Original Article

Five-Years Tigecycline Experience an Analysis of Real-Life Data

10.4274/haseki.42713

  • Fatih Temocin
  • Necla Eren Tülek
  • Şirin Hekimoğlu
  • Tuba Ilgar
  • Cemal Bulut
  • Fatma Şebnem Erdinç
  • Günay Tuncer Ertem
  • Çiğdem Ataman Hatipoğlu
  • Sami Kınıklı

Received Date: 16.07.2017 Accepted Date: 09.10.2017 Med Bull Haseki 2018;56(2):125-130

Aim:

Tigecycline has been approved by the Food and Drug Administration for the treatment of complicated intra-abdominal infections, skin and soft tissue infections and community-acquired pneumonia. In our study, we examined the efficacy of tigecycline in clinical practice and reported real life data from our hospital over a period of five years.

Methods:

The study was conducted between 2008 and 2013 on patients who received tigecycline for longer than 48 hours in Ankara Training and Research Hospital. Clinical success was defined as clinical recovery and microbiological cure in patients who used tigecycline. Any reason for discontinuation of tigecycline treatment was considered a clinical failure.

Results:

In our hospital, 320 patients were administered tigecycline between 2008 and 2013. Tigecycline was mainly used for pneumonia and skin and soft tissue infections. Tigecycline was used as monotherapy in 174 patients (54.1%). The most frequently isolated agent in tigecycline-treated patients was Acinetobacter baumannii (43.4%) followed by Enterococcus (6.9%). A change in treatment was not considered necessary in 243 (75.9%) patients who received tigecycline, while it was changed in 77 patients (24.1%).

Conclusion:

In conclusion, the use of tigecycline can be an effective treatment choice, either as monotherapy or as a combination antibiotic therapy.

Keywords: Tigecycline, real life data, minocycline

Introduction

Tigecycline, a derivative of minocycline, is the first glycylcycline antibiotic approved by the US Food and Drug Administration (FDA). It shows structural similarities to tetracycline. Tigecycline reversibly binds to the 30S ribosomal subunit and thereby inhibits protein synthesis (1,2). This drug can bypass the two significant resistance mechanisms of tetracycline. The first one is the tetracycline-specific efflux pump mechanism, for which tigecycline serves as a poor substrate. The second resistance mechanism is the Tet(M) protein-mediated modification that inhibits binding of tetracycline, but allows binding of tigecycline to the bacterial ribosomes (3).

Tigecycline is bacteriostatic in nature; however, reports of bactericidal activity have been demonstrated against certain microorganisms (4,5). It has a broad clinical spectrum of activity against many gram-negative bacteria such as those of Enterobacteriaceae family, including extended-spectrum-beta-lactamase-producing Enterobacteriaceae, and against many multi-drug resistant strains of Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus  and Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumonia and vancomycin-resistant Enterococcus. Also, tigecycline has an improved activity in vitro against Enterobacter, Acinetobacter and Stenotrophomonas maltophilia strains. However, it has no in vitro efficiency against Proteus spp., Providencia spp. and non-fermentative Pseudomonas aeruginosa. Tigecycline is very effective against anaerobic bacteria such as Bacteroides spp., including B. fragilis, B. Thetaiotaomicron and B. Uniformis, with some exceptions like Clostridium perfringens and Clostridium difficile (6-10).

Tigecycline has been approved by the FDA for the treatment of complicated intra-abdominal infections, skin and soft tissue infections and community-acquired pneumonia (11,12). However, information concerning the role of tigecycline in community-acquired pneumonia, ventilator-associated pneumonia, urinary infections, central nervous system infections, and bone infections is limited.

In our study, we examined the efficacy of tigecycline in clinical practice and reported real life data from our hospital over a period of five years.


Methods

A retrospective study was conducted by the department of infectious diseases and clinical microbiology at a 650-bed training and research hospital in Ankara, located in the capital city of Turkey. The study was conducted between 2008 and 2013 on patients who received tigecycline for longer than 48 hours in the hospital. All patients in the study received tigecycline doses recommended by the FDA (an initial loading dose of 100 mg, followed by 50 mg administered intravenously every 12 hours). All data were acquired by scanning the hospital database and patient files. Patients’ age, gender, ward type (clinic or intensive care), indication for tigecycline use, microbiological diagnosis, treatment modifications, combination antibiotic therapy, and clinical responses were recorded.

Clinical success was defined as clinical recovery and microbiological cure in patients who used tigecycline, alone or in combination. Any reason for discontinuation of tigecycline treatment was considered a clinical failure.


Statistical Analysis

Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) version 23 software program.


Results

In our hospital, 320 patients were administered tigecycline for more than 48 hours, between 2008 and 2013. Of these, 168 patients were female (52.5%) and 152 patients were male (47.5%). The average age of the patients was 59.6±19.22 (19-97) years. The average duration of tigecycline treatment was 10.6±6.6 days (2-35). The demographic and clinical characteristics of the patients and treatment indications are listed in Table 1.

Although tigecycline was mainly used for pneumonia indication, the other most common indications included complicated skin and soft tissue infections, and also intra-abdominal infections (Table 2).

Indications for tigecycline use, duration of treatment and clinical response rates are given in the ratio of tigecycline use and clinical effectiveness, in intensive care and non-intensive care units, are given in Table 3.

Tigecycline was used as monotherapy in 174 patients (54.1%), while it was used in combination with another antibiotic in 147 patients (45.9 %). The most preferred combination agents were aminoglycosides, and the most common indication for combination therapy was pneumonia. A list of preferred agents for combination therapy is shown in Table 4.

The most frequently isolated agent in tigecycline-treated patients was Acinetobacter baumannii (43.4%) followed by Enterococcus (6.9%). In many cases, some form of the empirical treatments (36.6%) was already started before the tigecycline treatment. The distribution of the isolated agents is shown in Table 5.

A change in treatment was not considered necessary in 243 (75.9%) patients who received tigecycline, while the treatment was changed in 77 patients (24.1%). This treatment change was due to unresponsiveness and side effects in 85.7% (66/77 and 20.6% of the total population) and 14.3% of the treated patients, respectively. Side effects that required treatment change were nausea/vomiting in 10 patients and an allergic reaction in one patient.


Discussion

In this analysis, we presented real life data of 320 patients who received tigecycline over a five-year period. Tigecycline is used for many indications other than those approved by the FDA. The rate of tigecycline use was 54.3% for the FDA approved indications, namely complicated skin and soft tissue infections (including surgical site infection), complicated intra-abdominal infections, and community-acquired pneumonia. Skin and soft tissue infections were the most common among these indications. The FDA and European Medicines Agency have reported a high mortality rate among patients treated with tigecycline in clinical trials (13,14). Due to its benefits and effectiveness, one must consider the risk-benefit ratio for tigecycline use, especially in resistant bacteria. Tigecycline has been used for many indications besides the FDA approved one. Although real life data about its use are limited, some studies involving intensive care patients have suggested promising results with tigecycline treatment (15,16). In this study, ventilator-associated pneumonia in intensive care patients was one of the most common causes of tigecycline use. The main reason behind this was identification of possibly resistant bacteria, and therefore tigecycline was combined with other antibiotics.

Clinical effectiveness of tigecycline treatment was analyzed with respect to the infection sites. High success rates were found in osteomyelitis, surgical site infections, complicated skin and soft tissue infections, and intra-abdominal infections. Even though tigecycline has no approved indication for osteomyelitis, it has demonstrated good bone penetration in previous studies, and has a broad-spectrum activity against nosocomial pathogens, which are a frequent cause of osteomyelitis (17-19). In our study, the success rate of tigecycline treatment was also high in prosthetic joint infections, even though the number of patients of this cause was low. Treatment failure with tigecycline was mostly observed in bloodstream infections, catheter-associated infections, Acinetobacter meningitis and ventilator-associated pneumonia. These findings are also in line with FDA warnings (20).

Tigecycline was generally preferred as monotherapy for skin and soft tissue infections and intra-abdominal infections, and it is mostly initiated as empirical therapy. It was used for targeted treatment and as a part of a combination antibiotic therapy in the remaining unidentified infections. The most common cause of targeted tigecycline use was A. baumannii infections.

Tigecycline was usually preferred in combination therapies of A. baumannii infections with multi-drug resistance. A. baumannii is a rapidly emerging pathogen that causes nosocomial infections, especially in intensive care units; and multi-drug resistant Acinetobacter infections face treatment difficulties. The rise of carbapenem-resistant A. baumanni presents a serious treatment control challenge. Colistin, a relatively old polymyxin drug, and the newer tigecycline, are being used in various antimicrobial combinations for the treatment of this infection (21). In this study, aminoglycosides were the most preferred antibiotics with tigecycline combination, followed by carbapenems.

Treatment change was required in one fourth of patients, 3% of which were due to unwanted side effects.

The retrospective nature of our study, presenting real life data, is important because there was no intervention in selection of patients. However, the key limitations of this study include absence of any other agent for comparative analysis, and lack of evaluation of any underlying causes that might have affected the treatment failure.


Conclusion

In the light of the increasing threat to multi-drug resistant infections, with limited treatment options, the use of tigecycline can be concluded to be an effective treatment choice, either as monotherapy or as a combination antibiotic therapy. Its low side effect profile also serves an added advantage. However, one must consider the risk of possible treatment failure in case of severe bacteremia infections.

Authorship Contributions

Surgical and Medical Practices: F.T., N.E.T., Ş.H., T.I., C.B. Concept: F.T., N.E.T., Ş.H., T.I., C.B. Design: F.T., N.E.T., Ş.H., T.I., C.B., F.Ş.E., G.T.E., Ç.A.H., S.K., Data Collection or Processing: F.T., N.E.T., Ş.H., T.I., C.B., F.Ş.E., G.T.E. Analysis or Interpretation: F.T., N.E.T., Ş.H., T.I., C.B., Ç.A.H., S.K. Literature Search: F.T., N.E.T., Ş.H., T.I., C.B., F.Ş.E., G.T.E. Writing: F.T., N.E.T.s

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.


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