Transcript Slide 1

Pulmonary Infections
Amar Safdar, MD, FACP
Associate Professor of Medicine
M. D. Anderson Cancer Center
BACKGROUND
Community-Acquired Pneumonia
• Incidence 2 to 12 cases per 1,000 population
per year
• 600,000 admissions per year
• 4,200,000 inpatients days
• Annual cost > $8.4 billion
– –Mostly
associated
withand/or
extended
length of
Recently,
guidelines
standardized
hospital
stay(SOSs)
[LOS] used by intensive clinical
order sets
case management (ICCM) substantially
reduced LOS while maintaining quality of
care.
Fishbane S, et al. Arch Intern Med 2007;167:1664–1669.
Pneumonia Severity Index (PSI)
• The mortality rate was higher in ICU vs. non-ICU
patients
(37% vs. 20%, respectively; p = 0,003).
Multivariate
analysis
Age–>A
80low
yr
0.09 3.95;
0.04–0.21
0.001
level of consciousness (OR,
95% CI, 2< to
5)
Liver
1.05–6.42
0.038
– cirrhosis
Shock (OR, 24.7; 95% CI, 14 2.60
to 44) were
associated
with
Diabetes
2.81
1.36–5.79
0.005
a higher risk of death.
Creatinine level > 1.6 mg/dL
1.24
1.04–1.47
0.012
Pa /F ratio < 250
2.58
1.24–6.10
0.002
O2
IO2
The modified ATS severity rule had
the best
accuracy0.012
in
2.76
1.2–3.9
predicting ICU admission and4.57
mortality.
pH < 7.35
2.50–8.34
< 0.001
Diastolic BP < 60 mm Hg
Valencia M, et al. Chest 2007;132:515–522.
Etiology of Community-Acquired
Pneumonia Among Patients who
Require Hospitalization
Organisms
Positive isolates, No.
Overall
(n = 457)
Non-ICU Patients
(n = 365)
ICU Patients
(n = 92)
203
139
64
S pneumoniae
101 (49.7)
71 (51.1)
30 (46.8)
P aeruginosa
24 (11.8)
14 (10.1)
10 (15.6)
Haemophilus influenzae
22 (10.8)
16 (11.5)
6 (9.3)
Legionella pneumophila
10 (4.9)
7 (5)
3 (4.6)
Staphylococcus aureus
6 (2.9)
2 (1.4)
4 (6.2)
Escherichia coli
13 (6.4)
10 (7.2)
3 (4.6)
2 (1)
1 (< 1)
1 (1.5)
Chlamydia pneumoniae
5 (2.4)
4 (2.9)
1 (1.5)
Mycoplasma
pneumoniae
3 (1.5)
3 (2.1)
2 (1)
1 (< 1)
1 (1.5)
Virus
10 (4.9)
7 (5)
3 (4.6)
Others
7 (3.4)
3 (2.1)
4 (6.2)
22 (10.8)
10 (7.2)
12 (18.7)
Moraxella catharralis
Coxiella burnetti
Polymicrobial
CAP
Treatment Response
Treatment of Community-Acquired
Pneumonia
• A pathogen directed treatment (PDT) approach
compared with an empirical broad spectrum
antibiotic treatment (EAT) strategy.
– No significant differences were found between the
two treatment groups in LOS, 30 day mortality, clinical
failure, or resolution of fever.
– Side effects, occurred more frequently in patients in
the EAT group than in those in the PDT group (60% v
17%, 95% CI –0.5 to –0.3; p<0.00).
Van der Eerden MM, et al. Thorax 2005;60:672–678.
Long-Term Follow up of Patients
with Community-Acquired
Pneumonia
• In this case-control
study of Medicare
patients with CAP,
with five control
subjects matched for
age, sex, and race
with each case, the
in-hospital and 1-year
mortality rates for
patients with CAP
were significantly
higher than those for
control subjects.
Kaplan, V, et al. Arch Intern Med 2003; 163,317-323
Current CAP Core Measures for
Admitted Patients
•
•
•
•
•
First dose of antibiotics within 4 h of arrival to hospital
Oxygenation assessment within 24 h of hospital admission
Correct antibiotic for admitted patients Non-ICU
ICU – Includes no monotherapy
Blood cultures within 24 h for all patients admitted to ICU in
first 24 h
• Blood for cultures drawn prior to antibiotics administration for
those drawn in emergency department
• Evaluation and offering of pneumococcal and influenza
vaccination
• Smoking cessation advice
Niederman MS. Am J Med 2004;117:51S–57S.
BACKGROUND
Healthcare-Associated Pneumonia
Pieracci EM, et al. Am Surg 2007:73:419–432.
Community–Acquired MRSA
Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the United
States. MRSA rates are according to US Census Bureau Regions. Data are
cumulative data from 1998 to March 2005. IP, inpatient; OP, outpatient. Adapted
from Styers et al.
SCCmec 4 Subtypes:
[mecA gene located on a mobile
cassette chromosome]
•
HA-MRSA – subtype I–III
•
CA-MRSA – subtype IV–V
Kahl BC, Peters G. Science 2007;315:1082–1083.
In a retrospective study conducted in the
United States and taken from a large
multi-institutional database examined rates
of CAP, HCAP, ventilator-associated
pneumonia, and HAP.
Approximately 50% of patients had CAP and
more than 20% had HCAP, with S aureus
being a major causative pathogen.
Kollef MH, et al. Chest. 2005;128;6:3854-3862.
• Results of
nonbronchoscopic BAL
fluid cultures collected
within 4 h of ICU
admission in 95 elderly
nursing-home patients
with aspiration
pneumonia admitted to
the ICU. The dominant
organism group was
enteric Gram-negative
pathogens, and
anaerobes were less
common and often part
of a mixed infection.
El Solh, AA, et al. Am J Respir Crit Care Med 2003;167,1650-1654
Stenotrophomonas maltophilia
pneumonia
• Patients at risk for developing Stenotrophomonas maltophilia
pneumonia:
– Critical Care Unit stays
– Mechanical ventilation
– Neutropenia
• Non-neutropenic, non-ICU cancer patients (Cases) with S.
maltophilia pneumonia, compared with neutropenic, non-ICU
patients had [1997-2004]:
– Higher exposure to carbapenem antibiotics (58 vs. 41%; p <
0.03)
– More frequent hematologic malignancy (95 vs. 64%; p <
0.0003)
– Presented with concurrent bacteremia more often (23 vs. 0%; p
< 0.0005).
Aisenberg G, et al. Eur J Clin Microbiol Infect Dis 2007;26:13-20.
– Hospital-acquired S. maltophilia pneumonia was more common
among neutropenic or ICU patients than non-neutropenic, nonCCU cancer patients (98 vs. 61%; p < 0.000002).
– Among the cases: 34% received outpatient oral antimicrobial
therapy and 28% were admitted to the ICU.
– The mean duration of ICU stay, even among these eight patients
(19 +/- 40 days), was comparable to that of patients with
neutropenia (23 +/- 26 days) and those who developed S.
maltophilia pneumonia during their ICU stay (34 +/- 22 days; p =
0.46).
– The overall infection-associated mortality in the 108 cancer
patients with S. maltophilia pneumonia was 25%.
– 20% of patients without traditional risk factors for S. maltophilia
pneumonia died due to progressive infection.
– In a multivariate logistic regression analysis, only admission to the
ICU predicted death (odds ratio 33; 95% confidence interval,
4.51-241.2; p < 0.0006). The results of this study indicate S.
maltophilia pneumonia is a serious infection even in nonneutropenic, non-ICU patients with cancer
Aisenberg G, et al. Eur J Clin Microbiol Infect Dis 2007;26:13-20.
Ventilator-Associated
Pneumonia
Pieracci EM, et al. Am Surg 2007:73:419–432.
Pieracci EM, et al. Am Surg 2007:73:419–432.
Clinical Pulmonary Infection Score (CPIS)
• Temperature
• Leukocyte count
• CXR infiltrates
• Volume of tracheal secretions
• PaO2:FIO2
• Culture and GS of tracheal aspirate
[0-2 points each yields 12 points; > 6 points indicates high
probability of VAP]
The National Nosocomial Infection Surveillance system
diagnostic criteria for nosocomial pneumonia
The negative predictive value of a GS showing no organisms in a
clinically stable patient approaches 100%
J Trauma 2007;62:1377–1383.
J Trauma 2007;62:1377–1383.
Pieracci EM, et al. Am Surg 2007:73:419–432.
HAP/ VAP OUTBREAKS
MULTIDRUG RESISTANT [MDR]
ORGANISMS
Large outbreak of infection due to clonal
Multidrug-Resistant Acinetobacter
baumannii caused significant morbidity
and expense.
Aerosolization of MDR A. baumannii
during pulsatile lavage debridement of
infected wounds and during the
management of respiratory secretions
from colonized and infected patients may
promote widespread environmental
contamination.
Young LS, et al. Infect Control Hosp Epidemiol 2007
• Infection control measures included the
following:
– Limitations on the performance of pulsatile lavage
wound debridement
– The removal of items with upholstered surfaces
– The implementation of contact isolation for patients
with suspected MDR A. baumannii infection.
CONTROL HAP OUTBREAKS
Multifaceted infection control
interventions decrease spread and
colonization/infection due to MDR
organisms among hospitalized
patients.
The current recommendations for empirical antibiotic
treatment of hospital-acquired pneumonia (American
Thoracic Society and Trouillet) showed a good ability to
predict the involved pathogen.
• The main reason was the failure to treat
• highly
The ATS
and Trouillet
antibiotic treatment
resistant
strains.
recommendations were adequate in 79% and
80% of the patients, respectively.
• The microorganisms implicated in the treatment
inadequacy of the ATS guideline were
Pseudomonas aeruginosa, Acinetobacter
baumanii, Stenotrophomonas maltophilia and
methicillin-resistant Staphylococcus aureus.
Viral Pulmonary Infections
• Respiratory Viruses
– Influenza virus
– Parainfluenza virus
– Respiratory syncytial virus
– Adenovirus
– Metapneumonvirus
Increasing Drug-Resistant
H5N1
POSTVIRAL SUPERINFECTIONS
•
•
•
•
•
Streptococcus pneumoniae
Staphylococcus aureus
Pseudomonas spp.
Stenotrophomonas maltophilia
Fungal infections
CONCLUSIONS
• CAP and HAP leads to serious morbidity and substantially
increases healthcare cost.
• Inappropriate/discordant antimicrobial therapy increases
risk of complications, prolongs hospital stay, treatment
failure and death.
• In most patients, inappropriate therapy is given for
pulmonary infections due to MDR organisms.
• Effective, multifaceted infection control surveillance and
infection control measures are pivotal in reducing the risk
of these life-threatening infections.
Pieracci EM, et al. Am Surg 2007:73:419–432.
MYCOBACTERIAL INFECTIONS
Tuberculosis Background
• 8 million new cases of M. tuberculosis are
estimated to occur yearly adding to the existing
burden of 1.7 billion cases worldwide [One-third
of worlds population is now estimated to be infected
with this potentially devastating infection]
• In 1993, the World Health Organization declared
tuberculosis as public health emergency, as 3
million patients were expected to die annually due
to complications arising from tuberculosis, making it
the most frequent cause of death due to an
infectious organism.
• Man is the only known reservoir of M. tuberculosis.
Background
• In the US, reported M. tuberculosis declined during the 20th
century until 1985.
• The unanticipated rise in the newly diagnosed cases
between 1985 and 1992 was attributed to HIV-AIDS, illicit
drug use, homelessness, and ineffective tuberculosis
control programs in the large urban centers.
• Since 1992, the decline in M. tuberculosis cases was
attributed to re-implementation of effective public health
surveillance `programs with emphasis on 1) early diagnosis
(interrupt infection transmission in the community), and 2)
DOT (ensured compliance of adequate anti-tuberculosis
therapy).
• These measures led to the lowest ever recorded new
tuberculosis cases in 1997.
Risk Factors
In the developing world
• Protein-calorie malnutrition.
• Residents of overcrowded communities with
inadequate sanitation, and poor-ventilation.
• Silicosis.
• HIV-AIDS, which has now replaced
Mycobacterium tuberculosis as the most common
cause of death due to a single infectious agent.
Risk Factors
In the developed world
•
•
•
•
•
•
•
•
•
•
•
HIV-AIDS.
Homelessness, stay in homeless shelters.
Illicit drug use.
Incarceration in correctional facilities.
Nursing home residents.
Silicosis.
Substantial rapid weight loss.
Previous gastrectomy.
Prolonged systemic corticosteroids (> 15 mg prednisone/day).
Chronic end-stage renal disease.
Tumor necrosis factor inhibitor therapy for rheumatoid
arthritis such as Infliximab, Adalimumab, etc.
Risk Factors
• Cancer: Hodgkin’s Disease, gastric, head and neck
malignancies. We have recently described patients
with AML, CML, and NHL also at risk for developing
tuberculosis. [0.2/1000 new cancer diagnosis,
1.3/1000 new leukemia diagnosis]
• Organ-transplant recipients have higher rate of
infection compared with patients undergoing HSCT.
• Patients undergoing HSCT in high M. tuberculosis
endemic areas have increased risk of infection.
• In the US, M. tuberculosis reactivation remains a
concern in foreign-born patients undergoing
immunosuppressive antineoplastic therapy.
De La Rosa et al. Eur J Clin Microbiol Infect Dis 2004;10:749-52.
Diagnosis of Active Tuberculosis
Diagnosis of Active Tuberculosis
Nontuberculous Pulmonary
Mycobacteriosis
• Mycobacterium avium intracellulare complex
(MAC)
• Men age 50 to 75 years, chronic smoker,
and have chronic obstructive pulmonary
disease (COPD)
• Hot tub use [hypersensitivity pneumonitis]
Marchetti N, et al. Lung 2004;182:271–277.
Nontuberculous Pulmonary
Mycobacteriosis
• Women age 30 to 70 years.
• Bronchiectasis, scoliosis, mitral valve
prolapse, and pectus excavatum deformity
[Lady Windermere Syndrome]
• Interferon-gamma defect
• High rates of treatment refractory disease
and infection relapse after therapy is
discontinued
Safdar A, et al. American Journal of Medicine 2002;113:756–759.
Safdar A, et al. Annals of Internal Medicine 2003;138:521.
Fungal Lung Infections
Refractory, Relapsed CLL Following Allogeneic HSCT
Antifungal Therapy
• Reducing causative immune defect
– Resolution of neutropenia
– Resolution of GVHD
• Immune enhancement strategies
– Donor granulocyte transfusions
– Recombinant cytokines: GM-CSF, Interferon-gamma
• Antifungal drugs
– Triazoles: Voriconazole, Posaconazole
– Echinocandins: Caspofungin, Micafungin, Anidulafungin
Safdar A. Bone Marrow Transplantation 2006;
Safdar A, et al.
Community-Acquired MRSA is Associated With High
Prevalence of PVL Toxin
PVL is a pore forming exotoxin complex (LukSPV +
LukFVP) that causes leukocyte destruction and tissue
necrosis.
• It is present in 2% of S aureus clinical isolates, PVL
positive MRSA infections are prevalent in several clinical
settings:
–PVL genes are detected in virtually all communityacquired furunculosis infections
–PVL MRSA is associated with severe necrotic
hemorrhagic pneumonia in adults and children
Zetola N et al. Lancet Infect Dis. 2005;5:275-286.
Gillet Y et al. Lancet. 2002;359:753-759.
Gonzalez BE et al. Clin Infect Dis. 2005;41:583-590.
Lowy FD. N Engl J Med 1998;339:520.