Antibiotics Across the Spectrum of Disease - PowerPoint Presentation

Slide1

Antibiotics Across the Spectrum of Disease

MAPA fall

cme

conference 2021

Andrew

zolp

, pa-c

Slide2

Disclosures

I have no disclosures to report.

Brand names are included for many of the antibiotics included in this lecture for reference purposes only

Slide3

Learning 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.

Slide4

Definitions

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)

Slide5

General 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

Slide6

General 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)

Slide7

GeneralConsiderations

Slide8

What’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

Slide9

Enteric 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

Slide10

Other 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

Slide11

Common Gram-Positive Bacteria

Staphylococci

As many as 40 subspecies

Streptococci

Many different variants

Enterococci

Slide12

Beta-lactams

Slide13

Beta-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

)

Slide14

Natural 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

Slide15

Antistaphylococcal

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)

Slide16

Aminopenicillins

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

Slide17

Penicillin/ 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!

Slide18

Cephalosporins

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.

Slide19

First- 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

Slide20

Second-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

)

Slide21

Third-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

Slide22

Fourth-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

Slide23

Fifth-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

Slide24

Carbapenems

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

Slide25

Monobactams

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

Slide26

Vancomycin

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.

Slide27

Miscellaneous 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

Slide28

Fluoroquinolones

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

Slide29

Fluoroquinolones

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.

Slide30

Aminoglycosides

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

Slide31

Aminoglycosides

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

Slide32

Tetracyclines 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

Slide33

Tetracyclines 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)

Slide34

Macrolides 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)

Slide35

Macrolides 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)

Slide36

Clindamycin

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

Slide37

Oxazolidinones

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

Slide38

Nitroimidazoles

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

(?)

Slide39

Nitrofurans 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.

Slide40

Folate 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.

Slide41

Closing 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!

Slide42

Sources

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

Slide43

Thank You!