Antibiotics 2018
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Antibiotics 2018

DisciplinaFarmacologia Farmacêutica590 materiais4.449 seguidores
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and	meropenem.	They	possess	a	beta-lactam	ring
and	share	the	same	mechanism	of	action	of	beta-lactams,	but	they	are
structurally	unique	and	differ	from	both	penicillins	and	cephalosporins.	Their
broad	spectrum	makes	them	both	appealing	and	unappealing	for	empiric
therapy,	depending	on	the	infection	being	treated	and	the	risk	factors	of	the
patient	for	a	resistant	organism.	Imipenem,	doripenem,	and	meropenem	have
similar	spectra	of	activity;	ertapenem	has	important	differences	in	its
spectrum	that	must	be	learned.
Mechanism	of	Action
All	beta-lactams	inhibit	cross-linking	of	peptidoglycan	in	the	cell	wall,	leading
to	autolysis	and	cell	death.
Good:	MSSA,	streptococci,	anaerobes,	enteric	GNRs,	Pseudomonas
(not	ertapenem),	Acinetobacter	(not	ertapenem),	ESBL-producing	GNRs
Moderate:	enterococci	(not	ertapenem)
Poor:	MRSA,	penicillin-resistant	streptococci
Adverse	Effects
Similar	to	those	of	other	beta-lactams,	but	imipenem	has	a	higher	propensity
to	induce	seizures.	Minimize	the	risk	by	calculating	appropriate	doses	for
patients	with	renal	dysfunction	and	avoiding	imipenem	use	in	patients	with
meningitis,	because	it	can	cross	the	blood\u2013brain	barrier	more	readily.
Important	Facts
Important	Facts
Imipenem	is	metabolized	in	the	kidney	to	a	nephrotoxic	product.	Cilastatin
blocks	the	renal	dehydropeptidase	that	catalyzes	this	reaction	and
prevents	this	metabolism	from	occurring.	It	is	always	coadministered	with
imipenem	for	this	reason.
Carbapenems	are	very	broad-spectrum	agents.	Imipenem,	doripenem,
and	meropenem	are	particularly	broad	and	should	not	be	used	empirically
for	most	community-acquired	infections.	They	are	good	choices	for	many
types	of	nosocomial	infections,	particularly	in	patients	who	have	received
many	other	classes	of	antibiotics	during	their	hospital	stay.
Although	ertapenem	has	weaker	activity	than	the	other	carbapenems	for
a	few	organisms,	this	activity	is	significant	enough	to	change	the	utility	of
the	drug	(think:	Ertapenem	is	the	Exception).	Ertapenem	is	a	poor	choice
for	many	nosocomial	infections,	particularly	nosocomial	pneumonia	in
which	both	Pseudomonas	and	Acinetobacter	are	important	pathogens.
However,	it	is	administered	only	once	a	day	and	thus	more	convenient
than	the	other	carbapenems,	so	it	may	be	a	better	choice	for	home-
infusion	therapy	for	susceptible	infections.
Carbapenems	may	uncommonly	elicit	an	allergic	reaction	in	patients	with
a	history	of	penicillin	allergy.	One	study	showed	the	incidence	of	such
reactions	to	be	as	high	as	47%	with	a	proven	penicillin	allergy	(keep	in
mind	that	many	penicillin	allergies	are	unproven),	but	more	recent	and
better-performed	studies	in	patients	with	anaphylaxis	to	penicillin	have
shown	this	number	to	be	much	lower	(close	to	1%).	However,	keep	in
mind	that	even	if	the	cross-reactivity	is	very	low	between	these	agents,
patients	with	a	history	of	allergy	to	any	drug	are	more	likely	to	react	to
another	one	even	if	they	are	not	related.
Carbapenemases	that	render	these	drugs	inert	exist	and	are	becoming
more	common.	In	the	United	States	they	are	most	common	in	the
Northeast;	they	are	very	common	in	some	other	parts	of	the	world.	Both
imipenem/cilastatin	and	meropenem	are	being	studied	in	combination	with
new	beta-lactamase	inhibitors	that	restore	their	activity	against
carbapenemase-producing	GNRs.
What	They\u2019re	Good	For
What	They\u2019re	Good	For
All:	mixed	aerobic/anaerobic	infections,	infections	caused	by	ESBL-
producing	organisms,	intra-abdominal	infections
Imipenem,	doripenem,	meropenem:	nosocomial	pneumonia,	febrile
neutropenia,	other	nosocomial	infections
Don\u2019t	Forget!
Check	your	dosing	in	patients	with	renal	dysfunction	to	minimize	the	risk	of
imipenem-induced	seizures.
Agent:	aztreonam
Aztreonam	is	the	only	monobactam	currently	available.	Structurally,
aztreonam	contains	only	the	four-membered	ring	of	the	basic	beta-lactam
structure,	hence	the	name	monobactam.	Aztreonam\u2019s	quirk	is	that	it	seems
to	be	safe	to	administer	to	patients	with	allergies	to	other	beta-lactams,
except	patients	who	have	a	specific	allergy	to	ceftazidime.	This	cross-
reactivity	seems	to	be	a	result	of	the	fact	that	ceftazidime	and	aztreonam
share	an	identical	side	chain	(note:	ceftolozane	also	shares	this	side	chain).
Ceftazidime	and	aztreonam	also	share	virtually	the	same	spectrum	of	activity.
It	is	reasonably	safe	to	remember	the	utility	of	aztreonam	by	thinking	of	it	as
ceftazidime	without	allergic	cross-reactivity	with	other	beta-lactams.
Mechanism	of	Action
Like	the	other	beta-lactams,	monobactams	inhibit	cross-linking	of
peptidoglycan	in	the	cell	wall,	leading	to	autolysis	and	cell	death.
Good:	Pseudomonas,	most	GNRs
Moderate:	Acinetobacter
Poor:	Gram-positive	organisms,	anaerobes
Adverse	Effects
Similar	to	those	of	other	beta-lactams,	but	with	a	low	incidence	of
Important	Facts
Aztreonam	shares	a	mechanism	of	action	and	pharmacodynamic	profile
with	other	beta-lactams.	Because	it	is	a	Gram-negative	drug	that	is	often
used	in	patients	with	penicillin	allergies,	it	is	often	confused	with
aminoglycosides.	It	is	chemically	unrelated	to	aminoglycosides	and	does
not	share	their	toxicities.
Aztreonam	can	be	administered	via	inhalation	to	patients	with	cystic
fibrosis	to	prevent	exacerbations	of	infection.
Aztreonam	is	a	type	of	beta-lactam,	and	combination	therapy	with	it	and
other	beta-lactams	against	the	same	organism	is	unwarranted.	Try	adding
a	non-beta-lactam	drug	to	your	empiric	regimen	for	serious	nosocomial
infections	instead.
What	It\u2019s	Good	For
Gram-negative	infections,	including	Pseudomonas,	particularly	in	patients
with	a	history	of	beta-lactam	allergy.
Don\u2019t	Forget!
Before	using	aztreonam	in	your	patients	with	beta-lactam	allergies,
investigate	whether	the	reaction	was	specifically	to	ceftazidime.	If	you	cannot
determine	this	and	the	reaction	was	serious,	proceed	with	caution	or	use	an
alternative	agent.
8:	Glycopeptides	and	Short-Acting
Agents:	vancomycin,	telavancin
To	date,	three	glycopeptides	are	in	clinical	use:	vancomycin,	teicoplanin,	and
telavancin.	Teicoplanin	is	not	available	in	the	United	States,	and	telavancin
was	recently	approved.
Vancomycin	is	invaluable,	because	it	has	activity	against	most	things	Gram-
positive	that	have	not	learned	to	become	resistant	to	it.	Many	enterococci
(especially	Enterococcus	faecium)	have	figured	this	out\u2014we	call	them
vancomycin-resistant	enterococci	(VRE).	A	few	staphylococci	have	learned
vancomycin	resistance	from	the	enterococci,	but	these	staphylococci	are
currently	very	rare.	In	general,	they	are	susceptible.
Telavancin	is	a	somewhat	different	agent.	It	is	a	lipoglycopeptide	that	was
modified	from	vancomycin\u2019s	structure.	It	has	some	unique	properties	that
may	be	advantageous	compared	with	vancomycin,	such	as	improved	activity
against	MRSA	that	is	less	susceptible	to	vancomycin,	but	its	place	in	therapy
is	still	being	determined.
Mechanism	of	Action
Glycopeptides	bind	to	terminal	D-ala-D-ala	chains	on	peptidoglycan	in	the	cell
well,	preventing	further	elongation	of	peptidoglycan	chains.	Telavancin	has	a
second	mechanism	where	the	drug	interferes	with	the	cell	membrane	also,
disrupting	membrane	function.
Good:	MSSA,	MRSA,	streptococci,	Clostridium	difficile
Moderate:	enterococci
Poor:	anything	Gram-negative
Adverse	Effects
Infusion-related	reactions:	A	histamine-mediated	reaction	called	red	man
syndrome	is	classically	associated	with	vancomycin.	When	it	occurs,	the
patient	may	feel	warm,	flushed,	and	may	develop	hypotension.	This
reaction	can	be	prevented	by	slowing	the	infusion	rate	and	is	not	a	true
allergy.	Antihistamines	can	also	ameliorate	the	reaction.	Because	the	core