Antibiotics 2018
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Antibiotics 2018

DisciplinaFarmacologia Farmacêutica522 materiais4.134 seguidores
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structure	of	telavancin	is	essentially	vancomycin,	it	may	cause	this
reaction	as	well.
Ototoxicity:	Vancomycin	has	historically	been	considered	an	ototoxic	drug,
but	evidence	linking	it	with	this	toxicity	is	unclear.
Renal:	Nephrotoxicity	is	an	adverse	effect	classically	assigned	to
vancomycin.	Although	the	historical	evidence	linking	this	with	vancomycin
is	poor,	recent	studies	have	shown	that	it	may	be	nephrotoxic	in	higher
doses,	including	the	higher	doses	that	are	commonly	used	to	treat	MRSA
infections	in	the	twenty-first	century.	The	early	formulation	of	vancomycin
was	brown,	and	clinicians	trying	to	amuse	themselves	dubbed	it
\u201cMississippi	mud.\u201d	The	current	formulation	is	clear	and	lacks	those
potentially	toxic	excipients.	Telavancin	has	renal	toxicity	issues	as	well.
Telavancin:	In	addition	to	the	above	reactions,	taste	disturbances	and
foamy	urine	occur	with	telavancin.	Telavancin	should	not	be	given	to
pregnant	women	because	of	problems	seen	in	animal	studies.
Dosing	Issues
Dosing	Issues
Vancomycin	is	often	pharmacokinetically	monitored.	Trough	concentrations
are	often	used	to	ensure	that	the	drug	is	not	being	eliminated	too	quickly	or
slowly,	and	different	indications	have	different	preferred	trough	ranges.
Recent	data	indicate	that	higher	troughs	may	be	associated	with
nephrotoxicity.	Peak	concentrations	are	only	useful	for	calculating	patient-
specific	pharmacokinetic	parameters.	They	do	not	seem	to	predict	efficacy
or	safety	and	should	not	be	drawn	for	most	patients.
Important	Facts
Oral	vancomycin	is	absorbed	very	poorly.	Its	only	use	is	for	the	treatment
of	Clostridium	difficile\u2013associated	disease.	Also,	IV	vancomycin	does	not
reach	intracolonic	concentrations	high	enough	to	kill	C.	difficile,	so	oral	is
the	only	way	to	go.
Oral	vancomycin	achieves	gut	concentrations	that	are	sky-high,	so	the
lowest	dose	is	the	best	one	for	the	majority	of	patients.
Do	not	overreact	if	your	vancomycin	trough	is	too	high.	Was	it	drawn
correctly?	If	so,	increase	your	dosing	interval.
Although	vancomycin	is	active	against	staphylococci,	it	does	not	kill	MSSA
as	quickly	as	beta-lactams	do.	Does	your	patient	have	MSSA?	Use
cefazolin	or	nafcillin	instead.
Recently,	a	phenomenon	described	as	\u201cMIC	creep\u201d	has	been	seen	with
staphylococci	and	vancomycin.	MICs	have	been	rising	to	vancomycin	in
many	institutions,	and	while	they	have	not	yet	reached	the	level	of
resistance,	they	are	increasing	within	the	range	labeled	as	susceptible,
that	is,	\u2264	2	mg/L.	However,	some	data	shows	that	patients	receiving
vancomycin	for	serious	infections	caused	by	staphylococci	with	an	MIC	=
2	mg/L	to	vancomycin	have	worse	outcomes	than	those	with	lower	MICs.
This	issue	warrants	careful	attention.
Telavancin	is	more	rapidly	bactericidal	than	vancomycin.	This	activity	may
be	an	advantage	in	the	treatment	of	some	infections,	but	clinical	evidence
that	shows	a	benefit	is	lacking	at	this	point.	It	may	be	useful	for	patients
not	responding	to	other	therapies	for	MRSA	infections.
Even	though	it	is	pregnancy	category	C,	telavancin	should	not	be	used	in
pregnant	women	unless	absolutely	necessary	since	developmental	issues
were	seen	in
What	They\u2019re	Good	For
Vancomycin	is	a	drug	of	choice	for	MRSA	infections	and	for	empiric	use
when	MRSA	is	a	concern,	such	as	for	nosocomial	pneumonia.	It	is	also	useful
in	other	Gram-positive	infections	when	the	patient	has	a	severe	beta-lactam
allergy.	Telavancin	is	indicated	for	skin	and	skin	structure	infections	and
hospital-acquired	pneumonia.	Its	role	is	still	being	defined.
Don\u2019t	Forget!
Are	you	sure	that	vancomycin	trough	concentration	was	drawn	correctly?
Mistimed	vancomycin	levels	are	very	common!
9:	Long-Acting	Glycopeptides
Agents:	dalbavancin,	oritavancin
Dalbavancin	and	oritavancin	are	unique	agent.	Pharmacologically,	they	start
with	the	base	structure	of	a	glycopeptide	and	have	been	designed	with
pharmacokinetic	characteristics	that	slow	their	elimination.	Both	can	be
dosed	intravenously	just	once	for	the	equivalent	of	2	weeks	of	therapy	since
each	has	a	half-life	of	over	a	week.
Both	drugs	have	strictly	Gram-positive	activity	that	includes	MRSA	and
streptococci.	This	begs	the	question	of	where	one	would	use	drugs	like
these?	Right	now,	they	are	both	indicated	for	infections	of	the	skin	and	skin
structure,	where	both	Staphylococcus	and	Streptococcus	cause	most
infections.	There	is	a	lot	of	appeal	to	giving	patients	just	one	dose	of	drug	for
a	full	course	of	therapy	(think	about	compliance!),	but	it	comes	with	a	price.
They	are	cheaper	than	a	hospital	admission,	but	the	cost	of	a	single	dose
could	buy	you	a	Hawaiian	vacation!
Mechanism	of	Action
All	glycopeptides	bind	to	terminal	D-ala-D-ala	chains	on	peptidoglycan	in	the
cell	well,	preventing	further	elongation	of	peptidoglycan	chains.
Lipoglycopeptides	have	a	second	mechanism	where	the	drug	interferes	with
the	cell	membrane	also,	disrupting	membrane	function.
Good:	MSSA,	MRSA,	streptococci,	enterococci	(oritavancin)
Moderate:	enterococci	(dalbavancin)
Poor:	anything	Gram-negative
Adverse	Effects
Adverse	Effects
In	clinical	trials,	nausea,	vomiting,	diarrhea,	and	rash	were	the	most	common
adverse	effects	with	both	drugs.	Infusion-related	reactions	can	occur	with
oritavancin	if	it	is	infused	quickly,	so	it	is	given	over	3	hours.
Oritavancin	inhibits	warfarin	metabolism	and	may	increase	the	risk	of
bleeding	when	given	with	it.
Important	Facts
The	prolonged	elimination	of	these	drugs	is	a	significant	advantage	that
can	enable	easy	outpatient	options	and	ensure	\u201ccompliance\u201d	(by	forcing	it
upon	the	patient	with	the	infusion).	However,	these	patients	still	need	to
be	monitored	for	both	treatment	success	and	adverse	effects.
Oritavancin	interferes	with	assays	for	prothrombin	time	(PT)	for	24	hours
and	activated	partial	thromboplastin	time	(aPTT)	for	48	hours,	which	are
used	to	monitor	warfarin	and	heparin,	respectively.	These	drugs	should
not	be	used	in	combination	with	oritavancin	during	those	time	periods
since	monitoring	will	be	unreliable.
Dalbavancin	has	different	dosing	depending	on	if	it	is	administered	twice
(1000	mg	on	day	1,	then	500	mg	a	week	later)	or	once	(1500	mg).	Why
would	one	use	the	two-dose	regimen,	you	ask?	We	don\u2019t	know,	but	it	was
studied	first.
What	They\u2019re	Good	For
Skin	and	skin	structure	infections	in	patients	whose	infections	are	either
known	or	highly	suspected	to	be	caused	by	Gram-positive	organisms.	The
paradigm	for	which	patients	are	best	for	these	interesting	drugs	is	still	being
Don\u2019t	Forget!
Patients	discharged	on	these	drugs	still	need	monitoring\u2014it\u2019s	not	just	\u201cset	it
and\u2026	forget	it!\u201d
10:	Fluoroquinolones
Agents:	ciprofloxacin,	levofloxacin,	moxifloxacin,
From	a	spectrum	of	activity	and	pharmacokinetic	standpoint,	many	of	the
fluoroquinolones	are	near-ideal	antibiotics:	they	have	broad-spectrum	activity
that	includes	Gram-positive,	Gram-negative,	and	atypical	organisms;	display
excellent	oral	bioavailability;	and	distribute	widely	into	tissues.	Unfortunately,
these	characteristics	have	led	to	overprescribing	and	the	inevitable	rise	in
resistance,	despite	recommendations	to	reserve	this	class.	In	particular,
although	activity	against	enteric	Gram-negative	organisms	(such	as
Escherichia	coli	and	Klebsiella)	historically	has	been	excellent,	in	some
geographical	regions	and	patient	populations	these	drugs	have	lost	much	of
their	activity,	and	they	are	no	longer	recommended	in	the	United	States	as
first-line	drugs	for	uncomplicated	urinary	tract	infections	(UTIs).	The	newer
drugs	(moxifloxacin,	gemifloxacin)	gain	increasing	Gram-positive	(mostly
pneumococcal)	activity	at	the	expense	of	some	Gram-negative	(mostly
Pseudomonas)	activity.	Significant	differences	among