Principles of Antibiotics Use & Spectrum of Some

Size: px

Start display at page:

Download "Principles of Antibiotics Use & Spectrum of Some"

Ashlee Terry
6 years ago
Views:

ID Unit and IPAC Committee- AL-Makassed Hospital-AlQuds Head of

1 Principles of Antibiotics Use & Spectrum of Some 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 1 RABEE_ODWAN@YAHOO.COM

2 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. 2

3 Some Principles 3

4 Start Smart! Always think on it as atriad:- Is it a Bacterial infection? HOST 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? BUG DRUG 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? 4

5 ANTIBIOTIC CHOICE 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 Reassess after hours (or when culture results available) 5

6 USE BUNDLE:- THE 6 DS:- The Right Diagnosis The Right Drug The Right Dose The best Route of Delivery Attention To Deescalation The appropriate Duration of Rx 6

7 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. 7

8 8

9 1.Use antibiotics only when needed; teach the patient how to manage symptoms of nonbacterial 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. 9

10 KILLING ABILITY Bactericidal:- agents kill the Bacteria Bacteriostatic:-agents inhibit the growth of Bacteria 10

ANTIMICROBIAL PK/PD Concentration Dependant:- Rate and extent of Killing is dependent on the ratio that can be achieved between the peak drug concentration and the

11 ANTIMICROBIAL PK/PD Concentration 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.

12 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 12

13 BACTERIA STRUCTURAL DIFFERENCES 13

14 14

Sulfonamides Trimethoprim Rifamycins Quinolones Metronidazole Aminoglycosides Tetracyclines (Tigecycline) Metabolism Transcription DNA Macrolides Clindamycin

15 Sulfonamides Trimethoprim Rifamycins Quinolones Metronidazole Aminoglycosides Tetracyclines (Tigecycline) Metabolism Transcription DNA Macrolides Clindamycin Chloramphenicol Synercid *Linezolid acts on the initiation complex Ribosomes 30 S 50 S mrna Colistin Daptomycin Glycopeptides B-Lactames Penecillins Carbapenems Monobactams Cephalosporins

16 Coverage Spectrum Of ATB

17 MOA of Action 17

18 Beta-lactams Members:- Penicillins Cephalosporins Carbapenems Monobactam MOA:- Cell wall synthesis inhibitors Antimicrobial Properties: Bactericidal Time dependant Killing

19 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%)

20 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

21 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)

22 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

23 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

25 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

26 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

27 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

28 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

29 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)

30 3rd Generation Cephalosporins (Cefdinir) Gram negative coverage: poor Gram Positive: good; NO staph aureus Coverage

31 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

32 CARBAPENEMS Ertapenem Meropenem Imipenem-cilastin Doripenem

33 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

34 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

35 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

36 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

37 Fluoroquinolones Members Gram Negative Ciprofloxacin Levofloxacin Moxifloxacin Gram Positive Gemifloxacin Antimicrobial Properties bactericidal concentration-dependent killing Mechanism of Action: inhibit DNA gyrase/topoisomerase inhibit DNA replication

38 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

39 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

40 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

41 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!

42 Aminoglycosides Members Tobramycin Gentamicin Amikacin Antimicrobial Properties bactericidal concentration-dependent killing Mechanism of Action: inhibit protein synthesis

43 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)

44 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

45 Macrolides Members Erythromycin Azithromycin Clarithromycin Antimicrobial Properties bacteriostatic Time-dependent killing Mechanism of Action: inhibit 50S ribosomal unit inhibit protein synthesis

46 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

47 Tetracyclines Members Tetracycline Doxycycline Minocycline Antimicrobial Properties bacteriostatic time-dependent killing Mechanism of Action: inhibit protein synthesis

48 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!

49 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

50 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!

51 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

52 Polymixin E (Colistin) 1962 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

53 Miscellaneous

54 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

55 Nitrofurantoin Relatively broad-spectrum: aerobic gram negatives: E.coli, Klebsiella, ESBLs Use for Cystitis & prophylaxis (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) 55

56 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! 56

Antibiotic. Antibiotic Classes, Spectrum of Activity & Antibiotic Reporting

Antibiotic. Antibiotic Classes, Spectrum of Activity & Antibiotic Reporting Antibiotic Antibiotic Classes, Spectrum of Activity & Antibiotic Reporting Any substance of natural, synthetic or semisynthetic origin which at low concentrations kills or inhibits the growth of bacteria