Antibiotics and surgery

Antibiotics Commonly Used in Surgical Infections

HALF-LIFE

TOXICITY

ANTIBACTERIAL
SPECTRUM

DRUG
Penicillins

MECHANISM OF ACTION COMMENT

Penicillin G

-Lactam mechanism:
Prototype. Hydrolyzed by all Short
inhibits bacterial cell wall by -lactamases
binding to penicillin-binding
proteins (PBPs). It inhibits
the final transpeptidation
step of peptidoglycan
synthesis in the bacterial
cell wall

Low, but rarely an allergic

reaction may be life
threatening

Streptococcal species
except enterococci and
penicillin-resistant
pneumococci, Neisseria
species except lactamaseproducing gonococci

-Lactam mechanism. Also First antistaphylococcal

penicillinase resistant and drug
acid stable

Short

Interstitial nephritis

Staphylococcal species
(methicillin sensitive) and
streptococcal species
except enterococcus

Oxacillin

Short

Interstitial nephritis

Narrow spectrum; generally

used for staphylococcal
infections only

Nafcillin

Short

Interstitial nephritis

Antistaphylococcal
Methicillin

Easy gram-negative
Ampicillin
-Lactam mechanism Hydrolyzed by all - Short
lactamases
Amoxicillin
Medium

Expanded spectrum
Carbenicillin
-Lactam mechanism Hydrolyzed by all - Short
lactamases

Ticarcillin

-Lactam mechanism Same

Short

Low; diarrhea and

rash

Streptococcal
species, including
many enterococci,
Neisseria species
(non lactamase
producing),
Haemophilus
influenzae (non
lactamase
producing), some
Escherichia coli and
Proteus mirabilis

High sodium load.

Greatly expanded
Inhibition of platelet gram-negative
aggregation
spectrum while still
active against
streptococcal
species, including
enterococci.
Moderate
antianaerobe activity.
May not be reliable
as the sole agent for
established gramnegative rod
infections

Same, but less

activity against
enterococci

-Lactamase
-Lactam
inhibitor
mechanism, plus
combination
Clavulanic acid plus Clavulanic acid
mechanism: lactamase inhibitor
that increases the
antibacterial activity
of -lactam
antibiotics
Ticarcillin

Amoxicillin

Sulbactam plus
Ampicillin

Tazobactam plus
Piperacillin

Low; same as

constituent -lactam

Oral only

Short
Medium

Short

Same as ticarcillin or
amoxicillin plus
staphylococci
(methicillin
sensitive),
lactamase-positive
H. influenzae and
some lactamaseproducing gramnegative rods, and
anaerobes

Similar to cefoxitin
with activity against
enterococci

Short

Similar to piperacillin

-Lactam
IV only
mechanism, plus
Sulbactam

mechanism: forms
enzyme-sulbactam
complex that inhibits
-lactamases
-Lactam

mechanism, plus
Tazobactam

Cephalosporins
First
generati
on
Short
half-life

-Lactam
mechanis
m

Cephalot
hin

Prototype Short
of class

Low

Cephapir
in

Short

Low

Longer
half-life

Cefazolin

Medium

Low

Streptococcal species except

enterococci, staphylococcal species
(methicillin sensitive), and easy
gram-negative rods

Second
generation
Poor
anaerobic
activity
Shorter
half-life

-Lactam
mechanism

Cefamandole

Short

Low

Cefuroxime
Longer halflife
Ceforanide
Cefonicid

Medium

Low

Good
anaerobic
activity
Short halflife
Cefoxitin

Reduced
Long
antistaphyloco Long
ccal activity

Same as above, plus many anaerobes

Short

Low

Longer halflife
Cefmetazole

Medium

Low

Cefotetan

Long

Prolonged
prothrombin
times

Same as first-generation cephalosporins with

expanded gram-negative activity not including
Pseudomonas, Acinetobacter, or Serratia

Third
generation

-Lactam
mechanism

Poor
Pseudomonas
activity
Short half-life
Cefotaxime
Ceftizoxime
Long half-life
Ceftriaxone

Short
Medium

Long

Low
Low

Low

Good
Pseudomonas
activity
Cefoperazone
Ceftazidime

Medium
Medium

Low
Low

Same as above plus

activity against
many Pseudomonas,
Acinetobacter, and

Very active against

most gram-negative
rods except
Pseudomonas,
Acinetobacter, and
Serratia. Poor
against anaerobes.
Less activity against
streptococcal and
staphylococcal
species than firstand secondgeneration
cephalosporins.

Monobactams
Aztreonam

-Lactam
Safe for most Short
mechanism:
patients with
preference to penicillin
PBP-3 of gram- allergy
negative
bacteria. Very
stable against
-lactamases

Low

Excellent
activity
against most
gramnegatives,
including
Pseudomonas
and Serratia.
Inactive
against grampositive cocci,
anaerobes,
and most
Acinetobacter
strains

Carbapenems -Lactam

Imipenem/cilastati Cilastatin
n
mechanism:
inactivates
dehydropeptidase
s, which would
normally break
the -lactam ring
of imipenem in
the proximal
tubule

Meropenem
Ertapenem

Provided in
Short
combination with
cilastatin to
prevent renal
breakdown and
renal toxicity

Low. Seizures in
certain high-risk
patients

Extremely broad
gram-positive and
gram-negative
aerobic and
anaerobic. Modest
activity against
enterococci.
Inactive against
Stenotrophomona
s (formerly
Xanthomonas)
maltophilia

Provided alone
Short
without cilastatin

Reduced potential Same activity as

for seizures
imipenem

Provided alone
Long
without cilastatin

Low

mechanism, plus

Better activity
against
Enterobacteriacea
e, less activity
against grampositive cocci,
Pseudomonas,
Acinetobacter,

Quinolones
Poor anaerobic
activity

Norfloxacin

Inhibit bacterial

enzyme DNA-gyrase,
thus inhibiting DNA
replication

Oral only; urine

levels only

Long

Low
Interaction leads to
accumulation of
theophylline

Ciprofloxacin

Oral and intravenous Long

(applies to all below)

Ofloxacin

Racemic mixture of Long

levofloxacin (active)
and dextrofloxacin
(inactive)

Long

Very broad Gramnegative activity.

Gram-positive and
very broad gramnegative activity,
including
Pseudomonas,
Acinetobacter, and
Serratia. Poor
activity against
anaerobes

Very long

Very long

As above plus better

gram-positive and
anaerobe coverage
Broad spectrum
against grampositive, gramnegative, and
anaerobes

Levofloxacin

Better anaerobic activity

Gatifloxacin

Moxifloxacin

Aminoglycosid Bind to a specific All have a low

protein in the 30S ratio of
es

Medium

Nephrotoxicity
and nerve VIII
toxicity, both
auditory and
vestibular

Extremely broad
coverage of gramnegative rods.
Poor activity
against
streptococci.
Some synergism
with penicillin or
vancomycin
against
enterococci. No
activity against
anaerobes
Most active
against
enterococci and
Serratia spp.
More active
against
Pseudomonas
spp.

subunit of the
bacterial
ribosome, which
leads to faulty
alignment or
recognition by
RNA during
initiation of
microbial peptide
chain formation

therapeutic-totoxic levels. All

are frequently
underdosed. All
exhibit a
significant
postantibiotic
effect[*]

Gentamicin

See above

Medium

See above

Tobramycin

See above

Medium

Amikacin

See above

Medium

Statistically but
questionably
clinically
significant
decrease in
nephrotoxicity
See above
Active against a
(aminoglycosides) significant
number of
gentamicin- and

Other Antianaerobes
Chloramphenicol Inhibits bacterial Oral or IV
protein synthesis
by reversibly
attaching to the
50S subunit of the
70S bacterial
ribosome

Long[]

Clindamycin

Inhibits bacterial Oral or IV

protein synthesis
by attaching to
the 50S subunit of
the bacterial
ribosome

Long[]

Metronidazole

Not fully
Oral or IV
elucidated Seems
to produce
cytotoxic effects
on anaerobes by
a reduction
reaction (nitro
group of
metronidazole)

Very long[]

Dose-dependent,
reversible bone
marrow
suppression
Rare (1/2500040000)
irreversible bone
marrow aplasia
Linked to
Clostridium
difficile diarrhea

Disulfiram-type
(Antabuse)
reaction.
Peripheral
neuropathy with
prolonged use

Many grampositive and easy

gram-negative
rods, H.
influenzae, most
anaerobes

Streptococcal
species except
enterococci,
staphylococci,
most anaerobes.
Inactive against
gram-negative
rods
Very active
against most
anaerobes.
Inactive against
facultative and
aerobic bacteria.
Active against
protozoa
(amoebae and

Glycopeptides
Vancomycin

Inhibits cell wall Only IV. No oral

synthesis by
absorption
binding to
carboxyl subunits
on peptide
subunits
containing free Dalanyl-D-alanine
(different site
from -lactams
no cross
resistance), plus
may affect
permeability of
membrane, plus
may inhibit RNA
synthesis

Very long

Hypotension and
histamine release
phenomena
(redman
syndrome) during
infusion.
Nephrotoxicity
and ototoxicity

Streptococcal
species, including
many enterococci,
staphylococci
(including
methicillinresistant strains),
Clostridium
species. No
activity against
gram-negative
rods

Medium

Reversible
transaminase
elevations

Most grampositive
pathogens,
including
vancomycinresistant
Enterococcus
faecium,
methicillin-

Streptogramins
Quinupristin/dalfo Binds to different Significant
pristin
sites on the 50S postantibiotic
subunit of
effect[*]
bacterial
ribosomes A 5- to
10-fold decrease
in the dissociation
constant of
quinupristin is

Oxazolidinones
Linezolid

Attaches to the
Oral or IV
50S subunit of the
bacterial
ribosome and
inhibits protein
synthesis

Long

Reversible
Most grammonoamine
positive bacteria,
oxidase inhibition including
with the potential methicillinto interact with
resistant S.
adrenergic or
aureus and
serotoninergic
vancomycindrugs and cause resistant
hypertension
enterococci
Reversible
myelosuppression
with
thrombocytopenia
, anemia, and
leukopenia

Attaches to the
Oral or IV
50S subunit of the
bacterial
ribosome and
may interfere with
translocation
reactions of the
peptide chains

Medium

Cholestasis with Most gramestolate (IV) form positive,

Neisseria,
Campylobacter,
Mycoplasma,
Chlamydia,
Rickettsia,
Legionella

Macrolides
Erythromycin

Tetracyclines
Tetracycline
Doxycycline

Inhibit protein
Oral or IV
synthesis by
attaching to the Oral or IV
30S subunit of the
bacterial ribosome

Long

Inhibit protein
IV
synthesis by
attaching to the
30S subunit of the
bacterial ribosome

Long

No major toxicities Good against

described yet
multidrugresistant
staphylococci and
streptococci
(including
enterococci). No
Pseudomonas
coverage

Very long

Elevation of liver
function test
result
Visual
disturbances,
fever

Very long

Stain teeth of
children
Same

Many grampositive, easy

gram-negative
rods, some
anaerobes,
Rickettsia,
Chlamydia,
Mycoplasma

Glycylcyclines
Tigecycline

Antifungal Triazoles
Fluconazole
Voriconazole

Inhibition of
cytochrome P450dependent
ergosterol
synthesis

Oral or IV

Long

Most fungi except

Candida krusei,
Candida glabrata
Most fungi

Polyenes
Amphotericin Binds to
IV
B
sterols of cell
wall and
interferes with
permeability

Very long

Nephrotoxicity Most fungi

, fevers and
chills

Very long

Fever.
Most fungi
Infusionrelated
complications

Echinocandins
Caspofungin

Inhibits glucan
synthase,
disrupts
integrity of
the cell wall,
and causes
cell lysis

IV

General principles
Whichever antibiotics are administered, the goal of therapy is to
achieve antibiotic levels at the site of infection that exceed the
minimum inhibitory concentration for the pathogens present.
Mild infections:
oral antibiotics
Severe surgical infections:
IV antibiotics

Why is the patient failing to improve?

The initial operative procedure was not adequate.
The initial procedure was adequate but complications has occurred.
A superinfection has occurred at another site.
The drug choice is correct, but not adequate dose was given.
Another or different drug is needed.

When to stop antibiotics?

No specific time.
until the patient has shown obvious clinical improvement based on
examination

clinical

has had a normal temperature for 48 hours or longer.

Signs of improvement include
improved mental status,
return of bowel function,
resolution of tachycardia, and
spontaneous diuresis.
A shorter course of antibiotics may be sufficient, but data supporting a specific
duration are not available.

Guidelines for choosing antibiotics for

empirical treatment
Ensure coverage of the presumed microorganisms involved.
Choose an antibiotic that is able to reach the site of the
infection.
Consider toxicity, particularly in critically ill patients.
Whenever an infection that will need antibiotics is identified,
aggressively dose the antibiotics.
Whenever starting an antibiotic regimen, set a time limit for the
period the antibiotic will be given.

Superinfection
A superinfection is a new infection that develops during
antibiotic treatment of the original infection.
Bacteria that remain resistant to the antibiotics being used
become the pathogens in superinfection.
Respiratory tract infections are common superinfections that
occur during the treatment of intra-abdominal infection. The
greater the severity of the abdominal infection and the greater
the risk of a poor outcome, the greater the risk for pneumonia
as well.

Antibiotic resistance
Risk factors for antibiotic resistance in a specific patient include
use of antibiotics,

the

prolonged hospital stay,

administration of broad-spectrum antibiotics,
use of invasive devices (endotracheal tubes, central lines,
catheters, etc.), and

Foley

the presence of outbreaks

The population at highest risk are ICU patients, in whom the potential
absence of effective antibiotic treatment correlates with higher mortality
rates.