Antibiotic resistance (AR) is a global phenomenon that has severe epidemiological ramifications world-wide. It has been suggested that antibiotics that have been discharged into the natural aquatic environments after usage or manufacture can promote the occurrence of antibiotic resistance genes (ARG). These environmental ARGs could serve as a reservoir and be horizontally transferred to human-associated bacteria and thus contribute to AR proliferation. The aim of this study was to investigate the anthropogenic load of antibiotics in Northern Pakistan and study the occurrence of ARGs in selected samples from this region. 19 sampling sites were selected; including six rivers, one dam, one canal, one sewage drain and four drug formulation facilities. Our results show that five of the rivers have antibiotic levels comparable to surface water measurements in unpolluted sites in Europe and the US. However, high levels of antibiotics could be detected in the downstream river in close vicinity of the 10 million city Lahore, 1100, 1700 and 2700 ng L(-1) for oxytetracycline, trimethoprim, and sulfamethoxazole respectively. Highest detected levels were at one of the drug formulation facilities, with the measured levels of 1100, 4100, 6200, 7300, 8000, 27,000, 28,000 and 49,000 ng L(-1) of erythromycin, lincomycin, ciprofloxacin, ofloxacin, levofloxacin, oxytetracycline, trimethoprim and sulfamethoxazole respectively. ARGs were also detected at the sites and the highest levels of ARGs detected, sulI and dfrA1, were directly associated with the antibiotics detected at the highest concentrations, sulfamethoxazole and trimethoprim. Highest levels of both antibiotics and ARGs were seen at a drug formulation facility, within an industrial estate with a low number of local residents and no hospitals in the vicinity, which indicates that the levels of ARGs at this site were associated with the environmental levels of antibiotics.
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The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period.
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Prospective, observational study.
To quantify the combined effect of a protein synthesis inhibitor and a bactericidal agent on B. anthracis toxin production, sporulation and cell growth.
Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.
The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.
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It is estimated that 50-70% of acute exacerbations of chronic bronchitis (AECB) are caused by bacterial infections. Appropriate selection of antimicrobials may lead to better outcomes and reduced healthcare costs. Respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) have a broad spectrum of activity against most AECB-causing pathogens and are used as first-line treatment in patients with comorbidity, severe airway obstruction or recurrent exacerbations. We review studies, identified through a MEDLINE search, that compared clinical efficacy and speed of recovery for short-course (≤ 5 days) fluoroquinolone therapy with commonly prescribed standard therapy (≥ 7 days). Among 177 studies reporting the use of fluoroquinolones for AECB treatment, 23 used a short-course regimen, shown to be at least as effective as standard therapy of 7 or more days duration. Furthermore, evidence suggests that short-course therapy offers faster resolution of symptoms, faster rate of recovery, fewer relapses, fewer and shorter hospitalizations, and longer time between recurrences.
This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache.
The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.
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Three Neisseria meningitidis serotype B strains displaying elevated ciprofloxacin MIC values (0.06 and 0.25 μg/mL) and a GyrA alteration at T91I have been described in the United States by Wu et al. [Wu et al., (2009) Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America. N. Engl. J. Med. 360:886-892] and were further evaluated here by reference broth microdilution against fluoroquinolones (FQ) and other antimicrobial agents. Additional quinolone resistance-determining region (QRDR) mutations and alterations in structure and expression of the mtrCDE efflux system, including its intergenic regions, were also analyzed. Two strains showed ciprofloxacin and levofloxacin MIC values at 0.25 μg/mL, and 1 strain had a ciprofloxacin MIC at 0.06 μg/mL. In addition to T91I, the 2 strains displaying higher FQ MIC values also possessed a T173A alteration on GyrA. All components of the efflux pump mtrCDE (also associated with rifampin resistance) were intact, excluding the presence of insertions/deletions within the pump operon. The promoter region (mtrR) was fully sequenced and was distinct from FQ-susceptible controls. Isolates with higher ciprofloxacin MIC values had identical promoter region, whereas the isolate displaying a lower ciprofloxacin MIC value possessed a different sequence. Expression experiments showed discrepancies of the mRNA in pump components. The most remarkable difference was for the outer membrane protein encoded by mtrE that was hyperexpressed (>3600× elevated compared to control) in the strain displaying a ciprofloxacin MIC value of 0.06 μg/mL. These results confirm that T91I alteration on GyrA had an important role in elevating ciprofloxacin MIC values; however, additional resistance determinants, including other gyrA mutations, also contribute to higher FQ MIC levels. Alterations in expression of mtrCED pump appear to have minimal influence on ciprofloxacin resistance, and this finding was supported by low rifampin susceptible-level results (MIC, ≤0.008 to 0.03 μg/mL).
In a randomised crossover study, 14 volunteers received a single oral dose of 500 mg levofloxacin or 500 mg ciprofloxacin in order to assess plasma concentrations by high-pressure liquid chromatography (up to 24 h), urinary excretion and urinary bactericidal titres (UBTs) at intervals up to 120 h. The median maximum concentration of levofloxacin in plasma was 6.1 mg/L and that of ciprofloxacin was 2.3 mg/L. The median cumulative level of renal excretion of the administered dose of the parent drug was 81.2% for levofloxacin and 36.2% for ciprofloxacin. UBTs were determined for a reference strain and nine clinical uropathogens. The median UBTs of both quinolones measured within the first 12h were between 0 and 1:> or =1024, correlating with the minimum inhibitory concentrations (MICs) of the strains. For Gram-negative strains, the UBTs of both quinolones were comparable despite the lower MICs of ciprofloxacin. During further time courses, however, the UBTs of levofloxacin were significantly higher than those of ciprofloxacin. For Gram-positive strains, for which the MICs of levofloxacin were equal to or lower than those of ciprofloxacin, the UBTs of levofloxacin were already significantly higher from the beginning. It can be concluded that overall the doses of the two tested fluoroquinolones may be considered equivalent with regard to treatment of complicated urinary tract infections, although the recommended dosing is twice daily for ciprofloxacin and once daily for levofloxacin.