WHO estimates, 450 million cases of pneumonia are recorded every year; about. this illness, accounting for 7% of total mortality (2011)

Transcription

1 WHO estimates, 450 million cases of pneumonia are recorded every year; about 4 million people die from this illness, accounting for 7% of total mortality (2011)

2 Pneumonias - consultation dr. Gergely Peskó SEMMELWEIS UNIVERSITY Faculty of Medicine 3rd Department of Internal Medicine Director: Professor Tamás Masszi

3 Airway infections Upper airway infections Pharyngitis Otitis media Sinusitis Stomatitis Lower airway infections Bronchitis Pneumonia Lung abscess, empyema

4 What we are going to focus on? Pneumonia: approach to a clinical syndrome Community-acquired pneumonia (CAP) Healthcare-associated pneumonia (HCAP)??? Hospital-acquired pneumonia (HAP) /not ventilatorassociated/ Ventilator-associated pneumonia (VAP) Concomitant or post influenza pneumonia Pneumonia in neutropenic patients The three questions needed to be answered: choice of AB therapy extent of testing appropriate site of treatment Pneumonia: approach to pathogens

5 Pneumonia general overview Pneumonia is an infection of the pulmonary parenchyma: patogen proliferaton at the alveolar level + host response Patogen gains access: small-volume aspiration, droplet inspiration, hematogenous spread, contiguous extension Host decense: hairs, turbinates, mucociliar clearance, gag reflex, cough, normal flora, alveolar macrophages When the capacity of the alveolar macrophages to ingest or kill the microorganisms is exceeded does clinical pneumonia become manifest. Host inflammatory response, rather than proliferation of microorganisms, triggers the clinical syndrome of pneumonia: IL-1, TNF-alfa fever; IL-8, GCSF neutrofils, leukocytosis localized capillary leak, alveolar filling = radiologic infiltrate, typical ascultation, hypoxemia /confusion/ (some patogen even interfere with hypoxemic vasoconstriction), sputum, pleuritic chest pain Increased respiratory drive respiratory alkalosis fatigue Decreased compliance dyspnea In the end: partial global respiratory failure

6 Pneumonia general overview About 30% of elderly patients do not show typical signs and symptomes New lung infiltrates may be difficult to identify in patients with chronic lung disease About 17% of patients who are hospitalized for CAP do not have an infection

7 Pneumonia general overview Pneumonia was defined in the 2005 IDSA guideline as new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation. Cause of significant morbidity and mortality Often misdiagnosed, mistreated and underestimated In addition to a constellation of suggestive clinical features, a demonstrable infiltrate by chest radiograph or other imaging technique, with or without supporting microbiological data, is required(?) for the diagnosis of pneumonia

8 Make a good guess

9 Infiltration/consolidation Alveoli fill with fluid or blood cells (air in bigger local airways ; air in parenchyma (alveoli) ) Lobar pneumonia Pulmonary edema Pulmonary hemorrhage Infiltrating pulmonary tumour Pulmonary embolism pulmonary infarct In massive infiltration: Secretion fills even the bronchi air in bigger local airways air in parenchyma (alveoli) ) NO bronchial breathing, NO increased tactile fremitus Syndrome name Chest expansion Percussion note trachea Breath sounds Adventitious sounds Tatile phremitus and TVS-s Infiltration / consolidation Unilaterally decreased dullness midline Bronchial over involved area Late inspiratory cracles, cracles (pleural rub) Increased with bronchophony, egophony, whispered pectoriloquy

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12 Bronchi are visible only up to the fourth order of branching You can see the trachea, main stem bronchi and the next order of bronchi Distal bronchi are surrounded by air filled alveoli, there is no contrast between air filled bronchi and surrounding air filled alveoli, thus, the bronchi are not visible If the alveoli are filled with liquid density (pneumonia, edema, and hemorrhage, etc.) there is contrast with air filled bronchi and they become visible as branching tubular structures through the density. visible air bronchogram implies that there is alveolar filling and the bronchi are patent

13 Community-aquired pneumonia (CAP) Individuals of all ages not recently hospitalized and lacking healthcare associated risk factors: 2005 IDSA HCAP - NOT WORKING reworked hospitalization for more than 2 days in an acute care hospital in the last 90 days residence in a skilled nursing facility recent intravenous antibiotic therapy, chemotherapy, or wound care in the last 30 days attending a hospital or hemodialysis clinic Immunosuppression The concept of HCAP was introduced by the authors of the 2005 ATS and IDSA s guidelines to address the concern of the shifting microbiology of patients presenting to the hospital with pneumonia. Recent or chronic contact with the health care system seemed to be a risk factor of infection with MDR pathogens. HCAP is a poor predictor of multidrug-resistant pathogens. The definition of HCAP needs further modification. HCAP guideline compliance did not result in better outcomes.

14 Community-aquired pneumonia (CAP) Individuals of all ages not recently hospitalized and lacking healthcare associated and risk factors and underlying patient characteristics: prior intravenous antibiotic use within 90 days or antibiotic therapy within the last 30 days hospitalization within 90 days severity of pneumonia immunosuppression poor functional status Renal replacement therapy

15 The risk score: Recent hospitalization for at least 48h-s in the last 90 days 4 points Admission from a long term care facility 3 points Chronic HD 2 points Admitted to ICU within 24h-s of evaluation 1 point

16 Community-aquired pneumonia (CAP) Historically divided into typical amd atypical syndromes but there is a significant overelap Nearly 20% of patients with CAP who have proven bacterial pneumonia are coinfected with a virus In the preantibiotic era, Streptococcus pneumoniae caused 95% of cases of pneumonia The key to appropriate therapy is adequate coverage of Streptococcus pneumoniae and the atypical bacterial pathogens (mycoplasma, chlamydophila, and legionella)

17 Community-aquired pneumonia (CAP) Site of care decision Hospital admission Objective scores, such as the CURB-65 score or the PSI, can assist in identifying patients who maybe appropriate for outpatient care, but the use of such scores must be tempered by the physician s determination of additional critical factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources. ICU admission patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP

18 CURB-65 score

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20 Severe CAP significant percentage of patients with CAP are transferred to the ICU in the first h after hospitalization. Mortality and morbidity among these patients appears to be greater than those among patients admitted directly to the ICU Additional risk factors: lactic acidosis, low ph, albumin under 3.5g/dl, Na under 130mmol/L, leukocitosis over 20000/mm 3, pulse over 125/min, over 80 years of age

21 Community-aquired pneumonia (CAP) pathogens

22 Community-aquired pneumonia (CAP) pathogens

23 Community-aquired pneumonia (CAP) pathogens Group I: outpatients, no cardiopulmonary disease, no modifying factors *, * Excludes patients at risk for HIV In roughly 50~90% of the cases no etiology was identified

24 Community-aquired pneumonia (CAP) pathogens Group II: outpatients, with cardiopulmonary disease, and/or other modifying factors *, Excludes patients at risk for HIV In roughly 50~90% of the cases no etiology was identified

25 Community-aquired pneumonia (CAP) pathogens Group III: inpatients, not in intensive care unit *, * Excludes patients at risk for HIV In roughly one-third to one-half of the cases no etiology was identified

26 Community-aquired pneumonia (CAP) pathogens Group IV: intensive care unitadmitted patients *, * Excludes patients at risk for HIV In roughly one-third to one-half of the cases no etiology was identified

27 Community-aquired pneumonia (CAP) diagnostic testing Patients with CAP should be investigated for specific pathogens that would significantly alter standard (empirical) management decisions, when the presence of such pathogens is suspected on the basis of clinical and epidemiologic clues Routine diagnostic tests to identify an etiologic diagnosis are optional for outpatients with CAP In patients requiring hospitalization, clinicians should make a conscientious effort to determine the causative organism. Pathogen-directed therapy greatly fosters antibiotic stewardship, decreasing the cost of care and reducing the risk of complications such as Clostridium difficile infection. Gram s staining and culture of sputum, blood cultures, testing for legionella and pneumococcal urinary antigens, and multiplex PCR assays for Myc. pneumoniae, Chl. pneumoniae, and respiratory viruses

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29 Community-aquired pneumonia (CAP) diagnostic testing Gram s staining and culture of sputum are positive in more than 80% of cases of pneumococcal pneumonia with a good-quality specimen (>10 inflammatory cells per epithelial cell) before, or within 6 to 12 hours after, the initiation of antibiotics. Blood cultures are positive in about 20 to 25% of inpatients with pneumococcal pneumonia but pretreatment blood cultures yielded positive results for a probable pathogen in 5% 14% in large series of nonselected patients hospitalized with CAP Hematogenous Staph. aureus pneumonia, blood cultures are nearly always positive, but they are positive in only about 25% of cases in which inhalation or aspiration is responsible for the CAP. ELISA of urine samples detected pneumococcal cell-wall polysaccharide in 77 to 88% of patients with bacteremic pneumococcal pneumonia and in 64% with nonbacteremic pneumonia. ELISA for legionella urinary antigen is positive in about 74% of patients with pneumonia caused by Legionella pneumophila serotype 1 PCR assays can detect most important respiratory viruses as well as Myc. pneumoniae and Chl. pneumoniae.

30 Community-aquired pneumonia (CAP) treatment Once the diagnosis of CAP is made, antimicrobial therapy should be started as soon as possible and at the site where the diagnosis is made. Outpatients with CAP are generally treated empirically. Several factors favor the use of a beta-lactam as empirical therapy for CAP in outpatients: most clinicians do not know the level of pneumococcal resistance in their communities, and Str. pneumoniae is more susceptible to penicillins than to macrolides or doxycycline it seems inappropriate to treat a patient with a macrolide or doxycycline to which 15 to 30% of strains of Str. pneumoniae are resistant if a patient does not have a prompt response to a beta-lactam, a macrolide or doxycycline can be substituted to treat a possible atypical bacterial infection where isolates produce betalactamase, amoxicillin clavulanate may be preferable to amoxicillin or penicillin, especially in patients with underlying lung disease

31 Community-aquired pneumonia (CAP) treatment outpatient IDSA The key to appropriate therapy is adequate coverage of Streptococcus pneumoniae and the atypical bacterial pathogens (mycoplasma, chlamydophila, and legionella) Macrolides, doxycycline, and fluoroquinolones are the most appropriate agents for the atypical bacterial pathogens.

32 Community-aquired pneumonia (CAP) treatment inpatient, non-icu IDSA These regimens have been studied extensively and generally produce a cure in about 90% of patients with CAP of mild or moderate severity

33 Community-aquired pneumonia (CAP) treatment inpatient, ICU IDSA When influenza is active in the community, patients with CAP should be treated with oseltamivir even if more than 48 hours have elapsed since the onset of symptoms Patients at high risk for Staph. aureus pneumonia (e.g., those taking glucocorticoids or those with influenza), vancomycin or linezolid should be added to treat MRSA Ceftaroline, which is active against Staph. aureus, including MRSA, as well as Str. pneumoniae and H. influenzae, may eventually replace ceftriaxone plus vancomycin or linezolid S. pneumoniae remains the most common cause of severe community-acquired pneumonia requiring ICU admission Observational evidence suggests that the macrolide combination may be associated with better outcomes explained by nonbactericidal effects, such as immunomodulation

34 CAP risk factors related to specific patogens

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37 Community-aquired pneumonia (CAP) additional therapies Many, but not all, retrospective studies have shown that the addition of a macrolide to a beta-lactam antibiotic to treat pneumococcal pneumonia or all-cause CAP reduces morbidity and mortality, presumably by inhibiting the inflammatory response Statins block the synthesis of HMG-CoA reductase, inhibiting the synthesis of farnesyl pyrophosphate and geranylgeranyl pyrophosphate (which are needed to activate G proteins), thereby dampening inflammatory responses. A randomized trial of adjunctive simvastatin in patients with ventilator-associated pneumonia was stopped early because no 28-day mortality benefit was seen in those who received this drug

38 Community-aquired pneumonia (CAP) durations of treatment Patients with CAP should be treated for a minimum of 5 days, should be afebrile for h, and should have no more than 1 CAP-associated sign of clinical instability before discontinuation of therapy The currently recommended duration of antibiotic therapy for community-acquired pneumonia is 5 to 7 days (or even shorter). There is no evidence that prolonged courses lead to better outcomes, especially in outpatients, or in inpatients who have a prompt response to therapy, unless they are immunocompromised. Hematogenous Staph. aureus pneumonia mandates treatment for at least 4 weeks, but segmental or lobar pneumonia that is caused by this organism may be treated for 2 weeks.

39 Community-aquired pneumonia (CAP) IV/PO treatment and discharge Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract. Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary!

40 Community-aquired pneumonia (CAP) other treatment considerations Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency. Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation (NIV) unless they require immediate intubation because of severe hypoxemia (arterial oxygen pressure/fraction of inspired oxygen [PaO2/FiO2] ratio, lower then 150) and bilateral alveolar infiltrates.

41 Community-aquired pneumonia (CAP) non-responding disease May be additionally needed: Cheast CT Thoracocentesis Bronchoscopy with BAL and/or biopsy

42 Community-aquired pneumonia (CAP) prevention Influenza vaccine: be offered to persons older than 50 years, residents of extendedcare facilities, and patients who have chronic heart and lung disorders, chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression Pneumococcus vaccine: Pneumococcal 13-valent conjugate (PCV13): immune response is strong, immunememory +, longer immunity, decrease nasopharyngeal carriage Pneumococcal polysaccharide (PPSV23): immune response is strong-intermediate, immunememory -, shorter immunity, no effect on nasopharyngeal carriage

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44 Community-aquired pneumonia (CAP) prevention Immunocompromising conditions that are indications for pneumococcal vaccination are congenital or acquired immunodeficiency (including B- or T-lymphocyte deficiency, complement deficiencies, and phagocytic disorders excluding chronic granulomatous disease), HIV infection, chronic renal failure, nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized malignancy, multiple myeloma, solid-organ transplant, and iatrogenic immunosuppression (including long-term systemic corticosteroids and radiation therapy). Anatomical or functional asplenia that are indications for pneumococcal vaccination are sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, splenic dysfunction, and splenectomy. Administer pneumococcal vaccines at least 2 weeks before immunosuppressive therapy or an elective splenectomy, and as soon as possible to adults who are newly diagnosed with asymptomatic or symptomatic HIV infection.

45 PCV13 and PPSV23

46 Hospital-aquired pneumonia (HAP=non-VAP) HAP is defined as a pneumonia not incubating at the time of hospital admission and occurring 48 hours or more after admission VAP is defined as a pneumonia occurring >48 hours after endotracheal intubation HAP and VAP continue to be frequent complications of hospital care. Together, they are among the most common hospital-acquired infections (HAIs), accounting for 22% of all HAIs in a multistate pointprevalence survey all-cause mortality associated with VAP has been reported to range from 20% to 50% even in HAP, generally considered to be less severe than VAP, serious complications occur in approximately 50% of patients, including respiratory failure, pleural effusions, septic shock, renal failure, and empyema

47 Hospital-aquired pneumonia (HAP) risk factors for MDR pathogens fifteen potential risk factors were included in meta-analysis. Only one risk factor was significantly associated with MDR HAP: prior intravenous antibiotic use in the last 90 days while other risk factors may be relevant, evidence is lacking: some evidence suggesting that a positive MRSA screen from nasal or respiratory samples may increase the risk of MRSA prior use of antibiotics, mechanical ventilation, and history of chronic obstructive pulmonary disease have been identified as potential risk factors for MDR P. aeruginosa infection patients with cystic fibrosis and bronchiectasis are more likely than patients with other pulmonary diseases to be chronically colonized with P. aeruginosa and are therefore also likely at increased risk for MDR P. aeruginosa It includes MRSA and MR Pseudomonas.

48 HAP - pathogens Early-onset (<5 days in the hospital, no other risk factors for MDR) Strep. pneumoniae Staph. aureus H. influenzae Enteric gram-negative bacilli Late-onset (>5days in the hospital, risk factors for MDR present) Staph. aureus (often MRSA) Gram-negaive enterics (often MDR) E. coli, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens, Pseudomonas aeruginosa, Acinetobacter beumanii ESKAPE pathogens in nearly 80% of patients

49 Hospital-aquired pneumonia (HAP) diagnostic measures patients with suspected HAP (non-vap) be treated according to the results of microbiologic studies performed on respiratory samples obtained noninvasively, rather than being treated empirically high value on the potential to accurately target antibiotic therapy and then deescalate antibiotic therapy based upon respiratory and blood culture results Noninvasive methods to obtain respiratory samples include the following: spontaneous expectoration sputum induction nasotracheal suctioning in a patient who is unable to cooperate to produce a sputum sample endotracheal aspiration in a patient with HAP who subsequently requires mechanical ventilation Some patients in whom a respiratory sample cannot be obtained noninvasively, there may be factors which could prompt consideration of obtaining samples invasively.

50 HAP use of PCT for diagnosis and initiation of therapy PCT PCT is a precursor of calcitonin that is constitutively secreted by C cells of the thyroid gland and K cells of the lung In healthy individuals, PCT is normally undetectable (<0.01 ng/ml) stimulated by endotoxin, PCT is rapidly produced by parenchymal tissue throughout the body; this PCT production has also been observed in diverse types of bacterial infections PCT may increase in response to sterile inflammation or viral infection, but it is less common The evidence indicates that serum PCT plus clinical criteria can diagnose HAP/VAP with a sensitivity and specificity of 67% and 83%. For patients with suspected HAP/VAP, it is recommended to use clinical criteria alone, rather than using serum PCT plus clinical criteria, to decide whether or not to initiate antibiotic therapy. (Same goes for CRP!)

51 HAP use of PCT for stoping antibiotic therapy For patients with HAP/VAP, using PCT levels plus clinical criteria to guide the discontinuation of antibiotic therapy is suggested, rather than clinical criteria alone A low serum procalcitonin concentration (<0.1 µg per liter) can help to support a decision to withhold or discontinue antibiotics Discontinuing antibiotics on the basis of PCT levels plus clinical criteria decreases antibiotic exposure compared with using clinical criteria alone; all other outcomes remain unchanged

52 HAP - treatment Lokal antibiotic resistance is critically important: all hospitals are to regularly generate and disseminate a local antibiogram, ideally one that is tailored to their HAP population empiric antibiotic regimens are to be based upon the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities

53 HAP treatment: not at high risk of mortality and no factors increasing the likelihood of MRSA Risk factors for mortality: need for ventilatory support due to pneumonia septic shock, (hypotension, rapid progression on CXR) Indications for MRSA coverage: include intravenous antibiotic treatment during the prior 90 days treatment in a unit where the prevalence of MRSA among S. aureus isolates is not known or is >20% Prior detection of MRSA by culture or non-culture screening may also increase the risk of MRSA if MRSA coverage is omitted, the antibiotic regimen should include coverage for MSSA. These AB-s cover MSSA, pseudomonas and G neg.!

54 HAP treatment: not at high risk of mortality but with factors increasing the likelihood of MRSA If patient has factors increasing the likelihood of gram-negative infection, 2 antipseudomonal agents are recommended: If patient has structural lung disease increasing the risk of gram negative infection (ie, bronchiectasis or cystic fibrosis), 2 antipseudomonal agents are recommended A high-quality Gram stain from a respiratory specimen with numerous and predominant gramnegative bacilli provides further support for the diagnosis of a gram-negative pneumonia, including fermenting and non-glucose-fermenting microorganisms Prior intravenous antibiotic use within 90 days increases the risk of pseudomonas infection.

55 HAP treatment: high risk of mortality or receipt of intravenous antibiotics during the prior 90 days PHARMACOKINETIC/PHARMACODYNAMIC OPTIMIZATION OF ANTIBIOTIC THERAPY: potential advantages of PK/PD-optimized dosing (decreased mortality, decreased ICU length of stay, and increased clinical cure rate) against the potential downsides (more burdensome and costly, possibly more toxicity among patients who require higher doses due to augmented clearance) D means: extended infusions may be appropriate.

56 HAP treatment: MRSA, Pseudomonas aeruginosa MRSA HAP/VAP be treated with either vancomycin or linezolid rather than other antibiotics or antibiotic combinations HAP/VAP due to P. aeruginosa: choice of an antibiotic for definitive (not empiric) therapy be based upon the results of antimicrobial susceptibility testing aminoglycoside monotherapy is NOT recommended not in septic shock or at a high risk for death, and for whom the results of antibiotic susceptibility testing are known, monotherapy is recommended in septic shock or at a high risk for death when the results of antibiotic susceptibility testing are known, combination therapy is suggested

57 HAP treatment: ESBL-producing G neg. bacteria, Acinetobacter HAP/VAP due to ESBL-producing gram negative bacilli: choice of an antibiotic for definitive (not empiric) therapy be based upon the results of antimicrobial susceptibility testing and patient specific factors failed to identify an agent that is clearly preferable to others in the treatment of HAP/VAP due to ESBL-producing gram-negative bacilli HAP/VAP caused by Acinetobacter species: treatment with either a carbapenem or ampicillin/sulbactam if the isolate is susceptible to these agents If it is sensitive only to polymyxins, intravenous polymyxin and adjunctive inhaled colistin is suggested If it is sensitive only to colistin, adjunctive rifampicin is NOT recommended use of tigecycline is NOT recommended

58 HAP treatment: carbapenem rezistant pathogens In patients with HAP/VAP caused by a carbapenemresistant pathogen that is sensitive only to polymyxins, intravenous polymyxins and adjunctive inhaled colistin are recommended

59 HAP optimal duration and deescalation of therapy For patients with HAP, a 7-day course of antimicrobial therapy is recommended There exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters: Staph. aureus, MRSA and more resistant organisms (Pseudomonas, Acinetobacter, Stenotrophomonas) may need longer therapy 14 days? For patients with HAP/VAP, antibiotic therapy should be de-escalated rather than fixed De-escalation refers to changing an empiric broad spectrum antibiotic regimen to a narrower antibiotic regimen by changing the antimicrobial agent or changing from combination therapy to monotherapy. In contrast, fixed antibiotic therapy refers to maintaining a broad-spectrum antibiotic regimen until therapy is completed.

60 HAP good to know P. aeruginosa pneumonia is characterized by fever, cyanosis, hypotension, and rapid cavitation (<72 hours) on chest radiography. Sputum recovered from these cases is typically greenish due to the pyocyanin pigment that is produced by the organism when it invades tissue. This is usually accompanied by an almond odor. Enterobacter species do not typically cause hospital-acquired pneumonia S. maltophilia and B. cepacia are common colonizers of respiratory secretions, but they rarely, if ever, cause nosocomial pneumonia in otherwise healthy hosts S. aureus (MSSA/MRSA) commonly colonizes respiratory secretions (30%-50%) but rarely, if ever, causes necrotizing cavity nosocomial pneumonia. Oropharyngeal anaerobes are unimportant from a therapeutic standpoint.

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62 Viral pneumonia: no clinical algorithm exists that will distinguish clearly the cause of pneumonia 100 million in children and 100 million in adults every year viruses are the putative causative agents in a third of cases of communityacquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses Laboratory diagnosis of viral pneumonia has relied on detection of virus or viral antigen in upper-respiratory specimens (eg, nasopharyngeal aspirates) and lowerrespiratory samples (eg, induced sputum)

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