tigecycline


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tigecycline

Tygacil

Pharmacologic class: Glycylcycline antibiotic

Therapeutic class: Anti-infective

Pregnancy risk category D

Action

Inhibits protein translation in bacteria by binding to 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into ribosomal A site, which in turn prevents incorporation of amino acid residues into elongating peptide chains

Availability

Powder for injection (lyophilized): 50 mg/5 ml in single-dose vial

Indications and dosages

Treatment of skin, skin-structure infections, and complicated intra-abdominal infections caused by susceptible organisms

Adults age 18 and older: 100 mg I.V. initially, followed by 50 mg I.V. every 12 hours for 5 to 14 days, depending on infection site and severity and patient's clinical and bacteriologic process

Community-acquired bacterial pneumonia caused by susceptible organisms

Adults age 18 and older: Initially, 100 mg I.V., followed by 50 mg I.V. q 12 hours for 7 to 14 days, depending on infection site and severity and patient's clinical and bacteriologic process

Dosage adjustment

• Severe hepatic impairment

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• mild to moderate hepatic impairment, complicated intra-abdominal infections secondary to perforation, ventilator-associated pneumonia

• pregnant and breastfeeding patients

• children younger than age 18.

Administration

• Reconstitute with 5.3 ml of normal saline solution injection or 5% dextrose injection to yield a concentration of 10 mg/ml (50 mg).

• Swirl vial gently until drug dissolves. Immediately withdraw 5 ml of reconstituted solution from vial and add to 100-ml I.V. bag for infusion. Maximum concentration in I.V. bag should be 1 mg/ml.

• Discard reconstituted solution that isn't yellow or orange.

• Administer through dedicated I.V. line or Y-site. If same I.V. line is used for sequential infusion of several drugs, flush before and after infusion, using either normal saline solution injection or 5% dextrose injection. Use infusion solution compatible with tigecycline and other drugs given through same line.

• Administer over 30 to 60 minutes.

• Don't give amphotericin B, chlorpromazine, methylprednisolone, or voriconazole simultaneously through same Y-site.

Adverse reactions

CNS: headache, dizziness, insomnia, asthenia, pseudotumor cerebri

CV: hypertension, hypotension, phlebitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, increased GI enzymes, pseudomembranous colitis, pancreatitis

Hematologic: anemia, leukocytosis, thrombocytopenia

Hepatic: hepatic dysfunction, hepatic failure

Metabolic: antianabolic action (with increased BUN, azotemia, acidosis, and hyperphosphatemia)

Musculoskeletal: back pain

Respiratory: increased cough, dyspnea

Skin: pruritus, rash, sweating, photosensitivity

Other: abscess, fever, infection, pain, peripheral edema, abnormal healing, superinfection, permanent tooth discoloration (during tooth development), increase in all-cause mortality, hypersensitivity reaction (including anaphylaxis)

Interactions

Drug-drug. Hormonal contraceptives: reduced contraceptive efficacy

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, blood glucose, blood urea nitrogen: increased

Blood protein, potassium, WBCs: decreased

Patient monitoring

• Monitor prothrombin time or other suitable anticoagulation tests if patient is receiving warfarin concomitantly.

Closely monitor liver function tests; watch for signs and symptoms of hepatic impairment.

Patient teaching

Instruct patient to immediately report rash and other signs or symptoms of allergic reaction.

• Tell patient to complete full course of therapy, even if he feels better.

• Advise patient taking oral hormonal contraceptives to use alternative birth control method during therapy.

• Caution female with childbearing potential to avoid pregnancy because drug may harm fetus.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

tigecycline

(tye-gi-sye-kleen) ,

Tygacil

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: glycylcyclines
Pregnancy Category: D

Indications

Complicated skin/skin structure infections, complicated intra-abdominal infections, or community-acquired bacterial pneumonia caused by susceptible bacteria (Should only be used when alternative treatments are not suitable; should NOT be used for diabetic foot infections).

Action

Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.

Therapeutic effects

Resolution of infection.
Active against the following Gram-positive bacteria: Enterococcus faecalis(vancomycin-susceptible strains only), Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains), Streptococcus agalactiae, Streptococcus anginosus, Streptococcus pneumoniae, and Streptococcus pyogenes.Also active against these Gram-positive organisms: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (beta-lactamase negative strains only), Legionella pneumophila, Klebsiella oxytoca, and Klebsiella pneumoniae.Additionally active against the following anaerobes: Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Widely distributed with good penetration into gall bladder, lung, and colon; crosses the placenta.
Metabolism and Excretion: Minimal metabolism; primary route of elimination is biliary/fecal excretion of unchanged drug and metabolites (59%), 33% renal (22% unchanged).
Half-life: 27.1 hr (after 1 dose); 42.4 hr after multiple doses.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVrapidend of infusion12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Diabetic foot infectionsHospital-acquired or ventilator-associated pneumonia Pediatric: Children.
Use Cautiously in: Complicated intra-abdominal infections due to perforation;Severe hepatic impairment (↓ maintenance dose recommended); Geriatric: May be more sensitive to adverse effects; Obstetric / Lactation: Use in pregnancy only when potential maternal benefit outweighs fetal risk; use cautiously during lactation.

Adverse Reactions/Side Effects

Central nervous system

  • somnolence

Dermatologic

  • stevens-johnson syndrome (life-threatening)

Gastrointestinal

  • pancreatitis (life-threatening)
  • pseudomembranous colitis (life-threatening)
  • nausea (most frequent)
  • vomiting (most frequent)
  • altered taste
  • anorexia
  • dry mouth
  • hepatotoxicity
  • jaundice

Genitourinary

  • ↑ serum creatinine

Endocrinologic

  • hyperglycemia
  • hypoglycemia

Fluid and Electrolyte

  • hypocalcemia
  • hyponatremia

Respiratory

  • pneumonia

Local

  • injection site reactions

Miscellaneous

  • death (life-threatening)
  • allergic reactions

Interactions

Drug-Drug interaction

May ↓ the effectiveness of hormonal contraceptives.Effects on warfarin are unknown (monitoring recommended).

Route/Dosage

Intravenous (Adults >18 yr) 100 mg initially, then 50 mg every 12 hr for 5–14 days (skin/skin structure infections and intra-abdominal infections) or 7–14 days (pneumonia).

Hepatic Impairment

Intravenous (Adults >18 yr) Child-Pugh C—100 mg initially, then 25 mg every 12 hr.

Availability

Lyophilized powder for reconstitution: 50 mg/vial

Nursing implications

Nursing assessment

  • Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
  • Obtain specimens for culture and sensitivity before initiating therapy. 1st dose may be given before receiving results.
  • Before initiating therapy, obtain a history of tetracycline hypersensitivity; may also have an allergic response to tigecycline.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.
  • Assess patient for signs of pancreatitis (nausea, vomiting, abdominal pain, increased serum lipase or amylase) periodically during therapy. May require discontinuation of therapy.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
  • Lab Test Considerations: May cause anemia, leukocytosis, and thrombocythemia.
    • May cause ↑ serum alkaline phosphatase, amylase, bilirubin, LDH, AST, and ALT.
    • May cause hyperglycemia, hypokalemia, hypoproteinemia, hypocalcemia, hyponatremia, and ↑ BUN level.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • May cause yellow-brown discoloration and softening of teeth and bones if administered prenatally or during early childhood. Not recommended for children under 8 yr of age or during pregnancy or lactation unless used for the treatment of anthrax.
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute each vial with 5.3 mL of 0.9% NaCl or D5W to achieve a concentration of 10 mg/mL. Diluent: Dilute further in 100 mL of D5W, LR, or 0.9% NaCl. Reconstituted solution should be yellow to orange in color. Do not administer solutions that are discolored or contain particulate matter. Infusion is stable for up to 24 hr at room temperature or for up to 48 hr if refrigerated.Concentration: Final concentration of infusion should be ≤1 mg/mL.
  • Rate: Infuse over 30–60 min. Flush line before and after infusion with 0.9% NaCl or D5W.
  • Y-Site Compatibility: acyclovir, alfentanil, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amphotericin B liposome, ampicillin, ampicillin/sulbactam, argatroban, azithromycin, aztreonam, bivalirudin, bumetanide, buprenorphine, busulfan, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, daunorubicin hydrochloride, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doripenem, doxorubicin hydrochloride, doxorubicin liposome, droperidol, enalaprilat, epinephrine, eptifibatide, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, lansoprazole, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, methyldopate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitomycin, mitoxantrone, morphine, moxifloxacin, mycophenolate, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pemtamidine, pentazocine, pentobarbital, phenobarbital, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propofol, propranolol, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, tacrolimus, telavancin, tenioposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tirofiban, tobramycin, topotecan, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, vinblastine, vincristine, vinorelbine, zidovudine, zoledronic acid
  • Y-Site Incompatibility: amiodarone, amphotericin B colloidal, amphotericin B lipid complex, bleomycin, chloramphenicol, chlorpromazine, dantrolene, diazepam, epirubicin, esomeprazole, hydralazine, idarubicin, nicardipine, phenytoin, quinupristin/dalfopristin, verapamil

Patient/Family Teaching

  • Advise patient that full course of therapy should be completed, even if feeling better. Skipping doses or not completing full course of therapy may result in decreased effectiveness and increased risk of bacterial resistance.
  • Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
  • Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools). Skin rash, pruritus, and urticaria should also be reported.
  • Advise female patient to use a nonhormonal method of contraception while taking tigecycline and until next menstrual period.

Evaluation/Desired Outcomes

  • Resolution of signs and symptoms of infection.
References in periodicals archive ?
morganii (Mm-141, and Mm-234) exhibited an extreme level of resistance against [beta]-lactam and non [beta]-lactam classes of antimicrobials, whereas out of 23 antibiotics Enterobacter cloacae (Ec-93 and Ec-188) were sensitive to tigecycline and Citrobacter freundii (Cf-276) to polymyxin-B, tigecycline and colistin only.
Tenders are invited for supply of exclusive medicines: palbociclib, axitinib, bosutinib, tigecycline, crizotinib for the health service of the principality of asturias
In comparison, tigecycline resulted in a CFU reduction in mean lung titers.
In vivo efficacy studies were also performed, comparing TP-2846 to cytarabine and tigecycline, a tetracycline antibacterial, in two AML mouse xenograft models.
(1) Therapeutic options against these infections are limited; "second line" agents include colistin, tigecycline, aminoglycosides, and carbapenems.
Among the isolates of Acinetobacter baumanii all the isolates were 100% sensitive to Colistin, Tigecycline and 100% resistance was seen to Ampicillin.
Tigecycline and colistin are often last-resort antibiotics for the treatment of infections associated with carbapenemase-producing organisms.
Tigecycline is an alternative for MDR Acinetobacter baumannii and Klebsiella pneumoniae carbapenemase-producing bacteria (KPC), but it is not recommended for bacteremia because it does not achieve adequate serum concentration levels and is associated to an increased risk of death (4-5).
coli, Klebsiella, Pseudomonas and Proteus were found sensitive to Imipenem, Meropenem and Tigecycline. Next to them Cefoperazone + Sulbactam has shown good sensitivity against all the gram negative isolates of our study.
MIC50 was 0.094 for Cefpirome, 0.125 Aztreonam, 0.25 imipenem and tigecycline, 2 cefpodoxime and 8 for azithromycin.
Antibiotic discs includingampicillin (AMP10 mg), augmentin (AMC 30 mg), doxycycline (DO 30 mg), levofloxacin (LEV 5 mg), gentamicin (10 mg), colistin (CT 10 mg), meropenem (MEM 10 mg), imipenem (IPM 10 mg), amikacin (AK 30 mg), piperacillin-tazobactam (TZP 110 mg), cefoperazone-sulbactam (SCF 105 mg), aztreonam (30 mg), polymixin-B (300 units), cefoperazone (CFP 75 mg), cefotaxime (CTX 30 mg), ceftazidime (CAZ 30 mg), ceftriaxone (CRO 30 mg), cefepime (FEP 30 mg), trimethoprim/sulfamethoxazole combination commonly known as co-trimoxazole (SXT 25mg), ciprofloxacin (CIP 5 mg), nitrofurantoin (NF 300 mg), fosfomycin (FOS 50 mg), tigecycline (TGC 15 mg) and tobramycin (10 mg) were applied on the plates.
Colistin and tigecycline are last-resort therapeutic options for these carbapenem-resistant Enterobacteriaceae.