Rizwana Khan MD PNEUMONIA COMMUNITY ACQUIRED PNEUMONIA Epidemiology 8 to 15 per 1000 persons per year Highest rates are at extremes of age There is seasonal variation, with more cases occurring during the winter months The rates of pneumonia are higher for men than for women, for black persons compared with Caucasians Pathogenesis Defect in host defenses Exposure to a particularly virulent microorganism An overwhelming inoculum Microaspiration is the most common mechanism Hematogenous spread from a distant site Direct spread from a contiguous focus Macroaspiration Bacterial virulence factors Chlamydophila pneumoniae produces a ciliostatic factor Mycoplasma pneumoniae can shear off cilia Influenza virus reduces tracheal mucus velocity within hours, for up to 12 weeks postinfection Streptococcus pneumoniae and Neisseria meningitidis produce proteases that can split secretory IgA Pneumococcus capsule inhibits phagocytosis; pneumolysin, neuraminidase, and hyaluronidase Mycobacterium spp, Nocardia spp, and Legionella spp, are resistant to the microbicidal activity of phagocytes Predisposing host conditions Alterations in the level of consciousness, which predispose to macro/ micro aspiration Alcohol consumption, Hypoxemia, Acidosis Toxic inhalations Pulmonary edema Uremia Malnutrition Solid organ or stem cell transplant recipients, or chemotherapy Mechanical obstruction of a bronchus Being elderly, there is a marked increase in the rate of pneumonia in persons ≥65 years Cystic fibrosis Bronchiectasis Chronic obstructive pulmonary disease (COPD) Previous episode of pneumonia or chronic bronchitis Immotile cilia syndrome Kartagener's syndrome (ciliary dysfunction, situs inversus, sinusitis, bronchiectasis) Young's syndrome (azoospermia, sinusitis, pneumonia) Drugs Increased risk with gastric acid-suppressive therapy, including proton pump inhibitors (PPIs) and H2 blockers Antipsychotic drugs associated with an almost 60 percent increase in the risk of pneumonia among elderly persons requiring hospitalization Current use of atypical (OR 2.61) or typical (OR 1.76) antipsychotic use was associated with a dose-dependent increased risk for CAP compared with past use Atypical antipsychotic use was also associated with an increase in the risk of fatal CAP (OR 5.97) Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. Laheij et al.JAMA.2004;292(16):1955-60 Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Gulmez et al. Arch Intern Med. 2007;167(9):950-5. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Sarkar et al. Ann Intern Med. 2008;149(6):391-8 Association of community-acquired pneumonia with antipsychotic drug use in elderly patients: a nested case-control study. Trifir et al. Ann Intern Med. 2010;152(7):418-25, W139-40. Microbiology Bacteria are the most common cause of CAP "Typical" organisms : S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria "Atypical― organisms: Legionella spp, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and C. psittaci A microbiologic diagnosis is confirmed in about 60 % of cases of CAP in research studies and in 20 % of cases in everyday practice Epidemiologic clues Know the local epidemiology and the patient's travel history (eg, endemic fungi such as Histoplasma, Coccidioides, Blastomyces, and Paracoccidioides spp; Hantavirus) Elicit history of specific exposures (eg, Histoplasma spp and bat or bird droppings, Chlamydophila psittaci and birds) Be aware of national and international outbreaks (eg, influenza or severe acute respiratory syndrome [SARS]) Never forget Mycobacterium tuberculosis Pneumocystis jirovecii is often forgotten as a cause of CAP Methicillin-resistant Staphylococcus aureus is an increasingly recognized cause of severe, occasionally necrotizing CAP Bacteria S. pneumoniae — most common cause of CAP but isolated in 5-18% H. influenzae — pneumonia in elderly adults and patients with cystic fibrosis and COPD M. pneumoniae —Infection rates are highest in school-aged children, military recruits, and college students Chlamydia pneumoniae — The infection is most common in those aged 65 to 79 years Legionella — Outbreaks associated with exposure to aerosol-producing devices, including showers, grocery store mist machine, cooling towers, whirlpool spas, and decorative fountains Community-associated methicillin-resistant S. aureus (CA-MRSA) is associated with severe necrotizing pneumonia CA-MRSA pneumonia may be associated with influenza infection Group A streptococcus —GAS, S. pyogenes can cause a fulminant pneumonia with early empyema formation young, immunocompetent hosts Anaerobes — may be the cause of aspiration pneumonia and lung abscess Neisseria meningitidis — an uncommon cause of CAP Pneumonia due to N. meningitidis should be reported to the health department and prophylaxis given as for meningitis or septicemia Mycobacterium tuberculosis — an important cause of CAP in developing countries and in some regions of the United States Other bacteria — Francisella tularensis (tularemia) and Coxiella burnetii (Q fever) Gram-negative bacilli — especially K. pneumoniae, Escherichia coli, Enterobacter spp, Serratia spp, Proteus spp, P. aeruginosa, and Acinetobacter spp, are uncommon causes of CAP except in patients with severe pneumonia requiring admission to an ICU where, as a group, they are among the most commonly isolated organisms after S. pneumoniae. Klebsiella pneumonia —in patients who have COPD, diabetes, and alcohol abuse Pseudomonas aeruginosa — Risk factors include bronchiectasis and the use of repeated antibiotic courses or prolonged glucocorticoids and in patients with COPD and pulmonary fibrosis Immunocompromise (eg, neutropenia, HIV infection, solid organ or hematopoietic stem cell transplantation) and previous hospitalization are other risk factors Acinetobacter spp —A. baumannii is emerging as a cause of severe CAP with high mortality Multidrug resistance is an increasing problem with Acinetobacter infection Moraxella catarrhalis —70% have predisposing factors such as neutropenia, malignancy, or COPD or malnutrition S. aureus — in elderly adults and in younger patients who are recovering from influenza (postinfluenza pneumonia) Viruses Influenza virus — Influenza A or B viruses cause an acute respiratory illness that occurs in outbreaks and epidemics, mainly in the winter season Influenza pneumonia occurs most frequently in patients with heart or lung disease, diabetes mellitus, renal disease, hemoglobinopathy, or immunosuppression; residents of nursing homes or chronic care facilities; and otherwise healthy individuals over age 65 Parainfluenza virus — in immunocompromised adults Respiratory syncytial virus —causes acute respiratory tract illness in persons of all ages Adenovirus — Adenoviral pneumonia was first described among military recruits in whom it causes an "atypical pneumonia― Human metapneumovirus — (HMPV) was first described in 2001 in the Netherlands. Symptomatic disease most often occurs in the young children or older adults Severe acute respiratory syndrome (SARS) — In November 2002, an outbreak started in Guangdong Province in southern China and spread worldwide affecting more than 8,000 persons. SARS was due to a novel coronavirus that jumped the species barrier from civet cats to man. The case fatality rate of the 2003 Hong Kong outbreak was 11%, but higher mortality was seen in elderly adults (≥60 years of age) and pregnant women Hantavirus — The illness is preceded by prodromal flu-like symptoms followed by noncardiogenic pulmonary edema and ARDS-like picture The virus is spread to humans from infected mice Avian influenza — The first association of avian influenza H5N1 with clinical respiratory disease occurred in Hong Kong in 1997, when 18 human cases occurred during a poultry outbreak of highly pathogenic H5N1 influenza in live-bird markets The WHO and the CDC consider avian influence a potential source for the next global influenza pandemic Varicella — Varicella pneumonia is the most frequent complication of varicella infection in normal healthy adults The case fatality rate is between 10 and 30 percent Fungi More common in the immunocompromised patient, particularly those with neutropenia, on chronic immunosuppressive therapy (eg, organ transplant recipients), and those infected with HIV Cryptococcus spp — found in the soil throughout the world In immunocompetent individuals, primary infections are usually discovered as an incidental finding on chest radiograph Cryptococcal pneumonia in immunocompromised patients is symptomatic with cough, fever, and dyspnea Histoplasma capsulatum — infection is most common in the Midwestern states located in the Ohio and Mississippi River valleys H. capsulatum proliferates best in soil contaminated with bird or bat droppings Symptomatic patients with acute histoplasmosis generally present with a flu-like illness with pulmonary complaints and radiographic abnormalities Coccidioides spp — endemic to certain lower deserts of the western hemisphere including southern Arizona, central California, southwestern New Mexico, and west Texas. They are also found in parts of Mexico, Central, and South America Other fungi — include Aspergillus spp and Pneumocystis jirovecii (formerly P. carinii) Clinical evaluation Cough, fever, pleuritic chest pain, dyspnea and sputum production Mucopurulent sputum production is most frequently found in association with bacterial pneumonia, while scant or watery sputum production is more suggestive of an atypical pathogen Gastrointestinal symptoms (nausea, vomiting, diarrhea), and mental status changes Chest pain occurs in 30 %, chills in 40 to 50%, and rigors in 15% On physical examination, approximately 80% are febrile A respiratory rate above 24 breaths/minute is noted in 45 to 70 % and may be the most sensitive sign in elderly patients; tachycardia is also common Chest examination reveals audible rales in most patients, while approximately one-third have evidence of consolidation The major blood test abnormality is leukocytosis (typically between 15,000 and 30,000 per mm3) with a leftward shift. Leukopenia can occur, and generally connotes a poor prognosis Radiologic evaluation A n infiltrate by chest radiograph or other imaging technique is required for the diagnosis Recommendations are less clear in what appears to be a viral infection with nasal congestion and cough; one approach in these cases is to obtain a chest x-ray when there is an abnormal vital sign with particular emphasis on a respiratory rate >20/min or a fever If the clinical syndrome favors pneumonia but the radiograph is negative, the radiograph may represent a false negative result. CT scan has higher sensitivity and accuracy for detecting CAP Volume depletion may produce an initially negative radiograph, which "blossoms" into infiltrates following rehydration (7% of patients ) For hospitalized patients with suspected pneumonia and a negative chest radiograph, it is reasonable to initiate empiric presumptive antibiotic therapy and repeat the chest radiograph in 24 to 48 hours Alternatively, a CT scan could be performed in patients with a negative chest radiograph when there is a high clinical suspicion for pneumonia Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Diagnostic testing for microbial etiology For outpatients with CAP, routine diagnostic tests are optional Hospitalized patients with specific indications should have blood cultures and sputum Gram stain and culture, or other tests as indicated diagnostic tests are optional for other hospitalized patients without severe CAP Patients with severe CAP requiring ICU admission should have blood cultures, urinary antigen tests, and sputum Some microbes are critical to detect because they require treatment different from standard empiric regimens: Legionella species Influenza, including avian influenza Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) Agents of bioterrorism Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Hospitalized patients Diagnostic yield of microbiologic tests in hospitalized patients with CAP: Pathogen identified -- 60 percent patients Adequate sputum samples obtained --15 percent Gram stain positive -- 82 percent Urinary pneumococcal antigen test positive -- 54 percent patients with pneumococcal pneumonia Blood cultures positive -- 16 percent Bronchoscopy is of additive diagnostic value – in 49 percent who do not expectorate sputum and 52 percent who fail treatment within 72 hours Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Blood cultures Pretreatment blood cultures are positive -- 7 to 16 percent of hospitalized patients Blood cultures are commonly advocated in hospitalized patients with CAP because: The microbial diagnosis is established This is the only diagnostic test done, in most cases The isolates identified are used for tracking resistance patterns of S. pneumoniae and to determine serotypes of S. pneumoniae to evaluate contemporary and future vaccines Counter arguments for not obtaining these tests are that: The blood culture positivity rate is relatively low There is a high rate of false positive blood cultures (10%) Positive cultures rarely lead to modification or narrowing of antibiotic therapy Variables associated with bacteremia included absence of prior antibiotic use, chronic liver disease, pleuritic pain, tachycardia (>125 beats per minute), tachypnea (>30 breaths per minute), and systolic hypotension (<90 mm Hg) The guidelines recommend blood cultures for hospitalized patients with specific indications, including all patients who require admission to the ICU for CAP, and consider them optional for other patients Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Sputum Sputum specimens are recommended for hospitalized patients with any of the following criteria: Intensive care unit admission Failure of antibiotic therapy (either outpatients or hospitalized patients) Cavitary lesions Active alcohol abuse Severe obstructive or structural lung disease Positive urine antigen test for pneumococcus Positive urine antigen test for Legionella (special culture needed) Pleural effusion The sensitivity of Gram stain compared to culture ranged from 15 to 100% and specificity 11 to 100% Culture results should be interpreted based upon the following findings: Quantitation of growth (heavy, moderate or light) Clinical correlation Correlation with the Gram stain Specimens collected after antibiotics are given are more likely to grow S. aureus or gram- negative bacilli (GNB), which usually represent early airway contaminants Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Urine antigen Advantages: More sensitive and specific than Gram stain and culture of sputum Urine specimens are usually available in the 30 to 40 % of patients who cannot supply sputum Results of urine antigen testing are immediately available The test retains validity even after the initiation of antibiotic therapy The test has high sensitivity compared with blood cultures and sputum studies The urinary antigen tests for Legionella and S. pneumoniae are FDA-cleared and provide results in minutes Disadvantages of the urine antigen assay for the diagnosis of pneumococcus : The sensitivity and specificity may be less in patients without bacteremia There is no microbial pathogen available for antibiotic sensitivity testing These tests require a licensed technician and cannot be done by the provider Disadvantage of the urine antigen assay for the diagnosis of Legionella Only useful for the diagnosis of L. pneumophila group 1 infection (accounts for 80 % CAP) Nosocomial Legionella infections often involve other serotypes, so sensitivity is decreased Pneumococcal urinary antigen test sensitivity and specificity of 82 and 97%, respectively Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 PCR/procalcitonin/CRP Diagnosis determined in 50 % patients by conventional techniques vs 76 %patients by RT-PCR Procalcitonin is a peptide precursor of calcitonin that is released by parenchymal cells in response to bacterial toxins, leading to elevated serum levels in patients with bacterial infections in contrast, procalcitonin is down-regulated in patients with viral infections In two trials, clinicians were strongly recommended not to prescribe antibacterials in patients with a procalcitonin level <0.1 mcg/L, but were encouraged to in patients with levels >0.25 mcg/L The analysis suggested the correct decision in 83 percent. In one small study, procalcitonin levels increased over time in non-survivors but decreased in survivors CRP has shown more limited utility, due in part to the paucity of studies One study showed a CRP >40 mg/L had a sensitivity and specificity for bacterial pneumonia of 70 and 90%, respectively Another report indicated particularly high CRP levels in patients with pneumococcal pneumonia (mean 178 mg/L) Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Indications for hospitalization The two most commonly used prediction rules are the Pneumonia Severity Index (PSI) and CURB-65 CURB-65 uses five prognostic variables: Confusion (based upon a specific mental test or disorientation to person, place, or time) Urea (blood urea nitrogen in the United States) >7 mmol/L (20 mg/dL) Respiratory rate >30 breaths/minute Blood pressure (systolic <90 mmHg or diastolic <60 mmHg) Age >65 years score of 0 to 1 are at low risk and could be treated as outpatients score of 2 should be admitted to the hospital score of 3 or more should be assessed for ICU care, particularly if the score was 4 or 5 Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Lim ET AL.Thorax. 2003;58(5):377-82. CRB-65 predicts death from community-acquired pneumonia. Bauer ET AL. J Intern Med. 2006;260(1):93-101 Principles of antimicrobial therapy Empiric therapy The selection of antimicrobial regimens is based upon: The most likely pathogen(s) Clinical trials proving efficacy Risk factors for antimicrobial resistance The choice of empiric therapy must take into account the emergence of antibiotic resistance among Streptococcus pneumoniae Medical comorbidities Potential for inducing antimicrobial resistance, pharmacokinetic and pharmacodynamic properties, safety profile, and cost Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 Risk factors for drug-resistant S. pneumoniae in adults Age >65 years Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months Alcoholism Medical comorbidities Immunosuppressive illness or therapy Exposure to a child in a day care center Recent therapy or a repeated course of therapy with beta-lactams, macrolides, or fluoroquinolones is a risk factor for pneumococcal resistance to the same class of antibiotic Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 GUIDELINES Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27 No comorbidities or recent antibiotic use Azithromycin (500 mg on day one followed by four days of 250 mg a day) 500 mg a day for three days, or 2 g single dose (microsphere formulation) are acceptable alternative regimens Clarithromycin XL (two 500 mg tablets once daily) for five days or until afebrile for 48 to 72 hours Doxycycline (100 mg twice a day) for 7 to 10 days The use of fluoroquinolones is discouraged unless there is a high prevalence of macrolide-resistant S. pneumoniae Comorbidities or recent antibiotic use • A respiratory fluoroquinolone (gemifloxacin 320 mg daily, levofloxacin 750 mg daily, or moxifloxacin 400 mg daily) • Combination therapy with a beta-lactam effective against S. pneumoniae • High-dose amoxicillin, 1 g three times daily or amoxicillin-clavulanate 2 g twice daily or cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily) • PLUS • A macrolide (azithromycin 500 mg on day one followed by four days of 250 mg a day or clarithromycin 250 mg twice daily or clarithromycin XL 1000 mg once daily) • Or doxycycline (100 mg twice daily) Treatment duration and response Ambulatory patients with CAP should be treated for a minimum of five days A meta-analysis of RCT of 2800 patients with mild to moderate CAP, found comparable clinical outcomes with less than seven days compared to more than seven days of antimicrobial therapy Antibiotic therapy should not be stopped until the patient is afebrile for 48 to 72 hours and is clinically stable Persistence of some symptoms is not an indication to extend the course of antibiotic therapy as long as the patient has demonstrated some clinical response to treatment Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Li et al. Am J Med. 2007;120(9):783-90. Time course of symptom resolution in patients with community-acquired pneumonia. Metlay et al. Respir Med. 1998;92(9):1137-42. Follow-up Routine chest x-rays for patients who are responding clinically are unnecessary Some recommend a follow-up chest x-ray at 7 to 12 weeks, for patients over age 40 years or smokers, to document resolution of the pneumonia and exclude malignancy Among patients with CAP, nonresponse is primarily seen in those who require hospitalization, occurring in 6 to 15% of such patients VACCINATION — Patients with CAP should be appropriately vaccinated for influenza and pneumococcal infection SMOKING CESSATION — Smoking cessation should be a goal for patients with CAP who smoke Practice guidelines for the management of community-acquired pneumonia in adults. Bartlett at al. Infectious Diseases Society of America. Clin Infect Dis 2000; 31:347 Hospitalized patients In the general wards -- an antipneumococcal fluoroquinolone (eg, levofloxacin, moxifloxacin) or the combination of a beta-lactam plus a macrolide ICU admission -- a beta-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam) plus either intravenous azithromycin Or an antipneumococcal fluoroquinolone If Pseudomonas is a concern, an antipseudomonal agent (piperacillin-tazobactam, imipenem, meropenem, or cefepime) PLUS an antipseudomonal fluoroquinolone (ciprofloxacin or high-dose levofloxacin) should be used If MRSA is a concern, either vancomycin or linezolid should be added Not in the ICU Combination therapy ceftriaxone (1 to 2 g IV daily),cefotaxime (1 to 2 g IV every eight hours), or ampicillin- sulbactam (1.5 to 3 g IV every six hours) plus a macrolide (azithromycin [500 mg IV or orally daily] or clarithromycin XL [two 500 mg tablets once daily]) Doxycycline (100 mg orally or IV twice daily) may be used as an alternative to a macrolide Oral therapy with a macrolide or doxycycline is appropriate only for selected patients without evidence of or risk factors for severe pneumonia Monotherapy with a respiratory fluoroquinolone given either IV or orally (levofloxacin 750 mg daily or moxifloxacin 400 mg daily or gemifloxacin 320 mg daily Admitted to an ICU Intravenous combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone 2 g daily, cefotaxime 2 g every eight hours, or ampicillin-sulbactam 1.5 to 3 g every six hours) PLUS either an advanced macrolide (azithromycin 500 mg daily) or a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg) In patients (particularly those with bronchiectasis or COPD and frequent antimicrobial or glucocorticoid use) who may be infected with Pseudomonas aeruginosa or other resistant pathogens: therapy with a beta-lactam and a fluoroquinolone, such as the following regimens: Piperacillin-tazobactam (4.5 g every six hours) OR Imipenem (500 mg IV every six hours) OR Meropenem (1 g every eight hours) OR Cefepime (2 g every eight hours) OR Ceftazidime (2 g every 8 hours) PLUS Ciprofloxacin (400 mg every 8 hours) OR Levofloxacin (750 mg daily) For beta-lactam allergic patients, options include: aztreonam (2 g every 6 hours) plus levofloxacin (750 mg daily) or aztreonam plus moxifloxacin plus an aminoglycoside If the Gram stain suggests S. aureus,treat MRSA with the addition of vancomycin (15 mg/kg every 12 hours, adjusted for renal function) Or linezolid (600 mg intravenously twice daily) until the results of culture and susceptibility testing are known empiric therapy of MRSA in patients with severe CAP who have risk factors for CA-MRSA (prior antimicrobial therapy or recent influenza-like illness) CA-MRSA CA-MRSA is susceptible to more antibiotics than HA-MRSA, but is more virulent TX with Vancomycin or linezolid is recommend Increasing MICs of MRSA may reduce the efficacy of vancomycin in pulmonary infection Linezolid has been shown to reduce toxin production Risk factors for CA-MRSA colonization: contact sport participants, injection drug users, those living in crowded conditions, men who have sex with men, prisoners CA-MRSA pneumonia should be suspected in young, previously healthy adults with a recent influenza-like illness Factors associated with rapid mortality include infection with influenza, the need for ventilator or inotropic support, onset of respiratory distress syndrome, hemoptysis, and leukopenia Timing of antimicrobial initiation The United States National Pneumonia Medicare Quality Improvement Project and the National Quality Forum have changed the recommended target for initial administration of antimicrobial therapy from four to six hours after arrival at the hospital The previously recommended four hour window resulted in the unintended consequence of overuse of antimicrobials before the diagnosis of pneumonia could be definitively established Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Houck ET AL.Arch Intern Med. 2004;164(6):637-44. TI JCAHO tweaks emergency departments' pneumonia treatment standards. Mitka ET AL. JAMA. 2007;297(16):1758-9. Clinical response to therapy Improvement in the patient's clinical course is seen within 48 to 72 hours Patients who do not demonstrate some clinical improvement within 72 hours are considered nonresponders The time to resolution of all symptoms and radiographic findings is more prolonged With pneumococcal pneumonia, for example, the cough usually resolves within eight days and auscultatory crackles clear within three weeks As many as 87% of inpatients with CAP have persistence of at least one pneumonia-related symptom at 30 days compared to 65% by history in the month prior to the onset of CAP Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Fine ET AL.Arch Intern Med. 1999;159(9):970-80. Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients. Menndez ET AL.Clin Infect Dis. 2004;39(12):1783-90. Radiographic response At day 7, 56% have clinical improvement but only 25% have resolution of CXR At day 28, 78% have attained clinical cure but only 53% have resolution of CXR Delayed radiographic resolution was independently associated with multilobar disease The chest x-ray usually cleared within four weeks in patients younger than 50 years of age without underlying pulmonary disease Resolution could be delayed for 12 weeks or more in older individuals and in those with underlying lung disease Duration of hospitalization It is not necessary to observe stable patients overnight after switching from intravenous to oral therapy No significant difference in 14-day hospital readmission rate OR 30-day mortality rate On the last day of hospitalization seven parameters of instability should be evaluated: temperature >37.8 ºC [100 ºF] respiratory rate >24/min heart rate (HR) >100 beats/min systolic BP ≤90 mmHg oxygen saturation <90 percent on room air inability to receive oral nutrition change of mental status from baseline At 60 days post discharge, patients with at least one parameter of instability at discharge ARE significantly more likely to have died or required readmission (death rates, 14.6 versus 2.1 percent; readmission rates, 14.6 versus 6.5 percent) Duration of therapy a minimum of five days Before stopping therapy, the patient should be: afebrile for 48 to 72 hours breathing without supplemental oxygen (unless required for preexisting disease) have no more than one clinical instability factor (defined as heart rate [HR] >100 beats/min, respiratory rate [RR] >24 breaths/min, and systolic blood pressure [SBP] ≤90 mmHg) Longer durations of therapy are needed in the following settings: If the initial therapy was not active against the subsequently identified pathogen If extrapulmonary infection is identified (eg, meningitis or endocarditis) If the patient has documented P. aeruginosa or S. aureus pneumonia, or pneumonia caused by some unusual and less common pathogens (eg, Burkholderia pseudomallei, fungus) Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Li ET AL, Am J Med. 2007;120(9):783-90. The nonresponding patient The absence or delay in achieving clinical stability after 72 hours of antibiotic therapy noninfectious entities to be considered: drug fever Malignancy interstitial lung disease inflammatory conditions heart failure hospital-acquired infection of another body system (eg, intravascular catheter infection, urinary tract infection or Clostridium difficile infection) The upper airway of hospitalized patients receiving antibiotics may become colonized, and repeat sputum cultures should be interpreted with caution Risk factors for Tx failure Multilobar pneumonia Pneumonia caused by Legionella or gram-negative organisms Pneumonia Severity Index (PSI) >90 Treatment with an antimicrobial agent to which the causative organism was not susceptible Further evaluation — repeating the history (including travel and pet exposures to look for unusual pathogens), chest x-ray, and sputum and blood cultures further diagnostic procedure, such as chest CT, bronchoscopy, and, lung biopsy can be performed Steroids Whether or not there is a benefit of glucocorticoids in severe CAP is presently being evaluated in a large Veteran Administration cooperative study Pending these results, glucocorticoids are not recommended as adjunctive therapy for CAP VACCINATION — Patients with CAP should be appropriately vaccinated for influenza and pneumococcal infection SMOKING CESSATION — Smoking cessation should be a goal for hospitalized patients with CAP who smoke Glucocorticoid treatment in community-acquired pneumonia without severe sepsis: no evidence of efficacy. Meduri ET AL. Am J Respir Crit Care Med. 2010;181(9):880-2. HAP /VAP/ HCAP Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare- associated pneumonia. American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171(4):388-416 Defintitions HAP occurs 48 hours or more after admission VAP is a type of HAP that develops more than 48 to 72 hours after endotracheal intubation HCAP occurs in a non-hospitalized patient with extensive healthcare contact: Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days Residence in a nursing home or other long-term care facility Hospitalization in an acute care hospital for two or more days within the prior 90 days Attendance at a hospital or hemodialysis clinic within the prior 30 days Epidemiology HAP is the Leading cause of death with mortality ranging from 20 to 50% Most cases of HAP occur outside of intensive care units However, the highest risk for HAP is in patients on mechanical ventilation (ie, VAP) Estimates of incidence range from four to seven episodes per 1000 hospitalizations, accounting for 13 to 18% of all nosocomial infections Pathogenesis The primary route of infection of the lungs is through microaspiration of organisms that have colonized the oropharyngeal tract or GIT 45% healthy subjects aspirate during sleep, and an even higher proportion of severely ill patients aspirate Endotracheal tube permits the aspiration of oropharyngeal material or bacteria of gastrointestinal origin Hospitalized patients often become colonized with microorganisms acquired from the hospital environment 75% of severely ill patients will be colonized within 48 hours Microbiology of VAP/HAP There is a paucity of data regarding whether the pathogens that cause VAP differ from those that cause HAP in patients who are not mechanically ventilated The infecting flora in patients with VAP includes MSSA, MRSA , P. aeruginosa , Stenotrophomonas maltophilia , Acinetobacter spp , and other spp The infecting flora in non-ventilated patients with HAP was similar, except non- Enterobacteriaciae gram-negative bacilli (P. aeruginosa, Acinetobacter, and S. maltophilia) were less likely Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Kollef et al. Chest. 2006;129(5):1210-8. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Kollef et al. Chest. 2006;129(5):1210-8. HCAP The clinical and microbiologic features of HCAP are more similar to HAP and VAP than to CAP The incidence of S. aureus in the HCAP and HAP groups are comparable (47%) and significantly higher than in the CAP group (26%) The rate of MRSA infection is also higher in HCAP and HAP; 27 and 23 versus 9% for CAP P. aeruginosa is the only other pathogen with a significant occurrence (25%) in HCAP patients Patients with HCAP had higher mortality (18 versus 7%) and longer length of hospitalization (19 versus 15%) compared with CAP patients Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes--proceedings of the HCAP Summit. Kollef et al. Clin Infect Dis. 2008;46 Suppl 4:S296-334; quiz 335-8. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Kollef et al. Chest. 2005;128(6):3854-62. MDR risk factors Host risk factors for infection with MDR pathogens include : Receipt of antibiotics within the preceding 90 days Current hospitalization of ≥5 days High frequency of antibiotic resistance in the community or in the specific hospital unit Immunosuppressive disease and/or therapy The risk factor of long-term care facility residence applies specifically to those who have more severe illness, prior antibiotic therapy in the preceding six months, or poor functional status Indicators of potentially drug-resistant bacteria in severe nursing home-acquired pneumonia. El Solh et al. Clin Infect Dis. 2004;39(4):474-80. Diagnosis HAP, VAP, or HCAP should be suspected in patients with a new or progressive infiltrate on lung imaging as well as clinical characteristics such as: Fever Purulent sputum Leukocytosis Decline in oxygenation The presence of a new or progressive radiographic infiltrate plus at least two of the three clinical features (fever >38ºC, leukocytosis or leukopenia, and purulent secretions) represents a clinically relevant combination of criteria for starting empiric antimicrobial therapy When findings at autopsy are used as a standard of reference, this combination of findings resulted in 69% sensitivity and 75% specificity for pneumonia Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post- mortem lung biopsies. Et al. Thorax. 1999;54(10):867-73. Treatment Appropriate antibiotic therapy significantly improves survival for patients with HAP, VAP, or HCAP When therapy is given, antimicrobial selection should be based upon risk factors for MDR pathogens Once the results of pretherapy cultures are available, therapy should be narrowed Mortality is significantly higher among patients who received inappropriate initial therapy compared with patients who received appropriate coverage (30 versus 18%); switching to an appropriate regimen did not reduce the risk of death Mortality is significantly lower among patients in whom therapy was deescalated compared to those whose therapy was either escalated or unchanged (17 versus 43 and 24%, respectively) Antimicrobial therapy escalation and hospital mortality among patients with health-care-associated pneumonia: a single-center experience. Zilberberg ET AL.Chest. 2008;134(5):963-8. Emperic treatment with no known risk factors for MDR pathogens with no known risk factors for MDR pathogens Ceftriaxone (2 g intravenously daily) Ampicillin-sulbactam (3 g intravenously every six hours) or piperacillin-tazobactam (4.5 g intravenously every six hours) if there is concern based on prevailing pathogens within an institution for gram-negative bacilli not treated by ampicillin-sulbactam (eg, Enterobacter spp, Serratia spp, Pseudomonas spp) Levofloxacin (750 mg intravenously daily) or moxifloxacin (400 mg intravenously daily) Ertapenem (1 g intravenously daily). With known mdr risk factors Empiric three-drug combination therapy including: Antipseudomonal cephalosporin: cefepime (2 g intravenously every eight hours) or ceftazidime (2 g intravenously every 8 hours) Antipseudomonal carbapenem: imipenem (500 mg intravenously every six hours) or meropenem (1 g intravenously every eight hours) or doripenem (500 mg intravenously every eight hours; administered over one hour for HAP or HCAP, administered over four hours for VAP) Piperacillin-tazobactam (4.5 g intravenously every six hours) For patients who are allergic to beta-lactam antibiotics: aztreonam (2 g intravenously every six to eight hours) PLUS Antipseudomonal fluoroquinolone, preferred regimen if Legionella is likely: ciprofloxacin (400 mg intravenously every eight hours) or levofloxacin (750 mg intravenously daily) Aminoglycoside: gentamicin or tobramycin (7 mg/kg intravenously per day adjusted to a trough level <1 mcg/mL) or amikacin (20 mg/kg intravenously per day adjusted to a trough level <4-5 mcg/mL) The aminoglycoside can be stopped after five to seven days in responding patients PLUS (if MRSA is suspected, there are MRSA risk factors, or there is a high incidence of MRSA ): Linezolid (600 mg intravenously every 12 hours; may be administered orally) Vancomycin (15 to 20 mg/kg intravenously every 8 to 12 hours for patients with normal renal function, with a target serum trough concentration of 15 to 20 mg/L.) In seriously ill patients, a loading dose of 25 to 30 mg/kg can be used to facilitate rapid attainment of the target trough If patients have recently received antibiotics, empiric therapy should generally be with a drug from a different class since earlier treatment may have selected pathogens resistant to the initial class Colistin, polymyxin, or inhaled aminoglycosides may be considered as potential additional antibiotics in patients with MDR gram-negative bacilli Aerosolization may increase antibiotic concentrations at the site of infection, and may be particularly useful for treatment of organisms that have high MICs to systemic antimicrobial agents Aerosolized antibiotics to treat ventilator-associated pneumonia. Luyt et al. Curr Opin Infect Dis. 2009;22(2):154-8. Duration There is no significant difference between patients treated for eight compared to 15 days in mortality or recurrent infection at 28 days Among patients who developed recurrent infections, MDR pathogens were isolated less frequently in those treated for eight days (42 versus 62% for those treated for 15 days) However, patients with VAP caused by nonfermenting gram-negative bacilli (eg, Pseudomonas spp) had a higher pulmonary infection recurrence rate when treated for eight versus 15 days (41 versus 25% with 15 days of treatment), although mortality was not different In patients who had S. aureus isolated, there was no significant difference based on treatment duration (8 or 15 days) for 28-day mortality or VAP recurrence Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. Chastre et al. JAMA. 2003;290(19):2588-98. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Singh et al. Am J Respir Crit Care Med. 2000;162(2 Pt 1):505-11. Prognosis The all-cause mortality rate for HAP and VAP is in the range of 33 to 50% Variables associated with increased mortality include: Serious illness at the time of diagnosis (eg, high APACHE score, shock, coma, respiratory failure, ARDS) Bacteremia Severe underlying comorbid disease Infection caused by an organism associated with multidrug resistance (Pseudomonas aeruginosa, Acinetobacter spp) Multilobar, cavitating, or rapidly progressive infiltrates on lung imaging Delay in instituting effective antimicrobial therapy Outcomes of patients hospitalized with community-acquired, health care-associated, and hospital-acquired pneumonia. Venditti et al. Ann Intern Med. 2009;150(1):19-26.