Hospital Medicine

Typical Bacterial Pneumonia

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Typical Bacterial Community-Acquired Pneumonia

I. What every physician needs to know.

Typical bacterial community-acquired pneumonia (often referred to as CAP) is a common cause of morbidity and mortality in the hospital. Patients with CAP typically present with fever, cough, and shortness of breath; however, in the geriatric population,the clinical presentation can just be altered mental status or weakness.

The diagnosis of CAP generally requires signs and symptoms consistent with CAP AND positive radiographic findings (most often a CXR). Note, though, up to 30% of patients admitted to the hospital with CAP can present with a normal CXR. There are no symptoms, physical examination features, or diagnostic tests which predict typical versus atypical organisms in CAP. Consequently, although there is some controversy, the evidence supports treating all patients diagnosed with CAP withanti-bacterial treatment for both "typical" and "atypical" bacteria. A typical regimen could be 3rd-generation cephalosporin AND a macrolide. Patients can be safely discharged from the hospital if they have normal vital signs and are able to take oral antibiotics. Most patients should get 5-7 days of antibiotics for CAP depending on the degree of illness.

II. Diagnostic Confirmation: Are you sure your patient has Pneumonia?

Per expert guidelines, the diagnosis of community-acquired pneumonia (from typical or atypical bacteria or viruses) requires:

1) Signs and symptoms consistent with community-acquired pneumonia

AND

2) Evidence of a new radiographic infiltrate (typically by chest radiograph)

An update by the Infectious Diseases Society of America published on-line ahead of print in July 2016 on Hospital Acquired Pneumonia (HAP) and Ventilator Acquired Pneumonia (VAP) removed the term Health Care Associated Pneumonia (HCAP). HCAP had previously refered to patients with one of the following risk factors for and a new diagnosis of pneumonia: 1) hospital admission for > 48 hours in the previous 3 months, 2) residence in a skilled nursing facility, 3) hemodialysis, or 4) chemotherapy, wound care, or recent intravenous antibiotics. Previously these patients were recommended to receive broad spectrum antibiotics to cover the possibility of multi-drug resistant (MDR) bacteria. This recent review found that the evidence did not support empiric treatment of all patients in the category for MDRs or extended gram negative bacteria. In general, patients who develop pneumonia outside of the hospital should be treated for typical community-acquired pneumonia. Yet, some patients may have unique risk factors (e.g. severe lung disease, prior MDR pneumonia, recent broad-spectrum antibiotics, etc.) which would necessitate treatment with broader-spectrum antibiotics. Patients should be considered on a case-by-case basis.

The diagnosis of CAP secondary to a specific typical bacteria requires isolation from a culture - sputum, blood, pleural fluid, etc.

A. History Part I: Pattern Recognition:

Patients with community-acquired pneumonia usually present with a brief (days) history of cough (>90%), sputum production (66%), fever (66%), and chest pain (50%). Non-respiratory complaints will dominate in 10-30% of patients these include headache, fatigue, and myalgias. In addition, elderly patients (> 65 years old) often do not have the classic features - over 40% will not have fever and nearly 50% will present with altered mental status. Unfortunately, there are no patient symptoms which accurately and reliably predict typical versus atypical bacteria as the underlying cause.

B. History Part 2: Prevalence:

There are multiple risk factors for typical bacteria community-acquired pneumonia including:

1) Age

2) Underlying lung disease (including COPD)

3) Immunocompromised state (e.g., AIDS, chemotherapy, etc.)

4) Dysphagia or swallowing disorders

5) Drug and alcohol use disorders

6) Smoking

7) Use of proton pump inhibitors (decreasing stomach acid can lead to increased bacterial growth in the stomach which via aspiration can lead to pneumonia).

C. History Part 3: Competing diagnoses that can mimic Typical Bacterial Pneumonia.

The differential diagnosis for typical bacterial community-acquired pneumonia includes:

1) Other "pneumonia" syndromes including aspiration pneumonia, healthcare-associated pneumonia, and post-obstructive pneumonia

2) Non-infectious causes including pulmonary edema, COPD exacerbation, pulmonary embolism, hypersensitivity pneumonitis or other interstitial lung disease, eosinophilic pneumonia, or cryptogenic organizing pneumonia.

D. Physical Examination Findings.

Patients with typical bacterial community-acquired pneumonia will have fever (80%), tachypnea (70%), and tachycardia (70%); they may also present with hypoxia. More than 90% will have a focal lung exam (most often crackles, bronchial breath sounds, or dullness to percussion). No examination features are specific for CAP, but the absence of fever, tachypnea, AND tachycardia makes CAP much less likely. As with the clinical presentation, elderly patients may not have the classic physical examination features so may have a clear lung exam and may have altered mental status. Unfortunately, there are no physical examination findings which predict the causative organism so the exam cannot be used to differentiate typical versus atypical bacteria.

E. What diagnostic tests should be performed?

N/A

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

For patients with suspected CAP admitted to the hospital, providers should check a white blood cell count - leukocytosis is common in patients with CAP and the differential may provide clues to the underyling disease (e.g., eosinophilia). However, the absence of leukocytosis does not rule out CAP, especially in the elderly. Some expert guidelines recommend checking electrolytes, BUN, creatinine, liver function tests although these are more for prognosis and less about confirming the diagnosis. There are currently multiple studies evaluating the utility of C-reactive protein and procalcitonin in the management of CAP but these are currently not recommended by national guidelines.

For microbiologic testing, blood cultures should be consideredin all patients admitted to the hospital with CAP but they are not mandatory. There are a number of problems with blood cultures in CAP: they are only positive in 7% of cases, up to 6% of blood cultures drawn will yield contaminants, and even with positive culture results, clinicians tailor antibiotics < 20% of the time in the real world. Targeting blood cultures in patients with CAP who are most likely to have positive cultures can increase the yield.Thus guidelines recommend obtainingblood cultures in patients with 1) severe CAP (admitted to the ICU), 2)cavitary lesions on imaging, 3)risk factors for unusual organisms (e.g., bronchiectasis) or 4)underlying liver disease.

There is controversy regarding sputum gram stain and culture testing in the setting of CAP but, for most patients, there is limited utility. Some patients cannot produce sputum and of those that can, most are unable to produce a high-quality specimen. Sputum testing should definitely be sent in patients with severe CAP (ICU) or risk factors for drug-resistant organisms (enteric gram-negative rods, MRSA, etc.). Properly obtained sputum should be collected prior to antibiotic therapy, include a deep expectorated specimen, and be transported directly to the laboratory.

In some institutions, the urinary pneumococcal antigen can be ordered. It is a simple urine test for Streptococcus pneumoniae-specific antigens. As a diagnostic test, it has high specificity - if it is positive in the setting of suspected CAP, a diagnosis of pneumonia secondary to S. pneumoniaeis highly likely. The main problems with this diagnostic test are: 1) cost and 2) it does not provide sensitivities - that is, it may confirm the pneumococcus as the causative organism but it does not help guide antibiotic selection and in areas with high penicillin or cephalosporin resistance, this may not change antibiotic selection. Thus, use of the pneumococcal antigen is not the standard of care at most institutions. Most expert guidelines recommend testing for Legionella with the urinary antigen (if available) for all patients with severe CAP (admitted to the ICU).

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The guidelines are clear - all patients with suspected CAP should have a chest radiograph (CXR) performed. Ideally this is a high-quality PA and lateral film. CXR findings in CAP vary from focal lobar consolidation to hazy focal infiltrate to bilateral interstitial opacities. While CXR has been viewed as the gold standard in the diagnosis of CAP, there are some limitations. According to one study, up to 30% of patients admitted to the hospital and given the diagnosis of CAP had clear CXRs on admission. Clinically, patients can present with classic signs and symptoms of CAP and have a clear CXR, only to have the infiltrate "blossom" within the first 24 hours after receiving intravenous fluids. This means a clinician may choose to treat a patient for CAP even with a clear chest x-ray but he or she should continue to search for other diagnoses.

Computed tomography (CT) scanning can also be used in the diagnostic evaluation of patients with suspected CAP. CT scanning has high sensitivity and specificity but these test characteristics must be weighed against the cost, radiation exposure, and consideration if the test will alter management. In general, CT scanning should not be used in the evaluation of CAP.

Unfortunately, there are no radiographic features which predict the causative organism. For example, a lobar consolidation can be secondary to Mycoplasma pneumoniae(an atypical bacteria) while hazy bilateral infiltrates can be secondary to Moraxella catarralis(a typical bacteria).

See Figure 1.

Figure 1.

Chest radiograph with bilateral infiltrates in the setting of CAP.

See Figure 2.

Figure 2.

Right middle lobe infiltrate in the setting of CAP.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

N/A

III. Default Management.

N/A

A. Immediate management.

Within hours of the diagnosis, patients with CAP should receive intravenous fluids (patients are oftenhypovolemic from decreased PO intake and insensible losses), anti-pyretics for fever, supplemental oxygen for hypoxia, and antibiotics. Regarding the timing of antibiotics, expert guidelines recommend that antibiotics in CAP be administered as soon as possible after the diagnosis is made and do not prescribe a specific time. The guidelines do state that for patients with CAP who are diagnosed in the Emergency Department, empiric antibiotics should be given while the patient is still in the ED.

Regarding antibiotic selection for patients admitted to the hospital with CAP, there are a number of key principles. First, less than 20% of patients will have a specific microbiologic diagnosis based on the diagnostic tests above so most will receive empiric therapy. Second, because there are no history, examination, laboratory, or radiographic features which predict typical versus atypical organisms, all patients with CAP must be treated with empiric regimens which cover both types of organisms. Third, despite some controversy regarding the need for treatment of atypical organisms, the preponderance of the evidence supports a benefit to atypical bacterial coverage.

Lastly, in addition to the usual organisms which cause CAP (Streptococcus pneumoniae, Haemophilus influenzae, Moraxallacatarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae), severe CAP may also be caused by Legionellaspp. and community-acquired methicillin-resistant Staphylococcus Aureus (MRSA). Empiric antibiotics for patients with severe CAP admitted to the ICU must reflect this risk – macrolidesas used in less severe disease as wellor a quinolone used as monotherapy for CAPwill treat Legionellaspp. The addition of vancomycin or linezolid should be usedfor coverage of MRSA. There is evidence showing a mortality benefit to the use of macrolides for the treatment of CAP requiring ICU admission.

Here are guideline-recommended regimens for the treatment of CAP in the hospital:

Non-ICU (admitted to a general medical ward):

- Intravenous beta-lactam + oral macrolide (e.g., ceftriaxone + azithromycin) or

- Intravenous fluoroquinolone (e.g., Levofloxacin)

(The beta-lactam choices include: cefotaxime, ceftriaxone, ampicillin/sulbactam. Alternative regimens include: ertapenem instead of a beta-lactam and doxycyline instead of the macrolide)

Intensive care unit (admitted to the ICU from the ED):

- Intravenous beta-lactam+ intravenous macrolide + vancomycin (e.g., ceftriaxone + azithromycin + vancomycin) or

(The beta-lactam choices include: cefotaxime, ceftriaxone, ampicillin/sulbactam)

Some patients with CAP may have unique underlying conditions which predispose them to drug-resistant organisms. The most common scenario is a patient with underlying lung disease (e.g., bronchiectasis, severe COPD) who is at increased risk for Pseudomonas aeruginosa. For these patients, empiric therapy should include broader-spectrum coverage; for example, such patients could be treated with piperacillin/tazobactam or cefepime + a fluoroquinolone (levofloxacin).

There are a few important principles in the ongoing management of anti-microbials in patients hospitalized with CAP. If diagnostic tests yield a specific organism, the antibiotic regimen should be tailed based on sensitivities (if they are available). For non-ICU patients, if there are no culture results, they should continue on the initial empiric regimen until the time of discharge (see below for specific criteria for discharge - generally if patients are able to be switched to oral antibiotics, they are ready for discharge).

For patients admitted to the ICU with CAP, the initial regimen should include vancomycin or linezolid to treat for MRSA. If the blood and sputum cultures done on admission do not grow MRSA, then the vancomycin or linezolid should be stopped and the other two antibiotics continued.

Based on high-quality meta-analyses, the total duration of therapy for CAP should, in general, be 7 days. Clinicians can consider treated for 5 days if the patient is afebrile with normal vital signs by day 3.

A systematic review and meta-analysis published in 2015 showed that in patients with CAP, adjunctive corticosteroids led to less mechanical ventilation, less ARDS, shorter time to clinical stability, and shorter length of stay. There was a trend toward mortality benefit. Most of the included studies were small and there was variable drug, dose, route, and duration. Based on this, steroids can be considered in patients with CAP but it is not yet the standard of care. More evidence is needed.

B. Physical Examination Tips to Guide Management.

In patients admitted to the hospital with CAP, there are a number of physical examination findings which can indicate response to therapy or development of complications. If treatment for CAP is effective, any abnormal vital signs (fever, tachycardia, tachypnea, hypoxia, etc.) should resolve gradually over the course of 2-4 days. Persistently abnormal vital signs (such as a persistent fever) may indicate inadequate treatment or the wrong diagnosis.

The lung examination should be monitored closely over the course of the hospitalization. While the focal exam findings present on admission may or may not improve, providers should carefully examine the lungs for evidence of a pleural effusion (i.e. decreased breath sounds, dullness to percussion).

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Although there are no formal guidelines, most providers will follow the white blood cell count over the first 1-2 days of the hospitalization to monitor response to therapy. If the patient presented with a leukocytosis, this should gradually resolve over the first 1-3 days. There is no indication for repeating the chest x-ray during the hospital to look for improvement in the infiltrate. Repeating the chest x-ray should be reserved for patients who are not clinically improving or if providers are concerned about the development of complications from the pneumonia (e.g., pleural effusion).

D. Long-term management.

Patients who have been hospitalized with CAP are at risk for a recurrence of the disease and should be screened and vaccinated with the appropriate pneumococcal vaccine and the seasonal influenza vaccine.

E. Common Pitfalls and Side-Effects of Management.

There are a number of common pitfalls in the management of community-acquired pneumonia. Diagnostically, because CAP is such a common disease, patients who present with the appropriate symptoms (fever, cough, shortness of breath, etc.) can sometimes be given the diagnosis of CAP without full consideration of the broader differential diagnosis. Clinicians can mis-diagnose pulmonary edema, pulmonary embolism, or another disease (e.g., hypersensitivity pneumonitis) as CAP.

Regarding management, a common error is to not recognize when CAP is not resolving. Most non-ICU patients with CAP should see resolution of abnormal vital signs and laboratory values within 4 days of presentation. If by hospital day 3 the patient is not showings signs of improvement, the provider should consider possible reasons why treatment is failing.

Regarding antibiotic therapy, there are two pitfalls. First, clinicians choose to not cover for atypical organisms because the clinical presentation is that traditionally associated with typical organisms (i.e. high fever, purulent sputum, lobar infiltrate). As described above, all patients with CAP need empiric therapy with antibiotics which cover both typical and atypical organisms. Second, often patients with CAP present quite ill; for example, they may present with septic shock or multi-organ failure. The temptation with this degree of illness in the setting of CAP is to treat with broader spectrum antibiotics, such as piperacillin/tazobactam or cefepime. This is a mistake. These antibiotics may have broader spectrum but they are actually less effective than 3rd-generation cephalosporins in treatingStreptococcus pneumonia, the most common cause of severe CAP.

The most common side effects of management are related to the antimicrobial agents. The most common side effects of cephalosporins are: rash, diarrhea (not necessarily Clostridium difficile), and more severe allergic reactions (anaphylaxis, etc.). The most common side effects of macrolides are: diarrhea, nausea, rash, and other allergic reactions. Fluoroquinolone side effects include: nausea, headache, and tendon injury or rupture (especially in older patients). Also, macrolides and fluoroquinolones can prolong the QTc so should be avoided in patients with underlying prolonged QTc or and used cautiously in patients on other medications known to prolong the QTc.

IV. Management with Co-Morbidities.

N/A

A. Renal Insufficiency.

Antibiotic doses may need to be adjusted depending on the antibiotic and the degree of renal failure. Clinicians should be aware that according to the Pneumonia Severity Index (the PSI or PORT Score) underlying renal disease is a risk factor for increased 30-day mortality.

B. Liver Insufficiency.

No change in standard management. Clinicians should be aware that according to the Pneumonia Severity Index (the PSI or PORT Score) underlying liver disease is a risk factor for increased 30-day mortality.

C. Systolic and Diastolic Heart Failure.

Clinicians may need to pay particular attention to fluid repletion and fluid balance in patients with underlying heart failure who have CAP.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

Patients with underlying diabetes who develop CAP are at risk for hyperglycemia and may require more aggressive insulin regimens.

F. Malignancy.

No change in standard management. Clinicians should be aware that according to the Pneumonia Severity Index (the PSI or PORT Score) underlying neoplasm is a significant risk factor for increased 30-day mortality.

G. Immunosuppression (HIV, chronic steroids, etc).

The degree and type of immunosuppression may impact the organisms causing the CAP. Patients with HIV/AIDS are at risk for the usual organisms that cause CAP but clinicians should also consider: pneumocystis jurevecii pneumonia (PCP), cryptococcus, histoplasmosis, atypical mycobacteria, etc. Patients on chronic steroids (at > 10mg per day) are at increased risk for pseudomonal pneumonia (and other resistant gram negatives) - see above for antibiotic recommendations.

H. Primary Lung Disease (COPD, Asthma, ILD).

Patients with severe underlying lung disease (e.g., bronchiectasis) who develop CAP are at risk for drug-resistant organisms such as Pseudomonas Aeruginosa; empiric antibiotic therapy should be adjusted accordingly.

I. Gastrointestinal or Nutrition Issues.

No change in standard management. Clinicians should be aware that according to some prior studies, malnutrition and low albumin are significant risk factors for increased 30-day mortality in CAP.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

N/A

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

No unique considerations.

B. Anticipated Length of Stay.

The typical length of stay for a non-ICU patient with CAP should be less than 4 days. For patients admitted to the ICU, the expected length of stay is variable depending on co-morbidities and degree of illness but generally should be 7-10 days.

C. When is the Patient Ready for Discharge.

There are standard and recognized criteria for stability in the setting of CAP which signify the patient is safe to be discharged:

Temperature < 37.8oC

Heart rate < 100 beats per minute

Respiratory rate < 24 breaths per minute

Systolic blood pressure > 90 mmHg

Oxygen saturation > 90% (on room air)

Ability to take oral medications

No evidence of active co-morbid conditions

Normal mental status (or a return to baseline)

Safe, appropriate outpatient follow-up

D. Arranging for Clinic Follow-up.

N/A

1. When should clinic follow up be arranged and with whom.

Most experts recommend follow-up in general medicine clinic (ideally with the primary care doctor) within 7 days.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None. There has been discussion in the past on indications for follow-up chest x-ray after a diagnosis of CAP (looking for underlying malignancy). The most recent expert guidelines do not comment on this specifically but experts state that follow-up chest radiograph can be considered in patients who are high-risk for malignancy (men, age > 65 years old, long smoking history).

E. Placement Considerations.

Frail, elderly, and demented patients are at increased risk for CAP and thus some percentage of all patients with CAP will require placement. For the most part, the need for placement will not be for intravenous antibiotics as most patients can be treated with oral antibiotics. There are no other special considerations for placement for patients with CAP.

F. Prognosis and Patient Counseling.

Counseling patients about CAP at discharge about expected recovery may help prevent readmission. The literature reveals that one week after discharge 80% of patients with CAP will have ongoing fatigue and cough and 50% of patients will have persistent dyspnea and sputum production. Patients can be told that the cough may take months to resolve.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

The publicly reported measures for CAP are:

1) Appropriate antibiotic selection for immunocompetent patients with CAP admitted to a non-ICU setting.

3) Readmission rate (30 days) for patients with CAP

4) Mortality (30 days) for patients admitted with CAP

5) Total payment to Medicare for patients older than 65 years-old who are admitted to the hospital with CAP

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Patients with CAP are at increased risk for venous thromboembolism while hospitalized so should be placed on appropriate prophylaxis. Patients with CAP are at increased risk for future episodes of CAP and should receive the pneumococcal vaccine and the influenza vaccine. As proton pump inhibitors (PPIs) are a risk factor for the development of CAP, if a patient is on a PPI, the clinician should ensure there is a clear indication for the medication.

What’s the Evidence?/References

Kalil, Andre C, Metersky, Mark L, Klompas, Michael. "Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society 2016".

Lee, JS, Giesler, DL, Gellad, WF, Fine, MJ. "Antibiotic therapy for adults hospitalized with community-acquired pneumonia. A systematic review". JAMA. vol. 315. 2016. pp. 593-602.

A systematic review of observational and randomized controlled trials which showed a lower mortality with empiric antibiotic regimens which include treatment for atypical organisms.

Siemieniuk, RA, Meade, MO, Alonso-Coella, P. "Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. A systematic review and meta-analysis". Ann Intern Med. vol. 163. 2015 Oct 6. pp. 519-28.

A systematic review and meta-analysis showed steroids in CAP result in less mechanical ventilation, less ARDS, earlier clinical stability, and shorter LOS (no mortality benefit).

Sigl, WI, Asadi, L, Eurich, DT. "Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis". Crit Care Med. vol. 42. 2014. pp. 420-432.

A systematic review and meta-analysis showed that for patients with CAP who require ICU care, empiric antibiotic regimens which include a macrolide lead to lower mortality when compared to other antibiotic regimens.
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