MAPA fall cme conference 2021 Andrew zolp pac Disclosures I have no disclosures to report Brand names are included for many of the antibiotics included in this lecture for reference purposes only ID: 909515
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Slide1
Antibiotics Across the Spectrum of Disease
MAPA fall
cme
conference 2021
Andrew
zolp
, pa-c
Slide2Disclosures
I have no disclosures to report.
Brand names are included for many of the antibiotics included in this lecture for reference purposes only
Slide3Learning Objectives
1. Relate the different antibiotics to their intended disease spectrums.2. Translate different
antibiotics
and their spectrums to clinical practice.
3. Choosing the appropriate antibiotic depending on patient presentation and disease state.
Slide4Definitions
Bactericidal—antimicrobial activity that not only inhibits growth but is lethal to bacteria
.
Bacteriostatic—antimicrobial activity that inhibits growth but does not kill the organisms. The host defense mechanisms are ultimately responsible for eradication of infection
.
Minimal inhibitory concentration (MIC)—a laboratory term that defines the lowest concentration (
μg
/mL) able to inhibit growth of the microorganism in vitro
.
Resistant,
nonsusceptible
—terms applied when organisms are not inhibited by clinically achievable concentrations of an antimicrobial agent
.
Sensitive, susceptible—terms applied to microorganisms indicating that they will be inhibited by concentrations of the antimicrobial that can be achieved clinically
.
Spectrum—an expression of the categories of microorganisms against which an antimicrobial is typically active. A narrow-spectrum agent has activity against only a few organisms. A broad-spectrum agent has activity against diverse types of organisms (
eg
, both gram-positive and gram-negative bacteria)
Slide5General Considerations
Probable/possible source of infection
Gram positive v gram negative
Aerobic vs anaerobic
Recent hospitalization
Recent antibiotic use
Risk factors for infection (population, chronic disease, exposure,
etc
)
Prophylactic vs empiric therapy
Renal clearance/ renal dosing of medications
Slide6General Considerations
Antibiotic allergy v side effects
Antibiotic resistance in your areas
Avoid using antibiotics for colonization or contamination
Use the most narrow spectrum agent
Proper dose
Dosing is not included in this review. Utilize your resources (
Epocrates
,
Pharmacopia
, etc) for specific conditions. Be aware of renal dosing when indicated.
Proper duration of time (shortest duration of therapy)
Slide7GeneralConsiderations
Slide8What’s common where?
Members of the Normal
Flora
Anatomic Location
Bacteroides
species
Colon, throat, vagina
Candida albicans
Mouth, colon, vagina
Clostridium
species
Colon
Corynebacterium
species (diphtheroids)
Nasopharynx, skin, vagina
Enterococcus
faecalis
Colon
Escherichia coli
and other coliforms
Colon, vagina, outer urethra
Gardnerella
vaginalis
Vagina
Haemophilus
species
Nasopharynx
Lactobacillus
species
Mouth, colon, vagina
Neisseria
species
Mouth, nasopharynx
Propionibacterium
acnes
Skin
Pseudomonas
aeruginosa
Colon, skin
Staphylococcus
aureus
Nose, skin
Staphylococcus
epidermidis
Skin, nose, mouth, vagina, urethra
Viridans streptococci
Mouth, nasopharynx
Slide9Enteric Gram-Negative Rods (GNRs)
Escherichia,
Shigella
, Salmonella,
Enterobacter
,
Klebsiella
,
Serratia
, Proteus, and
othersMost commonly found in the intestinal tract in humansSome are normal flora and only cause disease under varying conditionsShigella and Salmonella are regularly pathogenic for humans
Slide10Other Gram-Negative Rods
Pseudomonas
Acinetobacter
Most commonly found in soil and water
Pseudomonas
aeruginosa
sometimes colonized humans and is a major pathogen
Think nosocomial infections
Slide11Common Gram-Positive Bacteria
Staphylococci
As many as 40 subspecies
Streptococci
Many different variants
Enterococci
Slide12Beta-lactams
Slide13Beta-lactams
Penicillins
,
cephalosporins
and
carbapenems
Monobactams
are structurally similar, but lack cross reactivity
All beta-lactams have several things in common:
All can cause hypersensitivity reactions (rashes, hives, drug fever, acute interstitial nephritis, anaphylaxis)Seizures can occur at high doses (know the clearance of the medications [renal function])
All share the same mechanism of action
Inhibition of
transpeptidases
in the bacterial cell wall
Two beta-lactams given at the same time are not any more effective than one alone (most of the time)
LACK activity against atypical organisms such as
Mycoplasma pneumonia
LACK activity against MRSA (exception is
ceftaroline
)
Slide14Natural Penicillins
Penicillin G
Penicillin V
Spectrum:
Narrow spectrum (gram-positive
);
penicillinase
sensitive
Good:
Treponema
pallidum (syphilis), most streptococci including s. pneumonia
Moderate: enterococciPoor: almost everything else
What they are good for:
Syphilis, strep pharyngitis or endocarditis
Slide15Antistaphylococcal
Penicillins
Nafcillin
Oxacillin
Dicloxacillin
Spectrum:
Narrow spectrum (gram-positive
); synthesized
to be
penicillinase
resistant
Good: MSSA, streptococci
Poor: GNRs, enterococci, anaerobes, MRSA
What they are good for:
Infections caused by MSSA (endocarditis, skin and soft tissue)
Slide16Aminopenicillins
Amoxicillin (
Amoxil
)
Ampicillin
Spectrum:
Broad spectrum (some gram-negative activity also
);
penicillinase
sensitive
Good: streptococci, enterococci
Moderate: enteric GNRs, Haemophilus
Poor: staphylococci, anaerobes,
Pseudomonas
What they are good for:
Infections caused by susceptible GNRs, enterococci and streptococci.
URIs (strep pharyngitis), otitis media
Slide17Penicillin/ Beta-lactamase Inhibitor Combinations
Ampicillin/
sulbactam
(
Unasyn
)
Piperacillin/
tazobactam
(Zosyn)Amoxicillin/ clavulanate (Augmentin)
Spectrum:
Good: MSSA, streptococci, enterococci, many anaerobes, enteric GNRs,
P. aeruginosa
(
Zosyn
only)
Moderate: GNRs with advanced beta-lactamases
Poor: MRSA, extended-spectrum beta-lactamase producing GNRs
What they are good for:
Empiric therapy of nosocomial infections (nosocomial pneumonia), mixed infections (abdomen), diabetic ulcers, aspiration pneumonia
URIs (Augmentin is first line for true sinusitis)
Remember to narrow your therapy when culture results return!
Slide18Cephalosporins
All have some cross-reactivity with PCNs (5-10%). Know what the patient’s PCN allergy is
Cephalosporins
are generally more resistant to beta-lactamases compared to PCN
Grouped into generations
Several in each class, I’ve included the most popular ones here. Know what your hospital/pharmacy formulary carries.
Slide19First- Generation Cephalosporins
Cefazolin
(
Ancef
)
Cephalexin
(Keflex)
Spectrum:
Narrow spectrum similar to broad spectrum
penicillins
; sensitive to β-lactamases
Good: MSSA, streptococciModerate: some enteric GNRs
Poor: enterococci, anaerobes, MRSA,
Pseudomonas
What they are good for:
Skin and skin structure infections, surgical prophylaxis (cefazolin), MSSA endocarditis, osteomyelitis
Slide20Second-Generation Cephalosporins
Cefuroxime (
Ceftin
)
Cefoxitin
(
Mefoxin
)
Cefotetan
(Cefotan)Cefprozil (Cefzil
)
Spectrum:
Increased activity toward gram-negative organisms; increased
stability
Good: some enteric GNRs,
Haemophilus
, Neisseria
Moderate: streptococci, staphylococci, anaerobes (
cefotetan
,
cefoxitin
)
Poor: enterococci, MRSA,
Pseudomonas
What they are good for:
URIs, community acquired pneumonia, gonorrhea, surgical prophylaxis (
cefotetan
,
cefoxitin
)
Slide21Third-generation Cephalosporins
Ceftriaxone (
Rocephin
)
Cefotaxime
Ceftazidime
(
Fortaz)Cefdinir (Omnicef
)Cefpodoxime
(
Vantin
)
Spectrum:
Even broader in spectrum and more resistant to
β-lactamases
Good: streptococci (except
ceftazidime
), enteric GNRs,
Pseudomonas
(
ceftazidime
only)
Moderate: MSSA (except
ceftazidime
)
Poor: enterococci,
Pseudomonas
(except
ceftazidime
), anaerobes, MRSA
What they are good for:
Lower respiratory tract infections, pyelonephritis, nosocomial infections, Lyme disease, meningitis, gonorrhea, skin and skin structure infections, febrile neutropenia
Slide22Fourth-Generation Cephalosporins
Cefepime
(
Maxipime
)
Spectrum:
Gram-positive and gram-negative activity, especially against
Pseudomonas aeruginosa;
includes gram-negative organisms with multiple-drug resistance
patterns
Good: MSSA, streptococci, Pseudomonas, enteric GNRs
Moderate: Acinetobacter
Poor: enterococci, anaerobes, MRSA
What they are good for:
Febrile neutropenia, nosocomial pneumonia,
postneurosurgical
meningitis, nosocomial infections
Slide23Fifth-Generation Cephalosporin
Ceftaroline
(
Teflaro
)
Spectrum:
Gram-positive and gram-negative activity, especially against
Staphylococcus aureus
(including methicillin-susceptible and -resistant isolates),
Streptococcus
pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and
Klebsiella oxytoca
Should only be used for conditions that are proven or strongly suspected by the causative bacteria
Does not cover
Pseudomonas aeruginosa
What they are good for
:
Only acute bacterial skin and soft tissue structure infections (ABSSSI)
or
community acquired bacterial pneumonia (CABP)
that are proven or strongly suspected to be caused by susceptible bacteria
Slide24Carbapenems
Imipenem
/
cilastatin
(
Primaxin
)
Meropenem
(
Merrem
)Ertapenem (Invanz)Spectrum:
Good: MSSA, streptococci, anaerobes, enteric GNRs, Pseudomonas (except
ertapenem
), ESBL-producing GNRs,
Acinetobacter
(not
ertapenem
)
Moderate: enterococci (not
ertapenem
)
Poor: MRSA, PCN-resistant streptococci
What they are good for:
Mixed aerobic/ anaerobic infections, infections caused by ESBL-producing organisms, intra-abdominal infections
Imipenem
,
meropenem
: nosocomial pneumonia, febrile neutropenia, other nosocomial infections
Slide25Monobactams
Aztreonam
(
Azactam
)
Spectrum:
Good: Pseudomonas, most GNRs
Moderate:
Acinetobacter
Poor: Gram-positive organisms, anaerobes
What it is good for:
GN infections, particularly in patients with beta-lactam allergy
Slide26Vancomycin
Spectrum:Good: MSSA, MRSA, streptococci, c. difficile
Moderate: enterococci
Poor: anything Gram-negative
What it is good for:
Drug of choice for MRSA (empiric when it’s of concern), other Gram-positive infections.
Slide27Miscellaneous Cell Wall Synthesis Inhibitors
Bacitracin
binds
to a lipid carrier that transports cell wall precursors to the growing cell
wall
Significant nephrotoxicity
Spectrum of activity
Gram positive bacteria- staphylococcus and
streptococous
Daptomycin
lipopeptide antibiotic
It
binds to the membrane of the bacteria and causes a depolarization of the bacteria. This loss of membrane potential results in bacterial
death.
Spectrum of activity
Similar to that of vancomycin
Slide28Fluoroquinolones
Broad spectrum coverage of GP, GN and
atypicals
MOA- inhibit DNA
topsisomerases
. This leads to breaks in the bacterial DNA and the death of the bacteria cell
Slide29Fluoroquinolones
Ciprofloxacin (Cipro)
Levofloxacin (Levaquin)
Moxifloxacin
(
Avelox
)
Ciprofloxacin Spectrum:
Good: enteric GNRs
(E.coli, Proteus,
Klebsiella), H. influenzaModerate: Pseudomonas,
atypicals (Mycoplasma, Legionella)Poor: staphylococci, streptococci, anaerobes, enterococci
Levofloxacin/
Moxifloxacin
Spectrum:
Good: enteric GNRs,
S. pneumonia
,
atypicals
,
H. influenza
Moderate:
Pseudomonas
(Levofloxacin only), MSSA
Poor: Anaerobes (except
moxifloxacin
), enterococci
What they are good for:
Use caution! They are great drugs with coverage for many common pathogens, but FDA black box warning on all drugs in the class. Risks outweigh benefits most of the time in the treatment of sinusitis, bronchitis and uncomplicated UTIs.
Slide30Aminoglycosides
All of these drugs have a narrow therapeutic window
Proper dosing is a must!
Good at synergizing beta-lactams
MOA- bind to the 30S unit of the ribosome and cause a misreading of RNA leading to incorrect protein formation and interruption of protein synthesis
Slide31Aminoglycosides
Gentamycin
Tobramycin
Amikacin
Spectrum:
Good: GN (
E. coli,
Klebsiella
, Pseudomonas,
Acinetobacter
)Moderate: in combination with a beta-lactam staph [including MRSA], enterococci
Poor: atypicals, anaerobes, GP (monotherapy only)
What they are good for:
In combination with a beta-lactam they are good for life threatening infections
Slide32Tetracyclines and
Glycylcylines
Mostly used for niche indications
Useful in URIs
MOA- bind to the 30S unit of the ribosome and block the elongation of the amino acid chain
Slide33Tetracyclines and Glycylcylines
Doxycycline
Minocycline
Tetracycline
Spectrum:
Good:
atypicals
, rickettsia, spirochetes, Plasmodium
Moderate: staphylococci (includes MRSA),
S.
penumoniae
Poor: Most GNRs, anaerobes, enterococci
What they are good for:
Uncomplicated URIs, acute exacerbations of chronic bronchitis, sinusitis and CAP. Drugs of choice for tick-borne illnesses. Can be used for skin and soft tissue infections (if other agents are contraindicated)
Slide34Macrolides and Ketolides
Broad coverage, but not deep, of respiratory pathogens
Probably overused!
MOA- bind to the 50S unit of the ribosome preventing new amino acids from being added to the protein chain
Can be potent inhibitors of CYP450 (except azithromycin)
Slide35Macrolides and Ketolides
Clarithromycin
Azithromycin
Erythromycin
Spectrum:
Good:
atypicals
,
H.
influenzae
, M. catarrhalis, H. pylori, M. avium
Moderate: S. pneumonia
Poor: staphylococci, enteric GNRs, anaerobes, enterococci
What they are good for:
Upper and lower respiratory tract infections, chlamydia,
H. pylori
treatment (clarithromycin)
Slide36Clindamycin
Good for GP coverage, variable against MRSA. Some higher resistance of GN. Penetrates bone.
Think of this medication as a combination of vancomycin and metronidazole in terms of coverage and use
MOA- binds to the 50S ribosome and prevents protein synthesis
Spectrum:
Good: many GP anaerobes,
Plasmodium
Moderate:
S. aureus
(includes MRSA), GN anaerobes
Poor: enterococci, C. diff
(it probably caused it!), GN aerobes
What is it good for:
Skin and soft tissue infections, infections of the oral cavity, anaerobic intra-abdominal infections
Slide37Oxazolidinones
Linezolid (
Zyvox
)
MOA- inhibit the formation of a stable 70S ribosomal subunit, prevents translation
Spectrum:
Good: MSSA, MRSA, streptococci, enterococci (including VRE)
Moderate: some
atypicals
,
M. tuberculosisPoor: all GN, anaerobes
What they are good for:
Infections caused by GP organisms like MRSA and VRE. Pneumonia, soft tissue, UTI and other infections
Slide38Nitroimidazoles
Metronidazole (
Flagyl
)
This drug bats clean-up for what the other antibiotics miss
They do NOT have coverage for aerobic bacteria
MOA- activate part of the
nitroimidazole
molecule that forms free radicals and are thought to damage DNA and lead to cell death
Spectrum:
Good: GN and GP anaerobes, protozoaModerate:
H. pyloriPoor: Anything that needs oxygen to survive
What is it good for:
Infections with documented or suspected abdominal anaerobic bacteria with adjunct coverage with medication that covers aerobic bacteria.
Trichomoniasis
(BV), protozoa infections,
H. pylori, C. diff
(?)
Slide39Nitrofurans and
Fosfomycin
Nitrofurantoin (
Macrobid
)
Fosfomycin
MOA- nitrofurantoin (not well known),
fosfomycin
- inhibits bacterial cell wall synthesis (different than a beta-lactam)
Spectrum:
Good: E. coliModerate:
Citrobacter, Klebsiella, Proteus, enterococci
Poor:
Acinetobacter
What is it good for:
Uncomplicated cystitis (know renal function). That’s it. Nothing more.
Slide40Folate Antagonists
Trimethoprim/ sulfamethoxazole (Bactrim, Bactrim DS)
MOA- inhibits steps in folate biosynthesis. Leads to inhibition of DNA synthesis
Spectrum:
Good:
S. aureus
(including MRSA),
H.
influenzae
, Listeria, P.
jirovecii, T. gondiiModerate: enteric GNRs, S. pneumonia, Salmonella,
Shigella, S. pyogens
Poor:
Pseudomonas
, enterococci, anaerobes
What is it good for:
Uncomplicated UTIs (know resistance in your area), additive coverage for MRSA (skin), infections caused by the agents listed above
Be sure the patient drinks enough water while on this medication! Can cause crystallization in the renal calyx and cause stones.
Slide41Closing considerations
A careful history and good differential diagnosis will point you in the direction that’s needed for antibiotic coverage
Tailor your therapy
Narrow spectrum always (when appropriate)
Patient education!
Slide42Sources
Antibiotics Simplified, fourth edition. Gallagher, Jason C. Conan MacDougall, 2018
Pharmacology, fifth edition, Brenner and Stevens, 2018
Basic and Clinical Pharmacology, 14
th
edition,
Katzung
, Bertram G., 2018
Basic and Clinical Pharmacology,
15
th edition, Katzung, Bertram G., 2021Basic Concepts in Pharmacology: What You Need to Know for Each Drug Class,
5e., Stringer JL, 2017
.
AccessMedicine
, 2019-2021
Slide43Thank You!