minocycline and Skin-Diseases--Bacterial

Oral tetracyclines have been used in clinical practice for over 60 years. One of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with skin and soft infections (SSTIs), including acute bacterial skin and skin structure infections (ABSSSIs). The 2014 Infectious Diseases Society of America (IDSA) skin and soft tissue guideline strongly recommends sulfamethoxazole/trimethoprim, clindamycin, and tetracyclines as oral treatment options for patients with purulent SSTIs, especially when methicillin-resistant Staphylococcus aureus is of clinical concern. Despite the long-standing use of tetracyclines, practice patterns indicate that they are often considered after other guideline-concordant oral options for the treatment of patients with SSTIs. Clinicians may therefore be less familiar with the clinical data associated with use of commercially available tetracycline agents for treatment of patients with SSTI. This review summarizes the literature on the use of oral tetracyclines (ie, doxycycline, minocycline, and omadacycline) for the treatment of adult patients with SSTIs. As part of this review, we describe their common mechanisms of resistance, susceptibility profiles against common SSTI pathogens, pharmacokinetics and pharmacodynamics, and comparative clinical data.

Topics: Administration, Oral; Adult; Ambulatory Care; Anti-Bacterial Agents; Doxycycline; Humans; Minocycline; Skin Diseases, Bacterial; Tetracyclines

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

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

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.

Topics: Anti-Bacterial Agents; Communicable Diseases; Drug Resistance, Bacterial; Enterococcus; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Skin Diseases, Bacterial; Tigecycline; Vancomycin

Complicated skin and skin-structure infections (cSSSIs) are among the most common infections treated in the hospital setting. They are a significant clinical problem, partially owing to increasing resistance of infecting bacteria to current antibiotic therapies (nosocomial and community-acquired methicillin-resistant Staphylococcus aureus, extended spectrum beta-lactamase-producing-Enterobacteriaceae, and multidrug-resistant [MDR] Pseudomonas aeruginosa, among others). The optimal choice of antibacterial therapy among the few available options for infections caused by MDR pathogens is fundamental to maximize clinical effectiveness and minimize the likelihood of further resistance development. Few antimicrobial agents are currently available to treat MDR bacteria in cSSSIs. In this context, the use of new antibiotic agents (i.e., linezolid, daptomycin and tigecycline) and the optimization of the pharmacodynamic targets of classic antibiotics (i.e., carbapenems) is one potential solution to these problems, and some of these agents are highlighted in this article. The purpose of this article is to provide clinicians with an evidence-based review of MDR pathogens causing cSSSIs, the implications of resistance to currently used drug therapy, and to identify new therapeutic options for resistant pathogens causing cSSSIs.

Topics: Acetamides; Anti-Bacterial Agents; Carbapenems; Daptomycin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Skin Diseases, Bacterial; Tigecycline; Treatment Outcome

Cutaneous nocardiosis is an uncommon infectious disease that presents as a primary cutaneous infection or as a disseminated disease. It is often misdiagnosed because of its rarity and nonspecific clinical picture.. We report a case of each type. The first case is an immunocompetent patient who was infected by Nocardia while gardening and developed a superficial skin infection--one of the three clinical manifestations of primary cutaneous nocardiosis. The second case is an immunocompromised patient with pulmonary nocardiosis that extended to the skin as part of a disseminated disease.. The immunocompetent patient with primary cutaneous nocardiosis had the classical features of a superficial skin infection. He had a nodular–pustular lesion on the right arm, which appeared 7 days after gardening with bare hands. Nocardia was identified in a skin culture taken from a pustule, unfortunately not to the species level. Treatment with minocycline for 3 months resulted in full remission of the lesion. The immunocompromised patient with disseminated nocardiosis had high fever, productive cough, hemoptysis, and erythematous nodules and pustules on the extremities. N. brasiliensis was isolated from bronchial samples and skin. Treatment with a high dose of trimethoprim and sulfamethoxazole for five months resulted in full recovery from cutaneous and pulmonary complaints. No relapse of the infection was found on follow-up in either patient.. These cases demonstrate the need for a high degree of suspicion, focused clinical search, and appropriate laboratory procedures in the diagnosis and management of cutaneous nocardiosis.

Topics: Aged; Anti-Infective Agents; Diagnosis, Differential; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline; Nocardia; Nocardia Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Sulfamethoxazole; Trimethoprim

Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Humans; Minocycline; Skin Diseases, Bacterial; Tigecycline; Treatment Outcome

Tigecycline is a broad-spectrum antimicrobial agent structurally related to minocycline. Pancreatitis has been associated with the tetracycline class of antibiotics and concerns about tigecycline-induced acute pancreatitis have recently been raised. We describe a 69-year-old female who received tigecycline for treatment of a complicated skin and skin-structure infection. Following 7 days of tigecycline she developed severe abdominal pain and elevated pancreatic enzymes suggesting acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of her acute pancreatitis. Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of pancreatitis, including abdominal pain, during treatment with tigecycline.

Topics: Aged; Anti-Bacterial Agents; Female; Humans; Minocycline; Pancreatitis; Skin Diseases, Bacterial; Tigecycline

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

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

Nocardiosis is a mixed suppurative and granulomatous inflammatory disease caused by infection with Nocardia organisms, a group of aerobic actinomycetes. We recently encountered a 25-year-old woman with posttraumatic nocardiosis of the lower extremities. The clinical symptoms noted during her first visit included erythematous swelling of the right knee accompanied by white maceration of the center of the knee and erosions, shallow ulcers and satellite pustules. In addition, multiple erythematous areas (up to the size of the tip of the thumb) were linearly distributed on the right thigh. These lesions were painful, and right inguinal lymphadenopathy was also noted. No lesion was found in internal organs such as the lungs. Histopathologically, signs of nonspecific granulomatous inflammation were observed, as well as several filamentous branching bacilli positive on Grocott stain. The organisms isolated from culture of pus were acid-fast, Gram-positive long rods. The isolated strain was finally identified as Nocardia brasiliensis. The patient was therefore diagnosed with lymphocutaneous type of primary cutaneous nocardiosis caused by N. brasiliensis. Drip infusion of flomoxef sodium was initially performed to treat her condition. Because of exacerbation of erythematous swelling of the right knee and an increase in number of pustules, treatment was switched to oral minocycline hydrochloride therapy. The disease healed 9 weeks after the start of oral minocycline hydrochloride therapy. Our patient was free of systemic immunosuppression and was neither under 10 nor over 65 years of age. She may therefore be considered a rare case of lymphocutaneous type of nocardiosis. We present this case and discuss reported cases of primary cutaneous nocardiosis due to N. brasiliensis in Japan.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Japan; Lymphatic Diseases; Middle Aged; Minocycline; Nocardia; Nocardia Infections; Skin; Skin Diseases, Bacterial; Wound Infection

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of gram-positive, gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of vancomycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Interactions; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Tigecycline

This brief review summarizes recently published data on the pharmacokinetics and pharmacodynamics of tigecycline in man. Significant pharmacokinetic data are now available from the studies of infected patients, as is information on tissue distribution. Importantly, drug exposure-response relationships have been established for complicated skin and skin structure infections and intra-abdominal infection. These studies highlight the difficulties of undertaking pharmacodynamic studies in humans where account must be taken of both mixed pathogen infections and the potential impact of surgery. These data help to define the clinical role for tigecycline.

Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Female; Humans; Male; Minocycline; Peritonitis; Skin Diseases, Bacterial; Tigecycline; Tissue Distribution

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

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

The tetracyclines are a family of related natural products that were originally discovered by virtue of their antibacterial activities. As one of the earliest antibiotics to be marketed after penicillin and streptomycin, and because of their convenient oral dosing, tetracyclines have achieved wide clinical usage. However, this widespread clinical use, in addition to their use in animal feed, and even as an antibiotic spray for fruit and other crops, has produced widespread resistance that ultimately has limited the clinical utility of the entire family of tetracycline antibiotics. More recently, however, there has been renewed interest in this antibiotic class, with attempts being made to identify compounds capable of evading common bacterial resistance mechanisms and to search for potential uses beyond antibacterial therapy. This review will discuss the identification of 9-glycylamido-tetracyclines (glycylcyclines) and related compounds that have successfully evaded most bacterial resistance mechanisms, resulting in the approval of the first glycylcycline, tigecycline, for clinical use.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Endocarditis, Bacterial; Humans; Minocycline; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Tetracyclines; Tigecycline

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram-positive, gram-negative, and anaerobic activity, including certain multidrug-resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug-resistant gram-positive pathogens including methicillin-resistant and glycopeptide-intermediate and -resistant Staphylococcus aureus, as well as vancomycin-resistant enterococci. Multidrug-resistant gram-negative pathogens, such as Acinetobacter baumannii and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad-spectrum antimicrobials are available to combat multidrug-resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however, further clinical experience will clarify its role as a broad-spectrum agent.

Topics: Animals; Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Drug Administration Schedule; Drug Interactions; Drug Resistance, Multiple, Bacterial; Endocarditis, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Osteomyelitis; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Tigecycline

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

Tigecycline derived from minocycline. It is part of a new class of antibiotics called glycylcyclines. Tigecycline is given intravenously and has activity against a variety of gram-positive and gram-negative bacterial pathogens, many of which are resistant to existing antibiotics. Tigecycline successfully completed phase III trials in which it was at least equal to intravenous vancomycin and aztreonam to treat complicated skin and skin structure infections (cSSSI), and to intravenous imipenem and cilastatin to treat complicated intra-abdominal infections (cIAI). Tigecycline side effects are primarily digestive upset. It should be a valuable addition to the armamentarium to treat even the most resistant pathogens.

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

Treatment of complicated skin and skin structure infection (cSSSI) and complicated intra-abdominal infection (cIAI) currently present a therapeutic challenge because many of the pathogens involved are becoming resistant to standard antimicrobial therapy. Tigecycline is a novel glycylcycline that exhibits expanded broad-spectrum antibacterial activity against certain resistant pathogens. Results from randomised Phase III studies comparing the clinical and microbiological efficacy of tigecycline with combination antimicrobial therapy for the treatment of cSSSI and cIAI are encouraging. Tigecycline has the potential to be used as monotherapy for the treatment of cSSSI and cIAI.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Humans; Intestinal Diseases; Minocycline; Skin Diseases, Bacterial; Tigecycline

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37 degrees C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.

Topics: Administration, Oral; Anti-Bacterial Agents; Antitubercular Agents; Buttocks; Child; Coloring Agents; Cutaneous Fistula; DNA, Bacterial; Drug Resistance, Microbial; Female; Granuloma; Humans; Lymphocytes; Minocycline; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Periodic Acid; Phenols; Rosaniline Dyes; Skin Diseases, Bacterial; Tetracycline Resistance; Thigh

We report two cases of primary cutaneous nocardiosis due to Nocardia otitidiscaviarum. The first case is a mycetoma, the second, a cutaneous abcess: these two cases were imported into France (Vietnam, Zimbabwe). The literature on primary cutaneous nocardiosis due to N. otitidiscaviarum is reviewed.

Topics: Abscess; Adult; Anti-Bacterial Agents; Cephalexin; Cephalosporins; Female; France; Gentamicins; Humans; Male; Middle Aged; Minocycline; Mycetoma; Nocardia; Nocardia Infections; Skin Diseases, Bacterial; Travel; Vietnam; Zimbabwe

Mycobacterium marinum is a rare cause of skin infections, and its treatment has been based primarily on the personal experience and preferences of individual investigators without the benefit of large studies.. Thirty-one patients with confirmed M marinum infection were identified at 33 Kaiser Permanente Northern California Region medical centers by microbiologic records, and their charts were reviewed.. The upper extremity was affected in 90% of cases, and lymphatic or local spread was seen during the initial examination or during observation in 25 patients (81%). Granuloma was present in 22 (63%) of 35 biopsy specimens, and staining for acid-fast bacteria yielded positive results in two of 22 specimens. Cure or improvement occurred in 22 (81%) of 27 patients in whom outcome could be evaluated. Treatment with ethambutol plus rifampin appeared more successful (effective in five [100%] of five cases) than minocycline treatment (effective in 10 [71%] of 14 cases), although not significantly so (P = .28). Adverse reactions, most of which were gastrointestinal, occurred in five patients (18%).. Ethambutol plus rifampin appears more useful than minocycline in treating cutaneous M marinum infection. This result remains to be confirmed by larger clinical studies, which may be difficult because this infection is relatively rare.

Topics: Adult; Aged; Child; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Diseases, Bacterial

A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant Staphylococcus aureus (MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, -1.7 to 11.3). For microbiologically evaluable (ME) patients with S. aureus infections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.

Topics: Acetamides; Adolescent; Adult; Aged; Anti-Bacterial Agents; Aztreonam; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Oxazolidinones; Placebos; Skin; Skin Diseases, Bacterial; Staphylococcal Infections; Treatment Outcome

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum β-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Drug Therapy, Combination; Enterococcus; Escherichia coli; Female; Germany; Humans; Intensive Care Units; Intraabdominal Infections; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Multiple Organ Failure; Prospective Studies; Sepsis; Severity of Illness Index; Skin Diseases, Bacterial; Staphylococcus aureus; Tigecycline; Treatment Outcome; Young Adult

Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality.. In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196).. In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group.. Tigecycline was generally safe and effective in the treatment of cSSSIs.. ClinicalTrials.gov NCT00368537.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Skin Diseases, Infectious; Sulbactam; Tigecycline

To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections (cSSSIs).. Safety and efficacy data were analyzed for Indian (n = 86) and Taiwanese (n = 41) patients hospitalized with cSSSIs who participated in two international Phase 3, randomized, double-blind studies.. Patients were treated for 5-14 days. Cure rates at the test-of-cure assessment (12-92 days post-therapy) were generally similar between tigecycline and vancomycin-aztreonam in the clinically evaluable populations (India, 83.3% vs. 75.8%; Taiwan, 78.6% vs. 90%) and in the clinical modified intent-to-treat populations (India, 78.6% vs. 66.7%; Taiwan, 73.3% vs. 75.0%). Nausea and vomiting occurred more frequently with tigecycline, but overall safety and tolerability were comparable between the two treatments.. Tigecycline monotherapy is a safe and effective therapy for cSSSIs in geographically distinct populations in Asia.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; Double-Blind Method; Drug Therapy, Combination; Female; Humans; India; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Nausea; Skin Diseases, Bacterial; Taiwan; Tigecycline; Vancomycin; Vomiting

In a randomized, double-blind, multicenter, multinational, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. Three hundred eighty-five (385) were from Europe. The primary endpoint was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results and adverse event reporting. Of the patients enrolled in Europe, 376 patients were included in the c-mITT population (tigecycline group, n = 189; vancomycin/aztreonam group, n = 187), and 326 were clinically evaluable (tigecycline group, n = 167; vancomycin/aztreonam group, n = 159). The clinical responses in the tigecycline and the vancomycin/aztreonam groups in the clinically evaluable population were 89.8% versus 95.0%. Microbiologic eradication (documented or presumed) occurred in 84.8% of the European patients receiving tigecycline and 93.2% of the European patients receiving vancomycin/aztreonam. The number of European patients reporting adverse events was similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the vancomycin/aztreonam group. Current data support findings from the overall results in the Phase 3 study and suggest that tigecycline is safe and effective for the treatment of complicated skin and skin structure infections.

Topics: Anti-Bacterial Agents; Aztreonam; Double-Blind Method; Drug Therapy, Combination; Female; Humans; International Agencies; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Skin Diseases, Bacterial; Tigecycline; Treatment Outcome; Vancomycin

Exposure-response analyses were performed for the microbiological and clinical efficacy of tigecycline in the treatment of complicated skin and skin-structure infections, where Staphylococcus aureus and streptococci are the predominant pathogens. A prospective method was developed to create homogeneous patient populations for PK-PD analyses. Evaluable patients from three clinical trials were pooled for analysis. Patients received a tigecycline 100-mg loading dose/50 mg every 12 h or a 50-mg loading dose/25 mg every 12 h. At the test-of-cure visit, microbiologic and clinical responses were evaluated. Patients were prospectively evaluated and classified into cohorts based on baseline pathogens: S. aureus only (cohort 1), monomicrobial S. aureus or streptococci (cohort 2), two gram-positive pathogens (cohort 3), polymicrobial (cohort 4), or other monomicrobial infections (cohort 5). A prospective procedure for combining cohorts was used to increase the sample size. Logistic regression evaluated steady-state 24-h area under the concentration-time curve (AUC(24))/MIC ratio as a predictor of response, and classification and regression tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with pooled cohorts 2 and 3, the focus of these analyses, and included 35 patients with 40 S. aureus and/or streptococcal pathogens. CART analyses identified a significant AUC/MIC breakpoint of 17.9 (P = 0.0001 for microbiological response and P = 0.0376 for clinical response). The continuous AUC/MIC ratio was predictive of microbiological response based on sample size (P = 0.0563). Analysis of all pathogens combined decreased the ability to detect exposure-response relationships. The prospective approach of creating homogeneous populations based on S. aureus and streptococci pathogens was critical for identifying exposure-response relationships.

Topics: Adult; Aged; Anti-Bacterial Agents; Area Under Curve; Double-Blind Method; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tigecycline; Treatment Outcome

Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%-83.1%) versus 81.9% (95% CI, 78.3%-85.1%) (P = .4183); and clinically evaluable, 86.5% (95% CI, 82.9%-89.6%) versus 88.6% (95% CI, 85.1%-91.5%) (P = .4233). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; Bacteria; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Random Allocation; Skin Diseases, Bacterial; Tigecycline; Vancomycin

To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI).. A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting.. A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated patients.. This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.

Topics: Anti-Bacterial Agents; Aztreonam; Double-Blind Method; Drug Therapy, Combination; Female; Gram-Positive Cocci; Humans; India; Injections, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Nausea; North America; Skin Diseases, Bacterial; South America; Streptococcus pyogenes; Tigecycline; Treatment Outcome; Vancomycin; Vomiting

In a randomized, double-blind, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. The primary end point was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable (CE) populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results, and adverse event reporting. Five hundred twenty patients were included in the c-mITT population (tigecycline group, n = 261; combination group, n = 259), and 436 were clinically evaluable (tigecycline group, n = 223; combination group, n = 213). The clinical responses in the tigecycline and the combination vancomycin and aztreonam groups were similar in the c-mITT population (84.3% versus 86.9%; difference, -2.6% [95% confidence interval, -9.0, 3.8]; P = 0.4755) and the CE population (89.7% versus 94.4%; difference, -4.7% [95% confidence interval, -10.2, 0.8]; P = 0.1015). Microbiologic eradication (documented or presumed) occurred in 84.8% of the patients receiving tigecycline and 93.2% of the patients receiving vancomycin and aztreonam (difference, -8.5 [95% confidence interval, -16.0, -1.0]; P = 0.0243). The numbers of patients reporting adverse events were similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the combination vancomycin and aztreonam group. Tigecycline was shown to be safe and effective for the treatment of complicated skin and skin structure infections.

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Aztreonam; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Tigecycline; Vancomycin

Tigecycline is a broad-spectrum glycylcycline antibiotic being investigated for the treatment of serious infections in hospitalized patients. Tigecycline has been shown to be efficacious against serious infections in animals, and preliminary studies in healthy adults have shown that tigecycline has an acceptable tolerability profile.. This study compared the clinical and microbiological efficacy, pharmacokinetic properties, and tolerability of 2 doses of tigecycline in hospitalized patients with a complicated skin and skin-structure infection (cSSSI).. This Phase II, randomized, open-label study was conducted between September 1999 and March 2001 at 14 investigative centers across the United States. Patients were randomized to receive tigecycline 25 or 50 mg IV q12h for 7 to 14 days. The primary efficacy end point was the clinically observed cure rate among clinically evaluable (CE) patients at the test-of-cure visit. Secondary end points were the clinical cure rate at the end of treatment and bacteriologic response in microbiologically evaluable (ME) patients. Also, in vitro tests of susceptibility to tigecycline were performed for selected pathogens known to cause skin infections, including methicillin-resistant and methicillin-susceptible Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Tolerability assessments also were conducted.. A total of 160 patients received > or =1 dose of tigecycline; 109 patients were CE, and 91 were ME. The majority of patients (74%) were men, and the mean (SD) age was 49.0 (14.8) years. At the test-of-cure visit, the clinical cure rate in the 25-mg group was 67% (95% CI, 53.3%-79.3%) and in the 50-mg group was 74% (95% CI, 60.3%-85.0%). In the 25-mg group, 56% of the patients had eradication (95% CI, 40.0%-70.4%) of the pathogens compared with 69% (95% CI, 54.2%-82.3%) in the 50-mg group. Values for the minimum concentration of tigecycline that is inhibitory for 90% of all isolates ranged from 0.06 to 0.50 microg/mL for the selected pathogens. Both tigecycline doses were generally well tolerated. Nausea and vomiting were the most common adverse events.. In this study, tigecycline appeared efficacious and showed a favorable pharmacokinetic profile and an acceptable safety profile in the treatment of hospitalized patients with cSSSI. In patients who received 50-mg doses of tigecycline q12h, the clinical cure rates and microbial eradication rates were 74% and 70%, respectively, and were 67% and 56% in patients who received 25-mg doses.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Injections, Intravenous; Inpatients; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Tigecycline

Topics: Abscess; Anti-Bacterial Agents; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Humans; Lymphadenitis; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Diseases, Bacterial

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

Topics: Abscess; Amikacin; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Azithromycin; Drug Resistance, Multiple, Bacterial; Hip Joint; Humans; Male; Middle Aged; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Skin Diseases, Bacterial; Tigecycline

We present an interesting case of cutaneousMycobacterium chelonae in a 95-year-old woman.The lesion in question was localized to her rightarm; subsequent biopsy and culture studies wereconsistent with a mycobacterial infection. Historically,these infections are treated based on the immunologicstate of the patient. In this case, taking into accountthe age of our otherwise immunocompetent patient,a course of oral antibiotics was initiated. The patientwas unable to tolerate any oral regimens for longerthan several weeks. Remarkably, even in the absenceof recommended antibiotic therapy, the lesionclinically cleared over a course of 8 months.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arm; Clarithromycin; Female; Humans; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Skin Diseases, Bacterial

Enterobacteriaceae are currently causing the majority of healthcare-associated infections (HAI) and simultaneously expressing increasing levels of antibiotic resistance. The purpose of this study is to assess the in vitro sensitivity of MDR strains from the family Enterobacteriaceae to tigecycline in relation to their origin from patients hospitalized in intensive care units (ICUs) and non-ICUs.. The study involved 156 clinically significant strains of the Enterobacteriaceae family isolated from patients with complicated intraabdominal infections (cIAIs) and/or complicated skin and skin structure infections (cSSSIs) hospitalized in ICUs and other surgical departments. Tigecycline MICs were determined by Etest.. The highest percentage of tigecycline non-susceptible (intermediate + resistant strains) in vitro strains among the Enterobacteriaceae species were observed for Serratia spp. 77.3%, followed by Citrobacter spp. (76.9%) and Enterobacter spp. (70%); whereas K. pneumoniae and E. coli showed 73-73.8% tigecycline susceptibility rates.. Tigecycline demonstrates a high level of antimicrobial in vitro activity when tested against E. coli and K. pneumoniae, even those with the ESBL-phenotype. Tigecycline retained activity against merely 22-30% of Enterobacter, Citrobacter and Serratia genera.

Topics: Anti-Bacterial Agents; Cross Infection; Enterobacteriaceae; Humans; Intensive Care Units; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; 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

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Bacterial Vaccines; Drug Administration Schedule; Female; Granuloma; Humans; Immunotherapy; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Skin Diseases, Bacterial; Time Factors; Treatment Outcome

As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) we report antimicrobial resistance among Gram-positive and Gram-negative isolates collected globally from integumentary sources between 2010 and 2014.. Minimum inhibitory concentrations and antimicrobial resistance were determined according to Clinical and Laboratory Standards Institute guidelines (US Food and Drug Administration breakpoints against tigecycline). The Cochran-Armitage trend test was used to identify statistically significant changes in resistance.. Global rates of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii were 38% and 43%, respectively. No S. aureus isolates were resistant to linezolid or vancomycin; all isolates were susceptible to tigecycline. Two percent of Enterococcus faecalis and 28% of Enterococcus faecium were vancomycin-resistant. Extended-spectrum β-lactamase (ESBL) producers accounted for 22% of Klebsiella pneumoniae and 16% of Escherichia coli. Resistance to minocycline among E. faecalis, E. faecium, K. pneumoniae, and E. coli decreased significantly (p<0.0001). There were significant increases (p<0.0001) in A. baumannii resistance to cefepime, ceftazidime, ceftriaxone, levofloxacin, meropenem, and piperacillin-tazobactam.. Among isolates from integumentary sources, rates of MRSA and ESBL-producing Enterobacteriaceae are stabilizing. Carbapenems and tigecycline have retained their in vitro activity against Gram-positive and Gram-negative organisms. Few agents were active against A. baumannii; its increasing resistance is cause for concern.

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Skin; Skin Diseases, Bacterial; Tigecycline

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: Antibodies, Monoclonal; Arthritis, Rheumatoid; Azathioprine; Biological Products; Clarithromycin; Drug Substitution; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Infliximab; Middle Aged; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Prednisone; Skin Diseases, Bacterial; Tigecycline; Tumor Necrosis Factor-alpha

Complicated skin and skin structure infections (cSSSIs) and intra-abdominal infections (IAIs) are problematic due to decreasing therapeutic options available against multidrug-resistant pathogens common among these types of infections. A total of 2245 isolates from African and the Middle Eastern (AfME) countries were collected to determine in vitro activity for tigecycline and comparators during 2007-2012 as part of the Tigecycline Evaluation Surveillance Trial program. Tigecycline was launched in the AfME in 2007 and remains active against a wide range of targeted pathogens worldwide. Isolates were recovered from cSSSI (1990) and IAI (255) from 38 sites in 11 AfME countries. Staphylococcus aureus was the most common species from cSSSI (27.9%), and the methicillin-resistant S. aureus rate was 25%. Enterococcus spp. (7.1%) and Streptococcus agalactiae (2.9%) were other common Gram-positive pathogens represented. Enterobacter spp. (14.5%), Pseudomonas aeruginosa (13.9%), Escherichia coli (11.4%), Klebsiella spp. (10.9%), and Acinetobacter spp. (7.2 %) were the most common Gram-negative species collected. Tigecycline MIC(90) values were 0.25 μg/mL against S. aureus. E. coli and Enterobacter spp. had tigecycline MIC(90) values of 1 and 2 μg/mL, respectively. E. coli was the most frequently collected species from IAI (28.3%), followed by Klebsiella spp. (20.8%), Enterococcus spp. (11.8%), and Stenotrophomonas maltophilia (6.3%). Isolates collected from IAI had the following tigecycline MIC(90) values: E. coli (1 μg/mL), Klebsiella spp. and other Enterobacteriaceae (2 μg/mL), Enterococcus spp. (0.25 μg/mL), and S. maltophilia (1 μg/mL). Tigecycline in vitro activity was observed against a broad spectrum of bacterial species, including strains resistant to other antimicrobial classes.

Topics: Africa; Anti-Bacterial Agents; Bacteria; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Middle East; Minocycline; Skin Diseases, Bacterial; Tigecycline

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: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Colitis, Ulcerative; Humans; Hyperthermia, Induced; Male; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Neutrophil Infiltration; Ofloxacin; Prednisolone; Skin Diseases, Bacterial; Treatment Outcome

This analysis from the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) reports on 24 784 isolates collected from integumentary culture sources between 2004 and 2009.. Minimum inhibitory concentrations (MICs) and susceptibility were determined according to the Clinical and Laboratory Standards Institute guidelines (US Food and Drug Administration breakpoints applied against tigecycline).. All methicillin-resistant Staphylococcus aureus were susceptible to tigecycline, linezolid, and vancomycin. MIC(90)s for tigecycline against Enterococcus faecalis and Enterococcus faecium ranged between 0.12 mg/l and 0.25mg/l. Resistance to the carbapenems and tigecycline was low among the Enterobacteriaceae, with resistance at ≤ 2.0% between 2004 and 2009 for tigecycline against Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter spp, and Serratia marcescens, for imipenem against E. coli and Enterobacter spp, and for meropenem against E. coli, Enterobacter spp, and S. marcescens. Against the Acinetobacter baumannii collected in 2009, resistance to amikacin, ceftazidime, levofloxacin, meropenem, and piperacillin-tazobactam was >30%; between 2004 and 2009 resistance to minocycline varied between 1.4% and 4.8%, and tigecycline MIC(90)s were ≤ 2mg/l. Against the Pseudomonas aeruginosa collected, MIC(90)s were greater than the susceptibility breakpoint for cefepime, ceftazidime, imipenem, levofloxacin, and meropenem.. The problem of antimicrobial resistance is demonstrated by the data presented. T.E.S.T. continues to provide valuable information on antimicrobial resistance globally.

Topics: Acetamides; Acinetobacter baumannii; Carbapenems; Drug Evaluation; Drug Resistance, Bacterial; Enterococcus faecalis; Enterococcus faecium; Humans; Klebsiella pneumoniae; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Skin; Skin Diseases, Bacterial; Tigecycline; Vancomycin

We report a lymphocutaneous type of nocardiosis caused by Nocardia vinacea. A 62-year-old woman with polymyositis presented with some erythematous swellings and subcutaneous abscesses on her right middle finger and the dorsum of her hand, which had persisted for 2 weeks. Culturing of the excised nodule and pus revealed orange to orange-tan colonies with scanty whitish aerial mycelia. The isolate was identified as N. vinacea on the basis of its biochemical and chemotaxonomic characteristics and the results of molecular biological analysis. In our case, oral minocycline (MINO) and trimethoprim-sulfamethoxazole (TMP-SMX) for 7 weeks did not improve the clinical manifestation, even though in vitro susceptibility testing of the isolate predicted its susceptibility to MINO and TMP-SMX. Treatment with partial surgical excision followed by TMP-SMX and meropenem administration was effective. This is the first reported case of a lymphocutaneous type of nocardiosis caused by N. vinacea.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Debridement; DNA, Bacterial; DNA, Ribosomal; Female; Humans; Meropenem; Minocycline; Nocardia; Nocardia Infections; Polymyositis; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Skin Diseases, Bacterial; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Adult; Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Arthritis, Psoriatic; Arthritis, Rheumatoid; Bacterial Typing Techniques; Clarithromycin; Ethambutol; Female; Fingers; Fishes; Hand Dermatoses; Humans; Immunocompromised Host; Immunosuppressive Agents; Infliximab; Methotrexate; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Rifabutin; Skin Diseases, Bacterial; Tumor Necrosis Factor-alpha

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

A healthy 23-year-old man presented with a tender papular eruption confined to the grey pigment of a recently acquired professional tattoo. Atypical mycobacterial infection was suspected and culture of a tissue specimen grew Mycobacterium abscessus. He was successfully treated with minocycline and subsequently, clarithromycin. We present a brief review of M. abscessus infection, with a particular focus on its role in nosocomial infections and in the post-tattoo setting.

Topics: Adult; Anti-Bacterial Agents; Clarithromycin; Humans; Male; Minocycline; Mycobacterium; Mycobacterium Infections, Nontuberculous; Skin Diseases, Bacterial; Tattooing; Young Adult

Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value. Using a previously derived tigecycline population pharmacokinetic model and Monte Carlo simulation, a probability density function of steady-state area under the concentration-time curve for 24 h (AUC(SS(0-24))) values for 9999 patients was generated. AUC(SS(0-24)) values were divided by clinically relevant fixed MIC values to derive AUC(SS(0-24))/MIC ratios, which were used to calculate the clinical response expectation by MIC value based upon a logistic regression model for efficacy (1st approach). For the 2nd approach, the probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment was calculated as the proportion of patients with AUC(SS(0-24))/MIC ratios greater than the threshold value of 6.96, the PK-PD target associated with optimal clinical response. Probabilities of clinical response and PK-PD target attainment were poorly correlated at MIC values >0.25 mg/L. For instance, the median probability of clinical success was 0.76, whereas the probability of PK-PD target attainment was 0.27 at an MIC value of 1 mg/L, suggesting that the probability of PK-PD target attainment metrics underestimates the clinical performance of tigecycline at higher MIC values.

Topics: Anti-Bacterial Agents; Area Under Curve; Bayes Theorem; Computer Simulation; Dose-Response Relationship, Drug; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Skin Diseases, Bacterial; Tigecycline

Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population pharmacokinetic model and Monte Carlo simulation (9999 patients) were used to create a likelihood distribution of tigecycline exposure, as measured by the area under the concentration-time curve at 24 h (AUC(24)). Each resultant AUC(24) value was paired with a clinically relevant fixed MIC value ranging from 0.12 to 2 mg/L. For each AUC(24)-MIC pair, the probability of microbiologic response was calculated using an exposure-response relationship, which was derived from patients with complicated skin and skin structure infections that involved Staphylococcus aureus or streptococci or both. The median probability of microbiologic success was 94% or greater for MIC values up to and including 0.25 mg/L. The median probability of microbiologic success was 66% or less for MIC values of 0.5 mg/L or greater. These data support a susceptibility breakpoint of 0.25 mg/L for S. aureus and streptococci.

Topics: Anti-Bacterial Agents; Area Under Curve; Computer Simulation; Humans; Microbial Sensitivity Tests; Minocycline; Models, Biological; Models, Statistical; Monte Carlo Method; Regression Analysis; ROC Curve; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Tigecycline

Mycobacterium marinum is an atypical mycobacterium found worldwide and associated with swimming pools and aquariums. Infections typically present with subcutaneous nodules and lymphangitis.. A 61-year-old female presented with a two-month history of subcutaneous nodules. The patient had a significant recent history that included rose gardening and cleaning her aquarium at home. Biopsy for histology and tissue culture proved the presence of infection with Mycobacterium marinum and the patient was treated with minocycline. The nodules eventually healed and no new lesions appeared after initiation of treatment.. Mycobacterium marinum is one of many entities that must be considered in a patient with ascending nodules along the lymphatic drainage of an extremity.

Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Diagnosis, Differential; Doxycycline; Drug Therapy, Combination; Ethambutol; Female; Fishes; Forearm; Gardening; Hand Dermatoses; Hobbies; Humans; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Skin Diseases, Bacterial; Sporotrichosis; Water Microbiology

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

Mycobacterium mucogenicum is a recently characterized organism that rarely may cause human infections. This rapidly growing mycobacterium is commonly identified in tap water. Both immunosuppressed and immunocompetent patients may develop infections from Mycobacterium mucogenicum. Some patients have experienced lethal disease, including sepsis. Infections occurring in the skin and soft tissues have been described only after a preceding injury. We present the first case of infection with Mycobacterium mucogenicum occurring in a patient on the TNF-alpha antagonist etanercept and without any prior soft tissue injury.

Topics: Anti-Bacterial Agents; Arthritis, Rheumatoid; Clarithromycin; Etanercept; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Middle Aged; Minocycline; Mycobacterium Infections; Opportunistic Infections; Receptors, Tumor Necrosis Factor; Skin Diseases, Bacterial; Tumor Necrosis Factor-alpha

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 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

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Minocycline; Skin Diseases, Bacterial; Tigecycline; United Kingdom

The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 countries worldwide, involved patients with complicated skin and skin-structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, < or =2 microg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated skin and skin-structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated skin and skin-structure infections or complicated intra-abdominal infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials, Phase III as Topic; Drug Resistance, Multiple, Bacterial; Humans; Intestinal Diseases; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; 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

Sporotrichoid forms of atypical mycobacterial infections usually do not show a tendency to spontaneous healing. The therapy of choice in such cases is systemic antibiotics. We report three cases of sporotrichoid atypical mycobacterial infections of the skin which healed completely under long-term monotherapy with modern antibiotics (levofloxacin, clarithromycin, minocycline). We recommend confirming the diagnosis by means of culture, followed by monotherapy with low side-effect antibiotics, based on sensitivity studies. If pathogen proof is obtained by PCR, antibiotic therapy should be based on the known sensitivity of the pathogen in question.

Topics: Adult; Biopsy; Clarithromycin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Female; Forearm; Hand Dermatoses; Humans; Levofloxacin; Lymphadenitis; Male; Middle Aged; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Ofloxacin; Skin; Skin Diseases, Bacterial; Sporotrichosis; Treatment Outcome

The tetracycline antibiotic minocycline is widely used in dermatology, but can sometimes cause systemic lupus erythematodes, a serious autoimmune disorder. It is not known how it does this. However, recent data suggest that minocycline can protect cells from apoptosis by inhibition of caspase-dependent and independent cell death pathways. Here, it is suggested that this ability of minocycline is responsible for the induction of lupus. This idea is based on the recent insight that incomplete or failed apoptosis of damaged cells, particularly keratinocytes, may be responsible for the development of auto-immunity. The protection against apoptosis as conferred by minocyclin may be incomplete, with failed apoptosis and development of autoimmunity as a result. Experimental confirmation of the theory may be obtained by in vitro experiments using induction of apoptosis in cell types known to be affected by lupus. Next, mice that are sensitive to apoptosis may be used for in vivo experiments. Novel therapeutic approaches to drug-induced lupus may be based on induction of apoptosis; DNA-damaging immunosuppressive agents appear particularly useful. Such treatments can be tested in apoptosis-deficient mice that develop autoimmune disease.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Autoimmune Diseases; Caspases; Humans; Lupus Erythematosus, Systemic; Minocycline; Models, Biological; Models, Immunological; Skin Diseases, Bacterial

Actinomycosis is a granulomatous suppurative bacterial disease caused by anaerobic actinomyces, which presents primarily with the cervico-facial, thoracic, abdominal or pelvic form. Cutaneous involvement is well documented and it is usually secondary to local extension or exceptionally to ematogenous spreading from visceral sites. Primary cutaneous actinomycosis is very rare and usually associated with external trauma and/or local ischemia. We report on the case of a primary cutaneous actinomycosis of the forehead in a 59-year-old man with diabetes mellitus who had had a preceding cranial trauma and several cutaneous reconstructive surgical procedures. The patient was treated successfully with combined antibiotic therapy.

Topics: Actinomyces; Actinomycosis; Amoxicillin; Diabetes Mellitus; Diagnosis, Differential; Drug Therapy, Combination; Forehead; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial

Topics: Animals; Animals, Domestic; Anti-Bacterial Agents; Antibiotics, Antitubercular; Diabetes Mellitus, Type 2; Drug Resistance, Bacterial; Fishes; Hand Dermatoses; Humans; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Rifampin; Risk Factors; Skin Diseases, Bacterial; Spinocerebellar Degenerations; Water Microbiology

We report a case of atypical mycobacterial dermal infection caused by M. marinum, which was effectively treated with oral administration of minocycline and local hyperthermic treatment using chemical pocket warmers. A daily oral dose of 200 mg of minocycline was given, and local hyperthermic treatment was applied every evening for 5-6 hours with a disposable chemical pocket warmer. After 2.5 months of therapy, the lesion healed completely with scar formation. At 24 months after the completion of treatments, there is no sign of recurrence.

Topics: Administration, Oral; Adult; Combined Modality Therapy; Drug Administration Schedule; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Minocycline; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Skin Diseases, Bacterial; Treatment Outcome

We isolated 73 streptococcus strains (41 from infections, and 32 from colonization) from various skin diseases between March, 1994, and June, 1998. In 29 out of 41 cases of infective origin, Staphylococcus aureus strains were simultaneously isolated. Twenty-four out of 28 patients with impetigo were suffering from atopic dermatitis. We confirmed that impetigo lesions where Streptococcus pyogenes was dominant in number always showed thick-walled pustules on an erythematous base; these skin lesions were considered to be an early manifestation of streptococcal impetigo. We further confirmed that thick-crusted lesions in streptococcal impetigo, where S. aureus exceeded S. pyogenes in number, were a late manifestation. Antimicrobial agents such as minocycline, fusidic acid, ofloxacin and tosufloxacin, were more effective against S. aureus strains than against beta-hemolytic streptococcal strains. In contrast, ampicillin, cefdinir, imipenem, erythromycin and vancomycin were more effective against beta-hemolytic streptococcal strains.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Erythromycin; Fluoroquinolones; Fusidic Acid; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Ofloxacin; Penicillins; Skin Diseases, Bacterial; Species Specificity; Streptococcal Infections; Streptococcus; Vancomycin

Mycobacterium marinum infections have been reported for over 50 years, mostly in association with trauma in the setting of water exposure.. The differential diagnosis for nodules in a sporotrichoid distribution with simultaneous bursitis is discussed. Mycobacterium marinum treatment regimens for skin and joint involvement are reviewed.. Mycobacterium marinum was identified by skin tissue culture with Lowenstein-Jensen medium at 32 degrees C. Histopathologic findings support mycobacterial infection.. Bursitis and nodules resolved in the first 2 months of a 6-month course of minocycline treatment.. Bursitis is an extremely rare but significant complication of M. marinum.

Topics: Aged; Anti-Bacterial Agents; Bursitis; Diagnosis, Differential; Follow-Up Studies; Humans; Male; Minocycline; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Skin Diseases, Bacterial; Sporotrichosis

The incidence of cutaneous bacterial infection after carbon dioxide (CO2 laser resurfacing is increasing. Patients with staphylococcal colonization of their anterior nares may be at greater risk for postoperative cutaneous colonization and/or infection, which can potentially cause scarring.. We present a case report of methicillin-resistant Staphylococcus aureus secondary infection of the skin after CO2 laser resurfacing. We discuss the possible etiologies of this patient's infection, her postoperative management, and preoperative suggestions for possibly preventing infection.. A 49-year-old woman was treated with CO2 laser resurfacing for moderate actinic damage and facial rhytides. She developed a cutaneous infection with methicillin-resistant S. aureus, which caused diffuse linear scarring on her cheeks and upper lip.. The patient was successfully treated with oral minocycline, rifampin, and topical mupiricin ointment to her cutaneous erosions.. We propose that it would be helpful for patients undergoing CO2 laser resurfacing to have their nares cultured to see if they are staphylococcal carriers. If a patient is found to be a carrier, mupiricin ointment can be used preoperatively treat to the nares, to help decrease the risk of infection of the skin from this potential source.

Topics: Dermatologic Surgical Procedures; Drug Therapy, Combination; Facial Dermatoses; Female; Humans; Laser Therapy; Methicillin Resistance; Middle Aged; Minocycline; Mupirocin; Rifampin; Skin Aging; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus; Surgery, Plastic; Surgical Wound Infection

Actinomycosis is an uncommon infectious disease caused predominantly by Actinomyces israelii. The cutaneous disseminated form is usually caused by hematogenous dissemination from a primary extra-cutaneous lesion. We report here cutaneous disseminated actinomycosis without any detectable extra-cutaneous lesions in a 42-year-old Japanese woman with acute lymphocytic leukemia. Multiple soft nodules developed on her upper and lower extremities. Histopathological examination revealed "sulfur granules", which are a specific finding for actinomycosis. Cultures from biopsy specimens were not successful. There were no cervicofacial, thoracic, nor abdominal lesions. These findings suggest that cutaneous disseminated actinomycosis in our patient developed primarily in the skin. Although the patient was immunocompromised, antibiotic treatment with minocycline was effective.

Topics: Actinobacillus; Actinomycosis; Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Arm; Bacteremia; Biopsy; Cytoplasmic Granules; Female; Humans; Immunocompromised Host; Leg Dermatoses; Minocycline; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Skin Diseases, Bacterial

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia farcinica in a 49-year-old man with nephrotic syndrome. He had received systemic corticosteroid therapy for 5 months. He developed a submandibular abscess associated with sialoadenitis on the right submaxillary gland. Magnetic resonance imaging revealed connection between the submandibular abscess and the right submaxillary gland. The subcutaneous abscess spread from the submandibular triangle to the left axillary region, the left upper arm, the left hypochondriac region, the left scapular region, the right epigastric region, and the bilateral legs. A chest radiograph and computed tomograms of the chest and the brain did not reveal any pathologic changes. The patient was successfully treated by surgical drainage of the abscesses and by oral administration of minocycline.

Topics: Abdomen; Abscess; Anti-Bacterial Agents; Arm; Axilla; Drainage; Focal Infection; Humans; Leg; Magnetic Resonance Imaging; Male; Middle Aged; Minocycline; Nephrotic Syndrome; Nocardia; Nocardia Infections; Scapula; Shoulder; Skin Diseases, Bacterial; Submandibular Gland Diseases

Topics: Abscess; Aged; Anti-Bacterial Agents; Brain Abscess; Focal Infection; Humans; Immunocompetence; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Seizures; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Mycobacterium vaccae is a rapidly growing mycobacterial species that was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease, and three patients had cavitary lung disease. Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin.

Topics: Aged; Animals; Anti-Bacterial Agents; Cattle; Ciprofloxacin; Humans; Male; Middle Aged; Minocycline; Mycobacterium; Mycobacterium Infections; Neoplasms; Pneumonia, Bacterial; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

The authors report a case of cutaneous infection caused by Mycobacterium kansasii in an immunocompetent woman. The mycobacterium was identified after a search for mycolic acids and the species-specific phenol-glycolipid K1. As minocycline followed by ciprofloxacin were ineffective, a conventional antituberculous treatment was prescribed and was fully successful.

Topics: Ciprofloxacin; Drug Therapy, Combination; Female; Humans; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Skin Diseases, Bacterial