The clinical positioning of telavancin in Europe.

Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permits.

Preserving the efficacy of front-line fluoroquinolones through selective use to optimise clinical outcomes.

As antibiotic resistance is increasing worldwide, it is important to prescribe fluoroquinolone (FQ) antibiotics appropriately for a given infection to preserve class efficacy. Clinical studies reveal good efficacy and tolerability of the currently approved FQs (ciprofloxacin, levofloxacin and moxifloxacin) in a wide range of community- and hospital-acquired infections. However, certain features supporting their clinical efficacy suggest a rationale for inclusion of moxifloxacin and ciprofloxacin with complementary clinical benefit on a formulary rather than levofloxacin alone; it may also be more cost-effective. Ciprofloxacin has advantages over levofloxacin in the treatment of Gram-negative infections, whilst moxifloxacin has certain efficacy and ease of use advantages over levofloxacin in respiratory tract infections. To preserve the potential of FQs and to minimise the risk of resistance selection, agents with the highest in vitro activity and supportive pharmacokinetic/pharmacodynamic profiles should be used first-line, as appropriate for local guidelines and prescribing information.

Risks associated with the therapeutic use of fluoroquinolones.

INTRODUCTION: Quinolones are among the most often prescribed antimicrobial agents. Some types of toxicity observed during therapy with these drugs have gained much attention. AREAS COVERED: Here, we review the potential of the most widely used fluoroquinolones, ciprofloxacin, levofloxacin and moxifloxacin for adverse reactions. The rates of adverse events are similar for quinolones and other antibacterial agents. However, quinolone therapy can be associated with specific risks, which must be weighed against their benefit. In some studies, use of quinolones was associated with Clostridium difficile-associated diarrhea. Patients with impairments of the CNS (e.g., epilepsy or arteriosclerosis) should not be treated with quinolones. They should be avoided in patients with known prolongation of the QT interval or other risk factors for tachyarrhythmia. The risk for quinolone-associated tendinopathy is more pronounced among elderly persons, non-obese patients and individuals with concurrent use of glucocorticoids or chronic renal diseases. Quinolones are contraindicated in children because they cause destruction of the immature joint cartilage in animals. The use in paediatrics is restricted to life-threatening infections. EXPERT OPINION: Changes in the resistance situation and newly recognized adverse reactions require a continuing adjustment of therapeutic recommendations and constant educational efforts in the field of antimicrobial therapy.

Rational antibiotic therapy and the position of ampicillin/sulbactam.

In the current context of increasing antimicrobial resistance, it is important to use antibiotics rationally and to re-assess regularly the clinical usefulness of commonly used agents. This review focuses on the efficacy of the beta-lactam ampicillin co-administered with the beta-lactamase inhibitor sulbactam, either parenterally (ampicillin/sulbactam) or orally (sultamicillin), for the treatment of bacterial infections. Clinical findings from the past decade confirm the results of numerous older studies and together provide good evidence to support the continued use of ampicillin/sulbactam and sultamicillin in hospital- and community-acquired infections both in adults and children. This is also recognised in recent published national and international guidelines, many of which recommend ampicillin/sulbactam as first-line therapy for various respiratory and skin infections.

Gemifloxacin for community-acquired pneumonia.

BACKGROUND: Newer fluoroquinolones have become an important therapeutic choice in the treatment of community-acquired pneumonia (CAP). Gemifloxacin is one of the newest members of this class of antibiotics and has performed favourably in this indication. OBJECTIVE: To analyse the microbiological activity, pharmacokinetic/pharmacodynamic properties and clinical activity of gemifloxacin in CAP, as well as the safety reported in controlled clinical studies. METHODS: Literature research of English publications in the last 10 years addressing all aspects of gemifloxacin in CAP. RESULTS/CONCLUSIONS: Gemifloxacin is microbiologically the most active fluoroquinolone against Streptococcus pneumoniae--the leading pathogen of CAP. In several comparative studies gemifloxacin was highly effective and well tolerated in the treatment of mild-to-moderate severe CAP.

Moxifloxacin: update and perspectives after 8 years of usage.

Moxifloxacin has a broad spectrum of activity, including Gram-positive and Gram-negative organisms, atypical respiratory pathogens, anaerobes and penicillin- and macrolide-resistant Streptococcus pneumoniae. It achieves good tissue penetration and high concentrations in clinically relevant tissues and fluids. It is available in both an oral and intravenous formulation, has a once-daily administration and a good tolerance and safety profile. Moxifloxacin is used mainly for the treatment of acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, acute bacterial sinusitis, complicated skin and skin-structure infections and complicated intra-abdominal infections, as well as pulmonary TB, although it is not approved in this indication. The most recent studies covering these clinical indications are discussed.

Managing community-acquired pneumonia: a European perspective.

Community-acquired pneumonia (CAP) is a common disease and a frequent cause of morbidity and mortality worldwide. It puts an enormous burden on medical and economic resources, particularly if hospitalization is required. Initial antibacterial therapy for CAP is usually empirical, as culture and antibacterial sensitivity test results are rarely available at initial diagnosis. Any agent selected for empirical therapy should have good activity against the pathogens commonly associated with CAP, a favorable tolerability profile, and be administered in a simple dosage regimen for good compliance. Streptococcus pneumoniae remains the most common causative pathogen, although the incidence of this organism varies widely. Streptococcus pneumoniae strains with decreased susceptibility to penicillin have become increasingly prevalent over the past 30 years and are now a serious problem worldwide. In addition, an increase in the prevalence of pneumococci resistant to macrolides has been observed in Europe over recent years. Mycoplasma pneumoniae and Chlamydia pneumoniae are among the most common atypical pathogens isolated from patients with CAP. Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis are less commonly identified as causative organisms. The emergence and spread of resistance to commonly used antibiotics has challenged the management of CAP. Multiple sets of CAP guidelines have been published to address the continued changes in this complex disease.