Pulmonary Infections

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 with extended length of

hospital stay [LOS]– Recently, guidelines and/or standardized

order sets (SOSs) used by intensive clinical 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)

Multivariate analysis

Age > 80 yr 0.09 0.04–0.21 < 0.001

Liver cirrhosis 2.60 1.05–6.42 0.038

Diabetes 2.81 1.36–5.79 0.005

Creatinine level > 1.6 mg/dL 1.24 1.04–1.47 0.012

PaO2/FIO2 ratio < 250 2.58 1.24–6.10 0.002

Diastolic BP < 60 mm Hg 2.76 1.2–3.9 0.012

pH < 7.35 4.57 2.50–8.34 < 0.001

• The mortality rate was higher in ICU vs. non-ICU patients (37% vs. 20%, respectively; p = 0,003). – A low level of consciousness (OR, 3.95; 95% CI, 2 to 5) – Shock (OR, 24.7; 95% CI, 14 to 44) were associated with

a higher risk of death.

The modified ATS severity rule had the best accuracy in predicting ICU admission and mortality.

Valencia M, et al. Chest 2007;132:515–522.

Etiology of Community-Acquired Pneumonia Among Patients who Require Hospitalization

Organisms Overall (n = 457)

Non-ICU Patients(n = 365)

ICU Patients(n = 92)

Positive isolates, No. 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)

Moraxella catharralis 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)

Coxiella burnetti 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)

Polymicrobial 22 (10.8) 10 (7.2) 12 (18.7)

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.

BACKGROUNDHealthcare-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

Aisenberg G, et al. Eur J Clin Microbiol Infect Dis 2007;26:13-20.

• 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).

– Hospital-acquired S. maltophilia pneumonia was more common among neutropenic or ICU patients than non-neutropenic, non-CCU 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 non-neutropenic, non-ICU patients with cancer

Aisenberg G, et al. Eur J Clin Microbiol Infect Dis 2007;26:13-20.

Ventilator-Associated Pneumonia



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.


HAP/ VAP OUTBREAKSMULTIDRUG 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 ATS and Trouillet antibiotic treatment 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.

• The main reason was the failure to treat highly resistant strains.

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.


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 FactorsIn 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 De La Rosa et alet al. Eur J Clin Microbiol Infect Dis 2004;10:749-52.. Eur J Clin Microbiol Infect Dis 2004;10:749-52.

Diagnosis of Active Tuberculosis 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.

• 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.

Nontuberculous Pulmonary Mycobacteriosis

Fungal Lung Infections

Fungal conidia

Entrapped in mucus

Non-cellularDefense peptides(ALP, TAP,

Lysozyme)

Sp-A/DsIgA, CRPopsonization

Complementopsonization

Monocytes/Aveolar M

Lung parenchyma

PMN

Platelets

Cytokine production andrecruitment of

Inflammatory cells

Fungal conidia

Entrapped in mucus

Sp-A/DsIgA, CRPopsonization

ComplementopsonizationMonocytes/

Aveolar M

Lung parenchyma

PMN


Inflammatory cells

Conidial IFAFD

Conidial IFSODToxinsProteases

Chemotherapy-Induced damage of Respiratory epithelium

Dendritic cell

Migration to spleen/Other lymphoid organs

Blood vessel

Dissemination


Inflammatory cells

Hemorrhage/Necrosis

Blood vessel

Dissemination


Inflammatory cells

Hemorrhage/Necrosis

Angioneogenesis?

Migration to spleen/Other lymphoid organs

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 community-acquired 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.

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Pulmonary Infections