NAPLEX Chapter 22: Infectious Diseases I: Background & Antibiotics by Drug Class

What are transmissible diseases that are spread from person to person referred to as?

communicable or contagious

What are the primary factors that impact treatment decisions

the bug, the drug and the patient

Infection characteristics include

infection site

severity

whether it is community or hospital-acquired

Antibiotic characteristics include

spectrum of activity and ability to penetrate the site of infection

patient characteristics include

age, body weight, renal and hepatic function, allergies, comorbid conditions

Empiric treatment

antibiotics started before the pathogen is identified

usually broad-spectrum

Gram stain categorizes organism by

shape or morphology

Gram postive

thick cell wall

dark purple/bluish from the crystal violet stain

Gram negative

thin cell wall

pink or reddish from safranin

atypical organisms

do not stain

Gram positive cocci cluster organisms

Staph aureus

Gram positive cocci pairs & chains organisms

strep pneumoniae, streptococcus spp., enterococcus spp.

Gram positive rods

Listeria monocytogenes

Corynebacterium spp.

gram positive anaerobes

Peptostreptococcus

propionibacterium acnes

Clostridium

Atypicals

Chlamydia

Mycoplasma pneumoniae

Legionella spp.

Mycobacterium tuberculosis

Gram negative cocci

neisseria spp.

Gram negative rods that colonize the gut "enteric"

Proteus mirabilis

Escherichia coli

Klebsiella spp.

Serratia spp.

Enterobacter cloacae

Citrobacter spp.

Gram negative rods that are curved or spiral shaped

H. pylori

Campylobacter spp.

Treponema spp.

Borrelia spp.

Leptospira spp.

Gram negative rods that do not colonize the gut

- Pseudomonas aeruginosa

- Haemophilus influenzae (Hib)

- Providencia spp.

Gram negative coccobacilli

Acinetobacter baumannii

Bordetella pertussis

Moraxella catarrhalis

Gram negative anaerobes

Bacteroides fragilis

Prevotella spp.

Antibiograms aid in selecting ___ drug therapy and are used to monitor ___ trends over time

empiric

resistance trends

culture and susceptibility report identifies

the organism and the results of the susceptibility testing

minimum inhibitory concentration (MIC)

minimum concentration of each antibiotic that inhibits bacterial growth

What is intermediate susceptibility?

may be effective under specific circumstances (higher dose, extended infusions)

synergy

the effect of two antibiotics can be greater than the sum of the individual drugs

What is an example of two drug classes that work synergistically together

aminoglycosides and beta lactams

What do you monitor for treatment response?

fever trend

WBC trend

reduction in signs and symptoms of infection

Reasons for lack of response to treatment

antibiotic factors (inadequate spectrum of activity and/or dose, poor tissue penetration, DDIs, non-adherence, etc.)

microbiologic factors (resistance, alternative etiology, etc.)

Host factors (uncontrolled source of infection, immunocompromised)

What are the common mechanisms of antibiotic resistance?

intrinsic

selection pressure

acquired

enzyme inactivation

What is intrinsic resistance?

resistance is natural to the organism

ex. E. coli is resistant to vancomycin bc vancomycin is too large to penetrate the bacterial cell wall of E. coli

What is selection pressure?

Antibiotics kill off the susceptible bacteria, leaving behind the more resistant strains to multiply

What is acquired resistance?

Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments in the environment

what is enzyme inactivation?

enzymes produced by bacteria break down the antibiotic

ex. beta lactamases break down beta lactams

extended spectrum beta lactamases (ESBLs) break down all penicillins and most cephalosporins

carbapenem-resistant Enterobacteriaceae (CRE) are MDR

What is the mneumonic for common resistant pathogens and what does it stand for

Kill Each and Every Strong Pathogen

Klebsiella pneumoniae (ESBL, CRE)

E. coli

Acinetobacter baumannii

Enterococcus faecalis, Enterococcus faecium

Staph aureus

Pseudomonas

symptoms of C. diff

mild (loose stools and abdominal cramping)

severe (pseudomembranous colitis) can be fatal

Which antibiotics have a warning for c diff?

all antibiotics

clindamycin has a boxed warning

Which antibiotics are folic acid synthesis inhibitors?

sulfonamides

trimethoprim

dapsone

Which antibiotics are cell wall inhibitors?

beta lactams

monobactams

vancomycin, dalbavancin, telavancin, oritavancin

Which antibiotics are protein synthesis inhibitors?

aminoglycosides

macrolides

tetracyclines

clindamycin

linezolid, tedizolid

quinupristin/dalfopristin

Which antibiotics are cell membrane inhibitors

polymyxins

daptomycin

telavancin

oritavancin

Which antibiotics are DNA/RNA inhibitors?

Quinolones

Metronidazole, tinidazole

Rifampin

How can the dose of drugs with concentration-dependent killing be optimized?

aminoglycosides

dosed less frequently and in higher concentrations to maximize concentration above MIC

How can the dose of drugs with time-dependent killing be optimized?

beta lactams

dosed more frequently or longer duration to maximize time above MIC

What are beta lactam antibiotics?

penicillin, cephalosporins and carbapenems

How do beta lactams work?

inhibit bacterial cell wall synthesis by binding to penicillin binding proteins, preventing peptidoglycan synthesis in bacterial cell walls

As a class, what are penicillins NOT active against?

MRSA

atypical organisms

Natural penicillins are active against

gram positive cocci

Antistaphylococcal Penicillins have enhanced activity against

MSSA

Aminopenicillins combined with beta-lactamase inhibitors have added activity against

MSSA, more resistant gram negative (HNPEK) and gram negative anaerobes

extended-spectrum penicillins, combined with a beta-lactamase inhibitor (piperacillin/tazobactam) have

broad spectrum activity

expanded coverage of other gram-negative bacteria (CAPES) and pseudomonas

What are the natural penicillins?

Penicillin G

Penicillin V

Penicillin G Benzathine (Bicillin L-A) is administered how?

IM - not for IV use

What are the antistaphylococcal penicillins

dicloxacillin

nafcillin

oxacillin

What are antistaphylococcal penicillins preferred for?

MSSA

What is unique about nafcillin?

vesicant

- if extravasation occurs use cold packs and hyaluronidase injections

Do antistaphylococcal penicillins require renal dose adjustments?

No

What are the aminopenicillins?

amoxicillin

amoxicillin/clavulanate (Augmentin)

ampicillin

ampicillin/sulbactam (Unasyn)

which of the aminopenicillins have a chewable formulation and which have an injection?

chewable: amoxicillin & amox/clav

injection: ampicillin & amp/sulbactam

Which aminopenicillin is rarely used orally due to poor bioavailability?

ampicillin

What must IV ampicillin and amp/sulbactam be diluted in?

NS only

What is the extended spectrum penicillin?

Piperacillin/tazobactam (Zosyn)

What formulations does zosyn come in?

injection

How long is the prolonged or extended infusion for zosyn?

4 hrs

What are contraindications to penicillins?

CrCl < 30: do not use ER oral forms of amoxicillin or Augmentin XR or the 875mg dose of Augmentin

Side effects of penicillins

Seizures (with accumulation)

GI upset

diarrhea

rash (SJS/TEN)/allergic rxns/anaphylaxis

hemolytic anemia identified with positive Coombs test

What do you have to monitor with penicillins?

renal function

What is a key penicillin drug interaction?

probenecid can increase levels of beta lactams

In a patient with a beta-lactam allergy, what penicillins should be avoided?

all penicillins

Which penicillins increase the risk of seizures if accumulation occurs?

all penicillins

What is penicillin VK first-line treatment for?

strep throat

nonpurulent skin infections

What is amoxicillin first line treatment for?

acute otitis media

What is amoxicillin the drug of choice for?

infective endocarditis prophylaxis before dental procedures

Which penicillin is used in H. pylori treatment?

amoxicillin

What is amox/clav first-line treatment for?

acute otitis media

bacterial sinusitis

What is unique about dicloxacillin?

covers MSSA

no renal dose adjustment

What is Penicillin G Benzathine (Bicillin L-A) the drug of choice for?

syphilis

Not for IV use

What is unique about Zosyn?

only penicillin active against pseudomonas

extended infusions (4 hrs) can be used to maximize T > MIC

What are cephalosporins not active against?

enterococcus or atypicals

What active do first generation cephalosporins have?

excellent gram-positive cocci

MSSA

gram-negative rods (PEK)

What active do second generation cephalosporins have?

HNPEK

What second generation cephalosporins have added activity? and what is it?

cefotetan and cefoxitin

anaerobes (B. fragilis)

What are the two groups of third generation cephalosporins?

group 1: ceftriaxone, cefotaxime, cefdinir

group 2: ceftazidime (Fortaz)

What does group 1 of the third generation cephalosporins cover?

resistant streptococci

reisistant HNPEK

What does group 2 of the third generation cephalosporins cover?

lacks gram positive activity

covers pseudomonas

What drug is a fourth generation cephalosporin?

cefepime

What coverage dose cefepime have?

pseudomonas

What drug is a fifth generation cephalosporin?

ceftaroline

what coverage dose ceftaroline have?

broad gram positive activity

only beta lactam that covers MRSA

What coverage do beta-lactamase inhibitor combinations have?

MDR pseudomonas

MDR gram negative rods

What are first generation cephalosporins?

cefazolin, cephalexin (Keflex)

What is the oral dose of cephalexin?

250-500 mg Q6-12H

What are second generation cephalosporins?

cefuroxime

cefotetan (Cefotan)

What are the 3rd generation group 1 cephalosporins?

cefdinir, ceftriaxone, cefotaxime

What are the 3rd generation group 2 cephalosporins?

ceftazidime (Fortaz)

What is the 4th generation cephalosporin?

cefepime

What is the 5th generation cephalosporin?

Ceftaroline fosamil (Teflaro)

What are contraindications to ceftriaxone?

neonates (biliary sludging, kernicterus)

use with calcium-containing IV products in neonates less than or equal to 28 days old

What is a warning with all cephalosporins?

cross-sensitivity with PCN allergy

What is a warning with cefotetan

contains a side chain which can increase risk of bleeding and cause a disulfiram-like rxn with alcohol ingestion