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Julius Li, PharmD; Kristi Traugott, PharmD, BCPS Revised 03/
Spectrum of Activity Against Common Bacteria
Refer to hospital antibiogram for susceptibility rates of specific organisms Penicillin G Oxacillin^ Ampicillin Amox
- Clav Amp
- Sulb Pip
- Tazo Cefazolin Cefuroxime Cefoxitin Ceftriaxone Ceftazidime Cefepime^ Ceftaroline^ Ertapenem^ Imipenem Meropenem Aztreonam Aminoglycosies Ciprofloxacin Moxifloxacin Levofloxacin Doxycycline Minocycline Tigecycline Polymyxins Vancomycin Daptomycin Linezolid Quinu/Dalfo Clindamycin TMP - SMX Metronidazole Nitrofurantoin Azithromycin^ Clarithryomycin Beta-hemolytic streptococci (^) * + + + + + + + + + + + + + + + + + ± + + + + + + + ± + + Viridans group streptococci (^) + + + + + + + + + + + + + + + + + + + + + + + + + + Streptococcus pneumoniae (^) + + + + + + + + + + + + + + + + + + + + + + + + + + Staphylococcus aureus (MSSA) (^) ± * + + + * + + + + + + + + + + + + + + + + + + + + + + Staphylococcus aureus (MRSA) (^) + + + + + + * + + + + + + ± ± Enterococcus faecalis (^) + * + + + + + + + + + + + + + + Enterococcus faecium (^) ± + + + + + + + + + + Escherichia coli (^) + + + + + + + + + + + + + + + + + + + + + + + + + Klebsiella spp. (^) + + + + + + + + + + + + + + + + + + + + + + + + Enterobacter spp. (^) + + + * + + + + + + + + + + + + + + + Citrobacter spp. (^) + + + * + + + + + + + + + + + + + + + Serratia spp. (^) + + + * + + + + + + + + + + + + + Proteus spp. (^) + + + + + + + + + + + + + + + + + + + + Acinetobacter spp. (^) + + + + + + + + + + + + + + + + Pseudomonas aeruginosa (^) + + + + + + + + + + + Stenotrophomonas maltophilia (^) ± + + + * Bacteroides spp. (^) + + + + + + + + ± ± + + + + + + + Prevotella spp. (^) + + + + + + + + + + + + + + + + + Clostridium spp. (^) + + + + + ± ± + ± ± ± ± + + + + ± ± + + + + + + + Peptostreptococcus spp. (^) + + + + + + + + + + + + + + + + + + + + + + + + ± Atypicals (^) + + + + + + + + Bug Drug * = drug of choice
Pocket Guide for Antibiotic Pharmacotherapy
dependent- Concentration dependent- Time
Optimize killing by maximizing time above MIC
- More frequent administration or extended infusion increases efficacy by extending T>MIC lactam antibiotics- Ex: beta Optimize killing by maximizing peak concentrations Less frequent but higher doses increases efficacy by maximizing Cmax:MIC ratio Ex: aminoglycosides, daptomycin
Bacteriostatic versus Bactericidal
” Very Proficient For Complete Cell Murder“ ” ECSTaTiC for bacteriostatic “ rythromycin (macrolides) E lindamycin (lincosamides) C ulfonamides S rimethoprim T etracyclines T hloramphenicol C ancomycin V enicillins P luoroquinolones F ephalosporins C arbapenems C etronidazole M
Antibiotic Pharmacokinetics & Pharmacodynamics
Julius Li, PharmD; Kristi Traugott, PharmD, BCPS Revised 03/
Microbiome Man
“Where bacteria normally live”
Oral flora Streptococci Staphylococci spp. Lactobacillus Diphtheroids spp. Porphyromonas spp. Fusobacterium spp. Actinomyces Respiratory flora Streptococci Staphylococci Diphtheroids spp. Neisseria spp. Haemophilus spp. Moraxella Yeasts Gut flora Enterobacteriaceae spp. Bacteroides spp. Clostridium spp. Lactobacillus spp. Candida Streptococci Enterococci Staphylococci Skin flora Staphylococci Streptococci Diphtheroids Micrococci spp. Propionibacterium Peptostreptococci
Julius Li, PharmD; Kristi Traugott, PharmD, BCPS Revised 3/
- SPACE bugs = Serratia marcescens , Pseudomonas aeruginosa , Acinetobacter baumannii , Citrobacter freundii, Enterobacter spp. Approfed by P&T Committee 6/ 2015 Macrolides Erythromycin, azithromy- cin, clarithromycin GI upset (nausea, vomiting, diarrhea) QT prolongation Inhibits 3A (ery > clari >> azi)^ QT prolongation risk = ery >> clari > azi Glycopeptides Vancomycin Red man syndrome Nephrotoxicity Neutropenia (rare) None Red man syndrome can be prevented by slowing infusion rates or premedicate with diphenhydramine IV vanc for systemic infections, PO vanc for C. difficile infection Cyclic Lipopeptide Daptomycin Skeletal muscle toxicity Eosinophilic pneumonia None Generally reserved for severe, resistant gram-positive infections (e.g. MRSA, VRE) if vancomycin failure or resistant Not for pulmonary infections (deactivated by lung surfactant) Oxazolidinone Linezolid Thrombocytopenia Peripheral neuropathies Inhibits MAO (weak) p-glycoprotein substrate Generally reserved for severe, resistant gram-positive infections (e.g. MRSA, VRE) if vancomycin failure or resistant Highly bioavailable, PO = IV Higher toxicity risk with long-term therapy (>2 weeks) Higher risk for serotonin syndrome with due to MAO inhibition with serotonergic agents (e.g. SSRIs, TCAs) and foods (e.g. red wine) Lincosamide Clindamycin GI upset (diarrhea > nausea, vomiting) Elevated LFTs (minor) None^ Increasing resistance in S. aureus and streptococci may limit use Increasing resistance in anaerobes, particularly Bacteroides spp. Sulfonamides Trimethoprim- sulfamethoxazole Hypersensitivity reactions Leukopenia, anemia Hyperkalemia, renal failure None Highly bioavailable, PO = IV Dose for severe infections = 15 mg/kg/day based on TMP component (e.g. PCP, Nocardia spp.) Nitroimidazole Metronidazole GI upset (nausea) Peripheral neuropathy Taste disturbances (metallic) None Highly bioavailable, PO = IV Excellent anaerobic activity Avoid alcohol due to disulfiram reaction Higher risk for peripheral neuropathies with long-term therapy Nitrofurans Nitrofurantoin Peripheral neuropathy Pulmonary toxicity Hepatotoxicity (rare) None Only used for UTIs, but without pyelonephritis Do not use with poor renal function (low urinary penetration) Low resistance = good option for multidrug resistant organisms Aminoglycosides Gentamicin, tobramycin, amikacin Nephrotoxicity Ototoxicity Vestibular toxicity None Tobramycin preferred for P. aeruginosa infections May be used synergistically for severe gram-positive infections Ami = may have activity even if gent or tobra resistant Polymyxins Colistin, polymyxin B Nephrotoxicity Neurotoxicity (oral/peripheral paresthesias) None^ Last line for MDR-GNs due to high toxicity risk and limited efficacy Consider polymyxin B for systemic infections and colistin for UTIs
Antibiotic Adverse Reactions Drug Interactions Clinical Pearls
Penicillins Penicillin G, oxacillin, ampicillin, amoxicillin GI upset (nausea, diarrhea) Hypersensitivity reactions Leukopenia, thrombocytopenia (rare) Neurologic (altered mental status, seizures) Interstitial nephritis Hepatotoxicity (oxacillin) None Generally drugs of choice for bacteria once susceptibility known (e.g. MSSA, penicillin-susceptible S. pneumoniae , ampicillin- susceptible enterococci) Beta-lactam inhibitor combinations amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam None Excellent anaerobic activity Sulbactam has unique activity against Acinetobacter spp. (doses based on sulbactam, >6 g/day) Consider amox-clav 500-125 mg q8h dosing for gram-negative, an- aerobic, or mixed infections (more clavulanate needed) Cephalosporins Cefazolin, ceftriaxone, ceftazidime, cefepime, ceftaroline None Cross-reactivity with penicillin allergy <5% Caution with third generation cephalosporins (e.g. ceftriaxone) and SPACE bugs+^ (ampC producers) Carbapenems Ertapenem, imipenem, meropenem, doripenem None Generally reserved for multidrug resistant gram-negatives (MDR-GN) Drug of choice for ESBL producers Excellent anaerobic activity Cross-reactivity with penicillin allergy <5% Monobactams Aztreonam None^ Generally reserved for severe penicillin allergy (e.g. anaphylaxis), but may cross-react with ceftazidime allergy Fluoroquinolones Ciprofloxacin Moxifloxacin Levofloxacin GI upset (nausea, vomiting, diarrhea) Neurologic (dizziness, AMS, seizures) Phototoxicity Tendonitis, cartilage erosion QT prolongation Dysglycemia Peripheral neuropathies Caution with cations (reduced bioavailability) Inhibits 1A2 (cipro) Increasing resistance may limit use, particularly with E. coli Higher dose for P. aeruginosa (e.g. cipro 750 mg q12h, levo 750 q24h) Highly bioavailable, PO = IV Moxifloxacin = poor urine penetration (not used for UTIs) QT prolongation risk = moxi > levo >> cipro Tetracyclines Doxycycline Minocycline Tigecycline GI upset (nausea, vomiting, epigastric distress) Photosensitivity Teeth discoloration Vertigo (minocycline) Caution with cations (reduced bioavailability) Highly bioavailable, PO = IV (doxy, mino) Tige = severe nausea, may need scheduled antiemetics pre-dose Mino, tige = has activity against multidrug resistant organisms (even if tetra or doxy resistant)
Antibiotic Pharmacotherapy by Class
Refer to Guidelines for Dosing in Renal Failure for both dosing in normal renal function and renal dose adjustments
