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Biomedical subjects

Joseph M Blondeau

Publications and source records attributed to Joseph M Blondeau.

13 recordsLinked to original sources
PubMed2006

Mutant prevention concentration for ciprofloxacin and levofloxacin with Pseudomonas aeruginosa.

The mutant prevention concentration (MPC) was determined by population analysis using six fluoroquinolone-susceptible isolates of Pseudomonas aeruginosa applied to fluoroquinolone-containing agar plates. The MPCs were 3 mg/L and 9.5 mg/L for ciprofloxacin and levofloxacin, respectively. At high concentrations of either compound, single-step gyrA resistance mutants were recovered. Using a modified method for estimating the MPC, 151 clinical isolates were surveyed. Modal MPCs were 2 mg/L and 8 mg/L, respectively, for ciprofloxacin and levofloxacin. Thus, ciprofloxacin is three to four times more active than levofloxacin against resistant mutant subpopulations. For individual isolates, the MPC correlated poorly with the minimum inhibitory concentration (r(2) = 0.41 and 0.39 for ciprofloxacin and levofloxacin, respectively).

Anti-Bacterial Agents↗
PubMed2006

Optimal antimicrobial therapy: the balance of potency and exposure.

Antimicrobial therapy has evolved to be an essential component for treating bacterial infection; however, the optimal duration of therapy continues to be defined for a number of different infections. Previously, uncomplicated infections of the lower and upper urinary tracts required treatment durations of 10-14 days and can now be successfully managed with < or = 3-7 days of oral therapy. Similarly, optimal durations of therapy for community-acquired respiratory tract infections continue to be defined with shorter durations being approved, based on the clinical outcome of comparative trials. The shorter durations of therapy are thought to clearly benefit patient care with improved compliance. But, are all of the approved antimicrobial compounds ideal for shorter durations of therapy? Optimal use of these compounds involves re-evaluating each drug's antimicrobial spectrum, pharmacological characteristics, clinical outcome and side-effects profiles, and a reduced likelihood of selecting drug-resistant bacteria during therapy (due to the current environment of global antimicrobial resistance and fewer new antimicrobials under development).

Anti-Bacterial Agents↗
PubMed2004

Fluoroquinolones: mechanism of action, classification, and development of resistance.

The fluoroquinolones represent an evolving class of broad-spectrum antimicrobial agents used in the prevention and treatment of a variety of ocular infections; however, resistance to currently available agents in the class has been emerging among ocular pathogens. This article reviews the mechanism of action of existing and new fluoroquinolones and discusses the structure-activity relationship of the fluoroquinolones as it relates to the classification of these compounds. This article also highlights the mechanism of resistance among common ocular pathogens and discusses the potential need for newer fluoroquinolones in ophthalmology.

Anti-Infective Agents↗
PubMed2004

Gemifloxacin: a new fluoroquinolone.

Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.

Animals↗
PubMed2004

Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option.

Symptomatic urinary tract infections (UTIs) are a major public health concern in the developed world, accounting for almost 8 million annual outpatient and emergency department visits in the US alone, while also representing one of the most common hospital-acquired infections. The vast majority of uncomplicated UTIs are caused by the Gram-negative bacillus Escherichia coli, with other pathogens including enterococci, Staphylococcus saprophyticus, Klebsiella spp. and Proteus mirabilis. Effective management of UTIs in both the inpatient and outpatient settings has been complicated by the fact that many uropathogenic strains have developed resistance to antimicrobials, including cotrimoxazole (trimethoprim/sulfamethoxazole), the current first-line treatment for uncomplicated UTIs in the US and many other countries. In some countries, other antimicrobial therapies, such as trimethoprim and nitrofurantoin, are also used for treatment of uncomplicated UTIs. Antimicrobial resistance has been associated with an increased rate of clinical failure, and reports from Canada and the US indicate that the prevalence of cotrimoxazole resistance exceeds 15% and can be as high as 25%.The emergence and dissemination of antimicrobial resistance can be reduced with the use of agents that have favourable pharmacokinetic/pharmacodynamic profiles and convenient dose administration regimens that facilitate patient adherence and, therefore, pathogen eradication. Fluoroquinolones have been used successfully to treat a wide range of community- and hospital-acquired infections, and the rates of fluoroquinolone resistance have remained low. Use of fluoroquinolones is recommended for uncomplicated UTIs in areas where the incidence of cotrimoxazole resistance exceeds 10%, as well as for the treatment of complicated UTIs and acute pyelonephritis. Ciprofloxacin is a widely used fluoroquinolone with high bactericidal activity against uropathogens and well established clinical efficacy in the treatment of UTIs. A new, extended-release formulation of ciprofloxacin (Cipro XR) provides systemic drug exposure comparable with that achieved with twice-daily administration of conventional, immediate-release ciprofloxacin, while also attaining higher maximum plasma concentrations with less interpatient variability. Therapeutic drug concentrations with extended-release ciprofloxacin are established immediately after dose administration and maintained throughout the 24-hour dosage interval, permitting convenient, once-daily treatment. Clinical trial results confirm that extended-release ciprofloxacin is as safely used and effective as the conventional, immediate-release formulation of ciprofloxacin in patients with uncomplicated UTIs, complicated UTIs or acute uncomplicated pyelonephritis. These findings support the use of extended-release ciprofloxacin as a well tolerated, effective and convenient therapy for UTIs, which may improve patients' adherence to therapy and, thereby, reduce the risk of infection recurrence and emergence of antimicrobial resistance.

Anti-Infective Agents↗
PubMed2003

An outbreak of trichinellosis due to consumption of bear meat infected with Trichinella nativa, in 2 northern Saskatchewan communities.

In June 2000, bear meat infected with Trichinella nativa was consumed by 78 individuals in 2 northern Saskatchewan communities. Interviews and blood collections were performed on exposed individuals at the onset of the outbreak and 7 weeks later. All exposed individuals were treated with mebendazole or albendazole, and symptomatic patients received prednisone. Confirmed cases were more likely to have consumed dried meat, rather than boiled meat (P<.001). Seventy-four percent of patients completed the recommended therapy, and 87% of patients who were followed up in August 2000 reported complete resolution of symptoms. This outbreak of trichinellosis was caused by consumption of inadequately cooked bear meat contaminated with T. nativa. Apart from clinical symptomatology, blood counts, creatine kinase levels, serology test results, and analysis of the remaining bear meat helped establish the diagnosis. Treatment with antiparasitic drugs and prednisone was beneficial in limiting the severity and duration of the illness.

Adolescent↗
PubMed2002

The macrolides.

Erythromycin, which was introduced over 50 years ago, was the first macrolide to be used clinically. "New" macrolides, for the treatment of patients with various infectious diseases, were not clinically introduced until 40 years later. The pharmacokinetic and adverse events profile of erythromycin initially limited its use to an alternative agent for patients with allergy to beta-lactam agents. However, the emergence of atypical and/or new pathogens and the ongoing escalation of acquired antimicrobial resistance has impacted on the empirical and organism directed therapy of infectious diseases. Azithromycin and clarithromycin were developed by enhancing the basic macrolide structure. Some of the basic features associated with these new agents include a pharmacokinetic profiles that allow once or twice daily dosing with a much lower incidence of side effects and a substantially broader spectrum of activity which includes some Gram-negative bacilli, atypical pathogens and new, unconventional or uncommon pathogens. Clinical trial data has supported the use of "new" macrolides in a wide range of clinical indications, however, some specific indications are currently restricted to treatment with either azithromycin or clarithromycin. Macrolide resistance is a class effect and depending on the mechanism will confer either low or high level resistance. While resistance is problematic, it does not always result in clinical failure. The macrolides are a valuable class of antimicrobial agent and play an important role in the management of infectious diseases.

Anti-Bacterial Agents↗
PubMed2002

The evolution and role of macrolides in infectious diseases.

Two of the most significant changes in the field of infectious disease management during the last few decades are the emergence of atypical and/or new pathogens that may have devastating consequences and the re-emergence of well-recognised organisms that have acquired antimicrobial resistance through a variety of mechanisms. Erythromycin, the prototype macrolide, was originally marketed approximately five decades ago as a useful alternative agent in the treatment of patients allergic to beta-lactam antibiotics. While clinically useful, its pharmacokinetic and adverse-event profile limited the use of erythromycin to these individuals. Enhancements of the macrolide structure circumvented many of the limitations of erythromycin and resulted in the development of azithromycin and clarithromycin. The clinical uses of clarithromycin and azithromycin are substantially wider than erythromycin due to the wide spectra of activity against the atypical and newer pathogens. In addition, these agents are well-tolerated and have a pharmacokinetic profile that allows once- or twice-daily administration. Studies also indicate that the more common of the two mechanisms of macrolide resistance in the US and Canada imparts only low-level resistance. The multitude of studies substantiating clinical as well as bacteriological success with these two agents indicates that, when used appropriately, they will stand the test of time and continue to be useful antimicrobial agents.

Adult↗
PubMed2002

Quinupristin/dalfopristin.

Gram-positive pathogens are associated with both community- and hospital-acquired infections. These infections may be life-threatening in hospitalised patients, especially in those with significant underlying acute or chronic diseases. Prompt and appropriate antimicrobial therapy is essential for avoiding morbidity and mortality. The concept of appropriate therapy is being redefined by increasing antimicrobial resistance, especially amongst Gram-positive pathogens. This has been most dramatic with penicillin-resistant Streptococcus pneumoniae in the community, including cross-resistance to other classes of antimicrobial agents. In the US, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) with community isolates is significant. For hospital-acquired Gram-positive pathogens, MRSA, vancomycin-resistant Enterococcus species and vancomycin-intermediate resistant and -resistant S. aureus are a great concern, particularly as the frequency of recovery of these pathogens from infected patients increases. The net result of these various resistance issues is a reduction in the number of appropriate antimicrobial agents for treating infected patients. Quinupristin/dalfopristin is a parental streptogramin with a spectrum of activity that includes Gram-positive pathogens, including those resistant to other classes of antimicrobial compounds. In this review, data summarising the frequency of recovered Gram-positive pathogens from various infectious diseases, the escalating prevalence of resistance amongst Gram-positive pathogens and the factors making quinupristin/dalfopristin a suitable agent for treating patients infected with Gram-positive organisms will be discussed.

Animals↗
PubMed2002

The role of fluoroquinolones in skin and skin structure infections.

Skin and skin structure infections encompass a broad range of clinical presentations and disease severity. Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression. Fluoroquinolones are potent broad spectrum antimicrobial agents with the older agents characterized as having broad spectrum anti-Gram-negative activity, borderline activity against clinically important Gram-positive pathogens and little or no anti-anaerobic bacteria activity. In contrast, the new quinolones are characterized by having enhanced activity against Gram-positive pathogens, anti-anaerobic activity and they remain highly active against aerobic-Gram-negative bacilli. Several fluoroquinolones have been evaluated for the treatment of uncomplicated skin and soft tissue infection, difficult skin and soft tissue infection and serious skin and skin structure infections. Clinical cure rates were found to be equivalent to comparators suggesting a role for the fluoroquinolone in treating these infections. It may be necessary to use some fluoroquinolones in combination with anti-anaerobic agents for those infections with mixed aerobic and anaerobic pathogens. Some additional clinical trials are necessary to identify the full potential of newer fluoroquinolones for skin and skin structure infections. At present, quinolones are, in general, equivalent to beta-lactam agents in the treatment of skin and soft tissue infection.

Anti-Infective Agents↗