Community-acquired pneumonia (non Covid-19)

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

During the pandemic, consider any patient with cough, fever, or any other suggestive symptoms to have COVID-19 until proven otherwise.

This topic does not cover pneumonia due to COVID-19. See Coronavirus disease 2019 (COVID-19).

When a diagnosis of CAP is established, the next step is to determine whether or not the patient requires outpatient care, hospitalization, or admission to the intensive care unit (ICU). Microbial investigation as well as antimicrobial therapy will depend upon the site of care. Decisions about the site of care can vary widely between hospitals and practice sites and may be based on considerations other than severity.

Outpatient selection and management

Use a validated clinical prediction rule for prognosis, preferably the Pneumonia Severity Index (PSI) over CURB-65, in addition to clinical judgment, to determine whether the patient should be treated as an outpatient.[91] PSI is preferred over CURB-65, as PSI identifies larger proportions of patients as low risk and has a higher discriminative power in predicting mortality.[18][91]

Outpatient treatment is recommended for the following patients:[88][89]

Patients in PSI risk class I or II, with a PSI score ≤70 (low risk), and a predicted 30-day mortality risk of 0.1% to 2.8% [ Community-acquired pneumonia severity index (PSI) for adults Opens in new window ]
Patients with a CURB-65 score of 0 to 1 (low severity), and a predicted 30-day mortality risk <3%. Those with a score of 2 [moderate severity] and a mortality risk of 9% should be considered for brief inpatient care or supervised outpatient care. [ CURB-65 pneumonia severity score Opens in new window ]

Be aware of the limitations of severity scores and consider other factors when assessing a patient's suitability for outpatient management (e.g., contraindications to outpatient therapy such as inability to maintain oral intake, history of substance abuse, severe comorbid illnesses, cognitive impairment, and impaired functional status, or availability of outpatient support resources). Do not routinely use biomarkers to increase the performance of clinical decision rules when assessing whether to treat the patient as an outpatient.[91]

Advise patients not to smoke, to rest, and to stay well hydrated. Also advise them to report any symptoms of chest pain, severe or increasing shortness of breath, or lethargy.

Reassess patients at 48 hours. Symptoms should improve within this time with appropriate treatment. Consider hospital admission in patients who fail to improve within 48 hours. Approximately 10% of outpatients do not respond to antibiotic therapy and require hospitalization.[99]

Perform a repeat examination after 10-14 days if the patient's response to therapy is satisfactory. Routine follow-up chest imaging is not recommended if symptoms resolve within 5-7 days.[18]

Outpatients who recover without hospitalization are able to resume normal activities more quickly than those who are hospitalized. Hospitalization increases the risk of infection with antibiotic-resistant or more virulent bacteria.[100]

Empiric antimicrobial treatment in outpatients

The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines recommend the following oral empiric treatment options for outpatients:[18]

Healthy patients without comorbidities or without risk factors for drug-resistant pathogens:
- Amoxicillin
- Doxycycline
- A macrolide (e.g., azithromycin or clarithromycin).
- Only use a macrolide in areas with pneumococcal resistance to macrolides <25% and when there are contraindications to alternative therapies.
Patients with comorbidities (e.g., chronic heart, lung, liver, or renal disease; diabetes mellitus; alcohol abuse; malignancy; asplenia):
- Combination therapy with amoxicillin/clavulanate or a cephalosporin (e.g., cefpodoxime, cefuroxime) plus a macrolide or doxycycline
- Monotherapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin).

Broader-spectrum antibiotic regimens are required in patients with comorbidities as many of these patients have risk factors for drug-resistant pathogens (e.g., prior respiratory isolation of methicillin-resistant Staphylococcus aureus [MRSA] or Pseudomonas aeruginosa, recent hospitalization and administration of parenteral antibiotics in the past 90 days), and they are more vulnerable to poor outcomes if the empiric regimen is inadequate.[18]

Choice of antibiotic requires a risk-benefit analysis for each patient, weighing up local epidemiologic data, specific patient risk factors and comorbidities, contraindications, and possible adverse effects (e.g., cardiac arrhythmias with macrolides; vascular disease, musculoskeletal/neurologic adverse effects with fluoroquinolones). Despite the safety concerns associated with fluoroquinolones (see below), the ATS/IDSA panel believes that fluoroquinolone use is justified in adults with CAP and comorbidities who are managed in the outpatient setting.[18]

Risk factors for drug resistance

Risk factors for penicillin-resistant Streptococcus pneumoniae include use of a beta-lactam in the previous 3 to 6 months, hospitalization in the previous 3 months, aspiration, previous episodes of pneumonia in the past year, age <5 or >65 years, and COPD.[101][102][103][104][105]
Risk factors for macrolide-resistant S pneumoniae include use of a macrolide in the previous 3 months, age <5 or >65 years, and recent hospitalization.[101][102][103][104][105]
Risk factors for fluoroquinolone-resistant S pneumoniae include previous exposure to fluoroquinolones, residence in a nursing home, penicillin resistance, and COPD.[101][102][103][104][105]

Hospital admission

Use a validated clinical prediction rule for prognosis, preferably PSI over CURB-65, in addition to clinical judgment to determine whether the patient should be treated as an inpatient. PSI is preferred over CURB-65, as PSI identifies larger proportions of patients as low risk and has a higher discriminative power in predicting mortality.[18][91]

Hospital admission is recommended in the following situations:[88][89]

Patients with a PSI score of 71-90 (class III), who may benefit from a brief period of hospitalization [ Community-acquired pneumonia severity index (PSI) for adults Opens in new window ]
Patients with PSI class IV or class V pneumonia (who have a 9% and a 27% risk of death, respectively)
Patients with a CURB-65 score of ≥3, who should be hospitalized, and those with a score of 4 or 5 (with predicted mortality rates of 15% to 40%, respectively), who should be considered for ICU admission. [ CURB-65 pneumonia severity score Opens in new window ]

Admit patients with hypotension requiring vasopressor therapy or respiratory failure requiring mechanical ventilation to the ICU. In patients who do not require vasopressor therapy or mechanical ventilation, use the ATS/IDSA criteria for defining severe CAP (see Diagnostic criteria section) and clinical judgment to guide the need for higher levels of treatment intensity.[18][91] Admit patients with severe CAP (defined as one major criterion or three or more minor criteria) to the ICU.[18]

Administer oxygen therapy as necessary. Monitor oxygen saturation and inspired oxygen concentration with the aim of maintaining SaO₂ above 92%. High concentrations of oxygen can safely be given in uncomplicated pneumonia. [ ] Oxygen therapy in patients with COPD that is complicated by ventilatory failure should be guided by repeated arterial blood gas measurements.[106] Patients with respiratory failure, despite appropriate oxygen therapy, require urgent airway management and possible intubation.

Assess patients for volume depletion. Administer intravenous fluids if needed according to local protocols, and give nutritional support in prolonged illness.

Monitor temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration at least twice daily and more frequently in patients with severe pneumonia and in those requiring regular oxygen therapy. Monitor C-reactive protein (CRP) levels regularly as they are a sensitive marker of progress in pneumonia. Repeat chest x-rays in patients who are not progressing satisfactorily. Routine follow-up chest imaging is not recommended if symptoms resolve within 5-7 days.[18]

Empiric antimicrobial treatment in hospitalized patients not in ICU

The ATS/IDSA guidelines recommend the following intravenous empiric treatment options in inpatients with nonsevere CAP without risk factors for MRSA or P aeruginosa:[18]

Combination therapy with a beta-lactam (e.g., ampicillin/sulbactam, cefotaxime, ceftriaxone, ceftaroline) plus a macrolide (e.g., azithromycin, clarithromycin). Note that clarithromycin is only available as an oral formulation in the US, and so can only be used if the oral route is feasible
Monotherapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin)
Combination therapy with a beta-lactam plus doxycycline in patients who have contraindications to both macrolides and fluoroquinolones.

Additional empiric antibiotic cover is required in patients with risk factors for MRSA or P aeruginosa if locally validated risk factors for either pathogen are present:[18]

MRSA: add vancomycin or linezolid
P aeruginosa: add piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem/cilastatin.

The strongest risk factors for infection with MRSA or P aeruginosa are prior isolation of these organisms from the respiratory tract, and/or recent hospitalization and exposure to parenteral antibiotics in the past 90 days. Based on this, ATS/IDSA recommend the following:[18]

If the patient has a prior history of respiratory isolation of MRSA or P aeruginosa: add appropriate antibiotic cover and obtain cultures (or nasal polymerase chain reaction [PCR] for MRSA if available) to guide de-escalation or to confirm the need to continue additional cover.
If the patient has had a recent hospitalization and parenteral antibiotics in the past 90 days and has been locally validated for risk factors for MRSA: obtain cultures and nasal PCR. If PCR or cultures are negative, withhold additional cover. If PCR or cultures are positive, start additional cover.
If the patient has had a recent hospitalization and parenteral antibiotics in the past 90 days and has been locally validated for risk factors for P aeruginosa: obtain cultures but only initiate cover if cultures are positive.
Consider de-escalation to standard antibiotic therapy at 48 hours provided cultures do not reveal a drug-resistant pathogen and the patient is clinically improving.

Additional empiric antibiotic cover is required in patients with risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae. Consult an infectious disease specialist for guidance on an appropriate antibiotic regimen. Additional anaerobic cover for patients with suspected aspiration pneumonia is not recommended unless lung abscess or empyema is suspected.[18]

The recommendation to cover atypical pathogens in the empiric antibiotic regimen is debated;[107][108][109] however, the recommendation is supported by current data.[110][111] [ ]

Empiric antimicrobial treatment in ICU patients

The ATS/IDSA guidelines recommend the following intravenous empiric treatment options in inpatients with severe CAP without risk factors for MRSA or P aeruginosa:[18]

Combination therapy with a beta-lactam (e.g., ampicillin/sulbactam, cefotaxime, ceftriaxone, ceftaroline) plus a macrolide (e.g., azithromycin, clarithromycin); there is stronger evidence for this regimen compared with the regimen below. Although ATS/IDSA recommend clarithromycin in these patients, it is only available as an oral formulation in the US so is unlikely to be useful in this setting
Combination therapy with a beta-lactam plus a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin).

Additional empiric antibiotic cover is required in patients with risk factors for MRSA or P aeruginosa if locally validated risk factors for either pathogen are present:[18]

MRSA: add vancomycin or linezolid
P aeruginosa: add piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem/cilastatin.

Add additional antibiotic cover and obtain cultures (or nasal PCR for MRSA if available) to guide de-escalation of therapy or confirm the need to continue therapy. Consider de-escalation to standard antibiotic therapy at 48 hours provided cultures do not reveal a drug-resistant pathogen and the patient is clinically improving.[18]

Safety of fluoroquinolone antibiotics

Consider safety issues before prescribing fluoroquinolones. The Food and Drug Administration (FDA) has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[112][113]

The European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with fluoroquinolones in 2018. These adverse effects included tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Coadministration of a fluoroquinolone and a corticosteroid should be avoided if possible. This review resulted in prescribing restrictions in Europe, limiting the use of fluoroquinolones to severe infections only.[114]

Despite these concerns, ATS/IDSA guidelines recommend fluoroquinolones as a treatment option, including patients with comorbidities who are treated in the outpatient setting, nonsevere CAP in the hospital setting, and severe CAP.[18]

Route of antibiotic therapy

Start empiric antibiotic treatment as soon as possible, and give in the emergency department to avoid delay. Delayed administration has been associated with an increased risk in mortality in patients with severe CAP.[115]

The initial route for antibiotic therapy depends on severity, the patient’s condition, and the site of care. Guidelines recommend that oral antibiotics be used for outpatients while intravenous treatment is preferred for hospitalized patients. However, intravenous treatment should always be given in patients with severe CAP (at least within the initial hours following admission), with daily evaluation for switching to oral medication as soon as possible. Consider switching the patient to oral therapy when they are hemodynamically stable and improving clinically, can ingest oral medications, and have a normally functioning gastrointestinal tract. Switch to an oral formulation of the same drug or an oral formulation of a drug within the same drug class.[18]

Duration of antibiotic therapy

Treat for a minimum of 5 days. Duration of treatment should be guided by a validated measure of clinical stability (e.g., resolution of vital sign abnormalities, normal cognitive function, ability to eat).[18][116][117] Consider discontinuing therapy when the patient has been afebrile for 48-72 hours and there are no signs of complications (endocarditis, meningitis). A retrospective cohort study found that two-thirds of hospitalized patients with CAP received excess antibiotic therapy, and each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse effects after discharge.[118] In patients with bacterial CAP, one systematic review and meta-analysis showed a 5 day course of antibiotics to lead to similar clinical outcomes, with a similar safety profile, to longer courses (≥ 7 days).[119] One RCT found that in patients with moderately severe CAP who met clinical stability criteria, discontinuing beta-lactam treatment after 3 days was non-inferior to 8 days of treatment, suggesting that 3 days of antibiotics may be sufficient in immunocompetent, non-severely ill patients that are clinically improved at day 3.[120]

Longer treatment courses are recommended in patients with complications and in cases of pneumonia due to less common pathogens. A treatment course of 7 days is recommended in patients with MRSA or P aeruginosa.[18] Consult with an infectious diseases expert in these cases.

Microbiologically directed therapy

Consider switching patients to an organism-specific antimicrobial therapy guided by antibiotic sensitivity in patients in whom laboratory tests have revealed a causative organism.

Antiviral treatment in patients with influenza

Add antiviral treatment (e.g., oseltamivir) to antimicrobial treatment in patients with CAP who test positive for influenza in the inpatient setting, independent of duration of illness before diagnosis. Consider antiviral treatment in outpatients who test positive for influenza virus.[18]

Corticosteroid therapy in hospitalized patients

The use of corticosteroids in patients with severe CAP has been a long-debated issue. Current ATS/IDSA guidelines generally recommend against the use of corticosteroids in patients with nonsevere or severe CAP, although acknowledge that they may be considered in patients with refractory septic shock according to Surviving Sepsis Campaign guidelines, and can be used as clinically appropriate for comorbid conditions (e.g., COPD, asthma, autoimmune diseases). This recommendation is based on the fact that there are no data suggesting benefit in patients with nonsevere CAP with respect to mortality or organ failure, and only limited data to support their use in patients with severe CAP.[18]

Meta-analyses of studies of hospitalized adults with CAP found that the use of corticosteroids was associated with reduced need for mechanical ventilation, reduced hospital stay, lower clinical failure rates, fewer complications (including septic shock), decreased CRP levels, and reduced all-cause mortality. However, it appears that the reduction in mortality applies to only patients with severe CAP. In patients with nonsevere disease, adjunctive corticosteroids reduce morbidity, but not mortality.[121][122][123][124][125][126][127] [ ]

Patients treated with corticosteroids have an increased risk for hyperglycemia.[123][124] [ ] Other adverse effects include super infection and upper gastrointestinal bleeding.

Nonresponding pneumonia

Nonresponding CAP describes the clinical situation where there is an inadequate response after antibiotic treatment as assessed at day 3 to day 5. The causes of nonresponding pneumonia are classified as infectious, noninfectious, and of unknown origin. Multicenter studies have shown that between 6% and 24% of CAP cases will not respond to antibiotic treatment, and in cases of severe pneumonia, this rate can reach 31%.[19][128]

One study has described two different clinical patterns of nonresponding pneumonia:[129]

Progressive pneumonia that follows a course of clinical deterioration with respiratory failure or septic shock
The situation where clinical stability is not achieved and no other patient characteristics are responsible.

Biomarkers such as CRP and procalcitonin (PCT) have been found to be useful for predicting inadequate host response. High levels of CRP or PCT at initial presentation represent a risk factor for inadequate response,[80] whereas low levels are protective. The use of procalcitonin to guide initiation and duration of antibiotic treatment results in a lower risk of mortality, lower antibiotic consumption, and lower risk for side effects.[130][131] However, one review found no difference in short-term mortality in critically ill patients specifically,[132] while another study found that PCT-guided therapy did not result in decreased use of antibiotics.[133] The American College of Emergency Physicians does not recommend the routine use of biomarkers when deciding on administration of antibiotics in the emergency department.[91] Consensus algorithms that include PCT cut-off points for deciding when to initiate or discontinue antibiotics may help to facilitate safe and efficient implementation of PCT-guided therapy.[134]

The first response to nonresponse or deterioration should be to re-evaluate the initial microbiology results.[18] Results of cultures and sensitivity testing that were not available at presentation may now make the cause of clinical failure obvious. In addition, a further history of any risk factors for infection with unusual microorganisms, including viruses and fungi, should be sought if this has not already been done. Further diagnostic testing may also be warranted.

Specifically, if the patient with nonresponding pneumonia lives in or has recently traveled to regions either endemic for blastomycosis or coccidioidomycosis or where there has been a recent outbreak of these infections, enzyme immunoassay-based diagnostic testing for these fungal infections should be considered.[135] Similarly, if a patient with nonresponding CAP lives in or has traveled to regions endemic for histoplasmosis, or has had significant exposure to bat or bird droppings, or x-ray shows new nodules or lymphadenopathy, enzyme immunoassay based diagnostic tests for detection of histoplasmosis infection should be considered.[136] For more information on areas that would raise suspicion of these infections please refer to CDC guidance.[135][136]

Bundled interventions

While efficacy of individual interventions may demonstrate efficacy in clinical trials, a bundled intervention, which included adjunct corticosteroids, as well as early mobilization, nutrition screening, and early switch to oral antibiotics, was not found to have a significant effect on hospital stay length, mortality, or complications, but was found to increase the risk of gastrointestinal bleeding when compared with normal care. Therefore, the efficacy of individual interventions may not translate into effectiveness when these interventions are bundled and given in combination, and may even result in net harm.[137]

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