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

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.

Chest X-Ray

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

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

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.

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 -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. 2002;78:385-392.

Diekema DJ et al. Clin Infect Dis. 2001;32(suppl 2):S114-S132.
Deresinski S. Clin Infect Dis. 2005;40:562-573.
Zetola N et al. Lancet Infect Dis. 2005;5:275-286.

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. 2005;171:388-416.

Progression of Methicillin Resistance:

S aureus Among Intensive Care Unit (ICU) Patients
63%

CDC. Available at: http://www.cdc.gov/ncidod/hip/ARESIST/ICU_RESTrend1995-2004.pdf.

Accessed August 30, 2005.
Lowy FD. J Clin Invest. 2003;111:1265-1273.

Definitions
Hospital-acquired
pneumonia (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. 2005;171:388-416.

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 longterm care (LTC) facility
Attending a hospital or
hemodialysis clinic
Receiving immunosuppressive
therapy or wound care within 30
days of infection

How Do Pathogens Find the Patient?

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 respiratory
devices and equipment

ATS/IDSA. Am J Respir Crit Care Med. 2005;171:388-416.

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

Most Common Isolates: All ICU HAP vs VAP

20
18

18

18

18
17

Pneumonia (%)

16

All HAP*

14
12

11

VAP

12

10
8

5
4

2
0
S aureus

Pseudomonas
aeruginosa

Enterobacter spp

*January 1992-May 1999. 1990-1995.

NNIS. Am J Infect Control. 1999;27:520-532.
Fridkin SK et al. Infect Dis Clin North Am. 1997;11:479-496.

Klebsiella
pneumoniae

Candida
albicans

Escherichia coli

Haemophilus
influenzae

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. 2005;171:388-416.

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. 2005;171:388-416.

Heyland DK et al. Am J Respir Crit Care Med. 1999;159:1249-1256.

Improving Outcomes

Prevention
Decreasing resistance
Improving our antibiotic selections

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. 2004;18:939-962.

Singh N et al. Am J Respir Crit Care Med. 2000;162:505-511.
Lodise TP et al. Cin Infect Dis. 2003;36:1418-1423.
Kollef MH et al. Chest. 1999;115:462-474.

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

Hospital Mortality (%)

60

*P<.001

52*

50

42*

40
30

24

20

18

10
0
All-Cause Mortality
Inadequate antimicrobial treatment
(n=169)

ATS=American Thoracic Society; IDSA=Infectious Diseases Society of America.

Adapted from Kollef MH et al. Chest. 1999;115:462-474.
ATS/IDSA. Am J Respir Crit Care Med. 2005;171:388-416.

Infection-Related Mortality
Adequate antimicrobial treatment
(n=486)

Initial Empiric Therapy in Patients

Without Risk Factors for MDR Pathogens
Potential Pathogens

Recommended Antibiotic

Streptococcus pneumoniae*
H influenzae
Methicillin-sensitive
S aureus (MSSA)

Ceftriaxone/Azithromycin
or
Levofloxacin, moxifloxacin, or
ciprofloxacin
or
Ampicillin/sulbactam
or
Ertapenem

Antibiotic-sensitive, enteric,
gram-negative bacilli
E coli
K pneumoniae (ESBL-)
Enterobacter spp
Proteus spp
Serratia marcescens

ESBL=extended-spectrum -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. 2005;171:401. Table 3.

Initial Empiric Therapy for Late-Onset Disease, Risk

Factors, or MDR Pathogens
Potential Pathogens
MDR pathogens*
P aeruginosa
K pneumoniae (ESBL+)
Acinetobacter spp
Non-MDR, gram-negative bacilli
Legionella pneumophila
MDR, gram-positive cocci
MRSA

Initial, Broad-Spectrum,
Combination Antibiotic Therapy

Antipseudomonal cephalosporin
or
Antipseudomonal carbepenem
or
-Lactam/-lactamase inhibitor
plus
Antipseudomonal fluoroquinolone
or
Aminoglycoside
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 g/mL to 20 g/mL.

Adapted from ATS/IDSA. Am J Respir Crit Care Med. 2005;171:402. Tables 4 and 5.

Inpatient Antibiogram of SOMC

Special thanks to Timothy R. Cassity, Ph. D.

Outpatient Antibiogram SOMC (2004-2005)

Special thanks to Timothy R. Cassity, Ph. D.

Nursing Home Patients Antibiogram SOMC

Special thanks to Timothy R. Cassity, Ph. D.

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. 2001;1:181-199.

Linezolid Characteristics
A Small Molecule With Good Penetration Into Lung and Skin Tissue
O
O

N
F

O
O

N
H

CH3

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. 2002;46:1475-1480.
Adapted from French G. Int J Clin Pract. 2001;55:59-63.
Meka VG et al. Clin Infect Dis. 2004;39:1010-1015.

Lung Penetration Concentration vs MIC90 of Linezolid Against

Gram-Positive Organisms

Plasma and pulmonary

epithelial lining fluid (ELF)
linezolid concentrations
exceeded MIC90 for
staphylococci and
streptococci through the
dosing interval

Epithelial lining fluid

Plasma

Concentration (g/L)

5 doses of linezolid
600 mg q12h were
administered orally to 25
healthy volunteers

MIC90 S aureus
MIC90 Enterococcus spp
MIC90 S pneumoniae

Time After Last Dose (h)

MIC90=minimum concentration needed to inhibit 90% of organisms.

Adapted from Conte JE Jr et al. Antimicrob Agents Chemother. 2002;46:1475-1480.

Pharmacokinetic Characteristics of Linezolid in Adults

Parameter

Effect

Oral bioavailability

100%

Ingestion of food

No dose adjustment

Volume of distribution

Total body water, 40 L to 50 L

Dosage formulations

IV, tablets, oral suspension (PO)

Distribution

Readily distributes into well-perfused tissues

Protein binding

31%, independent of drug concentration

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

Peak

Trough

Plasma (mg/L)

17.74

2.41.2

ELF (mg/L)

14.45.6

2.61.7

Boselli E et al. Crit Care Med. 2005;33:1520-1533.

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

Clinical Cure (%)

70
60

53

58

55

52

50

46

50
40
30
20
10
0

86/161 74/142

Intent-to-treat (ITT)

31/56

19/41

S aureus NP

Linezolid 600 mg q12h IV

18/31

10/20

MRSA NP
Vancomycin 1 g 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. 2001;32:402-412.
Data on file. Pfizer Inc.

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.

Clinical Cure (%)

70
60

60
53

52

50

49
42

40

29

30
20
10
0

135/256 128/245

ITT

40/81

40/95

S aureus NP
Linezolid 600 mg q12h IV

18/30

12/41

MRSA NP
Vancomycin 1 g q12h IV

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. 2003;25:980-992.
Data on file. Pfizer Inc.

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)

Clinical Cure (%)

70
60

59

53

52

52

50

43
36

40
30
20
10
0

221/417 202/387

70/136 59/136

ITT

S aureus NP

Linezolid 600 mg q12h IV

36/61

MRSA NP
Vancomycin 1 g q12h IV

Linezolid was equally effective in the ITT and S aureus NP populations (P=NS).
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 (P<.01).
Wunderink RG et al. Chest. 2003;124:1789-1797.
Data on file. Pfizer Inc.

22/62

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.

Clinical Cure (%)

62
49

45
37

35
21

103/227

76/207

43/88

Linezolid 600 mg q12h IV

23/37

32/91

Vancomycin 1 g q12h IV

Linezolid was equally effective in the ITT and S aureus NP populations (P=NS).
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 (P<.01).
Kollef MH et al. Intens Care Med. 2004;30:388394.
Wunderink RG et al. Chest. 2003;124:1789-1797.

7/33

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 g/mL to 20
g/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 g/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. 2005;171:388-416.

Craven DE, et al. Infect Dis Clin North Am. 2004;18:939-962.

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. 2005;171:388-416.

Craven DE et al. Infect Dis Clin North Am. 2004;18:939-962.

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 (penicillinsusceptible 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.

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 (methicillinsusceptible only) or S pyogenes
Vancomycin-resistant Enterococcus
Vancomycin-resistant E faecium infections including cases with concurrent bacteremia

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

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

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)

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

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

Important Safety Considerations

Adverse Events

The most common adverse events include:

Incidence (%) of Adverse Events Reported in 2% of Adult Patients in Comparator-Controlled
Clinical Trials with linezolid
linezolid
(n=2046)

All Comparators*
(n=2001)

Diarrhea

8.3

6.3

Headache

6.5

5.5

Nausea

6.2

4.6

Vomiting

3.7

2.0

Insomnia

2.5

1.7

Constipation

2.2

2.1

Rash

2.0

2.2

Dizziness

2.0

1.9

Fever

1.6

2.1

Event

*Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; clarithromycin 250 mg PO
q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomvcin 1 g IV q12h.

Dosing

Special 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

Questions?

Opening Day April 7th

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. 1999;29:495-502.

Graffunder EM et al. J Antimicrob Chemother. 2002;49:999-1005.