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Treatment of MDR Gram-negative bacilli

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Green, susceptibility anticipated to be >80%; yellow, susceptibility anticipated to be 30% to 80%; red, intrinsic resistance or susceptibility anticipated to be <30%. 1, US Food and Drug Administration–approved agent; 2, synthetic tetracycline derivative; 3, imipenem-cilastatin–relebactam; 4, synthetic aminoglycoside; 5, polymyxin class. Abbreviations: KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase. (Tamma et al., 2024)

ESBL

  • Carbapenem
  • Fluoroquinolone (UTI)
  • TMP-SMX (UTI)
  • Aminoglycoside (UTI)
  • Fosfomycin (uncomplicated cystitis, E. coli only)
  • Pip/tazo (uncomplicated cystitis, clinically improving)
  • Cefepime (uncomplicated cystitis, clinically improving)

AmpC β-lactamase

  • Cefepime
  • TMP-SMX (UTI)
  • Fluoroquinolone (UTI)
  • Single-dose aminoglycoside (uncomplicated cystitis)
  • Ceftriaxone (uncomplicated cystitis)

CRE

R to ertapenem only

  • Extended-infusion meropenem or imipenem/cilastatin

UTI

  • TMP-SMX
  • Fluoroquinolone
  • Aminoglycoside
  • Cefiderocol
  • Ceftazidime-avibactam
  • Imipenem-cilastatin-relebactam
  • Meropenem-vaborbactam
  • Colistin (uncomplicated cystitis)
  • Fosfomycin (uncomplicated cystitis, E. coli only)

KPC

  • Ceftazidime/avibactam
  • Imipenem-cilastatin-relebactam
  • Meropenem-vaborbactam
  • Cefiderocol
  • Minocycline (non-UTI or BSI)
  • Tigecycline (non-UTI or BSI)

OXA-48

  • Ceftazidime/avibactam
  • Cefiderocol

NDM

  • Cefiderocol
  • Ceftazidime/avibactam + aztreonam

CRPA

  • Extended-infusion non-carbapenem β-lactam (if S)
  • Ceftazidime/avibactam
  • Cefiderocol
  • Ceftolozane-tazobactam
  • Imipenem-cilastatin-relebactam
  • Aminoglycoside (UTI)
  • Colistin (uncomplicated cystitis)

CRAB

  • Colistin + (sulbactam or fosfomycin)
  • High-dose minocycline (200mg Q12H)
  • High-dose tigecycline (100mg Q12H)
  • Cefiderocol（上述治療無效或沒其他藥可用時）
  • Sulbactam-durlobactam + (meropenem or imipenem/cilastatin)

Ampicillin/Sulbactam Dosage Adjustment Recommendations for Kidney Impairment when Treating Multidrug-resistant A. baumannii Infection

CrCl (mL/min) Traditional Intermittent Infusion (3 g IV every 4 hours over ≤30 min) Extended Infusion (9 g IV every 8 hours over 4 hours) Continuous Infusion (27 g IV over 24 hours)
≥90 to 130 No dosage adjustment necessaryb No dosage adjustment necessaryc,d No dosage adjustment necessary
60 to <90 No dosage adjustment necessaryb 6 g IV every 8 hours over 4 hoursc,d 18 g IV over 24 hoursc
30 to <60 3 g IV every 6 hoursb 3 g IV every 6 hours over 4 hoursc,d 12 g IV over 24 hoursc
15 to <30 3 g IV every 8 hoursb 3 g IV every 8 hours over 4 hoursc,d 9 g IV over 24 hoursc
<15 3 g IV every 12 hoursb 3 g IV every 12 hours over 4 hourse 6 g IV over 24 hourse

a The proposed renal dose adjustments are aimed at achieving pharmacokinetic/pharmacodynamic targets based on in-vitro or pharmacokinetic modeling. Clinical data are not available.
b Expert opinion derived from Yokoyama 2015. Doses in Yokoyama 2015 are in grams of sulbactam; the doses listed below are multiplied by 3 to account for both ampicillin and sulbactam components.
c Expert opinion derived from Jaruratanasirikul 2019. Doses in Jaruratanasirikul 2019 are in grams of sulbactam; the doses listed below are multiplied by 3 to account for both ampicillin and sulbactam components.
d Lower doses may be sufficient for patients with lower albumin concentrations (e.g., 1.7 to 2.4 g/dL) and isolates with lower minimum inhibitory concentrations. See Jaruratanasirikul 2019 for patient-specific recommendations.
e Expert opinion.

Ref: UpToDate

S. maltophila

  • TMP-SMX (10–15 mg/kg TMP)
  • Levofloxacin (750mg QD)
  • High-dose minocycline (200mg Q12H)
  • Cefiderocol

Reference

Tamma, P.D., Heil, E.L., Justo, J.A., Mathers, A.J., Satlin, M.J. & Bonomo, R.A. (2024) Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clinical Infectious Diseases. ciae403. doi:10.1093/cid/ciae403. 

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