Version July 2025
| Class | Agent | Dosage |
| Standard-spectrum antibiotics other than carbapenems, if susceptible | ||
| Fluoroquinolones | Ciprofloxacin | 400 mg IV every 8 hours or 750 mg orally every 12 hours |
| Levofloxacin | 750 mg IV or orally once daily | |
| Sulfonamides | Trimethoprim-sulfamethoxazole (co-trimoxazole) | Simple cystitis: 1 double-strength tablet (trimethoprim 160 mg and sulfamethoxazole 800 mg) orally every 12 hours. Infections other than simple cystitis: 8 to 12 mg/kg/day (trimethoprim component) IV or orally in 2 or 3 divided doses (eg, 2 double-strength tablets orally every 12 hours for a patient who weighs 70 kg). Maximum: 960 mg (trimethoprim component) per day. |
| Aminoglycosides | Gentamicin* | Simple cystitis: 5 mg/kg IV for one dose Infections other than simple cystitis: 7 mg/kg IV for the first dose with subsequent doses and dosing intervals based on pharmacokinetic evaluation |
| Tobramycin* | Simple cystitis: 5 mg/kg IV for one dose Infections other than simple cystitis: 7 mg/kg IV for first dose with subsequent doses and dosing intervals based on pharmacokinetic evaluation | |
| Plazomicin* | Simple cystitis: 15 mg/kg IV for one dose Infections other than simple cystitis: 15 mg/kg IV for first dose with subsequent dosing interval adjusted if needed based on trough concentration | |
| Other standard-spectrum antibiotics | Nitrofurantoin¶ | Simple cystitis: Macrocrystal/monohydrate (Macrobid) 100 mg orally every 12 hours |
| Fosfomycin¶ | Simple cystitis: 3 g orally for one dose | |
| MinocyclineΔ | 200 mg IV or orally every 12 hours | |
| Carbapenem antibiotics, if susceptible | ||
| Carbapenems | Meropenem | Simple cystitis: 1 g IV every 8 hours (infuse each dose over 30 minutes) Infections other than simple cystitis: 2 g IV every 8 hours (infuse each dose over 3 hours)◊ |
| Imipenem-cilastatin | Simple cystitis: 500 mg IV every 6 hours (infuse each dose over 30 minutes) Infections other than simple cystitis: 500 mg IV every 6 hours (infuse each dose over 3 hours)◊ | |
| Novel extended-spectrum antibiotics | ||
| Advanced beta-lactamase inhibitor combinations§ | Ceftazidime-avibactam | 2.5 g IV every 8 hours (infuse each dose over 2 to 3 hours)◊ |
| Meropenem-vaborbactam | 4 g IV every 8 hours (infuse each dose over 3 hours)◊ | |
| Imipenem-cilastatin-relebactam | 1.25 g IV every 6 hours (infuse each dose over 30 minutes) | |
| Aztreonam-avibactam | 2.67 g IV loading dose, followed by 2 g IV every 6 hours (infuse each dose over 3 hours) | |
| Siderophore cephalosporin | Cefiderocol | 2 g IV every 8 hours (infuse each dose over 3 hours)◊ |
| Novel tetracycline derivatives | TigecyclineΔ | 200 mg IV loading dose, followed by 100 mg IV every 12 hours |
| EravacyclineΔ | 1 mg/kg/dose IV every 12 hours | |
| Combination therapy¥ | Ceftazidime-avibactam plus Aztreonam | Ceftazidime-avibactam 2.5 g IV every 8 hours (infuse each dose over 3 hours)◊ plus Aztreonam 2 g IV every 8 hours (infuse each dose over 3 hours) administered at the same time as ceftazidime-avibactam, if possible |
CRE: carbapenem-resistant Enterobacterales; IV: intravenously; OXA-48: OXA-48-like carbapenemases.
* Aminoglycosides can be used as monotherapy for susceptible CRE urinary tract infections (UTIs) when other options are limited. They should not be used as single agents for infections outside the urinary tract. For patients >120% of ideal body weight, use adjusted body weight for aminoglycoside dosing; a calculator is available. For selection of dosing weight and determination of dose adjustments, refer to UpToDate content on dosing and administration of aminoglycosides.
¶ Nitrofurantoin and fosfomycin are effective for simple cystitis but neither agent should be used for complicated UTIs (eg, pyelonephritis) or for infections outside the urinary tract. Fosfomycin should only be used for simple cystitis caused by E. coli.
Δ Tigecycline and eravacycline are effective for intra-abdominal infections, but data supporting their use for CRE infections at other anatomical sites are scarce. Minocycline should not be used a monotherapy for intra-abdominal infections. None of these agents should be used to treat UTIs or bacteremia because they may not achieve adequate levels in the urine or blood.
◊ May administer first dose first dose over 30 minutes when rapid attainment of therapeutic drug concentrations is desired.
§ These agents have no activity against metallo-beta-lactamase carbapenemase (MBL)-producing isolates. Additionally, meropenem-vaborbactam and imipenem-cilistatin-relebactam have limited intrinsic activity against OXA-48-like-producing isolates.
¥ We generally avoid combination therapy. An exception is the combination of ceftazidime-avibactam and aztreonam for MBL-producing isolates, if aztreonam-avibactam is not available.
Adapted from: Tamma PD, Aitken SL, Bonomo RA, et al. Infectious Diseases Society of America 2023 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis 2023; ciad428.
Prepared with additional information from: Emblaveo (aztreonam and avibactam). US Food and Drug Administration (FDA) approved product information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217906Orig1s000lbl.pdf (Accessed on March 19, 2025).
