Infectious Diseases II
| (9) | Empiric colistin therapy: In an analysis of the association between covering empiric |
|---|
antibiotics and mortality for infections caused by carbapenem-resistant gram-
negative bacteria, the authors concluded that empiric use of colistin before pathogen
identification, with or without a carbapenem, was not associated with survival.
| (b) | Adverse reaction: Nephrotoxicity |
|---|---|
| (1) | Nephrotoxicity |
| (A) | 0%โ45% reported in recent literature, depending on the definitions used for renal |
dysfunction
| (B) | In general, seems to be dose-dependent |
|---|---|
| (C) | Usually reversible, with few cases leading to a prolonged need for renal |
replacement therapy
| (2) | Neurotoxicity |
|---|---|
| (A) | Ranging from paresthesia to apnea |
| (B) | Incidence of 8%โ27% reported in historical studies |
| (C) | Mentioned only in case reports in the current era of colistin use |
| (c) | Polymyxin B: |
| (1) | Mechanism of action, spectrum of activity, and adverse reactions similar to those of |
colistin
| (2) | Available in the United States but not in Europe and Australia |
|---|---|
| (3) | PK/PD |
| (A) | Administered as an active drug |
| (B) | PD targets similar to those of colistin |
| โข | Similar unknowns regarding best dosing regimen to achieve PD parameters |
| โข | Manufacturer-recommended dosing: 1.5โ2.5 mg/kg/day divided every 12 |
hours. Recommends renal dose adjustment, but recent studies suggest minimal
renal clearance.
| (C) | International consensus dosing recommendations |
|---|---|
| โข | Loading dose of 2โ2.5 mg/kg total body weight |
| โข | 1.25โ1.5 mg/kg total body weight every 12 hours |
| (d) | International consensus guidelines for the optimal use of polymyxins |
| (1) | Use therapeutic drug monitoring, when possible (see Pharmacokinetics/ |
Pharmacodynamics chapter for further information regarding colistin therapeutic
drug monitoring).
| (2) | Recommend hospitals have access to both polymyxins |
|---|---|
| (A) | Polymyxin B preferred for routine systemic use because of superior and more |
predictable PK
| (B) | Colistin preferred agent for UTIs |
|---|---|
| (C) | Recent systematic review suggests that polymyxin B is associated with less acute |
kidney injury than colistin.
iii.
Ceftazidime/avibactam
| (a) | Avibactam is a new ฮฒ-lactamase inhibitor approved by the FDA in 2015. |
|---|---|
| (b) | Spectrum of activity: Broad gram-negative activity, including multidrug-resistant |
Pseudomonas and Enterobacterales. Adding avibactam allows coverage against KPC-
producing bacteria, together with coverage against other ฮฒ-lactamases (OXA, CTX-M,
AmpC). Minimal coverage against metallo-ฮฒ-lactamase-expressing strains, Acinetobacter
spp., gram-positive, and anaerobes.