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PRACTICAL USAGE OF ANTIBACTERIAL AGENTS. Rema Merhi, D.O. PGY-3 Infectious Disease University of Nevada School of Medicine Pisespong Patamasucon, M.D. Professor of Pediatrics Director Pediatric Infectious Diseases University of Nevada School of Medicine. Penicillins. Carbenicillin

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PRACTICAL USAGE OF ANTIBACTERIAL AGENTS

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PRACTICAL USAGE OF ANTIBACTERIAL AGENTS

Rema Merhi, D.O.

PGY-3

Infectious Disease

University of Nevada School of Medicine

Pisespong Patamasucon, M.D.

Professor of Pediatrics

Director Pediatric Infectious Diseases

University of Nevada School of Medicine


Penicillins


Carbenicillin

Ticarcillin

Piperacillin

Ampicillin

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Nafcillin

Oxacillin

Methicillin


Penicillin

  • Gram-Positive Cocci

    • Streptococci

      • Except Enterococcus

  • Gram-Positive Rods

    • C. diphtheria

  • Gram-Negative Cocci

    • Neisseria

  • Spirochete

    • Treponema pallidum

  • Anerobic

    • Except Bacteroides fragilis

No Gram Negative Rod Coverage

Amino-penicillin


Gram Negative

Carbenicillin

Ticarcillin

Piperacillin

(low Na load)

Ampicillin

E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella

Pseudomonas, B. fragilis

GPC, GPR, GNC, SpirocheteAnaerobes

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Nafcillin

Oxacillin

Methicillin

Staphylococci

(MSSA)

*increased anaerobic coverage

Staphylococci

(MSSA)


Cephalosporins


Cephalosporin

  • Same mechanism as penicillin

    • If allergic to PCN can react to this too!

  • Bacteriostatic

  • Does not cover:

    • L- listeria

    • A- anaerobes*

    • M- MRSA

    • E- enterococcus

      **Cefoxitin, Cefotetan cover anaerobes


1st Generation Cephalosporin

(except H. influ)

Gram Negative

Carbenicillin

Ticarcillin

Piperacillin

Ampicillin

E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella

Pseudomonas, B.fragilis

GPC, GPR, GNC, SpirocheteAnaerobes

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Nafcillin

Oxacillin

Methicillin

Staphylococci

(MSSA)

Staphylococci

(MSSA)


Cephalosporin

  • 1st Generation:

    • Gram Positive

      • S. aureus, S. epidermidis, Streptococcus species

      • NO MRSA

    • Gram Negative

      • E. coli, K. pneumoniae, P. mirabilis

      • NO Enterococci

    • Anaerobes

      • NO B. fragilis


Cephalosporin

  • 1st Generation:

    • Cefazolin (Ancef)

      • IV

      • Given q 8º

      • Surgery prophylaxis

    • Cephalexin (Keflex)

      • PO

      • Skin 50mg/kg/day

      • Bone 2-3x skin dose

    • Cefadroxil (Duricef)

      • PO

      • Given q 12º

      • UTI

        • Especially for ampicillin and TMP/SMZ resistant


2nd Generation Cephalosporin


2nd Generation Cephalosporin

(including H. influ)

Gram Negative

Carbenicillin

Ticarcillin

Piperacillin

Ampicillin

E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ,

Klebsiella

Pseudomonas, B. fragilis

GPC, GPR, GNC, SpirocheteAnaerobes

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Nafcillin

Oxacillin

Methicillin

Staphylococci

(MSSA)

Staphylococci

(MSSA)


Cephalosporin

  • 2nd Generation:

    • Less GM+ coverage, More GNB coverage

    • Beta-Lactamase +/ Beta-Lactamase –

    • Add H.influ (with BL+ and -), Enterobacter, Neisseria

    • CNS penetration < than 3rd generation

  • Cefuroxime

    • CNS penetration

  • Cefoxitin

    • Anaerobic coverage!

      • Surgeons/ OB-GYNs

  • Cefotetan

    • Anaerobic coverage!

    • GN coverage (PID)


3rd Generation Cephalosporin


3rd Generation Cephalosporin

Gram Negative

Carbenicillin

Ticarcillin

Piperacillin

Ampicillin

E.Coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella

Pseudomonas, B.fragilis

GPC, GPR, GNC, SpirocheteAnaerobes

Nafcillin

Oxacillin

Methicillin

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Staphylococci

(MSSA)

Staphylococci

(MSSA)


Cephalosporin

  • 3rd Generation:

    • Great GN coverage; No staph coverage

    • CNS coverage

  • Ceftriaxone

    • IV q 24º

    • CNS penetration

    • High activity against beta-lactamase producing H.influ, N.gonorrhoeae

  • Cefotaxime

    • IV q 6º

    • CNS penetration

    • High activity against beta-lactamase producing H.influ, N.gonorrhoeae

  • Ceftazidime

    • Antipseudomonal


3rd Generation Cephalosporins

Gram Negative

1st Generation Cephalosporins

(except H. influ)

Carbenicillin

Ticarcillin

Piperacillin

Ampicillin

E.Coli, Shigella, Proteus, Salmonella, Listeria, H.influ

Pseudomonas, B.fragilis

2nd Generation Cephalosporins

(including H. influ)

GPC, GPR, GNC, SpirocheteAnerobes

Ampicillin + Sulbactam

Ampicillin + Clavulanate

Ticarcillin + Clavulanate

Piperacillin + Tazobactam

Nafcillin

Oxacillin

Methicillin

Staphylococci

(MSSA)

Staphylococci

(MSSA)


Cephalosporin

  • 4th Generation:

    • Cefepime- pseudomonas

      • Covers GN

        • Nosocomial GNB acinobacter

        • S. pneumo

      • Does NOT cover Extended Spectrum Beta-Lactamase

        • ESBL’s


ESBL’s

  • Extended Spectrum Beta-Lactamases

    • Enterococcus faecium

    • Serratia

    • Klebsiella pneumoniae

    • Acinetobacter baumanii

    • Providencia/pseudomonas

    • Enterobacter spp.

      • Salmonella, E. coli

  • Treatment:

    • Meropenem

    • Pipercillin+Tazobactam

      • Zosyn


  • Side Effects

    • Penicillin:

      • Black or hairy tongue

      • Exaggerated reflexes

      • Mild diarrhea

      • Nausea or vomiting

      • Pain, swelling, or redness at the injection site

      • Twitching

      • Anaphylaxis


    Side Effects

    • Cephalosporins:

      • Generally few side effects

        • Hypersensitivity if allergic to PCN

        • Mild stomach cramps

        • Nausea/vomiting/diarrhea

        • Yeast overgrowth


    Aminoglycosides

    • Amikacin

    • Gentamicin

    • Tobramycin

    • Paromomycin

  • Coverage:

    • Gram negative bacilli

      • Enterobacteriaceae, Pseudomonas spp., Haemophilus influenzae

      • Paromomycin covers protozoa

    • Bactericidal

      • Inhibits bacterial translocation

  • Concentration-dependent killing

    • Concentration of drug (relative to bacteria MIC) induces more rapid, and complete, killing of the pathogen


  • Aminoglycosides

    • Disadvantages

      • Target concentration

        • Peak and Trough levels

        • Frequent dose changes

    • Side Effects:

      • Ototoxicity

        • 2º to vestibular or cochlear damage

      • Nephrotoxic

        • 10-20%

      • Neuromuscular blockade

        • Blocks neuromuscular transmission at neuromuscular junction

          • Presynaptic (block acetylcholine synthesis/release) or Postsynaptic (at motor nerve end plate) action

          • Postsynaptic


    Vancomycin

    • Glycopeptide antibiotic

    • Bacteriostatic

    • Inhibits cell wall synthesis in GPB

    • Use to cover resistant Strep pneumo

      • Synergistic with PCN or Ampicillin

    • Coverage:

      • Gram positive bacteria

      • MRSA

      • Coag Neg Staph

      • C.diff

      • Enterococcus

        • Except VRE


    Vancomycin

    • Renal excretion

    • Side Effects:

      • Red-man syndrome

      • Hypotension

      • Steven Johnson Syndrome (SJS)

      • Toxic epidermal necrolysis (TENs)

      • Interstitial nephritis

    • Poor bone and brain penetration

      • 7-13% bone

      • <10% brain

        • 60/mg/kg

          • Usually 20-40 mg/kg


    Vancomycin

    • VRE- Vancomycin Resistant Enterococcus

      • Treatment:

        • Linezolid (Zyvox)

        • Daptomycin

          • Can not use to treat PNA surfactant in lung breaks down drug

        • Synercid

          • Quinupristin and dalfopristin

          • Enterococcus faecium (not faecalis)


    Clindamycin

    • Coverage: (PO=IV)

      • Gram positive cocci

        • Staph/Strep

      • Anaerobes

        • Above diaphragm

    • Bacteriostatic

      • But considered bactericidal against

        • Some staph, strep, and B.fragilis

    • Great BONE penetration 60%

      • Linezolid 50%

    • Side Effects:

      • Diarrhea

      • Allergic reactions


    Macrolides

    • Azithromycin

    • Clarithromycin

    • Erythromycin

    • Coverage:

      • GPC, Haemophilus spp, Moraxella catarrhalis

      • Atypical: Legionella, Chlamydia and Mycoplasma pneumoniae

      • Rickettsia, helicobacter, toxoplasma

    • Good tissue and intracellular penetration

    • Long half lives

      • Azithromycin ½ life is 68 hrs


    Macrolides

    • Side Effects:

      • Erythromycin:

        • Hypertrophic pyloric stenosis

        • Long QT syndrome

        • Interstitial nephritis

      • Azithromycin

        • Hepatotoxicity- increased LFT’s, cholestatic jaundice

      • All three (clarithromycin, erythromycin, azithromycin)

        • N/V/DIARRHEA

        • Anaphylaxis

        • SJS

        • Pseudomembranous colitis


    Miscellaneous Antibiotics

    • Tetracycline: (PO=IV)

      • Bacteriostatic

      • GP, GN, rickettsia, mycoplasma, chlamydia, spirochete (Borrelia), malaria, tularemia, leptospirosis, RMSF

      • Side effects:

        • Tooth discoloration

          • Do not take with milk

        • Use in patients > 8 yo

    • Fluoroquinolones:

      • Bactericidal

      • Use if >18 yo

        • Arthropathy, erosion of cartilage in weight bearing joints

      • GNB, GP except MRSA, some pseudomonas, chlamydia, mycobacteria

    • Metronidazole (Flagyl):

      • Anaerobes and CNS coverage

      • Below diaphragm


    CNS INFECTION


    Bacterial Meningitis: Treatment


    Duration of Treatment

    • Neonate

      • 10-14 days:

        • GBS, L.monocytogenes

      • 3 weeks:

        • gram-neg enteric meningitis

    • Infant/Child

      • 10-14 days:

        • N. meningitides 7 days

        • H. influenza

        • S. pneumoniae


    Pneumonia


    Etiology of Pneumonia in

    Infants and Children

    {

    Viral

    Agents

    Para 1,2,3

    Influenza

    A, B.

    Etc.

    Winter

    Summer

    S. Pneumoniae

    Mycoplasma

    RSV

    C. Trachomatis

    CMV

    1

    Staph

    2

    Staph

    Chlamydia

    Pneumoniae

    Strep.Gr.B

    E. Coli

    H. Inf. b

    1 mo 3 mo 6 mo 1 yr 3 yrs 5 yrs 10 yrs


    Antimicrobial Agents for Community Acquired Pneumonia in Various Pediatric Age Groups


    Children with Pneumonia Warranting Consideration of Inpatient Management

    • Toxic appearance

    • Respiratory distress

    • Pleural effusion

    • Immunocompromised host

    • Progression during outpatient therapy

    • Age factors

      • Less than 3 mos

      • Less than 3 yrs with lobar

      • Less than 5 years with more than 1 lobe

    • Those with chronic disease

      • Pulmonary

      • Cardiac

      • Renal

      • Diabetes

      • Metabolic disorders

      • Anemia

      • malignancies


    HEMATOGENOUS OSTEOMYELITIS


    Neonates


    Infants/ Children


    Initial Treatment of Osteomyelitis


    S. aureus Coverage

    • Semi-synthetic PCN

      • Nafcillin or Oxacillin

    • 1st generation cephalosporin

    • 2nd generation cephalosporin

    • Clindamycin/Vancomycin


    Important Information

    • Treatment less than 3 weeks associated with increase risk for recurrence

    • Treatment with IV less than 7 days associated with morbidity

    • Total duration of treatment 4-6 weeks

    • Time to stop – resolution of symptoms with normalized WBC, CRP, or ESR

      • CRP < 1

      • ESR < 15


    The # 1 “Scary Bug”

    MRSA


    Comparison of HA-MRSA and CA-MRSA


    MRSA

    • In 2005 60% of soft skin tissue infections (SSTI) were MRSA

    • Clindamycin resistance at UMC and sunrise 46%

      • 6% 26% 46% (in 2009)

    • Alternative treatment:

      • Vancomycin- slow so add gentamicin for synergy

      • Since it can still be MSSA….add Nafcillin or Oxacillin


    MRSA Treatment

    • Outpatient:

      • Tetracycline

      • Bactrim

      • Clindamycin

    • Inpatient:

      • Clindamycin

      • Vancomycin

      • Linezolid

      • Daptomycin

      • Synercid

        • Quinupristin and dalfopristin


    CA-MRSAAntibiotic Susceptibility

    • Vancomycin

    • Gentamicin/rifampin (synergy 3-5 days)

    • Trimethoprim-sulfamethoxazole

    • Clindamycin

    • Doxycycline/minocycline

    • Linezolid (Zyvox)

    • Daptomycin (Cubicin)

    • Quinupristin/dalfopristin (Synercid)


    Infectious Disease Clinics. Infect Dis Clin N Am 19 (2005) 747-757


    Board Review

    • You admit an 18yo boy to the hospital with RLL PNA. While gathering your history, you discover that 4 years ago he developed a rash and respiratory difficulty when he received IM ceftriaxone. Of the following, the BEST antimicrobial agent for this patient is:

      • Ceftriaxone

      • Levofloxacin

      • Meropenem

      • Penicillin


    Board Review

    • You admit an 18yo boy to the hospital with RLL PNA. While gathering your history, you discover that 4 years ago he developed a rash and respiratory difficulty when he received IM ceftriaxone. Of the following, the BEST antimicrobial agent for this patient is:

      • Ceftriaxone

      • Levofloxacin

      • Meropenem

      • Penicillin


    Board Review

    • Levofloxacin has broad spectrum activity against bacteria that cause LRTI, including GPB, GNB,and atypicals.

      • He had a previous reaction to ceftriaxone

      • Meropenem rarely needed for CA-PNA

      • Vancomycin monotherapy does not provide broad coverage of potential organisms


    Board Review

    • You are planning to treat a patient who has a PCN allergy with clarithromycin. The mother asks you about possible adverse effects of this medication. Of the following adverse effects, the MOST likely to expect is:

      • Diarrhea

      • Dizziness

      • Headache

      • Torsade's de points

      • Urticaria


    Board Review

    • You are planning to treat a patient who has a PCN allergy with clarithromycin. The mother asks you about possible adverse effects of this medication. Of the following adverse effects, the MOST likely to expect is:

      • Diarrhea

      • Dizziness

      • Headache

      • Torsade's de points

      • Urticaria


    Board Review

    • A 3 yo patient who has ALL is admitted to the PICU after developing severe sepsis 2º to Pseudomonas aeruginosa. She is intubated, ventilated, and requires intensive vasopressor support. Of the following, the MOST appropriate antibiotic regimen for the treatment of this patient is an aminoglycoside plus:

      • Cefazolin

      • Cefdinir

      • Ceftazidime

      • Ceftriaxone

      • Cefuroxime


    Board Review

    • A 3 yo patient who has ALL is admitted to the PICU after developing severe sepsis 2º to Pseudomonas aeruginosa. She is intubated, ventilated, and requires intensive vasopressor support. Of the following, the MOST appropriate antibiotic regimen for the treatment of this patient is an aminoglycoside plus:

      • Cefazolin

      • Cefdinir

      • Ceftazidime

      • Ceftriaxone

      • Cefuroxime


    Board Review

    • A 5 yo boy who has neuroblastoma is admitted to the PICU for treatment of fever, neutropenia, and severe hypotension, due to Klebsiella pneumoniae sepsis. Over the last several months, he has received multiple courses of vancomycin, ceftazidime to treat fever and neutropenia. Antibiotic susceptibility testing of the pathogen shows it to be susceptible to carbapenemand aminoglycoside classes of antibiotics. Of the following, the MOST likely mechanism of resistance in this organism is:

      • Alterations in penicillin-binding proteins

      • Decreased affinity for ribosomal target binding sites

      • Increased thickness for organism cell wall

      • Production of an efflux pump

      • Production of extended spectrum beta-lactamases


    Board Review

    • A 5 yo boy who has neuroblastoma is admitted to the PICU for treatment of fever, neutropenia, and severe hypotension, due to Klebsiella pneumoniae sepsis. Over the last several months, he has received multiple courses of vancomycin, ceftazidime to treat fever and neutropenia. Antibiotic susceptibility testing of the pathogen shows it to be susceptible to carbapenemand aminoglycoside classes of antibiotics. Of the following, the MOST likely mechanism of resistance in this organism is:

      • Alterations in penicillin-binding proteins

      • Decreased affinity for ribosomal target binding sites

      • Increased thickness for organism cell wall

      • Production of an efflux pump

      • Production of extended spectrum beta-lactamases


    Board Review

    • A 15 yo boy who has Mycoplasma pneumoniae is being treated with azithromycin. Of the following, the MOST likely adverse reaction would be:

      • Anorexia

      • Diarrhea

      • Dyspepsia

      • Headache

      • Rash


    Board Review

    • A 15 yo boy who has Mycoplasma pneumoniae is being treated with azithromycin. Of the following, the MOST likely adverse reaction would be:

      • Anorexia

      • Diarrhea

      • Dyspepsia

      • Headache

      • Rash


    Thank You

    • Dr. Pisespong Patamasucon


    THE END


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