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Osteomyelitis - Coggle Diagram
Osteomyelitis
Therapeutic Goals
Resolution of infection
Prevention of long term sequelae
Prevent amputation, decrease in QoL, recurrent infection
Therapeutic Goal Monitoring
monitor for s/sx of inflammation daily during start of treatment
WBC counts weekly until WNL
C-reactive protein or ESR weekly during therapy
culture and susceptibility before initiation only unless clinical failure
adherence to outpatient therapy for maximum effectiveness
CBC weekly because some antibiotics may cause blood abnormalities
Treatment
Vancomycin
Regimen: 15-20 mg/kg IV q8-12h
Usually 6 week duration
Adjust based on therapeutic monitoring
MOA: Inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to D-alanyl-D-alanine portion of cell wall precursor
PD/PK/PGx
Wide distribution (except CSF)
Primarily excreted through glomerular filtration
Not metabolized
Antimicrobial Activity: Gram +: Staphylococcus (MRSA), Streptococcus, Enterococcus, Cornyebacterium, Clostridium, Listeria
ADE: Nephrotoxicity, ototoxicity, Red Man Syndrome, Thrombophlebitis
BBW: Risk of embryo fetal toxicity (excipients: PEG 400, NADA)
Monitoring: CTrough, Sir, ADR (ototoxicity, Red Man Syndrome, Thrombophelbitis), resolution of infection
Trough: 15-20 mg/L
Warnings/Precautions
Concurrent nephrotoxic therapies
Baseline renal impairment
Secondary Infections (C.Diff)
Contraindication: Hypersensitivity
DDIs: other nephrotoxic agents
Special Populations
Geriatrics: Reduced Clearance
Pregnancy: Avoid PEG 400/NADA formulations
Renal Dose Adjustment
Education: when to pull trough levels
Cephalosporins
MOA
: Inhibits cell wall synthesis by binding to penicillin-binding proteins (PBPs), which in turn inhibits final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse
ADE
: Common: pruritus, rash, diarrhea, eosinophil count raised
Serious: SJS,
C. diff.
colitis, leukopenia, neutropenia, thrombocytopenia, hepatitis, anaphylaxis, hypersensitivity rxn, infection caused by multi-drug-resistant bacteria, renal failure
Monitoring
: weekly CBC and blood chemistries to assess renal fxn, liver fxn tests, and signs of anaphylaxis during first dose
warnings
: potential for elevated INR, hypersensitivity rxns, use with caution in its with hx of PCN allergy, prolonged use may result in fungal or bacterial superinfection, including
C. diff.
Regimen
: cefazolin: (Adult) 2 g IV q8h; (children) 100-150 mg/kg/day in 3 equal doses (max dose 6 g daily). (MSSA drug of choice; can be used in newborns, children, or adults)
cephalexin 500 mg PO q6h
ceftazidime 2 g IV q8h
cefepime 2 g IV q8h
ceftriaxone 2 g q24h (no MRSA coverage)
Linezolid
MOA:
Inhibit bacterial protein synthesis by binding to the ribosomal 23S subunit of the 50S, preventing formation of the 70S subunit needed for bacterial translation
Regimen:
Oral, IV 600 mg every 12 hours
Duration: 6 weeks
PD/PK/PGx:
Absorption: Rapid and extensive
D: Adult: 0.65 L/kg; Adolescent: 0.61 L/kg
Protein Binding: 31%
Excretion: Urine ( ~30% as parent drug; ~50% as metabolites)
Special Population:
Limited data in pregnancy; Present in breast milk
Dosage adjustment in obesity; not recommended in pediatrics
DDI:
MAOIs, any psychiatric medications with serotonin
Monitoring:
weekly CBC, in renal impairment: monitor for anemia, and neuropathic adverse events.
ADEs:
Diarrhea, decreased platelet counts, decreased WBC, lactic acidosis, myelosuppression, peripheral and optic neuropathy, serotonin infection, superinfection
Warning/Precautions:
Use with caution in people with carcinoid syndrome, diabetes, HTN, hyperthyroidism, Pheochromocytoma, seizure disorders
Clindamycin
BBW:
Colitis - C.Difficile -associated diarrhea
MOA:
Reversibly binds to 50s ribosome to prevent peptide formation thus inhibiting bacterial synthesis
Regimen:
Initial - 600 mg IV every 6-8 hours for 1-2 weeks
Followed by 300-450 mg every 6 hours
usually 4-6 weeks in duration
Contraindication:
Hypersensitivity to clindamycin, lincomycin, or any component of the formulation
ADE:
Metallic taste, hypotension, thrombophlebitis,
PD/PK/PGx
D: Distributed in body fluid and tissues
Protein binding: 94%
Metabolized into active form by CYP3A4 ( minor CYP3A5)
Excretion: 10% in urine; 3.6% in feces as active drug
DDIs:
BCG, live cholera vaccine, live typhoid vaccine
Monitoring:
Changes in bowels, colitis, resolution of symptoms. LFT in severe liver disease. CBC, liver and renal function in prolonged therapy
Special Populations:
- Pregnancy - clindamycin crosses the placenta; Breastfeeding - clindamycin is in the breast milk;
Doxycycline
Regimen: 100 mg IV q12h
PK/PD/PGx
Widely distributed into tissues/fluids
M: Not hepatic, partially inactivated in GI by chelation
E: Urine, feces
MOA: Inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane
ADR: Photosensitivity, GI Upset, increased AST/ALT
Monitoring: CBC, Renal and Liver Function
Warnings/Precautions: Intracranial Hypertension
Contraindications: Hypersensitivity
DDI
Antacids/Iron/Ca/Mg/Multivitamins/Etc (separate admin)
Warfarin
Special Pops: Renal dosing, reduced clearance
Not indicated in pregnancy
Education: Separating meds
Bactrim
MOA
sulfamethoxazole: prevents folic acid synthesis and grown by inhibiting para-aminobenzoic acid from becoming dihydrofolic acid
trimethoprim: inhibits reduction of dihydrofolic acid to tetrahydrofolate to inhibit enzymes in folic acid pathway
PK
A: rapid and almost complete absorption
D: middle ear fluic, sputum, vaginal fluid, bronchial secretions
M: hepatic
E: prolonged in renal failure
ADR: rash, urticaria, N/V, loss of appetite,
C diff, hepatotoxicity, hyperkalemia, hematologic effects, hypoglycemia, hyponatremia, hypersensitivity
Regimen
weight-based dosing based on TMP component
double strength: TMP 160 mg SMX 800 mg
single strength: TMP 80 mg SMX 400 mg
IV: TMP 16 mg/mL SMX 80 mg/mL
IV: 4 mg/kg/dose Q12H with rifampin
Monitoring
CBC, potassium, SCr, BUN
DDI:
dofetilide
amiodarone, chloroquine, erythromycin, fluconazole, clarithromycin, antipsychotics, digoxin, warfarin
Warnings: blood abnormalities, skin reactions, liver effects, hyperkalemia, hypoglycemia, hyponatremia, sulfa allergy, superinfection with prolonged use, thrombocytopenia
Special Populations: AIDS - increased risk of ADRs, elderly - increased risk of ADRs (hyperkalemia with spironolactone, ACE inhibitors, ARBs), G6PD deficiency, folate deficiency, porphyria, slow acetylators - increase risk of ADRs
can be used in pregnancy - sufficient maternal folic acid supplementation may decrease risk of neural tube defects (avoid in 3rd trimester, only use in 1st trimester if no other options available)
Education: may cause sensitivity to sun, stay hydrated to avoid crystalluria, contact doctor if develop skin reaction (SJS) or signs of hepatic necrosis (jaundice, abdominal pain), may cause anorexia/N/V
Contraindications: hypersensitivity to sulfa drugs or TMP, drug-induced immune thrombocytopenia with SMX or TMP, megaloblastic anemia due to folate deficiency, infants <2 months (package insert) or <4 weeks (CDC), severe hepatic or renal damage, use with dofetilide (cardiotoxicity)
use for osteomyelitis due to MRSA
Non-Pharm/CAM
Surgical debridement of infected tissue