Antibacterial DR Mostafa Alfishawy Antibiotic

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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

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