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References Pharmacotherapy: A Pathophysiologic Approach. 10th edition 2017. Applied Therapeutics: The Clinical Use of Drugs. 10th Edition.2013. Chapter 64. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27-72. (IDSA/ATS/CAP) Management of Adults With Hospital-acquired and Ventilatorassociated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) Guidelines for the management of community acquired pneumonia in adults: update 2009. British Thoracic Society Community Acquired Pneumonia in Adults Guideline Group. October 2009 Vol 64 Supplement III (BTS/CAP) 2 INTRODUCTION lower respiratory tract: tracheobronchial tree and lung parenchyma. The most common infections involving the lower respiratory tract include bronchitis, bronchiolitis, and pneumonia. Lower respiratory tract infections in children and adults are most commonly a result of either viral or bacterial invasion of lung parenchyma. The diagnosis of viral infections rests primarily on the recognition of a characteristic constellation of clinical signs and symptoms. In contrast, because bacterial pneumonia usually necessitates expedient, effective, and specific antibiotic therapy, its management depends, in large part, on isolation of the etiologic agent by culture from lung tissue or secretions. 3 Bronchitis and bronchiolitis are inflammatory conditions of the large and small elements, respectively, of the tracheobronchial tree. The inflammatory process does not extend to the alveoli. Bronchitis frequently is classified as acute or chronic. Acute bronchitis occurs in all ages, whereas chronic bronchitis primarily affects adults. Bronchiolitis is a disease of infancy. Respiratory syncytial virus is the most common cause of acute bronchiolitis, an infection that mostly affects infants during their first year of life. In the well infant, bronchiolitis is usually a self-limiting viral illness, whereas in the child with underlying respiratory or cardiac disease or both, the child may develop severe respiratory compromise (failure) necessitating in-hospital treatment, such as rehydration, oxygen, and in select patients, bronchodilators, ribavirin aerosol, or both. 4 Acute bronchitis occurs most commonly during the winter months, following a pattern similar to those of other acute respiratory tract infections. Cold, damp climates, the presence of high concentrations of irritating substances, such as air pollution or cigarette smoke, or both may precipitate attacks. 5 Acute bronchitis usually begins as an upper respiratory infection with nonspecific complaints. Cough is the hallmark of acute bronchitis and occurs early. The onset of cough may be insidious or abrupt, and the symptoms persist despite resolution of nasal or nasopharyngeal complaints. 6 Respiratory viruses are by far the most common infectious agents associated with acute bronchitis. Routine use of antibiotics in the treatment of acute bronchitis should be discouraged; however, in patients who exhibit persistent fever or respiratory symptoms for more than 4 to 6 days, the possibility of a concurrent bacterial infection should be suspected. When possible, antibiotic therapy should be directed toward anticipated respiratory pathogen(s) (S. pneumoniae, H. influenzae, M. pneumoniae). 7 Treatment of acute bronchitis General Approach to Treatment Treatment of acute bronchitis is symptomatic and supportive in nature. Reassurance and antipyretics frequently are all that are needed. Bed rest for comfort may be instituted as desired. Patients should be encouraged to drink fluids to prevent dehydration and possibly to decrease the viscosity of respiratory secretions. Mist therapy (use of a vaporizer) may promote the thinning and loosening of respiratory secretions. 8 Treatment of acute bronchitis Pharmacologic Therapy Mild analgesic–antipyretic therapy : aspirin (not children?), acetamenophen, ibuprofen. Antitussives; although not recommended for routine use, persistent, mild cough, which may be bothersome, can be treated with dextromethorphan Occasional antibiotics (Routine use, should be discouraged : Erythromycin or its analogues (clarithromycin, azithromycin). Alternatively and empirically, a fluoroquinolone with activity against the suspected bacterial pathogens (such as levofloxacin) may be used. 9 PNEUMONIA Pneumonia remains the most common cause of severe sepsis and infectious cause of death in children and adults in the United States, with a mortality rate of 30% to 40 where approximately 4 million cases are diagnosed annually at a cost of $23 billion redundant to the health care system. Pneumonia occurs throughout the year, with the relative prevalence of disease resulting from different etiologic agents varying with the seasons. It occurs in persons of all ages, although the clinical manifestations are most severe in the very young, the elderly, and the chronically ill. 11 Definition Acute infiltrate on chest radiograph, or Auscultatory findings such as altered breath sounds or localized rales حشرجة Pneumonia can be generally defined as inflammation of the lung parenchyma, in which: consolidation of the affected part and a filling of the alveolar air spaces with exudate, inflammatory cells, and fibrin is characteristic. 12 Acute infection of pulmonary parenchyma (alveoli) with at least some symptoms of acute infection accompanied by: BTS/CAP definition The clinical definition of CAP that has been used in community studies has varied widely but has generally included : a complex of symptoms and signs both from the respiratory tract and regarding the general health of the patient. Features such as : fever (>38°C), pleural pain, dyspnoea and tachypnoea and signs on physical examination of the chest (particularly when new and localizing) seem most useful when compared with the gold standard of radiologica diagnosis of CAP 13 Pneumonia is inflammation of the lung with consolidation. The cause of the inflammation is infection, which can result from a wide range of organisms. Community-acquired pneumonia (CAP) Patients who develop pneumonia in the outpatient setting and have not been in any health care facilities, which include wound care and hemodialysis clinics. (Pneumonia developing in patients with no contact to a medical facility) Aspiration is of either oropharyngeal or gastrointestinal contents. Hospital-acquired pneumonia (HAP): pneumonia that occurs 48 hours or more after admission. (Not changed based on HAP-VAP 2016) Ventilator-associated pneumonia (VAP) requires endotracheal intubation for at least 48 to 72 hours before the onset of pneumonia. VAP is defined as a pneumonia occurring >48 hours after endotracheal intubation(Not changed based on HAP-VAP 2016) 14 HAP accounts for about 25% of all ICU infections. 15 Intubation and mechanical ventilation increase the risk of HAP by 6 to 21-fold. Nearly 90% of ICU HAP occurs in mechanically ventilated patients (VAP). 50% of VAP occurs within the first four days of ventilation. HCAP 2005 Health care–associated pneumonia (HCAP): HCAP: Pneumonia developing in patients not in an acute care medical facility but two or more risk factors for MDR (multidrug resistant) pathogens: ((e.g., P. aeruginosa, Acinetobacter species, and MRSA] Recent hospitalization ≥2 days within past 90 days; Nursing home or long-term care facility resident; Recent (past 30 days) antibiotic use, chemotherapy, wound care or infusion therapy at either a healthcare facility or home; Hemodialysis patients; Contact with a family member with infection caused by MDR pathogen Risk factors for exposure to MDR bacteria in HCAP include the following: 1. Hospitalization for 2 or more days in an acute care facility within 90 days of current illness 2. Exposure to antibiotics, chemotherapy, or wound care within 30 days of current illness 3. Residence in a nursing home or long-term care facility 4. Hemodialysis at a hospital or clinic 5. Home nursing care (infusion therapy, wound care) 6. Contact with a family member or other close person with infection due to MDR bacteria 16 HCAP, 2016 new Healthcare-Associated Pneumonia The rationale for inclusion of the HCAP designation with the HAP/VAP guidelines in 2005 was that patients with HCAP were thought to be at high risk for MDR organisms by virtue of their contact with the healthcare system. Therefore, due to both the patients’ contact with the healthcare system and the presumed high risk of MDR pathogens, guidelines for these patients were included with guidelines for HAP and VAP, the HAPs. However, There is increasing evidence that many patients defined as having HCAP are not at high risk for MDR pathogens . Furthermore, although interaction with the healthcare system is potentially a risk for MDR pathogens, underlying patient characteristics are also important independent determinants of risk for MDR pathogens. For these reasons, the panel unanimously decided that HCAP should not be included in the HAP/VAP guidelines. HAP-VAP 2016 17 EPIDEMIOLOGY AND ETIOLOGY Most common organisms: S. pneumoniae is the predominant bacterial pathogen associated with CAP. (70 % of all cases) Mycoplasma pneumoniae. Nontypeable Hemophilus influenzae esp.: COPD patients and those with cystic fibrosis. Moraxella catarrhalis: the very young and the very old. (10-20 % of all cases) Chlamydia pneumoniae and Legionella Viruses are a common cause of CAP in children (~65%) and much less common in adults (~15%). 1. More common: influenza A (adult) and B and adenoviruses, 2. less common causes include rhinoviruses, enteroviruses, 18 cytomegalovirus, varicella-zoster virus, herpes simplex virus, and others. 18 In children, viral pneumonia is caused more commonly by: respiratory syncyntial virus, influenza A virus, and parainfluenza virus. In elderly patients admitted to the hospital with severe pneumonia, the mortality rate is up to 40% In the outpatient setting (mild to moderate disease), the mortality rate is less than 5%. 19 19 The term ‘‘atypical pathogens’’ is used to define pneumonia infections caused by: Mycoplasma pneumoniae; Chlamydophila pneumoniae; Chlamydophila psittaci (psittacosis, parrot fever); and Coxiella burnetii. (Q fever; cattle, sheep, goats and other domestic mammal) 20 21 22 Aspiration Pneumonia Aspiration of the oropharyngeal or gastric contents may lead to aspiration pneumonia or chemical (acid) pneumonitis. Aspiration pneumonia refers specifically to the development of an infectious infiltrate in patients who are at increased risk of oropharyngeal aspiration. Risk factors for aspiration include: Dysphagia (can be caused by stroke or other neurologic disorders, seizures, alcoholism, and aging) Change in oropharyngeal colonization (altered by oral/dental disease, poor oral hygiene, tube feedings, or medications) Gastroesophageal reflux (Acid suppression is an important factor in the treatment of GERD, which may allow enteric gram-negative bacilli to colonize the gastric contents) Decreased host defenses like: 1. 2. 3. impaired mucus production or cilia function, decreased immunoglobulin in secretions, altered cough reflex. The infection can result in a necrotizing pneumonia or lung abscess. 23 23 HAP and VAP Risk factors for the development of HAP fall into four general categories: 1. Intubation and mechanical ventilation: increase the risk of HAP/VAP 6- to 21-fold. 2. Aspiration: supine positioning of the patient, the presence of the endotracheal tube preventing closure of the epiglottis over the glottis, enteral feedings, gastroesophageal reflux, medications. 3. Oropharyngeal colonization: altered by oral/dental disease, poor oral hygiene, tube feedings, medications. use of antibiotics, oral antiseptics, poor infection control measures, which may decrease normal commensal flora and allow pathogenic organisms to colonize the oral cavity. 4. Hyperglycemia: two proposed mechanisms are: a. b. inhibiting phagocytosis providing additional nutrients for bacteria. 24 VAP: Colonization of the ventilator circuit. 24 25 DIAGNOSIS IDSA/ATS The diagnosis of CAP is based on: the presence of select clinical features (e.g., cough, fever, sputum production, and pleuritic chest pain) and is supported by imaging of the lung, usually by chest radiography. Physical examination to detect rales or bronchial breath sounds is an important component of the evaluation but is less sensitive and specific than chest radiographs. Both clinical features and physical exam findings may be lacking or altered in elderly patients. Pneumonia can be classified as typical or atypical, although the clinical presentations are often similar. 26 27 28 31 Physicians should begin their treatment decisions by assessing the need for hospitalization : using a prediction tool for increased mortality, such as the Pneumonia Severity Index (PSI), combined with clinical judgment. Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the PSI, can be used to identify patients with CAP who may be candidates for outpatient treatment. (Strong recommendation; level I evidence.) 32 PSI is based on 20 variables. Based on the score, patients are stratified into five risk categories based on 30day mortality. 33 PSI categories 34 BTS 2009 35 36 BTS 2007 37 38 GUIDELINES: SITE-OF-CARE DECISIONS (IDSA) Hospital Admission Decision Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment. (Strong recommendation; level I evidence) 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. (Strong recommendation; level II evidence) For patients with CURB-65 scores >2, more-intensive treatment—that is, hospitalization or, where appropriate and available, intensive in-home health care services—is usually warranted. (Moderate recommendation; level III evidence) Intensive Care Unit (ICU) Admission Decision Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence) Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in the Table below. (Moderate 39 recommendation; level II evidence) IDSA/ATS CAP criteria PaO2 to fraction of inspired oxygen The presence of 3 of the following minor criteria indicates severe CAP and suggests the likely need for ICUlevel care Direct admission to an ICU is mandated 40 Desired Outcomes The goal of antibiotic therapy is to: eliminate the patient’s symptoms, 2. minimize or prevent complications, 3. and decrease mortality. 1. Potential complications secondary to pneumonia include 1. further decline in pulmonary function in patients with underlying pulmonary disease, 2. prolonged mechanical ventilation, 3. bacteremia/sepsis/septic shock, and death. In addition, using an agent with the narrowest spectrum of activity that covers the suspected pathogen without having activity against organisms not involved in the infection is preferred. This is to minimize the 41 development of resistance. General Approach to Treatment Designing a therapeutic regimen for any patient with any type of pneumonia begins with three general categories of consideration: 1. Patient-specific factors that will affect therapy: a. age, b. renal function, c. drug allergies and/or drug intolerances, d. immune status (e.g., diabetes, neutropenia, or immunocompromised host), e. cardiopulmonary disease, f. pregnancy, g. medical insurance and prescription coverage, h. prior antibiotic exposure(s) (what agents and when). 42 42 General Approach to Treatment 2. The top one to three organisms likely causing the infection and resistance issues associated with each organism. Treating patients with HCAP?, HAP, or VAP is more complex than treating patients with CAP. 3. What antimicrobials: Will cover these organisms b. Will not be too broad or narrow in spectrum, c. Will penetrate into the site of infection, d. What they cost. a. 43 43 Factors influencing infection from a resistant organism: Antimicrobial therapy in preceding 90 days Current hospitalization of at least 5 days High occurrence of antibiotic resistance in the community or in the specific hospital unit 4) Presence of risk factors for HCAP: 1) 2) 3) 1) 2) 3) 4) 5) 6) 5) 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) Peritoneal or hemodialysis within 30 days Home wound care Close contact family member with MDR pathogen Immunosuppressive disease and/or therapy. Once these issues are addressed, antimicrobial therapy can be selected44 and initiated. 44 General Approach to Treatment The first priority in assessing the patient with pneumonia is to: evaluate the adequacy of respiratory function and to determine the presence of signs of systemic illness, specifically dehydration or sepsis with resulting circulatory collapse. Oxygen or, in severe cases, mechanical ventilation and fluid resuscitation should be provided as necessary. Further supportive care of the patient with pneumonia includes humidified oxygen for hypoxemia, administration of bronchodilators (albuterol) when bronchospasm is present, Additional therapeutic adjuncts include adequate hydration (IV if necessary), optimal nutritional support, and control of fever. Selection of an appropriate antimicrobial must be made based on the patient’s probable or documented microbiology, distribution in the respiratory tract, side effects, and cost. Respiratory tract infection diagnosis and treatment guideline reports have been published by authoritative professional organizations (BTS and ATS) 45 General Approach to Treatment Delayed antibiotic therapy has been associated with an increased length of stay and decreased survival in CAP; therefore, a rapid and correct diagnosis is imperative. The most recent IDSA/ATS CAP treatment guidelines recommend the first dose of antibiotic be given in the ED in effort to avoid treatment delays associated with the hospital admission process. Initial antimicrobial treatment is empirical because of the limited turnaround time, sensitivity, and specificity of currently available microbiological tests. All patients should be empirically treated for pneumococcus and atypical pathogens. In addition, the choice of the initial regimen should be based on medical comorbidities or epidemiological factors. In addition, an assessment of likelihood for infection caused by an antibiotic- resistant pathogen should take place. The most important consideration in the selection of empiric therapy is to determine risk for infection with DRSP (Table 64-6). 46 Approach to empiric antibiotic therapy in patients with communityacquired pneumonia FQ for PNC allergic FQ + aztreonam for for PNC allergic 47 48 Doses can be increased for more severe disease and may require modification in patients with organ dysfunction. a- Tetracyclines are rarely used in pediatric patients, particularly in those younger than 8 years because of tetracycline-induced permanent tooth discoloration. b- Higher-dose amoxicillin, amoxicillin– clavulanate (e.g., 90 mg/kg/day) is used for penicillin-resistant S. pneumoniae. c- Fluoroquinolones are avoided in pediatric patients because of the potential for cartilage damage; however, their use in pediatrics is emerging. Doses shown are extrapolated from adults and require further study. 49 ATS 2007 erythromycin is not often used now, because of gastrointestinal intolerance and lack of activity against H. influenzae. 50 51 52 53 ertapenem, as an acceptable b-lactam alternative for hospitalized patients with risk factors for infection with gram-negative pathogens other than Pseudomonas Aeruginosa. • • • • The severity of illness generally is increased (caused either by the organism itself or by underlying comorbidities in the patient). The pathogens are essentially the same as in the outpatient setting. Therapy should be initiated within the 4 hours of presentation to the emergency room or hospital. Conversion to oral therapy should occur within 48 to 72 hours for most patients, and discharge from the hospital should be within 5 days if there are no complications. 54 the majority of ICU patients would still require combinatio n therapy Patients admitted to the intensive-care unit (ICU) have severe pneumonia, and the etiology includes S. pneumoniae and H. influenzae as in the other categories; however, the incidence of Legionella pneumophila increases in this setting and should be included in the organism differential. In addition, enteric gram negative bacilli and S. aureus are more frequently the cause of the pneumonia. This combination therapy minimizes the risk of treatment failure owing to a resistant pathogen and also provides coverage against all the potential pathogens. 55 combination A consistent Gram stain of tracheal aspirate, sputum, or blood is the best indication for Pseudomonas Coverage Alternative regimens are provided for patients who may have recently received an oral fluoroquinolone, in whom the aminoglycoside-containing regimen would be preferred structural lung diseases, such as bronchiectasis, or repeated exacerbations of severe COPD MRSA 56 Special concerns If P. aeruginosa is suspected: Recommended regimens double-cover the Pseudomonas and S.pneumonia, include the use of: An antipneumococcal, antipseudomonal b-lactam (piperacillin- tazobactam, cefepime, imipenem, or meropenem) + either ciprofloxacin or levofloxacin (750 mg) or The above b-lactam + an aminoglycoside and azithromycin or The above b-lactam + an aminoglycoside and an antipneumococcal fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for above b-lactam) (moderate recommendation; level III evidence) If comminity-acquired MRSA (CA-MRSA ) is a consideration, add vancomycin or linezolid (moderate recommendation; level III evidence) 57 57 58 Switch from Intravenous to Oral Therapy Patients should be switched from intravenous to oral therapy when they are: IDSA/ATS 2007, table 10 hemodynamically stable improving clinically, are able to ingest medications, 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. 59 60 Duration of Therapy The duration of therapy for pneumonia should be kept as short as possible and depends on several factors: 1. 2. 3. 4. 5. type of pneumonia, inpatient or outpatient status, patient comorbidities, bacteremia/sepsis, the antibiotic chosen. If the duration of therapy is too prolonged, then it can have a negative impact on the patient’s normal flora in the respiratory and gastrointestinal tracts, vaginal tract of women, and the skin. This can result in colonization with resistant pathogens, Clostridium difficile colitis, or overgrowth of yeast. The longer antibiotics are administered, the greater is the chance for toxicity from the agent as well as an increase cost. 61 61 Duration of Therapy for CAP For treating outpatient CAP: two antibiotics are approved for a 5-day duration of therapy, levofloxacin (the 750-mg dose) and azithromycin. The duration of therapy for all other therapies is 7 to 10 days. For treatment of CAP in patients admitted to the hospital, the duration depends on whether or not blood cultures were positive. In negative blood cultures, the duration of therapy is 7 to 10 days. If blood cultures were positive, then the duration of therapy should be 2 weeks from the day blood cultures first became negative. 62 62 63 Transitioning inpatients with community-acquired pneumonia from IV to oral antibiotics 64 Pathogen-Directed Therapy Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial, therapy should be directed at that pathogen. (Moderate recommendation; level III evidence.) 66 Aspiration If a patient aspirates his or her oral contents and pneumonia develops, then anaerobes and Streptococcus spp. are the primary pathogens. Antibiotics active against these organisms include: 1. penicillin G, 2. ampicillin/sulbactam, 3. clindamycin, 4. metronidazole. 67 67 HAP and VAP • HAP: pneumonia not incubating at the time of admission and occurring 48 hours or more after admission • VAP: pneumonia occurring more than 48 hours after endotracheal intubation 68 Major Differences in New Guidelines • Removal of the concept of healthcare-associated pneumonia (HCAP)….CAP??? • Recommendation that each hospital generate antibiograms to base antimicrobial choice upon • Shorter duration of therapy independent of microbial etiology, as well as antibiotic de-escalation. Antibiograms • Empiric treatment regimens based on antibiograms • Minimize patient harm and exposure • Reduce the development of antibiotic resistance • Decrease the unnecessary use of dual gram-negative and empiric MRSA treatment • Specific to VAP populations (ICU) • Specific to HAP populations Table 2 72 Risk Factors for MDR Pathogens (table 2) MRSA or VAP HAP P. aeruginosa Prior IV antibiotic use within 90 day Septic shock at time of VAP ARDS prior to the occurrence of VAP 5 or more days of hospitalization prior to the occurrence of VAP Acute renal replacement therapy prior to the occurrence of VAP 74 Empiric Therapy for VAP • S. aureus, P. aeruginosa and other gram-negative bacilli • MRSA coverage if o Risk factors for antimicrobial resistance (table 2) o Units where >10%-20% of S. aureus isolates are methicillin resistant o Units where the prevalence of MRSA is not known o Vancomycin or linezolid. • MSSA coverage only, if o Without risk factors for antimicrobial resistance o ICUs where <10%-20% of S. aureus isolates are methicillin resistant o If MSSA empiric coverage is indicated the guidelines suggest using pippercillin-tazobactam, cefepime. Levofloxacin, imipenem, or meropenem. o If MSSA is proven the use of oxacillin, nafcillin, or cefazolin is recommended. - but not for empiric treatment Empiric Antipseudomonal Coverage VAP • Double Coverage o o o • Risk factors for resistance Units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy Susceptibility rates for ICU not available Monotherapy o o o No risk factors for resistance ICU’s where ≤ 10% of gram-negative isolates are resistant to the agent being considered for monotherapy Avoid aminoglycosides or colistin when possible 77 Empiric Therapy for HAP • S. aureus, P. aeruginosa and other gram-negative bacilli • MRSA coverage if o o o o IV antibiotics in last 90 days Unit where >20% of S. aureus isolates are methicillin resistant Prevalence of MRSA is not known High risk for mortality • MSSA coverage if o Empiric treatment and have no risk factors for MRSA o Not at high risk of mortality Empiric Antipseudomonal Coverage HAP • • Double Coverage o Risk factors for Pseudomonas or other gram-negative infection o IV antibiotics in the last 90 days o Structural lung disease o High risk of mortality Monotherapy o All other patients with HAP who are being treated empirically o Do not use aminoglycoside as sole antipseudomonal agent 80 Definitive Treatment Monotherapy vs. Combination therapy for P. aeruginosa • • Monotherapy o Not in septic shock or at high risk of death o Susceptibility results are known Combination therapy o Septic shock o High risk of death when the results of antibiotic susceptibility testing are known • Recommend against aminoglycoside monotherapy Duration of Therapy for HAP and VAP • 7 day course of antimicrobial therapy • Discontinue based on PCT levels + clinical criteria vs. clinical criteria alone • De-escalation of therapy recommended rather than fixed therapy DOUBLE COVERAGE FOR PSEUDOMONAS? Debate over whether or not double coverage for Pseudomonas is required. In vitro studies have shown that aminoglycosides exhibit synergistic killing against gram negative bacilli when combined with β-lactams. Dosing of the aminoglycosides depends on the patient’s renal function. A high-dose once-daily regimen (e.g., 4–7 mg/kg gentamicin or tobramycin or 15–20 mg/kg amikacin) can be used in patients with good renal function. 84 84 Advantages of double coverage when treating VAP, HAP, or : 1. synergistic effect, 2. broaden the coverage empirically to increase the likelihood of covering the majority of resistant pathogens. VAP is the most studied of these types of pneumonias and is often the most severe. Studies have demonstrated an increase in mortality when inadequate therapy is initiated for VAP. Crude mortality ranges from 35% to 92% with inadequate therapy compared with 25% to 47% with adequate therapy. Once a pathogen or pathogens have been identified, therapy should be narrowed to cover only those pathogens. 85 Use of broad-spectrum antibiotics for prolonged durations increases the risk of colonization with MDR pathogens. 85 Prevention http://www.cdc.gov/vaccines/hcp/acip-recs/vacc- specific/pneumo.html Pneumonia kills more children than any other illness; among approximately 9 million children aged <5 years who die each year worldwide, 1.6 million die from pneumonia. Through the Global Action Plan for Prevention and Control of Pneumonia, the World Health Organization and international partners recommend that the global health burden of pneumonia be reduced by: using vaccines against organisms that cause pneumonia. providing appropriate care and treatment for persons who contract pneumonia, and promoting preventive measures such as exclusive breastfeeding of infants during their first 6 months of life 86 Transmission Pneumococcus is in many people's noses and throats and is spread by coughing, sneezing, or contact with respiratory secretions. Why it suddenly invades the body and causes disease is unknown. 87 Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) account for approximately 60% of pneumonia deaths worldwide of children aged 1 month–5 years in countries that do not use pneumococcal or Hib conjugate vaccines. In the United States, pneumococcal and Hib conjugate vaccines are recommended for infants and children aged <2 years as part of the routine infant immunization schedule and have reduced morbidity and mortality from pneumococcal disease by 76% and from Hib disease by >99% among children aged <5 years In 2010, a 13-valent pneumococcal conjugate vaccine was licensed and recommended in the United States. Collaborative international efforts are expanding use of these vaccines in developing countries. 88 89 90 91 92 Who should receive PPSV23 All adults 65 years of age and older. Anyone 2 through 64 years of age who has a long-term health problem such as: heart disease, lung disease, sickle cell disease, diabetes, alcoholism, cirrhosis, leaks of cerebrospinal fluid or cochlear implant. Anyone 2 through 64 years of age who has a disease or condition that lowers the body’s resistance to infection, such as: Hodgkin’s disease; lymphoma or leukemia; kidney failure; multiple myeloma; nephrotic syndrome; HIV infection or AIDS; damaged spleen, or no spleen; organ transplant. Anyone 2 through 64 years of age who is taking a drug or treatment that lowers the body’s resistance to infection, such as: long-term steroids, certain cancer drugs, radiation therapy. Any adult 19 through 64 years of age who is a smoker or has asthma. Residents of nursing homes or long-term care facilities. 93 Influenza Influenza viruses A and B can cause pneumonia in pediatric and adult patients. Amantidine and rimantidine are available oral agents with activity against influenza virus type A. If started within 48 hours of the onset of the first symptoms, they reduce the duration of the illness by about 1.3 days. Oseltamivir (Tamiflu) and zanamivir also reduce the duration of the illness by about 1.3 days if initiated within 40 to 48 hours of the first symptoms. For active infection beyond the first 48 hours, none of these agents is 94 effective in treating the infection, and supportive care is the best treatment for these patients. 94 95 PREVENTION The influenza vaccine The influenza vaccine is available in two forms, injectable and nasal inhalation. The injectable is an inactivated vaccine (containing killed virus). The flu shot is approved for use in people older than 6 months of age, including healthy people and people with chronic medical conditions. The nasal-spray flu vaccine is made with live, weakened flu viruses that do not cause the flu (live attenuated influenza vaccine). This formulation is approved for use in healthy people 5 to 49 years of age who are not pregnant. The ability of the flu vaccine to protect a person depends on two key factors: 1. the age and health status of the person getting the vaccine 2. and the similarity or “match” between the virus strains in the vaccine and those in circulation. 96 96 Persons for Whom Annual Vaccination is Recommended (2012/2013) All persons aged 6 months and older should be vaccinated annually. Protection of persons at higher risk for influenza-related complications should continue to be a focus of vaccination efforts. When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to persons who: are aged 6 months--4 years (59 months); are aged 50 years and older; have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus); are immunosuppressed (including immunosuppression caused by medications or by human immunodeficiency virus); are or will be pregnant during the influenza season; are aged 6 months--18 years and receiving long-term aspirin therapy and who therefore might be at risk for experiencing Reye syndrome after influenza virus infection; are residents of nursing homes and other chronic-care facilities; are American Indians/Alaska Natives; are morbidly obese (body-mass index is 40 or greater); are health-care personnel; are household contacts and caregivers of children aged younger than 5 years and adults aged 50 years and older, with particular emphasis on vaccinating contacts of children aged younger than 6 months; and are household contacts and caregivers of persons with medical conditions that put them at higher risk for severe complications from influenza. 97 98 Case A.T., a 58-year-old man, is admitted to the hospital from home with fever, increased sputum production, tachypnea, and complaints of a knifelike chest pain that is made worse by coughing and breathing. Pertinent medical history includes a 12-year history of CB and chronic renal insufficiency. A.T. regularly produces two cups of sputum per day and continues to smoke two and one-half packs of cigarettes per day. He has been taking amoxicillin 250 mg BID prophylactically for the past 14 months. Physical examination reveals an elderly man lying restlessly in bed, awake, and oriented to person but not place or time; temperature, 101.5°F (38.6°C), blood pressure (BP), 145/88 mmHg; heart rate (HR), 105 beats/minute; and respiratory rate (RR), 33 breaths/minute. Chest examination reveals slight splinting on the right side with inspiration and fine crackling rales in the lower base of the right lung. Examination of the left lung is normal. Significant laboratory results include the following: WBC count, 16,200 cells/mm3 (normal, 5,000–10,000 cells/mm3); differential polymorphonuclear neutrophils (PMNs), 82% (normal, 45%–79%); bands, 9% (normal, 0%–5%); lymphocytes, 8% (normal, 16%– 47%); hematocrit (Hct), 40% (normal, 37%–47%); sodium, 141; potassium, 4.8; blood urea nitrogen (BUN), 32; creatinine, 3.8 mg/dL; glucose 148, mg/dL; arterial blood gases (ABGs), pH 7.46 (normal, 7.38–7.45), PO2, 68 mmHg (normal, 80–100 mmHg), PCO2, 36 99 mmHg (normal, 38–45 mmHg), HCO3, 24 mEq/L (normal, 22–26 mEq/L); and Gram stain reveals <10 epithelial cells, 20 to 25 PMNs, and predominance of Gram-negative rods. 99 Case Questions What are the normal respiratory defenses against infection? What factors present in A.T. make him susceptible to pulmonary infection? What clinical signs, symptoms, and laboratory tests are consistent with pneumonia in A.T.? How can the etiologic organism be determined? How should A.T. be treated? 100 100