Pneumonia is defined as chest infiltrates on chest radiography or chest CT scan associated with fever and an identified infectious etiology. From: Hematology [Seventh Edition], 2018
Fred F. Ferri MD, FACP, in Ferri's Clinical Advisor 2022, 2022 • Antibiotic therapy should be based on clinical, radiographic, and laboratory evaluation. Empiric therapy regimens for severe community-acquired pneumonia are summarized
inTable 5. Macrolides [azithromycin or clarithromycin] or doxycycline can be used for empiric outpatient treatment of CAP as long as the patient has not received antibiotics within the past 3 mo and does not reside in a community in which the prevalence of macrolide resistance is high. Updated guidelines from the American Thoracic Society and Infectious Diseases Society of America3 have added
amoxicillin as a first-line agent for healthy adult outpatients with CAP.Fig. 6 summarizesempiric therapy for CAP. The treatment of choice in suspectedLegionella pneumonia is either a quinolone [e.g., moxifloxacin] or a macrolide [e.g., azithromycin] antibiotic. A beta-lactam antibiotic is usually added to macrolides. In the hospital setting, patients admitted to
the general ward can be treated empirically with a second- or third-generation cephalosporin [ceftriaxone, cefotaxime, or cefuroxime] plus a macrolide [azithromycin or clarithromycin] or doxycycline. An antipseudomonal quinolone [levofloxacin or moxifloxacin] can be substituted in place of the macrolide or doxycycline. Empiric therapy in ICU patients: IV beta-lactam [ceftriaxone, cefotaxime, ampicillin-sulbactam] plus an IV quinolone
[levofloxacin, moxifloxacin] or IV azithromycin. In hospitalized patients at risk forP. aeruginosa infection, empiric treatment should consist of an antipseudomonal beta-lactam [meropenem, doripenem, imipenem, or piperacillin-tazobactam] with or without a second antipseudomonal agent such as an aminoglycoside or an antipseudomonal quinolone. In patients with
suspected methicillin-resistantS. aureus, vancomycin or linezolid is effective. Corticosteroids: Clinical trials evaluating adjunctive use of corticosteroids in severe CAP have produced mixed results. There is no evidence that adjunctive use of corticosteroids improves outcomes in mild to moderate CAP. Guidelines advise against adjunctive treatment of CAP with corticosteroids except in patients with other indications for their
use such as asthma, COPD, an autoimmune disease or CAP with septic shock that is refractory to fluid resuscitation and vasopressor support.4 Duration of antibiotic treatment ranges from 5 to 14 days. Trials have shown that in adults hospitalized with CAP, stopping antibiotic treatment after 5 days in clinically stable patients is reasonable and noninferior to usual care. HematogenousStaphylococcus
infection, abscesses, and cavitary lesions might require prolonged antibiotic therapy, sometimes until radiological resolution is documented.Pneumonia, Bacterial
Acute General Rx
Pneumonia
Stephen R.C. Howie, ... Stephen M. Graham, in International Encyclopedia of Public Health [Second Edition], 2017
Introduction
Pneumonia remains a major contributor to mortality and morbidity worldwide in all age groups and is the leading cause of death in infants and children globally, exceeding the combined mortality of malaria, tuberculosis and HIV infection. The lung is constantly exposed to microorganisms and the combined effects of pathogen, host, and environmental factors determine whether or not the clinical condition known as pneumonia occurs. Pneumonia is generally more prevalent in low- and middle-income countries. Incidence is highest at the extremes of ages such as the elderly and infants. The overwhelming majority of pneumonia deaths in infants and young children occur in low-income settings.
There are a number of classifications of pneumonia in use that have implications for etiology, management, and prognosis, such as classification based on the origin of the infection or its severity. The term ‘community-acquired pneumonia’ [CAP] refers to the appearance of infection in a non-hospitalized population with no risk factors for multi-drug-resistant pathogens whereas the term ‘hospital acquired pneumonia’ or ‘nosocomial pneumonia’ is used when there is no evidence that the infection was present or incubating at the time of hospital admission. The latter type of pneumonia is most frequently found in patients receiving mechanical ventilation, hence the term ‘ventilator-associated pneumonia.’ Another classification in common use in children with community-acquired pneumonia in resource-limited settings is based on clinical severity, and is used to guide management decisions such as antibiotic treatment, hospitalization and oxygen therapy.
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Overview of Pneumonia
Lee Goldman MD, in Goldman-Cecil Medicine, 2020
Noninfectious Considerations
Many noninfectious conditions cause patients to present with a syndrome consistent with acute or subacute pneumonia, and 15 to 20% of all patients admitted from the emergency department for suspected pneumonia may not be infected. Pulmonary edema [Chapter 52] is the most common noninfectious cause of a pneumonia syndrome in middle-aged and older patients. The diagnosis should be made based on history, physical examination, and radiographic findings, supported by elevated B-natriuretic peptide levels. Patients with lung cancer [Chapter 182] commonly present with fever and a pulmonary infiltrate, often called postobstructive pneumonia.9 Cavitary lesions may be present. Infection is actually not thought to be present in the majority of cases. Acute respiratory distress syndrome [Chapter 96] in response to a serious nonpulmonary infection is often indistinguishable from pneumonia because it commonly presents with fever, lung crackles, an elevated WBC count, and pulmonary infiltrates.
Cryptogenic organizing pneumonia [Chapter 85], acute interstitial pneumonia, eosinophilic pneumonia, sarcoidosis, and other interstitial pneumonias [Chapter 86] are uncommon conditions that are almost always initially misdiagnosed as community-acquired pneumonia. Pulmonary hemorrhage and vasculitis may also cause pulmonary infiltrates and fever. In ANCA-associated granulomatous vasculitis [Chapter 254], these infiltrates may also be associated with cavitary lesions. Attention to the patient’s history may reveal a longer history of symptoms, and careful review of earlier chest radiographs may reveal prior radiographic abnormalities, consistent with a chronic, noninfectious process. Pulmonary emboli with infarction [Chapter 74] can cause pleuritic chest pain and pulmonary infiltrates, with sputum that contains neutrophils but few or no bacteria. Patients with septic pulmonary emboli should be assessed for other foci of infection, such as an infected heart valve or intravascular device.
Treatment
Hospital Admission
Several scoring systems may help in the decision as to whether a patient should be hospitalized, including the pneumonia severity index [Tables 91-3 and91-4] and SMART-COP [Table 91-5]. A corollary decision, whether a patient should be admitted to an intensive care unit [ICU], can be guided by the mortality risks as assessed by the pneumonia severity index or by the SMART-COP algorithim [Table 91-6]. Other indicators of overwhelming infection that indicate a need for ICU admission include a WBC count of 6000/µL or lower in bacterial pneumonia [usually seen with increased band forms], thrombocytopenia, hypothermia, or a Po2 less than or equal to 90 in someone who has no underlying lung disease.
Supportive therapy should include fluid replacement to maintain blood pressure [e.g., an average of 4.5 liters of fluids with electrolytes are required in the first 24 hours to treat a patient with pneumonia and septic shock [Chapter 100]], oxygen for hypoxemia, and mechanical ventilation if adequate gas exchange cannot otherwise be achieved [Chapter 97].
Antibiotic Therapy
Based on good evidence that outcomes are worse with prolonged delays, initial antibiotics should be given as soon as the diagnosis of pneumonia is considered likely, regardless of whether that be in a physician’s office or an emergency department.10 Guidelines for the empirical antibiotic therapy of community-acquired pneumonia in outpatients [Table 91-7] focus on common infectious causes of pneumonia and are generally successful because a specific etiologic agent is only infrequently determined.11 However, this approach should not discourage the careful consideration of possible noninfectious causes of fever and pulmonary infiltrates or reasonable attempts to establish a specific infectious diagnosis.
For empirical outpatient therapy,12 guidelines from the Infectious Diseases Society of America and the American Thoracic Society recommend a macrolide, doxycycline, a “respiratory” quinolone [levofloxacin or moxifloxacin, but not ciprofloxacin, which is thought to be slightly less effective against pneumococci], or a β-lactam antibiotic together with a macrolide.12b These recommendations are based on a desire to provide therapy effective for common bacterial causes of pneumonia such asS. pneumoniae [Chapter 273],H. influenzae [Chapter 340],M. catarrhalis [Chapter 284], andLegionella [Chapter 298], as well as infections due toMycoplasma [Chapter 301] orChlamydia [Chapter 302].
In contrast, Swedish and UK guidelines recommend outpatient treatment for pneumonia with oral penicillin or amoxicillin. The rationale for this approach is that pneumococcus, which is the most likely potentially dangerous cause of pneumonia, is much better treated by penicillin or amoxicillin than by doxycycline or macrolides [to which a varying proportion of pneumococci are resistant], whereas a patient who fails to respond to penicillin or amoxicillin within a few days can be switched to a macrolide or doxycycline to treat potentialMycoplasma andChlamydia. In the United States, one third ofHaemophilus and the majority ofMoraxella produce β-lactamase, which would make amoxicillin plus clavulanic acid a better choice in patients who have underlying lung disease. Patients with pneumonia and a history of low-grade fever and cough for more than 5 to 6 days should be treated with a macrolide or doxycycline because of the likelihood thatMycoplasma orChlamydia are responsible.
In a patient who is sick enough to be hospitalized, the physician should make a conscientious effort to determine an etiologic agent. Initial therapy may be empirical, but identifying a causative organism has at least three advantages: [1] therapy can be tailored to an identified causative organism, thereby reducing antibiotic overuse and exposure of patients to antibiotics they do not need; [2] if a patient fails to respond promptly the physician can know whether simply to continue existing antibiotics or which ones to change to; [3] an alternative treatment can be selected appropriately for a patient who has an adverse drug reaction.
Recommended initial empirical antibiotic treatment of pneumonia that does not require ICU care [seeTable 91-7] includes a respiratory fluoroquinolone [levofloxacin or moxifloxacin, but not ciprofloxacin] or a β-lactam [cefotaxime, ceftriaxone, ampicillin-sulbactam], together with a macrolide.A3 Either of these regimens will treat pneumonia due toS. pneumoniae, and they will also be effective againstHaemophilus, methicillin-susceptibleS. aureus, Moraxella, Legionella, Mycoplasma, andChlamydia, as well as some less common organisms. Such combination therapy appears to result in more rapid clinical improvementA4 ut not shorter in-hospital length of stay or lower mortalityA5 compared with empirical β-lactam monotherapy. Newer options include lefamulin [150 mg intravenously every 12 hours]A5b,A5c or omadacycline [100 mg intravenously every 12 hours for 2 doses then once daily].A5d
To avoid overtreatment, every effort should be made to narrow treatment in accordance with identified pathogens. To avoid undertreatment, the risk of possibleS. aureus infection including MRSA should be considered, especially in patients who may have influenza or a history of injection drug use, chronic renal failure, prior corticosteroid therapy, or progression despite outpatient antibiotics. In such patients, the prevalence of these organisms in the community mandates further consideration of ceftaroline as the β-lactam or the addition of vancomycin or linezolid. The absence of nasal carriage of MRSA on PCR testing greatly reduces the likelihood that this organism is causing pneumonia.
For patients who require ICU admission, a β-lactam [cefotaxime, ceftriaxone, or ampicillin-sulbactam] should be given in combination with either azithromycin or a respiratory fluoroquinolone. WhenPseudomonas is a consideration [e.g., in patients who have pneumonia with predominant gram-negative rods on sputum examination; patients with end-stage COPD, bronchiectasis, or other structural lung disease; or patients who have been treated with glucocorticoids or other immunosuppressive drugs], an antipseudomonal β-lactam or carbapenem [piperacillin-tazobactam, cefepime, imipenem, or meropenem] should be selected. The benefit of adding a second antipseudomonal drug [so-called “double coverage”] has not been proven. A more important principle is that, once a diagnosis of gram-negative pneumonia is established, treatment should be based on the optimal dose of an appropriate antibiotic identified by susceptibility testing.
Data on the efficacy of low-dose corticosteroids [e.g., 30 mg methylprednisolone daily] in treating pneumonia have been conflicting. However, two recent meta-analyses concluded that 3 to 7 days of corticosteroids can reduce morbidity and mortality in patients with severe community-acquired pneumonia.A6,A7 By comparison, patients with severe COVID-19 benefit fromsystemic corticosteroids [e.g., dexamethasone 6 mg daily for up to 10 days or hydrocortisone 200–400 mg intravenously for about 7 days], which can reduce mortality by about one-third [Chapter 342A].A7b
Hospital Course
The value of aggressive attempts to determine the cause of pneumonia becomes obvious during a patient’s hospital course. The expected response to therapy includes defervescence, return of the WBC count to normal, and disappearance of the systemic signs of acute infection within a few days after antibiotics have been begun. Pulmonary infiltrates may resolve slowly, cough may persist for weeks, and fatigue may persist for months, especially in elderly persons.
Patients may not respond or may even deteriorate during the first day or two of treatment despite appropriate antibiotic therapy. A further reason to identify the infecting organism is to avoid the temptation to add antibiotics that may provide no further benefit and may have deleterious side effects. For patients who do respond, identification of the causative organism allows broad-spectrum antibiotics to be replaced by a simpler regimen, thereby potentially shortening the hospitalization, reducing the risk for complications such asClostridioides difficile colitis [Chapter 280], and avoiding uncertainty about the culprit medication should an adverse drug reaction occur.
Failure to Respond to Antibiotic Therapy
The failure to respond to antibiotic therapy raises a number of concerns [Table 91-8]. If the patient simply does not improve, the antibiotic may not be appropriate for the infecting organism. The first step should be to review culture results and antibiotic susceptibilities to ensure that the patient has received an adequate dose of an appropriate antibiotic. When patients show an initial partial response but then have a persistent low-grade fever and leukocytosis, the antimicrobial therapy may have been correct, and the causative organism may be susceptible, but there may be a loculated infection such as empyema [Chapter 92]. AMycobacterium or a nonbacterial organism [e.g., a virus12c or a fungus] may be responsible. Alternatively, a noninfectious disease such as lung cancer or pulmonary embolism, or an inflammatory lung condition such as eosinophilic pneumonia or interstitial lung disease [Chapter 86] may explain a newly recognized pulmonary infiltrate that is accompanied by other symptoms of pneumonia, such as fever, cough, and sputum production.
When antibiotics have been given empirically and cultures have not been obtained, the lack of a response creates a difficult therapeutic dilemma. For patients with a partial or inadequate response to initial therapy, the physician should aggressively pursue additional diagnostic measures, such as cultures, a chest CT scan, a thoracentesis if an effusion is present, bronchoscopy with bronchoalveolar lavage, and possibly transbronchial biopsy rather than simply changing or adding antibiotics.
Duration of Treatment
The optimal duration of therapy for pneumonia is uncertain. In general, outpatients with community-acquired pneumonia should be treated for 5 to 7 days. Patients who are hospitalized should receive parenteral therapy until they are hemodynamically stable and able to ingest and absorb oral antibiotics, after which oral antibiotics can be given. Three to 5 days of parenteral therapy and a final few days of oral treatment after the patient has become afebrile [temperature 39.0° C] children less than 5 years of age with a white blood count [WBC] greater than 20,000/mm3 identified a lobar infiltrate in 26% of patients [36 of 146] who had a radiograph performed and no signs of pneumonia.22
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Pneumonia
Jean Chastre, ... Alain Combes, in Mechanical Ventilation, 2008
PROGNOSTIC FACTORS AND PREDICTION RULES FOR DETERMINING DISEASE SEVERITY
Severe pneumonia can be defined as pneumonia requiring treatment in the intensive care unit [ICU]. In general terms, this definition includes patients with pneumonia who require [1] ventilatory support because of acute respiratory failure, inability to clear secretions, deterioration in gas exchange with hypercapnia, or persisting hypoxemia; [2] circulatory support because of hemodynamic instability and signs of peripheral hypoperfusion; or [3] intensive monitoring and treatment of other organ dysfunctions resulting either from a septic component of pneumonia or the underlying disease. In 1993 the American Thoracic Society adopted a statement on the initial management of patients with CAP in which severe illness was defined by the presence of any one of the following features: an admission respiratory rate of more than 30 per minute, a Pao2/Fio2 ratio of less than 250, the need for mechanical ventilation, the presence of bilateral or multilobar infiltrates or rapidly expanding infiltrates, shock, a need for vasopressors, oliguria, or acute renal failure.8 Although this definition was based on factors known to be associated with the need for intensive care, the definition is probably too liberal, and in one study 65% of all patients admitted to the hospital were found to have at least one feature of severe pneumonia present. To improve the specificity of the criteria, one suggestion has been to change the respiratory rate criterion to 35 breaths/min, but it is probable that severe CAP is best defined by patients having at least two of the severe pneumonia criteria mentioned previously. In one more recent study, the nine criteria for severe CAP were divided into five “minor” criteria that could be present on admission and four “major” criteria that could be present on admission or later in the hospital stay.9 The minor criteria included respiratory rate, 30/min; Pao2/Fio2 < 250; bilateral pneumonia or multilobar pneumonia; systolic blood pressure [BP], 90 mm Hg; and diastolic BP, 60 mm Hg. The major criteria included a need for mechanical ventilation, an increase in the size of infiltrates by >50% within 48 hours, septic shock or the need for vasopressors for >4 hours, and acute renal failure [urine output 2 mg/dL in the absence of chronic renal failure]. In this retrospective study, the need for ICU admission could be defined using a rule that required the presence of either two of three minor criteria [systolic BP, 90 mm Hg; multilobar disease; Pao2/Fio2 ratio < 250] or one of two major criteria [need for mechanical ventilation or septic shock]. When the other criteria for severe illness were evaluated, they did not add to the accuracy of predicting the need for ICU admission. With this rule the sensitivity was 78%, the specificity was 94%, the positive predictive value was 75%, and the negative predictive value was 95%.
In the British Thoracic Society [BTS] study, the authors formulated a simple discriminant rule based on the three variables that were consistently associated with death.5 The rule was considered positive when at least two of the following three factors were present: respiratory rate of 30/minute or more, diastolic blood pressure of 60 mm Hg or less, and blood urea nitrogen of more than 7 mmol/L. A positive rule was associated with a 21-fold increase in mortality, with a specificity of 79% and a sensitivity of 88%. However, the positive predictive value was low; only 21 patients of the 108 [19%] who met the rule died. A second rule, in which confusion was used instead of blood urea nitrogen, showed even higher specificity but low sensitivity. The BTS rules have now been validated by two studies, one prospective and one retrospective.10,11 Unfortunately, the positive predictive values of these rules are too low to permit transfer to the ICU of all patients who meet their definition. However, those patients and patients who present with one or more of the other negative prognostic factors have a higher risk for developing severe pneumonia and should be closely monitored for signs of deterioration. This monitoring should include regular checks of vital signs, mental status, fever, and oxygenation, as well as auscultation of the lungs or chest radiography for signs of spread of the pneumonia.7
Although the BTS studies attempted to identify patients with a worse prognosis at the time of admission to the hospital so that they could be targeted for special attention in an ICU, the focus of other studies was just the opposite—namely, to identify those patients with pneumonia who are at lower risk of death and do not need hospital care. Based on the analysis of data collected on 14,199 adult inpatients with pneumonia, Fine and colleagues derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days.12,13 This prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings [such as respiratory rate of 30 per minute or temperature of 40°C], and abnormal laboratory findings [such as pH < 7.35, a blood urea nitrogen concentration of 30 mg/dL [11 mmol/L], or a sodium concentration