Does anyone have any experience in taking Zyvox while doing a tune up?
Question: If pseudomonas is a gram negative bacteria and zyvox works on these
specifically why would it not be an FDA approved treatment option?
http://www.aafp.org/afp/2002/0215/p663.html#afp20020215p663-t3
Linezolid: Its Role in the Treatment of Gram-Positive, Drug-Resistant Bacterial
Infections
PAUL W. AMENT, PHARM.D., NAMIRAH JAMSHED, M.D., and JOHN P. HORNE, M.D., Latrobe
Area Hospital, Latrobe, Pennsylvania.
Am Fam Physician. 2002 Feb 15;65(4):663-671.
While the choices available for the management of gram-positive, drug-resistant
bacterial infections are becoming limited, antimicrobial resistance is becoming
increasingly problematic because of the widespread overuse of antibiotics.
Linezolid is a synthetic antibiotic belonging to a new class of antimicrobials
called the oxazolidinones. Linezolid disrupts bacterial growth by inhibiting the
initiation process of protein synthesis—a mechanism of action that is unique to
this class of drugs. It is well absorbed with high bioavailability that allows
conversion to oral therapy as soon as the patient is clinically stable. It has
been approved for certain gram-positive infections including certain
drug-resistant enterococcus, staphylococcus, and pneumococcus strains. It is
generally well tolerated, with myelosuppression being the most serious adverse
effect. As a nonselective inhibitor of monoamine oxidase, caution is recommended
when used with adrenergic or serotonergic agents (e.g., tyramine, dopamine,
pseudoephedrine, and selective serotonin reuptake inhibitors). Judicious use of
this medication should help physicians treat patients with multidrug-resistant
infections.
The growing antimicrobial resistance of certain microorganisms is now a
worldwide concern. The introduction of penicillin in 1944 was soon followed by
reports of resistance to Staphylococcus aureus. Physicians have encountered
problems with antimicrobial resistance ever since. During the 1970s, the problem
of drug-resistant, gram-negative bacteria and of methicillin-resistant S. aureus
emerged. Currently, the most pressing problem is that of multidrug-resistant,
gram-positive bacteria.
Factors Responsible for Antimicrobial Resistance
Multiple factors contribute to the development of resistance to antibiotics.
Their widespread and unnecessary use is the greatest contributing factor. It is
estimated that 50 million pounds of antibiotics are taken annually in the United
States1 and 30 percent of antibiotic prescriptions are for respiratory tract
infections, more than one half of which were probably viral.2 The increasing
problem of antimicrobial resistance in the hospital and the community parallels
the over-prescribing of antibiotics. Other contributing factors that have led to
changes in virulence, and thus, the development of resistance to antibiotics,
include societal changes (e.g., population growth and migration), an increasing
number of immunosuppressed patients, the globalization of food supplies and
changes in the way food is grown and produced, human behavior (e.g., widespread
and frequent international travel), and environmental changes (including
long-standing use of antibiotics in animal husbandry and agriculture).3
Resistance Problems Among Gram-Positive Organisms
The increasing resistance among gram-positive species is concerning because they
are responsible for one third of nosocomial infections.4 During the past two
decades, the prevalence of methicillin-resistant S. aureus increased from 2.0 to
39.7 percent in the United States.5 Between 1980 and 1989, the incidence of
bacteremia caused by coagulase-negative staphylococcal species, S. aureus, and
enterococcus increased by 176 and 124 percent, respectively.6 These three
pathogens are now the most common nosocomial-acquired causes of bacteremia.
Surveillance data report that nearly 79 and 25 percent of nosocomially acquired,
coagulase-negative staphylococcal species and S. aureus are
methicillin-resistant, respectively.6
The enterococcus species is recognized as a major nosocomial pathogen. During
the period of methicillin-resistant S. aureus emergence, enterococci became the
third most common cause of nosocomial infections.5 In 1993, it was reported that
13.9 percent of all enterococcal isolates were resistant to vancomycin
(Vancocin), representing a 20-fold increase from 1989.5 Previously, vancomycin
was often considered the final therapeutic option in cases in which resistance
to all other antibiotics was present. Unfortunately, the arrival of
vancomycin-resistant enterococcus changed this approach. Between 1990 and 1997,
the percentage of enterococcal species resistant to vancomycin increased from
less than 1 percent to 18 percent.7Enterococcus faecalis is responsible for 60
percent of these infections.8 A new threat of decreased susceptibility of S.
aureus to vancomycin now exists.8 This emerging resistance to vancomycin is
disturbing because it has been considered the last line of defense.
TABLE 1
Common, Antibiotic-Resistant Microorganisms
--------------------------------------------------------------------------------
Community-acquired resistantEscherichia coliHaemophilus
influenzaeMethicillin-resistant Staphylococcus aureusMultidrug-resistant
tuberculosisNeisseria gonorrheaNeisseria meningitidisSalmonella speciesShigella
speciesStreptococcus pneumoniaeStreptococcus viridans
Nosocomial-resistantBacteroides speciesCandida speciesCoagulase-negative
staphylococciEnterobacter speciesKlebsiella speciesMethicillin-resistant S.
aureusMultidrug-resistant tuberculosisProteus speciesPseudomonas
aeruginosaSerratia speciesVancomycin-resistant enterococci
--------------------------------------------------------------------------------
Adapted with permission from Hawkes CA. Antibiotic resistance: a clinician's
perspective. Mil Med 2000;165(7 suppl 2):43–5.
In the community setting, many antibiotic-resistant bacteria have emerged (Table
1).5 The prevalence of drug-resistant Streptococcus pneumoniae has increased
60-fold since 1980 with 51 percent and 8 percent of isolates demonstrating
intermediate- or high-level resistance to penicillin or third-generation
cephalosporins, respectively.9 Thus, pneumococcal pneumonia is becoming more
difficult to treat with first-line agents.
It is important to control the emergence of antimicrobial resistance and
minimize the inappropriate use of antibiotics through education. This is not a
small task and requires a multidisciplinary approach. All health care
professionals need to work toward the same goal. Some principles to control
antimicrobial resistance are outlined in Table 2.5
Against this background, newer therapeutic options are now available. Linezolid
(Zyvox), a novel antimicrobial agent, has been approved by the U.S. Food and
Drug Administration (FDA) primarily to fight resistant gram-positive cocci, such
as vancomycin-resistant enterococcus, methicillin-resistant S. aureus, and
penicillin-resistant pneumococci. Antibiotic therapy for these resistant
infections must be guided by laboratory testing; thus, appropriate cultures
should be obtained to determine the causative organism(s) and its susceptibility
to linezolid.
Mechanism of Action
Linezolid is a synthetic antibiotic belonging to a new class of antimicrobials
called the oxazolidinones. Linezolid disrupts bacterial growth by inhibiting the
initiation process in protein synthesis. This site of inhibition occurs earlier
in the initiation process than other protein synthesis inhibitors (e.g.,
chloramphenicol [Chloromycetin], clindamycin [Cleocin], aminoglycosides, and
macrolides) that interfere with the elongation process.10,11 Because the site of
inhibition is unique to linezolid, cross-resistance to other protein synthesis
inhibitors has not yet been reported.12 Linezolid may also inhibit virulence
factor expression and decrease toxin production in gram-positive pathogens.13
It is preferable to use an agent possessing bactericidal properties when
possible. It has been demonstrated that linezolid is bacteriostatic against
enterococci and staphylococci, and bactericidal for the majority of
streptococci.14
Pharmacokinetics
Linezolid is highly absorbed when administered orally, with a bioavailability of
approximately 100 percent.15 This allows conversion from intravenous to oral
therapy as soon as the patient is clinically stable; thus, it provides an
advantage over comparative therapy that can be delivered only parenterally
(i.e., vancomycin or quinupristin/dalfopristin [Synercid]). Linezolid is
metabolized via hepatic oxidation without any cytochrome P-450 pathways.
Elimination occurs through nonrenal, renal, and fecal mechanisms accounting for
65, 30, and 5 percent, respectively. The half-life is approximately five
hours.15 Generally, the dosing interval for an antibiotic is three times the
half-life—the dosing interval for linezolid is every 12 hours. Presently, no
dosage adjustment is recommended for patients with renal insufficiency; however,
linezolid is removed by hemodialysis and should be administered following
dialysis.14,15
Question: If pseudomonas is a gram negative bacteria and zyvox works on these
specifically why would it not be an FDA approved treatment option?
http://www.aafp.org/afp/2002/0215/p663.html#afp20020215p663-t3
Linezolid: Its Role in the Treatment of Gram-Positive, Drug-Resistant Bacterial
Infections
PAUL W. AMENT, PHARM.D., NAMIRAH JAMSHED, M.D., and JOHN P. HORNE, M.D., Latrobe
Area Hospital, Latrobe, Pennsylvania.
Am Fam Physician. 2002 Feb 15;65(4):663-671.
While the choices available for the management of gram-positive, drug-resistant
bacterial infections are becoming limited, antimicrobial resistance is becoming
increasingly problematic because of the widespread overuse of antibiotics.
Linezolid is a synthetic antibiotic belonging to a new class of antimicrobials
called the oxazolidinones. Linezolid disrupts bacterial growth by inhibiting the
initiation process of protein synthesis—a mechanism of action that is unique to
this class of drugs. It is well absorbed with high bioavailability that allows
conversion to oral therapy as soon as the patient is clinically stable. It has
been approved for certain gram-positive infections including certain
drug-resistant enterococcus, staphylococcus, and pneumococcus strains. It is
generally well tolerated, with myelosuppression being the most serious adverse
effect. As a nonselective inhibitor of monoamine oxidase, caution is recommended
when used with adrenergic or serotonergic agents (e.g., tyramine, dopamine,
pseudoephedrine, and selective serotonin reuptake inhibitors). Judicious use of
this medication should help physicians treat patients with multidrug-resistant
infections.
The growing antimicrobial resistance of certain microorganisms is now a
worldwide concern. The introduction of penicillin in 1944 was soon followed by
reports of resistance to Staphylococcus aureus. Physicians have encountered
problems with antimicrobial resistance ever since. During the 1970s, the problem
of drug-resistant, gram-negative bacteria and of methicillin-resistant S. aureus
emerged. Currently, the most pressing problem is that of multidrug-resistant,
gram-positive bacteria.
Factors Responsible for Antimicrobial Resistance
Multiple factors contribute to the development of resistance to antibiotics.
Their widespread and unnecessary use is the greatest contributing factor. It is
estimated that 50 million pounds of antibiotics are taken annually in the United
States1 and 30 percent of antibiotic prescriptions are for respiratory tract
infections, more than one half of which were probably viral.2 The increasing
problem of antimicrobial resistance in the hospital and the community parallels
the over-prescribing of antibiotics. Other contributing factors that have led to
changes in virulence, and thus, the development of resistance to antibiotics,
include societal changes (e.g., population growth and migration), an increasing
number of immunosuppressed patients, the globalization of food supplies and
changes in the way food is grown and produced, human behavior (e.g., widespread
and frequent international travel), and environmental changes (including
long-standing use of antibiotics in animal husbandry and agriculture).3
Resistance Problems Among Gram-Positive Organisms
The increasing resistance among gram-positive species is concerning because they
are responsible for one third of nosocomial infections.4 During the past two
decades, the prevalence of methicillin-resistant S. aureus increased from 2.0 to
39.7 percent in the United States.5 Between 1980 and 1989, the incidence of
bacteremia caused by coagulase-negative staphylococcal species, S. aureus, and
enterococcus increased by 176 and 124 percent, respectively.6 These three
pathogens are now the most common nosocomial-acquired causes of bacteremia.
Surveillance data report that nearly 79 and 25 percent of nosocomially acquired,
coagulase-negative staphylococcal species and S. aureus are
methicillin-resistant, respectively.6
The enterococcus species is recognized as a major nosocomial pathogen. During
the period of methicillin-resistant S. aureus emergence, enterococci became the
third most common cause of nosocomial infections.5 In 1993, it was reported that
13.9 percent of all enterococcal isolates were resistant to vancomycin
(Vancocin), representing a 20-fold increase from 1989.5 Previously, vancomycin
was often considered the final therapeutic option in cases in which resistance
to all other antibiotics was present. Unfortunately, the arrival of
vancomycin-resistant enterococcus changed this approach. Between 1990 and 1997,
the percentage of enterococcal species resistant to vancomycin increased from
less than 1 percent to 18 percent.7Enterococcus faecalis is responsible for 60
percent of these infections.8 A new threat of decreased susceptibility of S.
aureus to vancomycin now exists.8 This emerging resistance to vancomycin is
disturbing because it has been considered the last line of defense.
TABLE 1
Common, Antibiotic-Resistant Microorganisms
--------------------------------------------------------------------------------
Community-acquired resistantEscherichia coliHaemophilus
influenzaeMethicillin-resistant Staphylococcus aureusMultidrug-resistant
tuberculosisNeisseria gonorrheaNeisseria meningitidisSalmonella speciesShigella
speciesStreptococcus pneumoniaeStreptococcus viridans
Nosocomial-resistantBacteroides speciesCandida speciesCoagulase-negative
staphylococciEnterobacter speciesKlebsiella speciesMethicillin-resistant S.
aureusMultidrug-resistant tuberculosisProteus speciesPseudomonas
aeruginosaSerratia speciesVancomycin-resistant enterococci
--------------------------------------------------------------------------------
Adapted with permission from Hawkes CA. Antibiotic resistance: a clinician's
perspective. Mil Med 2000;165(7 suppl 2):43–5.
In the community setting, many antibiotic-resistant bacteria have emerged (Table
1).5 The prevalence of drug-resistant Streptococcus pneumoniae has increased
60-fold since 1980 with 51 percent and 8 percent of isolates demonstrating
intermediate- or high-level resistance to penicillin or third-generation
cephalosporins, respectively.9 Thus, pneumococcal pneumonia is becoming more
difficult to treat with first-line agents.
It is important to control the emergence of antimicrobial resistance and
minimize the inappropriate use of antibiotics through education. This is not a
small task and requires a multidisciplinary approach. All health care
professionals need to work toward the same goal. Some principles to control
antimicrobial resistance are outlined in Table 2.5
Against this background, newer therapeutic options are now available. Linezolid
(Zyvox), a novel antimicrobial agent, has been approved by the U.S. Food and
Drug Administration (FDA) primarily to fight resistant gram-positive cocci, such
as vancomycin-resistant enterococcus, methicillin-resistant S. aureus, and
penicillin-resistant pneumococci. Antibiotic therapy for these resistant
infections must be guided by laboratory testing; thus, appropriate cultures
should be obtained to determine the causative organism(s) and its susceptibility
to linezolid.
Mechanism of Action
Linezolid is a synthetic antibiotic belonging to a new class of antimicrobials
called the oxazolidinones. Linezolid disrupts bacterial growth by inhibiting the
initiation process in protein synthesis. This site of inhibition occurs earlier
in the initiation process than other protein synthesis inhibitors (e.g.,
chloramphenicol [Chloromycetin], clindamycin [Cleocin], aminoglycosides, and
macrolides) that interfere with the elongation process.10,11 Because the site of
inhibition is unique to linezolid, cross-resistance to other protein synthesis
inhibitors has not yet been reported.12 Linezolid may also inhibit virulence
factor expression and decrease toxin production in gram-positive pathogens.13
It is preferable to use an agent possessing bactericidal properties when
possible. It has been demonstrated that linezolid is bacteriostatic against
enterococci and staphylococci, and bactericidal for the majority of
streptococci.14
Pharmacokinetics
Linezolid is highly absorbed when administered orally, with a bioavailability of
approximately 100 percent.15 This allows conversion from intravenous to oral
therapy as soon as the patient is clinically stable; thus, it provides an
advantage over comparative therapy that can be delivered only parenterally
(i.e., vancomycin or quinupristin/dalfopristin [Synercid]). Linezolid is
metabolized via hepatic oxidation without any cytochrome P-450 pathways.
Elimination occurs through nonrenal, renal, and fecal mechanisms accounting for
65, 30, and 5 percent, respectively. The half-life is approximately five
hours.15 Generally, the dosing interval for an antibiotic is three times the
half-life—the dosing interval for linezolid is every 12 hours. Presently, no
dosage adjustment is recommended for patients with renal insufficiency; however,
linezolid is removed by hemodialysis and should be administered following
dialysis.14,15