Osteomyelitis

Therapeutic Goals

Therapeutic Goal Monitoring

Treatment

Non-Pharm/CAM

Vancomycin

Cephalosporins

Linezolid

Clindamycin

Doxycycline

Regimen: 15-20 mg/kg IV q8-12h

Bactrim

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)

Resolution of infection

Primarily excreted through glomerular filtration

Prevention of long term sequelae

Not metabolized

ADE: Nephrotoxicity, ototoxicity, Red Man Syndrome, Thrombophlebitis

Prevent amputation, decrease in QoL, recurrent infection

MOA

monitor for s/sx of inflammation daily during start of treatment

BBW: Colitis - C.Difficile -associated diarrhea

WBC counts weekly until WNL

C-reactive protein or ESR weekly during therapy

MOA: Reversibly binds to 50s ribosome to prevent peptide formation thus inhibiting bacterial synthesis

culture and susceptibility before initiation only unless clinical failure

adherence to outpatient therapy for maximum effectiveness

Antimicrobial Activity: Gram +: Staphylococcus (MRSA), Streptococcus, Enterococcus, Cornyebacterium, Clostridium, Listeria

CBC weekly because some antibiotics may cause blood abnormalities

PK

ADR: rash, urticaria, N/V, loss of appetite, C diff, hepatotoxicity, hyperkalemia, hematologic effects, hypoglycemia, hyponatremia, hypersensitivity

BBW: Risk of embryo fetal toxicity (excipients: PEG 400, NADA)

Regimen

Monitoring

DDI: dofetilideamiodarone, 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

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

Regimen: Initial - 600 mg IV every 6-8 hours for 1-2 weeks
Followed by 300-450 mg every 6 hours

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)

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

Monitoring: CTrough, Sir, ADR (ototoxicity, Red Man Syndrome, Thrombophelbitis), resolution of infection

A: rapid and almost complete absorption

D: middle ear fluic, sputum, vaginal fluid, bronchial secretions

M: hepatic

E: prolonged in renal failure

weight-based dosing based on TMP component

Warnings/Precautions

double strength: TMP 160 mg SMX 800 mg

single strength: TMP 80 mg SMX 400 mg

Concurrent nephrotoxic therapies

usually 4-6 weeks in duration

Baseline renal impairment

Secondary Infections (C.Diff)

Contraindication: Hypersensitivity to clindamycin, lincomycin, or any component of the formulation

IV: TMP 16 mg/mL SMX 80 mg/mL

Contraindication: Hypersensitivity

IV: 4 mg/kg/dose Q12H with rifampin

Surgical debridement of infected tissue

DDIs: other nephrotoxic agents

Special Populations

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

Geriatrics: Reduced Clearance

Pregnancy: Avoid PEG 400/NADA formulations

Renal Dose Adjustment

ADE: Metallic taste, hypotension, thrombophlebitis,

Education: when to pull trough levels

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

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

Regimen: 100 mg IV q12h

DDIs: BCG, live cholera vaccine, live typhoid vaccine

PK/PD/PGx

Widely distributed into tissues/fluids

M: Not hepatic, partially inactivated in GI by chelation

E: Urine, feces

Monitoring: Changes in bowels, colitis, resolution of symptoms. LFT in severe liver disease. CBC, liver and renal function in prolonged therapy

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

Trough: 15-20 mg/L

Special Populations: - Pregnancy - clindamycin crosses the placenta; Breastfeeding - clindamycin is in the breast milk;

CBC, potassium, SCr, BUN

ADR: Photosensitivity, GI Upset, increased AST/ALT

Monitoring: weekly CBC and blood chemistries to assess renal fxn, liver fxn tests, and signs of anaphylaxis during first dose

Monitoring: CBC, Renal and Liver Function

Warnings/Precautions: Intracranial Hypertension

Contraindications: Hypersensitivity

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)

DDI

Antacids/Iron/Ca/Mg/Multivitamins/Etc (separate admin)

Warfarin

Special Pops: Renal dosing, reduced clearance

Not indicated in pregnancy

Education: Separating meds

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

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.

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

use for osteomyelitis due to MRSA

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

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)

Warning/Precautions: Use with caution in people with carcinoid syndrome, diabetes, HTN, hyperthyroidism, Pheochromocytoma, seizure disorders