This term is used to help highlight drug-bug combinations where a high dose of drug would be required to treat the bug. This relates to clinical breakpoints set by EUCAST which the laboratory use to determine a level at which the organism should be deemed susceptible to a particular antibiotic.
| Susceptible, increase exposure (I) |
| A microorganism is categorised as Susceptible, Increased exposure* when there is a high likelihood of therapeutic success because exposure is increased by adjusting the dosing regimen or by its concentration at the site of infections. |
*Exposure is a function of how the mode of administration, dose, dosing intervals, infusion time, as well as distribution, metabolism and excretion of the antimicrobial agent will influence the infecting organism at the site of infection.
(Redefining S, I and R 2019 – www.eucast.org)
The antibiotic classes affected by increased dose requirements are:
The tables below are taken from EUCAST and focused for drugs used within our formulary. (https://www.eucast.org/clinical_breakpoints)
| Penicillins | Standard dosage | High dosage | Special situations |
| Benzylpenicillin | 0.6 g (1 MU) x 4 iv | 1.2 g (2 MU) x 4-6 iv | Meningitis caused by S. pneumoniae: For a dose of 2.4 g (4 MU) x 6 iv, isolates with MIC ≤0.06 mg/L are susceptible.Pneumonia caused by S. pneumoniae: breakpoints are related to dosage: For a dose of 1.2 g (2 MU) x 4 iv, isolates with MIC ≤ 0.5 mg/L are susceptible. For a dose of 2.4 (4 MU) g x 4 iv or 1.2 g (2 MU) x 6 iv, isolates with MIC ≤1 mg/L are susceptible. For a dose of 2.4 g (4 MU) x 6 iv, isolates with MIC ≤2 mg/L are susceptible. |
| Amoxicillin iv | 1 g x 3-4 iv | 2 g x 6 iv | Meningitis: 2 g x 6 iv |
| Amoxicillin oral | 0.5 g x 3 oral | 0.75-1 g x 3 oral | – |
| Amoxicillin-clavulanic iv | (1 g amoxicillin + 0.2 g clavulanic acid) x 3-4 iv | (2 g amoxicillin + 0.2 g clavulanic acid) x 3 iv | |
| Amoxicillin-clavulanic oral | (0.5 g amoxicillin + 0.125 g clavulanic acid) x 3 oral |
(0.875 g amoxicillin + 0.125 g clavulanic acid) x 3 oral | Amoxicillin-clavulanic acid has separate breakpoints for systemic infections and uncomplicated UTI. When amoxicillin-clavulanic acid is reported for uncomplicated UTI, the report must make clear that the susceptibility category is only valid for uncomplicated UTI. |
| Piperacillin-tazobactam | (4 g piperacillin + 0.5 g tazobactam) x 4 iv 30-minute infusion or x 3 iv by extended 4-hour infusion |
(4 g piperacillin + 0.5 g tazobactam) x 4 iv by extended 3-hour infusion |
A lower dosage of (4 g piperacillin + 0.5 g tazobactam) x 3 iv, 30-minute infusion, is adequate for some infections such as complicated UTI, intraabdominal infections and diabetic foot infections, but not for infections caused by isolates resistant to third-generation cephalosporins. |
| Cephalosporins | Standard dosage | High dosage | Special situations |
| Cefazolin | 1 g x 3 iv | 2 g x 3 iv | |
| Cefotaxime | 1 g x 3 iv | 2 g x 3 iv | Meningitis: 2 g x 4 iv S. aureus: High dose only |
| Ceftazidime | 1 g x 3 iv | 2 g x 3 iv or 1 g x 6 iv | – |
| Ceftriaxone | 2 g x 1 iv | 2 g x 2 iv or 4 g x 1 iv | Meningitis: 2 g x 2 iv or 4 g x 1 iv S. aureus: High dose only Uncomplicated gonorrhoea: 0.5-1 g im as a single dose |
| Cefuroxime iv | 0.75 g x 3 iv | 1.5 g x 3 iv | – |
| Cefuroxime oral | 0.25 g x 2 oral | 0.5 g x 2 oral |
| Carbapenems | Standard dosage | High dosage | Special situations |
| Imipenem | 0.5 g x 4 iv over 30 minutes | 1 g x 4 iv over 30 minutes | – |
| Meropenem | 1 g x 3 iv over 30 minutes | 2 g x 3 iv over 3 hours | Meningitis: 2 g x 3 iv over 30 minutes (or 3 hours) |
| Monobactams | Standard dosage | High dosage | Special situations |
| Aztreonam | 1 g x 3 iv | 2 g x 4 iv | Severe P. aeruginosa infections: 2 g x 4 with extended 3-hour infusion |
| Fluoroquinolones | Standard dosage | High dosage | Special situations |
| Ciprofloxacin | 0.5 g x 2 oral or 0.4 g x 2 iv | 0.75 g x 2 oral or 0.4 g x 3 iv | Meningitis: 0.4 g x 3 iv |
| Levofloxacin | 0.5 g x 1 oral or 0.5 g x 1 iv | 0.5 g x 2 oral or 0.5 g x 2 iv | – |
| Ofloxacin | 0.2 g x 2 oral or 0.2 g x 2 iv | 0.4 g x 2 oral or 0.4 g x 2 iv | – |
| Miscellaneous agents | Standard dosage | High dosage | Special situations |
| Chloramphenicol | 1 g x 4 oral or 1 g x 4 iv | 2 g x 4 oral or 2 g x 4 iv | Meningitis: 2 g x 4 iv |
| Trimethoprim-sulfamethoxazole | (0.16 g trimethoprim + 0.8 g sulfamethoxazole) x 2 oral or (0.16 g trimethoprim + 0.8 g sulfamethoxazole) x 2 iv |
(0.24 g trimethoprim + 1.2 g sulfamethoxazole) x 2 oral or (0.24 g trimethoprim + 1.2 g sulfamethoxazole) x 2 iv |
Meningitis: (5 mg/kg up to 0.48 g trimethoprim + 25 mg/kg up to 2.4 g sulfamethoxazole) x 3 iv |
RDUH Medical Microbiology – January 2024
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