5 MED II 1 - Pneumonia.docx

Medicine 5.1

PNEUMONIA OUTLINE I. Sample Cases II. Anatomy and Physiology III. Main Function of the Respiratory system IV. Pathogenesis of Pneumonia V. Routes of Transmission VI. Pathophysiology VII. Pneumonia VIII. Community Acquired Pneumonia IX. HAP, VAP, HCAP

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LECTURER: Dr. Zotomayor DATE: Jan. 06, 2015 coherent. Based on the local guidelines, the antibiotic of choice is: A. Cefixime B. Amoxicillin C. Doxicycline D. Co-amoxiclav Based on the Philippine CAP guidelines, this patient is considered as a low-risk CAP who is previously healthy. There is no such thing as a healthy smoker. Amoxicillin is the treatment of choice for this case.

ANATOMY AND PHYSIOLOGY References 1. Powerpoint lecture 2. Recording in ITALICS 1.

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SAMPLE CASES A 24 y.o. male is consulting because of cough and dyspnea of 10 days duration. Chest exam reveals bibasal crackles and wheezes. Chest x-ray shows clear lung fields. The diagnosis is: A. Pneumonia B. Lung abscess C. Acute bronchitis D. Upper respiratory infection Since it was given from the question that there are no infiltrates, pneumonia is eliminated.Pneumonia and lung abscess will show abnormal x-ray findings.Upper airway infection is also eliminated since chest exam reveals bibasal crackles and wheezes. Acute bronchitis is the answer since it mimics the infection of the lower respiratory tract but does not show any consolidation.

A 70 year old male smoker is hospitalized for fever, cough and dyspnea, history reveals that the patient has not received any form of treatment during the last year. Initial chest x-ray only shows hyperaeration consistent with emphysema. Twelve hours after admission, he is intubated for increasing dyspnea and is placed on mechanical ventilation. Repeat chest x-ray one hour after intubation now shows right lower lobe opacification with air bronchogram. He has: A. Community-acquired pneumonia (CAP) B. Hospital acquired pneumonia (HAP) C. Ventilator-associated pneumonia (VAP) D. Health-care associated pneumonia (HCAP) This is a typical presentation of a patient whose chronological presentation tells you what is going on. Initial x-ray: because this is a smoker, he probably has COPD. This is hyperaeration consistent with emphysema; remember that hyperaeration does not involve the presence of infiltrates. Repeat x-ray of right lower lobe opacification with air bronchogram, indicates presence of an air space consolidation that is compatible with pneumonia. The primary diagnosis would probably be COPD in acute exacerbation. But there is another component to his problem, and this is what is being asked of you. The acuteness of the development of signs and symptoms and the tests which are initially normal may be too soon to be able to tell you the abnormality. The Pneumonia that you saw after 13 hours of admission is likely an incubating community acquired pneumonia. Other choices are also eliminated since the patient has no recent hospital admission and usually the other choices occur after 48 hours of admission.

A 32 year old male, smoker from pasig city, is consulting for fever and cough of 4 days duration. He has no comorbidities. He also has no recent antibiotic intake. Chest x-ray shows left lower lobe pneumonia. VS are BP 124/80 HR 94 RR 24 and Te,p 38.3C. He is conscious and

Figure 1. Respiratory Tree

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The main function of our respiratory tree is to protect us from harmful particles and microorganisms that are in the air that we breathe. The larynx and vocal cords prevents aspiration through the gag and cough reflexes.

Figure 2. Lining of the airways, ciliated epithelium of the trachea

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Mucus is continuously swept into the throat. All of the collected particles including inanimate objects may be filtered and trapped in this mucus apparatus and moved to the throat, or may be expectorated or swallowed. Smokers’ respiratory flora is different from the flora of non smokers. The mucocillary apparatus is also affected for up to 6 to 8 hours per cigarette stick which makes it dysfunctional, increasing the risk of developing lower respiratory tract infections including pneumonia. Alveolar macrophages, are recruited when foreign and harmful organisms land on the alveoli and are very effective in elminating them. However, some particles ingested by the macrophage do not always result in the death of the organism. A good example would be tuberculosis, where the bacilli are just neutralized. MAIN FUNCTION OF THE RESPIRATORY SYSTEM Obtain oxygen from external environment and supply it to the cells Remove carbon dioxide produced by cellular metabolism from the body OTHER FUNCTIONS Phonation - production of sounds by the movement of air through the vocal cords Pulmonary defense mechanisms Pulmonary metabolism and the handling of bioactive materials PATHOGENESIS Results from host response to proliferation of pathogens in the alveoli

Microbial Factors Number of organisms Virulence Size of Inhaled Particle Host Factors/ Defenses Hair and turbinates of the nares - catch larger inhaled particles before they reach the lower respiratory tract Normal oropharyngeal flora - helps prevent the overflow of the more virulent pathogens; Gram (-) pneumonia is a result of alteration in the normal oropharygeal flora. Gag and Cough Reflexes - protection from aspiration Branching of the Tracheo-bronchial tree traps particles on the airway lining

Resident Alveolar Macrophages - extremely efficient at clearing and killing pathogens; assisted by local proteins that have intrinsic opsonizing properties or antibacterial/antiviral activity Lymphaticseliminates pathogens once engulfed by macrophages; pathogens then no longer represent an infectious challenge ROUTES OF TRANSMISSION 1. Aspiration of organisms that colonize the oropharynx o The most common mechanism for the production of pneumonia o Healthy individuals transiently harbor common pulmonary pathogens in the nasopharynx; microaspiration occurs frequently (e.g. during sleep) and more frequent ly when growing old (50s or 60s). And it is during this time that co-existing conditions normally occur (hypertension, diabetes, smoking related like COPD, malignancy) o Organisms: S. pneumoniae, H. influenzae, M. catarrhalis, anaerobes (gross aspiration), Enterobacteriaceae 2. Inhalation of Infectious Particles – Chlamydia and mycoplasma o Airborne droplet nuclei are small enough to bypass host defenses in the upper respiratory tract and airways o Include M. pneumoniae, C. pneumoniae, L. pnemophila 3. Hematogenous dissemination from extrapulmonary site o In patients with bacterial endocarditis, IV catheter infections (staphylococcus aureus) and extrapulmonary bacteremias (UTI and soft tissue infection that gain access to the systemic circulation) o Common in young individuals who developed infection of hair follicles or skin structures of the face. During pimple manipulation, there can be secondary infection of the skin that can gain access to the vascular system and spread systemically. This is usually caused by S. aureus, and instead of lobar consolidation, it will present with typical radiographic findings of multiple foci in the lungs at different stages, and may also cause extrapulmonary bacteremia. 4. Direct inoculation or contiguous spread o Tracheal intubation (oral flora) or stab wounds (skin flora) o Adjacent infection from the mediastinum or subphrenic space.

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A liver abcess that ruptured in the pleura or into the pleural space and gained access to the circulation, may present with hematogenous multiple foci; while a subphrenic abscess that ruptured in the right lower thoracic cavity may manifest with focal involvement mimicking a consolidation or a lung abscess.. When the upper airway is bypassed because there is a need to oxygenate or suction the lower respitary tree in an obtunded patient, some defense mechanisms are also bypassed which is why there is a need for adequate nursing care/ prevention of aspiration of oral cavity secretions since this may trickle down the sides of the ET tube and eventually reach the lower RT causing VAP. These are uncommon conditions and by history, you will have an inkling that you are dealing with these conditions.

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PATHOPHYSIOLOGY

This is important in the formulation of a treatment plan. Most of the community acquired pneumonias that are encountered are bacterial in origin, since the viral ones can be self-limiting. It is not being done here in the Philippines because the marker for pro calcitonin itself is much more expensive than the course of the antibiotics needed to treat the illness. PNEUMONIA Definition: an infection of the lung parenchyma Classification Community acquired pneumonia (CAP) Healthcare – associated pnemonia (HCAP) Hospital acquired (Nosocomial) pneumonia o Ventilator – associated pneumonia (it is a misnomer because it is not due to the ventilator itself but because of the endotracheal tube.) Try to prevent the use of ventilators.

Figure 4. Pneumonia Spectrum: Implications on Pathogens and Outcome Figure 3. Pathophysiology of Pneumonia.

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Most of the manifestations of pneumonia are not related to the organisms themselves, but to the host’s response to these pathogens. Inflamatory cells that are present to control the infection and the consequent inflammation that follows it causes the fever and purulent phlegm; and in order to get rid of this we tend to cough. If coughing is severe enough there is a tendency to become hypoxemic and eventually alkalotic. Dyspnea may follow, and with a decrease in lung compliance the labour of breathing becomes harder that respiratory failure may occur. At present, a new diagnostic technique is being introdueced where procalcitonin, a marker created by the parathyroid glands, is used. This substance is elevated in bacterial infections, and not in viral infections, allowing the physician to distinguish between the two.

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The risk for multidrug resistant pathogens increases from CAP to HCAP (transition between the two) to HAP, and VAP. When you have MDR pathogen, diagnosis and appropriate treatment will be delayed therefore morbidity and mortality of the patients also increases. Epidemiology

Figure 5. Percentage of Hospital Mortality

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CAP has 10% mortality rate and it doubles when you have HCAP (19.8), then triples when you have VAP (29.3%).

Table 1. In terms of morbidity, Pneumonia is the number 1 cause in 2007

MORBIDITY: TOP TEN CAUSES Number and Rate* -- 2007 2007 Diseases Numb Rate er 1. Acute Lower Respiratory 776, 929.4 Tract Infection and 562 Pneumonia 2. Bronchitis/Bronchiolitis 719,98 861.6 2 3. Acute watery diarrhea 577,11 690.7 8 4. Influenza 379,91 454.7 0 5. Hypertension 342,28 409.6 4 6. TB Respiratory 103,21 123.5 4 7. Chickenpox 46,779 56.0 8. Diseases of the Heart 37,092 44.4 9. Malaria 19,894 23.8 10. Dengue fever 15,838 19.0

Figure 6. After two years (2009), Pneumonia (purple) became the 4th cause of mortality. In decreasing order: Diseases of the heart (blue), Diseases of the Vascular system (red), Malignant neoplasms (yellow), Pneumonia (purple), and Accidents (cyan).

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A considerable proportion of patients with CAP require hospitalization Pneumonia treatment in tertiary hospitals in the Philippines cost Php 64M for 3861 reimbursements In 2010, Philhealth paid Php 2.042B (295,390 claims) for Pneumonia – highest among all cases claimed

Table 2. In terms of mortality, Pneumonia is the number 5 cause in 2007

MORTALITY: TOP TEN CAUSES Number and Rate* -- 2007 2007 Causes Numbe Rate r 1. Heart Disease 70,861 84.8 2. Vascular System 51,680 61.8 Diseases 3. Malignant Neoplasms 40,524 48.5 4. Accidents** 34,483 41.3 5. Pneumonia 32,098 38.4 6. Tuberculosis, all forms 25,870 31.0 7. Ill-defined and unknown 21,278 25.5 causes 8. Chronic lower 18,975 22.7 respiratory diseases 9. Diabetes Mellitus 16,552 19.8 10. Perinatal causes 13,180 15.8

% 17.6 12.8 10.1 8.6 8.0 6.4 5.3

Figure 7. LRTI is third leading cause of death worldwide. Pneumococcal pneumoniae is the leading known cause of lower respiratory infection mortality. Streptococcus pnuemoniae, most common strain.

COMMUNITY ACQUIRED PNEUMONIA MICROBIAL CAUSES OF CAP Typical Bacteria Atypical Bacteria  S. pneumonia  M. pneumonia -  H. influenzae  C. pneumonia -  Others (in selected cases):  Legionella spp.  Respiratory viruses o Staphylococcus aureus o Gram- negative bacilli o Anaerobes

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S. pneumonia is the most common cause of CAP Mycobacterium should also be consideredwhen suspecting CAP in Asian countries

Table 3. Commonly identified organisms in CAP in 8 Asian countries Group 19 | Pio, Raph, Jobs, Nica, Pao

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S. pneumoniae: Most Commonly identified Organism in CAP (8 ASIAN Countries) Pathogen Isolated No. of Isolates (%) (N = 390) S. pneumoniae 114 (29.2) Klebsiella 60 (15.4) pneumoniae Haemophilus 59 (15.1) influenza Pseudomonas 26 (6.7) aeruginosa Staphylococcus 19 (4.9) aureus Mycobacterium 13 (3.3) tuberculosis Moraxella catarrhalis 12 (3.1) Others 77 (19.7) Mycoplasma 61/556 (11.0) pneumoniae Chlamydia 55/411 (13.4) pneumoniae S. Pneumoniae contributes to a significant proportion of CAP regardless of age S. Pneumoniae disproportionately affects those at the extremes of age Comorbidities increase all-cause pneumonia risk in adults.

CAP

Alcoholism, asthma, COPD, CHF, CKD, immunosuppre ssion, institutionalization, old age

Pneumococcus Staphylococcus Enterobacteria ceae

Tobacco smoking (number 1 cause), COPDinfe ction, IV drug use Viral Recent hospitalizations, recent antibiotic treatment, alcoholism

P. aeruginosa

Structural lung disease, severe COPD, neutrope nia, systemic steroid use; recent use of antibiotics Diabetes, recent hote l stay or ship cruise, cell-mediated de ficiency

Legionella

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Tobacco smoking of >10 pack years is especially high risk, but there is no safe level of smoking. Recent use of broad spectrum antibiotics within the last 3 months because organism can develop reisistant patterns Individuals who have a history of staying in a hotel or cruise ship are at high risk for Legionella Pneumonia

EPIDEMIOLOGIC FACTORS SUGGESTING POSSIBLE CAUSES OF CAP Factor Possible Pathogens  Alcoholism S. pneumoniae, oral anaerobes, K. pneumoniae, Table 4. Microbial causes of CAP by site of care Acinectobacter spp., Microbial Causes of Community Acquired Pneumonia Mycobacterium By Site of Care tuberculosis Hospitalized Patients COPD and/or Smoking H. influenzae, P. Outpatient Non-ICU ICU aeruginosa, Legionella S. pneumoniae S. pneumoniae S. pneumoniae spp., S. pneumoniae, M. pneumoniae M. pneumoniae S. aureus Moraxella catarrhalis, H. influenzae C. pneumoniae Legionella spp. C. pneumoniae C. pneumoniae H. influenzae GramStructural Lung Disease P. aeruginosa, Respiratory Legionella spp. negativebacilli Burkholderia cepacia, Viruses Respiratory H. influenzae S. aureus Viruses Dementia, Stroke, Oral anaerobes, gram Decreased level of negative enteric  Respiratory viruses include – influenza A and B, Consciousness bacteria adenoviruses, respiratory syncytial viruses, and Lung abscess CA-MRSA (Community parainfluenza viruses. Acquired), oral  Outpatient and Non-ICU patients almost anaerobes, endemic have the same common causes of CAP. fungi, M. tuberculosis,  For ICU patients, the organisms are different atypical mycobacteria (but take note that the above table was from Travel to Ohio or St. Histoplasma Harrison’s which is North American and may not Lawrence River Valleys capsulatum reflect the organisms found in the Philippine ICU Travel to SW USA Hantavirus, setting). Coccidioides spp. Travel to SEA Burkholderia RISK FACTORS FOR CAP pseudomallei, avian ETIOLOGY RISK FACTORS influenza virus Stay in hotel or cruise Legionella spp. 

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MEDICINE 5.1 ship in previous 2 weeks Local influenza activity Exposure to bats or birds Exposure to birds Exposure to rabbits Exposure to sheep, goats, parturient cats

Influenza virus, S. pneumoniae, S. aureus H. capsulatum Chlamydophylia psittaci Francisella tularensis Coxiella burnetti

CLINICAL MANIFESTATIONS OF CAP Acute (to subacute) Hours to days to few weeks Course Any combination of cough, Respiratory symptoms purule nt sputum, dyspnea, pleuritic chest pain (signify inflammation of the parietal pleura) Constitutional Symptoms Freque ntly fe ver; chills, Extrapulmonary headache, obtundation, M anifestations diarrhea. In atypical organism, can also manifest with GI manifestations pleuritis +/Abnormal chest findings Consolidation, effusion, rales, whe ezes

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corresponds somehow to the apical segment of the right lower lobe or left lower lobe, still consider the possibility of TB. Rules in/out other diagnosis May be normal in some situations  If the patient comes to you, and x-ray is done within the first 24-48 hours, result may still be normal and yet there are adventitious sounds that tell you there is something there; this is referred to as the radiographic lag phase. Consider doing a repeat x-ray for the first 24-48 hour period, and then you might be able to see it. It only occurs for 2% of all cases.  Recall case #2 where the patient sought consult for a COPD exacerbation, xray was normal, and was then intubated 12 hours after. Repeat xray revealed an air bronchogram. Does that make him hospital acquired pneumonia or ventilator associated pneumonia? This is still considered community acquired pneumonia, because the patient was in the incubation period at the time of admission.

CLINICAL DIAGNOSIS Chest X-Ray o Required for the diagnosis o Confirms the presence and location of infiltrates  If normal consider tracheobronchitis  Lung abcessess indicates S. aureus as an etiologic agent o Assessment extent (severity) o Detects presence of effusion or cavitation  Consider when patient has pleural effusion since this can help decide whether to insert a chest tube  If multiple lobes are involve, this will show specific radiographic presentation like cavitation which suggests the presence of necrotizing pneumonia. If present, this should warrant close monitoring since it may indicate rapid deterioration.  If there is lung abscess, presence of air fluid level inside the parenchymal structure is noted, and this tells you that the patient is tremendously sick. It also tells you the possible etiologic agent, as multiple abscesses is typical of a S. aureus infection.  Cavitations in the apical segment may indicate Tuberculosis. If there are parenchymal infiltrates with a cavitary lesion in the middle of the chest which

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Figure 9. (Left) Chest X-Ray result showing consolidation of the right upper lobe and bulging of the minor fissure. There are a lot of exudates present there. This is a classical radiologic feature of Klebsiella pneumonia or Fried Lander’s bacillus. You also have to consider coexisting TB or that the pneumonia was caused by TB (Right) Pneumatocoele suggest Staphylococcal pneumonia in adult. In infant, pneumatocoele, indicates healing process

Figure 8. Homogenous opacification just like the heart, will not allow x-rays to penetrate or expose the film resulting in a radiopaque finding. Lung parenchyma is mainly air, and it allows exposure of films therefore it turns black. This is present on both the left and right lower lobes. The patient has bibasal pneumonia and PE findings should support the presence of consolidation on both sides.

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ETIOLOGIC DIAGNOSIS Sputum Examination o Gram Staining as performed initially indicates if sputum is good for culture o Low sensitivity and specificity o Good sputum: < 10 Squamous epithelial cells (SEC) and > 25 PMNs per LPF, indicates specimen is from lower respiratory tract. If there are abundant SEC, it means that the sample came from the upper respiratory tract. o May do sputum induction if no phlegm is produced  3% saline using ultrasonic nebulization

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MEDICINE 5.1 AFB smear is still the preferred method of diagnosing MTB in the Philippines. Serologic Test: for Mycoplasma, Chlamydia  This has an acute and convalescent phase, meaning a sample should be taken now, and again after 4-6 weeks. This is done to monitor patient recovery.

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MANAGEMENT: ADULT CAP GUIDELINES USA PHILIPPINES ATS 1993 1998 (PSMD) IDSA 1998 2004 (PSMD/PCCP/PAFP) IDSA 2000 2010 (PSMD/PCCP/PAFP/PCR) CDC 2000 ATS 2001 IDSA/ATS 2007

Figure 10. (Left) Poor sputum specimen with abundant SECs under low power. It suggests contamination with saliva and as a result cannot be used for diagnostic evaluation. (Right) Good sputum sample showing many WBCs and few SECs. Note presence of gram positive diplococci. 

Other Diagnostic Tests o 2 Blood Culture and Sensitivity (C/S) for some hospitalized patients  In only very sick individuals, intubated, requiring ICU admission, that is where some books would say blood cultures would be indicated. o Thoracentesis if (+) significant pleural effusion  Significant means on lateral decubitus film, there is 1cm layering of the fluid to the top. This may suggest a complicated parapneumonic effusion  Indicators of complicated effusion include: able to identify organism by gram staining, with pus/purulent, very low pH.  Monitor effusion as in might not only require Watch that thoracentesis but also insertion of a chest tube for drainage; to control source of infection o Urinary antigen tests for Legionella, Pneumococcus  It is a very high consideration. It is only able to identify 0-1, accounts for the majority of the Legionella disease in the clinics. It is sufficient enough. If it is negative, then you are not dealing with Legionella. o PCR for Legionella (research), Mycobacteria

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MANAGEMENT: SITE OF CARE Outpatient Medical Ward or Private Room ICU The purpose of this is to identify patients who can be treated on an outpatient basis in order to minimize cost. 80-90% can be treated as an outpatient while some require admission to a medical ward. 3-5% have severe presentation requiring ICU admission.

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MEDICINE 5.1 IDSA/ATS COMMUNITY ACQUIRED PNEUMONIA GUIDELINE OF 2007  Severity-of-illness scores, such as the CURB-65 Criteria (Confusion, Uremia, Respiratory Rate, Low Blood pressure, Age 65 or greater) or prognostic models, such as PSI,can be used to identify patients with CAP who may be candidates for outpatient treatment. CURB-65 CRITERIA Confusion Uremia/Increased BUN or creatinine BUN > 7 mmol/L (20 mg/dl) Respiratory rate >30cpm Low Blood pressure 130

Table 5. IDSA/ATS CAP Guidelines 2007

CURB-65 Recommendation 30-day Mortality Rate (%) 0.7 Outpatient 2.1 Outpatient 9.2 Ward 14.5 ICU 40 ICU 57 ICU 30-day mortality rate in studies tell us that patients may be best treated in an outpatient setting if their score is 0-1, wards with a score of 2, and ICU with scores of 3-5. Patients with scores of 3-5 will have a 15-50% mortality rate.

Score 0 1 2 3 4 5

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Table 6. Pneumonia Severity Index

Patient Characteristics Points Demographics Male Age in years Female Age in years – 10 Nursing home resident +10 Comorbid illness Neoplastic disease +30 Liver disease +20 Congestive Heart Failure +10 Cerebrovascular disease +10 Renal disease +10 Physical Examination Findings Altered mental status +20 Respiratory rate > 30 breaths per +20 minute blood pressure < 90mmHg Systolic +20 Temperature < 35oC or > 40OC +15 Pulse rate > 125 beats/min +10 Laboratory and Radiographic findings Arterial pH < 7.35 +30 BUN > 64 mg/dL (22.85 mmol/L) +20

+20 +10 +10 +10 +10

Low Low Low

Risk Clas s I II III

Modera te High

IV V

Risk

Mortality Recommend % ed 0.1(3,034 ) 0.6(5,778 ) 2.8(6,790 ) 8.2(13,10 4) 29.2(9,33 3)

Outpatient Outpatient Inpatient (briefly) Inpatient Inpatient

Pneumonia Severity index  More comprehensive, more accurate  Takes into account co-existing units such as demographics and co-morbid illness, abnormal PE findings and laboratory and radiographic findings.  Put together all the predictors and get the total score. If there are no predictors, then you have a low risk. If the score is > 70, then the patient will be treated in the inpatient setting and will have a higher risk.  It allows you to classify patients into low, moderate and high risks and allows you to make a decision to admit patients Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources – IDSA/ATS CAP Guidelines 2007 CRITERIA FOR ICU ADMISSION (SEVERE CAP) Minor Criteria o RR > 30 breaths/min o PaO2/FiO2 < 250 o Multilobar infiltrates o Confusion/disorientation o Uremia (BUN level > 20mg/dL) o Leukopenia ( WBC count < 4,000 cells/mm3) o Thrombocytopenia (Platelet count < 100,000 cells/mm3) o Hypothermia (Core temp < 36oC) o Hypotension requiring aggressive fluid resuscitation  Major Criteria o Invasive mechanical ventilation o Septic shock with the need for vasopressors *SEE APPENDIX FOR CAP RISK CLASSIFICATION AND SITE OF CARE DECISION 

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Management: Antibiotic Therapy Until more accurate and rapid diagnostic methods are available, the initial treatment for most patients will remain empirical (IDSA/ATS CAP Guidelines 2007) Antibiotics Classes Used in Bacterial Pneumonia: o Beta-lactams – more commonly used  Penicillins - prototype  Narrow spectrum: PCN-G, Phenoxymethylpenicillin (these drugs are directed against grampositive organisms)  Anti-staphylococcal: Methicillin (not available locally), Oxacillin (used for methicillin resistant staphylococcus aureus), Cloxacillin, Nafcillin  Extended-spectrum: Aminopenicillins: Ampicillin, Amoxicillin Anti-Pseudomonal: Ticarcillin, Piperacillin (can be combined with Tazobactam to become Tazocin)  Combined with Beta-Lactamase Inhibitors: Coamoxiclav, Ampicillin-sulbactam, Sultamicillin (combination of ampicillin and sulbactam; has its own antibiotic property so it has a better coverage than co-amoxiclav), Piperacillin-tazobactam  Cephalosporins  1st generation: no role in empiric treatment  2nd: Cefuroxime, Cefaclor (it is known to cause resistance so Cefuroxime is more commonly used) ; 2nd generation cephalosporins target gram positive organisms  3rd: Oral or parenteral Anti-Pseudomonal: Ceftazidime, Cefoperazone Without anti-pseudomonal coverage: Ceftriaxone, Cefotaxime, Cefpodoxime (Cefpodoxime is similar to 2 nd generation cephalosporins as far as antimicrobial coverage is concerned)  4th: Cefepime, Cefpirome; their effect is concentrated more on gram-negative organisms including Pseudomonas aeruginosa  In giving cephalosporins you should start from gram positive to gram

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negative and lastly to antipseudomonal coverage  Carbapenems – drug of choice for extended spectrum beta lactamase (ESBL)-producing organisms like klebsiella, proteus and E.coli.  Non-anti-Pseudomonal: Ertapenem (given once a day)  Anti-Pseudomonal: Imipenem (earliest), Meropenem, Doripenem (latest and has more SE such that when it is used in sepsis, patients are more commonly dying)  Monobactam – example is aztreonam Macrolides – good for atypical organisms and also covers for Streptococcus pneumoniae  Erythromycin – has more GI side effects like gastritis and vomiting  Clarithromycin, Dirithromycin – lesser GI side effects compared to erythromycin  Azithromycin –not a true macrolide but rather an azalide; its activity is similar to macrolide; used only once a day but in CAP it is given 3 times a day (tablet) Tetracyclines –considered as newer macrolides  Tetracycline – can cause dental staining  Doxycycline – available in the Philippines  Minocycline Fluoroquinolones  Weak anti-pneumococcal activity: Ciprofloxacin, Ofloxacin, Norfloxacin, Pefloxacin; they are good for gram-negative organisms as they are being used for typhoid fever but their activity is not good when used against Streptococcus pneumoniae  APFQ (Antipneumococcal fluoroquinolones): Moxifloxacin (has good activity against tuberculosis especially for the drug-resistant TB), Levofloxacin, Gatifloxacin, Gemifloxacin; newer fluoroquinolones and they have good activity against Streptococcus pneumonia and atypical organisms like mycoplasma and legionella; Gatifloxacin was pulled from the market because of hepatotoxicity Aminoglycosides – relatively cheap and has good gram-negative activity including Pseudomonas; adverse effect is ototoxicity and nephrotoxicity

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MEDICINE 5.1 Streptomycin, Gentamycin, IV q12h). Tobramycin, Amikacin – these drugs Table 9. Philippine CAP Guidelines 2010 have good activity against TB Risk Potential Empiric Therapy o Glycopeptides – examples are vancomycin Stratification Pathogens and bleomycin Low risk CAP  S. AMOXICILLIN Table 8. Empirical Antibiotic Teatment of Community (previously or pneumoniae Acquired Pneumonia healthy) EXTENDED  H. influenzae Outpatients MACROLIDES  C. Previously healthy and no antibiotics in past 3 (suspected atypical pneumoniae months pathogen)  M.  Macrolide [clarithromycin (500 mg PO bid) or pneumoniae azithromycin (500 mg PO once, then 250 mg qd)] or  M.  Doxycycline (100 mg PO bid) catarrhalis Comorbidities or antibiotics in past 3 months: select Amoxicillin is given 3 grams per day in 3 divided an alternative from a different class doses  Respiratory fluoroquinolone [moxifloxacin (400 mg Low Risk CAP  S. BETA LACTAMASE PO qd), gemifloxacin (320 mg PO qd), levofloxacin (stable coINHIBITOR pneumoniae (750 mg PO qd)] or morbid illness  H. influenzae COMBINATION or recent (BLIC)* OR  Beta-lactam [preferred: high-dose amoxicillin (1 g tid)  C. antibiotic 2ND GENERATION or amoxicillin/ clavulanate (2 g bid); alternatives: pneumoniae therapy) CEPHALOSPORIN ceftriaxone (1–2 g IV qd), cefpodoxime (200 mg PO  M. +/bid), cefuroxime (500 mg PO bid)] + Macrolide pneumoniae EXTENDED **In regions with a high rate of “high-level”  M. MACROLIDES pneumococcal macrolide resistance, consider catarrhalis Alternative: alternatives listed above for patients with  Enteric G(-) 3rd generation oral comorbidities bacilli CEPHALOSPORIN +/Inpatients extended Non-ICU MACROLIDE  Respiratory fluoroquinolone [moxifloxacin (400 mg Remember respiratory fluoroquinolone can replace PO or IV qd), gemifloxacin (320 mg PO qd), the two combinations because of the better levofloxacin (750 mg PO or IV qd)] or coverage and they have same bioavailability  Beta-lactam [cefotaxime (1–2 g IV q8h), ceftriaxone whether tablet or IV preparation as advantage (1–2 g IV qd), ampicillin (1–2 g IV q4–6h), ertapenem Moderate Risk  S. IV NON(1 g IV qd in selected patients)] + Macrolide [oral CAP PSEUDOMONAL pneumoniae clarithromycin or azithromycin (as listed above for BETA LACTAM  H. influenzae previously healthy patients) or IV azithromycin (1 g (BLIC/CEPHALOSP  C. once, then 500 mg qd)] ORIN/ pneumoniae ICU CARBAPENEM)  M.  Beta-lactam [cefotaxime (1–2 g IV q8h), ceftriaxone + pneumoniae (2 g IV qd), ampicillin-sulbactam (2 g IV q8h)] + EXTENDED  M. Azithromycin or a fluoroquinolone (as listed above MACROLIDE catarrhalis for inpatients, non-ICU) or  Enteric G(-) Special Concerns IV NPBL + bacilli If Pseudomonas is a consideration RESPIRATORY FQ  L.  Antipneumococcal, antipseudomonal Betapneumophila lactam [piperacillin/ tazobactam (4.5 g IV q6h),  Anaerobes* cefepime (1–2 g IV q12h), imipenem (500 mg IV q6h), Ertapenem is the non-pseudomonal carbapenem meropenem (1 g IV q8h)] + either Ciprofloxacin (400 that can be used for this purpose mg IV q12h) or Levofloxacin (750 mg IV qd) or IV NPBL + Respiratory fluoroquinolones are  The above Beta-lactams + an aminoglycoside reserved as last resort especially if resistance [amikacin (15 mg/kg qd) or tobramycin (1.7 mg/kg qd) happens and azithromycin] or High Risk CAP  S. IV NPBL  The above Beta-lactams + an aminoglycoside + an (no risk (BLIC/cephalospori pneumoniae antipneumococcal fluoroquinolone factors for P. n/ Carbapenem)  H. influenzae If CA-MRSA is a consideration aeruginosa) +  C.  Add linezolid (600 mg IV q12h) or vancomycin (1 g IV Extended pneumoniae 

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MEDICINE 5.1   

  High Risk CAP (with risk factors for P. aeruginosa)

M. pneumoniae M. catarrhalis Enteric gramnegative bacilli L. pneumophila Anaerobes*

Macrolide or IV Respiratory FQ

the one preferred now and not the old PPSV23 - IM

S. IV Antipneumococcal, pneumoniae Anti-Pseudomonal  H. influenzae Beta Lactam  C. (BLIC/Carbapenem pneumoniae / Cephalosporin)  M. + pneumoniae IV extended   M. macrolide + catarrhalis IV Aminoglycoside  Enteric OR gramIV APn, APs BL  negative + bacilli IV ciprofloxacin/  L. levofloxacin pneumophila   Anaerobes*  P. aeruginosa Levofloxacin 750mg daily has also antipseudomonas activity   

  



Complications Metastatic Infection o Unusual o E.g. endocarditis, brain abscess Lung abscess o Those with necrotizing infections Complicated parapneumonic effusion o Diagnosed by thoracentesis o Requires drainage Measures for Prevention of CAP Smoking cessation Vaccines: Influenza and Pneumococcal Reducing effect of comorbidities: control CHF, hyperglycemia

     

Anatomic asplenia (congenital asplenia and splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery])  Generalized malignancy  Solid organ or bone marrow transplants  Leukemia, Lymphoma  Multiple myeloma  Human immunodeficiency virus infection  Chronic renal failure or nephrotic syndrome  Receiving immunosuppressive therapy, including corticosteroids HAP, VAP, HCAP DEFINITION HAP (Hospital-Acquired Pneumonia) o Pneumonia that occurs 48 hours or more after hospital admission, which was not incubating at the time of admission VAP (Ventilator-Acquired Pneumonia) o Pneumonia that arises 48-72 hours after endotracheal intubation HCAP (Health Care-Associated Pneumonia)  Pneumonia in any patient who was hospitalized in an acute care hospital for 2 or more days within 90 days of infection; resided in a nursing home or long-term facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic 

RISK FACTORS FOR HCAP Hospitalization for 2 days or more in the preceding 90 days Residence in a nursing home or extended-care facility Home infusion therapy (including antibiotics) Chronic dialysis within 30 days Home wound care Family member with MDR pathogen

Table 11. Clinical Conditions Associated With and Likely Pathogens In Health Care-Associated Pneumonia Pathogen Target Individuals (age 50 P. years old) MRS Aci Risk Factor aerugin A spp. Immunocompromised osa

Table 10. 2012 Update of Routine Immunization for Filipino Adults

Vaccine Type/ Route PNEUMOCOCCAL  Polysaccharide (PPSV23) – IM/SC  Conjugate (PCV13) – this is

MDR Ent

Conditions Hospitalization for ≥ 48 h  Functional asplenia (sickle cell Hospitalization for ≥ 2 days in disease and other prior 3 months hemoglobinopathies, splenic Nursing home or extendeddysfunction) care-facility residence

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MEDICINE 5.1 Antibiotic therapy in preceding 3 months Chronic dialysis

  

Fungi Viruses Pneumocystis jiroveci

Home infusion therapy Home wound care Family member with MDR infection

**Aci spp.: Acinetobacter spp., MDR Ent: MDR Enteriobacteriociae,





Table 12. Empirical Antibiotic Treatment of Health Care– Associated Pneumonia

EPIDEMIOLOGY Early-onset HAP/VAP o Within first 4 days of hospitalization o Better prognosis o Caused by antibiotic-sensitive bacteria Late-onset HAP/VAP o > 5days of hospitalization o Caused by multidrug-resistant (MDR) pathogens o patient mortality and morbidity

Patients without Risk Factors for MDR Pathogens  Ceftriaxone (2 g IV q24h) or  Moxifloxacin (400 mg IV q24h), ciprofloxacin (400 mg IV q8h), or levofloxacin (750 mg IV q24h) or CANADIAN HAP AND VAP GUIDELINES 2008: RISK FACTORS  Ampicillin/sulbactam (3 g IV q6h) or  Oropharyngeal colonization with pathogenic  Ertapenem (1 g IV q24h) organisms Patients with Risk Factors for MDR Pathogens  Host factors: supine positioning, extensive  β-lactam: o Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–burns, mechanical ventilation, cardiothoracic surgery, ARDS, head trauma (head trauma is a 12h) or risk factor for acquiring MRSA; also o Piperacillin/tazobactam (4.5 g IV q6h), neurosurgical procedures) imipenem (500 mg IV q6h or 1 g IV q8h), or  Environmental factors: nasogastric tubes, meropenem (1 g IV q8h) plus ventilator tubing condensate (these can be  A second agent active against gram-negative potentially infected, and therefore, increase the risk of the patient for developing VAP) bacterial pathogens: o Gentamicin or tobramycin (7 mg/kg IV q24h) or Acid-suppressing drugs o Critically ill patients, especially trauma amikacin (20 mg/ kg IV q24h) or patients, have an increased risk of upper GI o Ciprofloxacin (400 mg IV q8h) or levofloxacin bleeding; therefore, they are routinely given (750 mg IV q24h) plus acid-suppressing drugs. When the pH of the  An agent active against gram-positive bacterial GIT is altered, it gets colonized by pathogens: organisms that can be vomited and o Linezolid (600 mg IV q12h) or aspirated into the respiratory tree. o Vancomycin (15 mg/kg, up to 1 g IV, q12h) ETIOLOGY OF HAP, VAP, HCAP Non-MDR Pathogens MDR Pathogens S. pneumoniae P. aeruginosa Other streptococcus MRSA spp. Acinetobacter spp. H. Influenzae ATB-resistant MSSA Enterobacteriaceae ATB-sensitive Enterobacter spp. Enterobacteriaceae ESBL-positive strains E. Coli Klebsiella spp. K. pneumoniae Legionella spp. Proteus spp. Bulkholderia cepacia Enterobacter spp. Aspergillus spp S. Marcescens  

UNCOMMON CAUSES OF VAP Legionella species Anaerobes

SOURCES OF MICROORGANISMS CAUSING HAP AND VAP Endogenou s Oropharynx Trachea Nasal carriage Sinusitis Gastric fluids

Exogenous



Aspirati on

Inhalati on







Health care workers Ventilatory circuits Nebulizers Biofilms*

 HAP and VAP  *Biofilms are subpopulations of microorganisms that develop inside the endotracheal tube. Inside the endotracheal tube, biofilms are not accessible to the antibiotic given, so when the patient’s secretions are suctioned, and the suction is moved

Blood

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MEDICINE 5.1 deeper into the respiratory tree, the biofilm is moved and inoculated into the lung parenchyma. Therefore patient will suffer the same infection from the same organism. Risk Factors for MDR Pathogens  Antimicrobial therapy in the preceding 90 days (some consider up to 6 months)  Current hospitalization of 5 days or longer  High frequency of antibiotic resistance in the community or specific hospital unit  Presence of risk factors for HCAP  Immunosuppressive disease and/or therapy 





Clinical Manifestations/Diagnosis Lower respiratory signs/symptoms o Cough o Rhonchi o Wheezing o Purulent sputum Changes in lab parameters o New/progressive radiodensities o Leukocytosis or leukopenia o Worsening of blood oxygenation Differential diagnosis o Pulmonary Thromboembolism o Pulmonary Edema o Pulmonary Hemorrhage o Drug Reaction o Tracheobronchitis

(Tracheal Aspirate) Progression of Chest Xray (Day 3)

growth No progression

or heavy growth

compatible with gram stain Progression, no CHF or ARDS



If CPIS score is 6 or more, it is more likely that you are dealing with ventilator-associated pneumonia.  Pulmonary function assessment through CPIS would indicate prognosis. An increasing pulmonary function would indicate that the patient may be on his way to recovery *SEE APPENDIX FOR DIAGNOSTIC ALGORITHM BASED ON CANADIAN HAP AND VAP GUIDELINES Microbiological Approach to the Diagnosis of HAP/VAP UK HAP Guidelines 2008: Respiratory Microbiological Sampling Methods  Endotracheal aspirate cultures o Not for the diagnosis of VAP o Constantly contaminated  Invasive sampling is preferred (PSB and BAL either blind or bronchoscopic) o Same performance o More likely not to be contaminated o Quantitative cultures of respiratory specimens should not be relied on for the diagnosis of HAP/VAP o Quantification of intracellular organisms in BAL specimens is a rapid and specific test and can be used as a guide for therapy  To discriminate between colonization and true infection by determining the bacterial burden o Quantitative ETA: 106 cfu/mL o Quantitative PSB: 103 cfu/mL o Bronchoscopic BAL: 104-105 cfu/mL

Clinical Strategy Diagnosis by new or progressive radiographic infiltrate plus at least 2 of the following: o Fever >38oC o Leukocytosis or leukopenia o Purulent secretions  In hospitalized patients, especially those on mechanical ventilator, application of clinical * PSB= Protected specimen brush; BAL= Bronchoalveolar criteria often results in overdiagnosis of lavage; ETA= Endotracheal aspirate pneumonia  In an attempt to reduce the tendency of Microbiologic Causes of VAP overdiagnosis, a modified CPIS score was Non-MDR Pathogens MDR Pathogens proposed and was first used in 1991 Streptococcus Pseudomonas aeruginosa pneumoniae Table 13. Clinical Approach to Diagnosis of HAP/VAP Other Streptococcus spp. MRSA CPIS pts 0 1 2 Haemophilus influenzae Actinobacter spp. Chest X-ray None Diffuse Localized MSSA Antibiotic-resistant Infiltrates Enterobacteriaceae Temperature 36.5 – 38.4 38.5 – 38.9 >39 Antibiotic-sensitive or 500 Proteus spp. Legionella pneumophila 240 or ARDS evidence of Serrata marcescens Aspergiulus spp. ARDS 

Microbiology (-) rare or light (+) moderate Group 19 | Pio, Raph, Jobs, Nica, Pao

(+) and

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MEDICINE 5.1 Antibiotic Therapy No Risk Factors for MDR Pathogens

     

Ceftriaxone Moxifloxacin Levofloxacin Ciprofloxacin Ampicillin/sulbactam Ertapenem

With Risk Factors for MDR Pathogens



Anti-pseudomonal betalactam PLUS  2nd Agent active against gram-negative bacteria PLUS  3rd Agent active against gram-positive bacteria

Prevention Strategies Pathogenic Mechanism Prevention Strategy Oropharyngeal Antibiotic paste in colonization (ventilator) oropharyngeal cavity Avoidance of prolonged Elimination of normal antibiotic courses (7-8 days flora unless its pseudomonas then do 21 days) Large-volume Short course of prophylactic oropharyngeal antibiotics for comatose aspiration around time patients of intubation Postpyloric enteral feeding; Gastroesophageal reflux avoidance of high gastric residuals; prokinetic agents Prophylactic agents that raise Bacterial overgrowth of gastric pH; selective stomach decontamination Hand washing, especially with Cross-infection from alcohol-based rub; Isolation; other colonized patients Proper sterilization of equipment Endotracheal intubation; Large-volume aspiration avoidance of sedation; decompression of small-bowel Microaspiration around endotracheal tube Endotracheal intubation Non-invasive ventilation Prolonged duration of Daily awekening from ventilation sedation; weaning protocols Abnormal swallowing Early percutaneous function tracheostomy Head of bed elevated; Secretions pooled Avoidance of reintubation; above endotracheal Minimize sedation; Avoid tube supine position Tight glycemic control (but not too low to avoid Altered lower hypoglycemia); lowering of respiratory host hemoglobin transfusion defenses threshold; specialized enteral feeding formula



Prevention o Alcohol-based hand disinfection o Surveillance of ICU infections o Avoiding or minimizing the duration of endotracheal intubation o Minimizing the risk of microaspiration o Preferential use of enteral nutrition o Use of restricted transfusion trigger policy for blood products

Summary: Best Practices in HAP Management  Diagnostic Strategies o Standardized o Cost-effective  Treatment Strategies o Appropriate/adequate initial empiric therapy o Local data (antibiogram) o Minimum effective period of antibiotics o Do not use antibiotic if not indicated o Immediately deescalate if with culture results  Non-antibiotic therapies  Preventive strategies o General infection control o Target modifiable factors  BEST STRATEGY: Hand washing

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MEDICINE 5.1 APPENDIX

CAP RISK CLASSIFICATION AND SITE OF CARE DECISION

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MEDICINE 5.1 Two or more of the following: Temp. >38oC or 6: likely pneumonia Score 4-6: if patient is intubated, may still consider VAP Recalculated daily: may stop or don’t start antibiotic therapy if