Imepenem / Cilastatin
Imipenem is an intravenous antibiotic that was developed in 1980. It is always administered as a combination of equal quantities of imipenem and cilastatin. Cilastatin helps imipenem work more effectively by preventing the breakdown of the antibiotic in the kidneys. Imipenem has a broad spectrum of activity and has been shown to be effective against the bacteria that cause TB. The imipenem/cilastatin combination is marketed by Merck & Co. under the names Primaxin, Tienam, and Zienam.
Dosage
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_Adults:_ 1000 mg IV every 12 hours
_Adults with liver damage:_
- For creatinine clearance 20–40 ml: 500 mg every 8 hours
- For creatinine clearance < 20 ml/min: 500 mg every 12 hours
_Children:_
- < 1 wk of age: 25 mg/kg every 12 hrs
- 1-4 wks of age: 25 mg/kg every 8 hrs
- 4 wks-3 mos. of age: 25 mg/kg every 6 hrs
_Notes on dosing:_
- Care should be taken when increasing the amoxicillin dose. Taking two tablets of 250mg/125mg of
amoxicillin/clavulanate is not the same as taking one tablet of 500mg/125 mg, because doing so
would result in a double dose of clavulanate.
- The maximum recommended daily dose of clavulanic acid in adults is 500mg.
- Children weighing <40 kg should not receive film-coated tablets with250 mg of amoxicillin, since
this preparation contains a high dose of clavulanate.
- Ampicillin/clavulanate is best tolerated and well absorbed when taken at the start of a meal.
How it works
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Imipenem inhibits cell wall synthesis in bacteria, so that the bacteria break up and die.
Side effects
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The most common side effects of imipenem/cilastatin are mild diarrhea, nausea, and vomiting. More severe and less common side effects include confusion, hallucinations, seizure, light-headedness, skin rash, chest pain, and fast or irregular heartbeat.
Clinical studies and approval
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Imepenem/cilastatin is categorized by the WHO as a Group 5 medication with an “unclear role” in the treatment of drug-resistant TB. Group 5 medications like imepenem/cilastatin should be used after drug options from Groups 1-4 have been exhausted or are unavailable. This is because there is a lack of clinical evidence establishing the effectiveness of imepenem/cilastatin for TB treatment.
A study done at the Univ. of California San Francisco investigated the effectiveness of imipenem in a mouse model of TB and in humans with MDR TB. TB-infected mice were treated with isoniazid or imipenem to compare the efficacy of the two drugs. Ten MDR TB-infected patients were treated with imipenem in combination with other first or second-line drugs.
The results of the study, which were published in 2005, indicate that imepenem/cilastatin is active against drug-resistnat TB. Although it is less effective then isoniazid, imipenem significantly reduced infection with TB bacteria and improved the survival rates of mice. Among the patient group, eight of ten individuals responded positively to imipenem therapy and experienced sputum conversions to negative. Seven of those remained negative when taken off therapy. The study concluded that imipenem has “antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis.”[^Chambers]
The effectiveness of imipenem/cilastatin as a treatment for TB has also been suggested by other reports of at least three patients with drug-resistant TB in the U.S. who have had their infections eliminated with a combination of imipenem and a drug called amikacin. These patients had no recurrence in 12 months of follow-up.[^Journal]
Pricing
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Imipenem 500 mg and Cilastatin Sodium 500 mg injection, 120 ml vial (for IV infusion): R121.10
Advocacy issues
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- Further studies are needed to establish the effectiveness of imipenem/cilastatin in the
treatment of drug-resistant TB.
- There is no pediatric formulation of the medication, and its safety and effectiveness in
pediatric patients below the age of 12 have not been established.
- Using the medication for an “off-label” purpose such as TB treatment poses liability issues that
may become an issue for healthcare providers if patients respond adversely.
[^Chambers]: H. Chambers et al. Imipenem for Treatment of Tuberculosis in Mice and Humans. Antimicrob Agents Chemoth. 2005; 49(7): 2816-2821.
[^Journal]: Journal of Antimicrobial Therapy. 2006; 58(5): 916-929.