minocycline and quinupristin-dalfopristin

After the report of first case of methicillin-resistant Staphylococcus aureus (MRSA) in 1961, MRSA become a major problem worldwide. Over the last decade MRSA strains have emerged as serious pathogens in nosocomial and community settings. Glycopeptides (vancomycin and teicoplanin) are still the current mainstay of therapy for infections caused by MRSA. In the last decade dramatic changes have occurred in the epidemiology of MRSA infections. The isolates with reduced susceptibility and in vitro resistance to vancomycin have emerged. Recently, therapeutic alternatives such as quinupristin/dalfopristin, linezolid, tigecycline and daptomycin have been introduced into clinical practice for treating MRSA infections. Nevertheless, these drugs are only approved for certain indication and resistance has already been reported. In this review, the new information on novel drugs for treating MRSA infections and the resistance mechanisms of these drugs were discussed.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Protein Synthesis Inhibitors; Staphylococcal Infections; Teicoplanin; Tigecycline; Vancomycin; Vancomycin Resistance; Virginiamycin

Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities.

Topics: Acetamides; Anti-Infective Agents; Cephalosporins; Daptomycin; Glycopeptides; Gram-Positive Bacterial Infections; Linezolid; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

The pharmacodynamic and pharmacokinetic characteristics of antimicrobial agents are the two fundamental pharmacological components which provide a rationale for the choice of therapy for intraabdominal infections, and especially serious infections. The most important PK-PD parameters are well known which can potentiate therapeutic efficacy. Antimicrobial agents can be subdivided into categories based on whether their activity is dependent on concentration or exposure time. Therefore, a correct dosing regimen for the time-dependent molecules (i.e. beta-lactams, linezolid, tigecycline) should prolong the maximum exposure time to maintain serum levels over the minimum inhibitory concentration (MIC). The concentration-dependent molecules, on the other hand, which include aminoglycosides and fluoroquinolones, should be given in order to reach maximum concentrations, since they are bactericidal in direct proportion to their concentrations and possess a prolonged post-antibiotic effect.

Topics: Abdominal Abscess; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactams; Digestive System Diseases; Drug Therapy, Combination; Fluoroquinolones; Humans; Linezolid; Metronidazole; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Peritonitis; Sepsis; Tigecycline; Treatment Outcome; Virginiamycin

Though the increased resistance to antibiotics observed worldwide is not a major concern in France, treatment of methicillin-resistant S. aureus has important limitations. New antibiotics have recently been marketed or will soon be (quinupristin-dalfopristin, linelozide, tigecyclin, daptomycin, ceftobiprole, dalbavancin). Their role, which has been documented in several forms of acute infections, remains to be established in infective endocarditis. At present, only treatment of methicillin-resistant S. aureus right-sided endocarditis justifies the use of daptomycin, preferably in association with rifampicin, when the use of vancomycin is not possible or contraindicated.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Endocarditis; Gram-Positive Bacterial Infections; Humans; Linezolid; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Linezolid; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcus aureus; Tigecycline; Vancomycin; Virginiamycin

We review data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). In this review, we cover findings reported in the English language medical literature up to February 2006. Despite the emergence of resistant and multidrug resistant S. aureus, five effective drugs for which little resistance has been observed are in clinical use: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a high minimum inhibitory concentration in the susceptible range. Linezolid looks promising in the treatment of MRSA pneumonia and skin and soft-tissue infections (SSTIs). Daptomycin displays rapid bactericidal activity in vitro, and it has been shown to be noninferior to comparator agents in the treatment of SSTIs and bacteremia. Tigecycline was also noninferior to comparator drugs in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, and minocycline are oral antistaphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are four drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of clinical testing: ceptobiprole and three new glycopeptides with potent bactericidal activity, oritavancin, dalbavancin, and telavancin. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary against which there are frequent treatment failures. The next goals are to determine the most appropriate indications and cost-effectiveness of each of these drugs in the treatment strategy against S. aureus.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Linezolid; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin; Virginiamycin

The advent of vancomycin-resistant enterococci in the 1990s and the threat posed by vancomycin resistance in Staphylococcus aureus led to the development of several new antimicrobial agents active against these pathogens. Quinupristin/dalfopristin was the first such drug to be commercially available but adverse effects have meant that the drug is now rarely used. Linezolid, the first antimicrobial of the oxazolidinone class, has met with more widespread use and has both an intravenous and an oral formulation. Daptomycin is a lipopeptide antimicrobial that is rapidly bactericidal against S. aureus. It is effective in the therapy of S. aureus bloodstream infections but is inactivated by pulmonary surfactant, making it of no use in the therapy of pneumonia. Tigecycline, by contrast, is bacteriostatic against most pathogens but has a broad spectrum of antimicrobial activity and has enhanced penetration into many tissues. Other new antibiotics (dalbavancin, telavancin, ceftobiprole and doripenem) are currently under clinical development and hold promise for widespread clinical use in the next decade.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Infections; Daptomycin; Humans; Linezolid; Minocycline; Oxazolidinones; Staphylococcal Infections; Streptococcal Infections; Tigecycline; Virginiamycin

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

This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004.. Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections.. The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Virginiamycin

Clonal complex (CC) 9 is a prevalent livestock-associated (LA) MRSA clone in Asia whose pathogenicity in humans remains unknown.. In 2012, we identified a patient with CC9-MRSA infection linked to livestock. After screening 3328 clinical MRSA isolates from a national database, eight isolates (0.24%) collected between 1998 and 2012 were further confirmed to be of CC9. The detailed molecular features of the nine human CC9 strains and phylogenetic relatedness to animal CC9 strains were characterized with WGS. The antibiotic susceptibilities were determined and the clinical information was abstracted from medical records.. WGS grouped the CC9 strains into two clades, which were respectively associated with distinct toxome profiles, resistance gene profiles and staphylococcal cassette chromosomes (SCCmecXII for 7 isolates and SCCmecVT for 2 isolates). The SCCmecXII strains were phylogenetically related to animal CC9-MRSA strains, negative for Panton-Valentine leucocidin and 100% resistant to ciprofloxacin, erythromycin, clindamycin, gentamicin and tigecycline. Four of the seven SCCmecXII isolates were associated with invasive diseases including bacteraemia leading to death (2) and osteomyelitis (2). Two SCCmecXII isolates were from patients with exposure to pigs before development of the MRSA diseases.. The CC9-SCCmecXII MRSA prevailing in pigs in Asia is multidrug resistant and potentially pathogenic to humans. It is critical to continuously monitor the local epidemiology of MRSA and implement effective control measures to limit the spread of LA-MRSA between animals, to humans and in healthcare facilities.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Child, Preschool; Ciprofloxacin; Clindamycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Farmers; Female; Gentamicins; Humans; Livestock; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Swine; Swine Diseases; Taiwan; Tigecycline; Virginiamycin

The aim of this study was to evaluate the antimicrobial susceptibility profile of 85 Staphylococcus epidermidis and 84 Staphylococcus haemolyticus strains isolated from blood cultures to oxacillin, vancomycin, tigecycline, linezolid, daptomycin, and quinupristin/dalfopristin over a period of 12 years. S. epidermidis and S. haemolyticus isolated from blood cultures of inpatients, attended at a teaching hospital, were analyzed for the presence of the mecA gene and by SCCmec typing. The minimum inhibitory concentration (MIC) values of tigecycline, linezolid, daptomycin, quinupristin/dalfopristin, and vancomycin were determined. Isolates exhibiting vancomycin MICs of ≥2 μg/ml were typed by pulsed-field gel electrophoresis (PFGE). The rate of mecA positivity was 92.9% and 100% in S. epidermidis and S. haemolyticus, respectively. The most frequent SCCmec types were type III (53.2%) in S. epidermidis and type I (32.1%) in S. haemolyticus. All isolates were susceptible to linezolid and daptomycin, but 7.1% of S. haemolyticus and 2.3% of S. epidermidis isolates were resistant to tigecycline, and 1.2% each of S. haemolyticus and S. epidermidis were resistant and intermediately resistant to quinupristin/dalfopristin, respectively. S. epidermidis exhibited higher vancomycin MICs (40% with MIC of ≥2 μg/ml). Clonal typing of strains with vancomycin MIC of ≥2 μg/ml revealed the presence of different PFGE types of S. epidermidis and S. haemolyticus over a period of up to 4 years (2002-2004, 2005-2008, 2006-2009, 2010-2011). Despite the observation of a high prevalence of mecA, the clinical strains were fully susceptible to vancomycin and to the new drugs linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. The PFGE types with vancomycin MIC of ≥2 μg/ml exhibited a great diversity of SCCmec cassettes, demonstrating that S. epidermidis and S. haemolyticus may easily acquire these resistance-conferring genetic elements.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Blood Culture; Brazil; Daptomycin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Hospitals, Teaching; Humans; Linezolid; Minocycline; Mutation; Oxacillin; Prevalence; Staphylococcal Infections; Staphylococcus epidermidis; Staphylococcus haemolyticus; Tigecycline; Vancomycin; Virginiamycin

Topics: Anti-Infective Agents; Daptomycin; Humans; Linezolid; Minocycline; Tigecycline; Vancomycin; Vancomycin Resistance; Vancomycin-Resistant Enterococci; Virginiamycin

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

The aim of this study was to determine whether vancomycin resistant Staphylococcus aureus (VRSA) and vancomycin intermediate susceptible S.aureus (VISA) strains were present among methicillin-resistant S.aureus (MRSA) strains isolated from patients hospitalised at intensive care units (ICU) of hospitals located at different regions of Turkey and to determine the minimum inhibitory concentration (MIC) values of teicoplanin, linezolid, tigecycline, quinupristin-dalfopristin and daptomycin, which are alternative drugs for the treatment of MRSA infections. A total of 260 MRSA clinical strains (isolated from 113 lower respiratory tract, 90 blood, 24 wound, 17 catheter, 13 nasal swabs, two urine and one CSF sample) were collected from nine health-care centers in eight provinces [Ankara (n= 52), Konya (n= 49), Antalya (n= 40), Istanbul (n= 7), Izmir (37), Diyarbakir (n= 15), Van (n= 12), Trabzon (n= 48)] selected as representatives of the seven different geographical regions of Turkey. Methicillin resistance was determined by cefoxitin disk diffusion in the hospitals where the strains were isolated and confirmed by oxacillin salt agar screening at the Refik Saydam National Public Health Agency. Screening for VISA and VRSA was conducted using the agar screening test and E-test. Susceptibility of the MRSA strains to other antibiotics was also determined by E-test method. None of the 260 MRSA strains were determined to be VRSA or VISA. All were susceptible to teicoplanin and linezolid, and susceptibility rates to daptomycin, tigecycline and quinupristin-dalfopristin were 99.6%, 96.9%, and 95%, respectively. Absence of VISA and VRSA among the MRSA strains surveyed currently seemed hopeful, however, continuous surveillance is necessary. In order to prevent the development of VISA and VRSA strains the use of linezolid, tigecycline, quinupristin-dalfopristin and daptomycin should be encouraged as alternative agents of treatment of MRSA infections.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Humans; Intensive Care Units; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

We compared the in vitro activity of dalfopristin and quinupristin combined with five intravenous antibiotics in a 3-dimensional model. We tested six strains of Staphylococcus aureus selected with different patterns of resistance to methicillin and erythromycin. Dalfopristin and quinupristin displayed a very synergistic activity against all the strains with a mean 16- or 32-fold decrease of inhibitory concentrations in combination. That synergy was even better against erythromycin-resistant strains. In combination with tigecycline or fosfomycin, the antibacterial activity could be consistently enhanced with the same decrease of inhibitory concentrations. A synergy was also observed, less regularly and at a lower level, with rifampin, gentamicin or vancomycin. Combinations of dalfopristin and quinupristin with tigecycline or fosfomycin could be very interesting in clinical practice because the inhibitory effect could be achieved with very low concentrations of each component, even when erythromycin-resistant strains are concerned.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Fosfomycin; Gentamicins; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcus aureus; Tigecycline; Vancomycin; Virginiamycin

This study was undertaken to test the in vitro activity of tigecycline against 117 clinically relevant Gram-positive pathogens and to correlate this activity with their resistance gene content. Overall, tigecycline showed a minimal inhibitory concentration (MIC) range of 0.015-0.5mg/L, able to inhibit potently all multiresistant streptococci, enterococci and MR staphylococci. Tigecycline was active against methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, with MICs for 90% of the organisms (MIC(90)) of 0.25 mg/L and 0.12 mg/L, respectively, being more active than linezolid (MIC(90)=2 mg/L) and quinupristin/dalfopristin (MIC(90)=0.5 and 2-4 mg/L, respectively). Molecular characterisation of resistance determinants demonstrated the concomitant presence of different classes of genes: in particular, tet(M), erm(B) and erm(C) in Streptococcus agalactiae; tet(O), variably associated with different erm genes, in Streptococcus pyogenes; vanA, tet(M) and erm(B) in Enterococcus faecalis, and vanA and erm(B) in Enterococcus faecium. All the MRSA strains harboured SCCmec and erm genes and 50% possessed tet(K) with tet(M) genes. Staphylococcus epidermidis strains were only resistant to erythromycin. These results clearly demonstrate that tigecycline has a MIC(90) range of 0.015-0.5 mg/L both against tetracycline-susceptible and -resistant isolates carrying other resistance determinants, suggesting that this drug could play an important role in the treatment of infections caused by these multiresistant Gram-positive pathogens.

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterococcus; Genes, Bacterial; Humans; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcus; Streptococcus; Tetracycline Resistance; Tigecycline; Virginiamycin

Topics: Anti-Bacterial Agents; beta-Lactams; Daptomycin; Ertapenem; Humans; Ketolides; Minocycline; Ofloxacin; Tigecycline; Virginiamycin

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecium; Glycopeptides; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

It is a hot clinical issue whether newly approved antimicrobial agents such as daptomycin, linezolid, quinupristin/dalfopristin (synercid) and tigecycline are active enough to be used for infections caused by vancomycin resistant bacteria. We performed susceptibility tests for mupirocin, which is in widespread clinical use in Korea, and four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline, against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium isolated from Korean patients in 1998 and 2005 to evaluate and compare the in vitro activity of these antimicrobials. Among these agents, quinupristin/dalfopristin, which is rarely used in hospitals in Korea, showed relatively high resistance to several vancomycin-resistant enterococci (VRE) isolated in 2005. Likewise, daptomycin, linezolid and tigecycline have not yet been in clinical use in Korea. However, our results showed that most of the 2005 VRE isolates were already resistant to linezolid and daptomycin (highest minimum inhibitory concentration (MIC) value >100 microg/ml). Compared with the other four antimicrobial agents tested in this study, tigecycline generally showed the greatest activity against VRE. However, four strains of 2005 isolates exhibited resistance against tigecycline (MIC >12.5 microg/ml). Almost all VRE were resistant to mupirocin, whereas all E. faecium isolated in 1998 were inhibited at concentrations between 0.8 to approximately 1.6 microg/ml. In conclusion, resistances to these new antimicrobial agents were exhibited in most of VRE strains even though these new antibiotics have been rarely used in Korean hospitals.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Korea; Linezolid; Microbial Sensitivity Tests; Minocycline; Mupirocin; Oxazolidinones; Tigecycline; Vancomycin Resistance; Virginiamycin

The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution. M. pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 microg/ml and evernimicin at 4 microg/ml, but it was resistant to linezolid. It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin. M. hominis was susceptible to linezolid, evernimicin, and GAR-936. It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin. U. urealyticum was susceptible to evernimicin (8 to 16 microg/ml) and resistant to linezolid. It was less susceptible to GAR-936 (4.0 microg/ml) than to tetracycline (0.5 microg/ml). Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 microg/ml). The new quinolone gatifloxacin was active against M. pneumoniae and M. hominis at 0.12 to 0.25 microg/ml and active against ureaplasmas at 1.0 microg/ml. The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M. pneumoniae as the pH increased from 6.9 to 7.8. A similar increase in susceptibility with increasing pH was also observed with ureaplasmas. Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.

Topics: 4-Quinolones; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Aza Compounds; Erythromycin; Fluoroquinolones; Gatifloxacin; Humans; Hydrogen-Ion Concentration; Ketolides; Linezolid; Macrolides; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Mycoplasma hominis; Mycoplasma pneumoniae; Oxazolidinones; Quinolines; Tetracyclines; Tigecycline; Ureaplasma urealyticum; Virginiamycin

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterococcus; Gram-Positive Bacterial Infections; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Penicillin Resistance; Staphylococcus aureus; Streptococcus pneumoniae; Tigecycline; Vancomycin Resistance; Virginiamycin

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Fluoroquinolones; Germany; Hospitals; Humans; Longitudinal Studies; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Staphylococcus aureus; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Virginiamycin

The in-vitro activities of five investigational antibiotics, RP59500 (a semisynthetic injectable streptogramin), CL 329,998 and CL 331,002 (two new glycylcyclines), trovafloxacin (a naphthyridone), and clinafloxacin (a dihalogenated quinolone), were examined and compared with those of minocycline, teicoplanin and vancomycin against 190 clinical isolates of Gram-positive cocci. The MICs for RP59500 against all isolates with the exception of Enterococcus faecalis were low. RP59500 was bactericidal against all except enterococcal isolates. CL 329,998 and CL 331,002 were significantly more active than minocycline against oxacillin-resistant Staphylococcus aureus (MIC90 0.25 versus 8 mg/L) and all enterococcal isolates (MIC90 0.125 versus 16 mg/L). Clinafloxacin was the most active agent against all staphylococcal isolates and was bactericidal. Trovafloxacin showed good activity against oxacillin-susceptible staphylococci and alpha-haemolytic streptococci (MIC90 < or = 0.125 mg/L). This study demonstrates the potential of the five investigational antibiotics as therapeutic agents for infections caused by Gram-positive cocci.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Fluoroquinolones; Gram-Positive Bacteria; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Quinolones; Teicoplanin; Tetracyclines; Vancomycin; Virginiamycin

The results of susceptibility testing of 48 phenotyped strains of glycopeptide antibiotic-resistant enterococci are reported. Minimum inhibitory and bactericidal concentrations (MICs and MBCs) were determined for 27 vanA, 17 vanB, and 4 vanC strains. Antibiotics exhibiting the greatest activity included novobiocin (MIC90 = 8 micrograms/ml and MBC90 = 32 micrograms/ml), ramoplanin (MIC90 = 2 micrograms/ml and MBC90 = 4 micrograms/ml), and the streptogramin RP59500 (MIC90 = 4 micrograms/ml and MBC90 = 32 micrograms/ml). These antibiotics warrant further investigation as potentially useful agents, either alone or in combination, for treating enterococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Depsipeptides; Drug Resistance, Microbial; Enterococcus; Fluoroquinolones; Fusidic Acid; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Novobiocin; Peptides, Cyclic; Quinolones; Teicoplanin; Vancomycin; Virginiamycin