Reviving Infectious Diseases

Antibacterials
2

Mostafa Alfishawy, MD
Diplomate of the American Board of internal Medicine
Diplomate of the American Board of Infectious Disease
Paul Ehrlich (1854–1915)

In order to use chemotherapy successfully, we

must search for substances which have an
affinity for the cells of the parasites and a
power of killing them greater than the damage
such substances cause to the organism itself
… This means … we must learn to aim, learn
to aim with chemical substances.
 Alexander Fleming (1881–1955)
It is not difficult to make microbes resistant
to penicillin in the laboratory by exposing
them to concentrations not sufficient to kill
them, and the same thing has occasionally
happened in the body. The time may come
when penicillin can be bought by anyone in
the shops. Then there is the danger that the
ignorant man may easily underdose himself
and by exposing his microbes to non-lethal
quantities of the drug, make them resistant.
Don’t use an antibiotic if you don’t
need to

• If a bacterial infection is not high in the differential and

the patient is not clinically toxic, forgo antibiotics.

• They are poor antipyretics.

Persistent fevers require work-up,
not more antibiotics.
• If you are treating with broad antibiotics and fevers
persist, stop them; they aren’t helping anyway.

• Look for undrained foci of infection/pus  drain it.

• Look for non-infectious cause  treat it.

• True FUO in a rapidly deteriorating patient may warrant

empiric anti-TB therapy  Call ID.
 BacteriCIDAL vs. BacterioSTATIC
A consideration in choosing treatments for serious
infection like sepsis or bacteremia of meningitis,
pneumonia, endocarditis, osteomyelitis, neutropenic fever.
A “cidal” drug kills quickly; a “static” drug slows or stops
replication and/or toxic production.
Antibacterial Mechanisms
PK/PD

https://www.futurelearn.com/info/courses/antimicrobial-stewardship/0/steps/
7565
Measuring MIC or Zone Diameter
• MIC = Minimum
Inhibitory Concentration
(lowest concentration of
drug to inhibit growth in
vitro).

• Zone Diameter = zone of

inhibition measured with
calipers.
Interpretation
(susceptible, intermediate,
susceptible dose
dependent, resistant)
The Right Prescription
Narrowest spectrum
Reach target
Right dose
Right duration Allergy
Right formulation
Always check interactions
Always check adjustments
Remember the pregnant and lactating females
Affordable
Bacterial Resistance
Without the right prescrption
Gram Stain
Gram
Positives
Gram
Negatives
 Penicillin


Benzylpenicillin or Pen G

Benzathine PCN= Long acting

Phenoxymethyl PCN or Pen V


SE : Allergy


Niche : Strep
 Oxacillin, Flucloxacillin &
Nafcillin


Antistaphylococcal penicillins


Niche: MSSA
 Amoxicillin


Niche : Strep
 Ampicillin

Aminopenicillin similar to amoxicillin

 Amoxicillin/Clavulante


Niche : Anaerobes, Strep and Gram
negatives with early Beta lactamases
 Ampicillin/Sulbactam


Niche : Anaerobes, Strep, Gram
negatives with early Beta lactamases
and Acinetobacter.
 Piperacillin/tazobactam


The work horse in US

Q6h or Q8h

Niche : Strep, MSSA, Enterococci,
Gram negatives including ESBL
and Pseuduomonas
 Cefazolin and first Gen


Drug of Choice for preoperative
prophylaxis


Niche : MSSA and Strep
 Cefuroxime


Better gram negative coverage

Still has MSSA and strep
 Cefotaxime


Dose in meningitis 2gm IV Q4h

Dose in SBP 2gm IV Q8h

Similar to Ceftriaxone but requires multiple
dosing
 Cefoperazone


High Biliary concentration

It releases free NMTT, which can cause
hypoprothrombinemia

Disulfiram like
 Cefoperazone/sulbactam


The work horse in India

Covers pseudomonas and anerobes
 Ceftriaxone


Used in Meningitis and in strep
endocarditis


Niche: Once daily dosing
Cefdinir & Cefpodoxime

rd

Niche : oral 3 Gen

oral Rocephin
 Ceftazidime


Niche: Pseudomonas
 Cefepime

th

4 Gen

Dose 1-2 gm Q8-12h

Active against SPICE

Antipseudumonal
 Ceftaroline

Niche: In vitro activity against
staphylococci (including MRSA),
most streptococci, and many Gram-
negative bacteria. Salvage therapy
for MRSAB


Holes : Pseudomonas, Acinetobacter
& Gram-negative anaerobes.
 Ceftolozane/
Tazobactam

Niche: Pseudomonas

Very expensive
 Ceftazime/
Avibactam

Niche: Carbapenem resistant
Enterobacterals

Very expensive
 Imipenem


The first carbapenem

Not stable for prolonged infusion

Higher seizure risk than other carbapenems
 Meropenem


Dose 1gm IV Q8h
 Ertapenem


It has in vitro activity against ESBL

Dosing once daily

Holes: Pseudomonas, Acinetobacter
Enteroccocus.
 Aztreona
m

Niche: NDM producing GNB

c
v
 Vancomycin


Niche: MRSA

Needs drug level

SE : Red man syndrome
 Daptomyci
• n
Niche : Gram positive
• Inhibited by surfactant
• Rhabdomyolysis
 Linezolid


Used in VISA & VRSA

MRSA & MRSE

Vancomycin failure

VRE

SE : Thrombocytopenia & Serotonin syndrome
 Clindamycin


Niche : Anaerobes

Bad reputation for C.Dif
 Rifampicin


Used in hardware infections as well
as for mycobacterial infections.

SE: Hepatotoxic

orange urine
 Erythromycin


The first macrolide

Used for diabetic gastroparesis

Many drug interactions
 Azithromycin


Most prescribed antibiotic

Half life 68h

SE Arrhythmia
 Clarithromycin


Used to treat H.Pylori and
nontuberculous mycobacteria.
 Gentamicin


A Shot in the ED

Needs drug level


Peak=efficacy

Trough=toxicity

Dosing can be once daily

Niche : Gram negatives
 Metronidazole


Also antiprotozoal

Disulfiram reaction

Niche: Anaerobes
 Doxycycline


No patient should die without Doxy on
board.

Also malaria prophylaxis

Niche atypical infections
 Tigecycline


Glycycycline with similar structure with
tetracycline, but 5 times stronger, big
volume distribution and long half-time in
the body.

Peak serum concentrations of Tigecycline
do not exceed 1 mcg/mL which limits its
use for treatment of bacteremia

Holes: Proteus & Pseudomonas
 Ciprofloxacin


Many drug interactions

Niche: Carbapenem sparing agent
 Levofloxacin


Quinolone with added coverage for
pneumonia
 Moxifloxacin


Cipro with added pneumonia
coverage without drug interactions.

Anaerobic activity
 Nitrofurantoin


Niche: UTI treatment and prophylaxis

SE: Interstitial pneumonitis
 Trimethoprim/sulfamethoxazole

It has in vitro activity against
Enterobacteriaceae spp., B.
cepacia, S.
maltophilia,Acinetobacter spp.,
Achromobacter spp., Nocardia
spp., Listeria,Pneumocystis
jirovecii (PCP), staphylococci
(including S. aureus and
Coagulase-negative staph)


Holes: Pseudomonas & anaerobes
 Fosfomycin


In vitro activity against large number
of Gram-negative and Gram-positive
organisms including E. coli, Klebsiella
spp., Proteus spp., Pseudomonas
spp., and VRE.


Holes : Acinetobacter
 Colistin Colistin)


It has in vitro activity against Acinetobacter spp. and
Pseudomonas.


Holes: Proteus, Serratia, Providentia, Burkholderia,
Stenotrophomonas, Gram-negative cocci, Gram-
positive organisms, or anaerobes.


Take care with dosing
Chloaramphenicol
MRSA AGENTS
Cephalosporins
Macrolides
Quinolones