Tigecycline

Drug information
Introduction
Antimicrobial activity
Dose/Routes of administration
Therapeutic Drug Monitoring (checking levels)
Pharmacokinetics
Allergy advice
Key interactions (include BNF black dot)
Side effects and monitoring required

Drug indications
Prophylaxis indications in LTHT
Treatment indications in LTHT
Prescribing restriction: Fully restricted outside of guidelines

This document provides guidelines for Microbiologists (including trainees) regarding the situations in which it would be appropriate to consider the use of Tigecycline . This document is supplementary to, and should be used in conjunction with, the summary of product characteristics.

Tigecycline is a glycylcycline, a class of antimicrobial derived from tetracyclines. Tetracycline allergic patients should not be prescribed tigecycline. It should be used with caution in children under 18 years because of a lack of safety and efficacy data.

It should not normally be used in the under eights because of discoloration of the teeth.

Tigecycline should not be used in pregnancy.

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Tigecycline has in vitro activity against:
Staphylococcus aureus (including meticillin-resistant strains)
Coagulase negative staphylococci
Streptococci (including Group A and group B beta-haemolytic streptococci, Streptococcus anginosus group, Streptococcus pneumoniae)
Enterococci
Escherichia coli (including ESBL+ strains), Klebsiella, Enterobacter, Serratia, Citrobacter spp.
Acinetobacter calcoaceticus baumannii complex
Haemophilus spp.
Moraxella catarrhalis
Chlamydophila pneumoniae
Mycoplasma pneumoniae
Anaerobes (Clostridium perfringens, Prevotella, Peptostreptococcus sp.)
Mycobacterium abscessus, Mycobacterium chelonae and Mycobacterium fortuitum

Tigecycline does not have in vitro activity against:

Pseudomonas aeruginosa
Mycobacterium avium complex

And may have reduced activity against Proteus, Providentia, Morganella spp., Stenotrophomonas maltophilia, Burkholderia cepacia complex.
Mycobacterium kansasii, Mycobacterium marinum

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Tigecycline is given as an intravenous infusion over 30-60minutes with a loading dose of 100mg followed by 50mg every 12 hours.

No dosage adjustment is recommended for patients based on gender, ethnicity or renal impairment.

For Treating Infections caused by Carbapenemase Producing Organisms (CPOs) intermediate sensitivities 100mg BD (unlicensed).
Dose adjustment in renal impairment/failure

No dosage adjustment is recommended No dosage adjustment is necessary in patients with renal impairment or in patients undergoing haemodialysis.

Dose in obesity
No doses above the standard regimen could be found.

Dose in liver failure
No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). Dosage adjustment is recommended in patients with severe hepatic impairment (Child Pugh C) - the dose of Tigecycline should be reduced to 25 mg every 12 hours following the 100 mg loading dose. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response.

Paediatric doses
Tigecycline should not be used in children under 8 years of age because of teeth discolouration, and is not recommended in adolescents below 18 years due to the lack of data on safety and efficacy.

A recent study by Purdy et al. concluded that a Tigecycline dosage of ∼1.2 mg/kg every 12 hours may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections.

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Not required.

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Absorption: Tigecycline must be given by intravenous infusion (100% bioavailability)

Distribution: Tigecycline distributes beyond plasma volume and concentrates into tissues. Blood-brain barrier penetration – not known.

Excretion/metabolism: <20% metabolised. Mostly excreted unchanged in urine and faeces, but urinary excretion is much less than faecal and Tigecycline is unsuitable for treatment of urinary tract infections.

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Hypersensitivity to the active substance or to any of the excipients. Patients hypersensitive to tetracycline class antibiotics may be hypersensitive to Tigecycline .

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Tigecycline possibly enhances anticoagulant effect of coumarins.
[THIS LIST IS NOT EXHAUSTIVE]

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Nausea (29.5%) vomiting (19.7%) and diarrhoea (12.7%).
The drug induced nausea may be controlled by antiemetics.

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Tigecycline has not been assessed as a prophylactic agent and should not be recommended for this purpose.

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The following LTH antimicrobial guidelines have recommendations for Tigecycline :

Breast abscesses and Mastitis, (breast cellulitis) in adults
Spontaneous bacterial peritonitis (SBP) in adults
Spontaneous bacterial peritonitis prophylaxis including acute variceal bleeding

Tigecycline can be used in patients:

1. With a surgical wound infection (Breedt et al., 2005; Sacchidanand et al., 2005) (purulent exudate and/or >1cm erythema and pain), in a patient without severe sepsis* or septic shock*

1. When the wound is potentially infected with mixed organisms including MRSA and/or ESBL-positive Enterobacteriaceae that are Tigecycline susceptible.
2. When the wound has not improved with 72 hours treatment with either a suitable penicillin or cephalosporin or vancomycin.
3. When the patient is allergic to or intolerant of penicillins, cephalosporins and vancomycin.
   * using standard definitions (Bone et al., 1992),
   
   NB. If the wound may be infected by Pseudomonas aeruginosa, an alternative therapy should be discussed with microbiology.
   

2. Who have suffered a perforated abdominal viscus and require post-operative antimicrobials for peritoneal contamination but are allergic to penicillins and cephalosporins and have no evidence of septic shock or severe sepsis (Oliva et al., 2005).
   
   NB. Note that ciprofloxacin plus metronidazole is the current recommendation for this situation and Tigecycline should be used as second line, or when susceptibility testing of the causative organism indicates Tigecycline would be appropriate.
   
   Unlicensed indication:
   
   
3. With cystic fibrosis as second line therapy (when first line has failed or if first line is excluded by allergy/toxicity concerns) for infections caused by non-Pseudomonas aeruginosa non-fermenters (e.g. Burkholderia cepacia complex, Alcaligenes xylosoxidans, Pandoraea apista).
   
   N.B this is an off-license use of Tigecycline that has been approved by the LTHT DTG and requires Microbiology Consultant approval.
   
   
4. Tigecycline can also be used for treatment of infections caused by rapid growing non-tuberculous mycobacteria according to LTHT guidelines.
   
   N.B this is an off-license use of Tigecycline that has been approved by the LTHT DTG and requires Microbiology Consultant approval.
   
   Tigecycline is also used for Treating Infections caused by Carbapenemase Producing Organisms (CPOs)

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Tigecycline can only be prescribed with approval from a consultant medical Microbiologist/infectious disease outside recommended LTH antimicrobial guidelines. The prescribing clinician will be required to provide a code.

Microbiology trainees can recommend Tigecycline in categories 1-3 but should discuss the recommendation with the on-call Consultant at the earliest opportunity.

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