rabee adwan. md - imet2000-palimet2000-pal.org/files/file/2017/antibiotic workshop... ·...
TRANSCRIPT
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Principles of Antibiotics Use & Spectrum of Some
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Rabee Adwan. MD Infectious Diseases Consultant (Pediatric and Adult)
Head Of ID Unit and IPAC Committee- AL-Makassed Hospital-AlQuds Head of IPAC Committee Istishri Arab Hospital-Ramallah
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DISCLAIMERS
There is No “fun” way to remember all Organisms and Antimicrobials :)
The goal of this talk is to provide you with some basics and principles.
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Some Principles
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Start Smart ! Always think on it as aTriad:-
• HOST: How sick is this person? Immunocompromised? Allergies? Ability to adhere to medications? comorbidities? pregnancy? Age?
• BUG: What organisms could be causing the problem? Does this patient have risk factors for resistant organisms?
• DRUG: Will it penetrate to the organ involved? Do you need a bactericidal drug (eg. for endocarditis/CNS infections)? Side effects? Renal or hepatic clearance?
HOST
BUG DRUG
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Is it a Bacterial infection?
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ANTIBIOTIC CHOICE
Reassess after 48-72 hours (or when culture results available)
Don't guess about which antibiotic(s) to use - look it up or ask for help
Don't delay giving antibiotics if the patient needs them (e.g., sepsis, meningitis)
Don't forget to obtain appropriate cultures prior to starting antibiotics
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USE BUNDLE:- THE 6 DS:-
The Right Drug
The Right Dose
The best Route of Delivery
Attention To Deescalation
The appropriate Duration of Rx6
The Right Diagnosis
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COMMON MISUSES OF ANTIBIOTICS
1. Prolonged Empiric Antimicrobial Treatment Without Clear Evidence of Infection.
2. Treatment of a Positive Clinical Culture in the Absence of Disease.
3. Failure to Narrow Antimicrobial Therapy When a Causative Organism Is Identified.
4. Prolonged Prophylactic Therapy.
5. Excessive Use of Certain Antimicrobial Agents.
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1.Use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections;
2.Select the adequate ATB; precise targeting is better than shotgun therapy;
3.Consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy;
4. Encourage patients’ compliance;
5.Use antibiotic combinations only in specific situations;
6.Avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore;
7.Discourage self-prescription;
8.Follow only evidence-based guidelines; beware those sponsored by drug companies;
9.Rely (rationally) upon the clinical microbiology lab; and
10.Prescribe ATB empirically – but intelligently; know local susceptibility trends, and also surveillance limitations.
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KILLING ABILITY
Bactericidal:- agents kill the Bacteria
Bacteriostatic:-agents inhibit the growth of Bacteria
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ANTIMICROBIAL PK/PDConcentration Dependant:- Rate and extent of Killing is dependent on the ratio that can be achieved between the peak drug concentration and the MIC of the infecting organism.
Time Dependant:- Rate and extent of killing is dependant on the Duration of time that the drug is above the MIC of infecting organism.
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BACTERIAL CLASSIFICATION: GRAM STAIN
Gram +ve (blue/purple)Thick peptidoglycan cell wall retains primary stain
Gram -ve (pink/red)Thin peptidoglycan cell wall does not retain primary stain
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BACTERIA STRUCTURAL DIFFERENCES
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DNA
mRNARibosomes
Metabolism
B-Lactames
CephalosporinsPenecillinsMonobactamsCarbapenems
Glycopeptides
Colistin Daptomycin
30 S
50 S
Aminoglycosides Tetracyclines (Tigecycline)
Macrolides Clindamycin Chloramphenicol Synercid
Quinolones Metronidazole
Transcription
Rifamycins
Sulfonamides Trimethoprim
*Linezolid acts on the initiation complex
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Coverage Spectrum Of ATB
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MOA of Action
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Beta-lactams
• Members:- • Penicillins• Cephalosporins• Carbapenems• Monobactam
• MOA:- • Cell wall synthesis inhibitors
• Antimicrobial Properties: • Bactericidal • Time dependant Killing
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Penicillin G/V
• •Narrow spectrum agent; mostly aerobic gram positive cocci
• Useful against: • ß- hemolytic streptococci (Group A, B, C & G) • Treponema pallidum (Syphillis) – Gram negative spirochete • N. menigitidis *note: resistance 1-3% • oral anaerobes (peptococcus, peptostreptococcus)
• enteroccocus (E. facaelis, NOT E. faecium)
• NOT useful against: • most gram negative organisms • beta-lactamase producing organisms (S. aureus - ~90%)
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Amoxicillin/Ampicillin
• narrow spectrum agent; mostly Gram positive aerobes, some Gram negative aerobes
• covers everything that penicillin does (streptococcus, enterococcus, oral anaerobes)
• Gram negative coverage (HiPEEL) - Non-beta-lactamase producing • – H. influenzae (~25% resistance) • – Proteus mirabilis • – E. coli (~30% resistance)
• Gram positive coverage • – better coverage of enterococcus (E.faecalis vs. penicillin) • – Listeria monocytogenes (HiPEEL)
• Useful against: ß- hemolytic streptococci (Group A, B, C & G), E. faecalis (<1% resistance), Listeria
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Amoxicillin-Clavulanic Acid
• Amoxicillin + ß-lactamase inhibitor • –broad-spectrum agent • –extends spectrum of amoxicillin to cover
more gram negatives (E.coli, H. influenzae, Salmonella, Shigella) + gut anaerobes (B. fragilis)
• Not useful against: Pseudomonas
• “Like an oral pip/tazo (minus Pseudomonal coverage)”
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Piperacillin-Tazobactam
• Piperacillin + ß-lactamase inhibitor • Most broad-spectrum penicillin; aerobic Gram positives
(including MSSA, E. faecalis), difficult aerobic Gram negatives (including Enterobacter, Klebsiella, Serratia, Pseudomonas, Acinetobacter), anaerobes (including B. fragilis)
• Useful against: Pseudomonas, harder to kill Gram negatives (traditional ß-lactamase producers), most aerobic Gram positives (including MSSA)
• NOT useful against: MRSA, E. faecium
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Cloxacillin
• Very narrow spectrum; gram positive aerobes • drug of choice for MSSA • maintains coverage for Streptococci (less so
than penicillin/amoxicillin) • some oral anaerobic coverage (less so than
penicillin/amoxicillin)
• Not useful against: enterococci, N. meningitis
• Niche: methicillin-sensitive S. aureus
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1st Generation Cephalosporins (cefazolin, cephalexin, cefadroxil)
• Narrow spectrum: • aerobic gram positives (MSSA, ß-hemolytic
Streptococcus) • Some aerobic gram negatives (PEcK: Proteus,
E.coli, Klebsiella) • oral anaerobes
• Useful for: MSSA, ß-hemolytic Streptococcus • Not useful for: Enterococci, gut anaerobes
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2nd Generation Cephalosporins (cefuroxime, cefaclor, cefoxitin)
• “Middle of the road” coverage* • Covers everything that 1st generations cover*:
• Gram positives: MSSA, Streptoccocus (↓activity vs. 1st generation)
• Gram negatives: PEcK + H. influenzae & Moraxella • oral anaerobes, NOT gut anaerobes*
• *exception: cefoxitin – poor Gram positive coverage; covers B. fragilis (but resistance ~20%)
• Place in Therapy: oral stepdown for CAP
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3rd Generation Cephalosporins (ceftriaxone, cefotaxime)
• Broad-spectrum • Gram positive coverage: MSSA (reasonable
coverage), Streptococcus (excellent coverage)
• Gram negatives: difficult to kill Gram negatives (Serratia, Enterobacter, Citrobacter), N.menigitidis, N.gonnorhea
• oral anaerobes
• NOT useful for: enterococcus, Pseudomonas, gut anaerboes
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3rd Generation Cephalosporins (ceftazidime)
• Less broad-spectrum vs. ceftriaxone/cefotaxime • Gram positive coverage: poor • Gram negatives: difficult to kill Gram negatives
(Serratia, Enterobacter, Citrobacter), Pseudomonas
• NOT useful for: enterococcus, gut anaerobes
• Useful for: treatment of documented Pseudomonal infections, empiric Gram negative coverage where Pseudomonal coverage is desired
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3rd Generation Cephalosporins (cefixime)
• Gram positive coverage: poor • Gram negatives: good; N. gonnorhea
• NOT useful for: enterococcus, gut anaerobes, Pseudomonas
• Useful for: treatment of N. gonnorhea (niche)
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3rd Generation Cephalosporins (Cefdinir)
• Gram negative coverage: poor • Gram Positive: good; NO staph aureus
Coverage
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4th Generation Cephalosporins (cefepime)
• broad-spectrum • Like ceftriaxone, but:
• – Gram positives: better activity vs. MSSA • – Gram negatives: Pseudomonas
• NOT useful for: enterococcus, gut anaerobes
• Useful for: treatment of documented Pseudomonal infections, empiric Gram negative coverage where Pseudomonal coverage is desired
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CARBAPENEMS
• Ertapenem • Meropenem • Imipenem-cilastin • Doripenem
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CARBAPENEMS
•“Tanks” of the ß-lactams • Extremely broad-spectrum:
• most aerobic Gram positives • most aerobic Gram negatives- including
ESBLs!!! • most anaerobes
• Drugs of choice for ESBLs
• Reserve for serious infections with resistant organisms! :) NOT CRE
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CARBAPENEMS (Ertapenem)
• Least broad-spectrum carbapenem
• Useful for: aerobic gram negatives (including ESBLs), aerobic gram positives (MSSA, Streptococcus), anaerobes
• • Not useful for: enterococcus, Acinetobacter,
Pseudomonas (“Pseudomonal sparing”), MRSA • Doesn't Cross BBB
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CARBAPENEMS (Meropenem, Imipenem, Doripenem)
• Most broad-spectrum of all the carbapenems
• like ertapenem, but also cover: • Pseudomonas aeruginosa • Enterococcus • Acinetobacter
• Generally all 3 agents considered clinically equivalent, but based on MIC data:
• E.faecalis (I > M = D) • Pseudomonas (D > M > I) • Acinetobacter ( I > M = D)
• Bottom line: basically cover everything, except for MRSA, VRE
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Vancomycin • Bactericidal • Time-dependent killing • Inhibits cell wall formation
• Narrow spectrum - ONLY Gram positives: • Aerobes: Staphylococci (MRSA, MSSA, CNST), Enterococci
(E. faecalis & E. faecium) • Anaerobes: C. difficile, Propionibacterium spp.
• Useful for: gram positive infections (MRSA, E. faecium)
• Not useful for: any gram negative, VRE
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Fluoroquinolones
• Members • Ciprofloxacin • Levofloxacin • Moxifloxacin • Gemifloxacin
• Antimicrobial Properties • bactericidal • concentration-dependent killing
• Mechanism of Action: • – inhibit DNA gyrase/Topoisomerase – inhibit DNA
replication
Gram Negative
Gram Positive
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Fluoroquinolones (Ciprofloxacin)
• Relatively narrow spectrum • mostly aerobic gram negatives (including
Pseudomonas) • unreliable gram positive coverage • unreliable anaerobic coverage (gut & oral)
• Useful for: aerobic gram negatives (Pseudomonas if susceptible)
• Not useful for: gram positive or anaerobic infections
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Fluoroquinolones (levofloxacin, moxifloxacin, Gemifloxacin)
• Respiratory fluoroquinolones (cover S. pneumoniae) • Broad-spectrum
• aerobic gram positives (excellent S. pneumoniae coverage, reasonable MSSA coverage)
• aerobic gram negatives • atypicals (Chlamydia, Mycoplasma, Legionella)
• Differences between agents: • Gram negatives: L > M (moxifloxacin has inferior Gram neg. coverage) • Pseudomonas: levofloxocin (note increasing resistance ~30%), NOT
moxifloxacin or Gemi • gut anaerobes: moxifloxacin (note: increasing resistance ~30%) NOT
levofloxacin or Gemi
• Useful for: aerobic gram positives/Gram negatives, atypicals (classic indication: CAP)
• Not useful for: MRSA, enterococcus
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Metronidazole (Flagyl)
• Bactericidal with Concentration-dependent activity • Free radical formation ( DNA damage)
• Narrow spectrum: anaerobes only • Highly active against: gut anaerobes (B. fragilis,
Clostridium spp) • Variably active against: Peptostreptococcus (oral
anaerobe) • Inactive against: E. corrodens (human bite pathogen),
Actinomyces (oral anaerobe), Propionibacterium spp. • Other: Trichomonas spp., Giardia spp.
• Useful for: intra-abdominal anaerobic infections, C. difficile infections
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Cotrimoxazole (Trimethoprim/Sulfamethoxazole)
• Bactericidal with Time-dependent activity Inhibits folate synthesis
• Broad-spectrum • variable activity against MRSA/ MSSA) & streptococci!
(check C&S before using) • most aerobic gram negatives, ESBLS, NOT Pseudomonas • others: Pneumocystis, Burkholderia cepacia (GNB),
Stenotrophomonas maltophilia (GNB), Nocardia (GPB)
• Niches: MRSA (check C&S), ESBLs, Pneumocystis, Burkholderia cepacia, Stenotrophomonas maltophilia, Nocardia
• If have a highly resistant organism, consider It!
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Aminoglycosides
• Members • Tobramycin • Gentamicin • Amikacin
• Antimicrobial Properties • bactericidal • concentration-dependent killing
• Mechanism of Action: • inhibit protein synthesis
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Aminoglycosides
• Narrow spectrum; aerobic gram negatives only (including ESBLs)
• Can be used for synergy with a ß-lactam against Gram positives (streptococci, enterococci)
• Differences between agents: • Klebsiella, Serratia: G > T > A • Pseudomonas: T > G >A • Amikacin has lowest resistance; but 4X higher MICs
• Useful for: aerobic gram negatives, ESBLs, Pseudomonas (Tobramycin)
• Not useful for: gram positives (except synergy with ß-lactams)
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Clindamycin • Bacteriostatic • Time-dependent activity • Inhibit protein synthesis
• Narrow spectrum: Gram positives & anaerobes • Gram positive aerobes: Staphylococcus (MSSA, CA-MRSA
– note increasing resistance ~30%), Streptococcus (note increasing resistance)
• anaerobes: gut anaerobes (B. fragilis, Clostridium spp), oral anaerobes
• Useful for: MSSA/MRSA(check C&S), oral anaerobes • Not useful for: any aerobic gram negative, enterococcus • Caution: gut anaerobes, Staphylococcus
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Macrolides
• Members • Erythromycin • Azithromycin • Clarithromycin
• Antimicrobial Properties • bacteriostatic • Time-dependent killing
• Mechanism of Action: • inhibit 50S ribosomal unit – inhibit protein
synthesis
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Macrolides
• Relatively broad-spectrum • Gram positives: Streptococci (note increasing
resistance with S. pneumoniae ~20%) • some Gram negatives (A & C only): H.
influenzae, M. cattarhalis • atypicals • NO anaerobic coverage
• Niche: RTIs, Legionella • Not useful for: MRSA, enterococcus
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Tetracyclines
• Members • Tetracycline • Doxycycline • Minocycline
• Antimicrobial Properties • bacteriostatic • time-dependent killing
• Mechanism of Action: • inhibit protein synthesis
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Tetracyclines
• broad-spectrum • Aerobic Gram positives: Streptococci, Staphylococci
(including MRSA!), Listeria • Aerobic Gram negatives: easy to kill (E.coli, Klebsiella),
N. menigtidis, Brucella spp. • Atypicals • Others: P. acnes, Vibrio, Treponema pallidum, H.
pyelori, Plaspmodium spp. (malaria), Bartonella, spp., Rickettsiae
• Niches: MRSA, atypicals, Rickettsiae, Bartonella
• If have a highly resistant organism, consider a tetracycline!
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Linezolid (Zyvox)
• Bacteriostatic • Time-dependent activity • Inhibition of protein synthesis
• Spectrum: narrow - aerobic Gram positives • Staphylococci (MSSA, MRSA, CNST) • Streptococci (penicillin-resistant) • Enterococci (E. faecalis, E. faecium, VRE)
• Useful for: resistant aerobic Gram positives • Not useful for: any gram negative, any anaerobe
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Daptomycin• Bactericidal • Concentration-dependent • Disruption of the bacterial cell membrane
• Narrow spectrum – aerobic Gram positives • Staphylococci (MSSA, MRSA, CNST) • Streptococci (penicillin-resistant) • Enterococci (E. faecalis, E. faecium, VRE)
• Useful for: resistant aerobic Gram positives
• Not useful for: any gram negative, any anaerobe, Chest infection!
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Tigecycline (Tygacil)
• Bactericidal Time- dependent activity Inhibit – inhibit protein synthesis
• “Special” member of the Tetracycline family
• VERY broad-spectrum: • aerobic Gram positives: MSSA/MRSA, Streptococci,
Enterococci (-faecalis, -faecium, VRE)
• most gram negatives, ESBLS, CREs (NOT 3Ps: Pseudomonas, Providencia, Proteus & Morganella)
• –anaerobes: mostly oral (poor activity vs. B. fragilis)
• Useful for: most aerobic Gram positives & negatives, including resistants (MRSA, VRE, ESBLs)
• Not useful for: Pseudomonas, Proteus, Morganella, Providencia, gut anaerobes
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Polymixin E (Colistin)
• Bactericidal • Concentration-dependent • Disruption of the bacterial outer membrane
• Narrow spectrum: aerobic Gram negatives • Reliable activity against: ESBLs, CREs, Pseudomonas, Acinetobacter
• Less reliable against: Serratia spp, Proteus, spp, Providencia spp. B. Cepatia
• Useful for: highly resistant aerobic gram negative infections where there are no other options
• Not useful for: Gram positives
1962
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Miscellaneous
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Fosfomycin
• Act on Cell wall synthesis • Available as PO option
• Niche: indicated for the treatment of cystitis only (NOT pyelonephritis, abscess) caused by:
• E.coli (including ESBLs) • E. faecalis
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Nitrofurantoin
• Relatively broad-spectrum: • aerobic gram negatives: E.coli, Klebsiella, ESBLs
• (NOT: Proteus, Serratia, Pseudomonas)
• aerobic Gram positives: Enterococci (-faecalis, -faecium, VRE)
• Niche drug: urinary tract (cystitis ONLY) – useful for ESBL cystitis
• Caution: insufficient serum levels to treat pyelonephritis (+/- bacteremia)
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Use for Cystitis &prophylaxis
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Take home Messages
• Antibiotics use is the single most important factor leading to antibiotic resistance.
• Up to 50% of all antibiotics prescribed are not needed.
• What to do? Promote appropriate antibiotics use (ASP).
Start Smart and then go with 6 Ds Bundle!