Tigecycline, a derivative of the tetracycline minocycline, is the first available glycylcycline antibiotic Overview of Antibacterial Drugs Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more . Tigecycline inhibits protein synthesis by binding to the 30S ribosomal subunit. It is bacteriostatic.
Tigecycline is given IV. Tigecycline has a large volume of distribution (> 12 L/kg), penetrating well into bone, lung, liver, and kidney tissues. However, because of its extensive distribution into tissue, blood levels are low, so tigecycline is probably not a good choice for patients with bacteremia especially those with intravascular sources of infection.
Most of the drug is excreted in bile and feces. No dosing adjustment is required in patients who have renal insufficiency.
Indications for Tigecycline
Tigecycline is effective against many resistant bacteria, including those with resistance to tetracyclines. Tigecycline has in vitro activity against the following:
Many gram-positive bacteria, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus Staphylococcal Infections Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more , Streptococcus pneumoniae Streptococcal Infections Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more that are penicillin-susceptible, and vancomycin-susceptible Enterococcus faecalis Enterococcal Infections Enterococci are gram-positive, facultative anaerobic organisms. Enterococcus faecalis and E. faecium cause a variety of infections, including endocarditis, urinary tract infections... read more
Many gram-negative bacteria, such as multidrug-resistant Acinetobacter baumannii Acinetobacter Infections Acinetobacter species are gram-negative organisms that can cause suppurative infections in any organ system; these bacteria are often opportunists in hospitalized patients. Acinetobacter... read more , Stenotrophomonas maltophilia, beta-lactamase–negative Haemophilus influenzae Haemophilus Infections The gram-negative bacteria Haemophilus species cause numerous mild and serious infections, including bacteremia, meningitis, pneumonia, sinusitis, otitis media, cellulitis, and epiglottitis... read more , and most Enterobacterales (formerly Enterobacteriaceae; including some strains that produce extended-spectrum beta-lactamases [ESBLs] and other strains that were carbapenem-resistant based on production of a carbapenemase or metallo-beta-lactamase)
Many atypical respiratory pathogens (chlamydiae Chlamydia Three species of Chlamydia cause human disease, including sexually transmitted infections and respiratory infections. All are susceptible to macrolides (eg, azithromycin), tetracyclines... read more , Mycoplasma Mycoplasmas Mycoplasmas are ubiquitous bacteria that differ from other prokaryotes in that they lack a cell wall. Mycoplasma pneumoniae is a common cause of pneumonia, particularly community-acquired... read more species), Mycobacterium abscessus Nontuberculous Mycobacterial Infections There are over 170 recognized species of mycobacteria, mostly environmental. Environmental exposure to many of these organisms is common, but most exposures do not cause infection and many infections... read more , M. fortuitum, and anaerobes Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more , including Bacteroides fragilis, Clostridium perfringens Clostridium perfringens Food Poisoning Clostridium perfringens food poisoning is acute gastroenteritis caused by ingestion of contaminated food. Symptoms are watery diarrhea and abdominal cramps. Diagnosis is by identifying... read more , and Clostridioides difficile Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more (formerly Clostridium difficile)
It is not effective against Pseudomonas aeruginosa, Providencia species, Morganella morganii, or Proteus species.
Tigecycline is indicated for
Complicated intra-abdominal infections
However, a recent meta-analysis showed that patients treated with tigecycline (particularly those treated for ventilator-associated pneumonia Hospital-Acquired Pneumonia Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more ) had a higher mortality than those given other antibiotics, resulting in a black box warning from the U.S. Food and Drug Administration. In general, tigecycline should be reserved for infections with multidrug-resistant (MDR) organisms when other treatment options are more toxic or less effective. Because of its parenteral activity against C. difficile, tigecycline may be a useful antibiotic when a patient requires concurrent treatment of an MDR infection and a C. difficile infection.
Contraindications to Tigecycline
Tigecycline is contraindicated in patients who have had an allergic reaction to it and in children < 8 years of age.
Tigecycline has a black box warning because it increases the risk of mortality and so should be reserved for situations where there are no suitable alternatives.
Use During Pregnancy and Breastfeeding
Tigecycline, like tetracyclines Use During Pregnancy and Breastfeeding Tetracyclines are bacteriostatic antibiotics that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis. Specific tetracyclines are Doxycycline Eravacycline (IV... read more , can affect fetal bones and teeth. If a pregnant woman takes it during the 2nd or 3rd trimester, it may cause permanent discoloration of the fetus's teeth.
Whether tigecycline enters breast milk and is safe to use during breastfeeding is unknown; however, it has limited oral bioavailability.
Adverse Effects of Tigecycline
Adverse effects of tigecycline include
Nausea, vomiting, and diarrhea
Nausea and vomiting are common. Increases in serum amylase, total bilirubin concentration, prothrombin time, and transaminases can occur in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Many of tigecycline’s adverse effects are similar to those of tetracyclines Adverse Effects Tetracyclines are bacteriostatic antibiotics that bind to the 30S subunit of the ribosome, thus inhibiting bacterial protein synthesis. Specific tetracyclines are Doxycycline Eravacycline (IV... read more (eg, photosensitivity).
Dosing Considerations for Tigecycline
Dose is adjusted in patients with hepatic dysfunction but not in those with renal dysfunction.
Serum levels of warfarin may increase, but international normalized ratio does not appear to increase.