J: Antiinfectives for systemic use
Group J holds the anti-infectives for systemic use: antibacterials, antimycotics (antifungals), antimycobacterials and antivirals, together with immune sera, immunoglobulins and vaccines [1].
In 1928, Alexander Fleming noticed by chance, in his London laboratory, a zone around a contaminating mold on an agar plate in which bacteria did not grow. The first person to receive penicillin, in February 1941, was an Oxford policeman. The supply ran out before he could be fully treated, and he died. Fleming, Chain and Florey shared the 1945 Nobel Prize in Physiology or Medicine [2].
| Description | In plain terms | Example drug | |
|---|---|---|---|
| J01 | Antibacterials for systemic use | Amoxicillin (J01CA04) / ceftriaxone (J01DD04) | |
| J02 | Antimycotics for systemic use | antifungals taken into the bloodstream | Fluconazole (J02AC01) / caspofungin (J02AX04) |
| J04 | Antimycobacterials | drugs against tuberculosis and leprosy | Rifampicin (J04AB02) / isoniazid (J04AC01) |
| J05 | Antivirals for systemic use | Dolutegravir (J05AJ03) / sofosbuvir (J05AP08) | |
| J06 | Immune sera and immunoglobulins | ready-made antibodies given as instant protection | Normal human immunoglobulin for intravascular administration (J06BA02) / nirsevimab (J06BD08) |
| J07 | Vaccines | Influenza, inactivated, split virus or surface antigen (J07BB02) / covid-19, RNA-based vaccine (J07BN01) |
Exposure relative to the MIC
For antimicrobial agents, PK/PD indices relate drug exposure to the minimum inhibitory concentration (MIC) of the infecting organism, and there is a standard terminology for them, in which the unbound (free) concentration is marked with an f, as in fAUC/MIC [3]. The indices themselves are described under J01.
Only the unbound fraction of a drug in plasma can pass into and equilibrate with the extravascular space. Penetration matters because most bacterial and fungal infections occur in the interstitial fluid of tissues or in body fluids other than blood. There is no standardization for pharmacodynamic models that account for protein binding in vitro [4].
Toxicity and drug monitoring
Some antimicrobials have well-defined dose-dependent toxicities, but for many others the exposure-toxicity relationship is poorly defined or has not been evaluated. The data support an upper exposure limit for therapeutic drug monitoring for the aminoglycosides, vancomycin, linezolid and the polymyxins among the antibacterials, and for voriconazole (J02AC03) and flucytosine (J02AX01) among the antifungals [5]. The antibacterial and antiviral cases are described under J01 and J05.