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Diagnosis, Treatment and Prevention of Hospital Acquired Pneumonia

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Title: Diagnosis, Treatment and Prevention of Hospital Acquired Pneumonia


1
Diagnosis, Treatment and Prevention of Hospital
Acquired Pneumonia
  • Michael Zgoda, MD
  • Asst. Professor, Division of Pulmonary, Critical
    Care and Sleep Medicine
  • Director, Interventional Pulmonology
  • University of Kentucky, Lexington, KY

2
A Case Study
  • Day 1
  • A 76-year-old white male is sent to the local
    hospital from a long-term care (LTC) facility for
    evaluation of a pneumonic process
  • Past medical history reveals multiple admissions,
    with a history of diabetes, hypertension, and
    foot ulcer
  • The patient was discharged 10 days ago following
    a cholecystectomy.
  • The patient is admitted for pneumonia. Necessary
    blood work, cultures, and labs are performed.
    Ceftriaxone and azithromycin IV are started.

3
Chest X-Ray
4
A Case Study
  • Day 3
  • The patient is still febrile and has developed a
    cough (mucoid). He is uncomfortable and very
    restless. Staff notes that he is somewhat
    disoriented to time and place. The patient has no
    history of dementia
  • Follow-up information sent from the LTC facility
    shows that the patient has been on oral
    dicloxacillin, for previous infections, with poor
    results
  • Current laboratory test values denote increased
    white blood cell count and Gram-positive cocci

5
A Case Study
  • Days 5 to 7
  • The patients therapy was reviewed by the
    attending physician
  • Therapy was changed on day 3 by adding
    levofloxacin
  • At present the patient is worsening and requires
    intubation and mechanical ventilation
  • Several hours later he continues to spike
    temperatures at 102 degrees and becomes
    hypotensive despite 6 liters of lactated ringers
    IVF.
  • Pressors are started and the patient is then
    transferred to a tertiary care hospital

6
A Case Study
  • Day 7
  • Culture results from referring hospital reveal
  • Species of bacteria S aureus
  • Strain of bacteria MRSA
  • The patient is treated with appropriate
    antibiotics upon arrival to tertiary care
    hospital and the pneumonia resolves. He has a
    prolonged ICU stay of 28 days at which point the
    family decides to withdraw care because profound
    malnutrition and subsequent ICU associated
    complications from his underlying diabetes
    including a NSTEMI, pseudomonas sinusitis, and
    Pseudomembranous colitis with associated diarrhea
    and a stage 3 sacral ulcer requiring debridement.

7
Nosocomial Infections and Resistance
  • 2 million nosocomial infections per year in US
    hospitals
  • 60 involve antibiotic-resistant bacteria
  • Staphylococcus aureus is the most common overall
    bacterial cause of infection involving
    bloodstream, respiratory tract, and skin/soft
    tissue, according to the SENTRY Antimicrobial
    Surveillance Program
  • Strains of S aureus that have acquired resistance
    to ß-lactam antibiotics, most commonly through
    inheritance of the mecA resistance gene, are
    known as methicillin-resistant S aureus (MRSA)
  • MRSA accounts for 29 to 35 of all clinical
    isolates of S aureus in US and European hospitals
  • Estimated excess costs related to antibiotic
    resistance approach 30 billion per year in US
    hospitals

Haddadin AS et al. Postgrad Med J.
200278385-392. Diekema DJ et al. Clin Infect
Dis. 200132(suppl 2)S114-S132. Deresinski S.
Clin Infect Dis. 200540562-573. Zetola N et al.
Lancet Infect Dis. 20055275-286.
8
The MRSA Story
  • Infections due to gram-positive cocci, eg, S
    aureus, particularly MRSA, are
  • Rapidly emerging in the United States
  • More common in certain patient populations
  • Diabetes mellitus
  • Head trauma
  • Intensive-care unit (ICU)
  • ?50 of ICU infections (US) caused by S aureus
    are MRSA

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416.
9
Progression of Methicillin Resistance S aureus
Among Intensive Care Unit (ICU) Patients
63
CDC. Available at http//www.cdc.gov/ncidod/hip/A
RESIST/ICU_RESTrend1995-2004.pdf. Accessed August
30, 2005. Lowy FD. J Clin Invest.
20031111265-1273.
10
Definitions
  • Health care-associated pneumonia (HCAP)
  • Includes HAP and VAP
  • Pneumonia in patients
  • Hospitalized for ?2 days in an acute care
    facility within 90 days of infection
  • Residing in a nursing home or long-term care
    (LTC) facility
  • Attending a hospital or hemodialysis clinic
  • Receiving immunosuppressive therapy or wound
    care within 30 days of infection
  • Hospital-acquiredpneumonia (HAP)
  • Pneumonia occurring ?48 hours post-hospital
    admission
  • Ventilator-associated pneumonia (VAP)
  • Pneumonia occurring ?48-72 hours post-intubation

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416.
11
How Do Pathogens Find the Patient?
  • Routes of bacterial entry into the lower
    respiratory tract
  • Aspiration of oropharyngeal pathogens
  • Leakage around endotracheal tube cuff
  • Embolization of infected biofilm in the
    endotracheal tube to distal airways may play a
    role
  • Sources of infections
  • Healthcare devices
  • Environment (air, water, equipment, fomites)
  • Staff-patient/patient-patient transfer of
    microorganisms
  • Host- and treatment-related
  • colonization factors
  • Severity of underlying disease
  • Prior surgery
  • Exposure to antibiotics
  • Other medications
  • Exposure to invasive respiratorydevices and
    equipment

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416.
12
Most Common Isolates All ICU HAP vs VAP
20
18
18
18
18
17
16
All HAP

14
VAP

12
12
11
10
8
7
7
6
5
5
4
4
4
4
4
2
0
S aureus
Pseudomonas
Enterobacter spp
Klebsiella
Candida albicans
Escherichia coli
Haemophilus
aeruginosa
pneumoniae
influenzae
January 1992-May 1999. 1990-1995.
NNIS. Am J Infect Control. 199927520-532.
Fridkin SK et al. Infect Dis Clin North Am.
199711479-496.
13
Risk Factors for Multidrug-Resistant
(MDR)Pathogens Causing HAP, HCAP, and VAP
  • Antimicrobial therapy in preceding 90 days
  • Current hospitalization of ?5 days
  • High frequency of community or hospital-unit
    antibiotic resistance
  • Presence of risk factors for HCAP
  • Hospitalization for ?2 days in preceding 90 days
  • Residence in a nursing home or LTC facility
  • Home infusion therapy (including antibiotics)
  • Chronic dialysis within 30 days
  • Home wound care
  • Family member with MDR pathogen
  • Immunosuppressive disease and/or therapy

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416.
14
HAP, VAP, and HCAP Mortality
  • Crude mortality rate for HAP may be as high as
    30 to 70
  • However, many critically ill patients with HAP do
    not die of pneumonia, but rather of their
    underlying disease
  • Mortality attributable to HAP estimated at 33 to
    50
  • Increased mortality rates were associated with
  • Bacteremia
  • P aeruginosa or Acinetobacter spp
  • Medical, not surgical, illness
  • Ineffective antibiotic therapy

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416. Heyland DK et al. Am J Respir
Crit Care Med. 19991591249-1256.
15
Improving Outcomes
  • Prevention
  • Decreasing resistance
  • Improving our antibiotic selections

16
Benefits of Early, Appropriate Therapy
  • Cumulative evidence from multiple studies has
    demonstrated that early, appropriate therapy is
    associated with
  • Shorter duration of antibiotic therapy
  • Short-course therapy is only an option when the
    right antibiotic is used from the start
  • Decreased length of ICU or hospital stay
  • Lower total cost
  • Decreased mortality
  • Appropriate antimicrobial therapy reduces
    infection-related and all-cause
    mortality

Craven DE et al. Infect Dis Clin North Am.
200418939-962. Singh N et al. Am J Respir Crit
Care Med. 2000162505-511. Lodise TP et al. Cin
Infect Dis. 2003361418-1423.Kollef MH et al.
Chest. 1999115462-474.
17
Importance of Initial, Appropriate Antibiotic
Therapy
selection of initial appropriate antibiotic
therapy (ie, getting the antibiotic treatment
right the first time) is an important aspect of
care for hospitalized patients with serious
infections. ATS/IDSA Guidelines
A Study by Kollef and Colleagues Evaluating the
Impact of Inadequate Antimicrobial Therapy on
Mortality
60
52
Plt.001
50
42
40
Hospital Mortality ()
30
24
18
20
10
0
All-Cause Mortality
Infection-Related Mortality
Inadequate antimicrobial treatment (n169)

Adequate antimicrobial treatment (n486)

ATSAmerican Thoracic Society IDSAInfectious
Diseases Society of America.
Adapted from Kollef MH et al. Chest.
1999115462-474. ATS/IDSA. Am J Respir Crit Care
Med. 2005171388-416.
18
Initial Empiric Therapy in Patients Without Risk
Factors for MDR Pathogens
ESBLextended-spectrum ß-lactamase producer. The
frequency of penicillin-resistant S pneumoniae
and MDR S pneumoniae is increasing. Levofloxacin
or moxifloxacin are preferred to ciprofloxacin
and the role of other new quinolones, such as
gatifloxacin, has not been established.
Adapted from ATS/IDSA. Am J Respir Crit Care Med.
2005171401. Table 3.
19
Initial Empiric Therapy for Late-Onset Disease,
Risk Factors, or MDR Pathogens
Initial, Broad-Spectrum,
Potential Pathogens
Combination Antibiotic Therapy
Antipseudomonal cephalosporin or Antipseudomonal
carbepenem or ?-Lactam/?-lactamase
inhibitor plus Antipseudomonal fluoroquinolone or
Aminoglycoside
MDR pathogens P aeruginosa K pneumoniae
(ESBL) Acinetobacter spp Non-MDR,
gram-negative bacilli Legionella
pneumophila MDR, gram-positive cocci MRSA
plus Linezolid 600 mg q12h or Vancomycin 15
mg/kg q12h
Including pathogens from slide 19, (S
pneumoniae, H influenzae, MSSA, E coli, K
pneumoniae (ESBL-), Enterobacter spp, Proteus
spp, S marcescens. If an ESBL strain K
pneumoniae or MDR Acinetobacter spp is suspected,
a carbepenem is suggested as initial therapy. If
L pneumophila is suspected, the combination
antibiotic regimen should include a macrolide or
a fluoroquinolone rather than an
aminoglycoside. If MRSA is suspected or there is
a high incidence locally. Trough levels for
vancomycin should be 15 µg/mL to 20 µg/mL.
Adapted from ATS/IDSA. Am J Respir Crit Care Med.
2005171402. Tables 4 and 5.
20
Inpatient Antibiogram of SOMC
Special thanks to Timothy R. Cassity, Ph. D.
21
Outpatient Antibiogram SOMC (2004-2005)
Special thanks to Timothy R. Cassity, Ph. D.
22
Nursing Home Patients Antibiogram SOMC
Special thanks to Timothy R. Cassity, Ph. D.
23
Oxazolidinone Birth of a New Antimicrobial Agent
Class
  • 1987 First report of oxazolidinone family of
    molecules at the 27th ICAAC meeting. Early
    studies illustrated
  • Potent activity against Gram-positive organisms,
    including S aureus (MSSA and MRSA),
    Staphylococcus epidermidis, Streptococcus
    pneumoniae, and enterococci modest activity
    against a few fastidious Gram-negative bacteria
    was noted
  • Equally effective when administered orally
  • Novel inhibition of protein synthesis
  • 1995 25 presentations at the 35th ICAAC meeting,
    including the first phase I study results
  • 2000 FDA approval based on 9 trials in more than
    4000 patients

Ford CW et al. Curr Drug Targets Infect Disord.
20011181-199.
24
Linezolid Characteristics
A Small Molecule With Good Penetration Into Lung
and Skin Tissue
  • Available in oral and intravenous formulations
  • Oral formulation has 100 bioavailability
  • Has activity against most clinically important
    Gram-positive pathogens
  • Resistance remains uncommon
  • Linezolid inhibits bacterial protein synthesis
    through a mechanism of action different from that
    of the other antibacterial agents therefore,
    cross-resistance between linezolid and other
    classes of antibiotics is unlikely

Pharmacokinetics in healthy volunteers and in
vitro activity do not necessarily imply a
correlation with clinical effectiveness.
Conte JE Jr et al. Antimicrob Agents Chemother.
2002461475-1480. Adapted from French G. Int J
Clin Pract. 20015559-63. Meka VG et al. Clin
Infect Dis. 2004391010-1015.
25
Lung Penetration Concentration vs MIC90 of
Linezolid Against Gram-Positive Organisms
Epithelial lining fluid Plasma MIC90 S
aureus MIC90 Enterococcus spp MIC90 S pneumoniae
  • 5 doses of linezolid 600 mg q12h were
    administered orally to 25 healthy volunteers
  • Plasma and pulmonary epithelial lining fluid
    (ELF) linezolid concentrations exceeded MIC90 for
    staphylococci and streptococci through the dosing
    interval

Concentration (µg/L)
Time After Last Dose (h)
MIC90minimum concentration needed to inhibit 90
of organisms.
Adapted from Conte JE Jr et al. Antimicrob Agents
Chemother. 2002461475-1480.
26
Pharmacokinetic Characteristics of Linezolid in
Adults
27
Linezolid Pharmacokinetics in VAP
  • 16 critical-care patients with late-onset VAP (5
    days on the ventilator)
  • Pharmacokinetic profile was evaluated after 2
    days of linezolid (600 mg q12h IV) therapy. ELF
    samples were collected by mini-BAL brush

Steady State Concentrations in 16 VAP Patients
Boselli E et al. Crit Care Med. 2005331520-1533.
28
First Prospective Comparison of Linezolid vs
Vancomycin for Empiric Treatment of Nosocomial
Pneumonia (NP)
A randomized, double-blind, multicenter,
multinational, comparator-controlled trial to
compare the safety and efficacy of linezolid
versus vancomycin for NP
70
58
55
53
60
52
50
46
50
40
Clinical Cure ()
30
20
10
19/41
31/56
18/31
10/20
86/161
74/142
0
Intent-to-treat (ITT)
S aureus NP
MRSA NP
Vancomycin 1 g q12h IV
Linezolid 600 mg q12h IV
Safety and efficacy of linezolid versus
vancomycin were compared in 402 patients with NP,
including VAP 398 patients received at least 1
dose of study medication. Patients were treated
for 7 to 21 days, with optional aztreonam 1 g to
2 g q8h. Clinical cure rates were assessed 12 to
28 days after end of therapy.
Rubinstein E et al. Clin Infect Dis.
200132402-412. Data on file. Pfizer Inc.
29
Second Prospective Comparison of Linezolid vs
Vancomycin for Empiric Treatment of NP
A randomized, double-blind, multicenter,
multinational, comparator-controlled trial to
compare the safety and efficacy of linezolid
versus vancomycin for NP.
60
53
52
49
42
Clinical Cure ()
29
12/41
18/30
128/245
135/256
40/95
40/81
The safety and efficacy of linezolid IV versus
vancomycin IV were compared in 623 patients with
NP, including VAP. Patients were treated for 7 to
21 days, with optional aztreonam 1 g to 2 g q8h.
Clinical cure rates were assessed 15 to 21 days
after end of therapy.
Wunderink RG et al. Clin Ther. 200325980-992. Da
ta on file. Pfizer Inc.
30
Linezolid Demonstrates Excellent Efficacy in a
Retrospective Analysis of Two Prospective
Clinical Trials
A retrospective analysis of the combined results
from the 2 prospective, identical design trials
in 1019 patients with NP including
ventilator-associated pneumonia (VAP)
70
59
53
60
52
52
43
50
36
40
Clinical Cure ()
30
20
10
221/417
36/61
202/387
22/62
70/136
59/136
0
S aureus NP
ITT
MRSA NP
Linezolid 600 mg q12h IV
Vancomycin 1 g q12h IV
Linezolid was equally effective in the ITT and S
aureus NP populations (PNS). The outcome
difference in the MRSA NP subgroup is provided as
a descriptive measure only. No further inference
should be drawn due to the retrospective nature
of the analysis (Plt.01).
Wunderink RG et al. Chest. 20031241789-1797. Dat
a on file. Pfizer Inc.
31
Linezolid Demonstrates Excellent Efficacy in a
Retrospective Analysis of Two Prospective
Clinical Trials
A retrospective analysis of 544 patients with VAP
from the two prospective, identical design trials
in 1019 patients with NP.
62
49
45
37
35
Clinical Cure ()
21
103/227 76/207
23/37 7/33
43/88 32/91
Linezolid was equally effective in the ITT and S
aureus NP populations (PNS). The outcome
difference in the MRSA NP subgroup is provided as
a descriptive measure only. No further inference
should be drawn due to the retrospective nature
of the analysis (Plt.01).
Kollef MH et al. Intens Care Med.
200430388-394. Wunderink RG et al. Chest.
20031241789-1797. Data on file. Pfizer Inc.
32
Key Points About Vancomycin Recommendations
  • The new ATS/IDSA guidelines recommend dosing
    vancomycin by body weight (mg/kg) and adjusted
    for renal impairment
  • Monitor and adjust trough levels to maintain 15
    µg/mL to 20 µg/mL
  • Clinical trials report 40 or greater failure
    rate for MRSA pneumonia with vancomycin at
    standard dosing (1 g q12h)
  • No prospective clinical trials have shown the
    value of dosing vancomycin to achieve a trough
    level at 15 µg/mL or more
  • Combination therapy with vancomycin rifampin,
    or vancomycin aminoglycosides has not been
    proven effective in randomized controlled trials

ATS/IDSA. Am J Respir Crit Care Med.
2005171388-416. Craven DE, et al. Infect Dis
Clin North Am. 200418939-962.
33
Key Points About Linezolid in Treating MRSA HAP
  • linezolid is now recommended as empiric therapy,
    on a par with vancomycin, for late-onset HAP or
    for patients with risk factors for MRSA
  • Clinical setting where linezolid may be
    preferred
  • Patients at risk for, or already with, renal
    insufficiency
  • In these patients, physicians may have a stronger
    tendency to prescribe less adequate doses of
    vancomycin
  • Patients at increased risk of nephrotoxicity or
    on concomitant nephrotoxic drugs

ATS/IDSA. Am J Crit Care Med. 2005171388-416. Cr
aven DE et al. Infect Dis Clin North Am.
200418939-962.
34
Indication
  • Linezolid formulations are indicated for the
    treatment of infections caused by susceptible
    strains of the designated microorganisms
  • Pneumonia
  • Nosocomial pneumonia caused by Staphylococcus
    aureus (methicillin-susceptible and -resistant
    strains), or Streptococcus pneumoniae (including
    multi-drug resistant strains MDRSP).
    Combination therapy may be clinically indicated
    if the documented or presumptive pathogens
    include gram-negative organisms
  • Community-acquired pneumonia caused by
    Streptococcus pneumoniae (penicillin-susceptible
    strains only), including cases with concurrent
    bacteremia or S aureus (methicillin-susceptible
    strains only)

MDRSP refers to isolates resistant to 2 or more
of the following antibiotics penicillin,
second-generation cephalosporins, macrolides,
tetracycline, and trimethoprim/sulfamethoxazole.
35
Indication
  • Skin infection
  • Complicated skin and skin structure infections,
    including diabetic foot infections without
    concomitant osteomyelitis, caused by S aureus
    (methicillin-susceptible and -resistant strains),
    S pyogenes, or S agalactiae. linezolid has not
    been studied in the treatment of decubitus
    ulcers. Combination therapy may be clinically
    indicated if the documented or presumptive
    pathogens include gram-negative organisms
  • Uncomplicated skin and skin structure infections
    caused by S aureus (methicillin-susceptible only)
    or S pyogenes
  • Vancomycin-resistant Enterococcus
  • Vancomycin-resistant E faecium infections
    including cases with concurrent bacteremia

36
Important Safety Considerations Contraindications
  • Linezolid is contraindicated in patients who have
    known hypersensitivity to linezolid or any of the
    other product components
  • Warnings
  • Pseudomembranous colitis
  • Pseudomembranous colitis has been reported with
    nearly all antibacterial agents, including
    linezolid, and may range in severity from mild to
    life-threatening. It is important to consider
    this diagnosis in patients who present with
    diarrhea subsequent to the administration of any
    antibacterial agent

37
Important Safety Considerations Warnings
  • Myelosuppression
  • Myelosuppression (including anemia, leukopenia,
    pancytopenia, and thrombocytopenia) has been
    reported in patients receiving linezolid
  • In cases where the outcome is known, when
    linezolid was discontinued, the affected
    hematologic parameters have risen toward
    pretreatment levels
  • Complete blood counts should be monitored weekly
    in patients who receive linezolid, particularly
    in those who receive linezolid for longer than 2
    weeks, those with preexisting myelosuppression,
    those receiving concomitant drugs that produce
    bone marrow suppression, or those with a chronic
    infection who have received previous or
    concomitant antibiotic therapy
  • Discontinuation of therapy with linezolid should
    be considered in patients who develop or have
    worsening myelosuppression

38
Important Safety Considerations Precautions
  • Lactic acidosis
  • Lactic acidosis has been reported with the use of
    linezolid. In reported cases, patients
    experienced repeated episodes of nausea and
    vomiting. Patients who develop recurrent nausea
    or vomiting, unexplained acidosis, or a low
    bicarbonate level while receiving linezolid
    should receive immediate medical evaluation
  • Serotonin syndrome (linezolid serotonergic
    agent)
  • Spontaneous reports of serotonin syndrome
    associated with co-administration of linezolid
    and serotonergic agents, including
    antidepressants such as selective serotonin
    reuptake inhibitors (SSRIs), have been reported
  • Patients who are treated with linezolid and
    concomitant serotonergic agents should be closely
    observed for signs and symptoms of serotonin
    syndrome (eg, cognitive dysfunction,
    hyperpyrexia, hyperreflexia, incoordination)
  • If any signs or symptoms occur, physicians should
    consider discontinuation of either one or both
    agents (linezolid or concomitant serotonergic
    agents)

39
Important Safety Considerations Precautions
  • Peripheral/optic neuropathy
  • Peripheral and optic neuropathy have been
    reported in patients treated with linezolid,
    primarily those patients treated for longer than
    the maximum recommended duration of 28 days
  • In cases of optic neuropathy that progressed to
    loss of vision, patients were treated for
    extended periods beyond the maximum recommended
    duration
  • Visual blurring has been reported in some
    patients treated with linezolid for less than 28
    days
  • If patients experience symptoms of visual
    impairment, such as changes in visual acuity,
    changes in color vision, blurred vision, or
    visual field defect, prompt ophthalmic evaluation
    is recommended
  • Visual function should be monitored in all
    patients taking linezolid for extended periods
    (3 months) and in all patients reporting new
    visual symptoms regardless of length of therapy
    with linezolid
  • If peripheral or optic neuropathy occurs, the
    continued use of linezolid in these patients
    should be weighed against the potential risks

40
Important Safety Considerations Precautions
  • Drug interactions
  • Linezolid is a reversible nonselective inhibitor
    of monoamine oxidase. Therefore, linezolid has
    the potential for interaction with adrenergic and
    serotonergic agents
  • A reversible enhancement of the pressor response
    with either pseudoephedrine HCl or
    phenylpropanolamine HCl was observed when
    linezolid was administered to healthy
    normotensive subjects. Patients should inform
    their physician if they are taking medications
    containing pseudoephedrine HCl or
    phenylpropanolamine HCl, such as cold remedies
    and decongestants
  • A significant pressor response has been seen in
    normal adult subjects receiving linezolid and
    tyramine doses of more than 100 mg. Advise
    patients to avoid large quantities of foods or
    beverages with high tyramine content while taking
    linezolid

41
Important Safety Considerations Adverse Events
  • The most common adverse events include

42
DosingSpecial Populations
  • Renal insufficiency
  • The pharmacokinetics of the parent drug,
    linezolid, are not altered in patients with any
    degree of renal insufficiency
  • Both linezolid and its metabolites are eliminated
    by dialysis. Approximately 30 of dose was
    eliminated during a 3-hour dialysis therefore,
    linezolid should be administered after
    hemodialysis
  • Two primary metabolites may accumulate in
    patients with renal insufficiency in the absence
    of information on the clinical significance of
    metabolite accumulation, use of linezolid in
    patients with renal insufficiency should be
    weighed against the risks of metabolite
    accumulation
  • Because similar plasma concentrations of
    linezolid are achieved regardless of renal
    function, no dose adjustment is recommended for
    patients with renal insufficiency
  • Hepatic Insufficiency
  • No adjustment recommended for mild-to-moderate
    hepatic insufficiency
  • Pharmacokinetics in severe hepatic insufficiency
    have not been evaluated

43
Questions?
  • Opening Day April 7th

44
Summary
  • The progressive emergence of gram-positive
    organisms as dominant isolates in nosocomial
    infections has become a primary health care
    concern
  • As demonstrated, a multitude of risk factors
    exist for the development of MRSA, including
    previous hospitalization, longer length of stay
    before infection, previous surgery, enteral
    feedings, and previous use of antibiotics
  • Linezolid is an effective treatment for NP due to
    MRSA

Jones RN. Clin Infect Dis. 199929495-502. Graffu
nder EM et al. J Antimicrob Chemother.
200249999-1005.
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