Guide to selection of fluoroquinolones in patients with lower respiratory tract infections

Newer fluoroquinolones such as levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin have several attributes that make them excellent choices for the therapy of lower respiratory tract infections. In particular, they have excellent intrinsic activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and the atypical respiratory pathogens. Fluoroquinolones may be used as monotherapy to treat high-risk patients with acute exacerbation of chronic bronchitis, and for patients with community-acquired pneumonia requiring hospitalisation, but not admission to intensive care. Overall, the newer fluoroquinolones often achieve clinical cure rates in > or =90% of these patients. However, rates may be lower in hospital-acquired pneumonia, and this infection should be treated on the basis of anticipated organisms and evaluation of risk factors for specific pathogens such as Pseudomonas aeruginosa. In this setting, an antipseudomonal fluoroquinolone may be used in combination with an antipseudomonalbeta-lactam.Concerns are now being raised about the widespread use, and possibly misuse, of fluoroquinolones and the emergence of resistance among S. pneumoniae, Enterobacteriaceae and P. aeruginosa. A number of pharmacokinetic parameters such as the peak concentration of the antibacterial after a dose (C(max)), and the 24-hour area under the concentration-time curve (AUC24) and their relationship to pharmacodynamic parameters such as the minimum inhibitory and the mutant prevention concentrations (MIC and MPC, respectively) have been proposed to predict the effect of fluoroquinolones on bacterial killing and the emergence of resistance. Higher C(max)/MIC or AUC24/MIC and C(max)/MPC or AUC24/MPC ratios, either as a result of dose administration or the susceptibility of the organism, may lead to a better clinical outcome and decrease the emergence of resistance, respectively. Pharmacokinetic profiles that are optimised to target low-level resistant minor subpopulations of bacteria that often exist in infections may help preserve fluoroquinolones as a class. To this end, optimising the AUC24/MPC or C(max)/MPC ratios is important, particularly against S. pneumoniae, in the setting of lower respiratory tract infections. Agents such as moxifloxacin and gemifloxacin with high ratios against this organism are preferred, and agents such as ciprofloxacin with low ratios should be avoided. For agents such as levofloxacin and gatifloxacin, with intermediate ratios against S. pneumoniae, it may be worthwhile considering alternative dose administration strategies, such as using higher dosages, to eradicate low-level resistant variants. This must, of course, be balanced against the potential of toxicity. Innovative approaches to the use of fluoroquinolones are worth testing in further in vitro experiments as well as in clinical trials.     

Respiratory tract infections: at-risk patients, who are they? Implications for their management with levofloxacin

Two of the most serious respiratory tract infections are community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB). The most common pathogens found in patients with these infections are Haemophilus influenzae and Streptococcus pneumoniae. Pseudomonas aeruginosa is also relatively common, particularly in elderly patients with AECB. S. pneumoniae and P. aeruginosa are also of concern in relation to the development of resistance to antimicrobial drugs. The administration of antibiotics at doses that result in concentrations exceeding the mutant prevention concentration at the site of infection is one strategy to prevent the development of drug-resistant pathogens. AECB is associated with a high risk of in-hospital mortality, particularly in patients treated in the intensive care unit. CAP is also associated with significant risks and often requires treatment under hospital supervision. Several patient-related factors help identify those patients who are most at risk of mortality and morbidity. Treatment should be tailored towards the severity of the disease. The fluoroquinolones, such as levofloxacin, are an effective treatment option for AECB and CAP. Compared with many other antibiotics, resistance to levofloxacin remains low for most infecting pathogens. The oral bioavailability of levofloxacin is over 99%, enabling simple switching from intravenous to oral therapy during treatment. It is also preferentially distributed to compartments in the lung, thus achieving high concentrations at the site of respiratory tract infections. Combined with cover of the major infecting pathogens found in patients with AECB and CAP, and a cost-effective treatment compared with many alternative therapies, levofloxacin is an attractive option for the treatment of at-risk patients with these respiratory tract infections.     

Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections

We determined the susceptibility of bacteria which were isolated from the patients with respiratory infections between January and October 2005, to tosufloxacin and other fluoroquinolones. A total of 900 isolate including 300 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 100 Moraxella catarrhalis, 200 Haemophilus influenzae, 100 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa were tested. Tosufloxacin, gatifloxacin, levofloxacin, moxifloxacin, ciprofloxacin and prulifloxacin were used as the test antimicrobials. Tosufloxacin, gatifloxacin and moxifloxacin were potent antibiotics tested for the antibacterial activity against Streptococcus including penicillin-resistant S. pneumoniae; the MIC90 were 0.12-0.5/ micromL. Fluoroquinolones exerted the potent antibacterial activity against M. catarrhalis and H. influenzae; the MIC90 of fluoroquinolones tested were < or =0.06 microg/mL. Tosufloxacin, ciprofloxacin and prulifloxacin showed to be more active against K. pneumoniae and P. aeruginosa, but parts of some strains were resistant. These results indicate that tosufloxacin has the potent antibacterial activity against major organisms detected from patients with respiratory infections. Since it was approved in 1990, tosufloxacin was considered to be useful as a therapeutic antimicrobial for the treatment of respiratory infections.     

Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.     

What is the place of fluoroquinolones in the treatment of community-acquired respiratory tract infections?

The newest (third generation) fluoroquinolones are potentially useful agents in the management of community-acquired respiratory tract infections. This is mainly due to their increased activity against Streptococcuspneumoniae, a pathogen poorly susceptible to the second-generation compounds, and playing a major role in upper and lower respiratory tract infections. Also, their spectrum includes the other main pathogens involved in those infections, comprising Haemophilus influenzae and intracellular agents, against which the newest fluoroquinolones exhibit a similar activity to that of the previous compounds. The pharmacokinetic and pharmacodynamic properties of the newest quinolones make them suitable for effective therapy of lower respiratory tract infections. However, careful attention should be paid to the dose and dosing regimen of each compound in clinical usage in order to select the most adapted drug. In clinical trials, the fluoroquinolones have been shown to be at least as effective as the comparators in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis (AECB) or sinusitis, including documented pneumococcal infections. Their tolerance is generally considered to be good. The main question regarding the fluoroquinolones in the treatment of community-acquired respiratory tract infections is their role as first-line agents used in single drug therapy. Cost-effectiveness studies are needed to define this role further. Identification of subpopulations of patients at risk of being infected by penicillin-resistant pneumococci or Gram-negative bacilli who could benefit from a fluoroquinolone could be useful. Also, it must be considered that a large use of fluoroquinolones as first-line agents in very common infections such as AECB or sinusitis could contribute to the selection of bacteria, including S. pneumoniae, resistant to this class of antibiotics. Careful control of fluoroquinolone usage and development of bacterial resistance is of great importance.     

Therapeutic advances of new fluoroquinolones

Fluoroquinolone antimicrobials have been available for over 10 years. Recent modifications to nuclear side-chains have enhanced both the antimicrobial and pharmacokinetic profiles of this class. Rapidly increasing antimicrobial resistance among community and hospital bacterial pathogens has diminished therapeutic options. Infections caused by such pathogens, including drug-resistant Streptococcus pneumoniae and multi-resistant Enterobacteriaceae are now treatable by few classes of antibacterials, one of these being the fluoroquinolones. Ciprofloxacin was one of the first effective agents available in both iv. and oral formulations for the treatment of Gram-negative infection, resistant to other antibiotics. More recent developments, such as sparfloxacin and grepafloxacin, are more effective in vitro against Gram-positive pathogens, although their safety profile may be less promising. Fluoroquinolones not yet in widespread clinical use, including trovafloxacin, clinafloxacin and moxifloxacin, hold considerable promise as community ‘respiratory antimicrobials’ and the results of clinical trials are awaited with anticipation. In this review, the three generations of fluoroquinolone development are examined and the relative antimicrobial, pharmacokinetic, clinical and safety profiles of available and developmental quinolones are compared.     

Therapeutic advances of new fluoroquinolones

Fluoroquinolone antimicrobials have been available for over 10 years. Recent modifications to nuclear side-chains have enhanced both the antimicrobial and pharmacokinetic profiles of this class. Rapidly increasing antimicrobial resistance among community and hospital bacterial pathogens has diminished therapeutic options. Infections caused by such pathogens, including drug-resistant Streptococcus pneumoniae and multi-resistant Enterobacteriaceae are now treatable by few classes of antibacterials, one of these being the fluoroquinolones. Ciprofloxacin was one of the first effective agents available in both iv. and oral formulations for the treatment of Gram-negative infection, resistant to other antibiotics. More recent developments, such as sparfloxacin and grepafloxacin, are more effective in vitro against Gram-positive pathogens, although their safety profile may be less promising. Fluoroquinolones not yet in widespread clinical use, including trovafloxacin, clinafloxacin and moxifloxacin, hold considerable promise as community 'respiratory antimicrobials' and the results of clinical trials are awaited with anticipation. In this review, the three generations of fluoroquinolone development are examined and the relative antimicrobial, pharmacokinetic, clinical and safety profiles of available and developmental quinolones are compared.     

Moxifloxacin in respiratory tract infections

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.     

Moxifloxacin: a review of its clinical potential in the management of community-acquired respiratory tract infections

Moxifloxacin is an extended-spectrum fluoroquinolone which has improved coverage against gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, while retaining good activity against gram-negative bacteria. The antibacterial spectrum of moxifloxacin includes all major upper and lower respiratory tract pathogens; it is one of the most active fluoroquinolones against pneumococci, including penicillin- and macrolide-resistant strains. In in vitro studies, emergence of bacterial resistance was less common with moxifloxacin than with some other fluoroquinolones, but this requires confirmation in large-scale clinical studies. As with other fluoroquinolones, moxifloxacin achieves good penetration into respiratory tissues and fluids. It shows a low potential for drug interactions and dosage adjustment is not required for patients of advanced age or those with renal or mild hepatic impairment. The efficacy of oral moxifloxacin has been demonstrated in large, well-designed clinical trials in patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Moxifloxacin 400 mg once daily achieved bacteriological and clinical success rates of approximately 90% or higher. It was as effective as, or more effective than, comparators including clarithromycin, cefuroxime axetil and high dose amoxicillin in these trials. The most commonly reported adverse events in patients receiving moxifloxacin are gastrointestinal disturbances. Moxifloxacin is also associated with QTc prolongation in some patients; there are, as yet, no data concerning the possible clinical sequelae of this effect in high-risk patients. Moxifloxacin has a low propensity for causing phototoxic reactions relative to other fluoroquinolones, and animal data suggest that it has a low potential for causing excitatory CNS and hepatotoxic effects. Conclusions: As an extended-spectrum fluoroquinolone, moxifloxacin offers the benefits of excellent activity against pneumococci, once daily administration and a low propensity for drug interactions. Although studies are needed regarding its tolerability in at-risk patients with QT interval prolongation, available data suggest that moxifloxacin is likely to become a first-line therapy option for the treatment of community-acquired lower respiratory tract infections, particularly in areas where drug-resistant S. pneumoniae or H. influenzae are common.     

Grepafloxacin: an overview of antibacterial activity, pharmacokinetics, clinical efficacy and safety

The treatment of respiratory tract infection is the most common reason for antibiotic prescribing. However, therapeutic options are diminishing as antibiotic resistance to penicillins and macrolides in key respiratory pathogens is increasing. As resistance increases, there are parallel rises in the number of treatment failures and the total cost of infection management. New generation broad-spectrum fluoroquinolones, such as grepafloxacin, have recently been recommended as a first-line treatment option in guidelines for lower respiratory tract infection. Grepafloxacin is an oral fluoroquinolone, with a microbiological and clinical profile that is particularly suited to the treatment of community-acquired respiratory infections. In vitro, it is rapidly bactericidal, and compared with earlier quinolones, its broad spectrum activity encompasses all important respiratory pathogens; Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila, including strains which are resistant to penicillin, other beta-lactam antibiotics and macrolides. In addition, grepafloxacin achieves high lung concentrations, and its long half-life (up to 15 h) enables once daily dosing. Overall, grepafloxacin combines the positive properties of the beta-lactam antibiotics against conventional Gram-positive and Gram-negative respiratory pathogens, with the activity of the macrolides against atypical pathogens. In patients with bacteriologically documented infections, clinical studies in community-acquired pneumonia have shown that treatment for 7-10 days once daily (o.d.) with approximately 600 mg is equivalent to that with either twice daily (b.i.d.) clarithromycin 250 mg, or three times daily (t.i.d.) cefaclor 500 mg, and superior to that with t.i.d. amoxycillin 500 mg. In these studies, grepafloxacin proved effective in the treatment of both typical and atypical pneumonia. In acute bacterial exacerbations of chronic bronchitis (ABECB), 7-10 days treatment with o.d. grepafloxacin 400 mg or 600 mg has been shown to be equivalent to that with either t.i.d. amoxycillin 500 mg, or b.i.d. ciprofloxacin 500 mg. In patients with a documented bacterial pathogen, microbiological success with both grepafloxacin dosage regimens was superior to amoxycillin 500 mg t.i.d. In addition, short course treatment of ABECB with 400 mg of grepafloxacin given o.d. for five days has been shown to be as effective, clinically and microbiologically as a ten-day course of the same dose. The safety profile of grepafloxacin has been well-characterised from data from over 12,000 patients treated in Phase II/III and post-marketing studies, and over 400,000 patients treated worldwide in routine clinical practice. The most commonly reported adverse events are gastrointestinal, mainly nausea and unpleasant taste. The potential for photosensitivity and central nervous system effects is low, and there have been no reports of convulsions. No unique or unexpected.     

Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections

Several new fluoroquinolones have been marketed since the late 1990s. Fluoroquinolones are an effective treatment for most community-acquired respiratory tract infections, including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. However, other antibiotics, including β-lactams, macrolides, tetracyclines and trimethoprim-sulfamethoxazole, are also effective against these respiratory infections. From a managed care perspective, it is the subtle differences between the drugs in the eradication of bacterial pathogens, adverse effects, dose regimens, compliance issues, bacterial resistance and cost that determine the best choice for the management of pneumonia, sinusitis or exacerbations of chronic bronchitis. The potential for bacterial resistance is perhaps the only significant barrier to extensive fluoroquinolone use in community-acquired respiratory tract infections. Cost-effectiveness must be balanced with quality care, both from an individual perspective and that of the greater society.     

Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections

Several new fluoroquinolones have been marketed since the late 1990s. Fluoroquinolones are an effective treatment for most community-acquired respiratory tract infections, including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. However, other antibiotics, including beta-lactams, macrolides, tetracyclines and trimethoprim-sulfamethoxazole, are also effective against these respiratory infections. From a managed care perspective, it is the subtle differences between the drugs in the eradication of bacterial pathogens, adverse effects, dose regimens, compliance issues, bacterial resistance and cost that determine the best choice for the management of pneumonia, sinusitis or exacerbations of chronic bronchitis. The potential for bacterial resistance is perhaps the only significant barrier to extensive fluoroquinolone use in community-acquired respiratory tract infections. Cost-effectiveness must be balanced with quality care, both from an individual perspective and that of the greater society.     

Clinical studies of garenoxacin

Garenoxacin mesylate hydrate (GRN) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. It has favourable pharmacokinetic profiles for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), with good penetration into sputum and otorhinolaryngological tissues. In clinical studies, the efficacy of GRN ranged from 92% to 96% in patients with bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia and acute bronchitis. Efficacy was 85% in acute infectious exacerbations of chronic respiratory disease and ranged from 81% to 95% in otorhinolaryngological infections. Bacterial eradication was 90.9% for Staphylococcus aureus, 99.2% for Streptococcus pneumoniae, 98.2% for Haemophilus influenzae, 96.6% for Moraxella catarrhalis, 100% for penicillin-resistant S. pneumoniae, 100% for beta-lactamase-negative ampicillin-resistant H. influenzae and beta-lactamase-positive H. influenzae, and 96.2% for beta-lactamase-positive M. catarrhalis. Garenoxacin concentrations in plasma and tissues using GRN 400mg once a day were higher than the MIC90 (minimum inhibitory concentration for 90% of the organisms) of major causative pathogens. The trough concentration (Cmin) in plasma was 1.92 microg/mL, a level that was higher than the mutant prevention concentration, suggesting that GRN is unlikely to induce the selection of resistant strains during treatment. In clinical studies, GRN did not produce class adverse effects of fluoroquinolones such as QTc prolongation, blood glucose abnormality or severe liver damage. No serious adverse events were observed during the trials. The results indicate that GRN is very effective in treating patients with upper and lower respiratory tract infections.     

Pharmacokinetics and pharmacodynamics of the new fluoroquinolones: focus on respiratory infections.

High occurrence of penicillin-resistant and multidrug-resistant Streptococcus pneumoniae and reports of resistance with Haemophilus influenzae and Moraxella catarrhalis are influencing the empiric treatment of community-acquired respiratory infections and allowing the new fluoroquinolones to serve as important treatment alternatives. Recent analysis of the pharmacokinetic and pharmacodynamic properties of the new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) have shown high bioavailability (> or = 70%) and long serum half-lives (> or = 7 h), allowing for once-daily dosing. They concentrate in respiratory tract tissues and fluids at levels that exceed serum concentrations. Concentration-dependant killing is evident and the pharmacodynamic parameters that best correlate with bacteriological eradication, clinical efficacy and minimization of resistance have now been identified. The new fluoroquinolones display excellent pharmacokinetic and pharmacodynamic properties against community-acquired respiratory pathogens, making them ideal agents for the empirical treatment of community-acquired respiratory infections.     

Activities of antimicrobial agents against 8,474 clinical isolates obtained from 37 medical institutions during 2000 in Japan

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.     

Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting

A national multicentre prevalence study was undertaken to determine the bacterial strains associated with mild-to-moderate acute exacerbations of chronic bronchitis (AECB) in the primary care setting and the susceptibility of isolated pathogens to different antimicrobials usually prescribed to these patients. All samples were processed by a central reference laboratory. Microdilution tests were carried out to establish the minimum inhibitory concentration (MIC) of various antimicrobials. A double-disk test was performed to establish the macrolide resistance phenotype in Streptococcus pneumoniae. Tests to detect the presence of beta-lactamase in Haemophilus influenzae and Moraxella catarrhalis and polymerase chain reaction to detect the presence of ermB and mefA genes in S. pneumoniae isolates were also performed. A total of 1537 patients were included in the trial and 468 microorganisms were isolated from sputum samples, with the most frequent isolates being S. pneumoniae (34.8%), M. catarrhalis (23.9%) and H. influenzae (12.6%). Resistance rates of pneumococci were 47.2% for penicillin, 1.2% for amoxicillin, 34.3% for macrolides (87.5% of which showed high-level resistance), 13.6% for cefuroxime/axetil and 4.2% for levofloxacin. No bacterial isolates showed resistance to telithromycin. Empirical antibiotic treatment was prescribed to 98.3% of patients, including macrolides to 36.6%, amoxicillin with or without clavulanic acid to 32.3% and fluoroquinolones to 16.1%. In conclusion, S. pneumoniae was the most frequently isolated bacteria in patients with mild-to-moderate AECB. Despite the high rates of resistance of pneumococci to macrolides, they continue to be the most widely used antibiotics in primary care to treat AECB.     

A critical review of the fluoroquinolones: focus on respiratory infections.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids). The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections. Their broad spectrum of activity which includes respiratory pathogens such as penicillin and macrolide resistant S. pneumoniae, favourable pharmacokinetic parameters, good bacteriological and clinical efficacy will lead to growing use of these agents in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. These agents may result in cost savings especially in situations where, because of their potent broad-spectrum activity and excellent bioavailability, they may be used orally in place of intravenous antibacterials. Prudent use of the new fluoroquinolones will be required to minimise the development of resistance to these agents.     

The safety profile of moxifloxacin and other fluoroquinolones in special patient populations

ABSTRACT

Background: Fluoroquinolones, including ciprofloxacin, levofloxacin, gemifloxacin, and moxifloxacin, represent a major advance in the development of antimicrobial agents. They offer significant activity against Gram-negative pathogens, while more advanced generation fluoroquinolones including levofloxacin, gemifloxacin, and moxifloxacin are significantly active against Gram-positive (e.g., Streptococcus pneumoniae for some members of the class), typical, atypical, and anaerobic pathogens. Fluoroquinolones have a pharmacokinetic/pharmacodynamic profile that exhibits concentration-dependent killing and good oral absorption, allowing for once-daily dosing.

Objective: Review of data from fluoroquinolone studies, with an emphasis on the associated rare, but potentially clinically important, adverse events in specific patient populations. Review of clinical efficacy is included where relevant to the topic under discussion.

Methods: A literature search was conducted using terms including fluoroquinolones, moxifloxacin, ciprofloxacin, levofloxacin, gatifloxacin, gemifloxacin, safety, adverse events, drug interactions, and pharmacokinetic parameters to identify literature providing information regarding the safety profile of specified fluoroquinolones in special patient populations (i.e., the elderly, patients with liver disease, kidney disease, glycemic disorder, those at risk for cardiovascular events). Although specific date criteria were not applied to the search, preference was given to more recent publications. Online databases searched include MEDLINE and EMBASE and relevant textbooks were utilized as well.

Findings: Fluoroquinolones, when used either as monotherapy or as combination therapy depending on their individual indications, attain adequate concentrations for treating infections in different target sites, including epithelial lining fluid, alveolar macrophages, skin, and gastrointestinal tissues. Overall, fluoroquinolones have predictable and mild-to-moderate adverse-event profiles and are generally well tolerated. Findings of this review are limited by the availability of publications and case reports.

Conclusions: Fluoroquinolones, are associated with rare, but clinically important, adverse events in special patient populations (including the elderly; those with hepatic, renal, or glycemic disorders; and those at risk for cardiovascular events). Recognition of differences in the clinical efficacy and safety profiles of fluoroquinolones in special patient populations should lead to better antimicrobial agent selection.     

儿童感染性肺炎痰培养病原菌分布特点及耐药性分析

目的:了解本地区儿童感染性肺炎病原菌的分布及其耐药情况,为临床治疗提供参考。方法:收集2017年3月至2018年2月在我院儿科住院的肺炎患儿病例资料进行回顾性分析。结果:517例患儿痰液细菌培养阳性213例,阳性率41.20%。共分离出致病菌239株,依次为肺炎链球菌(34.73%)、流感嗜血杆菌(33.05%)、卡他莫拉菌(19.25%)及金黄色葡萄球菌(6.69%)。肺炎链球菌对红霉素、克林霉素耐药率高(>95%),对青霉素、万古霉素、利奈唑胺敏感性高。金黄色葡萄球菌对氨苄西林、青霉素的耐药率达100%,对红霉素、克林霉素耐药率93.75%,对利奈唑胺、万古霉素、替考拉宁均敏感。流感嗜血杆菌及卡他莫拉菌对阿奇霉素均有较高的耐药性,流感嗜血杆菌对氨苄西林、头孢克洛及头孢呋辛有较高的耐药性,均>60%,对头孢噻肟、阿莫西林/克拉维酸等耐药性较低。卡他莫拉菌对红霉素耐药率达78.57%,对阿莫西林/克拉维酸高度敏感。结论:肺炎链球菌、流感嗜血杆菌是本地区儿童肺炎的主要病原菌,在不同季节检出率有所不同。治疗时应根据病原菌种类及药敏结果合理选择抗菌药物,减少耐药菌株的产生。     

临床病原菌的年度分布及耐药分析

目的 对7419株临床病原菌进行年度分布及耐药分析,为临床合理应用抗菌药物提供依据.方法 采用ATB细菌鉴定分析统计软件对2008～2011年7419株临床病原菌进行分析,主要观察病原菌年度检出率、病原菌种类、 比例及耐药情况.结果 送检标本病原菌检出率为68.2％,各年度无明显变化.革兰阳性球菌占27.5％,各年度呈降低趋势;革兰阴性杆菌占52.8％,各年度呈升高趋势;真菌各年度无明量变化.大肠埃希菌、肺炎克雷伯菌、肺炎链球菌、阴沟肠杆菌、流感嗜血杆菌为最主要的5种病原菌,其中大肠埃希菌、肺炎克雷伯菌、流感嗜血杆菌百分率呈升高趋势,肺炙链球菌百分率呈降低趋势.耐甲氧西林金黄色葡萄球菌(MRSA)及耐甲氧西林凝固酶阴性葡萄球菌(MRSCN)呈升高趋势.铜绿假单胞菌、阴沟肠杆菌、鲍曼不动杆菌对亚胺培南耐药率呈升高趋势.结论 革兰阴性杆菌比例呈升高趋势,耐药率升高,应合理选用抗菌药物,减少耐药细菌的产生或延缓其发展.