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Transcript of An
Lippincott’s pharmacology 5th ed
Determined by a technique called
Gram +ve & gram -ve bacteria:
Microbiology a systems approach 2nd ed
All mycoplasmas lack a cell wall and, therefore, all are inherently
antibiotics (e.g., penicillin).
Mycoplasmas are bacteria that naturally
a cell wall.
the mycoplasma cell membrane is stabilized by sterols and is resistant to lysis.
In order to enter a cell,
require an energy-dependent
or nitrate, Because anaerobes do not utilize oxygen or nitrate, aminoglycosides
enter anaerobic cells to inhibit ribosomal activity
Are bacteria that does not require oxygen for growth.
anaerobe : die in the presence of oxygen
anaerobes : can grow with
Administration of broad-spectrum antibiotics can drastically
the nature of the normal bacterial flora and precipitate a
of an organism such as
, the growth of which is normally kept in check by the presence of other microorganisms
-affect a wide variety of microbial species
-agents acting only on a limited group of microorganisms
against gram-negative rods and is
against other organisms, such as S. pneumoniae.
bacteria at drug serum levels achievable in the patient
the growth and replication of bacteria thus limiting the spread of infection until the body’s immune system eliminates the pathogen. (Ex :
concentration of antibiotic that
anti-microbial therapy, the clinically obtainable antibiotic
concentration in body tissues and fluids should be
r than the MIC
Minimum inhibitory concentration (MIC)
-Giving drugs that exhibit this concentration-dependent killing by a
bolus infusion achieves high peak levels, favoring
of the infecting pathogen.
-Antibiotics that show a significant increase in the rate of bacterial killing as the
from 4- to 64-fold the MIC of the drug for the infecting organism . Ex :
Clinicians can utilize
(generally 3 to 4 hours) or continuous (24 hour) infusions to achieve prolonged time above the MIC and kill
Time-dependent (concentration-independent) killing
increasing the concentration of antibiotic to higher multiples of the MIC does not significantly increase the rate of kill The clinical efficacy of antimicrobials that have a non-significant, dose-dependent killing effect is best predicted by the percentage of
that blood concentrations of a drug
the MIC .
In 1945, Alexander Fleming, who discovered penicillin, warned that bacteria could become resistant to these remarkable drugs.
DECREASED DRUG ACCUMULATION IN THE BACTERIUM
ex: resistance genes in the plasmid code for inducible proteins in the bacterial membrane, which promote energy-dependent efflux of the antibiotic , and hence resistance
treatment with antibiotics can induce an increased number of copies for pre-existing resistance genes such as antibiotic-destroying enzymes and efflux pumps.
Mechanisms of antibiotic resistance
ALTERATION OF DRUG-SENSITIVE OR DRUG-BINDING SITE
ex : The aminoglycoside-binding site on the 30S subunit of the ribosome may be altered by chromosomal mutation
PRODUCTION OF AN ENZYME THAT INACTIVATES THE DRUG
ex: Staphylococci producing β-lactamase
was first introduced it was an effective treatment for
infections, but resistance had already developed during the 1940s.
-This resistance was mediated by the production of a
enzyme that inactivates drugs such as penicillin, ampicillin and amoxicillin.
) as well as beta-lactamase inhibitors (e.g.
) that could be combined with the antibacterial drugs were developed.
Gram-negative bacteria have developed several pathways to
the most concerning are β-lactamases,
that destroy the β-lactam antibiotics .
-Some β-lactamases destroy narrow spectrum drugs (only active against penicillins)
β-lactamases (e .g .
found in carbapenem-resistant Enterobacteriaceae or CRE) are active against
β-lactam antibiotics .
-The first strains of MRSA emerged during the
-Initially, MRSA was mainly a problem in hospital-acquired infections.
-Over the past decade,
has increased significantly in a number of countries.
How Resistance spreads
1-by transfer of bacteria
2-by transfer of resistance genes
(usually on plasmids)
3-by transfer of resistance genes between genetic elements
antibiotic treatment options are
by resistance or are unavailable, healthcare providers are
to use antibiotics that may be
to the patient and frequently
-Common infections in
are increasingly becoming
, and sometimes
, to treat.
-Antibacterial drugs used to prevent
postoperative surgical site
infections have become
, one of the most common of all bacterial infections in women, which readily responded to oral treatment in the past, may
to be treated by
drugs, imposing additional
for patients and health systems, or become
infections such as pneumonia, which used to be readily treatable after the introduction of penicillin, may
to available or recommended drugs in many settings, putting the lives of patients at risk
Who report on Antibiotic resistance 2014
, including resistance conferred by extended spectrum beta-lactamases (ESBLs), and to
Countries that notified at least one case of
) by the end of 2012 (WHO)
Antibiotic resistance is a global threat
Antibiotic discovery is declining
-skin and skin structure infections caused by S. aureus and Streptococcus pyogenes
-Community-Acquired Bacterial Pneumonia
-Skin & Skin Structure Infections
-skin and skin structure infections
-Complicated Intra-abdominal Infection
-complicated skin and skin structure infections
-complicated intra-abdominal infections and(CAP).
Antibiotics approved in the last 10 years (from 2004 to 2014)
Duration of therapy:
days, should be
of therapy may be needed if initial therapy was not active against the
pathogen or if it was
by extrapulmonary infections
suspected CAP patients, in light of better outcomes with the earliest possible interventions the Infectious Diseases Society of America (IDSA) recommends
antimicrobial therapy until
can be obtained to guide more specific therapy
Community acquired pneumonia(CAP)
-those with existing QT interval prolongation
-uncompensated heart failure
-those receiving antiarrhythmic drugs
course of therapy with beta-lactams, macrolides, or
to the same class of antibiotic. Thus, an antimicrobial agent from an
class is preferred for a patient who has
received one of these agents.
Health care professionals should
Tygacil for use in situations when
suitable. (FDA 2013)
is one of the recommended beta-lactam antibiotics for CAP in immunocompetent,
-account for approximately
of all CAP cases
-mainly caused by
antibiotics if there is no evidence of infection
IV to Oral
antibiotics – ideally to a narrower spectrum – or broader if required
4. Continue and
again after a further 24 hours
Antibiotic Therapy (OPAT)
There is no single template for a program to optimize antibiotic prescribing in hospitals.
How to Rationalize Antibiotic use
to this include some serious infections where exceptionally high antibiotic
tissue concentrations are essential (e.g.
by reducing the need for intravenous access
-IV antibiotics should be
and, if appropriate, the patient
to an oral equivalent within
l efforts aimed at changing prescribing practices of physicians
of hospital formulary through pharmacy and therapeutics Committee
with infectious diseases subspecialists for certain antimicrobial choices
Methods to implement antibiotic control or restriction policy
All clinicians should perform a
after antibiotics are initiated to answer these key questions:
-Does this patient have an
that will respond to antibiotics?
-If so, is the patient on the
antibiotic(s), dose, and route of administration?
-Can a more
antibiotic be used to treat the infection (
should the patient receive the antibiotic(s)?
As soon as the
pathogen has been identified,
should be performed
by selecting the most appropriate antimicrobial agent that covers the pathogen
Because patients with
have little margin for error in the choice of therapy, the initial selection of antimicrobial therapy should be
to cover all likely pathogens
anti-microbial therapy is initiated if such cultures
do not cause significant
(> 45 minutes) in the start of antimicrobial(s) Administration
in situations where therapy might be
duplicative including simultaneous use of
spectra e.g. anaerobic activity, atypical activity,
and resistant Gram-positive activity.
- Lippincott's Pharmacology 5th edition
- Rang & dale’s pharmacology 7th edition
- Infectious Diseases Society of America latest guidelines
- Centers for Disease Control and Prevention recommendation on use of antibiotics
- Royal United Hospital antibiotic guidelines
-the clinical features alone do not reliably discriminate between bacterial and viral Pharyngitis except when overt
- 1st line =
= 1st generation cephalosporin (
-if allergic to
of cases of Pharyngitis
need antibiotic therapy
- Antimicrobials that should
be used :
: high prevalence of
eradicate group A streptococcus(GAS)
activity against GAS
and have an
broad spectrum of activity and are therefore not recommended for routine treatment of bacterial pharyngitis
of viral sinusitis may develop
of rhinosinusitis is due to
infections (don’t need antibiotic therapy)
of antibiotic therapy ranges from
1- Macrolides (
) because of high rate of
among S. pneumonia
) both S. pneumoniae and Haemophilus inﬂuenzae are
3-Second generation cephalosporins(
) also have
rates of resistance
-Treatment of asymptomatic bacteriuria
of Symptomatic infection
episodes of asymptomatic bacteriuria.
Acute Uncomplicated Cystitis
(Amoxil™ ) or
be used for empirical treatment given the relatively
efﬁcacy, and the very high prevalence of antimicrobial
to these agents worldwide
(Amoxicillin , Cephalexin)
) encodes the protein
). PBP2A has a
for beta-lactam antibiotics such as methicillin and penicillin. This enables transpeptidase activity in the presence of beta-lactams,
them from inhibiting cell wall synthesis.
Antibiotics that may be released soon in the market
(by end of 2014)
-infections caused by certain
bacteria, including those caused by (MRSA).
) caused by
(including MRSA) and
urinary tract infections
(caustive agent for many dental infections )
responses occur when the concentrations
the MIC for their target organism at the site of infection
-once daily dosage
be used in
Strains of S. aureus
to these penicillinase-stable antibacterial drugs have acquired a novel gene (
) that codes for a novel
; these strains are termed
transposons can jump from chromosomal DNA to plasmid DNA and back, allowing for the transfer and permanent addition of genes .
of all the antibiotics prescribed for people are
or are not optimally effective as prescribed
CDC report on Antibiotic resistance
of aminoglycosides will also depend on
, plus any
and at least one of three injectable second-line drugs (i.e.,
Pneumococcal conjugate vaccine (PCV13) is recommended for
years old and for
A new version of the pneumococcal conjugate vaccine (PCV13) introduced in
against infections with the most
by blocking the
of resistant S. pneumoniae strains.
Risk factors :
-Persons with functional or anatomic asplenia
lasting for more than
(39 or more) +
When to give antibiotics :
is recommended as
to penicllins :
becomes 1st line
-In Managing the Patient With
to Respond to Empiric Treatment With
Agents, It Is Important to Obtain
to Document Whether There Is Persistent Bacterial Infection and Whether Resistant Pathogens Are Present.
Antibiotics that shouldn’t be used :
-An alternative management strategy is recommended if symptoms
empiric antimicrobial therapy
means presence of bacteria in the urine culture but with
apparent symptoms on the patient (
pain in women)
an indication for
women should be screened for bacteriuria by
at least once in early pregnancy, and they should be
if the results are positive
of asymptomatic bacteriuria before
resection of the prostate is
other urologic procedures for which
(Uvamin )(100 mg twice daily for 5 days) is an appropriate choice for therapy due to
resistance and propensity for collateral damage and efficacy
(Septrin DS) (twice-daily for 3 days) is an appropriate choice for therapy, given its
as assessed in numerous clinical trials
Antibiotics that should not be used as 1st line :
(tavanic™), are highly efﬁcacious in 3-day regimens but have a propensity for collateral damage and should be
for important uses other than acute cystitis and thus should be considered alternative antimicrobials for acute cystitis
-In patients suspected of having pyelonephritis, a
should always be
, and initial empirical therapy should be tailored appropriately on the basis of the infecting uropathogen
(500 mg twice daily) for 7 days, is an appropriate choice for therapy in patients not requiring hospitalization
(750 mg for 5 days), is an appropriate choice for therapy in patients not requiring hospitalization
Antibiotics that should not be used as 1st line :
effective and will require
duration of therapy (14days) thus should not be used as 1st line treatment
Monitoring antibiotic prescribing and resistance patterns with regular reporting of information on antibiotic use and resistance to doctor , nurses and relevant staff
Tracking & Reporting :
The five Antimicrobial Prescribing Decision options are:
< 37.5 °C for 24 hours
and symptoms of infection are
• patient able to
oral food and fluids
• absence of on-going or potential problem of
• oral formulation or suitable oral
IV to Oral
Oral switch criteria :
Antibiotic “Time outs.”
can cause a
which can result in torsades de pointes and death.
Patients at particular risk include:
Dose = 600 mg IV q12h
in these cases
is a good alternative
Ceftazidime + Levofloxacin + Amikacin
Ceftazidime + levofloxacin