minocycline and Soft-Tissue-Infections

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, mortality and length of hospital stay. MRSA is a major pathogen in hospitals and an important pathogen in community infections with few severe and fatal cases. However, MRSA causes the majority of skin and soft tissue infections in the US. The burden of community MRSA is much smaller in Europe, but there are reports of livestock-associated MRSA (LA-MRSA) isolated from pigs and cattle causing significant infections in the people who are connected to these farms. MRSA has been present in Croatia for more than 45 years, and it exerts a different impact on health-care infections. A remarkable increase in MRSA percentage was noted in primarily sterile samples in 2002 (37%) in comparison to 2001 (31%). This percentage remained quite high until 2008, when the first signs of a reduced trend were observed. The lowest percentage was 22% in 2012.

Topics: Animals; Anti-Bacterial Agents; Carrier State; Cattle; Croatia; Daptomycin; Humans; Linezolid; Livestock; Methicillin-Resistant Staphylococcus aureus; Minocycline; Prevalence; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Swine; Teicoplanin; Tigecycline; Vancomycin; Zoonoses

Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Ceftaroline; Cephalosporins; Daptomycin; Female; Fluoroquinolones; Glycopeptides; Hospitalization; Humans; Iatrogenic Disease; Internal Medicine; Linezolid; Lipoglycopeptides; Male; Minocycline; Oxazolidinones; Skin Diseases, Infectious; Soft Tissue Infections; Teicoplanin; 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 approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) in adults. In this analysis the safety and tolerability profile of tigecycline (used alone or in combination) for the treatment of patients with approved indications of cSSTI and cIAI were examined under real-life clinical conditions.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). A total of 254 cSSTI and 785 cIAI patients were included. The mean age was 63 years; 34.4% and 56.6% were in intensive care units, 90.9% and 88.1% had at least one comorbidity and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the beginning of treatment were 15.0 ± 7.9 and 16.9 ± 7.6, respectively.. Data on adverse events (AEs) were available for 198 cSSTI and 590 cIAI patients in three studies. Nausea and vomiting were reported in ≤ 2% of patients. The most common serious AEs were multi-organ failure (4.0% and 10.0% in cSSTI and cIAI patients, respectively) and sepsis (4.0% and 6.1%, respectively). Death was recorded for 24/254 (9.4%) cSSTI and 147/785 (18.7%) cIAI patients. Mortality rates were higher in the group with a baseline APACHE II score of >15 compared with those with a score of ≤ 15 (18.7% versus 3.5% for cSSTI patients and 23.8% versus 16.0% for cIAI patients). A similar trend was seen when cIAI patients were stratified by Sequential Organ Failure Assessment (SOFA) score.. The safety and tolerability of tigecycline, alone and in combination, are consistent with the level of critical illness among patients in these real-life studies.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Antimicrobial drug resistance is a growing problem in Europe and, even with differences in epidemiology, it is of great concern. The treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) is hindered further by pathogens that are resistant to methicillin, carbapenems, third-generation cephalosporins and glycopeptides.. An analysis of the microbiological results from five European observational studies (July 2006 to October 2011) evaluating the efficacy of tigecycline (prescribed as monotherapy or in combination with other antibacterials) for the treatment of cSSTI and cIAI is presented.. In total, 213 cSSTI and 623 cIAI patients were included; 34.4% and 56.6%, respectively, were critically ill in intensive care units. At baseline, at least one pathogen was isolated in 167 (78.4%) cSSTI and 464 (74.5%) cIAI patients, and 32.9% and 49.1% of infections were polymicrobial. In cSSTI, Staphylococcus aureus and Escherichia coli (52.7% and 18.0%, respectively) were the most frequently isolated pathogens, whereas in cIAI most infections were due to E. coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%). Clinical response was observed in >80% of patients with E. coli in both cIAI and cSSTI. In cSSTI patients, the clinical response rate to S. aureus was 80.8%. For cIAI, 77.4% of E. faecium and 79.5% of E. faecalis patients responded to treatment.. Tigecycline when given alone or in combination with other antibacterials appeared to be efficacious against multiple pathogens, affirming its role in real-life clinical practice as a broad-spectrum antibacterial for the treatment of patients with cSSTI and cIAI, including the critically ill, across Europe.

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

There is limited information on the use of tigecycline in real-life clinical practice. This analysis aims to identify and understand tigecycline prescribing patterns and associated patient outcomes for approved indications.. A pooled analysis of patient-level data collected on the prescription of tigecycline in five European observational studies (July 2006 to October 2011) was conducted.. A total of 1782 patients who received tigecycline were included in the analysis. Of these patients, 61.6% were male, the mean age was 63.4 ± 14.7 years, 56.4% were in intensive care units, 80.2% received previous antibiotic treatment and 91% had one or more comorbid conditions. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 17.7 ± 7.9 and 7.0 ± 4.0, respectively. The majority of patients (58.3%) received tigecycline for treatment of complicated skin and soft-tissue infections (cSSTIs; n = 254) or complicated intra-abdominal infections (cIAIs; n = 785). Tigecycline was given at the standard dose (100 mg plus 50 mg twice daily) to 89.3% of patients for a mean duration of 11.1 ± 6.4 days. The main reasons for prescribing tigecycline were failure of previous therapy (46.1%), broad-spectrum antibiotic coverage (41.4%) and suspicion of a resistant pathogen (39.3%). Tigecycline was prescribed first-line in 36.3% of patients and as monotherapy in 50.4%. Clinical response rates to treatment with tigecycline alone or in combination were 79.6% (183/230; cSSTIs) and 77.4% (567/733; cIAIs).. Although tigecycline prescription behaviour showed some heterogeneity across the study sites, these results confirm a role for tigecycline in real-life clinical practice for the treatment of complicated infections, including those in critically ill patients, across Europe.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Prescriptions; Europe; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

Treatment of uncomplicated skin and soft-tissue abscesses caused by meticillin-sensitive Staphylococcus aureus or meticillin-resistant S. aureus (MRSA) is problematic. Incision and drainage aside, oral antibiotic therapy for uncomplicated community-acquired MRSA (CA-MRSA) is limited and frequent choices include clindamycin, doxycycline or trimethoprim-sulfamethoxazole (TMP-SMX). The most common oral antibiotics used for CA-MRSA are doxycycline or TMP-SMX, which often fail to eradicate the infection. With MRSA, in vitro susceptibilities do not always predict in vivo effectiveness. In situations where doxycycline or TMP-SMX fails in the treatment of uncomplicated cutaneous abscesses due to CA-MRSA, minocycline is reliably effective.

Topics: Abscess; Administration, Oral; Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections; Tigecycline; Treatment Outcome

Antibiotic-resistant organisms causing both hospital- and community-acquired complicated skin and soft-tissue infections (cSSTI) are increasingly reported. A substantial medical and economical burden associated with MRSA colonisation or infection has been documented. The number of currently available appropriate antimicrobial agents is limited. Good quality randomised, controlled clinical trial data on antibiotic efficacy and safety is available for cSSTI caused by MRSA. Linezolid, tigecycline, daptomycin and vancomycin showed efficacy and safety in MRSA-caused cSSTI. None of these drugs showed significant superiority in terms of clinical cure and eradication rates.To date, linezolid offers by far the greatest number of patients included in controlled trials with a strong tendency of superiority over vancomycin in terms of eradication and clinical success.. - Tigecycline is an alternative in polymicrobial infections except by diabetic foot infections. Daptomycin might be a treatment option for cases of cSSTI with MRSA bacteremia. cSSTI caused by resistant Gram-negative bacteria are a matter of great concern. The development of new antibiotics in this area is an urgent priority to avoid the risk of a postantibiotic era with no antimicrobial treatment options. An individual approach for every single patient is mandatory to evaluate the optimal antimicrobial treatment regimen.

Topics: Acetamides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Microbial; Humans; Linezolid; Minocycline; Oxazolidinones; Skin Diseases; Soft Tissue Infections; Tigecycline; Vancomycin

The available clinical experience with tigecycline is analyzed under the perspective of a systematic review of the literature, so in the already approved indications as in those off label indications reported in the recent literature. The safety profile is checked in the above mentioned clinical trials. The available information allows supporting tigecycline efficiency in the managing of complicated skin and soft tissues infections, complicated intrabdominales infections and community acquired pneumonias. Its usefulness is insinuated in addition in the managing infection by pathogen with high-level of resistance to antimicrobial. Nevertheless it is needed of major evidence in the matter and of a very sensible policy of use in the healthcare institution setting.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Gastrointestinal Diseases; Humans; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Tigecycline is the first of a new class of antibiotics, the glycylcyclines, with properties which can overcome many common resistance mechanisms, making it appropriate for treatment of many serious and life-threatening infections for which other antibiotics are no longer appropriate. its wide antibacterial spectrum includes most methicillin-resistant staphylococci, vancomycin-resistant enterococci, ESBL-producing and other multi-resistant Gram-negative bacteria such as Acinetobacter and Stenotrophomonas spp. it is also active against anaerobes and atypical pathogens. Tigecycline is available only as parenteral formulation. it has a high volume of distribution (>10 L/kg) and long half-life (36 h). It is approved in the USA and europe for treatment of complicated skin and soft tissue infections and complicated communityacquired intra-abdominal infections. Phase II studies for treatment of community- and nosocomial-acquired pneumonia and sepsis due to multidrug resistant pathogens are ongoing.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Digestive System Diseases; Humans; Infections; Minocycline; Soft Tissue Infections; Tigecycline

Therapeutic strategies in the management of skin and soft tissue infections should take account of different variables: epidemiological trends (community or hospital acquired infections), pathogen or pathogens involved, virulence, seriousness of pathology (possible co-morbidities, knowledge of local epidemiology and antimicrobial susceptibility patterns of community and hospital strains. Therapy often should be started promptly, and on an empiric base, once microbiological analysis have been performed, waiting for culture and antimicrobial susceptibility testing. Surgical incision and drainage represent essential therapeutic procedures in the treatment of many complicated skin and soft tissue infections such as abscesses and fasciitis. Gram-positive bacteria and specifically Staphylococcus aureus, are the main cause of such kind of infections. Therefore antistaphylococcal beta-lactams represents a first choice in empirical antimicrobial chemotherapy. Considering high incidence of MRSA in Italian hospitals, treatment of hospital acquired skin and soft tissue infections should be based on glycopeptides combined with third generation cephalosporins, piperacillin-tazobactam, carbapenems or fluoroquinolones. Recently, new drugs (as linezolid, daptomycin, tigecycline) demonstrated good efficacy in the treatment of serious infections caused by multi-drug resistant microorganisms. Most recent guidelines for the diagnosis and treatment of skin and soft tissue infections were published in 2005 by Infectious Diseases Society of America (IDSA). In Italy, the multidisciplinary group of Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) published guidelines for the treatment of skin and soft tissue infections in Internal Medicine wards in 2005. General approach and methodology in writing test were based on analysis of data from available scientific literature and comparing them with actual Italian epidemiological trends and drug prescribing policy. Considering these guidelines, we updated the newest antimicrobial drugs suggested for the treatment of skin and soft tissue infections, such as daptomycin and tigecycline.

Topics: Acetamides; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Cross Infection; Daptomycin; Debridement; Drainage; Drug Therapy, Combination; Humans; Italy; Linezolid; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Sepsis; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Wound Infection

In the present review, the authors focus on skin and soft tissue infections (SSTIs), a set of commonly observed pathologies which can present different features in terms of site and localization, clinical characteristics, and the aetiological agent responsible; their severity is related to the depth of the affected sites. After a brief introduction to the diverse classification criteria which are currently adopted by various authors, the aetiology and role of the most frequently occurring pathogen, Staphylococcus aureus, often methicillin-resistant is discussed, as well as the possible therapeutic options. We first present the internationally recommended guidelines, and stress that SSTI management has to conform to different criteria, in accordance with the different clinical settings: mild infections require simple and cost-saving treatments while severe infections make timely and aggressive treatments mandatory. The review then reports the recent data concerning the efficacy of new antimicrobials for treating SSTIs. In particular, results observed with linezolid, tigecycline, and daptomycin are discussed.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Daptomycin; Humans; Linezolid; Methicillin Resistance; Middle Aged; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Skin Diseases, Infectious; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Tigecycline; Time Factors; Treatment Outcome

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

Complicated skin and skin structure infections encompass a diverse range of diseases frequently caused by Gram-positive pathogens, and most commonly by Staphylococcus aureus and Streptococcus pyogenes. Treatment of these infections represents a growing clinical challenge as increases in multi-drug-resistant organisms and cross-resistance to antimicrobial therapy have made empiric therapeutic choices more difficult, particularly for patients with known risk factors or who are immunocompromised. Complicating this issue has been the relative lack of new agents with antimicrobial potency against prevalent resistant species such as meticillin resistant S. aureus (MRSA). Tigecycline, a novel glycylcycline, is a broad-spectrum antibiotic with potent microbiological activity against the wide variety of organisms implicated in the aetiology of complicated skin and skin structure infections. Recent phase III clinical data confirm previous observations on the safety and efficacy of tigecycline for the treatment of complicated skin and skin structure infections. Tigecycline was shown to be non-inferior to combination vancomycin-aztreonam regimens and exhibited high clinical success rates. MIC(90) values for tigecycline were uniformly low for both susceptible and resistant pathogens. Adverse events were similar in incidence for both patient populations, with nausea and vomiting reported more frequently with tigecycline treated patients while rash and elevated liver transaminases were most commonly observed in the vancomycin-aztreonam treatment group. Tigecycline helps to address the urgent need for new antimicrobial agents to combat the emergence of multi-drug-resistant Gram-positive pathogens. Current clinical, microbiological and safety data support the use of tigecycline as a valuable therapeutic option in the treatment of complicated skin and skin structure infections.

Topics: Anti-Bacterial Agents; Humans; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Mycobacterium abscessus is the most pathogenic and chemotherapy-resistant rapid-growing mycobacterium. It is commonly associated with contaminated traumatic skin wounds and with post-surgical soft tissue infections. It is also one of the mycobacteria that are most often isolated from cystic fibrosis patients. It is essential to differentiate this species from the formerly indistinct "M. chelonae-complex", as chemotherapy is especially difficult in M. abscessussenso strictu. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents with an effect on M. abscessus, and should preferably be supplemented with other drugs since long-term monotherapy may cause resistance. Amikacin is a major parenteral drug against M. abscessus that should also be given in combination with another drug. The recently introduced drug tigecycline may prove to be an important addition to chemotherapy, but has yet to be fully clinically evaluated as an antimycobacterial agent. Surgery can be curative, or at least helpful, in the healing of M. abscessus infection, and if conducted, it should include the removal of all foreign or necrotic material. There is increasing awareness of M. abscessus as an emerging pathogen.

Topics: Administration, Oral; Amikacin; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Respiratory Tract Infections; Skin; Soft Tissue Infections; Species Specificity; Surgical Wound Infection; Tigecycline; Tuberculosis, Cutaneous; Wounds and Injuries

Patients with serious bacterial infections such as intra-abdominal infections and complicated skin and soft tissue infections are often treated empirically because a delay in appropriate initial antimicrobial therapy has been shown to significantly increase morbidity and mortality. Furthermore, pathogens that have developed resistance to mainstay therapeutic options are increasing in prevalence making these infections a challenge for physicians. Treatment guidelines for surgical and intra-abdominal infections recommend selection of an agent or a combination of agents with activity to cover both Gram-positive, Gram-negative organisms and anaerobes. Recommended agents include second-generation cephalosporins with anaerobic coverage, beta-lactam/beta-lactamase inhibitor agents, fluoroquinolone/metronidazole combinations and carbapenems. However, the effectiveness of these agents has come into question as once susceptible organisms are now showing signs of resistance to such antimicrobial therapies. Alternative agents specifically designed to overcome mechanisms of microbial resistance have been sought. The result of that search has been the development of a new class of antimicrobials termed glycylcyclines. The first of these novel antibacterials is tigecycline, with a broad spectrum of activity that includes coverage against vancomycin-resistant enterococci, methicillin-resistant S. aureus, and many species of multidrug-resistant Gram-negative bacteria. Tigecycline also has activity against most penicillin-susceptible and resistant Gram-positive organisms. Clinical trial experience with tigecycline has shown it to be at least as effective as current recommended regimens for the treatment of intra-abdominal infections and complicated skin and soft tissue infections. This new agent thus holds promise as an alternative to the beta-lactams and fluoroquinolones for the initial empiric treatment of serious bacterial infections.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Clinical Trials as Topic; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Tigecycline, the first glycylcycline to be approved by the US Food and Drug Administration, is a structural analogue of minocycline that was designed to avoid tetracycline resistance mediated by ribosomal protection and drug efflux. It is indicated for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections and is available for intravenous administration only.. This article summarizes the in vitro and in vivo activities and pharmacologic and pharmacokinetic properties of tigecycline, and reviews its clinical efficacy and tolerability profile.. Relevant information was identified through a search of MEDLINE (1966-April 2006), Iowa Drug Information Service (1966-April 2006), and International Pharmaceutical Abstracts (1970-April 2006) using the terms tigecycline, GAR-936, and glycylcycline. Also consulted were abstracts and posters from meetings of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1999-2006) and documents provided for formulary consideration by the US manufacturer of tigecycline.. Like the tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and inhibits protein synthesis by preventing the incorporation of amino acid residues into elongating peptide chains. In vitro, tigecycline exhibits activity against a wide range of clinically significant gram-positive and gram-negative bacteria, including multidrug-resistant strains (eg, oxacillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae), and anaerobes (eg, Bacteroides spp). In pharmacokinetic studies in human adults, tigecycline had a large Vd (7-9 L/kg), was moderately bound to plasma protein (71%-89%), had an elimination t(1/2) of 42.4 hours, and was eliminated primarily by biliary/fecal (59%) and renal (33%) excretion. Dose adjustment did not appear to be necessary based on age, sex, renal function, or mild to moderate hepatic impairment (Child-Pugh class A-B). In patients with severe hepatic impairment (Child-Pugh class C), the maintenance dose should be reduced by 50%. In 4 Phase III clinical trials in patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, tigecycline was reported to be noninferior to its comparators (vancomycin + aztreonam in 2 studies and imipenem/cilastatin in 2 studies), with clinical cure rates among clinically evaluable patients of >80% (P < 0.001 for noninferiority). The most frequently reported (> or =5 %) adverse events with tigecycline were nausea (28.5%), vomiting (19.4%), diarrhea (11.6%), local IV-site reaction (8.2%), infection (6.7%), fever (6.3%), abdominal pain (6.0%), and headache (5.6%). The recommended dosage of tigecycline is 100 mg IV given as a loading dose, followed by 50 mg IV g12h for 5 to 14 days.. In clinical trials, tigecycline was effective for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. With the exception of gastrointestinal adverse events, tigecycline was generally well tolerated. With a broad spectrum of activity that includes multidrug-resistant gram-positive and gram-negative pathogens, tigecycline may be useful in the treatment of conditions caused by these pathogens.

Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Multiple, Bacterial; Economics, Pharmaceutical; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Only few data are available on the efficacy of tigecycline in critically ill patients.. This prospective, multicenter, non-interventional study investigated the efficacy and safety of tigecycline in hospitalized, severely ill patients with complicated intra-abdominal infections (cIAI) and/or complicated skin and soft tissue infections (cSSTI). Documentation included diagnosis, clinical findings, Acute Physiology and Chronic Health Evaluation II score, laboratory assessments, surgery, clinical outcomes, and adverse events.. Six hundred and fifty-six patients (mean Acute Physiology and Chronic Health Evaluation II score 19.1) with cIAI (41%), cSSTI (16%), multiple infection sites (13%) and/or other severe infections (31%) received tigecycline - 51% as monotherapy - due to failure of previous antibiotics (55%) or since resistant pathogens were suspected or proven (45%); clinical cure/improvement rates were 75, 82, 76 and 67% for cIAI, cSSTI, other severe infections and multiple infection sites, respectively. Drug-related adverse events occurred in 6.7% of patients.. The efficacy and safety of tigecycline was demonstrated in a population of severely ill patients with complicated infections.

Topics: Aged; Anti-Bacterial Agents; Escherichia coli; Female; Germany; Humans; Infections; Male; Middle Aged; Minocycline; Prospective Studies; Severity of Illness Index; Soft Tissue Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Tigecycline; Treatment Outcome

To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital.. A descriptive study.. Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021.. Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed.. A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin.. The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections.. Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

Topics: Agar; Amikacin; Animals; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Female; Furunculosis; Humans; Impetigo; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rifampin; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Teicoplanin; Vancomycin

Complicated skin and soft tissue infections constitute a heterogeneous group of severe disorders, with surgical site infections being the most common hospital-acquired ones. The aim of our study was to investigate the synergistic and bactericidal activities of antimicrobial combinations of fosfomycin with rifampicin and tigecycline against Enterococcus faecalis, Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, and also to evaluate their in vivo effects in a mouse wound infection model. In in vitro studies, the combinations of fosfomycin with rifampicin and tigecycline were both synergistic. These synergies were confirmed in in vivo studies: the drug combinations showed the highest antimicrobial effects compared to monotherapy. In conclusion, the efficacy of fosfomycin combinations, also confirmed in our in vivo model, may suggest new directions in the treatment of infected skin and a possible alternative way to control bacterial skin infection.

Topics: Animals; Anti-Bacterial Agents; Enterococcus faecalis; Enterococcus faecium; Fosfomycin; Gram-Positive Cocci; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Rifampin; Skin Diseases, Bacterial; Soft Tissue Infections; Surgical Wound Infection; Tigecycline

Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (cSSTIs). The selection of antimycobacterial agents for successful treatment of such infections is a critical issue.. To investigate the antimicrobial susceptibility patterns of MABC isolates from skin and soft tissue to a variety of antimycobacterial agents.. Sixty-seven MABC isolates were collected and partial gene sequencing of secA1, rpoB and hsp65 was used to classify them into three subspecies: M. abscessus subsp. abscessus (MAB), M. abscessus subsp. massiliense (MMA) and M. abscessus subsp. bolletii (MBO). The MICs of 11 antimycobacterial agents for these 67 isolates were determined using a broth microdilution method and commercial Sensititre RAPMYCOI MIC plates, as recommended by CLSI.. In total, 28 MAB, 38 MMA and 1 MBO were isolated from patients with cSSTIs at our hospital. Most MABC strains were resistant to ciprofloxacin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin and trimethoprim/sulfamethoxazole. In addition, most MABC strains were intermediately susceptible or resistant to cefoxitin. Eighteen of the 28 MABs and 1 MBO isolate harboured the T28 polymorphism in the erm(41) gene. Two of the 38 MMA isolates had an rrl A2059G point mutation. Most of the MABC strains were susceptible to amikacin and tigecycline.. In Taiwan, amikacin, clarithromycin and tigecycline have good activity against MMA and MAB erm(41) C28 sequevar isolates, whereas amikacin and tigecycline, rather than clarithromycin, have good activity against both MBO and MAB erm(41) T28 sequevar isolates. Clinical trials are warranted to correlate these data with clinical outcomes.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; Clarithromycin; Drug Resistance, Bacterial; High-Throughput Nucleotide Sequencing; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Minocycline; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Skin; Skin Diseases, Bacterial; Soft Tissue Infections; Taiwan; Tertiary Care Centers; Tigecycline

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ciprofloxacin; Colonic Diseases; Drug Synergism; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Fosfomycin; Hernia, Abdominal; Herniorrhaphy; Humans; Intestinal Fistula; Minocycline; Postoperative Complications; Prosthesis-Related Infections; Soft Tissue Infections; Surgical Mesh; Tigecycline

We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Prospective Studies; Soft Tissue Infections; Tigecycline; Urinary Tract Infections

Infections caused by Acinetobacter baumannii are difficult to cure due to the acquisition of resistance by these bacteria and lead to an increase in the general costs of hospitalization. The aim of this study was to determine tigecycline susceptibility of Acinetobacter baumannii strains isolated from intensive care unit and non-intensive care unit patients with skin and soft tissue infections.. MICs were tested by Etest among 70 Acinetobacter baumannii isolates.. The MIC range was from 0.5 to 8.0 mg L⁻¹. For ESBL-producing Acinetobacter baumannii, as well as for strains without carbapenemases, the highest MIC to tigecycline value was 8.0 mg L⁻¹. For AmpC-producing Acinetobacter baumannii, the highest MIC to tigecycline value was 6.0 mg L⁻¹ and, for MBL-producing strains, 2.0 mg L⁻¹.. The majority of Acinetobacter baumannii strains isolated from ICU and non-ICU patients demonstrated high values of MIC range, MIC50 and MIC90 to tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Infectious; Soft Tissue Infections; Tigecycline

This study assessed the efficacy and safety of tigecycline in children with life-threatening infections.. We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre.. The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea.. Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Soft Tissue Infections; Tigecycline

We report a first human case of Porphyromonas pogonae causing soft tissue infection in a patient with open fracture. Strong β-hemolytic, aerotolerant, and non-pigmented gram-negative coccobacilli which matched Porphyromonas pogonae by PCR for 16S rRNA genes were identified from the pus specimen. The clinical course of the patient improved with repeated surgical drainage and tigecycline administration.

Topics: Adult; Anti-Bacterial Agents; Bacteroidaceae Infections; Ciprofloxacin; DNA, Bacterial; Fractures, Bone; Humans; Male; Minocycline; Porphyromonas; Rifampin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Soft Tissue Infections; Suppuration; Tigecycline

Methicillin-resistant Staphylococcus aureus (MRSA) producing Panton-Valentine leukocidin (PVL) is highly virulent. This study aimed to compare the efficacy of tigecycline versus vancomycin in experimental thigh abscess by a PVL-producing MRSA isolate. One hundred and ninety-six Wistar rats were divided into five groups: group A, controls; groups B and C, administered vancomycin starting 1 and 6 h after bacterial challenge respectively; groups D and E, administered tigecycline starting 1 and 6 h after bacterial challenge respectively. Treatment was continued every 12 hours for three consecutive days. Survival was recorded; separate animals were killed for quantitative cultures. Serum samples were collected for estimation of malondialdehyde (MDA). Survival of group D was prolonged compared to all other groups. The bacterial load of blood, liver, spleen and lung was significantly decreased within group D compared to group B at 36 hours. Treatment with tigecycline was accompanied by significant reduction of serum MDA at 24 hours. Tigecycline is comparable to vancomycin for the treatment of soft tissue infections by PVL-producing MRSA.

Topics: Abscess; Animals; Anti-Bacterial Agents; Bacterial Load; Bacterial Toxins; Drug Administration Schedule; Exotoxins; Immunocompromised Host; Injections, Intraperitoneal; Kaplan-Meier Estimate; Leukocidins; Lipid Peroxidation; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Random Allocation; Rats, Wistar; Soft Tissue Infections; Staphylococcal Infections; Thigh; Tigecycline; Vancomycin; Virulence

Necrotizing skin and soft tissue infections (NSTI) form a group of aggressive diseases that require radical debridement for infection control. Simultaneously, a high-dose broad spectrum antibiotic regimen needs to be initiated with control of septic complications in the intensive care setting. The aim of this work is to analyze the efficacy and safety of tigecycline in a subpopulation of hospitalized, severely ill surgical NSTI patients who were documented in a large multicenter non-interventional study on tigecycline use in routine clinical practice.. A total of 1,025 patients with severe infections including complicated skin and soft-tissue infections (cSSTI, n=163; 15,9%) were enrolled in a prospective multi-center non-interventional study. Patients were to receive an initial intravenous dose of 100 mg tigecycline, followed by 50 mg twice daily. Prospectively documented parameters included clinical findings, APACHE II score, microbiological and standard laboratory assessments, surgical measures, and clinical outcomes including adverse events.. Of 163 patients were treated for cSSTI, with the largest subgroup being NSTI patients (n=50, 30.7% of all cSSTI, mean age 61 y, median APACHE II score 20). Forty-eight NSTI patients (96%) had at least one comorbidity. In 80% of patients, the treatment was started after previous antibiotic treatment had failed and in 34% resistant pathogens were isolated (28% methicillin resistant Staphyloccocus aureus [MRSA], 4% extended-spectrum-beta-lactamase (ESBL)-producing bacteria, and 2% vancomycin-resistant Enterococci (VRE). Tigecycline was administered as a single agent in 32 patients; 17 received combination regimens. Data from one patient were not reported. Rates of clinical cure or improvement with tigecycline treatment were 90.2%. Two patients (4%) had drug related adverse events (one thrombocytopenia and one fever/chills); 10 patients (20%) died.. Tigecycline alone or in combination therapy was an effective and safe antibiotic treatment in critically ill and antimicrobially pre-treated patients with NSTI frequently caused by resistant pathogens.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies).

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Survival Analysis; Tigecycline; Treatment Failure

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Soft Tissue Infections; Staphylococcal Skin Infections

Given increasing resistance, therapeutic options to treat MRSA soft tissue infections should be evaluated. This pooled analysis evaluated data from subjects enrolled in 6 tigecycline clinical trials with documented MRSA complicated skin and skin structure infections or diabetic foot infections (DFIs). Baseline characteristics were compared between subjects with and without molecularly classified community-acquired (CA) MRSA, specifically staphylococcal cassette chromosome mec (SCCmec) IV. Clinical response was compared by CA-MRSA designation and treatment group. A total of 378 subjects with MRSA soft tissue infections were identified, including 79 with DFI. A total of 249 (65.9%) were molecularly classified as CA-MRSA. Clinical response rates for MRSA soft tissue infection were similar between tigecycline and vancomycin (treatment difference, 1.0%; 95% confidence interval: -9.3, 12.0) as well as by infection type, SCCmec, and Panton-Valentine leukocidin (PVL) status. Tigecycline demonstrated comparable efficacy for treatment of MRSA soft tissue infections regardless of infection type, SCCmec, or PVL status.

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials as Topic; Diabetic Foot; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Molecular Typing; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Female; Humans; Intraabdominal Infections; Male; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Tigecycline, a new glycylcycline antimicrobial agent, is indicated for the treatment of complicated skin structure infection (cSSTI), intra-abdominal infection (cIAI) and community acquired pneumonia. We aimed to evaluate the clinical and microbiological data together about tigecycline therapy.. Patients with cIAIs and cSSTIs were included in a prospective, observational follow-up. Patient follow-up forms were developed and clinical and microbiological data were recorded.. Of the 107 patients, 67 had cSSTIs, 40 had cIAIs. Tigecycline was used empirically in 37.5% of cIAIs and in 50.7% of cSSTIs. In 85.0% of the patients with cIAI and in 73.1% of the patients with cSSTI, clinical and/or microbiological response could be achieved. A drug change was made in 26.9% and 7.5% of the patients with cSSTI and cIAI respectively. Superinfection was detected in 14.9% of the cSSTI and 7.5% of the cIAI patients.. As a result, tigecycline can be safely used in the treatment of different infections. Compared with cSSTIs, the treatment response is better and the duration of treatment is shorter in cIAIs. However, MIC value must be determined at any rate if tigecycline is to be used in the treatment of Acinetobacter (MDR Acinetobacter, in particular) infections. Clinical cure and microbiological eradication rate of tigecycline therapy changes according to different clinical diagnosis and microorganism.

Topics: Anti-Bacterial Agents; Drug Substitution; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Superinfection; Tigecycline; Treatment Outcome

This Supplement in the Journal of Antimicrobial Chemotherapy comprises a series of papers reporting on 'real-life' clinical experience with tigecycline. The data reported are derived from five European observational studies on the use of tigecycline, either as monotherapy or in combination with other antibiotics, for the treatment of complicated skin and soft-tissue infections or complicated intra-abdominal infections. Taken together, this collection of articles gives clinical insight into the use of tigecycline for the treatment of complicated infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Humans; Intraabdominal Infections; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Humans; Intraabdominal Infections; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Carrier State; Clinical Trials as Topic; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Off-Label Use; Opportunistic Infections; Practice Guidelines as Topic; Salvage Therapy; Soft Tissue Infections; Stenotrophomonas maltophilia; Tigecycline

To gain additional data concerning the anti-anaerobic activity of tigecycline in serum, we analyzed blood samples from six patients with a complicated skin/soft tissue infection who were receiving IV tigecycline 50 mg every 12 h. Venous blood samples were obtained after multiple doses of tigecycline at 1, 6 and 12 h after the initiation of a 1 h IV infusion. Sera from these samples were tested to determine serum inhibitory and bactericidal activity over time against 4 anaerobic bacteria (Bacteroides fragilis, Peptoniphilus asaccharolyticus, Prevotella bivia and Finegoldia magna). An analysis of serum titers found that tigecycline exhibited early (1 h) and prolonged (12 h) inhibitory activity against each study isolate. Moreover, it provided bactericidal activity for 12 h against these strains with the exception of F. magna. Tigecycline was found to exhibit antibacterial activity at serum concentrations below the MICs of the anaerobic bacteria tested. This finding further supports that the antimicrobial activity of tigecycline can be greater than that suggested by the free fraction of drug and that serum appears to enhance this antibacterial activity.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Serum Bactericidal Test; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Resistant pathogens are the cause of clinical infections which threatening the patients lives and challenging the health systems through their economic importance. Therefore, new antibacterial agents with a broader spectrum of activity that protect against development of resistance are required. Tigecycline (Tygacil, Wyeth) is a relatively new FDA and EMEA approved glycylcycline antimicrobial with an expanded broad-spectrum activity against pathogens involved in complicated skin and skin structure infections. In this study we evaluated the in vitro activity of tigecycline in comparison to 14 other antibiotics against 182 clinical pathogens by use of the micro dilution method. In overall, tigecycline exhibited the lowest Minimum Inhibitory Concentration (MIC) values in almost all bacteria with a mean of 0.52 ± 1.25mg/L, followed by meropenem and levofloxacin (mean MIC values 1.29 ± 2.52 and 1.45 ± 3.078 mg/L, respectively). MIC50 and MIC90 values of tigecycline were: 0.06 and 0.15 mg/L for E. coli, 0.12 and 1.00 mg/L for Klebsiella sp., 0.12 and 0.85 mg/L for various Enterobacter sp., 1.00 and 8.00 mg/L for Pseudomonas sp., 0.25 and 1.00 mg/L for Acinetobacter sp., 0.06 and 0.12 mg/L for Serratia sp., 0.12 and 0.25mg/L for Staphylococcus aureus, 0.5 and 5.00 mg/L for Streptococcus sp. The MIC values recorded were among the lowest in recent literature for Acinetobacter sp. (included A. baumannii), and comparable to those obtained for Klebsiella, Serratia and Enterobacter indicating that tigecycline has a promising in vitro activity.

Topics: Anti-Bacterial Agents; Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Tigecycline, a derivative of minocycline, has antibacterial activity against common pathogens associated with complicated skin and soft tissue infections (cSSTIs), including methicillin-resistant Staphylococcus aureus. At present, there is a paucity of data concerning its penetration into skin and soft tissue (SST).. This study evaluated the penetration of tigecycline into SST in 25 patients (mean age, 52 years) with cSSTIs requiring surgical intervention. After a 100-mg loading dose, each patient received 50 mg of tigecycline infused intravenously over 1 h every 12 h. Blood samples were obtained on the day of surgery at 1 h (peak), during surgery, and 12 h (trough) after the beginning of a 50-mg infusion. A viable SST sample was harvested at the infection site. Tissue and concomitant serum concentrations were grouped into three time intervals: 2-4 h (median, 3 h), 5-7 h (median, 7 h), and 8-10 h (median, 9h), and analyzed for tissue penetration.. Tissue and blood samples were obtained one to six days (mean 2.5 days) after initiation of tigecycline treatment. The mean serum peak and trough concentrations of tigecycline were 0.56±0.25 mg/L and 0.26±0.12 mg/L, respectively. The mean tissue:serum ratios at the three study time periods were 3.8 (range 0.7-5.5), 5.2 (range 0.8-7.1), and 2.8 (range 0.8-8.8).. In general, we found higher concentrations of tigecycline in SST than in the serum at the same time point.

Topics: Adult; Aged; Anti-Bacterial Agents; Connective Tissue; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Minocycline; Skin; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

We describe an immunocompromised patient with disseminated Legionella pneumophila infection. A chronic leg ulcer was probably the port of entry for the infection. Treatment required several operations and prolonged antimicrobial treatment. To our knowledge, this is the first case report of Legionella soft tissue infection and pneumonia treated with tigecycline.

Topics: Anti-Bacterial Agents; Humans; Immunocompromised Host; Leg Ulcer; Legionella pneumophila; Legionnaires' Disease; Male; Middle Aged; Minocycline; Pneumonia; Soft Tissue Infections; Tigecycline

Topics: Adolescent; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Soft Tissue Infections; Stenotrophomonas maltophilia; Tigecycline

Tigecycline is a novel antimicrobial agent recently licensed in the United Kingdom (UK), United States and Europe. It is a broad spectrum glycylcycline antibiotic which has structural similarities to the tetracyclines but is more potent against tetracycline-resistant organisms. It is only available as an intravenous (IV) preparation. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of tigecycline. The article also discusses the warnings and precautions associated with the use of this drug. Tigecycline may be used for complicated intra-abdominal and complicated skin and soft tissue infections. It is also likely to find a role in the treatment of infections caused by multi-resistant organisms such as Acinetobacter species.

Topics: Anti-Bacterial Agents; Bacterial Infections; Critical Care; Critical Illness; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Europe; Humans; Microbial Sensitivity Tests; Minocycline; Patient Selection; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; United Kingdom; United States

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Topics: Abdominal Cavity; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Labeling; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Tigecycline; Treatment Outcome; Young Adult

The overall expected coverage for tigecycline and selected antimicrobial regimens based upon prevailing susceptibility rates was evaluated for the empirical therapy of complicated skin and skin-structure infections (cSSSIs). Consecutive, non-duplicate bacterial isolates collected from 2000-2005 from patients with documented cSSSI in 57 medical centres located in the USA (38 centres), France (6 centres), Germany (7 centres), Italy (3 centres) and Spain (3 centres) were used to evaluate the frequency of pathogen occurrence and susceptibility rates of select parenteral antimicrobials (SENTRY Program). By applying pathogen-specific susceptibility rates to the frequency of pathogen occurrence in each country, the overall expected coverage for each treatment regimen was measured. The most frequently isolated pathogens were Staphylococcus aureus (33.3-49.9%), Pseudomonas aeruginosa (8.3-17.2%), Escherichia coli (6.6-13.9%) and enterococci (4.1-8.8%). Tigecycline was highly active against the most common pathogens, except for P. aeruginosa and Proteus mirabilis. The highest overall expected empirical coverage was obtained with combination therapy regimens, including vancomycin plus either imipenem (94.4-99.3%) or piperacillin/tazobactam (92.5-98.2%). Among the monotherapy regimens evaluated, tigecycline provided the highest overall expected coverage in the USA (90.6%), France (89.9%) and Italy (83.3%), whilst piperacillin/tazobactam showed the highest expected coverage in Germany (93.1%) and imipenem in Spain (87.7%). Our results suggest that tigecycline represents a viable additional option for the empirical treatment of cSSSI in these countries.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Models, Biological; Population Surveillance; Prevalence; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; United States

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

GAR-936 is a new semisynthetic glycylcycline with a broad antibacterial spectrum, including tetracycline-resistant strains. The in vitro activities of GAR-936, minocycline, doxycycline, tetracycline, moxifloxacin, penicillin G, and erythromycin were determined by agar dilution methods against 268 aerobic and 148 anaerobic strains of bacteria (including Pasteurella, Eikenella, Moraxella, Bergeyella, Neisseria, EF-4, Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Propionibacterium, Peptostreptococcus, and Actinomyces) isolated from infected human and animal bite wounds in humans, including strains resistant to commonly used antimicrobials. GAR-936 was very active, with an MIC at which 90% of the strains are inhibited (MIC(90)) of < or =0.25 microg/ml, against all aerobic gram-positive and -negative strains, including tetracycline-resistant strains of Enterococcus, Streptococcus, and coagulase-negative staphylococci, except for Eikenella corrodens (MIC(90), < or =4 microg/ml). GAR-936 was also very active against all anaerobic species, including tetracycline-, doxycycline-, and minocycline-resistant strains of Prevotella spp., Porphyromonas spp., Bacteroides tectum, and Peptostreptococcus spp., with an MIC(90) of < or =0.25 microg/ml. Erythromycin- and moxifloxacin-resistant fusobacteria were susceptible to GAR-936, with an MIC(90) of 0.06 microg/ml.

Topics: Animals; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bites and Stings; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Infectious; Soft Tissue Infections; Tigecycline

A 49-year-old man, who had a 3-year history of liver dysfunction but had not been treated, was admitted to the hospital with a sudden onset of fever and generalized muscle pain. He subsequently developed generalized purpura with scattered hemorrhagic bullae of the skin and massive bloody stools. Aeromonas sobria was proven by culture of both blood and bullous fluid. In spite of the extensive treatment with antibiotics and other medications in the intensive care unit (ICU), the patient went into septic shock and died 2 days after admission. Pathological examination on autopsy revealed segmental necrotizing gastroenteritis with bacterial colonies and alcoholic liver cirrhosis, in addition to extensive severe soft tissue damage involving cellulitis and rhabdomyolysis and epidermolysis. Although the prognosis for Vibrio vulnificus infection with severe soft tissue damage in patients with liver cirrhosis, malignancy, diabetes mellitus or other pre-existing diseases is poor, the unfavorable progression of Aeromonas species, especially A. sobria infection is rare. This is thought to be the first report of an autopsied case.

Topics: Aeromonas; Dopamine; Enterocolitis, Necrotizing; Fatal Outcome; Gastroenteritis; Gram-Negative Bacterial Infections; Humans; Imipenem; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Minocycline; Multiple Organ Failure; Norepinephrine; Shock, Septic; Soft Tissue Infections

Ten patients with soft-tissue infections due to Staphylococcus aureus were treated with minocycline, a semisynthetic tetracycline with potent in vitro antistaphylococcal effects. Serum concentrations averaged three to five times the concentration of minocycline required to inhibit growth of S. aureus in vitro. Clearing of the infecting organism was slow (less than 50% of lesions were sterile on day 10 of therapy), but clinical improvement was noted in 8 of 10 patients.

Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Soft Tissue Infections; Staphylococcal Infections