Drug Monograph
Tygacil (Tigecycline)
tigecycline — glycylcycline antibacterial
Pharmacokinetic Profile
Half-Life
~42 h (multiple dose)
Metabolism
Minimal; glucuronidation, N-acetylation
Protein Binding
71–89% (non-linear)
Bioavailability
100% (IV administration)
Volume of Distribution
500–700 L (7–9 L/kg)
Clinical Information
Drug Class
Glycylcycline
Available Doses
50 mg vial (lyophilized powder)
Route
IV infusion (30–60 min)
Renal Adjustment
None required
Hepatic Adjustment
Child-Pugh C: reduce maintenance to 25 mg q12h
Pregnancy
May cause fetal harm — avoid in 2nd/3rd trimester (tooth/bone effects)
Lactation
Avoid breastfeeding >3 weeks; pump & discard during + 9 days after
Schedule / Legal Status
Prescription only (not scheduled)
Generic Available
Yes
Black Box Warning
Yes — Increased All-Cause Mortality
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Complicated skin and skin structure infections (cSSSI) | Adults ≥18 years | Monotherapy | FDA Approved |
| Complicated intra-abdominal infections (cIAI) | Adults ≥18 years | Monotherapy | FDA Approved |
| Community-acquired bacterial pneumonia (CABP) | Adults ≥18 years | Monotherapy | FDA Approved |
Tigecycline provides broad-spectrum coverage against gram-positive organisms (including MRSA and VRE), gram-negative bacteria (excluding Pseudomonas aeruginosa), and anaerobes. Due to the FDA boxed warning regarding increased all-cause mortality, tigecycline should be reserved for situations where alternative antibacterials are not suitable. It has demonstrated clinical efficacy in polymicrobial infections where broad-spectrum empiric coverage is needed, particularly when MRSA or multi-drug resistant organisms are suspected.
Limitations of use: Tigecycline is not indicated for diabetic foot infections (failed to demonstrate non-inferiority) or hospital-acquired/ventilator-associated pneumonia (increased mortality and decreased efficacy observed in clinical trials). Tigecycline has reduced activity against Proteus spp., Providencia spp., and Morganella spp.
Off-Label Uses
Multi-drug resistant Acinetobacter baumannii infections: Tigecycline has been used as salvage therapy for MDR A. baumannii infections when no other options exist, though resistance via efflux pumps has been reported. Evidence quality: Low.
Refractory Clostridioides difficile infection: Case series have described tigecycline as adjunctive therapy for severe, refractory C. difficile colitis unresponsive to standard treatment. Evidence quality: Very low.
Rapidly growing non-tuberculous mycobacteria: In vitro activity exists against M. abscessus and M. fortuitum; used in combination regimens for pulmonary or soft-tissue disease. Evidence quality: Low.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Complicated skin & soft tissue infection — empiric therapy | 100 mg IV ×1 | 50 mg IV q12h | 50 mg q12h | Duration 5–14 days; infuse over 30–60 min Reserve for cases with suspected MRSA or polymicrobial etiology when alternatives are unsuitable |
| Complicated intra-abdominal infection — peritonitis, abscess, complicated appendicitis | 100 mg IV ×1 | 50 mg IV q12h | 50 mg q12h | Duration 5–14 days Avoid monotherapy in intestinal perforation with clinical sepsis — consider combination approach |
| Community-acquired bacterial pneumonia — requiring IV therapy | 100 mg IV ×1 | 50 mg IV q12h | 50 mg q12h | Duration 7–14 days Covers S. pneumoniae (penicillin-susceptible), H. influenzae, L. pneumophila |
| Severe hepatic impairment (Child-Pugh C) — any indication | 100 mg IV ×1 | 25 mg IV q12h | 25 mg q12h | CL reduced by ~55%; t½ prolonged by ~43% Monitor closely for treatment response; no adjustment for Child-Pugh A or B |
Pediatric Dosing (Use Only When No Alternatives Available)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Ages 8–11 years — no suitable alternative available | 1.2 mg/kg IV q12h | 50 mg q12h | No loading dose; infuse over 30–60 min Safety and efficacy not established; use only as last resort (FDA PI) | |
| Ages 12–17 years — no suitable alternative available | 50 mg IV q12h | 50 mg q12h | No loading dose Based on PK bridging data; avoid under age 8 due to tooth/bone effects | |
Clinical Pearl: Reconstitution and Administration
Reconstitute each 50 mg vial with 5.3 mL of NS, D5W, or Lactated Ringer’s to yield 10 mg/mL. Withdraw 5 mL and add to a 100 mL IV bag. The reconstituted solution should be yellow to orange; discard if green or black. Stable at room temperature for up to 24 hours total (up to 6 hours in vial + remainder in IV bag), or 48 hours if refrigerated at 2–8°C.
Pharmacology
Mechanism of Action
Tigecycline is a glycylcycline derived from minocycline that halts bacterial protein synthesis by binding to the 30S ribosomal subunit. This blocks the attachment of aminoacyl-tRNA to the ribosomal A-site, preventing peptide chain elongation. The addition of a t-butylglycylamido substituent at the C9 position confers up to five-fold higher ribosomal affinity than minocycline and renders tigecycline effective against the two primary tetracycline-resistance mechanisms: ribosomal protection proteins and efflux pumps. While generally bacteriostatic, tigecycline demonstrates bactericidal activity against Streptococcus pneumoniae and Legionella pneumophila. Its spectrum encompasses gram-positive aerobes (including MRSA and VRE), many gram-negative organisms, anaerobes, and atypical pathogens, though it lacks reliable activity against Pseudomonas aeruginosa, Proteus spp., Providencia spp., and Morganella spp.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV only; 100% bioavailable; Cmax ~0.63 µg/mL (steady-state, 60-min infusion) | No oral formulation exists; no concerns about food interactions or absorption variability |
| Distribution | Vss 500–700 L (7–9 L/kg); protein binding 71–89% (non-linear); tissue:serum ratio high in alveolar cells (~78×), gallbladder (~38×), lung (~3.7×), colon (~2.3×) | Extensive tissue penetration supports use in intra-abdominal and pulmonary infections; low bone and synovial fluid levels limit orthopaedic utility |
| Metabolism | Not extensively metabolised; trace glucuronide and N-acetyl metabolites (≤10% of dose each); does not inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, or 3A4; P-gp substrate | Low CYP interaction potential; clearance unlikely to be affected by CYP inducers or inhibitors |
| Elimination | t½ ~42 h (steady-state); CL ~24 L/h; 59% biliary/faecal, 33% renal (22% unchanged); not removed by haemodialysis | Long half-life allows sustained tissue levels; no dose adjustment for renal impairment or haemodialysis; dose reduction needed only in severe hepatic impairment (Child-Pugh C) |
Side Effects
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 26% | Typically emerges within first 1–2 days of therapy; severity is predominantly mild (17%) or moderate (8%), with only 1% rated severe. Higher in cSSSI trials (35%) than cIAI (25%) or CABP (24%) |
| Vomiting | 18% | Co-occurs with nausea early in the treatment course; mild in 11%, moderate in 6%, severe in 1%. Consider prophylactic antiemetic if prior GI intolerance to tetracyclines |
| Diarrhea | 12% | Monitor for C. difficile if persistent or bloody; rate comparable to comparators (11%) |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Infection (superinfection) | 7% | Includes fungal superinfection; monitor for oral/vaginal candidiasis |
| Abdominal pain | 6% | Distinguish from pancreatitis; check lipase if severe or persistent |
| Headache | 6% | Usually self-limiting; assess for pseudotumor cerebri (tetracycline class effect) if persistent or accompanied by visual changes |
| Hypoproteinaemia | 5% | Anti-anabolic effect of tetracycline class; monitor albumin in prolonged courses |
| Anaemia | 5% | May also reflect underlying infection; monitor CBC |
| SGPT (ALT) increased | 5% | Liver enzyme elevations reported more frequently post-therapy than on-therapy; monitor LFTs |
| SGOT (AST) increased | 4% | Transaminase rises are usually transient; evaluate for hepatotoxicity if >3× ULN |
| Phlebitis | 3% | Infusion-site reaction; rotate IV sites and ensure adequate dilution |
| Asthenia | 3% | Generalised weakness; often overlaps with underlying illness |
| BUN increased | 3% | Anti-anabolic effect; does not necessarily reflect true renal impairment |
| Dizziness | 3% | Comparable to comparator rates; assess for other causes |
| Rash | 3% | Discontinue if SJS/TEN suspected; photosensitivity is a tetracycline class effect |
| Amylase increased | 3% | Evaluate for pancreatitis; check lipase if clinical suspicion |
| Alkaline phosphatase increased | 3% | Part of the hepatobiliary profile to monitor during therapy |
| Bilirubinemia | 2% | Hepatic adverse effects can progress; monitor total and direct bilirubin |
| Dyspepsia | 2% | Part of GI side-effect profile; usually manageable |
| Hyponatraemia | 2% | Check baseline and periodic electrolytes in critically ill patients |
Serious
Serious Adverse Effects (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Increased all-cause mortality | 4.0% vs 3.0% comparator (pooled data) | During treatment course | Reserve for situations when alternatives are unsuitable; use is subject to FDA boxed warning |
| Acute pancreatitis (including fatal cases) | Rare (post-marketing) | Variable; reported in patients with and without risk factors | Discontinue tigecycline; obtain lipase/amylase, imaging; supportive care. Patients usually improve after cessation |
| Hepatic failure / severe hepatic dysfunction | Rare (post-marketing) | Days to weeks; may occur after discontinuation | Monitor LFTs; discontinue if evidence of progressive hepatic injury; evaluate risk-benefit |
| Anaphylaxis / anaphylactic reactions | Rare (post-marketing) | During or shortly after infusion | Immediate discontinuation; emergency treatment with epinephrine, supportive care; permanent discontinuation |
| Hypofibrinogenaemia | Reported (post-marketing) | Days into therapy | Obtain baseline fibrinogen and coagulation parameters; monitor regularly during treatment; consider cryoprecipitate if critically low |
| Stevens-Johnson syndrome / severe skin reactions | Very rare (post-marketing) | Days to weeks | Immediate discontinuation; dermatology consultation; supportive care |
| Severe hypoglycaemia | Rare (post-marketing) | Variable | Monitor glucose; note maltose-containing formulations may cause false glucose meter readings — use glucose-specific assays |
| Sepsis / septic shock (cIAI with intestinal perforation) | 2% tigecycline vs 1% comparator | During treatment | Avoid monotherapy in intestinal perforation; consider combination therapy; escalate care as indicated |
| Clostridioides difficile-associated diarrhea | Uncommon | During or up to 2 months post-treatment | Test for C. difficile toxin; discontinue tigecycline if confirmed; initiate appropriate anti-C. difficile therapy |
Discontinuation
Discontinuation Rates
Adults (Pooled Trials)
7% vs 6% comparators
Top reasons: Nausea (1%), vomiting (1%)
Comparators
6% (vancomycin/aztreonam, imipenem, levofloxacin)
Top reason: Nausea (<1%)
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Nausea | 1% | Most common reason for treatment-limiting toxicity; onset in first 1–2 days |
| Vomiting | 1% | Co-occurs with nausea; slow infusion rate may help |
| Other adverse reactions | 5% (combined) | Includes hepatic enzyme elevations, infection-related complications, and rash |
Managing Nausea and Vomiting
GI symptoms are the most treatment-limiting adverse effects and occur predominantly during the first 48 hours. Slowing the infusion to the full 60 minutes and pre-medicating with ondansetron may reduce severity. Nausea rates vary by indication: up to 35% in cSSSI trials compared with 24–25% in CABP and cIAI trials. Most episodes are mild to moderate and do not require drug discontinuation.
Drug Interactions
Tigecycline has a relatively favourable drug interaction profile. It does not inhibit or induce any of the major CYP450 isoforms (1A2, 2C8, 2C9, 2C19, 2D6, 3A4), so CYP-mediated interactions are minimal. It is a substrate of P-glycoprotein, and co-administration with P-gp inhibitors or inducers may theoretically affect tigecycline exposure. The most clinically relevant interaction is with warfarin.
Major
Warfarin
MechanismDecreased clearance of R-warfarin (40%) and S-warfarin (23%); AUC increased by 68% (R-warfarin) and 29% (S-warfarin); Cmax increased by 38% and 43%, respectively
EffectIncreased warfarin exposure and potential for supratherapeutic anticoagulation, though INR was not significantly altered in a single-dose study
ManagementMonitor PT/INR closely during and after tigecycline therapy; adjust warfarin dose as needed
FDA PI
Major
Calcineurin Inhibitors (Tacrolimus, Cyclosporine)
MechanismNot fully characterised; may involve P-gp-mediated transport effects or altered metabolism
EffectIncreased serum trough concentrations of calcineurin inhibitors, raising risk of nephrotoxicity and neurotoxicity
ManagementMonitor calcineurin inhibitor trough levels during and after tigecycline treatment; adjust doses to maintain therapeutic range
FDA PI
Moderate
Oral Contraceptives
MechanismPotential disruption of enterohepatic recycling of ethinylestradiol (tetracycline class effect)
EffectPossible reduced contraceptive efficacy
ManagementRecommend additional or alternative contraceptive method during tigecycline therapy
FDA PI
Moderate
P-glycoprotein Inhibitors (e.g., Ketoconazole)
MechanismTigecycline is a P-gp substrate; co-administration with P-gp inhibitors could increase tigecycline exposure
EffectPotential for increased tigecycline serum levels and adverse effects
ManagementClinical significance not established; monitor for GI toxicity and consider interaction in patients on strong P-gp inhibitors
FDA PI / In Vitro
Moderate
P-glycoprotein Inducers (e.g., Rifampicin)
MechanismInduction of P-gp efflux transporters could lower tigecycline tissue and serum concentrations
EffectPotential for reduced tigecycline efficacy
ManagementClinical significance not established; monitor clinical response if co-administration is necessary
FDA PI / In Vitro
Minor
Digoxin
MechanismTigecycline slightly reduced digoxin Cmax by 13% without affecting AUC or clearance
EffectNo clinically significant pharmacodynamic or pharmacokinetic change
ManagementNo dose adjustment required for either agent
FDA PI
IV Compatibility Note
Tigecycline is Y-site compatible with amikacin, dobutamine, dopamine, gentamicin, haloperidol, lidocaine, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, propofol, ranitidine, theophylline, and tobramycin in NS or D5W. It is incompatible with amphotericin B, amphotericin B lipid complex, diazepam, esomeprazole, and omeprazole. Flush lines before and after infusion if sharing IV access.
Monitoring
-
Coagulation Parameters (incl. Fibrinogen)
Baseline, then regularly during treatment
Routine Hypofibrinogenaemia has been reported post-marketing. Obtain PT, aPTT, INR, and fibrinogen at baseline. Continue monitoring throughout therapy, especially in patients on concurrent anticoagulants or with bleeding risk factors. -
Hepatic Function (LFTs)
Baseline, then periodically
Routine Monitor AST, ALT, total bilirubin, and alkaline phosphatase. Hepatic dysfunction may develop or worsen during therapy, and has been reported even after discontinuation. Evaluate risk-benefit if LFTs rise significantly. -
Pancreatic Enzymes (Amylase / Lipase)
If abdominal pain develops
Trigger-based Acute pancreatitis, including fatal cases, has been reported. Check lipase and amylase promptly in patients with new or worsening abdominal pain, nausea, or vomiting that differs from the expected GI side-effect profile. -
Blood Glucose
During therapy, especially in diabetic patients
Routine Symptomatic hypoglycaemia has been reported. Additionally, maltose-containing formulations may cause falsely elevated glucose readings on certain meters. Use glucose-specific assay methods (glucose oxidase or glucose dehydrogenase with NAD cofactor). -
Renal Function (BUN, Creatinine)
Baseline, then periodically
Routine BUN elevation occurs in ~3% due to anti-anabolic effects (tetracycline class). While no renal dose adjustment is needed, rising BUN should be interpreted in context and not necessarily attributed to renal injury. -
INR / PT (if on Warfarin)
Before, during, and after co-administration
Trigger-based Tigecycline decreases warfarin clearance and increases exposure. Monitor anticoagulation closely and adjust warfarin dose as needed. -
Signs of Superinfection
Throughout therapy
Routine Monitor for oral or vaginal candidiasis and for C. difficile-associated diarrhea. CDAD can present up to two months after antibacterial use. -
Calcineurin Inhibitor Levels
During and after co-administration
Trigger-based If co-prescribed with tacrolimus or cyclosporine, monitor drug trough concentrations to avoid nephrotoxicity and neurotoxicity.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to tigecycline — anaphylactic reactions have been reported and may be life-threatening.
Relative Contraindications (Specialist Input Recommended)
- Known tetracycline-class hypersensitivity — structural similarity may confer cross-reactivity; avoid unless no alternatives exist and risk-benefit supports use.
- Hospital-acquired or ventilator-associated pneumonia — higher mortality and lower cure rates observed in clinical trials. Not an approved indication; use for HAP/VAP requires clear documentation of clinical rationale.
- Complicated intra-abdominal infection with clinically apparent intestinal perforation — monotherapy associated with higher rates of sepsis/septic shock in this subpopulation. Combination therapy should be strongly considered.
- Pregnancy (2nd and 3rd trimester) — risk of permanent tooth discolouration and reversible inhibition of bone growth in the fetus. Use only if potential benefit clearly outweighs risk and alternatives are unavailable.
Use with Caution
- Severe hepatic impairment (Child-Pugh C) — clearance reduced by ~55%; requires dose reduction to 25 mg q12h after loading dose; close monitoring for treatment response is essential.
- Paediatric patients under 8 years — risk of permanent tooth discolouration and enamel hypoplasia; tetracycline class effect.
- Patients with history of pancreatitis or risk factors for pancreatitis — fatal cases of acute pancreatitis have been reported.
- Patients on anticoagulants — risk of hypofibrinogenaemia and interaction with warfarin.
- Critically ill patients — altered pharmacokinetics in sepsis/septic shock may affect tissue concentrations. The boxed mortality warning applies particularly to severely ill populations.
- Prolonged therapy — anti-anabolic effects (elevated BUN, azotaemia, acidosis) and superinfection risk increase with duration.
FDA Boxed Warning
Increased All-Cause Mortality
A meta-analysis of 13 Phase 3 and 4 clinical trials demonstrated higher all-cause mortality in tigecycline-treated patients (4.0%) compared with comparator-treated patients (3.0%), yielding an adjusted risk difference of 0.6% (95% CI 0.1, 1.2). The cause of this mortality difference has not been established; deaths were generally attributed to worsening infection, complications of infection, or underlying co-morbidities. Tigecycline should be reserved for use when alternative treatments are not suitable.
Patient Counselling
Purpose of Therapy
Tigecycline is an intravenous antibiotic reserved for treating serious bacterial infections when other antibiotics are not suitable. It works against a wide range of bacteria, including some that are resistant to other treatments. It is used in hospital settings and given through a vein over 30 to 60 minutes, typically twice daily. It does not treat viral infections such as colds or influenza.
How to Take
Tigecycline is administered by healthcare professionals in a clinical setting. The infusion should be completed exactly as scheduled; skipping doses or stopping early may reduce effectiveness and promote resistance. The usual treatment course ranges from 5 to 14 days depending on the type of infection.
Nausea and Vomiting
Tell patient
Nausea and vomiting are the most common side effects, usually starting in the first 1–2 days. These symptoms are typically mild to moderate and tend to improve as treatment continues. Anti-nausea medication may be given before each infusion to help.
Call prescriber
If nausea or vomiting is severe, persistent, or accompanied by abdominal pain that worsens over time.
Diarrhea
Tell patient
Diarrhea may occur during or after treatment. Mild diarrhea is common with antibiotics and usually resolves on its own. However, a serious bowel infection (C. difficile) can develop up to two months after treatment.
Call prescriber
Immediately if diarrhea is watery, bloody, or frequent (more than 3 loose stools daily), or if abdominal cramping and fever develop.
Infusion-Site Reactions
Tell patient
Redness, pain, or swelling at the IV site can occur. Nursing staff will monitor the infusion site and rotate it as needed.
Call prescriber
If the infusion site becomes increasingly painful, swollen, or shows streaking redness along the vein.
Allergic Reactions
Tell patient
Although uncommon, serious allergic reactions can occur. Inform your care team before starting treatment if you have any known allergies, especially to tetracycline-type antibiotics (such as doxycycline or minocycline).
Call prescriber
Immediately if experiencing difficulty breathing, swelling of the face or throat, severe rash, or hives during or after the infusion.
Pregnancy and Breastfeeding
Tell patient
Tigecycline may cause permanent tooth staining and affect bone development in an unborn baby if used during the second or third trimester. If breastfeeding, avoid nursing for longer than 3 weeks during treatment. You may pump and discard breast milk during treatment and for 9 days after the last dose.
Call prescriber
If you become pregnant during treatment or are planning to breastfeed.
Completing the Full Course
Tell patient
Even if symptoms improve early, the full prescribed course must be completed. Stopping treatment prematurely may allow bacteria to survive and develop resistance, making the infection harder to treat in the future.
Call prescriber
If symptoms are not improving after several days of therapy, or if symptoms return after treatment is completed.
Sources
Regulatory (PI / SmPC)
- Tigecycline for Injection, USP — Full Prescribing Information (Amneal Pharmaceuticals). Revised 05/2021. FDA Label (NDA 211158) Primary regulatory source for all dosing, indications, contraindications, adverse reactions, and pharmacokinetic data in this monograph.
- TYGACIL (tigecycline) — Full Prescribing Information (Pfizer/Wyeth). Revised 2016. FDA Label (NDA 021821) Original brand-name label; provides additional context for clinical trial data and historical labelling revisions.
- FDA Drug Safety Communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new Boxed Warning. September 2013. FDA Safety Communication Source for the FDA boxed warning details and the regulatory context for the mortality signal.
Key Clinical Trials
- Ellis-Grosse EJ, Babinchak T, Dartois N, et al. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis. 2005;41(Suppl 5):S341–S353. doi:10.1086/431675 Pivotal phase 3 trials establishing efficacy and safety in complicated skin and soft-tissue infections.
- Babinchak T, Ellis-Grosse E, Dartois N, et al. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis. 2005;41(Suppl 5):S354–S367. doi:10.1086/431676 Pivotal phase 3 trials demonstrating non-inferiority to imipenem/cilastatin in complicated intra-abdominal infections.
- Tanaseanu C, Bergallo C, Teglia O, et al. Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008;61(3):329–338. doi:10.1016/j.diagmicrobio.2008.04.009 Phase 3 community-acquired pneumonia data supporting the CABP indication.
- Cai Y, Wang R, Liang B, et al. Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother. 2011;55(3):1162–1172. doi:10.1128/AAC.01402-10 Independent meta-analysis corroborating the efficacy and mortality signal data from the FDA pooled analysis.
Guidelines
- Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133–164. doi:10.1086/649554 SIS/IDSA guideline that positions tigecycline as an option for empiric therapy in cIAI when other agents are unsuitable.
Mechanistic / Basic Science
- Petersen PJ, Jacobus NV, Weiss WJ, et al. In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob Agents Chemother. 1999;43(4):738–744. doi:10.1128/AAC.43.4.738 Foundational study characterising the in vitro and in vivo antibacterial activity and spectrum of tigecycline (GAR-936).
- Bradford PA, Weaver-Sands DT, Petersen PJ. In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis. 2005;41(Suppl 5):S315–S332. doi:10.1086/431673 Microbiology data from phase 3 trial isolates confirming the susceptibility profile for approved indications.
Pharmacokinetics / Special Populations
- Muralidharan G, Micalizzi M, Speth J, et al. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob Agents Chemother. 2005;49(1):220–229. doi:10.1128/AAC.49.1.220-229.2005 Phase 1 pharmacokinetic study establishing key PK parameters (half-life, Vd, clearance) in healthy volunteers.
- Meagher AK, Passarell JA, Cirincione BB, et al. Exposure–response analyses of tigecycline efficacy in patients with complicated skin and skin-structure infections. Antimicrob Agents Chemother. 2007;51(6):1939–1945. doi:10.1128/AAC.01084-06 Population PK/PD analysis linking AUC/MIC to clinical outcomes in cSSSI patients.
- Van Wart SA, Owen JS, Ludwig EA, et al. Population pharmacokinetics of tigecycline in patients with complicated intra-abdominal or skin and skin structure infections. Antimicrob Agents Chemother. 2006;50(11):3701–3707. doi:10.1128/AAC.01636-05 Population PK model identifying weight, renal function, and gender as significant covariates on tigecycline clearance.
- Doan TL, Fung HB, Mehta D, Riska PF. Tigecycline: a glycylcycline antimicrobial agent. Clin Ther. 2006;28(8):1079–1106. doi:10.1016/j.clinthera.2006.08.011 Comprehensive review of tigecycline pharmacology, clinical efficacy, and safety at the time of initial approval.