principles of infectious diseases and antibiotics · 2011-05-06 · principles of infectious...

2011/3/25

11

指導幹部：湯珍珍藥師

指導藥師：盧志嘉、張佳鈴藥師

報告組員：陳琨勝、呂依真、曾詠新

Principles of Infectious Diseases

and Antibiotics

2011/3/25

22

Contents

Infectious Diseases

Classification of Antibiotics

Case Report

Case Discussion4

1

2

3

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Infectious Diseases

Introduction

Establishing the presence of infections

Identification of the pathogens

Selection of antimicrobial therapy

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Introduction

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Establishing the presence of

infections(1)

Signs and symptoms

1. Fever：BT>37°C(axillary)

Infection induced (not always)

drug induced (Drug fever：phenytoin 、

amphotericin B)

other disease induced (autoimmune disease、

neoplasms)

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infections(2)

Signs and symptoms

2.WBC

normal：4800-10800 mm3

commonly ↑with infection (not always)

Neutrophil：(a)segment (b)band (left shift)

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infections(3)

Left shift

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infections(4)

Signs and symptoms

3.clinical symptoms

pulmonary：tachypenea、yellow-green

sputum、hypoxemia

gastrointestinal：abdominal pain、diarrh、

bowel sounds

urinary tract：dysuria、flank pain

superficial：erythema、abscess、swelling

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infections(5)

Signs and symptoms

4.asymptom

immunodeficency： (a)drug related

(b)disease related

covert infection-virus

other infection

latent infection

opportunistic infection

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Identification of the pathogens(1)

Gram stain (G(+)、G(-))

Aerotolerance (aerobic, anaerobic)

India ink and KOH stain (fungi)

Acid-fast bacilli stain (Tb)

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Culture and susceptibility

1.Disk diffusion(Kirby-Bauer test)

2.Broth dilution

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Identification of the pathogens(3) Aerobic

Gram-positive Cocci

- Streptococci: pneumococcus, viridans streptococci; group A streptococci- Enterococcus

- Staphylococci: Staphylococcus aureus, Staphylococcus epidermidis

Rods (bacilli)

- Corynebacterium- Listeria

Gram-negative Cocci

- Moraxella- Neisseria (Neisseria meningitides. Neisseria gonorrhoeae)

Rods (bacilli)- Enterobacteriaceae (Escherichia coli, Klebsiella, Enterobacter, Citrobacter,

Proteus,Serratia, Salmonella, Shigella, Morganella, Providencia)- Campylobacter- Pseudomonas- Helicobacter- Haemophilus (coccobacilli morphology)- Legionella

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AnaerobicGram-positive Cocci

- Peptococcus- Peptostreptococcus

Rods (bacilli)- Clostridia (Clostridium perfringens, Clostridium tetani, Clostridium difficile)- Propionibacterium acnes

Gram-negative Cocci

- None Rods (bacilli)

- Bacteroides (Bacteroides fragilis, Bacteroides melaninogenicus)- Fusobacterium- Prevotella

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Selection of antimicrobial therapy(1)

Empiric therapy

Host factors

Drug factors

Monitoring therapeutic response

Combination of antimicrobial therapy

Failure of antimicrobial therapy

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Empiric therapy1.before blood culture and sensitivity2.consideration： the site of infection localization antibiogram community or nosocomial host factors or drug factors

Broad spectrumNarrow spectrum

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Host factors1.the site of infection

(1) respiratory

(2) UTI

(3) skin and soft tissue

(4) intra-abdominal

(5) gastroenteritis

(6) endocarditis

(7) meningitis

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Host factors

2.age

(1) different pathogens

meningitis:

(a.) neonates(<1yr) (Escherichia coli, Listeria,

group B streptococci )

(b.) adults (Streptococcus pneumoniae, Neisseria

meningitides )

(2) drug toxicities：Tetracycline、FQs

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Host factors

3. Pregnancy

Avoid：Tetracycline、FQ、Chloramphenicol

4. Genetics

(a) allergy

(b) G6PD deficiency

(c) metabolism

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Host factors

5. Organic dysfunction (Dose adjust)：

Liver

dysfunction

Macrolides, Clindamycin, Chloramphenicol,

Linezolid

Renal

dysfunction

β-lactams, Tetracycline, FQs, AMGs,

TMP/SMX, Quinupristin/Dalfopristin

Liver: Cefoperazone, Ceftriaxone, Doxycyline,

Moxifloxacin

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Host factors

6. Concomitant disease

AIDS

DM

Neoplasm (chemotherapy)

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Drug factors

1.Pharmacodynamics

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(1) conc.-dependent bactericidal activity peak/MIC ratio：AMGs, FQs,Daptomycin

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(2) time- dependent bactericidal activity time(T) = the conc. is above MIC (T > MIC) ：

β-lactams, Vancomycin, Clindamycin,

Macrolides, Tetracyclines, Linezolid

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Drug factors

2.Tissue penetration

The importance of tissue penetration varies with

site of infection.

Penetrate B.B.B：Ampicillin、Cefuroxime (2

generation)、Cephalosporins (3 generation)、

Chloramphenicol

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Drug factors3.Toxicity and side effectβ-lactams：Allergy (anaphylaxis), diarrheaAMGs：Nephrotoxicity, ototoxicityMacrolides：Nausea, vomiting, diarrheaTetracyclines：Teeth and bone deposition and

discoloration, photosensitivityFQs：Cartilage toxicity, CNS, QT prolong

4.Cost

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Monitoring therapeutic response1.CultureBroad spectrum Narrow spectrum

2.Clinical symptomsrelieve or not？

3.Serum concentrationaminoglycoside, chloramphecicol, vancomycin

4.Lab dataWBC count, seg./band, CRP, ESR

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Combination of antimicrobial therapy1.Broadening the Spectrum of Coverage

Empiric therapy

Mixed infections (DM,intraabdominal)

2.Decrease toxicity

Lower the dose

3.Synergism

1+1>2

4.Preventing Resistance

Especially for TB

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1.Drug factors

(1) Subtherapeutic dose

absorption

penetrate

protein binding

(2) Wrong drug

(3) Antagonism(1+1<2)

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2.Microbial factors (Resistance)

Overuse antibiotics

β-lactamases production

PBPs (penicillin-binding proteins) change

MRSA (Methicillin-resistant Staphylococcus Aureus)

VRE (Vancomycin-Resistant Enterococci)

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3.Host factors

immunosupressed patient

poor circulation

abscesses or necrotic tissue

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Classification of Antibiotics

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Classification

Bacterial cell wall synthesis inhibitors

Bacterial protein synthesis inhibitors

Antimetabolites

Fluoroquinolones

Antimycobacterial agents

Miscellaneous antimicrobial agent and

antiseptics

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Overview

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Bacterial cell wall synthesis

inhibitors

β-lactam antibioticsPenicillins

Cephalosporins

Carbapenems: Imipenem, meropenem, ertapenem

Monobactam : Aztreonam

Glycopeptides：Vancomycin, Teicoplanin

Lipopeptide：Daptomycin

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Penicillins(1)

Subclass Activity

spectrum

Pharmacokinetic Toxicities

Narrow

spectrum

Penase-susceptible

Penicillin G (IV)

Penicillin V (oral)

Procaine and

benzathine form of

Penicillin G (IM)

Streptococci

Meningococci

G(+) bacilli

Syphilis

Rapid renal

elimination;

short half-lives

necessitate

frequent dosing

Hypersensitivity

reations

Penase-resistant

Nafcillin

Oxacillin

Methicillin

Staphylococcal

Infection

Biliary

clearance

Interstitial

nephritis

(Methicillin)

Neutropenia

(Nafcillin)

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Penicillins(2)

Wide

spectrum

(+/-)

Penicillinase

susceptible

Activity spectrum

& Clinical Use

Pharmacokinetic

& Interaction

Toxicities

Ampicillin

Amoxicillin

G(-) bacilli

Enterococci,

Listeria (with AMG)

monocytogenes;

E. coli;

Proteus mirabilis;

H. influenzae

Unasyn :

Ampicillin / sulbactam

Augmentin :

Amoxicillin/ clavulanic acid

GI distress and

Maculopapular

Rash(ampicillin)

Nausea and

diarrhea(oral),

Pseudomembr-

anous colitis

(ampicillin)

Piperacillin

Ticarcillin

G(-) rods,

Paeudomonas,

(Piperacillin

> Ticarcillin)

Enterbacter,

Klebsiella,(with

AMG)

Tazocin:

Piperacillin/

Tazobactam

Timentin:

Ticarcillin/

clavulanic acid

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3737

Cephalosporins(1)

Generation Activity spectrum&Clinical use Pharmacokinetic

& Interaction

1st

Cephalexin(oral)

Cefazolin(IV)

G(+)cocci,

E. coli,

K. pneumoniae,

Surgical prophylaxis

Skin,soft tissue infection

Minimal activity:

G(-) cocci, G(-) rods

Enterococci

MRSA

Oral use (older drugs)

Mostly IV (newer drugs)

Renal elimination ,

Cephalosporin with side

chains undergo hepatic

metabolism

(cefoperazone,ceftriaxone)

2nd

Cefotetan

Cefoxitin

Cefamandole

Cefuroxime

Cefaclor

Less activity against G(+) than

1st generation but extend G(-) coverage

S. pneumoniae

Bateroides fragilis (cefotetan,cefoxitin)

H. influenzae, M. catarrhalis

(cefamandole,cefuroxime,cefaclor)

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Cephalosporins(2)

Generation Activity spectrum& Clinical Used Pharmacokinetic

3rd

Ceftazidime

Cefoperazone

Cefotaxime

Ceftizoxime

Ceftriaxone(IV)

Cefixime(oral)

Meningitis: gonorrhea (cetriaxone,cefixime)

Providencia,

Serratia marcescens,

H influenzae,

Neisseria,

PRSP strains (Cetriaxone,cefotaxime)

Pseudomonas (cefoperaxone,cetazidime)

B fragilis(cefizoxime)

Otitis media:A single dose

ceftriaxone=amoxicillin (10 days)

3rd drug enter CNS

(except

cefoperazone and

cefixime)

Cefoperazone and

ceftriaxone excreted

in the bile

4th

Cefepime

Cefpirome

G(+): similar activity against G(+) as 1st

G(-): 4th have a greater resistance to beta-

lactamases than the 3rd generation (ex.

Enterobacter)

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Other beta-lactam drugs

Subclass Activity spectrum&

Clinical Use

Pharmacokinetic

& Interaction

ADR

Monobactam

Aztreonam(IV)

Activity to G(-) rods

(Klebsiella,Pseudomonas,

Serratia)

but no activity against

G(+), anaerobes

Bind to PBP3

(penicillin-binding

protein), synergistic

with AMG

Renal elimination

Superinfection

Vertigo

Headache

Hepatoxicity

Skin rash (no

cross-allergenicity

with penicillins)

Carbapenems

Imipenem

Meropenem

Ertapenem

Wide activity against

G(+) cocci (including

PRSP) (not MRSA),

G(-) rods, anaerobes.

Pseudomonal infection

(with AMG)

Imipenem/cilastatin

(dehydropeptidase)

(Cilastatin inhibits

renal metabolism

of imipenem)

Renal elimination

CNS toxicity

(Seizure

Confusion,

encephalopathy)

Nephrotoxic

metabolite

(Imipenem)

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4040

Other cell wall or membrance-active agent(1)

Subclass Activity spectrum

&Clinical Used

Pharmacokinetic

&Interaction

ADR

Glycopeptides

Vancomycin

Teicoplanin

G(+) activity

includes MRSA and

PRSP strains

(combination with 3rd

cephalosporin)

Parenteral (oral for

C. difficile)

Renal elimination

IV only, long half-

life

Vancomycin:

Red –man

syndrome

Nephrotoxicity

Ototoxicity

Lipopeptide

DaptomycinG(+) activity;used in

endocarditis and

sepsis

Renal elimination Myopathy：monitor CPK

weekly

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4141

Other cell wall or membrance-active

agent(2)

Fosfomycin

1. An antimetabolite inhibitor of cytosolic enolpyruvate

2. Minimal inhibitory concentrations for many UTI

3. Synergistic with B-lactam and quinolone antibiotics

4. Diarrhea is common

Cycloserine

only used to treat tuberculosis when first-line drug useless

Bacitracin

Because of its marked nephrotoxicity,the drug is limited to

topical use.

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4242

Bacterial cell wall synthesis

inhibitors

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43

Bacterial protein synthesis

inhibitors

Bind to 30s：Tetracycline, Aminoglycoside

Bind to 50s：Chloramphenicol, Streptogramins,

Macrolides

Bind to 23s of 50s：Linezolid

43

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4444

Tetracycline(1)

Tetracycline der. : Tetracycline, Minocycline, Doxycycline

Glycylcycline der. : Tigecycline

Mechanism Bind 30s ,Broad-spectrum bacteriostatic antibiotics

Pharmacokinetics

Oral absorption is variable: May be impair by food and

multivalent cations

Wide tissue distribution and cross placental barrier

Drugs eliminated primarily in the urine (except doxycycline )

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4545

Tetracycline(2)

Activity1. G(+),G(-) bacteria (Rickettsia, Chlamydia, Mycoplasma),

some protozoa

2. Proteus, pseudomonas resistance to all of Tetracycline

(including Tigecycline)

Clinical use

1. Infections due to chlamydiae, mycoplasma, rickettsiae,

spirochetes ,and H.poly (Doxycycline is an alternative to

macrolide in the initial treatment of CA-pneumonia)

2.Treatment of acne (low dose)

3.Tetracycline: alternative drugs in the treatment of syphilis

4.Tigecycline : MRSA, VRE, anaerobes, Chlamydiae, mycobacteria

β-lactamase-producing G(-) bacteria

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4646

Tetracycline(3)

Toxicity

1. Gastrointestinal disturbances

2. Bony structures and teeth dysplasia

3. Hepatic toxicity : high dose

4. Photosensitivity : especially demeclocycline

5. Vestibular toxicity : doxycycline, minocycline

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4747

Chloramphenicol(1)

Mechanism

Bind to 50S ribosomal subunit ; usually bacteriostatic

Activity& Clinical use

1. Wide spectrum (H.influenzae, Nesseria menibgitidis,

bacteroides)

2. Backup drug for serve infection by Salmonella

3. Treatment Peumococcal and Meningococcal in the

person who is β-lactam hypersensitive

4. Topical use

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4848

Chloramphenicol(2)

Toxicity 1. Gastrointestinal disturbance

2. Bone marrow : dose dependent and reversible (except

aplastic anemia )

3. Gray baby syndrome

Drug interationChloramphenicol inhibits hapatic drug-metabolizing

enzymes

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4949

Macrolides(1)

Machanism of action

Bind to 50S ribosomal subunit, bacteriostatic

Pharmacokinetics

Oral ; IV : erythromycin, azithromycin; Heaptic clearence

Long half-life: azithromycin

Activity& Clinical use

Community-acquired pneumonia, pertussis,

corynebacteria, chlamydial infections

Toxicity

GI upsets, hepatic dysfunction, QT elongation, CYP450

inhibition (not azithromycin)

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5050

Macrolides(2)

Drug Spectrum Clinical uses

Erythromycin

Campylobacter jejuni,

Chlamydia , Trachomatis,

Mycoplasma , Legionella

G(+) cocci (not PRSP,

MRSA)

Clarithromycin

Chlamydia, Toxoplasma

Mycobacterium avium

G(+) cocci , G(-) organism

Used for prophylaxis

against M avium ,

H pylori

Azithromycin

Chlamydia, Toxoplasma

Mycobacterium avium

H. Influenzae,

Moraxella catarrhalis, Neisseria

Gonorrhea,

Syphilis,

Community-acquired

Pneumonia

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Macrolides(3)

Drug Pharmacokinetics Clinical uses Toxicity

Ketolide

Telithromycin

Orally once daily

E liminated in the

bile and the urine

Community-acquired

pneumonia including

infections by

mutidrug-resistant

organism

Hepatic dysfunction

Long QTc syndrome

Lincosamide

Clindamycin

Cross-resistance

with macrolide is

common.

Undergo hepatic

metabolism

Anaerobe

Backup drug

against

G(+) cocci (including

community-acquired

strains of MRSA)

Prophylaxis of

endocarditis

Pneumocystis

jiroveci

Pseudomenbranous

colitis

Gastrointestinal

irritation

Skin rash

Neutropenia

Hepatic dysfunction

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5252

Aminoglycosides(1)

Machanism of action

Binding to 30S ribsosomal subunit, bactericidal

Concetration-dependent action, postantibiotic effect

Pharmacokinetics

IV, IM ; oral and topical (neomycin, gentamycin)

Renal clearance with half-life 2~4h; once-daily dosing

effective with less toxicity

Used in combination with β- lactam antibiotic

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Aminoglycosides(2)

Activity& Clinical uses

1. Gentamicin, Tobramycin, Amikacin : Aerobic G(-) bacteria

(including E. coli, Enterobacter, Klebsiella, Proteus,

Providencia, Pseudomonas)

2. Streptomycin : enterocococcal carditis , tuberculosis,

plague, tularemia

3. Neomycin, Kanamycin: Topical or oral use (to eliminate

bowel flora)

4. Spectinomycin : It is a backup drug for treament of

gonorrhea

5. Netilmicin

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5454

Aminoglycosides(3)

Toxicity

1. Ototoxicity: auditory or vestibular damage, irreversible

2. Nephrotoxicity: reversible

3. Neuromuscular Blockade: curare-like block may occur

at high dose, may result in respiratory paralysis

4. Skin Reaction: neomycin usually occur

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5555

Streptogramins

Quinupristin-dalfopristin

Mechanism

Bind to 50S ribososomal subunit, bactericidal

Activity & Clinical uses

Staphyloccal infections, vancomycin-resistant E faecium

Pharmacokinetics

IV; renal clearance

Toxicity

Infusion-related arthralgia and myalgia, CYP450 inhibition

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Oxazolidinone

Linezolid

Mechchanism

Bind to 23s RNA of 50S subnit; bacteriostatic

Activity & Clinical use

Including MRSA, PRSP and VRE strains

Pharmacokinetics

Oral, IV; hepatic clearance

Toxicity

1. Dose-related anemia, neuropathy, optic neuritis

2. serotonin syndrome with SSRIs

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5757

Bacterial protein synthesis inhibitors

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5858

Antimetabolite mechanism

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5959

Trimethoprim-sulfamethoxazole

Mechanism

Synergistic inhibition of folic acid synthesis

The combination is bactericidal ”sequential blockade”

Activity & Clinical use

1. Urinary tract, respiratory, ear, sinus infections

2. P jiroveci pneumonia; Toxoplasmosis; Nocardiosis

Pharmacokinetics

Oral, IV

Renal clearance , half-life: 8h

Toxicity

1. Rash, fever, bone marrow supression, hyperkalemia

2. High incidence of aderse effects in AIDS

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6060

Other folate antagonist(1)

Sufonamides:

Sulfisoxazole: Simple UTI

Sulfacetamide: ocular infection

Mafenide, siver sulfadiazine: Burn infections

Sulfadiazine + pyrimethamine: Toxoplasmosis

Mechanism

Sulfonamides inhibit dihydropteroate synthase

Trimethoprim and pyrimethamine inhibit dihydrofolate

reductase

Activity

Most G(+),G(-),Chlamydia, Nocardia

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6161

Other folate antagonist(2)

Toxicity

1. Hypersentivity : cross-allergenicity

2. Gastrointestinal

3. Hematotoxicity

4. Nephrotoxicity

5. Kernicterus

Drug interaction

Competition with plasma protein binding

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6262

Fluoroquinolones(1)

Narrow spectrum

1st generation

Wide spectrum

2nd generation

3rd generation

4th generaion

Background

Nalidixic acid derivatives

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6363

Fluoroquinolones(2)

Mechanism

Inhibits DNA replication via binding to DNA gyrase, and

topoisomerase Ⅳ; bactericidal

Pharmacokinetics

Oral

Interaction with multivalent cations

Renal elimination

Resistance

Production of efflux pump or change in the porin

2nd : Campylobacter jejuni, gonococci, G(+) cocci,

P.aeruginosa

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6464

Fluoroquinolones(3)

Generation Drug Activity Clinical use

1st Norfloxacin G(-) UTI

2nd Ciprofloxacin

Oflxacin

G(-) G(+) cocciAtypicals

SystemicUTI

3rd

(Respiratory

Flouroquinolone)

Levofloxacin

Gemifloxacin

Sparfloxacin

G(+) MRSAG(-)

Atypicals

SystemicUTI

4th Moxifloxacin G(+), G(-), Atypicals,

AnaerobesSystemic

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6565

Fluoroquinolones(4)

Toxicity

GI distress

Abnomal liver function

Phototoxicity

Damage growing cartilage and cause arthropathy

Newer fluoroquinolones prolong the QTc interval

(gemifloxacin, levofloxacin, moxifloxacin)

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6666

Case Report

2011/3/25

6767

Patient profile(1)

Patient information

L女士 68y/o 158cm 55kg

DOA: 2010/12/28

DOD: 2011/01/22

Chief complaint

Fever with chillness since 3 days ago

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6868

Patient profile(2)

History of present illness

Fever up to 38℃ with chills

Elevated blood pressure (SBP 210mmHg)

A Perm catheter over right subclavian area, an AV fistula over right forearm and a wound with discharge over right big toe

Hemogram: WBC 11900/cumm WBC 15300/cumm

CRP 1.26mg/dL CRP 11.07mg/dL

Blood culture yielded GPC in cluster (x2)

Urine routine showed proteinuria (100mg/dL)

Antibiotic: Tazocin and then Teicoplanin+ Ceftazidime

Teicoplanin+ Ciprofloxacin for bacteremia

(Perm-cath infection), IE

2011/3/25

6969

Patient profile(3)

Past History

Catheter infection related infective endocarditisSepsis, septic arthritis at right knee End stage renal disease with uremic syndrome Hypertension ,Type II DM , Hyperlipidemia Heart failure, NYHA Fc II Coronary artery disease Duodenal ulcer Chronic obstructive pulmonary disease Cerebellar infarction with hydrocephalus

2011/3/25

7070

Patient profile(4)

Personal History

Alcohol: denied

Betel nut: denied

Cigarette smoking: denied

Drugs allergy: denied

Travel: denied

Animal contact: denied

Family History

diabetes

2011/3/25

7171

Patient profile(5)

Physical Examination

General appearance: ill-looking; conscious: clear

Skin: dry, eczema on left elbow, obvious

erythematous papules (-)

Chest: (+)Symmetric expansion

Extremities: A wound, about 0.2 cm in diameter over

right big toe, discharge freely movable(-), pitting

edema(-), clubbing fingers(-)

Back: lower back and CP angle knocking pain (-)

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7272

Patient profile(6)

Impression

MRSA related perm catheter infection

Plan to do & Goal

Keep antibiotic use : Teicoplanin + Ciprofloxacin

Follow blood culture

Keep hemodialysis

Wound care over right big toe

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7373

Lab Data日期 K ALB CA LDH IP BUN CREA CK CRP

2010/12/25 1.26

2010/12/26 11.07

2010/12/30 4.4 39 2.83 10

2011/01/05 4.9

2011/01/07 4.7 3.3 9.7 249 4.1 1.7

2011/01/20 4.9

日期 WBC HGB RBC HCT MCV MCH MCHC RDW

2010/12/26 11900 11.1 3.13 32.4 103.7 35.3 34.1 14.8

2010/12/26 15300 10.5 2.94 30.1 102.4 35.8 35 14.4

2010/12/30 7500 9.2

2011/01/05 9100 8.6

2011/01/07 9100 8.5

2011/01/20 5900 7.6

2011/3/25

74

Blood Culture

2011/3/25

75

Tip / line Culture

2011/3/25

7676

TPR(1)

Targocid 2 3 4 Targocid

(DC)

Ciprocin 2 3 Ciprocin

(DC)

Targocid 2 3

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7777

TPR(2)

Targocid 4 5 6 Targocid

(DC)

Cubicin 2 3 4

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7878

TPR(3)

Cubicin 5 6 7 8 9 10 11

2011/3/25

7979

TPR(4)

Cubicin 12 13 14 Cubicin

(CDC)

2011/3/25

8080

Drug Profile(1)

藥名/含量/劑量/頻次/途徑日期

12

/

28

29 30

1/

1 3 5 7 9 11 13 15 17 19 21

出院帶藥1/22~2/5

Allermin inj 5 mg/ml 1ml

ST IVA

Aprovel FC 300 mg 1tab

QD PO

※

Concor FC 1.25 mg 1tab

QD PO

※

Norvasc tab 5 mg 1tab QD

PO

※

Ciproxin "Bayer*inf 200 mg

Q12H

Targocid inj 400 mg/3ml

QOD IVA

Cubicin inj 500 mg QOD IVA

BID

Q3D

2011/3/25

8181

Drug Profile(2)

藥名/含量/劑量/頻次/途徑

日期 12

/

28

30

1

/

1

3 5 7 9 11 13 15 17 19 21

出院帶藥1/22~2/5

Depyretin 500 mg 1tab

Q6HV PO

※

Nexium 40 mg 1tab

QDAC PO

※

Trental 100 mg 1tab

TID PO

※

Remeron 30 mg 1tab

HS PO

※

Sinequan 25 mg 1cap

HS/QD PO

※

Calowlin 667mg 1tab

TID PO

Folica 5 mg 1tab QD PO

QD

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Case Discussion

Catheter related infection

MRSA related infection

Antibiotics dose with hemodialysis patient

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Catheter related infection

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Catheter-related Bacteremia(1)

Pathogens

1. Staphylococcus epidermidis

2. Staphylococcus aureus (27% to 39%)

3. Enterococcus

4. Gram-negative bacilli

5. Candida spp.

6. Coagulase-negative Staphylococcus (CoNS)

7. Mycobacteria

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Risk factor

1. Diabetes mellitus

2. Prolonged duration of usage catheter

3. Iron overload

4. Staphlococcus aureus nasal colonization

5. Old age

6. Low hemoglobin

7. Low serum albumin

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Therapy

involves proper catheter management

a minimum of 3 weeks of parenteral bactericidal antibiotics

should start as broad-spectrum therapy

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Bacteria Therapy

MSSA beta-lactam antibiotics

cefazolin (due to its thrice weekly dosing)

MRSA vancomycin + antibiotic with suitable G(-)

coverage (3rd cephalosporin or aminoglycoside)

VRSA daptomycin

linezolid (thrice weekly)

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MRSA related infection

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Introduction

Methicillin-resistant Staphylococcus Aureus

(MRSA) is a type of staph bacteria that is

resistant to certain antibiotics called β-lactams.

Methicillin resistance is mediated by PBP-2a, a

penicillin binding protein encoded by the mecA

gene that permits the organism to grow and

divide in the presence of methicillin and other

beta-lactam antibiotics.

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Epidemiology

The prevalence of MRSA has steadily increased since the first clinical isolate was described in 1961, with an estimated 94,360 cases of invasive MRSA disease in the United States in 2005.

Health care-associated MRSA (HA-MRSA)

increased from 22 to 57 percent between 1995 and 2001

Community-associated MRSA (CA-MRSA)

422 patients with skin and soft tissue infections seen in emergency departments in August 2004

- S. aureus ：76 %

- CA-MRSA ：97%

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Risk Factor

Invasive device

MRSA infection

Surgery

Hospitalization or in a long-term care facility

HIV infection

Antibiotic use：particularly cephalosporin and

fluoroquinolone use

Hemodialysis

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Antimicrobial therapy(1)

Clindamycin Rifampin

Daptomycin Tetracyclines

Linezolid TMP-SMX

Quinupristin-

DalfopristinVancomycin

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Antimicrobial therapy(2)

Daptomycin、 Linezolid

Vancomycin、Teicoplanin

Daptomycin、 Linezolid、 Tigecycline

MRSA (MIC ≤2 mcg/mL)

VRSA (MIC ≥16 mcg/mL)

Semi-synthetic penicillin (IV: Nafcillin, Oxacillin,

Oral: Dicloxacillin)

1st cephalosporins (Oral: Cephalexin, IV:Cefazolin)

MSSA (MIC ≤ 4 mcg/mL)

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Antibiotic dose with

hemodialysis patients

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Antibiotic dose with hemodialysis

patients(1)

Ciprofloxacin

chelate (Oral)

- divalent elements (Calowlin)

- phosphate binders (Sevelamer, Lanthanum)

Conc. dependent

- prolong dose interval better than reduce dose

- but in ESRD：variability of T1/2

IV drip 1 hr

Not remove by hemodialysis

Common adults 400mg,Q12H

End stage renal failure (ESRD) 200mg,Q12H

Case 200mg,Q12H

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patients(2)

Daptomycin

Adverse effect

- Myopathy with creatine phosphokinase(CK)↑

(prolong high trough more than 25 μg/mL)

Conc. dependent

IV infusion over 30 mins after hemodialysis

Common adults 6mg/kg, once daily

End stage renal failure (ESRD) 6mg/kg, QOD

Case 500 mg, QOD

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patients(3)

Teicoplanin

Similar to Vancomycin：cover G(+)

IV drip 5 min or IM

Not remove by hemodialysis

Loading dose Maintaining dose

Common adults 400 mg, Q12H 400 mg, QD

End stage renal

failure (ESRD)

400 mg, Q12H Day 4:

400 mg, Q3D

Case 400 mg, QOD 400 mg, Q3D

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patients(4)

Conclusion

Shift dose (standard dose reconsider)

- reach Pharmacodynamic targets

- attain Pharmacokinetic goals

Challenge

- advancing dialysis technology

→remove more drug than studies

Follow up outcome

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References(1)

Applied Therapeutics: The clinical use of drug, 2009, 9th.

Chapter 56

Pharmacotherapy: a pathophysiologic approach, 2008,7th.

Chapter108 &109

Epidemiology of methicillin-resistant Staphylococcus aureus

infection in adults, John M Boyce, Daniel J Sexton, Elinor L Baron, MD,

DTMH, 2010 Form UPTODATE

Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children

Clinical Infectious Diseases Advance Access published January 4, 2011

References(2)

Antibiotic Pharmacokinetic and Pharmacodynamic

Considerations in Patients With Kidney Disease Rachel F.

Eyler and Bruce A. Mueller, 2010 by the National Kidney Foundation

Treatment of invasive methicillin-resistant

Staphylococcus aureus infections in adults Franklin D Lowy,

Daniel J Sexton, Elinor L Baron, 2010 Form UPTODATE

Tunneled, cuffed hemodialysis catheter-related

bacteremia Michael Allon, Daniel J Sexton, Jeffrey S Berns, Theodore

W Post, 2010 Form UPTODATE

Vancomycin-intermediate and vancomycin-resistant

Staphylococcus aureus infections Franklin D Lowy, Daniel J

Sexton, Elinor L Baron, 2010 Form UPTODATE

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Thanks for your listening !

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Bacteremia

Vancomycin (AII)

Adult：15–20 mg/kg/dose IV q8–12 h

Pediatric：15 mg/kg/dose IV every 6 h

The addition of gentamicin (AII) or rifampin (AI) to

vancomycin is not routinely recommended.

Daptomycin (AI/CIII)

Adult：6 mg/kg/dose IV QD

Pediatric：6–10 mg/kg/dose IV QD

For adult patients, some experts recommend higher

dosages of 8–10 mg/kg/dose IV QD (BIII).

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Perm catheter AV fistula

principles of infectious diseases and antibiotics · 2011-05-06 · principles of infectious...

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