCR-restriction fragment length polymorphism assay, we screened 496 levofloxacin-susceptible invasive pneumococcal strains (MIC

Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines.

The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.

SARS clinical features, United States, 2003.

We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.

Interspecies recombination in type II topoisomerase genes is not a major cause of fluoroquinolone resistance in invasive Streptococcus pneumoniae isolates in the United States.

Mutations in the topoisomerase type II enzymes account for fluoroquinolone resistance in Streptococcus pneumoniae. These mutations can arise spontaneously or be transferred by intraspecies or interspecies recombination, primarily with viridans streptococci. We analyzed the nucleotide sequences of the quinolone resistance-determining regions of 49 invasive levofloxacin-resistant pneumococcal isolates and did not find any evidence for interspecies recombination.

Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers.

The pharmacokinetics of ertapenem and ceftriaxone were investigated in an open, randomized, two-period crossover study after single- and multiple-dose administration in 10 healthy volunteers (five women and five men). Both antibiotics were administered intravenously once daily for 7 days at dosages of 1 g (ertapenem) and 2 g (ceftriaxone). The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). For ertapenem the maximum concentration of the drug in plasma (C(max)) was 256 mg/liter, the half-life was 20.7 h, and the area under the plasma concentration-time curve (AUC) was 830 mg. h/liter. The concentrations in fecal samples were (mean value) 37.2 and 32.7 mg/kg on day 4 and day 8, respectively. Ceftriaxone exhibited a mean C(max) of 315 mg/liter, a half-life of 7.6 h, and an AUC of 1,556 mg. h/liter. The mean concentrations in fecal samples were 153 and 258 mg/kg on day 4 and day 8, respectively. No accumulation of ertapenem or ceftriaxone was detected at steady state. A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers. No serious adverse event was observed. Both antibiotics induced a marked decrease in the anaerobic microflora (4-log-unit decreases in lactobacilli, bifidobacteria, clostridia, and bacteroides) and Escherichia coli, whereas the number of enterococci increased (4 log units). A slight overgrowth of yeasts was observed with both regimens. In all cases the microflora returned to normal levels on days 21 to 35.

Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine.

The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.

Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study.

Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log(10) CFU per ml of sputum per day, respectively. According to the data from our study, moxifloxacin exhibits an early bactericidal activity that is comparable to that of isoniazid.

Immune-mediated neuropathies: etiology and pathogenic relationship to aging processes.

Immune-mediated peripheral neuropathies are more frequent in aged populations. Equally, underlying diseases such as vasculitis and paraproteinemia are more prevalent in the elderly. Accumulating evidence is linking the aging process of the immune system, immunosenescence, to the susceptibility of older individuals for paraproteinemic, vasculitic and inflammatory demyelinating neuropathies. Why an individual develops a particular disease is likely due to a number of factors. These include mutations in neural tissue-specific B and T cells, decreased central tolerance, increased proinflammatory environment due to cytokine shifts and higher functional capacity of innate immune cells.