Exam 1 Beta Lactams

Beta lactams - Safe in pregnancy - Time dependent killing - Meropenem and ampicillin  enter CSF - Cefazolin and Zosyn  do not enter CSF - Don’t need dose adjustment o Nafcillin o Oxacillin o Ceftriaxone - Ceftriaxone and ertapenem  take 24 hour o Rest are short half lives - Natural pencillins o DOC for   Syphilis. Strep throat Erysipelas - Aminopenicillins treats o Enterococcus infections (DOC for E. faecalis) o Listeria (DOC) Penicillinase-Resistant Penicillins treat o MRSA Antipseudomonal Penicillins o Piperacillin  works better with combination  Combined with tazobactam (zosyn) - - Beta Lactams ADRs o Hypersensitivity o Low white blood cell (neutropenia) o Seizure o N/V/D o More serious Pseudomembranous Colitis (linked to overgrowth of C. difficile)  especially with the use of extended/broad-spectrum cephalosporins) Cephalosporins - First gen  surgery prophylaxis o Cefazolin (anicef)  o Cephalexin (Keflex) - - Second gen  useful for intra-abdominal surgery o IV  Cefoxitin (Mefoxin)  Cefotetan (Cefotan) o IV/PO  Cefuroxime (Zinacef, Ceftin) Third gen o IV  Ceftazidime (Fortaz) o - - PO Fourth gen o IV  • active against Pseudomonas aeruginosa Ceftriaxone (Rocephin)   Cefdinir (Omnicef) Cefixime (Suprax) Cefepime (Maxipime) • active against Pseudomonas aeruginosa fifth generation o IV  Ceftaroline (Teflaro) • complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP)  cephalosporins ADRs - Allergic Reactions: Rash, itching, and rare anaphylaxis. Gastrointestinal Issues: Diarrhea, nausea, and risk of C. difficile infection. Hematologic Changes: Low blood counts like neutropenia. Renal Toxicity: Potential kidney issues, especially with pre-existing conditions. Seizures: Risk in high doses or kidney impairment Carbapenems • • Most broad-spectrum β-lactam Effective for ESBL (Extended-Spectrum Beta-Lactamase) infections and anaerobes. 1. Imipenem/Cilastatin (Primaxin®) o CNS toxicity: Risk of seizures, particularly at high doses. o Pregnancy Category: C 2. Meropenem (Merrem®) o Meningitis: FDA-approved for treatment. o Pseudomonas and Acinetobacter: Active, but combination therapy is recommended. o Renal dose adjustment 3. Doripenem (Doribax®) 4. Ertapenem (Invanz®) 5. Imipenem and Meropenem • Broad spectrum: Effective against G(+), G(-), anaerobes, and Pseudomonas. 6. Ertapenem (Invanz® IV) o o o o No activity against: Pseudomonas aeruginosa and Enterococcus faecalis. Active against anaerobes: Especially Bacteroides fragilis. IV Dilution: Saline only. ONCE daily dose Carbapenems ADRs 1. Cross Hypersensitivity with Penicillin: Occurs in about 1% of cases. 2. CNS Side Effects: o Seizures: More common with imipenem/cilastatin. Monobactam - Activity: Only active against G(-) aerobic bacteria Safe for patients with penicillin allergy in nosocomial infections o Exception: Patients with ceftazidime allergy (due to identical side chain with ceftazidime) Glycoproteins - Vancomysin Telavancin Dalbavancin Oritavancin Vancomycin (Vancocin®) IV/PO • Spectrum of IV Vancomycin: Active against Gram (+) bacteria, especially MRSA. • PO Vancomycin: Only used for C. difficile (not absorbed in the bloodstream). Adverse Drug Reactions (ADRs) – IV: 1. Nephrotoxicity 2. Ototoxicity 3. Vancomycin Flushing Syndrome (Redman Syndrome) Vancomycin IV Administration: • Infusion rate: 1g/hour to prevent Vancomycin Flushing Syndrome (VRS) = Redman Syndrome Therapeutic Drug Monitoring (TDM): • PD target: AUC/MIC 400-600 • Conventional method: Trough level 10-20 mcg/mL, before the 4th dose. New Vancomycin Monitoring Guidelines: • • Serious MRSA infections: Target AUC of 400-600. Dosing: 15-20 mg/kg every 8-12 hours based on actual body weight. Daptomycin (Cubicin® IV) • • • Mechanism of Action (MOA): Bactericidal in a concentration-dependent manner. Spectrum: Effective against MRSA, VRSA (Vancomycin-resistant S. aureus), and VRE. No Pneumonia Coverage: Alveolar surfactant deactivates daptomycin. Indications: • cSSSIs (Complicated skin and soft tissue infections): 4 mg/kg/day. • Bone infections: 6 mg/kg. • Bloodstream infections or endocarditis: 8-10 mg/kg. Daptomycin (Cubicin®) • ADR: Possible Rhabdomyolysis (elevated CPK). o If on statins: Be careful, check CPK. o Stop when CPK is 5x upper normal limit (UNL = 1000). Polymyxins ADRs - Nephrotoxicity - Neurotoxicity Fosfomycin - Urinary concentrations: Effective for 3 days. UTIs, uncomplicated: Main use. Older Fluoroquinolones: • Ciprofloxacin (Cipro®): o Gram (-) only. o Indications: Anthrax, UTI, IAI (intra-abdominal infections). Newer Fluoroquinolones: • Levofloxacin (Levaquin®): o Gram (+) and Gram (-) activity. • Moxifloxacin (Avelox®): o Gram (+), Gram (-), and anaerobes. • Delafloxacin (Baxdela®): o MRSA + Pseudomonas coverage. Pseudomonas: - Covered by Cipro and Levo. UTI: - Covered by Cipro and Levo Fluoroquinolones: Key Facts • Kills based on concentration (AUC/MIC). • 100% bioavailability (works well both PO and IV). • Elimination: o Levo and Cipro: Mostly through kidneys (need dose adjustment for kidney problems). o Moxifloxacin: Mostly through liver (no dose adjustment needed, but doesn't work for UTIs). Fluoroquinolones: Spectrum • Gram (-) bacteria: Cipro > Levo > Moxi. o Pseudomonas: Covered by Cipro and Levo. o UTI: Covered by Cipro and Levo (some resistance exists). Fluoroquinolones: Key Facts • Kills based on concentration (AUC/MIC). • 100% bioavailability (works well both PO and IV). • Elimination: o Levo and Cipro: Mostly through kidneys (need dose adjustment for kidney problems). o Moxifloxacin: Mostly through liver (no dose adjustment needed, but doesn't work for UTIs). Fluoroquinolones: Side Effects • QTc prolongation (heart rhythm issues): o Avoid if QTc > 500 mSec or with other QTc drugs. • Not for children: Risk of cartilage injury. • Photosensitivity: Especially with older drugs in this class. Fluoroquinolones: ADRs • Collateral Damage: o Increased use leads to more resistant bacteria (e.g., MRSA, resistant E. coli in ICU). o Reserve for patients with no other options. • Drug Interactions: o Avoid cations (e.g., antacids). o QTc prolongation and CYP450 inhibition (increased INR with warfarin). Black Box Warnings: • QTc prolongation • Hypersensitivity • Tendon rupture (> 60 years, steroid use, transplant) • Peripheral neuropathy and CNS effects • Aortic aneurysm or rupture • Glucose intolerance (withdrawal of gatifloxacin) • Hepatotoxicity (withdrawal of trovafloxacin) • Phototoxicity Trimethoprim/Sulfamethoxazole (TMP/SMX) – Bactrim® / Septra® • DOC for uncomplicated UTI • Community-acquired MRSA • DOC for Stenotrophomonas. • PJP (Pneumocystis jirovecii pneumonia): Used for prophylaxis and treatment. Dextrose Only: Do not refrigerate. ADRs: • • • Hypersensitivity (Sulfa allergy) Photosensitivity Rash, Stevens-Johnson Syndrome. Saline Only - Ampicillin - Unasyn - Invanz - CUbicin Dextrose only - Trimethoprim/Sulfamethoxazole (TMP/SMX )