By
Dr. Amina Unis
Bacteremia: is the presence of viable
bacteria in the blood stream.
Bacteremia can result from a serious infection
or from something as harmless as vigorous
toothbrushing.
Most often, only a small number of bacteria
are present, and they are removed by the
body on its own.
However, occasionally, bacteremia leads to
infections, sepsis, or both.
Sepsis: Bacteremia associated with
serious inflammatory response from the
body , characterized by rapid breathing,
low blood pressure and fever .
Severe sepsis: Sepsis plus either the
failure of an essential system in the body
or inadequate blood flow to parts of the
body due to an infection.
Septic shock: Sepsis that causes
dangerously low blood pressure ( shock) is
called septic shock. As a result, internal
organs typically receive too little blood,
causing them to malfunction.
Septic shock is life threatening.
PREVENTION OF BACTEREMIA
People who are at high risk of complications
due to bacteremia must be given prophylactic
antibiotics
1. before dental procedures for those who
have an artificial heart valve or joint or certain
heart valve abnormalities.
2.Surgical treatment of infected wounds
3.Insertion of bladder catheters
TREATMENT OF BACTEREMIA
Usually ,we start with Empiric
therapy (immediate administration of
drug(s) prior to bacterial identification
and susceptibility testing ,based on
previous clinical experience.)
TREATMENT OF BACTEREMIA
Drug choice (empiric therapy) in the
absence of susceptibility data is
influenced by:
1.the site of infection
2. the patient’s history(for example, previous
infections, age, recent travel history, recent
antimicrobial therapy, immune status, and
whether the infection was hospital- or
community-acquired).
TREATMENT OF BACTEREMIA
In empiric therapy Broad-spectrum
therapy
may be indicated initially when the organism is
unknown or polymicrobial infections are likely.
Often, two or three antibiotics are given
together to increase the chances of killing the
bacteria, particularly when the source of the
bacteria is unknown.
TREATMENT OF BACTEREMIA
In empiric therapy, care should be taken in
choice of antibiotics according to the
patient condition in relation to way of
elimination of commonly used
antimicrobial agents
Mechanism of action of Penicillins
The penicillins mainly interfere with the last
step of bacterial cell wall synthesis
(transpeptidation or cross-linkage.)
Penicillins are only effective against rapidly
growing organisms that synthesize a
peptidoglycan cell wall.
Consequently, they are inactive against
organisms devoid of this structure, such as
mycobacteria, protozoa, fungi, and viruses.
Mechanism of action of penicillins
I. Bacterial cell wall synthesis inhibition:
•Bacterial cell wall is cross-linked polymer of
polysaccharides and pentapeptides
• Penicillins interact with cytoplasmic
membrane-binding proteins(PBPs) to inhibit
transpeptidation reactions involved in cross-
linking, the final steps in cell-wall synthesis
II. Production of autolysins: destruction of
the existing cell wall
1. narrow spectrum or Natural penicillins
Natural penicillins (penicillin G and penicillin V)
are obtained from fermentations of the fungus
Penicillium chrysogenum.
• Penicillin G (benzyl-penicillin) remains the drug
of choice for the treatment of gas gangrene
(Clostridium perfringens) and syphilis
(Treponema pallidum).
• Penicillin V has a similar spectrum to that of
penicillin G, but it is not used for treatment of
2 very narrow spectrum or Antistaphylococcal
penicillins
•Methicillin, nafcillin, oxacillin.
•Their use is restricted to the treatment of infections
caused by penicillinase-producing staphylococci,
including methicillin sensitive Staphylococcus
aureus (MSSA). (NOT MRSA)
•[Note: Because of its toxicity (interstitial nephritis),
methicillin is not used clinically in the United States
except in laboratory tests to identify resistant strains of
S. aureus.
3. Broad spectrum penicillins:
• Ampicillin and amoxicillin have an antibacterial
spectrum similar to that of penicillin G but are more
effective against gram negative bacilli.
•Ampicillin is the drug of choice for the gram-positive
bacillus Listeria monocytogenes ,susceptible
enterococcal species and helicobacter pylori
•These broad spectrum agents are also widely used in
the treatment of respiratory infections, and amoxicillin
is employed prophylactically by dentists in high-risk
patients.
4. Extended spectrum or
Antipseudomonal penicillins:
•Piperacillin and ticarcillin are called
antipseudomonal penicillins because of their
activity against Pseudomonas aeruginosa.
•These agents are available in parenteral
formulations only.
•Piperacillin is the most potent of these
antibiotics.
Resistance :
1-One of the major causes of resistance to
penicillins and cephalosporins is the production of
penicillinases, the beta lactamase enzymes.
Those are Bacterial enzymes that hydrolyze the
beta-lactam ring of certain penicillins and
cephalosporins.
To decrease such resistance ,penicillins now are
combined with beta lactamase inhibitors
e.g.Clavulanic acid, sulbactam.
Causes of resistance
2. Decreased permeability to the drug:
Decreased penetration of the antibiotic through
the outer cell membrane of the bacteria prevents
the drug from reaching the target PBPs. The
presence of an efflux pump can also reduce the
amount of intracellular drug .
3. Structural changes in penicillin binding
proteins (PBPs): Modified PBPs have a lower
affinity for β-lactamAntibiotics. This explains MRSA
resistance to most commercially available β-
Pharmacokinetics
• Most are eliminated via active tubular
secretion with secretion blocked by
probenecid; dose reduction needed only in
major renal dysfunction
• Nafcillin and oxacillin eliminated largely in
bile; ampicillin undergoes enterohepatic
cycling, but excreted by the kidney.
Adverse reactions
1.Hypersensitivity:(types I–IV).
Approximately 5% percent of patients have
some kind of reaction, ranging from rashes to
angioedema (marked swelling of the lips,
tongue, and periorbital area) and
anaphylaxis.
Cross-allergic reactions occur among the β-
lactam antibiotics.
Bridge to Immunology
Drug Hypersensitivity Reactions
I. IgE mediated: rapid onset; anaphylaxis,
angioedema, laryngospasm
II. IgM and IgG antibodies fixed to cells: vasculitis,
neutropenia, positive Coombs test
III. Immune complex formation:
vasculitis, serum sickness, interstitial nephritis
IV. T-cell mediated: urticarial and maculopapular
rashes, Stevens- Johnson syndrome
2. GIT : especially with ampicillin
• Diarrhea is a common problem that is caused by a
disruption of the normal balance of intestinal
microorganisms.
•It occurs to a greater extent with those agents that
are incompletely absorbed and have an extended
antibacterial spectrum.
•Pseudomembranous colitis may occur.
3. Nephritis:
Penicillins, particularly methicillin, have the potential
to
4.Jarisch-Herxheimer reaction in treatment of
syphilis: a reaction to endotoxin-like products
released by the death of harmful microorganisms
within the body during antibiotic treatment.
•can be life-threatening as they can cause a
significant drop in blood pressure and cause acute
end organ injury, eventually leading to failure.
• Prophylaxis and treatment with an anti-
inflammatory agent may stop progression of the
reaction
5. Neurotoxicity:
The penicillins are irritating to neuronal tissue, and
they can provoke seizures if injected intrathecally
or if very high blood levels are reached.
Epileptic patients are particularly at risk due to the
ability of penicillins to cause GABAergic inhibition.
6. Hematologic toxicities:
Decreased coagulation may be observed with high
doses of piperacillin, ticarcillin, and nafcillin (and, to
some extent, with penicillin G).
Cephalosporins
• Mechanisms of action and
resistance: identical to penicillins
Subgroups and antimicrobial activity:
–– First generation: cefazolin, cephalexin
oo Spectrum: gram-positive cocci (not MRSA),
E. coli, Klebsiella pneumoniae, and some
Proteus species
oo Common use in surgical prophylaxis
oo Pharmacokinetics: none enter CNS
Second generation: cefotetan, cefaclor,
cefuroxime
oo Spectrum: ↑ gram-negative coverage,
including some anaerobes
oo Pharmacokinetics: no drugs enter the CNS,
except cefuroxime
Third generation: ceftriaxone (IM) and
cefotaxime (parenteral), cefdinir and cefixime
(oral)
oo Spectrum: gram-positive and gram-
negative cocci (Neisseria gonorrhea), plus
many gram-negative rods
oo Pharmacokinetics: most enter CNS;
important in empiric management
of meningitis and sepsis
Fourth generation: cefepime (IV)
oo Even wider spectrum
oo Resistant to most beta-lactamases
oo Enters CNS
Pharmacokinetics:
–– Renal clearance similar to penicillins, with
active tubular secretion blocked by probenecid
–– Dose modification in renal dysfunction
–– Ceftriaxone is largely eliminated in the bile
Side effects:
–– Hypersensitivity: oo Incidence: 2%
oo Wide range, but rashes and drug fever most
common
Positive Coombs test, but rarely hemolysis
oo Assume complete cross-allergenicity between
individual
cephalosporins and partial cross-allergenicity with
penicillins (about 5%)
oo Most authorities recommend avoiding
cephalosporins in patients allergic to penicillins (for
gram-positive organisms, consider macrolides; for
Clinical Correlate
Ceftaroline is an unclassified (fifth
generation) cephalosporin that can
bind to the most often seen mutation
of the PBP in MRSA.
Classic Clues
Organisms not covered by cephalosporins
are “LAME”:
Listeria monocytogenes
Atypicals (e.g., Chlamydia,
Mycoplasma)
MRSA
Enterococci
