minocycline and Gram-Positive-Bacterial-Infections

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Combinations; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Complicated infections caused by vancomycin-resistant enterococci (VRE) represent a therapeutic challenge, since adequate treatment options are limited and antibiotic resistance to the available agents has already been described. The most frequently used antibiotic in VRE treatment is linezolid. Tigecycline is an alternative to linezolid, however, clinical data for severe infections such as sepsis or endocarditis are scarce. Daptomycin on the one hand is an option but has not yet been approved for the treatment of enterococcal infections in Germany on the other hand. The present review critically evaluates the clinical significance of the antibiotics in question for VRE therapy based on existing data.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Enterobacteriaceae; Evidence-Based Medicine; Gram-Positive Bacterial Infections; Humans; Linezolid; Minocycline; Oxazolidinones; Tigecycline; Treatment Outcome; Vancomycin-Resistant Enterococci

New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Cephalosporins; Daptomycin; Drug Resistance, Multiple, Bacterial; Drugs, Investigational; Genes, Bacterial; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; Tigecycline; Vancomycin

Tigecycline is an approved treatment for complicated skin and soft-tissue infections (cSSTIs). The efficacy of tigecycline as monotherapy or in combination with other antibacterials in the treatment of cSSTI in routine practice is described.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).. A total of 254 cSSTI patients who received tigecycline were included (mean age 63.2 ± 14.9 years). Of these, 34.4% were in intensive care units, 54.5% acquired their infection in hospital and 90.9% had at least one comorbidity. Infection most commonly affected the limbs (62.4%) and 43.8% of infections were classified as necrotizing. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 15.0 ± 7.9 (n = 205) and 5.8 ± 3.9 (n = 32), respectively, indicating high disease severity. Staphylococcus aureus (52.7%), Escherichia coli (18.0%) and Enterococcus faecium (12.0%) were the most frequently isolated pathogens; 32.9% of infections were polymicrobial and 30.5% were due to resistant pathogens. Overall, 71.8% received tigecycline as monotherapy and 28.2% as combination therapy for a mean duration of 12 days. Clinical response rates at the end of treatment were 79.6% for all patients who received the standard dosage (183/230), 86.7% for patients who received tigecycline as monotherapy (143/165), 75.0% for patients with a nosocomial infection (96/128), 75.3% for patients with an APACHE II score >15 (61/81) and 58.3% for patients with a SOFA score ≥ 7 (7/12).. In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cSSTI with a high severity of illness.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).. A total of 785 cIAI patients who received tigecycline were included (mean age 63.1 ± 14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9 ± 7.6 (n = 614) and 7.0 ± 4.2 (n = 108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n = 430) received tigecycline as monotherapy and 45.2% (n = 355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score >15 (250/330) and 54.2% (32/59) for patients with a SOFA score ≥ 7.. In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome; Young Adult

Tigecycline is a broad-spectrum antibiotic with activity against difficult-to-treat pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., Acinetobacter baumannii, and Gram-negative bacterial strains that produce extended-spectrum β-lactamases. Minimal organ toxicity and lack of dosage adjustment in most patients are important considerations for tigecycline use. Tigecycline has been shown to be as effective and safe as standard antimicrobial therapy for treatment of adults with complicated intra-abdominal infections, complicated skin and skin structure infections, and community-acquired bacterial pneumonia. The clearest applications of tigecycline are for on-label indications. Whether tigecycline should be utilized as therapy for other infections including hospital-acquired infections with a high likelihood of multidrug-resistant pathogens is a complex issue that requires ongoing assessment. This article offers an updated overview of tigecycline clinical studies, current microbial resistance patterns, pharmacokinetic/pharmacodynamic investigations, and safety analyses.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Tigecycline

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

Antibacterial drug discovery and development has slowed considerably in recent years, with novel classes discovered decades ago and regulatory approvals tougher to get. Traditional approaches and the newer genomic mining approaches have not yielded novel classes of antibacterial compounds. Instead, improved analogues of existing classes of antibacterial drugs have been developed by improving potency, minimizing resistance and alleviating toxicity.. This article is a comprehensive review of newer classes of antibacterial drugs introduced or approved after year 2000.. It describes their mechanisms of action/resistance, improved analogues, spectrum of activity and clinical trials. It also discusses new compounds in development with novel mechanisms of action, as well as novel unexploited bacterial targets and strategies that may pave the way for combating drug resistance and emerging pathogens in the twenty-first century.. The outlook of antibacterial drug discovery, though challenging, may not be insurmountable in the years ahead, with legislation on incentives and funding introduced for developing an antimicrobial discovery program and efforts to conserve antibacterial drug use.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Drug Delivery Systems; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drugs, Investigational; Glycopeptides; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Macrolides; Minocycline; Oxazolidinones; Tigecycline

Tigecycline has been investigated in combination with other antibacterials against a wide range of susceptible and multiresistant Gram-positive and Gram-negative bacteria. Combinations have been analysed in vitro, in animal models and in human case reports. In vitro, tigecycline combined with other antimicrobials produces primarily an indifferent response (neither synergy nor antagonism). Nevertheless, synergy occurred when tigecycline was combined with rifampicin against 64-100% of Enterococcus spp., Streptococcus pneumoniae, Enterobacter spp. and Brucella melitensis isolates. Combinations of tigecycline with amikacin also showed synergy for 40-100% of Enterobacter spp., Klebsiella pneumoniae, Proteus spp. and Stenotrophomonas maltophilia isolates. Moreover, bactericidal synergisms occurred with tigecycline plus amikacin against problematic Acinetobacter baumannii and Proteus vulgaris, and with colistin against K. pneumoniae. Data from animal experiments and case reports, although limited, displayed consistent beneficial activity of tigecycline in combination with other antibacterials against multiresistant organisms, including vancomycin against penicillin-resistant S. pneumoniae in experimental meningitis, gentamicin against Pseudomonas aeruginosa in experimental pneumonia, daptomycin against Enterococcus faecium endocarditis, and colistin against K. pneumoniae bacteraemia and P. aeruginosa osteomyelitis. Antagonism was extremely rare in vitro and was not reported in vivo. Thus, tigecycline may be combined with a second antimicrobial as part of a combination regimen.

Topics: Animals; Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Rapid emergence of resistance against antibacterials emphasizes the need for the development of novel and/or more potent antibacterials. Tigecycline is the first representative of a new drug class, the glycylcyclines, and was approved in 2005 by the US FDA for the treatment of complicated skin and skin structure infections, as well as complicated intra-abdominal infections. Tigecycline distributes extensively into the intracellular space of tissue and accumulates in cells, which may qualify it for the treatment of intracellular infections. The pharmacokinetics of tigecycline are complex with both linear and non-linear characteristics. The reason for this complexity is still not fully understood. Non-linearity can be found in the volume of distribution possibly due to extensive and variable tissue and/or plasma protein binding. In contrast, clearance and area under the plasma concentration-time curve are dose-independent. Tigecycline has a high incidence of mild adverse effects, mainly nausea and vomiting, but is otherwise well tolerated.

Topics: Animals; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Minocycline; Tigecycline

Tigecycline is a glycylcycline antibacterial agent derived from minocycline with a broad spectrum of activity. Like tetracycline agents, it inhibits bacterial protein synthesis but is able to bind to target sites with higher affinity and overcome tetracycline-resistance mechanisms due to structural modifications. The safety and efficacy of tigecycline has been demonstrated in clinical trials for complicated intra-abdominal and complicated skin and skin-structure infections. It has received approval for these indications in several countries, including the USA in 2005, and European Union in 2006. Aside from approved indications and in vitro data, growing clinical experience suggests a potential role for tigecycline in the management of multi-drug resistant infections due to drug-resistant pathogens. Further study is necessary to determine the ultimate role of tigecycline in treating these types of infections.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Minocycline; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

Glycopeptides have been the antimicrobials most commonly used for infections by Gram-positive organisms and methicillin resistant S. aureus (MRSA). In recent years, however, glycopeptide resistance and tolerance have become a serious problem. Thus, enterococci highly resistant to vancomycin, vancomycin-intermediate/ resistant S. aureus (VISA), and vancomycin tolerance in S. aureus are found, and increased therapeutic failure and mortality are clinically reported with vancomycin MIC for S. aureus > or = 1.5-2 microg/mL. When faced with these organisms, we therefore need potent bactericidal antimicrobials that may be empirically administered, effective against susceptible and resistant pathogens, easily dosed, with few adverse effects and no significant interaction with other drugs, and that can be administered in an outpatient setting. In bacteremia by methicillin-susceptible S. aureus, use of vancomycin is associated to a greater failure and mortality rate as compared to semisynthetic penicillins. New treatment options for MRSA infections include daptomycin, linezolid, tygecycline, and quinupristin/dalfopristin. New anti-MRSA drugs are also under development, including glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. This paper reviews the new antimicrobials against Gram-positive organisms.

Topics: Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Humans; Methicillin Resistance; Minocycline; Tigecycline

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

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

Multi-antibiotic resistant Gram-positive cocci represent emerging pathogens especially in the setting of the immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are of concern, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics and/or immunosuppressive drugs are widely administered. The spectrum of available antimicrobial compounds for an effective management of these relevant infections is significantly impaired in selection and clinical efficacy by the emerging and spread of methicillin-resistant and more recently glycopeptide-resistant Gram-positive microbial strains linezolid, together with the recently licensed quinupristin-dalfopristin, daptomycin and tigecycline, followed by a number of glycopeptides, fluoroquinolones, and other experimental compounds represent an effective response to these concerns, due to their innovative mechanisms of action, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also when compromised patients are of concern. The main problems related to the epidemiological and clinical features of multiresistant Gram-positive infection, the potential clinical indications of all recently available compounds compared with the standard of treatment of resistant Gram-positive infections, and updated data on efficacy and tolerability of linezolid have to be clarified.

Topics: Acetamides; Administration, Oral; Anti-Infective Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Enterococcus; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Staphylococcus aureus; Streptococcus pneumoniae; Teicoplanin; Tigecycline; Time Factors; Vancomycin; Virginiamycin

Tigecycline is a novel compound in the antimicrobial class known as the glycylcyclines. In vitro studies have shown it to have activity against the vast majority of Gram-positive pathogens, including multi-drug resistant Staphylococcus aureus and vancomycin-resistant enterococci. Tigecycline has also shown excellent in vitro activity against a broad range of Gram-negative enteric organisms including strains resistant to other antimicrobials as well as anaerobes. Tigecycline is not affected by the ribosomal protection and efflux mechanisms transmitted by the known tetracycline resistance genes. Tigecycline represents an exciting new class of glycylcycline antimicrobial agents for the treatment of multi-drug resistant Gram-positive bacteria. Although its broad spectrum of activity, which also includes Gram-negative enterics, makes it a candidate for empiric therapy for intra-abdominal infections, its spectrum against multi-drug resistant Gram-positive organisms makes it a very attractive choice for empiric treatment of Gram-positive infections in patients at risk for resistant strains. The two pivotal Phase II clinical trials involving complicated skin and soft tissue infections and intra-abdominal infections have shown the drug to be safe and effective.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline, the first-in-class glycylcycline, was developed to recapture the broad spectrum of activity of the tetracycline class and to treat patients with difficult-to-treat bacterial infections. Tigecycline's in vitro spectrum of activity encompasses aerobic, facultative and anaerobic Gram-positive and -negative bacteria, including antimicrobial-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Clinical trials involving patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, including patients infected with methicillin-resistant S. aureus, demonstrated that tigecycline was bacteriologically and clinically effective with mild-to-moderate gastrointestinal adverse events (i.e., nausea, vomiting and diarrhea) the most commonly reported. Tigecycline is a promising new broad-spectrum parenteral monotherapy for the treatment of patients with Gram-positive and -negative bacterial infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Clinical Trials as Topic; Drug Resistance, Bacterial; Female; Gastrointestinal Diseases; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Skin Diseases, Bacterial; Tigecycline; Treatment Outcome

Vancomycin is considered the workhorse for the treatment of most drug-resistant gram-positive bacterial infections. However, concerns have been raised regarding the increasing rates of vancomycin-resistant enterococci and the clinical shortcomings of vancomycin in the treatment of invasive Staphylococcus aureus infections. Resources have been committed to the development of antimicrobial agents with activity against these organisms. This review will focus on the newer antibacterial agents that have been developed for the treatment of resistant gram-positive pathogens. Included in this review are the agents: quinupristin-dalfopristin, linezolid, daptomycin, telithromycin, and tigecycline.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Ketolides; Minocycline; Peptides, Cyclic; Tigecycline

Tigecycline, is a novel broad-spectrum glycylcycline antibiotic, which has activity against a broad range of Gram-positive, Gram-negative, atypical, anaerobic and antibiotic-resistant bacteria. This includes activity against MRSA, VRE and penicillin resistant Streptococcus pneumoniae. Whilst exhibiting antibacterial activities typical of earlier tetracyclines, it has more potent activity against tetracycline-resistant organisms. Although a bacteriostatic compound in vitro, its effectiveness in clinical trials suggests that traditional laboratory thinking about using bacteriostatic drugs in serious infections needs to be revised. Unlike existing tetracyclines, tigecycline is only available as an intravenous preparation, is administered twice daily although its long half life and post-antibiotic effect may make once daily dosing possible, appears to have good tissue penetration (e.g. skin) and requires no adjustment in the presence of renal or hepatic diseases. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. In three trials, it was well tolerated despite increased frequency of nausea and vomiting. In the light of these early clinical data and the likelihood that this agent will become available for clinical use within the next 12-24 months, this review aims to summarise the key clinical data and potential formulary considerations for the future use of this agent, subject to further clinical trials and publication of clinical human data.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Resistance, Bacterial; Formularies as Topic; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Minocycline; Tigecycline

Bacterial resistance to currently available antimicrobials is an increasing concern, particularly among various gram-positive organisms such as drug-resistant pneumococci, methicillin-resistant staphylococci, and drug-resistant enterococci. Tigecycline is an investigational glycylcycline antibiotic that shows promising activity against these resistant gram-positive organisms.. : This paper reviews the pharmacology, pharmacokinetic and pharmacodynamic properties, in vitro and in vivo activity, safety profile, and potential role of tigecycline in the management of gram-positive infections involving resistant microbes.. Articles included in this review were identified through a search of MEDLINE from 1998 through 2004 using the terms tigecycline and GAR-936. Abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1998 to 2003 were searched using the same terms. The reference lists of identified articles were also reviewed for pertinent publications.. Whereas resistance has developed with many of the earlier tetracycline derivatives, tigecycline appears to have a reduced potential for resistance. Several reports have evaluated the in vitro activity of this agent against a number of organisms. It has exhibited pronounced activity against most gram-positive microbes, including resistant strains (eg, drug-resistant pneumococci, methicillin-resistant staphylococci, resistant enterococci). Tigecycline has also shown useful activity against many clinically important gram-negative microbes. In vivo studies of tigecycline are limited. Only 2 clinical trials have been reported to date, one in patients with complicated skin and skin-structure infections and the other in patients with complicated intra-abdominal infections. In these studies, tigecycline therapy resulted in clinical cures in more than two thirds of evaluable patients. Tigecycline was well tolerated in both studies; nausea and vomiting were the most common adverse events.. Although published clinical trials involving tigecycline are limited and additional trials are needed, preliminary reports on its use in the treatment of gram-positive infections are encouraging. Tigecycline has favorable pharmacokinetic properties and, apart from gastrointestinal adverse events, appears to be well tolerated.

Topics: Animals; Anti-Bacterial Agents; Clinical Trials, Phase II as Topic; Drug Resistance, Bacterial; Drugs, Investigational; Gram-Negative Bacteria; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The advent of multidrug-resistant gram-positive aerobes such as Staphylococcus aureus, Streptococcus pneumoniae, and the enterococci, which are resistant to beta-lactams, vancomycin, and a host of other commonly used antimicrobials, has complicated our approach to antibiotic therapy. Despite marketing of the first oxazolidinone, linezolid, and the streptogramin combination, quinupristin-dalfopristin, an urgent need exists for more agents to combat these pathogens. Two such agents, the glycopeptide oritavancin (LY333328) and the glycylcycline tigecycline (GAR-936), are in phase III clinical trials. These agents, which require parenteral administration, exhibit substantial in vitro activity against a variety of gram-positive aerobes and anaerobes, including the multidrug-resistant organisms listed previously. Only tigecycline demonstrates useful activity against gram-negative organisms. Combination therapy of these agents with ampicillin or aminoglycosides frequently leads to synergistic in vitro activity against multidrug-resistant staphylococci and streptococci. These agents are also active in a variety of animal models of systemic and localized infections. Few published efficacy and tolerability data are available in humans. If controlled clinical trial data verify these agents' efficacy and tolerability, both drugs should become welcome additions to the available antimicrobials. However, restricting their use to the treatment of infections caused by bacteria resistant to other antimicrobials, especially multidrug-resistant staphylococci and streptococci, may prolong their clinical utility by retarding the development of resistance. Careful surveillance of bacterial sensitivity to these agents should be undertaken to assist clinicians in the decision whether or not to use these agents empirically to treat infections caused by suspected multidrug-resistant gram-positive pathogens.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drugs, Investigational; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Lipoglycopeptides; Minocycline; Tigecycline

We evaluated a catheter-lock solution consisting of N-acetylcysteine, tigecycline, and heparin for catheter salvage in patients with hemodialysis catheter-associated bacteremia. Eighteen case patients received the catheter-lock solution for 14 days plus systemic antibiotic therapy. Treatment was successful for 15 (83%) of the 18 case patients within 90 days of follow-up, with a median catheter retention interval of 64.5 days.

Topics: Acetylcysteine; Anti-Bacterial Agents; Bacteremia; Catheterization; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pilot Projects; Prospective Studies; Renal Dialysis; Tigecycline; Treatment Outcome

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection.. A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment.. For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid.. Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.

Topics: Acetamides; Aged; Anti-Bacterial Agents; Cross Infection; Double-Blind Method; Enterococcus; Female; Gram-Positive Bacterial Infections; Hospitalization; Humans; Linezolid; Male; Methicillin Resistance; Middle Aged; Minocycline; Oxazolidinones; Staphylococcus aureus; Tigecycline; Treatment Outcome; Vancomycin; Vancomycin Resistance

Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where Escherichia coli and Bacteroides fragilis are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s): E. coli only (cohort 1), other mono- or polymicrobial Enterobacteriaceae (cohort 2), at least one Enterobacteriaceae pathogen plus an anaerobe(s) (cohort 3), at least one Enterobacteriaceae pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35 E. coli pathogens) and 2 (16 patients, 24 Enterobacteriaceae). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses (P values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response (P = 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections.

Topics: Abdominal Cavity; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria, Anaerobic; Double-Blind Method; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Child; Drug Therapy, Combination; Enterococcus; Enterococcus faecalis; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Immunity; Male; Middle Aged; Minocycline; Neoplasms; Pain; Vancomycin Resistance; Virginiamycin

The in vitro activity of tigecycline and comparator agents was evaluated against Gram-positive and Gram-negative isolates collected in Latin American centers between 2004 and 2015 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) global surveillance study.. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution methodology according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Antimicrobial susceptibility was determined using CLSI breakpoints, except for tigecycline for which the US Food and Drugs Administration breakpoints were used.. This study of isolates from Latin America shows that linezolid, vancomycin and tigecycline continue to be active in vitro against important Gram-positive organisms such as MRSA, and that susceptibility rates to meropenem and tigecycline against members of the Enterobacteriaceae, including ESBL-producers, were high. However, we report that Latin America has high rates of MRSA, MDR A. baumannii and ESBL-producing Enterobacteriaceae which require continued monitoring.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Epidemiological Monitoring; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; Tigecycline

Colonization, infection, and clonal dissemination of vancomycin-resistant enterococcus (VRE) have been reported in the literature. We aimed to investigate the incidence rate of VRE acquisition and route of transmission of VRE within the medical intensive care unit (ICU) to prove whether subclinical transmission occurs in medical ICUs.. Between March 1, 2012 and September 30, 2013, rectal cultures were obtained from all inpatients on admission and after admission to medical ICU. Strain types of VRE were determined by both multilocus sequence typing and pulsed-field gel electrophoresis.. A total of 66 of the 405 rectal swab surveillance cultures obtained from 46 inpatients were positive for VRE, among which 27 inpatients were culture-positive for VRE on admission to medical ICU, and 19 inpatients were initially culture-negative but converted to culture-positive after admission. All isolates carried vanA gene consisting of 51 Enterococcus gallinarum, 13 Enterococcus faecium, and two Eenterococcus casseliflavus. Of the 51 E. gallinarum isolates, 40 were type ST 341, seven were ST 252, two were ST 78, and two were ST 64. The Enterococcus spp., MLST and PFGE subtypes were almost similar among these two groups of inpatients. Linezolid and tigecycline were most active against VRE in vitro.. Subclinical VRE cross transmission may occur in ICU. Active surveillance and maximal barrier precautions of VRE are required at ICU with high colonization rate of VRE and shall be beneficial.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Cross Infection; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Infection Control; Intensive Care Units; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multilocus Sequence Typing; Taiwan; Tigecycline; Vancomycin; Vancomycin Resistance; Vancomycin-Resistant Enterococci

Topics: Anti-Bacterial Agents; Child; Cross Infection; Drug Resistance, Bacterial; Enterococcus faecium; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acetamides; Daptomycin; Gram-Positive Bacterial Infections; Humans; Minocycline; Oxazolidinones; Vancomycin-Resistant Enterococci

Topics: Acetamides; Daptomycin; Gram-Positive Bacterial Infections; Humans; Minocycline; Oxazolidinones; Vancomycin-Resistant Enterococci

Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of the three pairs were sensitive to tigecycline [minimum inhibitory concentration (MIC) of 0.125 mg/L]. Following tigecycline therapy, the second isolate in each pair demonstrated increased resistance to tigecycline. Two isolates (1R and 2R) were resistant (MIC of 8 mg/L) and one isolate (3I) demonstrated reduced susceptibility (MIC of 0.5 mg/L). Mutations distinguishing each pair of sensitive and resistant isolates were determined through alignment to a reference genome and variant detection. In addition, a de novo assembly of each isolate genome was constructed to confirm mutations. A total of 16 mutations in eleven coding sequences were determined. Mutations in the rpsJ gene, which encodes a structural protein forming part of the 30S ribosomal subunit, were detected in each of the pairs. Mutations were in regions proximal to the predicted tigecycline-binding site. Predicted amino acid substitutions were detected in 1R and 3I. The resistant strains were additionally associated with deletions of 15 nucleotides (2R) and 3 nucleotides (1R). This study confirms that amino acid substitutions in rpsJ contribute towards reduced susceptibility to tigecycline and suggests that deletions may be required for tigecycline resistance in E. faecium.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; DNA, Bacterial; Drug Resistance, Bacterial; Enterococcus faecium; Genome, Bacterial; Gram-Positive Bacterial Infections; Microbial Sensitivity Tests; Minocycline; Molecular Sequence Data; Ribosomal Proteins; Sequence Analysis, DNA; Sequence Deletion; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum β-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC90 (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.

Topics: Africa; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle East; Minocycline; Tigecycline

Topics: Acne Vulgaris; Anti-Bacterial Agents; Benzoyl Peroxide; Dermatologic Agents; Doxycycline; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Isotretinoin; Minocycline; Propionibacterium acnes; Zinc

Tetracycline class agents vary widely in their activity against emerging important antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter spp. Also, published susceptibility breakpoints are discordant between the Clinical and Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and regulatory-approved documents. We have assessed the impact of these differences for tetracycline HCL and minocycline when tested against contemporary Gram-positive pathogens. The SENTRY Antimicrobial Surveillance Program (2011) compared minocycline and tetracycline HCL activity via reference methods (M07-A9) using a worldwide collection of S. aureus (SA; 4917 strains with 1955 MRSA), Streptococcus pneumoniae (SPN; 1899), S. pyogenes (GRA; 246), and S. agalactiae (GRB; 217). Regardless of applied categorical breakpoints, minocycline exhibited wider coverage (% susceptible) than tetracycline HCL of 4.5-11.8/0.5-2.6/1.4-2.3/0.4-0.4% for MRSA/SPN/GRB/GRA, respectively. Lower EUCAST susceptible breakpoints produced reduced susceptibility rates for minocycline ranging from no difference (≤0.5 μg/mL) for GRA to -8.9% (≤1 μg/mL) for MRSA (97.2% susceptible by CLSI; 88.3% by EUCAST). Use of tetracycline HCL-susceptible results to predict minocycline susceptibility was very accurate (99.0-100.0%), with absolute categorical agreement rates ranging from 92.1% to 98.4% (CLSI) to 98.4% to 99.6% (EUCAST) for streptococci; greatest predictive error was noted using the CLSI breakpoints (14.7%) compared to EUCAST criteria (only 5.0%; acceptable), both for MRSA testing dominated by false-resistant results for minocycline. In conclusion, minocycline demonstrates continued superior in vitro activity compared to tetracycline HCL when testing SA (especially MRSA) and pathogenic streptococci. When testing tetracyclines, laboratories must recognize the expanded spectrum of minocycline against certain pathogens and utilize methods minimizing interpretive error. We conclude that EUCAST breakpoint criteria (≤0.5 or ≤1 μg/mL) represent the most conservative (better recognize strains with tet resistance mechanisms) and accurate tetracycline breakpoint guidelines for testing contemporary isolates of Gram-positive cocci.

Topics: Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcus aureus; Streptococcus; Tetracycline

Intra-abdominal infection (IAI) is a frequent complication found in surgical intensive care unit (SICU) and continues to be associated with considerable mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad spectrum of activity against a wide range of bacteria commonly found in IAI. This observational retrospective study aimed to describe the experience with tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23 consecutive patients admitted to SICU with serious nococomial IAI who had received empirical treatment with tigecycline. In all cases, IAI was diagnosed via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed septic shock. Oncological disease was the most common comorbidity (60%). The mean Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis was 57.5±14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus spp. (30.4%, respectively). All but one patient received tigecycline in combination (95.7%), particularly with fluconazole (52.2%), followed by piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered adequate in 95%. The mean duration of treatment was 8.5±4.5 days. A favorable response was achieved in 78%. Failure of the antibiotic therapy was not observed in any patient. None of the patients discontinued tigecycline due to adverse reactions. SICU mortality was 13%, with no deaths attributable to tigecycline. These findings suggest that tigecycline combination therapy is an effective and well tolerated empirical treatment of serious nosocomial IAI in the SICU.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Critical Care; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Postoperative Complications; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

We evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log10-CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gentamicins; Gram-Positive Bacterial Infections; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Rabbits; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) commenced in 2004 to longitudinally monitor global changes in bacterial susceptibility to a suite of antimicrobial agents. The current study examined the activity of tigecycline and comparators against isolates collected across Eastern Europe between 2004 and 2010. Minimum inhibitory concentrations were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodologies. Antimicrobial susceptibility was determined using CLSI interpretive criteria, and tigecycline susceptibility was established using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. This study included 10 295 Gram-negative and 4611 Gram-positive isolates from 42 centres. Extended-spectrum β-lactamases (ESBLs) were reported among 15.3% of Escherichia coli and 39.3% of Klebsiella pneumoniae isolates; the highest rates were observed in Turkey (30.9%) and Bulgaria (53.8%), respectively. Imipenem-non-susceptible K. pneumoniae were identified only in Turkey. ESBL-positive E. coli were highly susceptible to imipenem (95.1%), meropenem (98.0%) and tigecycline (98.5%). Most antimicrobials showed poor activity against Acinetobacter baumannii and Pseudomonas aeruginosa. Vancomycin resistance was noted among 0.9% of Enterococcus faecalis and 11.7% of Enterococcus faecium isolates. High rates of susceptibility were reported for linezolid (99.7%) and tigecycline (100%) against E. faecium. One-quarter of Staphylococcus aureus isolates were meticillin-resistant S. aureus (MRSA), with the highest rate in Romania (51.5%); all MRSA were susceptible to linezolid, tigecycline and vancomycin. Antimicrobial resistance is high in much of Eastern Europe, with considerable variation seen among countries. Tigecycline and the carbapenems retain excellent activity against many pathogens from Eastern Europe; linezolid and vancomycin are active against most Gram-positive pathogens.

Topics: Anti-Bacterial Agents; Europe, Eastern; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (TEST) was designed to monitor global longitudinal changes in bacterial susceptibility to a panel of antimicrobial agents, including tigecycline. In this study, we examine susceptibility among Gram-positive isolates collected from pediatric patients globally between 2004 and 2011. A total of 9,422 Gram-positive isolates were contributed by 1,255 centers, predominantly from Europe and North America. One-third of Staphylococcus aureus isolates were methicillin resistant, peaking in prevalence in 2007. All S. aureus isolates (n = 3,614) were susceptible to linezolid, tigecycline, and vancomycin; minocycline, imipenem, and meropenem were also highly active (>92% susceptibility). Ampicillin and penicillin susceptibility increased significantly during the study period (P < 0.0001 for both). Streptococcus pneumoniae isolates (n = 3,373) were highly susceptible to vancomycin (100%), linezolid (>99%), and levofloxacin and tigecycline (both >96%); imipenem susceptibility was low (32%) in Africa while minocycline susceptibility was low in Asia-Pacific Rim (38%). Penicillin resistance occurred in one-fifth of all S. pneumoniae isolates, with penicillin susceptibility ranging from 14% in Africa to 65% in Europe. Streptococcus agalactiae isolates (n = 1,056) were highly susceptible to most antimicrobials, although only 16% were susceptible to minocycline. Enterococcus faecalis isolates (n = 1,112) were highly susceptible (>97%) to ampicillin, linezolid, penicillin, tigecycline, and vancomycin globally, but only 34% were minocycline susceptible; minocycline susceptibility decreased significantly from 2004 to 2011 (P < 0.001). Tigecycline and linezolid were highly active against Enterococcus faecium (n = 267) globally (100% and 98% susceptible, respectively). Tigecycline and linezolid were highly active against Gram-positive pathogens from pediatric patients in TEST 2004 to 2011, with vancomycin and the carbapenems performing well against most pathogens.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Female; Global Health; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Microbial Sensitivity Tests; Minocycline; Tigecycline

We investigated the efficacy of tigecycline and rifampin alone or combined in preventing ureteral stent infection due to Enterococcus faecalis.. The activities of the two antibiotics were previously studied in vitro in absence or in presence of biofilm. For in vivo research, the study included a control group without bacterial challenge to evaluate the sterility of surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and, for each bacterial strain, three challenged groups that received: (1) 2 mg/kg intraperitoneal tigecycline, immediately after stent implantation; (2) rifampin-coated ureteral stents where 0.2 cm(2) sterile ureteral stents were incubated in 10 mg/L rifampin solution for 30 min immediately before implantation; and (3) intraperitoneal tigecycline plus rifampin-coated ureteral stent at the above concentrations. Ureteral stents were explanted at d 5 following implantation and biofilm bacteria enumerated.. The in vitro studies showed that the biofilm was strongly affected by the presence of rifampin and, in its presence, tigecycline had MICs and MBCs lower than those obtained in the absence of rifampin. Intraperitoneal tigecycline exerted stronger effect than rifampin on bacterial numbers. The combination rifampin plus tigecycline showed efficacies higher than that of each single compound.. These results highlight the potential usefulness of tigecycline in preventing enterococcal ureteral stent infections and the role of rifampin as an interesting antibiotic enhancer.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biofilms; Disease Models, Animal; Drug Therapy, Combination; Enterococcus faecalis; Female; Gram-Positive Bacterial Infections; In Vitro Techniques; Minocycline; Rats; Rats, Wistar; Rifampin; Stents; Tigecycline; Treatment Outcome; Ureter

Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option.. We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant Lactobacillus rhamnosus. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy.. Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Drug Resistance, Multiple, Bacterial; Female; Gram-Positive Bacterial Infections; Humans; Lacticaseibacillus rhamnosus; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

The aim of this work was to determine the in vitro activity of tigecycline and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with six clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 10(7) colony-forming units (CFU) of Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, three groups singly treated with tigecycline, rifampin, and daptomycin, and two groups that received tigecycline treatment plus rifampin or daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin were active against all of the 48 Gram-positive isolates. The combination of tigecycline with rifampicin and daptomycin was synergistic against S. aureus and Enterococcus spp. In the in vivo studies, all groups treated with single drugs showed statistically significant results compared to the control group. The two groups treated with a combination of drugs showed the highest antimicrobial efficacy. In conclusion, our results suggested a strong activity of tigecycline alone and in combination with other antimicrobial agents against multi-resistant Gram-positive organisms isolated from wound infections.

Topics: Animals; Anti-Bacterial Agents; Daptomycin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Rifampin; Surgical Wound Infection; Tigecycline; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Male; Microbial Sensitivity Tests; Minocycline; Omeprazole; Postoperative Complications; Tigecycline

A total of 10948 clinical isolates was collected throughout the Asia-Pacific region as part of the Tigecycline Evaluation Surveillance Trial (TEST) during 2004-2010, consisting of 7549 Gram-negative and 3399 Gram-positive pathogens. Susceptibility trends for all species demonstrated several significant species-dependent susceptibility changes to multiple antibiotics. The most notable was minocycline, for which significant decreases in susceptibility (P<0.001) were observed for six of the ten species studied. In contrast, statistically significant susceptibility changes for tigecycline were observed in only two of the ten species, namely Klebsiella pneumoniae and Serratia marcescens. Seven years following the introduction of tigecycline into clinical use, this agent remains highly active against a wide range of pathogens from the Asia-Pacific region.

Topics: Anti-Bacterial Agents; Asia; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Population Surveillance; Species Specificity; Tigecycline

Criteria of tigecycline (Tygacil) use for the treatment of surgical site infections in oncologic inpatients were developed. High efficacy of tigecycline in vitro and in vivo against multiresistant hospital strains persistent in the surgical department of the gastrointestinal oncologic division was shown.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Neoplasms; Surgical Wound Infection; Tigecycline

To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline's activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Germany; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Young Adult

Propionibacterium acnes plays an important role in the development of acne, and inflammatory lesions are improved by antibiotics. Long-term use of antibiotics may result in development of resistant strains and treatment failure. The aim of the present study was to investigate the isolation rate of P. acnes and to evaluate its antibiotic susceptibility to widely used antibiotics in acne in Korea. Among 46 patients, 31 P. acnes strains were cultured. Isolated P. acnes was measured for minimum inhibitory concentration (MIC) of tetracycline, doxycycline, minocycline, erythromycin and clindamycin using an Epsilometer test. Age, disease duration and previous history of antibiotic therapy for acne were compared in relation to the MIC. The mean MIC of tetracycline, minocyclines, doxycycline, clindamycin and erythromycin were all below the breakpoint of antibiotic resistance. The patients with acne vulgaris with disease duration of more than 2 years documented higher MIC values in doxycycline, erythromycin, and clindamycin than those of less than 2 years. The patients who were previously treated with topical or systemic antibiotics showed higher MIC in doxycycline. Antibiotic resistance of P. acnes is still low in Korea, but at this point, there is an increasing trend of MIC. Caution and acknowledgement of increased risk of antibiotic resistant P. acnes should be advised in acne antibiotic treatment to minimize and avoid the emergence of the resistant strain.

Topics: Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Child; Clindamycin; Doxycycline; Drug Resistance, Microbial; Erythromycin; Female; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Male; Microbial Sensitivity Tests; Minocycline; Propionibacterium acnes; Republic of Korea; Tetracycline; Young Adult

Although polymicrobial infections, such as peri-implantitis or periodontitis, were postulated in the literature to be caused by synergistic effects of bacteria, these effects remain unclear looking at antibiotic susceptibility. The aim of this study is to compare the antibiotic susceptibilities of pure cultures and definite cocultures.. Laboratory strains of Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), Capnocytophaga ochracea (Co), and Parvimonas micra (Pm) (previously Peptostreptococcus micros) were cultivated under anaerobic conditions, and their susceptibilities to 10 antibiotics (benzylpenicillin G, ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, minocycline, metronidazole, linezolid, azithromycin, and moxifloxacin) were tested using the Epsilometertest. Cocultures, each consisting of two or three bacteria, were treated analogously.. All four cocultures showed lower susceptibilities to azithromycin and minocycline than to pure cultures. The coculture Aa-Co showed a lower susceptibility to moxifloxacin as did the coculture Aa-Pm to benzylpenicillin G; the coculture Co-Pm showed a lower susceptibility to amoxicillin, amoxicillin/clavulanic acid, metronidazole, and benzylpenicillin G. However, the coculture Co-Pm showed a higher susceptibility to ampicillin, linezolid and moxifloxacin as did Aa-Pm and Aa-Co-Pm to linezolid.. In addition to established in vitro assays, it was demonstrated that antimicrobial cocultures caused antibiotic susceptibilities that differed from those of pure cultures. Bacterial cocultures frequently showed lowered susceptibilities to antibiotics.

Topics: Acetamides; Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Capnocytophaga; Coculture Techniques; Coinfection; Drug Resistance, Bacterial; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Linezolid; Metronidazole; Microbial Interactions; Minocycline; Moxifloxacin; Oxazolidinones; Penicillin G; Peptostreptococcus; Peri-Implantitis; Periodontitis; Quinolines; Sulbactam

This study reports the antimicrobial activity of tigecycline and comparator antimicrobials, including linezolid, against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) between 2004 and 2009. Minimum inhibitory concentrations (MICs) were determined using broth microdilution methodology according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Antimicrobial susceptibility was determined according to CLSI criteria. For tigecycline, the US Food and Drug Administration (FDA)-approved criteria were used. Overall, 41.3% (8249/19 982) of S. aureus collected were meticillin-resistant S. aureus (MRSA). All MRSA were susceptible to linezolid and 99.98% were susceptible to tigecycline. A total of 2.3% of E. faecalis (201/8576) and 39.7% of E. faecium (1226/3088) were vancomycin-resistant. Linezolid and tigecycline MIC(90) values (MIC at which 90% of isolates inhibited) against the Enterococcus spp. were 2mg/L and ≤ 0.25 mg/L, respectively. All S. pneumoniae [including 6.2% (599/9618) penicillin-non-susceptible] were susceptible to linezolid and vancomycin; tigecycline MIC(90) values were ≤ 0.12 mg/L. This report demonstrates the continuing good activity of tigecycline and linezolid against Gram-positive isolates globally, including resistant organisms such as MRSA, vancomycin-resistant enterococci and penicillin-resistant S. pneumoniae, with antimicrobial activity maintained over the 6 years of isolate collection.

Topics: Acetamides; Anti-Bacterial Agents; Czech Republic; Enterococcus; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcus aureus; Streptococcus pneumoniae; Tigecycline

In this study, the in vitro activity of tigecycline against 1140 enterococci collected from humans, food products, animals and the environment in Portugal (1996-2008) was analysed. Ten isolates (seven Enterococcus faecalis and three Enterococcus spp.) non-susceptible to tigecycline (minimum inhibitory concentrations of 0.5-1.0 mg/L), which were also resistant to tetracycline and minocycline, were mostly observed in samples collected before the introduction of tigecycline in the therapeutic arsenal. The E. faecalis isolates were recovered from hospitalised patients (n=2; ST319/CC2 and ST34), healthy humans (n=2; ST21/CC21), chicken meat (n=1; ST260) as well as from two swine samples. The remaining isolates were also recovered from chicken meat (n=1; Enterococcus gallinarum) and swine (n=2; Enterococcus hirae and Enterococcus spp.). Recovery of enterococcal isolates with reduced susceptibility to tigecycline amongst different reservoirs, including animals for food consumption, suggests that selection of tigecycline-resistant isolates by antibiotics other than tigecycline might occur in non-clinical settings.

Topics: Animals; Anti-Bacterial Agents; Carrier State; Chickens; Enterococcus; Gram-Positive Bacterial Infections; Hospitals; Humans; Meat; Microbial Sensitivity Tests; Minocycline; Portugal; Swine; Tetracycline; Tigecycline

Topics: Aged, 80 and over; Bacteremia; Daptomycin; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Tigecycline; Vancomycin Resistance

The Tigecycline Evaluation and Surveillance Trial (TEST) was initiated in 2004 to chart the activity of tigecycline and comparator antimicrobial agents against gram-positive and gram-negative organisms globally.. This study aimed to provide an analysis of the antimicrobial susceptibility of gram-positive organisms collected from the 9 census regions of the United States between 2004 and 2009.. The MICs and antimicrobial susceptibility were determined using Clinical and Laboratory Standards Institute methodology. For tigecycline, US Food and Drug Administration susceptibility criteria were used.. A total of 8782 Staphylococcus aureus isolates (54.5% methicillin-resistant S aureus) were collected, with the highest percentage of MRSA isolates collected from the South Central region (67.9%). All S aureus isolates were susceptible to tigecycline, linezolid, and vancomycin. Overall, 4.6% of Enterococcus faecalis (n = 3753) and 69.1% of Enterococcus faecium (n = 1417) isolates were vancomycin resistant, with the highest rates in the East North Central region for E faecalis (7.1%) and the South Atlantic region for E faecium (79.5%). Small numbers of linezolid nonsusceptible E faecalis (n = 13) were identified. MIC(90) values for tigecycline were ≤0.25 mg/L against E faecalis and 0.12 mg/L against E faecium. Of the Streptococcus pneumoniae isolates collected (n = 4541), 1.1% were penicillin resistant. All S pneumoniae isolates were susceptible to linezolid and vancomycin; susceptibility to tigecycline varied between 80.9% (Pacific region) and 95.2% (West North Central region).. The rates of MRSA and vancomycin-resistant Enterococcus spp varied among the 9 census regions; however, susceptibility to linezolid, vancomycin, and tigecycline remained consistent, with low MIC(90) values and high rates of antimicrobial susceptibility.

Topics: Acetamides; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Streptococcus pneumoniae; Tigecycline; Treatment Outcome; United States; Vancomycin Resistance

Activity of tigecycline against nosocomial secondary peritonitis isolates collected along 18 months in 29 Spanish hospitals was tested by Etest in a central laboratory, considering Food and Drug Administration (FDA)/British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A total of 600 facultative/aerobic isolates (392 Gram negative, 208 Gram positive) and 100 anaerobes were tested. None of the 220 Escherichia coli isolates was resistant to tigecycline (MIC(50)/MIC(90) = 0.25/0.5 microg/mL), with 0.5% (FDA breakpoint) and 3.6% (BSAC/EUCAST breakpoint) intermediate strains. All Extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (15 strains), all Klebsiella pneumoniae, and Klebsiella oxytoca isolates (42 strains) were susceptible to tigecycline. No isolates resistant to tigecycline were found among Streptococcus viridans, Staphylococcus aureus, and Enterococcus faecium, but 18.9% of Enterococcus faecalis strains were intermediate following BSAC/EUCAST breakpoints. All (but 1) isolates of the Bacteroides fragilis group (n = 45) were tigecycline susceptible, as well as Gram-positive anaerobes. Tigecycline offers an adequate activity profile against isolates from secondary peritonitis when tested by Etest regardless of the breakpoints used for categorization.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Cohort Studies; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Peritonitis; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Vancomycin-resistant enterococci (VRE) have emerged to become a significant nosocomial pathogen. However, detection may be challenging and treatment possibilities are limited. Reports of resistance to linezolide, daptomycin and tigecycline underline the need for reliable susceptibility testing with respect to these compounds. We evaluated the in vitro activity of vancomycin, linezolid, daptomycin and tigecycline against a panel of VRE and vancomycin-susceptible enterococci by broth microdilution (BMD). Etest for determination of minimum inhibitory concentration of these four antibiotics and two disc diffusion assays for detecting VRE and for susceptibility testing against tigecycline and linezolid were evaluated. Before susceptibility testing, all isolates were classified by polymerase chain reaction as vanA or vanB gene positive or vanA/B gene negative. Linezolid, daptomycin and tigecycline had excellent in vitro activity towards all isolates. For daptomycin and tigecycline, the overall agreement between BMD and Etest was suboptimal. For both disc diffusion assays, use of current break points was inadequate to detect vancomycin resistance for isolates carrying the vanB gene. Inspection of the inhibition zone for a diffuse edge, as recommended, accurately predicted presence of the vanB gene.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Daptomycin; DNA, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Polymerase Chain Reaction; Reproducibility of Results; Tigecycline; Vancomycin; Vancomycin Resistance

To determine the in vitro activity of tigecycline and comparator common use antimicrobial agents tested against contemporary bacterial pathogens from the Asia-Western Pacific region.. As part of the SENTRY Antimicrobial Surveillance Program, a total of 5759 Gram-positive and Gram-negative isolates were collected from 28 medical centers in eight Asia-Western Pacific countries during 2008. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution method and interpreted using CLSI breakpoints. United States Food and Drug Administration (US-FDA) breakpoints were used to interpret tigecycline susceptibility.. Antimicrobial resistance was found to be widespread and prevalence varied considerably between the eight countries. Against pathogens for which breakpoints were available, >98% of all isolates were susceptible to tigecycline. Against all Gram-positive isolates, including methicillin (oxacillin)-resistant Staphylococcus aureus, penicillin- and multidrug-resistant pneumococci, and vancomycin-resistant enterococci, the highest tigecycline MIC found was 1 microg/ml. Against all Enterobacteriaceae, including extended-spectrum beta-lactamase phenotypes, tigecycline susceptibility was 97.5%. Tigecycline had good activity against Acinetobacter spp. but was much less active against Pseudomonas aeruginosa.. Tigecycline demonstrated excellent sustained in vitro activity against a wide spectrum of contemporary Gram-positive and -negative pathogens from Asia-Western Pacific countries.

Topics: Anti-Bacterial Agents; Asia, Eastern; Asia, Southeastern; Australia; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; New Zealand; Sentinel Surveillance; Tigecycline

A total of 206 clinical isolates of Finegoldia magna were collected during the period 2007-2009 from six European countries. The majority of isolates were from body fluids (n = 83; 40.3%) or wounds (n = 82; 39.8%). All isolates were susceptible to tigecycline, meropenem, metronidazole and piperacillin / tazobactam, though susceptibility to penicillin (86.4-87.4%) and clindamycin (78.2-93.3%) were more variable.

Topics: Anti-Bacterial Agents; Body Fluids; Europe; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; Wounds and Injuries

Topics: Amylases; Anti-Bacterial Agents; Child; Enterobacter cloacae; France; Gram-Positive Bacterial Infections; Humans; Lipase; Male; Minocycline; Pancreatitis, Acute Necrotizing; Sepsis; Tigecycline

The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacterial Infections; Computational Biology; Daptomycin; Drug Delivery Systems; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Forecasting; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Minocycline; Oxazolidinones; Pharmacogenetics; Systems Biology; Tigecycline; Virginiamycin

A multicentre surveillance of tigecycline activity against relevant pathogens in the UK.. Forty-three representative UK hospitals were each asked to test 150 consecutive, clinically significant isolates from hospitalized patients, excluding those from urine or faeces. The sentinel laboratories tested all these isolates against a panel of antibiotics by the BSAC disc method and a selection of isolates were retested centrally by the BSAC agar dilution method.. The isolates collected comprised Staphylococcus aureus (39.9%), Escherichia coli (13.3%), streptococci (11.9%), enterococci (6.3%), Klebsiella (6.1%), coagulase-negative staphylococci (6.1%), Enterobacter spp. (3.9%), Proteus spp. (2.2%) and other Gram-negative species (10.3%). The laboratories' disc susceptibility testing found that 4% of isolates were resistant to tigecycline, using the zone breakpoints in place at that time. However, centralized retesting by agar dilution showed that many of these 'resistant' isolates were susceptible, with resistance only confirmed in a range of Gram-negative isolates and one S. aureus. These findings reduced the estimated resistance rate to 2.4%, or to 0.8% if Proteus spp. were ignored as intrinsically resistant to tigecycline. Sixty-two percent of the isolates found resistant by the disc method but susceptible by agar dilution had zones of inhibition within experimental error (4 mm) of the published breakpoints.. Tigecycline resistance was rare in isolates causing clinically significant infections in the UK and was overestimated ∼2-fold by the BSAC disc method. Adjustment of the breakpoints might overcome this problem but at the risk of increasing the false susceptibility rate. The best advice is to perform dilution tests, e.g. by gradient strip test on isolates with borderline results, especially in severe infection and when tigecycline use is intended.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Sentinel Surveillance; Tigecycline; United Kingdom

Bacterial infections in patients with hematological neoplasms carry high morbidity and mortality. Gram-positive microorganisms can cause more than half of the bacterial infections in patients with febrile neutropenia, especially bacteremias. Effective coverage against these infections in these hosts, especially the immunodepressed, is required.. We reviewed the literature published in the last decade on infections in patients with hematological malignancies, with or without febrile neutropenia. Emphasis was placed on publications analyzing the processes caused by Gram-positive microorganisms and the management of these infections (whether bacteremic or otherwise) through traditional drugs (glycopeptides) and the new antibiotics (linezolid, tigecycline and daptomycin).. There was a notable scarcity of studies on the treatment of infections due to Gram-positive microorganisms in patients with cancer through treatment with the new antimicrobial drugs. Especially striking was the lack of comparative studies. Specifically, in the case of daptomycin, there were no randomized comparative trials in patients with febrile neutropenia, although there were observational retrospective studies or case studies [European Cubicin(®) Outcome Registry and Experience (EUCORE)] with a large number of patients (around 200) with oncological malignancies. In the three main studies, the overall favorable response rates were between 65% and 90%, with a therapeutic success rate of 85% in patients with severe febrile neutropenia. At the same time, the safety profile of daptomycin was shown to be highly favorable with good tolerability and a low rate of adverse effects (< 10% for those directly related to the antibiotic) which, on very few occasions, were severe or led to treatment withdrawal. The nephrotoxicity rate was much lower than that caused by vancomycin in historical control groups, although there were no statistically significant differences.. Daptomycin is a safe and effective therapeutic alternative in the treatment of bacterial infections due to Gram-positive microorganisms in patients with cancer, with or without neutropenia. However, further studies are required to support the use of this drug in the empirical treatment of febrile neutropenia.

Topics: Acetamides; Anti-Bacterial Agents; Antineoplastic Agents; Daptomycin; Databases, Factual; Europe; Glycopeptides; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Immunocompromised Host; Kidney Diseases; Linezolid; Microbial Sensitivity Tests; Minocycline; Multicenter Studies as Topic; Neutropenia; Oxazolidinones; Registries; Retrospective Studies; Risk Factors; Tigecycline; Treatment Outcome

As part of the Tigecycline Evaluation and Surveillance Trial (TEST), Gram-negative and Gram-positive organisms were collected from 31 medical centres in nine countries in the Asia-Pacific Rim between 2004 and 2007. Overall, 34.2% of Acinetobacter spp. were multidrug-resistant, and 17.0% of Klebsiella pneumoniae and 10.6% of Escherichia coli produced extended-spectrum beta-lactamases. A total of 39.5% of Staphylococcus aureus were meticillin-resistant and 21.7% of Enterococcus faecium were vancomycin-resistant. Tigecycline MIC(90) values (minimum inhibitory concentration for 90% of the organisms) were

Topics: Anti-Bacterial Agents; Asia; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Oceania; Tigecycline; Vancomycin Resistance

Tigecycline is a broad-spectrum antimicrobial agent that has been approved for the treatment of skin and soft-tissue infections as well as intra-abdominal infections. The Tigecycline Evaluation and Surveillance Trial (TEST) is a global, longitudinal surveillance study established in 2004 to monitor the in vitro activity of tigecycline and comparator agents against key Gram-negative and Gram-positive pathogens. This report examines data obtained for 24748 isolates collected across 24 European countries between 2004 and 2007. Tigecycline, meropenem and imipenem were the most active antimicrobial agents against most Gram-negative isolates including multidrug-resistant Acinetobacter baumannii (15.7% of the A. baumannii isolates in this study), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (8.5% of E. coli) and ESBL-producing Klebsiella pneumoniae (13.6% of K. pneumoniae). Only amikacin was active against >90% of Pseudomonas aeruginosa isolates (92.8% susceptible). Tigecycline, linezolid and vancomycin were the most active agents against Gram-positive agents across Europe between 2004 and 2007, with tigecycline displaying the lowest MIC(90) values (minimum inhibitory concentration for 90% of the organisms) against meticillin-resistant Staphylococcus aureus (26.5% of the collected S. aureus isolates), vancomycin-resistant Enterococcus faecium (15.7% of the E. faecium strains) and penicillin-resistant Streptococcus pneumoniae (9.3% of the S. pneumoniae strains). Longitudinal analysis showed no increase in tigecycline MIC values over the 4-year study period, whilst increased resistance was noted for several comparator agents.

Topics: Anti-Bacterial Agents; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Tigecycline

In the last years, the increase of antibiotic resistances of gram-positive and gram-negative bacteria is an important therapeutic problem. The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 750 bacterial isolates from 30 centers in Spain.. Multicenter and retrospective study. In 2005, thirty laboratories participated in this study. Data collected in this study included antimicrobial susceptibilities for S.aureus resistant to methicillin (MRSA), ESBL- E. coli or ESBL- K. pneumoniae, E. coli resistant to quinolons (E.coli- QR), Klebsiella spp and E. faecalis. Trains were obtained of the each Hospital s collection (5 strains of each microorganisms). The susceptibility determinations were performed locally by each laboratory following the standard method usually performed. The tigecycline susceptibility determinations were performed with E/test.. Tigecycline was the most potent agent against MRSA, E. faecalis, E.coli-QR and ESBLs enterobacteriaceae; with MIC50-MIC90 values of: 0.125-0.25 g/ml; 0.125-0.5 g/ml; 0.25-0.75 g/ml and 0.38-1.5 g/ml; respectively.. The results of this study confirm the excellent in vitro activity of tigecycline against gram-positive and gram-negative pathogens, including multirresistant microorganisms.

Topics: Anti-Bacterial Agents; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Klebsiella; Laboratories, Hospital; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Retrospective Studies; Spain; Tigecycline

Although earlier pleuromutilin analogues showed potent in vitro antibacterial activity against some Gram-positive pathogens, their in vivo efficacy was low because of insufficient pharmacokinetic properties. We designed novel thioether pleuromutilin derivatives having a purine ring as a polar and water solubilizing group and identified a promising pleuromutilin analogue 6 with good solubility in water ( approximately 50 mg/mL). Compound 6 exhibited excellent in vitro and in vivo antibacterial activity against some Gram-positive strains, including drug-resistant pathogens.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Drug Design; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Molecular Structure; Pleuromutilins; Polycyclic Compounds; Solubility; Stereoisomerism; Water

Topics: Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Greece; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria in Taiwan. This study, part of TIST-2006 study, aimed to compare the in-vitro activity of tigecycline against clinical isolates of Gram-positive bacteria. A total of 805 isolates of Gram-positive bacteria were collected from patients treated at 20 teaching hospitals. Minimum inhibitory concentrations (MICs) of tigecycline for these isolates were determined by the broth microdilution method according to the guidelines of the Clinical and Laboratory Standards Institute, and by the Etest as per the manufacturer's instructions. Susceptibility results were interpreted by the MIC criteria recommended by the US FDA. Agreement between the two methods was low: 80.7% for methicillin-resistant Staphylococcus aureus (MRSA), 27.2% for Streptococcus pneumoniae, 22.8% for other Streptococcus spp., and 30.8% for vancomycin-resistant E. faecium (VRE). There were no very major or major errors noted. Tigecycline exhibited excellent in-vitro activity against Gram-positive cocci, including MRSA, VRE, S. pneumoniae and other Streptococcus spp. isolates in Taiwan. Correlation between MIC values determined using the broth microdilution and Etest methods for these organisms was poor.

Topics: Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Taiwan; Tigecycline

Tigecycline activity was evaluated against 11808 pathogens isolated from 30 US medical centers. Susceptibility testing was performed by reference broth microdilution methods. Tigecycline (MIC(50/90), 0.12/0.25 microg/mL) was highly active against Staphylococcus aureus and coagulase-negative staphylococci, regardless of oxacillin resistance. This glycylcycline (MIC(50), 0.12 microg/mL) was 8- and 16-fold more potent than penicillin and linezolid against enterococci and was the most potent agent tested versus Streptococcus pneumoniae. Against Enterobacteriaceae, tigecycline (MIC(90), 1 microg/mL; 98.9% susceptible) was as active as imipenem. This study demonstrated the sustained potency of tigecycline against contemporary clinically relevant Gram-positive and Gram-negative pathogens; tigecycline resistance was rare (0.3%).

Topics: Anti-Bacterial Agents; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; United States

In this study (part of the global TEST program), the in vitro activity of tigecycline, a member of a new class of antimicrobial agents, the glycylcyclines, against clinical isolates collected in Italy was evaluated.. A total of 200 clinical isolates were collected and identified in our institution during 2005. Minimum inhibitory concentrations (MICs) of the antimicrobial agents were determined by the broth microdilution method recommended by the CLSI in 2005.. Globally, 135 Gram-negative and 65 Gram-positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli, Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae with MIC(90)

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Italy; Microbial Sensitivity Tests; Minocycline; Tigecycline

In-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin, linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria were determined using the broth microdilution method for ten blood isolates each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was tested in a time-kill synergism assay of daptomycin combined with oxacillin, imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro bactericidal activity against all the isolates tested, with no tolerance or synergism effects when combined with other agents, except with rifampicin against VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did teicoplanin. Linezolid had the poorest bactericidal activity against the isolates tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90% of the vancomycin-resistant E. faecium isolates.

Topics: Acetamides; Anti-Infective Agents; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Glycopeptides; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcus aureus; Streptococcaceae; Taiwan; Teicoplanin; Tigecycline; Time Factors; Vancomycin

As part of the tigecycline evaluation and surveillance trial (TEST), bacterial isolates were collected from 39 centres in France, Germany, Italy, Spain and the UK between January 2004 and August 2006. Antimicrobial susceptibilities were determined according to CLSI guidelines. Italy had the highest rate of methicillin-resistant Staphylococcus aureus (36.4%), and was the only country to report vancomycin-resistant Enterococcus faecalis (8.6%). Tigecycline was the only agent to which all Gram-positive isolates were susceptible. For many of the Gram-negative organisms collected, antimicrobial susceptibilities were lowest among isolates from Italy and highest among isolates from Spain. The notable exception was Acinetobacter baumannii, where the poorest susceptibility profile was among isolates from Spain. For A. baumannii, MIC(90)s of imipenem varied from 1 mg/L for isolates in France and Germany to > or =32 mg/L for isolates from Italy and Spain. Tigecycline was the only agent to maintain an MIC(90) of < or =1 mg/L against isolates from all five countries. The in-vitro activity of tigecycline against both Gram-positive and Gram-negative isolates may make it valuable in the treatment of hospital infections, including those caused by otherwise antimicrobial-resistant organisms.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Population Surveillance; Tigecycline

In clinical trials tigecycline was similar to vancomycin/aztreonam for complicated skin and skin structure infections, but data comparing it with other widely used antibiotics are lacking. We predicted the pharmacodynamic cumulative fraction of response (CFR) of tigecycline against bacteria implicated in complicated skin and skin structure infections and compared it with the CFRs for piperacillin/tazobactam, ceftriaxone, levofloxacin, and imipenem/cilastatin.. A 5,000-patient Monte Carlo simulation using a two-compartment intravenous infusion model was used to simulate steady-state concentrations for common dosages of these antibiotics. Population pharmacokinetics data from infected patients were employed. The CFR was calculated against Staphylococcus aureus (42% methicillin-resistant S. aureus [MRSA]), streptococci, coagulase-negative staphylococci, Escherichia coli, Enterobacter, enterococci, Proteus mirabilis, Klebsiella, and Pseudomonas aeruginosa collected from worldwide surveillance (TEST and SENTRY) and weighted by prevalence of involvement in complicated skin and skin structure infections.. Excluding MRSA, the weighted CFR was greatest for imipenem/cilastatin and piperacillin/tazobactam regimens (93.9%-95.9%). With 42% MRSA added to the model, only tigecycline monotherapy achieved a high CFR (88.2%). The addition of vancomycin raised the CFR to 91.0%, 89.5%, 88.3%, 82.9%, and 78% for imipenem/cilastatin 500 mg q6h, imipenem/cilastatin 500 mg q8h, piperacillin/tazobactam, levofloxacin, and ceftriaxone regimens, respectively.. Tigecycline monotherapy had a likelihood of achieving its requisite pharmacodynamic exposure similar to that of combinations of piperacillin/tazobactam or imipenem/cilastatin plus vancomycin for the empiric treatment of complicated skin and skin structure infections.

Topics: Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Minocycline; Models, Statistical; Monte Carlo Method; Skin Diseases, Bacterial; Tigecycline

The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10x MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Quinolones; Thiazoles

Adequate antimicrobial therapy is of crucial importance for the survival of critically ill patients with severe nosocomial infections. Tigecycline is an important therapeutic option for the treatment of infections caused by multi-resistant Gram-positive and Gram-negative bacteria including vancomycin-resistant enterococci (VRE). A large randomised study (patients with APACHE-II-score >30 excluded/mean APACHE-II-score 6) demonstrated that tigecycline is not inferior to imipenem/cilastatin for treatment of complicated intra-abdominal infections. However, no case has been reported with microbiological eradication and clinical cure in a patient with septic shock due to peritonitis caused by VRE and treatment with tigecycline monotherapy. Clinical details of a patient suffering from postoperative peritonitis are presented. The patient developed severe septic shock after pancreatic surgery (multiple organ failure, APACHE-II-score 34). As the site of anastomotic leakage was very small and could not be exactly identified, irrigation-suction drains were placed followed by closed postoperative continuous lavage. The pathogen responsible was identified as a vancomycin-resistant Enterococcus faecium, therefore monotherapy with tigecycline was started which resulted in microbiological response and clinical cure. Tigecycline is a new therapeutic option for the treatment of intra-abdominal infections and from an economic point of view financially rewarding when used as monotherapy.

Topics: Anti-Bacterial Agents; APACHE; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pancreatitis; Peritonitis; Shock, Septic; Tigecycline; Vancomycin Resistance

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

Topics: Actinobacteria; Aged; Anti-Bacterial Agents; Critical Illness; Female; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tigecycline

We assessed the in vitro effect of exposing various bacteria to minocycline/rifampicin-impregnated vascular catheters on the antimicrobial activity of the catheters and the antimicrobial susceptibility of tested organisms.. Segments of minocycline/rifampicin-impregnated catheters were placed in agar plates inoculated with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus (VRE). Zones of inhibition were measured at 24 h, and colonies from the edge of this zone were retrieved after 72 h and inoculated onto new agar plates. A total of seven 72 h cycles were completed. We then measured the MICs of minocycline, rifampicin, vancomycin and linezolid for the collected strains.. The zones of inhibition of the four organisms remained stable after 21 days of sequential exposure to the impregnated catheters. The MICs of the antimicrobials remained constant, except for the MICs of rifampicin for MRSA and linezolid for MRSE, which increased slightly but remained within the susceptible range.. Minocycline/rifampicin-impregnated catheters remain effective against MSSA, MRSA, MRSE and VRE, as evidenced by stable zones of inhibition following 21 day sequential exposure to these catheters. The increase in MIC of rifampicin for MRSA may be clinically relevant if the catheter remains in place for >12 days though the strain remained susceptible to minocycline, there was no concurrent increase in the MIC of other tested drugs, and the zones of inhibition remained stable.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Drug Resistance, Bacterial; Equipment Contamination; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Time Factors

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Linezolid; Male; Middle Aged; Minocycline; Oxazolidinones; Tigecycline; Treatment Outcome; Vancomycin

Gram-positive isolates were collected from 76 medical centers within the 9 census regions across the United States.. Antimicrobial susceptibilities were determined according to Clinical and Laboratory Standards Institute guidelines.. Vancomycin resistance among Enterococcus faecium isolates varied from 45.5% (New England) to 85.3% (East South Central). The lowest concentrations at which 90% of the isolates were inhibited (MIC90) were for tigecycline (0.06-0.12 microg/mL) and for linezolid (2-4 microg/mL). Methicillin-resistant Staphylococcus aureus (MRSA) varied from 27.4% (New England) to 62.4% (East South Central). All MRSA were susceptible to tigecycline, linezolid, and vancomycin. Penicillin-nonsusceptible Streptococcus pneumoniae ranged from 23.3% in the Pacific region to 54.5% in the East South Central region. Tigecycline, imipenem, levofloxacin, linezolid, and vancomycin all maintained MIC90 of < or =1 microg/mL against penicillin-nonsusceptible S pneumoniae in vitro, irrespective of region.. This study demonstrates the variable rate of antimicrobial-resistant gram-positive organisms in the United States. Tigecycline may make a useful addition to the antimicrobial armamentarium.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Sentinel Surveillance; Tigecycline; United States; Vancomycin Resistance

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

Complicated cutaneous and intra-abdominal infections: no progress.

Topics: Anti-Bacterial Agents; Drug Costs; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Minocycline

The in vitro activities of tigecycline and selected antimicrobials were evaluated against a variety of multiple-drug-resistant clinical isolates, including extended-spectrum beta-lactamase- and/or metallo-beta-lactamase-producing gram-negative strains, colistin-resistant strains, vancomycin- and/or linezolid-resistant enterococci, and methicillin-resistant Staphylococcus aureus (MRSA). Tigecycline showed excellent activity against a collection of difficult-to-treat pathogens currently encountered in the hospital setting.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Greece; Humans; Minocycline; Tigecycline

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 1102 bacterial isolates from 20 centers in Spain. The MIC of tigecycline at which 90% (MIC(90)) of the pneumococci tested were inhibited was the lowest (0.06 microg/mL) of all the antibiotics tested. The MICs of tigecycline against enterococci ranged from 0.03 to 0.125 microg/mL. All staphylococci were inhibited by < or =0.25 microg/mL of tigecycline, and 99.6% of Enterobacteriaceae isolates were inhibited by < or =2 microg/mL of tigecycline. Tigecycline demonstrated good activity against Bacteroides fragilis group organisms with an MIC(90) of 4 microg/mL. The results of this study confirm the excellent activity of tigecycline against multiresistant Gram-positive and Gram-negative pathogens.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Sentinel Surveillance; Spain; Tigecycline

Tigecycline is the first glycylcycline antimicrobial in phase III clinical trials. This study compares the in vitro activity of tigecycline to 12 other predominately broad-spectrum antimicrobials against 3049 recent inpatient isolates from 38 clinical centers in 17 countries. The minimum concentration at which tigecycline inhibited 90% of the isolates for the entire collection, excluding Pseudomonas aeruginosa, was 1 microg/mL, including vancomycin-resistant enterococci-, extended-spectrum beta-lactamase-, and methicillin-resistant Staphylococcus aureus-resistant phenotypes.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle East; Minocycline; South Africa; Tigecycline

Topics: Adult; Anti-Bacterial Agents; Drug Approval; Gram-Positive Bacterial Infections; Humans; Methicillin Resistance; Minocycline; Staphylococcus aureus; Tigecycline; United States

The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the in vitro activity of tigecycline over a large population of organisms from geographically diverse sites. Tigecycline was compared to amikacin, ampicillin, amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and vancomycin against 3989 commonly encountered clinical Gram-negative and Gram-positive pathogens collected from sites in the United States during 2004. The tigecycline activity was equivalent to imipenem against Enterobacteriaceae. Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro results for tigecycline were similar to other broad-spectrum antimicrobial agents against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin susceptibility. Tigecycline MIC values were unaffected by penicillin nonsusceptibility and beta-lactamase production among fastidious respiratory pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity against most of the commonly encountered nosocomial and community-acquired bacterial pathogens.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline, a new glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Respiratory Tract Infections; Sensitivity and Specificity; Skin Diseases, Infectious; Tigecycline; United States

The in vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) were assessed in an experimental murine thigh infection model in neutropenic mice. Mice were infected with one of several strains of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, or Klebsiella pneumoniae. Most infections were treated with a twice-daily dosing schedule, with administration of 0.75 to 192 mg of GAR-936 or WAY 152,288 per kg of body weight. A maximum-effect dose-response model was used to calculate the dose that produced a net bacteriostatic effect over 24 h of therapy. This dose was called the bacteriostatic dose. More extensive dosing studies were performed with S. pneumoniae 1199, E. coli ATCC 25922, and K. pneumoniae ATCC 43816, with doses being given as one, two, four, or eight equal doses over a period of 24 h. The dosing schedules were designed in order to minimize the interrelationship between the various pharmacokinetic and pharmacodynamic parameters studied. These parameters were time above 0.03 to 32 times the MIC, area under the concentration-time curve (AUC), and maximum concentration of drug in serum (C(max)). The bacteriostatic dose remained essentially the same, irrespective of the dosing frequency, for S. pneumoniae 1199 (0.3 to 0.9 mg/kg/day). For E. coli ATCC 25922 and K. pneumoniae ATCC 43816, however, more frequent dosing led to lower bacteriostatic doses. Pharmacokinetic studies demonstrated dose-dependent elimination half-lives of 1.05 to 2.34 and 1.65 to 3.36 h and serum protein bindings of 59 and 71% for GAR-936 and WAY 152,288, respectively. GAR-936 and WAY 152,288 were similarly effective against the microorganisms studied, with small differences in maximum effect and 50% effective dose. The glycylcyclines were also similarly effective against tetracycline-sensitive and tetracycline-resistant bacteria. Time above a certain factor (range, 0.5 to 4 times) of the MIC was a better predictor of in vivo efficacy than C(max) or AUC for most organism-drug combinations. The results demonstrate that in order to achieve 80% maximum efficacy, the concentration of unbound drug in serum should be maintained above the MIC for at least 50% of the time for GAR-936 and for at least 75% of the time for WAY 152,288. The results of these experiments will aid in the rational design of dose-finding studies for these glycylcyclines in humans.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Colony Count, Microbial; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Half-Life; Mice; Mice, Inbred ICR; Minocycline; Muscle, Skeletal; Neutropenia; Survival Analysis; Tigecycline

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

The treatment of moderate to severe acne often relies on antibiotherapy in order to eradicate as much as possible microorganisms such as Propionibacterium spp colonizing the sebaceous follicles. In recent years, bacterial resistances against specific antibiotics have emerged. Both the antibiotic and its administration modalities must be considered in order to control the risk. With regard to this conundrum, minocycline is a medication of choice among the diverse anti-acneic therapies.

Topics: Acne Vulgaris; Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Drug Resistance, Microbial; Gram-Positive Bacterial Infections; Hair Follicle; Humans; Minocycline; Propionibacterium acnes; Risk Factors; Sebaceous Glands

Two new glycylcyclines, CL 329,998 and CL 331,002, were tested for in-vitro activity against 178 clinical strains of enterococci which were resistant to one or more of the commonly used agents (ampicillin, high level gentamicin, vancomycin and teicoplanin). Both glycylcyclines demonstrated good activity (MICs < or = 0.5 mg/L) against all isolates tested, including those strains which demonstrated multiple resistance. As resistant enterococci are increasing in importance, new agents with activity against these strains are urgently required. Glycylcyclines have in-vitro activity which suggests they may be useful agents for treatment of infections caused by these organisms.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple; Enterococcus; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Phenotype; Tetracyclines

The glycylcyclines designated CL 329,998 and CL 331,002 are N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 microgram/ml versus 4 micrograms/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of < or = 0.5 microgram/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline-resistant and multidrug-resistant isolates, were inhibited at < or = 0.5- and < or = 1.0-microgram/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by time-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline.

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tetracyclines; Time Factors