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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of </=4 mg/l, was evaluated in patients with respiratory infections caused by S. pneumoniae, including PRSP (penicillin MICs 2-16 mg/l). Data from nine clinical studies were combined (total intent-to-treat N=5531). Six randomized, double-blind studies used levofloxacin 500 mg od in acute bacterial sinusitis (ABS), levofloxacin 500 mg od in acute exacerbations of chronic bronchitis (AECB), clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators. The three remaining studies (two in ABS and one in CAP) were non-comparative. In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S. pneumoniae infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA MICs of >/=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.
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PMID:Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate. 1238 78

(1) Moxifloxacin is the fourth fluoroquinolone to be licensed in France with indications covering ENT and respiratory tract infections. (2) In community-acquired pneumonia, acute bacterial sinusitis and acute exacerbations of chronic bronchitis, moxifloxacin seems no more effective than other fluoroquinolones available in France (with which it has not been compared) or the other antibiotics with which it has been compared. (3) Moxifloxacin has the usual adverse effects of fluoroquinolones, but carries a greater risk of QT prolongation than ciprofloxacin, levofloxacin and ofloxacin.
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PMID:Moxifloxacin: new preparation. A me-too with more cardiac risks. 1246 94

Evidence from studies in otitis media, acute bacterial sinusitis and acute exacerbations of chronic bronchitis indicate that clinical efficacy is dependent on bacterial eradication. Failure to eradicate bacterial pathogens increases the potential for clinical failure, incurring further costs, and may also select and maintain bacteria that are resistant to a wide range of antimicrobials. Bacteriologically confirmed clinical failures have been reported in pneumococcal pneumonia with both macrolides and older fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin). These failures were due to the involvement of resistant pathogens (macrolides) or suboptimal pharmacokinetics/pharmacodynamics (PK/PD) (quinolones). However, persistent positive blood cultures have not been reported during therapy with adequate doses of benzylpenicillins or aminopenicillins. Treatment failure, driven by the failure to eradicate pathogens, leads to both economic and environmental costs, hospitalization being the major cost driver. Failure to achieve bacterial eradication may also lead to the development and spread of resistance. Different types of antimicrobials appear to be driving resistance to different extents, and this may be due to suboptimal PK/PD. In conclusion, factors to consider when prescribing include an accurate diagnosis, knowledge of local epidemiology, the role of PK/PD principles in antimicrobial choice, clinical outcomes in relation to bacteriologic efficacy, and resistance and its bacteriologic and clinical impact. The vicious cycle of infection, inappropriate therapy, bacteriologic failure, selection/spread of resistance and further infection needs to be broken by the use of appropriate treatments to achieve bacterial eradication.
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PMID:Why do we need to eradicate pathogens in respiratory tract infections? 1283 2

Community-acquired bacterial respiratory tract infections are among the most common health disorders requiring medical care and are associated with substantial morbidity, mortality, and direct and indirect costs. Recent increases in the prevalence of antimicrobial resistance have resulted in reduced susceptibility of the most common respiratory tract bacterial pathogens to a number of antimicrobials. Amoxicillin/clavulanate potassium extended release (ER) tablets (Augmentin XR, GlaxoSmithKline) is a new formulation of amoxicillin/clavulanate that retains activity against betalactamase-producing organisms whilst increasing the activity against Streptococcus pneumoniae through elevated and sustained plasma amoxicillin concentrations. The bilayer tablet provides immediate release of clavulanate and both immediate and sustained release of amoxicillin to maintain therapeutic concentrations of amoxicillin over longer periods of the dosing interval. In clinical trials of acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), amoxicillin/clavulanate ER was shown to have excellent bacteriological and clinical success rates, even in patients infected with antimicrobial-resistant pathogens, and was found to be generally well tolerated. Amoxicillin/clavulanate ER is approved in the US for the treatment of patients with ABS or CAP caused by beta-lactamase-producing pathogens (ie, Haemophilus influenzae, Moraxella catarrhalis, Haemophilus parainfluenzae, Klebsiella pneumoniae, or methicillin-susceptible Staphylococcus aureus) and S. pneumoniae with reduced susceptibility to penicillin (penicillin minimum inhibitory concentration = 2.0 microg/ml).
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PMID:Amoxicillin/clavulanate potassium extended release tablets: a new antimicrobial for the treatment of acute bacterial sinusitis and community-acquired pneumonia. 1452 93

Gatifloxacin (Tequin, Kyorin Pharmaceutical Co. Ltd) is a new fluoroquinolone with a broad spectrum of activity for pathogens implicated in community-acquired respiratory tract infections, including Gram-positive, -negative and atypical bacteria. Excellent oral bioavailability, a half-life allowing once-daily administration and excellent penetration into respiratory tissues are desirable pharmacokinetic characteristics of gatifloxacin. Monte Carlo simulation of gatifloxacin in Streptococcus pneumoniae infection demonstrates that adequate levels of pharmacokinetic/pharmacodynamic parameters are obtained with gatifloxacin in almost all instances. In randomised, controlled trials and a large open-label, community-based study, gatifloxacin has shown excellent clinical and bacteriological efficacy in acute bacterial sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. Current guidelines recommend the initial empiric use of gatifloxacin (along with the other new fluoroquinolones) for community-acquired respiratory tract infection in patients who have increased likelihood of infection with resistant pathogens. Another group of patients where this agent is recommended for initial antimicrobial therapy are those who, because of underlying disease and/or comorbid conditions, need an antibiotic with high antimicrobial efficacy to achieve optimal outcomes.
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PMID:Gatifloxacin in community-acquired respiratory tract infection. 1452 94

Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community-acquired respiratory tract infections. Amoxicillin/clavulanate was developed to provide a potent broad spectrum of antibacterial activity, coverage of beta-lactamase-producing pathogens and a favourable pharmacokinetic/pharmacodynamic (PK/PD) profile. These factors have contributed to the high bacteriological and clinical efficacy of amoxicillin/clavulanate in respiratory tract infection over more than 20 years. This is against a background of increasing prevalence of antimicrobial resistance, notably the continued spread of beta-lactamase-mediated resistance in Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and quinolone resistance in Streptococcus pneumoniae. The low propensity of amoxicillin/clavulanate to select resistance mutations as well as a favourable PK/PD profile predictive of high bacteriological efficacy may account for the longevity of this combination in clinical use. However, in certain defined geographical areas, the emergence of S. pneumoniae strains with elevated penicillin MICs has been observed. In order to meet the need to treat drug-resistant S. pneumoniae, two new high-dose amoxicillin/clavulanate formulations have been developed. A pharmacokinetically enhanced tablet dosage form of amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR in the USA), has been developed for use in adult respiratory tract infection due to drug-resistant pathogens, such as S. pneumoniae with reduced susceptibility to penicillin, as well as beta-lactamase-producing H. influenzae and M. catarrhalis. Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600) is for paediatric use in persistent or recurrent acute otitis media where there are risk factors for the involvement of beta-lactamase-producing strains or S. pneumoniae with reduced penicillin susceptibility. In addition to high efficacy, amoxicillin/clavulanate has a well known safety and tolerance profile of the two new high-dose formulations are not significantly different from those of conventional formulations. Amoxicillin/clavulanate is included in guidelines and recommendations for the treatment of bacterial sinusitis, acute otitis media, community-acquired pneumonia and acute exacerbations of chronic bronchitis. Amoxicillin/clavulanate continues to be an important agent in the treatment of community-acquired respiratory tract infections, both now and in the future.
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PMID:Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. 1472 31

Using pharmacokinetic/pharmacodynamic principles, pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily was designed to provide adequate levels of amoxicillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP, penicillin MICs > or = 2 mg/L) with amoxicillin MICs of at least 4 mg/L. The clinical efficacy of amoxicillin/clavulanate 2000/125 mg was evaluated in patients with respiratory tract infections caused by S. pneumoniae, including isolates with elevated penicillin (2-8 mg/L) MICs. Data from 10 clinical studies were combined: seven randomised (1:1), double-blind, controlled trials (efficacy intent-to-treat [ITT]N = 3376): amoxicillin/clavulanate 2000/125 mg twice daily vs. levofloxacin 500 mg once daily in acute bacterial sinusitis (ABS); levofloxacin 500 mg once daily in acute exacerbations of chronic bronchitis (AECB); clarithromycin 500 mg twice daily in AECB; amoxicillin/clavulanate 875/125 mg twice daily/three times daily and 1000/125 mg three times daily in community-acquired pneumonia (CAP) and three noncomparative studies (efficacy ITT N = 3024): two in ABS, one in CAP. The bacteriological per-protocol (PP) population at follow up (days 14-39) comprised 1295 patients for amoxicillin/clavulanate 2000/125 mg and 241 for comparators. With amoxicillin/clavulanate 2000/125 mg at follow-up, outcome was successful (clinical success and eradication/presumed eradication) in 85/90 (94.4%) patients with S. pneumoniae in comparative studies and 421/445 (94.6%) in noncomparative studies, and with comparators 58/70 (82.9%) were successes. In the amoxicillin/clavulanate 2000/125 mg group at follow up, 52/552 S. pneumoniae isolates were resistant to penicillin. At follow up, 50/52 (96.2%) patients with PRSP were successes, including 6/7 with amoxicillin MICs of 4 mg/L and 7/8 with amoxicillin MICs of 8 mg/L. Success rates for amoxicillin/clavulanate 2000/125 mg against PRSP were similar for CAP (96.0%[24/25]), AECB (100%[3/3]) and ABS (95.8%[23/24]). There were six PRSP isolates in the comparator group (two isolates were from one patient), and three of five patients in this group were successes. In conclusion, amoxicillin/clavulanate 2000/125 mg demonstrated combined clinical/bacteriological success against 50/52 patients with PRSP, including 13/15 strains with amoxicillin MICs of 4-8 mg/L. These results for the pharmacokinetic-enhanced formulation of amoxicillin/clavulanate 2000/125 mg are in line with the high efficacy against PRSP predicted using pharmacokinetic/pharmacodynamic parameters.
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PMID:Performance in practice: bacteriological efficacy in patients with drug-resistant S. pneumoniae. 1475 31

Community-acquired respiratory tract infections (CARTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis, remain substantial sources of morbidity and mortality in the US. The increasing prevalence of antimicrobial-resistant strains among the common respiratory pathogens, particularly Streptococcus pneumoniae, has complicated the choice of antimicrobials and threatens the efficacy of treatment for CARTIs. This highlights the need both for ongoing surveillance efforts to track current resistance patterns and for the development of new antimicrobial agents effective against resistant organisms. To provide current and ongoing antimicrobial resistance surveillance data, including comparisons of telithromycin (the first ketolide to undergo clinical development and be approved by the Food and Drug Administration) with other agents, a longitudinal global surveillance study--Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT)--was launched in 1999. A US component of this study was initiated in 2000, and results from the first respiratory infection tracking season (2000-2001) are discussed in this article. Providing resistance data on the national, regional, and local levels, PROTEKT US has thus far confirmed the increasing prevalence of resistant S. pneumoniae isolates to beta-lactams and macrolides, as well as the emergence of fluoroquinolone resistance in the US. Importantly, telithromycin was highly active against S. pneumoniae, including resistant isolates.
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PMID:Increased bacterial resistance: PROTEKT US--an update. 1522 91

Telithromycin, the first member of the ketolide antibacterials, has good activity against community-acquired respiratory pathogens, including multiple-drug-resistant strains of Streptococcus pneumoniae. Telithromycin 800 mg once daily has been US FDA approved for the treatment of acute bacterial sinusitis (ABS; treatment duration 5 days), acute bacterial exacerbations of chronic bronchitis (AECB; 5 days) and mild-to-moderate community-acquired pneumonia (CAP; 7-10 days). In patients with CAP, telithromycin was as effective as amoxicillin 1000 mg three times daily for 10 days, clarithromycin 500 mg twice daily for 10 days or trovafloxacin 200 mg once daily for 7-10 days. In patients with AECB, telithromycin was as effective as a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg three times daily, cefuroxime axetil 500 mg twice daily or clarithromycin 500 mg twice daily. In patients with ABS, telithromycin was as effective as a 10-day course of amoxicillin/clavulanic acid 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily. Telithromycin was generally well tolerated and most adverse events were of mild-to-moderate severity and transitory. The most common adverse events with telithromycin were diarrhoea and nausea (10.8% and 7.9% of 2702 patients in clinical trials); these events occurred in 8.6% and 4.6% of 2139 comparator-treated patients.
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PMID:Telithromycin. 1525 29

Moxifloxacin (Avelox) is a fluoroquinolone antibacterial with a methoxy group in the C-8 position and a bulky C-7 side chain. Moxifloxacin is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), acute bacterial sinusitis and uncomplicated skin and skin structure infections (approved indications may differ between countries). Moxifloxacin has a broad spectrum of antibacterial activity, including activity against penicillin-resistant Streptococcus pneumoniae. It achieves good tissue penetration and has a convenient once-daily administration schedule, as well as being available in both intravenous and oral formulations in some markets. Moxifloxacin has good efficacy in the treatment of patients with AECB, CAP, acute bacterial sinusitis and uncomplicated skin and skin structure infections, and is generally well tolerated. Thus, moxifloxacin is an important option in the treatment of bacterial infections.
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PMID:Moxifloxacin: a review of its use in the management of bacterial infections. 1545 31


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