minocycline and telavancin

Bacterial infections, particularly those due to gram-positive bacteria, continue to predominate in patients with cancer. Coagulase-negative and coagulase-positive staphylococci and enterococci remain as common pathogenic microorganisms. Clostridium difficile has emerged as a significant pathogen. Major clinical syndromes include vascular catheter-related infection, febrile neutropenia, diarrhea and colitis. Rising antimicrobial resistance among gram-positive bacteria is of serious concern. The clinical utility of penicillin against streptococci and vancomycin against coagulase-negative and coagulase-positive staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of vancomycin during neutropenic fever needs careful reconsideration. Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin. However, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Lipoglycopeptides; Minocycline; Neoplasms; Oxazolidinones; Tigecycline

There is a constant need for new antibacterial agents because of the unavoidable development of bacterial resistance that follows the introduction of antibiotics in clinical practice. As observed in many fields, innovation generally comes by series. For instance, a wide variety of broad-spectrum antibacterial agents became available between the 1970s and the 1990s, such as cephalosporins, penicillin/beta-lactamase inhibitor combinations, carbapenems, and fluoroquinolones. Over the last 2 decades, the arrival of new antibacterial drugs on the market has dramatically slowed, leaving a frequent gap between isolation of resistant pathogens and effective treatment options. In fact, many pharmaceutical companies focused on the development of narrow-spectrum antibiotics targeted at multidrug-resistant Gram-positive bacteria (e.g. methicillin-resistant Staphylococcus aureus, penicillin resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecium). Therefore, multidrug-resistant Gram-negative bacteria (e.g. extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii) recently emerged and rapidly spread worldwide. Even if some molecules were developed, new molecules for infections caused by these multidrug-resistant Gram-negative bacteria remain remarkably scarce compared to those for Gram-positive infections. This review summarises the major microbiological, pharmacological, and clinical properties of systemic antibiotics recently marketed in France (i.e. linezolid, daptomycin, tigecycline, ertapenem, and doripenem) as well as those of antibacterial drugs currently in development (i.e. ceftobiprole, ceftaroline, dalbavancin, telavancin, oritavancin, iclaprim, and ramoplanin) or available in other countries (i.e. garenoxacin, sitafloxacin, and temocillin).

Topics: Acetamides; Aminoglycosides; Anti-Infective Agents; beta-Lactams; Carbapenems; Cephalosporins; Daptomycin; Doripenem; Drug Resistance, Bacterial; Ertapenem; Fluoroquinolones; France; Humans; Linezolid; Lipoglycopeptides; Minocycline; Oxazolidinones; Penicillins; Pyrimidines; Teicoplanin; Tigecycline

Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections.. A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus.. For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Critical Illness; Daptomycin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Virginiamycin

Combination therapy is recommended for infections with carbapenemase-producing Klebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producing K. pneumoniae (MBL-KP). Two VIM- and two NDM-producing K. pneumoniae strains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log10 decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10 decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producing K. pneumoniae. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.

Topics: Aminoglycosides; Anti-Bacterial Agents; Aztreonam; beta-Lactamases; Ciprofloxacin; Colistin; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Fosfomycin; In Vitro Techniques; Klebsiella pneumoniae; Lipoglycopeptides; Meropenem; Microbial Sensitivity Tests; Minocycline; Rifampin; Thienamycins; Tigecycline; Vancomycin

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pneumonia, Staphylococcal; Tigecycline; Vancomycin; Virginiamycin

Coagulase-negative staphylococci (CoNS) have emerged as important nosocomial pathogens. CoNS resistance to meticillin and other semisynthetic penicillins is now common. Elevated vancomycin minimal inhibitory concentrations (MICs) have been reported and are associated with worse treatment outcomes. Several newer antibiotics have recently become available for the treatment of Gram-positive infections. The purpose of this study was to assess the in vitro activity of telavancin, daptomycin, linezolid and tigecycline in comparison with oxacillin and vancomycin against 653 non-duplicate clinical isolates of CoNS by the agar dilution method. The greatest variability in MIC was observed for oxacillin. Presence of the mecA gene conferred higher MICs for oxacillin but did not influence MICs to all other antibiotics tested. Telavancin tended to have MICs that were 1-2 dilutions lower than vancomycin. Daptomycin had good activity against all isolates. Staphylococcus haemolyticus, Staphylococcus hominis subsp. novobiosepticus, Staphylococcus saprophyticus, Staphylococcus schleiferi and Staphylococcus simulans were the most daptomycin-susceptible CoNS species tested. The validity of the agar dilution method for daptomycin was confirmed, with >90% isolates having MICs that were within 1 dilution of parallel Etest results. Within-species MIC variation was most restricted for linezolid and tigecycline, with the exception of Staphylococcus epidermidis and Staphylococcus haemolyticus that demonstrated higher overall MICs to tigecycline.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Daptomycin; DNA, Ribosomal; Linezolid; Lipoglycopeptides; Microbial Sensitivity Tests; Micrococcal Nuclease; Minocycline; Oxacillin; Oxazolidinones; Penicillin-Binding Proteins; Polymerase Chain Reaction; Staphylococcus; Tigecycline; Vancomycin

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Osteomyelitis; Oxazolidinones; Staphylococcal Infections; Tigecycline; Vancomycin

Increasingly frequent reports of vancomycin treatment failures for serious methicillin-resistant Staphylococcus aureus (MRSA) infections provide impetus for comparative in vitro studies to assess the activity of newer antimicrobial agents against a range of MRSA isolates.. A sample of 168 MRSA derived from a long-term MRSA collection was subjected to susceptibility testing to telavancin, daptomycin, linezolid, tigecycline and vancomycin by broth micro-dilution. Data were reviewed for sporadic occurrence of isolates with reduced susceptibility. Analyses were performed to test for temporal trends toward decreasing susceptibility and to compare susceptibility of isolates from different infection sites.. No MRSA isolate from any time period was resistant to test antibiotics. For daptomycin, linezolid and tigecycline, there were no susceptibility differences between the pre- and postclinical availability periods. All newer agents were active against MRSA isolates with minimum inhibitory concentrations (MICs) of vancomycin >1 mg/l, but there were significant correlations in susceptibility among several pairs of antibiotics.. Telavancin and other newer antistaphylococcal agents were fully active against MRSA from various infection sites including isolates with vancomycin MIC >1 mg/l.

Topics: Acetamides; Aminoglycosides; Anti-Infective Agents; Daptomycin; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Tigecycline; Vancomycin

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is characterized by variations (sometimes extreme) by country and geographic region. The conventional association of MRSA with healthcare settings has been upset by the emergence of community-associated MRSA infections in many areas. With this surge in MRSA comes a renewed interest in alternative agents to vancomycin for treatment of MRSA infections, including older drugs, such as clindamycin, doxycycline and trimethoprim- sulfamethoxazole. Newer agents, such as linezolid and daptomycin, are aiming to improve on the poor cure rates found with vancomycin in serious MRSA infections, but definitive studies showing superiority of these drugs are not yet available. Finally, the drug-development pipeline contains a number of agents for the treatment of MRSA infections, including enhanced glycopeptides (dalbavancin, oritavancin and telavancin) and anti-MRSA cephalosporins (ceftobiprole). As MRSA becomes the 'new normal' in many areas, clinicians will have to sort out the proper role of a dozen or more anti-MRSA drugs.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Clindamycin; Daptomycin; Doxycycline; Folic Acid Antagonists; Global Health; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin; Methicillin Resistance; Minocycline; Oxazolidinones; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Teicoplanin; Tigecycline; Trimethoprim; Vancomycin

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Drug Design; Humans; Incidence; Lipoglycopeptides; Methicillin Resistance; Minocycline; Molecular Structure; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Thiazoles; Tigecycline