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Dosing of antibiotics for carbapenem-resistant Enterobacterales infections in adults with normal renal function

Dosing of antibiotics for carbapenem-resistant Enterobacterales infections in adults with normal renal function
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)
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
This table lists typical doses for use in CRE infection among patients with normal renal function. Antimicrobial susceptibility should be confirmed for clinical isolates. Higher doses may be warranted for infections of the central nervous system.

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.
Reference:
  1. Tamma PD, Aitken SL, Bonomo RA, et al. IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections: Version 1.0. Infectious Diseases Society of America. Available at: https://www.idsociety.org/practice-guideline/amr-guidance (Accessed October 4, 2022).
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