Volume 17, Supplement 5, 2009
Review
From Pneumococcus to Pseudomonas: the antibacterial behaviour through the time
Rossolini Gian Maria
The worldwide use of fluoroquinolones in community and hospital settings, due to their high efficacy and tolerability, to the wide antibacterial spectrum and to the availability of an oral formulation, has created a relevant selective pressure for the emergence of resistant bacterial strains towards this antimicrobial class. Nevertheless, twenty years after development of first fluoroquinolones (e.g. norfloxacin and ciprofloxacin) and ten years after levofloxacin introduction, the antibacterial activity of these drugs remains, on the whole, high.
PK/PD profile and post-marketing surveillance
Pea Federico
Ten years after introduction in therapeutic handbook, levofloxacin still plays a main role in treating bacterial infections. In particular, the deeper knowledge of kinetic-dynamic characteristics has allowed to highlight that high dosage approach in short term therapy might reveal as extremely interesting in a setting of critical patients. In addition, the good tissue diffusion, documented by pharmacokinetic studies performed in different districts, including the ones protected by anatomic barriers, lets to assume a good efficacy in the treatment of infection localized in deep tissues, as observed in different animal models, and successively confirmed by clinical studies. Use of levofloxacin for infections localized at particular body sites, such as bones and joints, has allowed to evidence a good tolerability profile in the long term tolerability, as well.
Therapeutic experience in pneumonia and COPD
Blasi Francesco
The possible usefulness of levofloxacin in the empirical therapy of community acquired pneumonia, as monotherapy, (as alternative to the β-lactam + macrolide combination) in once-a-day administration is supported by a body of evidence emerged from a wide world clinical documentation. Related to its possible use in sequential therapy, clinical and economic advantages are also been shown. In fact, a number of clinical experimental studies have evidenced that levofloxacin allows an earlier attainment of clinical stabilization, and resulting therapeutic switch, and is also associated with a more rapid and efficient achievement of outcomes, either early (microbiological response, time to clinical stabilization, length of stay) or late (clinical cure, radiological resolution, and mortality indexes), revealing a very favourable impact on cost-efficacy ratio.
Published clinical studies concerning acute bacterial exacerbation of chronic bronchitis (ABECB) or chronic obstructive pulmonary (COPD) disease are also available, evidencing clinical and bacteriological efficacy of levofloxacin when compared to different therapeutic regimens, used at any severity grade, its use being related with a higher bacteriological eradication rate.
However, caution must be observed in the use of fluoroquinolones for treatment of acute bacterial exacerbation of COPD, due to rising concern about possible bacterial resistance, especially in S. pneumonaie e P. aeruginosa, that might emerge towards this antimicrobial class, although, to date, levofloxacin appears to be only marginally affected, in terms of resistance rates and of clinical significance.
From cystitis to bacterial prostatitis
Mirone Vincenzo
According to data reported by Naber (2008), urinary tract infections (UTIs), represent the main nosocomial acquired infection (40%); these infections are second, in order of frequency, only to respiratory tract infections in ambulatory setting, and account for 20% of ambulatory uro-nephrologic disease. Nowadays, the UTI’s classification recognizes five different groups, represented by acute, non complicated lower urinary tract infections (cystitis), acute non complicated pyelonephritis, complicated UTI’s with/without pyelonephritis, urosepsis and special forms, such as prostatitis, epididimitis, and orchitis.
With regard to therapy, and specifically to fluoroquinolones, the European urologists’ scientific community is unanimous in considering that levofloxacin plays a very important activity in the urological field, its antimicrobial spectrum being extended to Gram positive and “atypical” microrganisms as well.
Experience accumulated in hospital setting, in monotherapy and in association therapy
Petrosillo Nicola
Levofloxacin possesses a wide antimicrobial spectrum which encompasses Gram positive (also including penicillin-resistant Streptococcus pneumoniae) and Gram negative, and atypical respiratory pathogens Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) as well. Comparative clinical studies (macrolides, β-lactams, and other fluoroquinolones), have evidenced bacteriological and clinical efficacy in community-acquired pneumonia (CAP), acute exacerbation of chronic bronchitis, urinary tract infections, and skin and soft tissue infections. In clinical practice, levofloxacin in sequential therapy allowed to reduce length of stay, the efficacy being maintained unaltered. In severe pneumonia, or when a pseudomonas aetiology is suspected, an association therapy is suggested, although a reliable body of clinical evidence is still lacking. Recent in vitro studies showed a synergism between levofloxacin and imipenem against multiresistant Pseudomonas aeruginosa strains.
A recent Italian clinical study evidenced the good efficacy and tolerability profile of prophylactic use of levofloxacin in neutropenic patients with cancer. Such a prophylaxis reduced number of febrile episodes, at a statistically significant level, and mortality (although at a not statistically significant level)
