Introduction to Antibiotics.pdf

Introduction to Antibiotics Alexander Kashmanian, PharmD, BCPS, BCIDP Clinical Pharmacy Specialist – Internal Medicine Rhode Island Hospital [email protected] Johnson & Wales University August 5, 2024 ...

Introduction to Antibiotics Alexander Kashmanian, PharmD, BCPS, BCIDP Clinical Pharmacy Specialist – Internal Medicine Rhode Island Hospital [email protected] Johnson & Wales University August 5, 2024  Objectives 1. Recognize the mechanism of action of the antibiotic classes and give examples of antibiotics in each class 2. Define antimicrobial‐related terminology: − Bactericidal and bacteriostatic − Minimum inhibitory concentration (MIC) 3. Recognize the selection of antibiotics based upon the relative spectrum towards Gram positive and Gram negative bacteria 4. Identify the preferred dosing strategy for an antibiotic based on its pharmacodynamic properties: − Concentration‐dependent vs time‐dependent 5. Describe common adverse effects of antibiotics 6. Interpret culture results and de‐escalate from broad‐spectrum empiric antibiotic therapy 7. Evaluate a patient’s antibiotic allergy and determine the safety of administering alternative antimicrobials Bacterial Identification: Gram Stain Bacterial Identification: Gram Stain  Gram Positive Organisms S. pneumoniae Alpha hemolytic Viridans group Streptococcus Aerobic Gram (+) Cocci Group A Strep Beta hemolytic Pairs and Group B Strep Chains E. faecalis Gamma Enterococcus hemolytic E. faecium Coagulase Negative Clusters Staphylococcus Coagulase Staphylococcus Positive aureus  Gram Negative Organisms Pseudomonas Non-Lactose Aerobic Gram (-) Pathogens Acinetobacter Fermenters Bacilli (Rods) Stenotrophomonas Lactose Enterobacterales Fermenters Escherichia coli Coccobacilli H. influenzae Proteus mirabilis Klebsiella pneumoniae Klebsiella oxytoca N. meningitides Klebsiella aerogenes Enterobacter cloacae Serratia marcescens Citrobacter freundii Cocci N. gonorrhoeae Citrobacter koserii M. cattarhalis  Anaerobic Organisms Spore forming Clostridium spp. Anaerobic Pathogens Actinomyces Gram positive Propionibacterium Non-spore forming Peptostreptococcus Bacteroides Lactobacillus Gram negative Fusobacterium Prevotella  Atypical Organisms  Intracellular pathogens  Difficult to grow on routine media  Important atypical organisms − Legionella pneumophila − Chlamydia pneumoniae − Mycoplasma pneumoniae Empiric Antimicrobial Coverage  What are you treating?  What patient-factors are − Clinical diagnosis / Site present that may alter of infection treatment decisions? − Presence of risk factors  What are the likely for drug resistant pathogens? pathogens − Location / Exposures − Recent antibiotic therapy − Clinical practice − Other co-morbidities guidelines & primary (immunosuppression) literature − Allergies − Pregnancy/Breastfeeding  What resistance − Renal/liver dysfunction patterns do you expect? − Drug-drug interactions − Previous cultures − Antibiogram  Susceptibility Testing  Minimum inhibitory concentration (MIC) − Minimum concentration at which an antimicrobial agent inhibits the growth of the organism  Susceptibility Testing  Kirby-Bauer Disk Diffusion and E-test  Susceptibility Interpretation  Breakpoints − Determines whether an organism is susceptible, intermediate or resistant to the antibiotic − Set MIC values or diameter of zone of inhibition Susceptible Intermediate Resistant High likelihood of clinical success if exposure is enhanced by High likelihood of Less likely to adjusting the dose clinical success achieve clinical regimen or if the success antibiotic is concentrated at the site of infection Susceptibility Results Susceptibility Results Antibacterial Targets  Beta-Lactams Bactericidal, inhibit bacterial cell wall synthesis by binding to penicillin binding proteins (PBPs)  Beta-Lactams: Adverse Effects  Gastrointestinal most common − Nausea, vomiting, diarrhea − Absorption affected by food, take on an empty stomach  Allergy – penicillin most reported antibiotic allergy − Rash/hives -> anaphylaxis  Renal − Acute interstitial nephritis (AIN) − Most require renal dose adjustments  Neurotoxicity at high doses − Encephalopathy, seizures  Penicillins  4 Subclasses 1. Natural penicillins − Penicillin G & V 2. Penicillinase resistant (anti-staphylococcal) − Nafcillin, oxacillin, methicillin, dicloxacillin 3. Aminopenicillins ± β-lactamase inhibitor − Amoxicillin, ampicillin − Amoxicillin-clavulanate, ampicillin-sulbactam 4. Extended-spectrum penicillins (anti-pseudomonal) − Piperacillin-tazobactam  Natural Penicillins  Penicillin G (IM/IV) and Penicillin VK (PO)  Spectrum: − Streptococcus spp., Enterococcus faecalis (NO staphylococcal coverage) − Gram positive anaerobes (Peptostreptococcus, Clostridium spp., Actinomyces spp.)  Uses: − Syphilis (including neurosyphilis) − Pharyngitis − Endocarditis (streptococcal and enterococcal) − S. agalactiae (GBS) prophylaxis during L&D  Penicillinase-Resistant Penicillins  Methicillin (IV), nafcillin (IV), oxacillin (IV), dicloxacillin (PO)  Spectrum: − Gram positives only (NO enterococcal coverage) − Staphylococcus spp. (NOT MRSA), Streptococcus spp.  Uses: − SSTI − Osteomyelitis − Endocarditis  Pearls: − No renal adjustment required − Monitor LFTs for nafcillin and oxacillin since eliminated via biliary tract  Aminopenicillins  Amoxicillin (PO), ampicillin (IV/PO)  Spectrum: − Same as penicillin plus increased activity against some Gram negatives − Gram positive: Streptococcus spp., Enterococcus spp., Listeria monocytogenes, Actinomyces spp., Peptostreptococcus − Gram negative: variable coverage of E. coli, Proteus mirabilis, H. influenzae, Shigella  Uses: − Respiratory tract infections (pharyngitis, sinusitis, CAP) − Otitis media − Meningitis (Listeria) − UTI (limited due to Gram negative coverage) Beta-lactamase Enzymes  Beta-lactamase Inhibitors  Clavulanic acid, sulbactam, tazobactam, avibactam, vaborbactam, relebactam − Little to no antibacterial activity except sulbactam for Acinetobacter spp. − Fixed combination doses  Potent inhibitors of β-lactamase − Expands spectrum of activity − Effective against β-lactamases produced by: − MSSA, H. influenzae, N. gonorrhoeae, Salmonella, Shigella, E. coli, Klebsiella pneumoniae Aminopenicillins + β-lactamase Inhibitor  Amoxicillin-clavulanic acid (PO), ampicillin-sulbactam (IV)  Expanded spectrum: − Gram positive: Staphylococcus spp. including MSSA, Streptococcus spp., Enterococcus spp., Listeria monocytogenes, Actinomyces spp., Peptostreptococcus, Clostridium spp. − Gram negative: E. coli, H. influenzae, M. catarrhalis, Proteus spp., Klebsiella spp., Acinetobacter (ampicillin-sulbactam only) − Anaerobes: Bacteroides spp.  Expanded uses: − Intra-abdominal − CAP − SSTI  Extended-Spectrum Penicillins  Piperacillin-tazobactam (IV)  Spectrum: − Gram positive: Staphylococcus spp. including MSSA (NO MRSA), Streptococcus spp., Enterococcus spp., Actinomyces spp., Peptostreptococcus, Clostridium spp. − Gram negative: Pseudomonas spp., Serratia spp., Klebsiella spp., Proteus spp., E. coli, H. influenzae, M. morganii, M. catarrhalis − Anaerobes: Bacteroides spp.  Uses: − Reserved for nosocomial infections: pneumonia, neutropenic fever, intra-abdominal infections and complicated SSTI  Penicillin Allergies  Approximately 10% of the U.S. population reports having an allergic reaction to a penicillin class antibiotic  Fewer than 1% have true IgE-mediated reactions  Approximately 80% of patients with IgE-mediated penicillin allergy lose their sensitivity after 10 years  9 out 10 patients who claim to be allergy to penicillin’s are NOT truly allergic when assessed by skin testing  Preferred β-lactam therapy is avoided in > 50% of patients even when a NON-severe prior reaction is reported Salkind AR et al. JAMA 2001;285:2498‐505.; Pichichero ME et al. Ann Allergy Asthma Immunol 2014;112:404‐12. McFadden D et al. Clin Infect Dis 2016;63:904‐10.  Penicillin Allergies – Why do we care?  β-lactams are the preferred antibiotic for many infections  Risk of true allergic reaction − Case fatality rates ~ 0.25 – 0.33% among hospitalizations or ED presentations with anaphylaxis diagnosis  Implications of penicillin “allergy” − Increased adverse effects − Longer hospital stays, more re-admissions − Development of MDR infections − Increased use of broad-spectrum antibiotics (fluoroquinolones, clindamycin, vancomycin) − Increased antibiotic costs (63% higher than those without reported allergy) MacFadden DR et al. Clin Infect Dis. 2016;63:904‐10. Macy E et al. J Allergy Clin Immunol 2014;133:790‐6. MacLaughlin EJ et al. Arch Fam Med 2009;9:722‐6.; Charneski L et al. Pharmacother 2011;31:742‐7.; Macy E. et al. J Allergy Clin Immunol 2014;133:790‐6.  Penicillin Allergy Documentation  Allergy history documentation is poor − Re-challenge with β-lactams more likely to occur when allergic reactions well documented  Update allergy records in medical record − Detail allergy history − Tolerance to other β-lactams  In patients with TRUE penicillin allergy − Antibiotic desensitization available (ID Consult, Order Panel, ICU admission)  Beta-lactam Cross-Reactivity Image: https://asp.nm.org/uploads/9/0/7/8/90789983/cross_rxn__graded_challenge__final_update_10.19.19_.pdf  Cephalosporins  5 Subclasses divided into “generations” 1. First generation − Cefazolin, cephalexin, cefadroxil 2. Second generation − Cefuroxime, cefotetan, cefoxitin, cefaclor 3. Third generation − Ceftriaxone, cefotaxime, ceftazidime, cefpodoxime, cefdinir, cefixime 4. Forth generation − Cefepime 5. Fifth generation (New generation) − Ceftaroline, ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol, ceftobiprole, cefepime-enmetazobactam  Cephalosporins  In general, progression from 1st to 5th generation: − Broadening Gram negative coverage − Lose some Gram positive coverage − Exception = 4th generation has good Gram positive and negative coverage  NO activity against Enterococcus spp., Listeria, atypicals, or anaerobes  Only ceftaroline and ceftobiprole have activity against MRSA  Only ceftazidime, cefepime, ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol have activity against Pseudomonas spp.  1st Generation Cephalosporins  Cefazolin (IV), cephalexin (PO), cefadroxil (PO)  Spectrum: − Gram positive: Staphylococcus spp. including MSSA (NOT MRSA), Streptococcus spp. − Some Gram negative: E. coli, Proteus spp., Klebsiella spp.  Uses: − Surgical prophylaxis − MSSA infections − SSTI & BJI − UTI (limited due to Gram negative coverage)  2nd Generation Cephalosporins  Cefoxitin (IV), cefotetan (IV), cefuroxime (IV/PO), cefaclor (PO)  Spectrum: − Reduced activity to MSSA and Streptococcus spp. − Extended Gram negative coverage − Activity against anaerobes − Cefoxitin and cefotetan only  Uses: − UTI − SSTI & BJI − Respiratory tract infections & otitis media − Intra-abdominal infections  3rd Generation Cephalosporins  Ceftriaxone (IV/IM), cefotaxime (IV), ceftazidime (IV), cefpodoxime (PO), cefdinir (PO), cefixime (PO)  Spectrum: − Gram positive: Staphylococcus spp., Streptococcus spp. including penicillin-resistant S. pneumoniae − Unreliable for ceftazidime – mostly Gram negatives − Extensive Gram negative − Ceftazidime ONLY one that also covers Pseudomonas spp.  Uses: − Pneumonia − UTI & STIs − Endocarditis − Meningitis (high dose ceftriaxone needed)  4th Generation Cephalosporins  Cefepime (IV)  Spectrum: − Broad-spectrum Gram positive activity − Nosocomial Gram negative including Pseudomonas spp.  Uses: − Neutropenic fever − HAP & VAP − Intra-abdominal infections (+/- metronidazole)  Clinical Pearl: − 2012 FDA Safety Communication on risk of seizures in patients not receiving renal dose adjustments − CrCl < 60 mL/min  5th Generation Cephalosporins  Ceftaroline (IV)  Spectrum: − Broad spectrum Gram positive including MRSA − Extensive Gram negative except Pseudomonas spp. − Similar to ceftriaxone  Uses: − SSTI − Pneumonia − MRSA infections  New Generation Cephalosporins  Ceftolozane-tazobactam (IV), ceftazidime-avibactam (IV), cefiderocol (IV)  Spectrum: − Multi-drug resistant (MDR) Gram negative bacteria  Uses: − Reserved for severe infections with MDR organisms (MDROs) when there are no other treatment options − NOT routine for empiric use − Requires ID Consult usually − Commonly used for MDR P. aeruginosa and carbapenem-resistant Enterobacterales (CRE)  Carbapenems  Meropenem (IV), imipenem-cilastatin (IV), ertapenem (IV)  Spectrum: − Broad spectrum Gram positive (NO MRSA) − Limited coverage of Enterococcus spp. (imipenem > meropenem) − Nosocomial Gram negatives including ESBL organisms and Pseudomonas spp. − Ertapenem DOES NOT COVER Pseudomonas spp. − Anaerobes  Uses: − Reserved for severe MDR infections − HAP & VAP − Intra-abdominal infections − Meningitis  New Carbapenems  Meropenem-vaborbactam (IV), imipenem-cilastatin- relebactam (IV)  Spectrum: − Multi-drug resistant (MDR) Gram negative bacteria − Meropenem-vaborbactam has no added Pseudomonas spp. activity compared to meropenem alone  Uses: − Reserved for severe infections with MDR organisms (MDROs) when there are no other treatment options − NOT routine for empiric use − Requires ID Consult usually  Monobactam  Aztreonam (IV)  Spectrum: − Gram negative coverage ONLY including Pseudomonas spp. − Similar to ceftazidime − Generally poor susceptibilities  Uses: − Alternative Gram negative coverage for true β-lactam allergy − Structurally different enough to avoid cross-reactivity − Except those who specifically react to ceftazidime due to similar side chain  Fluoroquinolones  Bactericidal, inhibits bacterial DNA synthesis via inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV  Ciprofloxacin (IV/PO), levofloxacin (IV/PO), moxifloxacin (IV/PO), delafloxacin (IV/PO)  Spectrum: − Gram positive: Streptococcus spp. (NOT ciprofloxacin) − Gram negative: Enterobacterales, H influenzae, M. catarrhalis, Pseudomonas spp. (NOT moxifloxacin) − Atypicals − Anaerobes – only moxifloxacin & delafloxacin  Uses: − UTI & Prostatitis (NOT moxifloxacin) − Pneumonia − Osteomyelitis − Intra-abdominal infections (+/- metronidazole) Fluoroquinolones: Adverse Effects  Gastrointestinal (N/V/D) most common  Absorptions reduced with divalent cations (Ca, Mg, Fe) and dairy products − Antacids, oral electrolyte supplements, multivitamins with minerals − Administer metal cations 2 hours before or 6 hours after  Tendon rupture − Black box warning  QTc prolongation − Not a concern with delafloxacin  Peripheral neuropathy & CNS toxicity  Tetracyclines  Bacteriostatic, inhibit protein synthesis by binding to the 30S ribosome  Doxycycline (IV/PO), minocycline (IV/PO), tetracycline (PO) − Newer tetracyclines: tigecycline (IV), omadacycline (IV/PO), eravacycline (IV)  Spectrum: − Gram positive: MSSA/MRSA, S. pneumoniae − Unreliable for other Streptococcus spp. − Unreliable Gram negative coverage − Atypicals − Other: − Spirochetes (Syphilis, Borrelia (Lyme disease), Leptospira), Protozoa (Malaria), Rickettsiae and other tick-borne illnesses  Uses: − Pneumonia − SSTI − STIs & Prostatitis  Tetracyclines: Adverse Effects  Photosensitivity  Esophageal ulceration − Due to formulation, counsel to take with adequate fluid  Absorptions reduced with divalent cations (Ca, Mg, Fe) and dairy products − Antacids, oral electrolyte supplements, multivitamins with minerals − Administer metal cations 2 hours before or 6 hours after  Stains developing teeth in children − Do NOT routinely use in children < 8 years of age  Nausea, vomiting, & diarrhea  Macrolides  Bacteriostatic, inhibit protein synthesis by reversibly binding to the 50S ribosome  Azithromycin (IV/PO) − Used commonly for atypical bacteria including Legionella, as well as STIs and Mycobacterium spp. − Extremely long tissue t1/2 (68-72 hrs) allows for short courses − Has anti-inflammatory properties  Clarithromycin (PO) − Intermediate tolerability, more active in respiratory infections than erythromycin − More active than azithromycin for Mycobacterium avium complex (MAC), H. pylori  Erythromycin (IV/PO) − Oldest form, least tolerable, least active − No longer commonly used for systemic infections  Macrolides: Adverse Effects  Gastrointestinal (N/V/D) most common − Erythromycin > clarithromycin > azithromycin  QTc prolongation − Erythromycin/clarithromycin >>>> azithromycin  CYP 450-mediated drug interaction − May require dose adjustments/temporary discontinuation of some medications − Erythromycin is a moderate inhibitor 3A4 − Clarithromycin is a strong inhibitor 3A4 − Azithromycin DOES NOT have CYP 450-mediated drug interactions  Fidaxomicin  Also part of the macrolide class, inhibits protein synthesis by reversibly binding to the 50S ribosome  Spectrum & uses: − C. difficile infection  Adverse effects: − Nausea/vomiting  Clinical pearls: − Only available PO and is not systemically absorbed so CANNOT be used to treat any other infection other than CDI  Sulfamethoxazole-Trimethoprim  Bactericidal, interferes with bacterial folic acid synthesis and bacterial growth  Spectrum: − Gram positive: MSSA/MRSA − Unreliable for Streptococcus spp. − Gram negative: good coverage, no activity against Pseudomonas spp.  Uses: − UTI − SSTI & PJI  Clinical Pearls: − Dosing based on trimethoprim component  Sulfamethoxazole-Trimethoprim: Adverse Effects  Hyperkalemia − Trimethoprim blocks sodium channels in the distal nephron, inhibiting potassium secretion − Important to monitor, especially with other medications that cause hyperkalemia  False elevation in serum creatinine − Inhibits tubular secretion of creatinine without decreasing renal function  Gastrointestinal − Nausea, vomiting, diarrhea  Urinary Agents  Nitrofurantoin (PO), Fosfomycin (PO)  Broad spectrum agents with some activity against resistant organisms  Do NOT achieve significant serum or tissue concentrations − NOT for systemic infection or other sites of infection (including pyelonephritis)  Nitrofurantoin  Spectrum: − Most Gram negative organisms, some Gram positive organisms − E. coli, Enterococcus spp. (including VRE), Streptococcus spp.  Uses: − Uncomplicated cystitis  Pearls: − Contraindicated with CrCl < 30 mL/min − Short duration of 5 days  Fosfomycin  Spectrum: − VRE, E. coli, Klebsiella spp., Proteus spp. − Some carbapenemase and ESBL producing organisms  Uses: − Uncomplicated cystitis − Off label: complicated cystitis − Cystitis in patients with multiple antibiotic allergies and/or when no other oral options available  Available as oral packet, which is mixed with cool water before ingestion  Nitroimidazoles  Bactericidal, inhibits protein synthesis through free radical generation and DNA disruption  Metronidazole (IV/PO), Tinidazole (PO)  Spectrum: − Anaerobic bacteria: Bacteroides spp., Prevotella spp., Fusobacterium spp., Clostridiodes difficile, Gardnerella vaginalis − Protozoa: Giardia, Entamoeba, Trichomonas vaginalis  Uses: − Intra-abdominal infections and C. difficile infection − Brain abscess − Bacterial vaginosis and other STIs − Amebiasis  Nitroimidazoles: Adverse Effects  Gastrointestinal most common − Nausea/vomiting, metallic taste  CNS effects − Peripheral neuropathy, encephalopathy, seizures − More likely to occur with higher cumulative doses or prolonged courses − Usually reversible within days-weeks of discontinuation  Clindamycin  Bacteriostatic, binds to 50s ribosome subunit to inhibit protein synthesis  Spectrum: − Gram positive: Streptococcus spp., Staphylococcus (including MRSA) − No Gram negative aerobic coverage − Anaerobes: some Bacteroides spp., Gram positive anaerobes  Uses: − SSTI − PID − Toxin inhibition for Streptococcus spp. and Staphylococcus aureus − TSS, SSSS, necrotizing fasciitis  Clindamycin: Adverse Effects  Clostridiodes difficile infection − Black box warning  Gastrointestinal most common − Nausea/vomiting, abdominal pain  Hypersensitivity and rash are common with prolonged use  Linezolid  Bacteriostatic, binds to 23s ribosomal portion of 50s subunit  Spectrum: − Gram positive activity ONLY − MSSA, MRSA, Enterococcus spp. (including Vancomycin Resistant Enterococcus (VRE))  Uses: − SSTI − Pneumonia − Osteomyelitis when fail other therapies  Linezolid: Adverse Effects  Drug interactions − Acts as a weak MAO inhibitor − Avoid use with multiple SSRIs, SNRIs – risk of serotonin syndrome  Myelosuppression − Thrombocytopenia (> 10-14 days)  Optic neuritis  Peripheral neuropathy (> 28 days)  Daptomycin  Bactericidal, inserts into cell membrane, leading to leakage of intracellular cations resulting in depolarization  Spectrum: − Gram positive activity ONLY − MSSA/MRSA, Streptococcus spp., Enterococcus spp. (including VRE)  Uses: − MRSA bacteremia or endocarditis who fail or have contraindications to vancomycin − INEFFECTIVE for pneumonia – inactivated by lung surfactant  Clinical Pearls: − Dosed using actual body weight − Dose dependent on indication 4 mg/kg – 12 mg/kg  Daptomycin: Adverse Effects  Myalgias − Reversible upon stopping  Arthralgias rhabdomyolysis  CPK elevation − Monitor at baseline and at least weekly − Discontinue when: − CPK 5 x ULN with muscle pain/weakness − CPK 10x ULN with or without muscle pain/weakness  Vancomycin  Bactericidal glycopeptide, inhibits cell wall synthesis  Spectrum: − Gram positive activity ONLY − MSSA (less effective than β -lactams e.g. nafcillin, cefazolin) − C. difficile (PO vancomycin only)  Uses: − SSTI − Pneumonia − Bacteremia − Endocarditis − Osteomyelitis − C. difficile infection  Vancomycin Dosing  Dosed based on patient specific PK/PD − Age, weight, renal function  Adjusted based on therapeutic drug monitoring − Peak levels not indicated − Trough levels easiest and most accurate method to monitor efficacy and toxicity − Goal 15-20 mcg/mL − Timing of levels extremely important (30 min prior to 4th dose) − AUC monitoring now recommended in the updated vancomycin guidelines − Goal 400-600 mg·h/L − Difficult to calculate Rybak MJ et al. Am J Health-Syst Pharm 2020;77:835‐864  Vancomycin: Adverse Effects  Nephrotoxicity most common − Usually reversible with discontinuation or lower doses of vancomycin − Avoided with appropriate dosing and monitoring  Ototoxicity − Tinnitus, hearing loss, dizziness, vertigo − Rare  Infusion related reaction (previously called “Redman Syndrome”) − NOT a contradiction to vancomycin − Can be resolved with premedication and longer infusion times  Aminoglycosides  Bactericidal, inhibit protein synthesis by binding to the 30s ribosome  Gentamicin (IV), tobramycin (IV), amikacin (IV)  Spectrum: − Broad-spectrum Gram negative coverage − Gram positives – only for synergy − No anaerobic coverage  Always part of combination therapy  Aminoglycosides  Gentamicin − Monotherapy ONLY for UTIs − Combination therapy for life-threatening Gram negative infections − Commonly used for Gram positive synergy − Endocarditis caused by Enterococcus spp., Staphylococcus aureus, Viridians group Streptococci  Tobramycin − Combination therapy for life-threatening Gram negative infections − Has better activity for Pseudomonas spp. − Commonly used for cystic fibrosis (CF) exacerbations  Amikacin − Commonly used for Non-Tuberculosis Mycobacteria (NTM) − No synergy for Enterococcus spp. − Less resistance than gentamicin and tobramycin Aminoglycosides: Adverse Effects  Nephrotoxicity  Ototoxicity − Accumulation in − Loss of hearing, renal cortex ringing − Usually reversible − Vestibular damage – − Increased risk: clumsiness, − Age dizziness, N/V − Liver disease − May be irreversible − Concomitant − Related to nephrotoxic agents cumulative dose − High troughs − Length of therapy  Bactericidal vs Bacteriostatic Bactericidal Bacteriostatic  Lethal to microorganisms  Inhibits bacterial growth  Causes irreversible  Requires patients own damage to bacterial cells immune system to “mop leading to cell death up” infection  Examples:  Examples: − Beta-lactams − Clindamycin − Vancomycin − Tetracyclines − Fluoroquinolones − Linezolid − Macrolides  Antibiotic Dosing Strategies  Time-Dependent − Time above MIC  Optimize duration of exposure  Antibiotics: − Beta-lactams − Macrolides − Linezolid − Clindamycin  Antibiotic Dosing Strategies  Concentration- Dependent − Peak to MIC − AUC to MIC  Maximize antibiotic concentration  Antibiotics: − Vancomycin − Fluoroquinolones − Aminoglycosides − Metronidazole Questions? Introduction to Antibiotics Alexander Kashmanian, PharmD, BCPS, BCIDP Clinical Pharmacy Specialist – Internal Medicine Rhode Island Hospital [email protected] Johnson & Wales University August 5, 2024