The Beta-Lactam Antibiotics

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Slide 1

The Beta-Lactam Antibiotics Cell divider dynamic specialists Prevent the last stride in the amalgamation of the bacterial cell divider Range from extremely limit range to exceptionally expansive range

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β - lactam ring β - Lactams

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How would they work? The β - lactam ties to Penicillin Binding Protein (PBP) PBP can't crosslink peptidoglycan chains The microscopic organisms can't incorporate a steady cell divider The microbes is lysed

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"Penicillin restricting protein" Peptidoglycan Synthesis

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PK/PD The β - lactams are "time-subordinate" executioners The impact is straightforwardly corresponding to the measure of TIME the convergence of the anti-toxin at the site of disease is ABOVE the MIC of the living being. The β - lactams are BACTERIOCIDAL … (at remedially feasible levels)

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"Time Dependant" H Derendorf

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"Time Dependant" WA Craig

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such a large number of decisions… which one to pick? What is the imaginable creature? What's its real method of resistance? Where's the disease? What's my nearby surroundings? the UNC Hospital antibiogram What does the smaller scale lab say? in vitro affectability testing

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Classification Penicillins Natural penicillins PenG, PenVK, Benzathine Pen, Procaine Pen Aminopenicillins Ampicillin, Amoxicillin Anti-Staph penicillins Oxacillin, Dicloxacillin Anti-Pseudomonal [Carboxy] Ticarcillin [Ureido] Piperacillin

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Classification Cephalosporins 1 st Generation Cephalexin, Cefazolin 2 nd Generation Cefoxitin, Cefuroxime, Cefotetan 3 rd Generation Cefotaxime, Ceftriaxone, Ceftazidime 4 th Generation Cefepime

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Penicillin G Available PO, IM, IV (dosed in units) Drug of Choice (DoC) [2-4 MU IV q4h] T. pallidum, N. meningitidis, Group A Strep, and Actinomycosis Long-acting structures Procaine PenG (12 hrs) Benzathine Pen (5 days) [2.4 MU IM for syphilis] Adverse Reactions – other than skin rash Penicillin "serum infection"/tranquilize fever Jarisch-Herxheimer response (1 ° and 2° syphilis) Hemolytic iron deficiency, pancytopenia, neutropenia

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Ampicillin/Amoxicillin Amp (IV, PO) Amox (PO) Spectrum: PenG + H. influenza and some E. coli DoC: Listeria monocytogenes and Enterococcus [Amp 2g IV q4h] Dental Prophylaxis Amox 1 gram PO x 1 before appt. Vital in H. pylori regimens ADRs Non-unfavorably susceptible rashes (9%) – esp. at the point when connected with a viral sickness (mononucleosis - EBV) Amox better endured PO and better consumed (Amp must be gone up against purge stomach)

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Oxacillin IV DoC – MSSA, MSSE [2g IV q4h] Actually less dynamic against Pen vulnerable disengages than Pen More dynamic than Vanc versus MSSA Significant hepatic digestion system No compelling reason to dosage conform for renal weakness ADRs Hepatotoxicity (cholestatic hepatitis) Neutropenia Kernicterus in neonates

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Dicloxicillin Oral NOT identical to IV Ox (restoratively) Poor oral retention ~50% (better on exhaust stomach) Dose: 250-500mg po QID

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Piperacillin IV DoC: Pseudomonas Spectrum: most Enterobacteriaceae (E. coli, Proteus, Klebsiella, Enterbacter, Serratia, Citrobacter, Salmonella and Shigella) Most dynamic penicillin versus Pseudomonas Often utilized as a part of blend with Aminoglycoside or Cipro/Levofloxacin ADRs Bleeding (platelet brokenness) Neutropenia/Thrombocytopenia

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β - Lactamase Inhibitors How would you dodge a β - lactamase? Utilize a non-β - lactam specialist Steric Inhibition Penicillins with vast side chains Cephalosporins β - lactam + β - lactamase inhibitors Not all β - lactamases are inhibitable (!)

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Clavulanic Acid Augmentin (Amox/Clav) PO Spectrum: MSSA and upper respiratory contaminations (S. pneumo, H. influenza, M. catarrhalis) and most anaerobes Clav is in charge of a large portion of the GI symptoms seen with Amox/Clav Variable proportions of Amox/Clav in fluids/tabs/chewtabs

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Sulbactam Unasyn (Amp/Sulbactam) Spectrum: Amp + most anaerobes + numerous enteric Gm (- ) poles, OSSA DoC: for GNR blended disease – E.coli, Proteus, anaerobes when Pseudomonas is not ensnared Diabetic foot (once Pseudomonas discounted) Wound contaminations Sulbactam alone is extremely dynamic against Acinetobacter spp.

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Tazobactam Zosyn (Pip/Tazo) THE most expansive range penicillin Tazobactam may enhance the movement of piperacillin versus gram-negative poles, including anaerobes 4.5g IV q8h = 3.375g IV q6h 4.5g IV q6h for Pseudomonas

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The Cephalosporins (summed up) *Not powerful versus Enterococcus or Listeria

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Cephalexin/Cefazolin PO/IV Stable versus Staph penicillinase Spectrum: MSSA, PSSP, generally E. coli, and some Klebs Can be dosage thrice week by week in HD pts [1.5 grams IV TIW] DoC: surgical prophylaxis, bacterial peritonitis in CAPD pts [1 gm in the abide bag] ADRs Positive Coombs' test (however, hemolytic iron deficiency is uncommon)

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Cefuroxime IV/PO Extensive use in pediatrics Spectrum: Strep pneumo, Viridans Strep, generally H. influenza, N. meningitidis DoC: uncomplicated CAP (esp. H. influenza), UTI/pyelo

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Cefotaxime IV Spectrum: Strep pneumo, Neisseria spp., most Gram (- ) enterics, M. catarrhalis and H. influenza (counting β - lactamase +) DoC: bact meningitis (esp. in peds + amp if < 4 weeks), CAP, confused UTI/pyelonephritis, Bacterial Peritonitis

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Ceftriaxone IV Once every day dosing (95% protein bound = long half-life) Spectrum: Strep. pneumoniae, most Enterbacteriaceae, Excretion: half pee, half bile = no compelling reason to modify for renal deficiency CSF infiltration: 5-15% in meningitis, 1.5% without aggravation DoC: bacterial meningitis, CAP, Strep. viridans endocarditis (+ gent) ADRs Cholestasis Elevated bilirubin (uprooting) Diarrhea

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Ceftazidime IV Spectrum: Enteric GNR (counting Pseudomonas ; some Acinetobacter ) No anaerobic action (same for cefotaxime and ceftriaxone) DoC: Pseudomonas infx

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Third Generation Cephs: Issues β - lactamase acceptance? ESBLs De-restraint of chromosomal β - lactamases Selective weight for VRE?

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Cefepime IV NON - Spectrum: MRSA, C. diff, Burkholderia, Stenotrophomonas, gram-negative anaerobes Stable versus de-subdued chromosomal β - lactamases, yet not ESBL Less β - lactamase acceptance than 3 rd Cephs DoC: HAP, febrile neutropenia

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Carbapenems Imipenem, Meropenem, Ertapenem Broad-range scope: Gram positive: PSSP, MSSA, VSE Gram negative: most gram-negative living beings (Acinetobacter sp., Pseudomonas sp.) Lack of scope: Ertapenem: Pseudomonas sp., Acinetobacter sp. All: Stenotrophomonas, Legionella sp., MRSA, VRE

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Carbapenems Distribution: like penicillins Excretion: renal leeway Adverse responses: Hypersensitivity: rash, urticaria, cross-reactivity Imipenem: seizures (uncommon) High measurements Renal brokenness Most likely can happen with all carbapenems at high dosages

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Carbapenems Resistance: Gram negative: more often than not blend of instruments (Carbapenemase creation + diminished section) Imipenem Decreased generation of OprD (external film protein for carbapenems) Imipenem uses OprD > meropenem, ertapenem Pseudomonas, Enterobacter Susceptible to efflux framework in Enterobacter Meropenem: substrate for multi-medicate efflux frameworks May have expanded MIC for meropenem however not imipenem All: low liking PBPs

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Monobactams: Aztreonam Spectrum: ONLY ��  Gram negative oxygen consuming microorganisms Lack of Coverage: Some safe P. aeruginosa, E. cloacae, and C. freundii Acinetobacter sp., Stenotrophomonas sp. Pharmacokinetics: Well dispersed into tissues, esp. excited tissues Excretion: renal leeway Adverse responses: Skin rash No cross-reactivity with Beta-Lactam class

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What about penicillin hypersensitivities? Writing reports a ceph/pen cross-reactivity of 1 – 10% The cross-reactivity of aztreonam/pen or ceph is basically 0% The cross-reactivity of carbapenems/penicillins is additionally around 10% (like that of ceph/pen) Decision making: Severity of response Eos

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