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C. Diff Infection/Skin & Soft Tissue Infection - Coggle Diagram
C. Diff
Infection/Skin & Soft Tissue Infection
Metronidazole
Used for nonsevere or fulminant C diff In combination with vancomycin
Dosing (C diff)
:
Nonsevere
- 500 mg PO q8h for 10 days;
Fulminant
- 500 mg IV q8h + vancomycin 500 mg q6h via NG or PO
Hepatic Impairment
Child-Pugh class A/B: No dosage adjustment necessary; use with caution
Child-Pugh class C: Reduce by 50% (IR tabs, Injection); do not use ER tabs
Renal Impairment
CrCl ≥10 mL/minute: No dosage adjustment necessary (expert opinion; manufacturer's labeling); monitor for AEs d/t accumulation of metabolites (CrCl <30 mL/minute), particularly with prolonged courses of therapy
CrCl <10 mL/minute: No dosage adjustment necessary (expert opinion; manufacturer's labeling); monitor for AEs d/t accumulation of metabolites, particularly with prolonged courses of therapy. A dose of 500 mg every 12 hours may be adequate to achieve therapeutic plasma levels
Pearls
Metalic taste
Use should be limited to Initial episodes of nonsevere CDI or In combo with vancomycin
Disulfiram-like rxn w/ alcohol!
BBW
: Carcinogenic (mice/rats) - unnecessary use should be avoided
bug: gram (+) and gram (-) anaerobes
AEs
: CNS effects (peripheral neuropathy, confusion, ataxia, encephalopathy, seizures, vertigo); disulfiram-like rxn (used with alcohol); nausea, vaginitis, headache
Onset: median of 28 days reported; also median of 54 days reported
Risk factors: High doses, high cumulative doses, or prolonged or repeated courses
CIs
: hypersensitivity, pregnant pts (1st trimester) with trichomoniasis, use of disulfiram In last 2 weeks, alcohol
Warnings
: carcinogenic, CNS effects, superinfection (CDAD), blood dycrasias, alcohol, renal/hepatic Impairment, seizure disorder, Cockayne syndrome
Monitoring
: CBC w/ differential at baseline, during, and after prolonged or repeated courses of therapy. LFTs (Cockayne syndrome). Monitor elderly patients and patients with severe hepatic/renal impairment for adverse reactions. Monitor neurologic symptoms
MOA
: passive diffusion Into anaerobic bacteria cytoplasm; interacts with intracellular DNA resulting in the inhibition of DNA synthesis and degradation and ultimately bacterial death
PK
A: oral, well absorbed
D: To bile, seminal fluid, bone, liver, and liver abscesses, lung and vaginal secretions; crosses blood-brain barrier; saliva and CSF concentrations similar to those in plasma; protein binding <20%
t1/2: 8 hours (range 6 to 12 hours)
M: Substrate of CYP2A6 (major); Inhibits CYP2C9 (weak)
E: Urine (unchanged drug and metabolites: 60% to 80%; ~20% of total as unchanged drug)
Dosing (SSTI)
Necrotizing infection: IV: 500 mg every 6 hours. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48-72 hours
Surgical site infection, incisional (eg, intestinal or GU tract; axilla or perineum), warranting anaerobic coverage: IV: 500 mg every 8 hours in combination with other appropriate agents. Duration depends on severity, need for debridement, and clinical response
Vancomycin (Oral)
Pearls
Ineffective for treating systemic infections (ie. SSTI); may be taken with food
Dosing
NONSEVERE:
125mg 4x daily for 10 days
(initial occurrence); Pulsed-tapered regimen:
125 mg 4 times daily for 10 to 14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2 or 3 days for 2 to 8 weeks
(first recurrence when vanc was used initially);
125mg 4x daily for 10 days
if metronidazole/fidoxamicin was used initially
SEVERE:
125mg 4x daily
FULMINANT (sudden/severe in onset)
500mg 4x daily with IV metronidazole
Special Populations
No renal/hepatic dose adjustment d/t low systemic absorption; standard doses used in pregnancy
Adverse Effects
hypokalemia, nausea, abdominal pain
Bug
: C. diff (gram (+) anaerobe)
Monitoring
serum vanc levels may be appropriate in patients with colitis/renal failure d/t mucosal disruption
MOA
Inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to D-alanyl-D-alanine portion of cell wall precursor
PK/PD
Very poor oral absorption; excreted in feces; no apparent metabolism
Fidaxomicin
MOA:
inhibit RNA polymerase subunit which inhibits protein synthesis and causes cell death; bactericidal
PK/PD/PGx
A: Oral absorbed; minimal systemic absorption
D: Largely confined in GI
M: Intestinal metabolism to inactive metabolites
E: Mostly in feces ( > 92% unchanged); urine ( <1% unchanged)
Special Population:
Pregnancy - limited systemic absorption may affect fetal exposure; Breastfeeding - no data; Geriatric: Plasma concentration may be 2-4 fold higher; Pediatric: Weight-based dosing
Warning/Precautions:
Hypersensitivity; Macrolide allergy; DO NOT USE for systemic infections; use only in patients with proven or strongly suspected
C.diff
infections
Dosing:
(Oral) - 200 mg BID for 10 days for
C.Diff
infection
No adjustment needed for hepatic and renal impairment
Pediatric dosing:
Indicated only for multiple reoccurrence of infection
Based on weight - 16 mg/kg/dose twice daily for 10 days; maximum dose: 200 mg/dose
Pearls:
Fidaxomicin is recommended as tx option for initial
C.Diff
episode, first reoccurrence or second and subsequent reoccurrence; May be administered with or without food
ADR:
Nausea (adult) ; Fever ( infant, children and adolescent);
DDIs:
Live typhoid vaccine; cholera vaccine; Mizolastine; Sodium Picosulfate
bug: C diff (gram (+) anaerobe)
Bezlotoxumab
MOA: Human monoclonal antibody that binds to C.Diff toxin B and neutralizes it to prevent toxic effects (does NOT bind to toxin A)
PK/PD/PGx
Metabolized/Excreted via catabolism
T1/2~19 days
Regimen: 10 mg/kg IV once
Warnings/Precautions: Heart Failure
Contraindications: None listed per package insert, but has not been studied in Peds
DDI: None known
ADR: Exacerbation of heart failure, headache, nausea, infusion related reactions
Special Populations
Has not been studied in Peds
Can exacerbated underlying CHF
Education: this won't treat your infection, only helps to prevent it from coming back in the future
bug: C diff (gram (+) anaerobe)
Monitoring: N/A
Amoxicillin/clavulanate
PK: Well-absorbed PO, extensive hepatic metabolism, amoxicillin: 50-70% renal excretion unchanged
cclavulanic acid: 25-40% renal excretion unchanged
MOA: clavulanic acid binds to and inhibits beta-lactamases that inactivate amoxicillin = amoxicillin expanded spectrum of activity. Amoxicillin is beta lactam and inhibits cell wall synthesis of bacterial cells
ADR: GI upset (diarrhea, nausea, vomiting), rash, SJS, hepatotoxicity, anaphylaxis
Regimen (general, based on amoxicillin dose):
PO: IR 500 mg q8-12h OR 875 mg q12h; ER 2 g q12h
diabetic foot infection (off-label): may be used alone or for mild infections after clinical response to parenteral therapy in its without risk factors or concern for infection caused by
P. aeruginosa
IR 875/125 mg PO q12h. Duration tailored to individual; most respond in 1-2 weeks
Mild/Moderate SSTI: IR 500/125 mg PO q12h or 250/125 mg PO q8h.
Severe SSTI: IR 875/125 mg (amoxicillin component) PO q12h or 500/125 mg PO q8h
bug: gram (+) (and gram (+) anaerobes) and gram (-)
Monitoring: CBC for clinical response, culture/susceptibility tests if appropriate to monitor for therapeutic effect and bacterial resistance, resolution of s/sx of infection, hepatic fxn, especially in hepatically impaired
Duration: Depends on infection type
Warings/Precautions: prolonged use may lead to fungal or bacterial superinfection. Due to clavulanic acid component, not all formulations are interchangeable. Inappropriate use may lead to diarrhea or sub therapeutic clavulanic acid concentrations leading to decreased clinical efficacy
Interactions: penicillins may interfere with serum concentrations of multiple drugs, including allopurinol, lactobacillus, tetracyclines, vitamin K antagonists (warfarin), and others.
Special populations: Dose-adjust in CrCl <30 ml/min
Pediatrics have own dosing.
Education: May cause GI upset including N/V/D; take at the beginning of a meal to avoid upset stomach and enhance absorption.
C. diff
Goals
resolution of infection
avoid adverse effects
maximize adherence
limit risk factors: acid suppression, antimicrobials
Monitoring
resolution of diarrhea
adverse effects: metallic taste, nausea, abdominal pain, CNS effects)
monitor use of other agents that may cause C. diff
ensure adherence
Non-pharm
fluid/electrolyte replacement therapy
removal of offending antimicrobial
SSTI
Goals
quickly resolve infection
prevent further complications
avoid unnecessary antimicrobials (increase resistance, minimize toxicities, affordable)
preserve limb function (diabetic foot infection)
Monitoring
monitor for efficacy and ensure that selected antimicrobial is working
blood/tissue culture - change therapy if necessary
Non-pharm
Elevation and immobilization of the involved area to decrease swelling
Cool sterile saline dressing may decrease pain (can be followed later with moist heat)
Surgical intervention rarely indicated, may be useful in more severe or complicated cases3