Antibiotics 2018
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Antibiotics 2018

DisciplinaFarmacologia Farmacêutica519 materiais4.128 seguidores
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pneumoniae).	To	combat	this	resistance,	the	ketolide	derivatives	(including
telithromycin)	have	been	introduced	with	better	coverage	of	resistant	S.
pneumoniae.	Unfortunately,	telithromycin	appears	to	have	a	significant	risk	of
hepatotoxicity.	Although	erythromycin	is	the	class	patriarch,	because	of	its
adverse	effects,	drug	interactions,	and	frequent	dosing,	it	has	little	use
except	as	a	GI	stimulant.
Mechanism	of	Action
Macrolides	and	ketolides	bind	to	the	50S	subunit	of	bacterial	ribosomes,
preventing	the	ribosomes	from	shuffling	along	and	adding	a	new	amino	acid
to	the	elongating	protein	chain.
Good:	atypicals,	Haemophilus	influenzae,	Moraxella	catarrhalis,
Helicobacter	pylori,	Mycobacterium	avium
Moderate:	S.	pneumoniae	(telithromycin	>	macrolides),	Streptococcus
Poor:	staphylococci,	enteric	GNRs	(azithromycin	>	clarithromycin),
anaerobes,	enterococci
Adverse	Effects
Adverse	Effects
Gastrointestinal:	Significant	GI	adverse	effects	(nausea,	vomiting,
diarrhea)	have	been	associated	with	the	macrolides.	Erythromycin	is	the
worst	offender\u2014it	is	employed	as	a	prokinetic	agent	for	patients	with
impaired	GI	motility.
Hepatic:	Rare	but	serious	adverse	hepatic	events	have	been	associated
with	the	macrolides.	Telithromycin	has	been	associated	with	hepatic
failure	leading	to	death	or	the	need	for	transplantation.
Cardiac:	Prolongation	of	the	QT	interval	has	been	seen	with	the
macrolides,	again	most	commonly	with	erythromycin.	Use	with	caution	in
patients	with	preexisting	heart	conditions,	those	on	antiarrhythmic	drugs,
or	those	taking	interacting	drugs	(see	next	section).
Important	Facts
Drug	interaction	alert!	These	drugs	(with	the	exception	of	azithromycin)
are	potent	inhibitors	of	drug-metabolizing	cytochrome	P450	enzymes.	Be
sure	to	screen	your	patient\u2019s	regimen	before	starting	these	agents.
Azithromycin	has	a	prolonged	half-life	such	that	a	short	course	may	be
adequate	for	most	infections.	This	makes	use	of	the	Z-pak	and	the
extended-release,	single-dose	Z-max	possible.
Macrolides	are	bacteriostatic	drugs	and	are	not	appropriate	for	infections
in	which	cidal	activity	is	usually	required	(meningitis,	endocarditis,	etc.).
Prevpac	is	a	combination	of	drugs	prescribed	for	eradication	of	H.	pylori
and	the	treatment	of	peptic	ulcer	disease.	In	addition	to	clarithromycin
and	lansoprazole,	it	contains	amoxicillin.	Be	sure	to	screen	patients	for
both	beta-lactam	allergies	and	drug	interactions	before	administering	it.
The	spectrum	of	activity	of	macrolides	makes	them	an	ideal	choice	for	the
treatment	of	community-acquired	pneumonia,	but	the	high	rates	of
resistance	in	S.	pneumoniae	make	them	risky	choices	as	monotherapy
for	patients	with	an	infection	that	is	any	worse	than	mild.	Treat	your	more
fragile	patients	with	something	else,	or	add	a	beta-lactam	active	against
S.	pneumoniae.
What	They\u2019re	Good	For
What	They\u2019re	Good	For
Upper	and	lower	respiratory	tract	infections,	chlamydia,	atypical
mycobacterial	infections,	and	traveler\u2019s	diarrhea	(azithromycin).
Clarithromycin	is	a	key	component	in	the	treatment	of	H.	pylori\u2013induced	GI
ulcer	disease	in	combination	with	other	drugs	and	acid-suppressive	agents.
Don\u2019t	Forget!
Sure,	macrolides	are	good	respiratory	tract	drugs	and	are	relatively	benign,
but	do	you	really	need	to	be	treating	your	patient\u2019s	nonspecific	(possibly	viral)
cough	and	cold	with	any	antibiotic?	Besides	causing	possible	adverse
reactions	and	wallet	toxicity,	overuse	of	these	drugs	has	contributed	to
increasing	resistance.	How	about	some	decongestants,	acetaminophen,	and
chicken	soup	instead?
14:	Oxazolidinones
Agents:	linezolid,	tedizolid
With	the	introduction	of	tedizolid,	there	are	now	two	oxazolidinones.	They
share	many	characteristics,	including	broad	Gram-positive	activity	and
excellent	oral	bioavailability.	Differences	between	the	agents	appear	to	be
minor,	though	linezolid	is	dosed	twice	daily	and	tedizolid	is	once	daily.
Linezolid	has	been	on	the	market	for	longer	and	has	an	advantage	over	other
agents	active	against	MRSA	in	its	clinical	trial	data	supporting	its	use	for
MRSA	pneumonia.
Mechanism	of	Action
Oxazolidenones	are	protein	synthesis	inhibitors	that	bind	to	the	50S
ribosomal	subunit,	blocking	the	formation	of	a	stable	70S	initiation	complex
and	preventing	translation.	This	binding	site	is	distinct	from	other	protein
synthesis	inhibitors.
Good:	MSSA,	MRSA,	streptococci	(including	multidrug-resistant
Streptococcus	pneumoniae),	enterococci	(including	VRE),	Nocardia
Moderate:	some	atypicals,	Mycobacterium	tuberculosis
Poor:	all	Gram-negatives,	anaerobes
Adverse	Effects
Both	drugs	are	generally	well	tolerated,	but	they	can	cause	bone	marrow
suppression,	most	commonly	thrombocytopenia.	Bone	marrow	suppression
tends	to	occur	after	2	or	more	weeks	with	linezolid	therapy	and	warrants
monitoring.	Tedizolid	seems	to	have	the	same	effects,	though	studies	of
longer	duration	are	limited.	With	linezolid,	it	is	known	that	peripheral
neuropathy	or	lactic	acidosis	may	occur	after	even	more	prolonged	therapy
(months)	because	of	toxicity	to	mitochondria.
Important	Facts
Linezolid	and	tedizolid	have	bioavailability	of	over	90%	and	oral
formulations	that	greatly	increases	their	utility.
Linezolid	is	an	inhibitor	of	monoamine	oxidase	(MAO)	and	can	cause
serotonin	syndrome	when	given	concurrently	with	serotonergic	agents
such	as	selective	serotonin	reuptake	inhibitors	(SSRIs)\u2014avoid	concurrent
use	if	possible.	Recent	evidence	has	shown	this	reaction	to	be
uncommon,	but	it	does	occur.	Animal	models	have	shown	tedizolid	to	have
minimal	if	any	MAO	inhibition	but	human	data	is	limited.
Linezolid	has	dual	hepatic	and	renal	elimination,	and	doses	do	not	need	to
be	adjusted	in	cases	of	renal	or	hepatic	dysfunction.	Tedizolid	is
eliminated	primarily	by	the	liver	and	may	not	be	sufficiently	concentrated
in	the	urine	to	treat	UTIs.
Tedizolid	was	studied	as	a	6-day	therapy	for	skin	and	skin	structure
infections	and	was	comparable	to	10	days	of	linezolid.	The	short	course
is	nice,	but	it	is	possible	that	shorter	courses	would	work	with	other	drugs
Linezolid	has	historically	been	very	expensive	but	recently	became
generic	and	prices	should	drop	substantially.	Either	way,	oral	formulations
are	less	expensive	and	more	convenient	than	home-infusion	vancomycin
and	a	nurse.
What	They\u2019re	Good	For
Infections	caused	by	resistant	Gram-positive	organisms	such	as	MRSA	and
VRE.	Linezolid	is	useful	for	pneumonia,	skin	and	skin	structure	infections,
UTIs,	and	other	uses.	Tedizolid	is	currently	only	indicated	for	skin	and	skin
structure	infections	but	may	be	useful	for	other	types.
Don\u2019t	Forget!
Monitor	patients	for	bone	marrow	suppression,	particularly	during	long-term
therapy.	Avoid	concurrent	serotonergic	drug	use	with	linezolid,	if	possible.
Remember	that	many	SSRIs	have	long	half-lives,	so	simply	discontinuing
SSRI	use	does	not	avoid	a	potential	interaction.	Monitor	patients	for	signs
and	symptoms	of	serotonin	syndrome	if	the	interaction	cannot	be	avoided.
15:	Nitroimidazoles
Agents:	metronidazole,	tinidazole
Nitroimidazoles	are	around	to	clean	up	organisms	that	the	big	drug	classes\u2014
penicillins,	cephalosporins,	fluoroquinolones,	macrolides,	etc.\u2014for	the	most
part	miss.	Worried	about	gut	anaerobes?	Metronidazole	is	there	for	you.
Thinking	about	parasites	in	your	patient	with	diarrhea?	Try	metronidazole	or
its	cousin	tinidazole,	which	has	a	spectrum	of	activity	similar	to	that	of
metronidazole	but	is	approved	only	for	parasitic	infections.	And	of	course,	if
you	have	gone	overboard	with	the	antibiotics	and	your	patient	has	(mild)
Clostridium	difficile	colitis,	turn	to	metronidazole.	Just	remember	the
limitations	of	these	drugs:	they	do	not	have	adequate	activity	against