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Home , Cefditoren, Cefotetan, Cefpodoxime, Ceftibuten, Oxacillin

8/28/19

Disclosure 2

E. Monee’ Carter-Griffin DNP, MA, RN, ACNP-BC has no financial relationships with commercial Review interests to disclose. Any unlabeled and/or E. Monee’ Carter-Griffin, DNP, MA, RN, ACNP-BC unapproved uses of drugs or products will be Associate Chair for Advanced Practice Nursing disclosed. University of Texas at Arlington, College of Nursing & Health Innovation Dallas Pulmonary & Critical Care, PA

• Identify the general characteristics of • Susceptibility à determine which . antibiotics a bacteria is sensitive to • Discuss the mechanism of action, • à , and spectrum of activity MIC lowest concentration of drug that inhibits growth of the bacteria for the most common antibiotic drug classes. Antibiotic Objectives • Identify commonly prescribed antibiotics • Trough à lowest concentration of within the drug classes including dosage Lingo drug in bloodstream range and indication for prescribing. – Collect prior to administration of • Identify special considerations for specific drug antibiotics and/or drug classes. • Peak à highest concentration of • Practice appropriate prescribing for common drug in bloodstream bacterial infections.

• Review basic antibiotic stewardship 3 4 principles.

• • Bactericidal or bacteriostatic • • Narrow or broad spectrum • General • Can elicit allergic responses Antibiotic • Characteristics • Affect normal body flora Drug Classes • Macrolides • Fluoroquinolones • Sulfonamides • Tetracyclines

5 6

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• Penicillins – Natural penicillins 8 – Penicillins Penicillins – Anti-staphylococcal penicillins • Mechanism of action àbactericidal à – Anti-pseudomonal penicillins interrupts synthesis

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• Pharmacokinetics • Spectrum of Activity – Gram positive organisms Natural – G à mostly given IM, but Natural • Streptococcus species (e.g. S. Penicillins one variation can be given IV Penicillins pyogenes) • Poorly absorbed via PO • Some species (e.g. E. faecalis) – Penicillin V à given PO Penicillin G Penicillin G • Staphylococci à only minority; most Penicillin V • Increased gastric acid stability Penicillin V are resistant • Listeria monocytogenes – Gram negative organisms à limited – Anaerobes • Bacteroides 9 10 • Fusobacterium species

Drug Dosage Route Indication • Special Considerations Natural – Do not administer next to nerve or Penicillin G 1.2 – 2.4 MU IM Most commonly Penicillins artery benzathine used to treat Group A strep (e.g. – Probenecid decreases renal Penicillin G procaine 2.4 MU x 1 dose IM ), and Penicillin G clearance of penicillins. syphilis • Co-administration can be used to Penicillin V Penicillin G 12 – 24 MU daily IV increase concentration levels (parenteral) – Decrease parental dosage when CrCl Penicillin V 125-500 mg every 6- PO is less than 50 ml/min 8h – Allergy 11 12

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Penicillins:

• Pharmacokinetics – +/- clavulanate à given 13 Beta-lactamase Inhibitors Aminopenicillins PO • Stable in gastric acid (clavulanate) Amoxicillin • Best absorbed penicillin Amoxicillin/Clavulanate – +/- sulbactam Ampicillin • Ampicillin can be given PO, IM, or Ampicillin/Sulbactam IV • With the addition of the sulbactam

can only be given IM or IV 14

Penicillins:

Drug Dosage Route Indication • Spectrum of Activity – Same activity as natural penicillins Aminopenicillins à susceptible gram-positive Amoxicillin (Amoxil) 250-500 mg every PO , 8h meningitis, organisms 500-875 mg BID susceptible UTIs, Amoxicillin – Improved gram-negative coverage Amoxicillin/ 250-500 mg every PO Soft skin infections Clavulanate 8h related to group A • Amoxicillin/Clavulanate Enterobacteriaceae (Augmentin) 875 mg every 12h strep, Otis media, Ampicillin • H. pylori à used as part of multi- Ampicillin 250-500 mg every PO, IM, IV drug treatment 6h Ampicillin/Sulbactam • H. influenzae Ampicillin/ 1.5-3 g every 6h IM, IV

15 Sulbactam (Unasyn) 16

Penicillins:

• Special Considerations • Pharmacokinetics Anti- – à given PO – Of note, dosing of drugs with beta- staphylococcal Aminopenicillins lactamase inhibitors is based on the • Delayed absorption when given amoxicillin or ampicillin NOT the Penicillins with meals – à given IM or IV Amoxicillin inhibitor. Dicloxacillin • Poor oral absorption Amoxicillin/Clavulanate – Decrease parental dosage when * • CrCl is less than 50 ml/min Primarily metabolized through the Ampicillin Nafcillin liver – MSSA coverage with Amoxicillin/ Ampicillin/Sulbactam – Oxacillin à given IM or IV Clavulanate but none with • Poor oral absorption Amoxicillin only 17 • Primarily metabolized through the 18 – No pseudomonas coverage. liver

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Anti- • Spectrum of Activity Drug Dosage Route Indication staphylococcal – Drug class also known as the Penicillins Penicillinase-Resistant Penicillins – Gram-positive organisms Dicloxacillin 125-500 mg every PO Drug of choice for 6h MSSA infections à Dicloxacillin • Staphylococcal species cellulitis, Nafcillin 0.5-2 g every 4-6h IV endocarditis, Nafcillin – MSSA* osteomyelitis, and bacteremia Oxacillin • Streptococcal species 0.5 g every 4-6h IM

Oxacillin 0.25-2 g every 4-6h IM, IV

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• Anti- • Special Considerations Anti- Pharmacokinetics – +/- tazobactam à IV staphylococcal – No MRSA coverage pseudomonal Penicillins – Nafcillin tends to be better tolerated Penicillins • Piperacillin can also be given IM – Oxacillin à drug-induced hepatitis • Piperacillin is NOT absorbed when Dicloxacillin • Usually reversible with discontinuation of Piperacillin given orally. the drug – +/- clavulanate Nafcillin – Dose adjustments for Nafcillin and Piperacillin/tazobactam potassium à IV only Oxacillin Oxacillin for patients with severe hepatic Ticarcillin and renal dysfunction Ticarcillin/clavulanate potassium 21 22

• Anti- Spectrum of activity Drug Dosage Route Indication – Typically referred to the extended- pseudomonal spectrum penicillins Penicillins – Gram-positive activity Piperacillin (Pipracil) 3-4 g every 4-6h IV, IM Intra-abdominal infections, Piperacillin • Staph. and Strep. pneumonia, severe soft/skin and tissue Piperacillin/tazobactam • NO MRSA coverage. Piperacillin/tazobactam 3.375-4.5 g every IV (Zosyn) 6-8h infections, sepsis, etc. Ticarcillin – Gram-negative activity Ticarcillin/clavulanate • Including Ticarcillin +/- clavulanate 0.25-2 g every 4- IV potassium • Also has coverage against potassium (Timentin) 6h Enterobacteriaceae. 23 24 – Anaerobic coverage

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• Special Considerations Anti- • Cephalosporins – Dosage considerations for patients – 1st Generation pseudomonal with renal dysfunction – 2nd Generation Penicillins • Elimination half-life can increase 2- fold in mild to moderate dysfunction – 3rd Generation Piperacillin to 6-fold in severe dysfunction Cephalosporins – 4th Generation – Use caution with Ticarcillin in patients Piperacillin/tazobactam – 5th Generation Ticarcillin with HF due to the high sodium load – High levels of Ticarcillin can increase Ticarcillin/clavulanate seizure risk in patients with seizure potassium disorders 25 26

Penicillins:

• Pharmacokinetics st – , Cephalexin, & 27 1 Generation Cephalosporins Cephradine à PO Cephalosporins • Rapidly absorbed from the GI tract • Mechanism of action àbactericidal à • Wide distribution but do NOT cross interrupts cell wall synthesis Cefadroxil the blood-brain-barrier – Cefazolin à IM, IV Cephalexin • Widely distributed as well but poor Cephradine CSF penetration

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Penicillins:

• Spectrum of Activity Drug Dosage Route Indication st – Primarily active against gram- 1 Generation positive cocci. Cephalosporins Cefadroxil (Duricef) 1-2 g/daily in two PO Skin and soft tissue • Staphylococcus divided doses infections, respiratory Cefadroxil • Streptococcus Cefazolin (Ancef) 1-2g every 8h IM, IV infections, some UTIs, and Cefazolin • NO MRSA coverage. Cephalexin – Minor gram-negative activity Cephalexin (Keflex) 250-1000mg every PO 6-12h • E. coli Cephradine Cephradine (Velosef) 250-500mg every PO • H. influenzae 6-12h • Klebsiella 29 30

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Penicillins: Penicillins:

• Special Considerations • Pharmacokinetics – If cross-sensitivity reaction is to – & à PO 1st Generation 2nd Generation occur with a penicillin, it is most • Rapidly absorbed from the GI tract Cephalosporins likely to occur with 1st generation Cephalosporins • Cefaclor slowed absorption with cephalosporins. Cefadroxil Cefaclor food. • Cefadroxil • Cefprozil is not affected by food. Cefazolin – Cefazolin can cross the blood-brain- Cephalexin – Cefotetan & Cefoxitin à IM, IV barrier in severe renal – à PO, IM, IV Cephradine dysfunction/failure Cefprozil • Rapidly absorbed from the GI tract • Encephalopathy Cefuroxime 31 • Increased absorption when taken 32 • Seizures with food (PO form)

Penicillins:

• Spectrum of Activity Drug Dosage Route Indication – Gram-positive coverage 2nd Generation Cefaclor 250-500mg every PO Skin & soft tissue • 8h infections, UTIs, Staphylococcus respiratory tract Cephalosporins Cefotetan 1-2g every 12h IM, IV • Streptococcus infections Cefaclor – Extended gram-negative coverage Cefoxitin 1-2g every 6-8h IM, IV Cefotetan • Same as 1st generation but ADD Cefprozil 250-500mg every PO 12-24h Cefoxitin coverage against Neisseria, Proteus – Anaerobic coverage Cefuroxime PO: 250-500mg PO, IM, IV Cefprozil every 12h • Cefoxitin IM, IV: 0.5-1g every Cefuroxime 6-8h • Cefotetan 33 34

Penicillins:

• Special Considerations • Pharmacokinetics 3rd Generation nd – Cefotetan à possible -like – , , , 2 Generation reaction with alcohol Cephalosporins , & à PO Cephalosporins – Generally safe in pregnancy Cefdinir • Rapidly absorbed from the GI tract Cefditoren Cefaclor • Cefpodoxime increased absorption Cefixime when taken with food Cefotetan • Cefixime & Ceftibuten are not Cefoxitin Cefpodoxime affected by food. Cefprozil – Cefotaxime, Ceftazidime, & Cefuroxime Ceftibuten à IM, IV 35 36 Ceftriaxone

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Drug Dosage Route Indication • Spectrum of Activity Cefdinir 300mg every 12h PO Respiratory tract 3rd Generation – Broader activity against gram-negative 600mg every 24h infections, skin & soft Cephalosporins tissue infections, organisms Cefditoren 200-400mg every PO UTIs, sepsis*, intra- Cefdinir • There are some exceptions. 12h abdominal Cefixime 400mg daily PO infections*, CNS Cefditoren • Some have broader gram-negative Cefotaxime 1-2g every 4-12h IM, IV infections* Cefixime coverage compared to others. Cefpodoxime 100-400mg every PO – Some gram-positive coverage BUT Cefotaxime 12h minimal Cefpodoxime Ceftazidime 50omg to 1g every IM, IV Ceftazidime • Streptococcus pneumoniae 8h Ceftibuten • Ceftibuten 400mg/daily PO 37 38 Ceftriaxone – Minimal anaerobic coverage Ceftriaxone (Rocephin) 1-2g every 12-24h IM, IV

Penicillins:

• Special Considerations • Pharmacokinetics 3rd Generation – Ceftriaxone à calcium salt – à IM, IV 4th Generation Cephalosporins precipitate in the gallbladder that • Good penetration into fluids/tissues Cefdinir can be mistaken for gallstones • Penetrates CSF Cefditoren • Cholelithiasis Cefepime • Excreted in the urine Cefixime – Caution when giving Cefotaxime à Cefotaxime arrhythmias noted with IV Cefpodoxime – Avoid Cefditoren in patients with a Ceftazidime milk protein allergy. Ceftibuten 39 40 Ceftriaxone

Penicillins:

• Spectrum of Activity – Good gram-positive activity th 4 Generation • Staphylococcus Drug Dosage Route Indication Cephalosporin • Streptococcus – Good gram-negative activity Cefepime IM: 0.5-1g every IM, IV Pneumonia, intra- Cefepime abdominal infections, • Enterobacteriaceae 12h IV: 1-2g every 8- UTI, and skin & soft – Escherichia 12h tissue infections – Klebsiella – Pseudomonas – 41 42 – Proteus

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Penicillins: Penicillins:

• Special Considerations • Pharmacokinetics – Dosage needs to be adjusted for – Ceftaroline à IV only 4th Generation 5th Generation renal dysfunction • Good penetration into fluids/tissues Cephalosporin Cephalosporin • Neurotoxicity à seizures, • Penetrates CSF encephalopathy Cefepime Ceftaroline • Excreted in the urine – Be aware à it can cause patients to have a positive Coombs Test – Can cause glycosuria

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Penicillins:

• Spectrum of Activity – Gram-positive activity 5th Generation Cephalosporin • Staphylococcus aureus Drug Dosage Route Indication • Streptococcus pneumoniae Ceftaroline 600mg every 12h IV Pneumonia (CAP), Ceftaroline – Gram-negative activity skin & soft tissue • Relatively similar coverage to other infection cephalosporins. • NO Pseudomonas coverage.

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Penicillins:

• Special Considerations • th – Dosage adjustments in moderate to • 5 Generation severe renal dysfunction • /cilastatin Cephalosporin – Dosage adjustments in the elderly* • Ceftaroline Carbapenems • Meropenem/

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• Pharmacokinetics – All Carbapenems are à IV • Ertapenem can also be administered Carbapenems 49 Carbapenems IM Doripenem – Imipenem/cilastatin à inhibits • Mechanism of action àbactericidal à dehydropeptidase I Ertapenem interrupts cell wall synthesis • Doripenem, Ertapenem, and Imipenem/cilastatin Meropenem do not require a dehydropeptidase inhibitor Meropenem – Meropenem à well distributed in body Meropenem/vaborbactam tissues/fluids including CSF – Imipenem/cilastatin and Ertapenem à 50 distributed in body tissues/fluids BUT low CSF concentrations

• Spectrum of Activity Drug Dosage Route Indication – Broad spectrum activity against Skin & soft tissue gram-positive and gram-negative Doripenem 500mg every 8h IV Carbapenems infections*, intra- bacteria. abdominal Ertapenem 1g daily IM, IV Doripenem infections*, – Pseudomonas aeruginosa coverage respiratory Ertapenem EXCEPT Ertapenem Imipenem/cilastatin 500-1000mg every IV infections*, UTI*, 6-8h sepsis* Imipenem/cilastatin – ESBL (extended spectrum beta- Meropenem 1.5 to 6g daily in 3 IV Meropenem lactamases) coverage divided doses Meropenem/vaborbactam 4g every 8h IV Meropenem/vaborbactam

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• Special Considerations • – The dose must be adjusted in Carbapenems patients with renal disease Doripenem • Ertapenem à CrCl less than 30 ml/min Monobactam Ertapenem • Meropenem à CrCl less than 50 Imipenem/cilastatin ml/min Meropenem • Imipenem/cilastatin à less than 90 Meropenem/vaborbactam ml/min – Increased seizure risk in patient with 53 54 CNS/seizure disorders.

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• Pharmacokinetics – Aztreonam à IM, IV • IV is the preferred mode for Monobactam 55 administering • Mechanism of action àbactericidal à • Inhalation version à not readily used interrupts cell wall synthesis Monobactam – Distributed throughout tissues and Aztreonam fluids • Including CSF – Excreted renally

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• Spectrum of Activity – Gram-negative organisms • Enterobacteriaceae (e.g. Citrobacter, Enterobacter, Proteus, Serratia, etc.) Drug Dosage Route Indication • Pseudomonas aeruginosa Aztreonam 1-2g every 8-12h IM, IV UTI, respiratory tract Monobactam • infections, sepsis, skin & soft tissue Aztreonam infections, intra- abdominal infections, gynecological infections

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• Special Considerations • Erythromycin – Recommend pretreating patient with bronchodilator prior to inhalation • Clarithromycin administration • Azithromycin – Not uncommon to use double • Fidaxomicin Monobactam coverage with Pseudomonas infections Macrolides Aztreonam – Studies has indicated tolerance in patients with penicillin and cephalosporin allergy • ?Ceftazidime cross-allergy reaction

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• Pharmacokinetics – All the preparations can be given PO. • Azithromycin & Clarithromycin à Macrolides 61 Macrolides excellent oral absorption • Mechanism of action àbacteriostatic* à Azithromycin • Erythromycin à variations in PO preparation dictate absorption inhibits protein synthesis Clarithromycin • Fidaxomicin à minimal systemic Erythromycin absorption à primarily confined to the Fidaxomicin* GI tract à undetectable serum concentrations – Good tissue distribution 62 • Minimum blood-brain-barrier penetration

• Spectrum of Activity Drug Dosage Route Indication COPD, CAP, MAC, – Atypical bacteria Azithromycin PO: 250-600mg IV, PO, daily ophthalmic skin & soft tissue • Chlamydia IV: 250-500mg daily drops infections, streptococcal Macrolides • Legionella pharyngitis, N. gonorrhea Azithromycin • Mycoplasma Clarithromycin 250-500mg every PO H. pylori, CAP, MAC, Clarithromycin • Mycobacterium 12h skin & soft tissue infections Erythromycin • Neisseria Erythromycin Varies drastically IV, PO, All bacterial Fidaxomicin* – Gram-positive bacteria depending on the ophthalmic infections, colorectal base. drops, topical surgical prophylaxis – Gram-negative bacteria Fidaxomicin 200mg twice daily PO Clostridium difficile • Haemophilus 63 infections 64 • Moraxella

• Special Considerations • Besofloxacin – Monitor for QT prolongation • Cinoxacin – Liver disease • Ciprofloxacin* • Macrolides Avoid erythromycin estolate is • Delafloxacin Azithromycin contraindicated 2/2 to hepatic dysfunction with or without Fluroquinolones • Gatifloxacin à IV form removed from Clarithromycin jaundice market Erythromycin – Reversible deafness has occurred • Gemifloxacin à no longer available in US with Clarithromycin Fidaxomicin* • Levofloxacin* – Significant drug interactions can • occur with Erythromycin and Moxifloxacin* Clarithromycin 65 • Norfloxacin à no longer available in US 66 • Inhibitors of CYP3A4 • Ofloxacin*

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• Pharmacokinetics – All the fluroquinolones (listed here) à PO and ophthalmic drops Fluroquinolones 67 Fluroquinolones • All PO well-absorbed – Widely distributed throughout tissues • Mechanism of action àbactericidalà Ciprofloxacin inhibits DNA synthesis • CSF Levofloxacin – Excretion varies Moxifloxacin • Ciprofloxacin à Urine, bile/feces Ofloxacin • Levofloxacin à Primarily urine • Moxifloxacin à Urine, feces 68 • Ofloxacin à Primarily urine

• Spectrum of Activity Drug Dosage Route Indication – Gram positive organisms • Staphylococcus Ciprofloxacin PO: 250-750mg PO, IV, UTIs*, respiratory every 12h topical, infections, skin & soft Fluroquinolones – Gram negative organisms IV: 200-400mg ophthalmic tissue infections, intra-abdominal • Enterobacteriaceae every 12h Ciprofloxacin infections*, • Haemophilus Levofloxacin 250-750mg daily PO, IV, Levofloxacin ophthalmic, • Pseudomonas Moxifloxacin inhalation – Atypical organisms Moxifloxacin 400mg daily PO, IV, Ofloxacin ophthalmic • Legionella • Chlamydia Ofloxacin 200-400mg every PO, 69 12h ophthalmic 70 • Mycoplasma • Mycobacterium

• Special Considerations • Sulfamethoxazole/trimethoprim – Fluroquinolones are recommended for more severe infections 2/2 side effect profile. Fluroquinolones – Concurrent use with NSAIDs à may Ciprofloxacin increase the risk of seizures Sulfonamides Levofloxacin – Can prolong QT interval à Moxifloxacin Ciprofloxacin, Levofloxacin, and Moxifloxacin Ofloxacin – Antacids decrease absorption

71 72

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• Pharmacokinetics – Good PO absorption • Rapid Sulfonamides 73 Sulfonamides – Good penetration of tissues and fluids including the CSF • Mechanism of action àbacteriostaticà Sulfamethoxazole/ inhibits steps in folate synthesis – Excreted renally trimethoprim

74

• Spectrum of Activity – Gram positive coverage • Staphylococcus Sulfonamides • Streptococcus à some Drug Dosage Route Indication – Gram negative coverage Sulfamethoxazole/ Sulfamethoxazole/ PO: 800/160 mg PO, IV UTI, COPD • Enterobacteriaceae trimethoprim (Bactrim) every 12-24 hours exacerbation, PJP trimethoprim IV: 8-20 mg/kg/day prophylaxis and • Haemophilus treatment, traveler’s – Other organisms diarrhea, and shigellosis • Pneumocystis à yeast-like fungus • Stenotrophomonas à gram negative 75 76 • Toxoplasma à parasite • Nocardia à gram positive

• Special Considerations • Demeclocycline* – The IV dosing is based on the trimethoprim component • Doxycycline • Weight based dosing based on the • Minocycline Sulfonamides trimethoprim component Tetracyclines • Tetracycline* Sulfamethoxazole/ • Maximum 960 mg/day trimethoprim – Require renal-based dosing in setting of poor renal function – Total body clearance of trimethoprim is decreased in the elderly

– Side effects 77 78

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• Pharmacokinetics – Both can be given PO or IV. • Good PO absorption Tetracyclines 79 Tetracyclines • Can be given with or without food – Widely distributed throughout body • Mechanism of action àbacteriostaticà Doxycycline inhibits protein synthesis and tissues Minocycline – Small percentage excreted in the urine as well as feces/biliary

80

• Spectrum of Activity – Gram positive organisms Drug Dosage Route Indication • Staphylococcus Tetracyclines • Streptococcus – Gram negative organisms Doxycycline PO: 100-200mg/ PO, IV Respiratory tract daily infections, skin & soft Doxycycline • E. coli IV: 100mg every 12h tissue infections, Minocycline • Enterobacter cholera, STIs, Minocycline Initial for PO/IV à PO, IV rickettsial infections, • Klebsiella 200 mg cholera, meningitis, • Acinetobacter Maintenance PO: malaria prevention 100mg every 12h • Haemophilus OR 5omg 4x daily – Atypical organisms 81 Maintenance IV: 82 • Mycoplasma 100mg every 12h • Chlamydia

• Special Considerations – Minocycline à lupus-like reaction – Tetracyclines can increase liver Tetracyclines . • Hepatitis and liver failure have been Doxycycline reported with Minocycline Other Minocycline • Avoid in patients with hepatic insufficiency Antibiotics… – Okay to use doxycycline in renal failure because only small percentage excreted renally 83

This Photo by Unknown Author is licensed under CC BY

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• Mechanism of action à bacteriostatic à inhibits protein synthesis • Mechanism of action à bactericidal • Can be given IM, IV, or PO à inhibits DNA synthesis & – Good and rapid PO absorption degradation Clindamycin – Poor CSF penetration • Can be given PO or IV • Active against gram positive organisms Metronidazole – Well absorbed PO and anaerobes – Good CNS penetration • Indications à bacteremia, skin & soft • Active against anaerobes and tissue infections, intra-abdominal infections, respiratory tract infections, & protozoal parasites gynecological infections • Side effects: headache, dizziness, 85 86 • Side effects: site reaction, GI symptoms nausea, vaginitis

• Mechanism of action à bactericidalà • Mechanism of action à bactericidal inhibits DNA, RNA, and cell wall protein à inhibits cell wall synthesis synthesis • Can be given PO or IV • Given PO – Well absorbed – PO poorly absorbed • Antibiotic coverage varies slightly based – Widely disturbed when given IV Nitrofurantoin on medication. – Excreted renally – Macrobid à E. Coli and Staphylococcus • Active against gram positive – Macrodantin à Enterococcus, organisms only Staphylococcus, E. Coli, Klebsiella, Enterobacter • Side effects: • Indications à acute uncomplicated – PO: nausea, abdominal pain, & 87 88 cystitis hypokalemia • Side effects: GI symptoms, headache

• Lefamulin (Xenleta) – FDA Approved August 2019 – Completely new mechanism of action in last 20 years. • inhibits the synthesis of a bacterial protein needed for the bacteria to grow Drugs to look – Can be given PO and IV out for… – Treatment for CAP Antibiotic • Imipenem/Cilastatin/ (Recarbio) – FDA Approved July 2019 Stewardship – Can be given IV – Treatment for UTI and intra-abdominal infections • Omadacycline (Nuzyra) – FDA Approved October 2018 – Can be given PO or IV 89 – Treatment for CAP and skin & soft tissue infections This Photo by Unknown Author is licensed under CC BY

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• Prescribing antibiotics when they • Excess healthcare costs are not needed • Preventable adverse drug events • Failure to narrow antibiotics – Cause approximately 142,000 adult Antibiotic • Expanding duration of antibiotics Consequences ED visits annually Resistance longer than needed of Antibiotics • Contributes to antibiotic • Using the wrong antibiotic and/or resistance wrong dose – 2 million or more people acquire antibiotic resistant infections annually

91 – At least 23,000 die from antibiotic- 92 resistant infections

• Clostridioides (Clostridum) difficile • Penicillins • Streptococcus pneumoniae • Cephalosporins • MRSA • Carbapenems Antibiotic Antibiotics with • Monobactam • Enterobacteriaceae Resistant Resistant • Macrolides • Pseudomonas aeruginosa Infections Bacteria • Fluoroquinolones • Neisseria gonorrhoeae • Sulfonamides • Group A and B Streptococcus • Tetracyclines • Aminoglycosides 93 94 •

• If there are guidelines for treatment, FOLLOW them. • Narrow the spectrum of the antibiotic • Shorten the duration Antibiotic • STOP treating asymptomatic bacteriuria and Stewardship viral upper respiratory infections such as acute Prescribing Principles • Prescribe supportive care Case Studies • Hospital-based – De-escalate – Shorter durations 95 – Antibiograms

– Consult ID when appropriate

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• Mrs. Smith is a 70-year-old woman with past • Mrs. Smith has no physical complaints. medical history of diabetes mellitus type II, • Vital signs are stable. There are no changes stroke, chronic kidney disease stage 2, from her baseline. hypertension, and dementia with moderate • The physical exam is unremarkable. functional impairment who resides a nursing facility. The family reports her mental status • Diagnostics return: Case Study #1 appears different and they are concerned that Case Study #1 – CBC à unremarkable she may have an infection. Her baseline mental – CMP à unremarkable status is conversive but pleasantly confused. – UA à evidence of bacteria à greater than 105 • The provider evaluates the patient and to • The patient has evidence of bacteriuria plus appease the family runs diagnostics to rule out mild changes in her mental status. an infectious process as an indication for the mild change in her mental status. • She has no known drug allergies. 97 98

• What is the next course of action for Mrs. • Mr. Young is 48-year-old man with past medical Smith? history of poorly controlled diabetes mellitus – Would you prescribe an antibiotic based on the type II recently treated for a right lower findings? extremity cellulitis with Clindamycin. – If so, what antibiotic would you prescribe? • Now he presents with complaints of fever, Case Study #1 a) Ciprofloxacin Case Study #2 abdominal tenderness, and diarrhea x 3-4 days. b) Macrobid • He reports completing Clindamycin five days ago. c) Bactrim • The NP has a high suspicion of C. difficile. d) Augmentin – If you chose not to prescribe an antibiotic, why? • Culture results are positive. • He has no known drug allergies.

10 99 • What antibiotic therapy would be most 0 appropriate to prescribe?

• Ms. Jones is a 52-year-old woman with no • Common bacteria implicated are: Streptococcus significant past medical history who presents pneumonia, Haemophilus influenzae, and with complaints of fever, productive cough, . mild chest discomfort and shortness of breath. • Based on what is known about Ms. Jones, what • Vital signs of unremarkable with exception of a is the most appropriate antibiotic to prescribe? Case Study #3 fever with temperature 100.1F. Case Study #3 a) Augmentin 2g twice daily • On physical exam she has rales to the left lower b) Doxycycline 100mg twice daily lobe and dullness to percussion. c) Azithromycin 500 mg x 1 dose, followed by 250 • She has no recent history of antibiotic use. mg x 4 days • She reports an allergy to Levofloxacin d) Moxifloxacin 400 mg PO (Levaquin).

• The NP diagnoses her with a community 10 10 1 2 acquired pneumonia.

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• Ms. Williams is a 62-year-old woman with past • Mrs. Banks is a 68-year-old woman with past medical history of COPD who presents to the ED medical history of HFpEF, diabetes mellitus type II, with fever, worsening productive cough, mild hypertension, paroxysmal atrial fibrillation, and chest discomfort and moderate shortness of hyperlipidemia. She presents with complaints of breath. urinary urgency, dysuria, and foul-smelling urine x 2 days. • Vital signs: 101.8F – 102 – 118/68 – 26 – 92% on RA Case Study #4 Case Study #5 • UA is consistent with a UTI. • On physical exam she has rales to the left lower lobe and dullness to percussion. • Home medications include: Glyburide, Lisinopril, Amlodipine, Warfarin, and Atorvastatin. • She has no recent history of antibiotic use. • Which antibiotic therapy is most appropriate? • She reports no known drug allergies. a) Sulfamethoxazole/trimethoprim (Bactrim) • She is admitted to the hospital for community b) Nitrofurantoin (Macrobid) acquired pneumonia. 10 10 3 c) Levofloxacin (Levaquin) 4 • What antibiotic therapy is most appropriate? d) Cefaclor

• Mr. Post is a 37-year-old man with no significant • Mr. Post returns approximately 1-1.5 weeks later with medical history who presents with nasal drainage, resolution of the cough and scratchy throat, but now congestion, facial pain/pressure, cough, and reports purulent nasal drainage, congestion, and facial scratchy throat x 3-4 days. pain/pressure that has failed to improve. • He has no known drug allergies. • He has no known drug allergies. • His vital signs are unremarkable. • His vital signs are unremarkable. Case Study #6 Case Study #6 • The NP diagnoses a sinusitis. • The NP diagnoses an upper respiratory infection and sinusitis. • Common bacteria implicated are: Staphylococcus, Streptococcus, or Haemophilus influenza. • What is the most appropriate antibiotic to • What is the most appropriate antibiotic to prescribe for prescribe for his sinusitis? his sinusitis? a) Amoxicillin 10 b) Ceftriaxone 10 5 6 c) Ampicillin/Sulbactam d) Azithromycin

• Mrs. Reno is a 75-year-old woman with extensive • In HAP, you want to ensure you cover for gram- past medical history/multiple co-morbid negative organisms. Gram positive coverage conditions admitted to the hospital for (especially if concerned for resistance) is necessary symptomatic atrial fibrillation with a syncopal if high gram-positive isolates or recent antibiotic episode prior to presentation. She has no recent therapy within 90 days. hospitalizations. • What is the most appropriate antibiotic therapy Case Study #7 • On Day 4, the plan was to discharge her; however, Case Study #7 for Mrs. Reno? on evaluation, the patient has a low-grade fever, a) Ceftriaxone plus azithromycin shortness of breath, and is requiring 2L oxygen to b) Doxycycline maintain sats >92%. c) Levofloxacin • On CBC à presence of leukocytosis. d) Cefepime • CXR reveals a right lower lobe infiltrate. 10 10 • The NP diagnoses her with a hospital acquired 7 8 pneumonia (HAP).

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• Mr. Andrews is a 50-year-old man with • Mr. Wright is a 61-year-old man with a past uncontrolled diabetes mellitus type II, medical history of COPD, Gold Stage III on chronic hypertension, and chronic kidney disease, stage II home O2 2L nasal cannula. He presents with who presents with redness, tenderness, edema, worsening dyspnea and increased sputum and erythema to his right lower extremity. purulence. • He has no known drug allergies. • Over the last 2-3 days, he’s had to increase his O2 Case Study #8 • The NP provide diagnoses him with a mild, non- Case Study #9 requirements to 4L nasal cannula. purulent cellulitis. • He is allergic to penicillins and Azithromycin à • Common bacteria implicated are: Staphylococcus severe, diffuse rash. and Streptococcus. • The NP diagnoses him with a COPD exacerbation. • What is the most appropriate antibiotic therapy to • He’s started on supportive therapy including oral prescribe? steroids. He is to return for follow-up in 3-4 days 10 11 9 after starting treatment. 0 • What antibiotic is most appropriate to start?

• Ms. Jewels is a 31-year-old woman with past • The NP orders an ultrasound. The results indicate: medical history of asthma who presented to the – Pericholecystic fluid, gallbladder wall thickening, ED with complaints of fever, chills, severe and multiple gallstones. epigastric pain, and nausea/vomiting x 3-4 hours. • The patient is admitted for cholecystitis. • On exam, the patient appears uncomfortable. • Surgery is consulted and orders are written. There is tenderness to palpation à mostly noted • The patient has a known penicillin allergy. to the epigastric region. Case Study #10 Case Study #10 However, she has been prescribed other beta- • Vital signs: 101F – 118 – 147/90 – 26 – 96% on RA lactam antibiotics in the past with no allergic • Labs reveal: response. – Leukocytosis with shift • Common bacteria implicated are: Klebsiella, E. – Mild elevation of AST and ALT Coli, and anaerobes. – Lipase negative 11 • What antibiotic therapy would you prescribe? 11 1 2 – Pregnancy test negative

Questions??

Thank you!

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