Morbidity and mortality associated with community-acquired pneumonia in adults

INTRODUCTION — 

Community-acquired pneumonia (CAP) is common and associated with considerable morbidity and mortality, particularly in older adult patients and those with significant comorbidities. Traditionally, CAP has been considered an acute respiratory infection that can have short-term complications such as empyema, lung abscess, or sepsis. However, as data on long-term outcomes accumulate, CAP is increasingly recognized as a systemic illness that can impact long-term health.

Short-term (within 30 days of diagnosis) morbidity and mortality and long-term (>30 days postdiagnosis) morbidity and mortality will be reviewed here. Other issues related to CAP are discussed separately:

●(See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults".)

●(See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

●(See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care".)

●(See "Treatment of community-acquired pneumonia in adults in the outpatient setting".)

●(See "Treatment of community-acquired pneumonia in adults who require hospitalization".)

●(See "Aspiration pneumonia in adults" and "Epidemiology of pulmonary infections in immunocompromised patients" and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults".)

●(See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")".)

SHORT-TERM MORBIDITY AND MORTALITY

Mortality

●Mortality rate variability – Mortality varies considerably amongst patients with CAP, particularly between outpatients and those who are ill enough to require hospitalization. As examples:

•The mortality associated with CAP in adults was evaluated in a 1996 meta-analysis of 127 studies that reported medical outcomes in over 33,000 patients [1]. Mortality ranged from 5.1 percent for combined ambulatory and hospitalized patients (data were not reported for ambulatory patients alone), to 13.6 percent in hospitalized patients, to 36.5 percent in patients admitted to the intensive care unit (ICU).

•The prospective, multicenter observational Pneumonia Patient Outcomes Research Team study additionally evaluated outcomes of 944 outpatients and 1343 inpatients with CAP between 1991 and 1994 [2]. The following findings were noted at 30 days after presentation:

-Among outpatients, there were six deaths (0.6 percent), three of which were related to pneumonia.

-Among inpatients, the mortality rate was 8 percent, 76 percent of which were attributed to pneumonia; most deaths occurred during hospitalization.

•Other data from the Centers for Medicare and Medicaid Services database estimate the 30-day mortality rate of CAP patients (mostly >65 years of age) requiring admission in the United States to be approximately 12 percent [3].

The above mortality rates represent overall values. Factors at presentation can be used to stratify patients into those at low risk who can usually be treated as outpatients and patients at higher risk who require hospitalization or even direct admission to an ICU. (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care".)

●Mortality trends over time – It is not clear whether mortality rate in CAP is decreasing over time, with mixed evidence from observational studies. The differences may be related to differences in populations studied, changes to diagnostic classification in administrative data, as well as effects related to the coronavirus disease 2019 (COVID-19) pandemic.

In a study of over two million cases of CAP between 1987 and 2005 in patients ≥65 years of age in the United States detected through a review of Medicare claims, the age- and sex-adjusted 30-day mortality rate decreased from 13.5 percent to 9.7 percent [4]. After adjustment for comorbidities, there was an even larger reduction in the risk of mortality between 1987 and 2005 (adjusted odds ratio 0.46, 95% CI 0.44-0.47).

In a subsequent study using data from the United States Nationwide Inpatient Sample (the largest all-payer, publicly available national hospital database) between 2003 and 2009, there was a significant decrease in inpatient mortality rate from 5.8 to 4.2 percent (absolute risk reduction 1.6 percent, 95% CI 1.4-1.9) when only a primary diagnosis of pneumonia was assessed [5]. However, when a primary diagnosis of pneumonia was combined with a primary diagnosis of sepsis or respiratory failure associated with a secondary diagnosis of pneumonia, age- and sex-adjusted inpatient mortality rate increased slightly from 8.3 to 8.8 percent (absolute risk increase 0.5 percent, 95% CI 0.1-0.9). Notably, over the same time period, there was an increase in the primary diagnosis of sepsis with pneumonia as a secondary diagnosis that counterbalanced the apparent decrease in mortality from pneumonia. These results suggest that a temporal change in diagnostic coding affects longitudinal outcomes in studies that use administrative data [6].

However, some studies have not shown that mortality rates have changed substantially over time. In one cohort study of over 7000 patients hospitalized for CAP in the United States between 2014 and 2016, 30-day mortality was 13 percent, six-month mortality was 23 percent, and one-year mortality was 30 percent [7]. Similarly, in a population-based study of patients hospitalized for CAP in Germany in 2015, in-hospital mortality was 18.5 percent, 30-day mortality was 23 percent, and one-year mortality was 44.5 percent [8].

Morbidity — In the Pneumonia Patient Outcomes Research Team study [2], 76 percent of outpatients reported at least one residual symptom (most often fatigue) compared with 45 percent in the month before the onset of CAP. However, most resumed their usual activities within seven days. Among inpatients, 87 percent had at least one residual symptom at 30 days after hospital discharge compared with 65 percent in the month before the onset of CAP. Return to normal activities occurred at a median of 24 days for those not employed and 15 days for those employed who returned to work at a median of 22 days. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Clinical response to therapy'.)

Prognostic factors — Key factors that predict short-term mortality include severity of illness, age ≥65, and the presence of morbidities (particularly multiple comorbidities) [1,9-12]. Other factors include the cause of pneumonia, antibiotic selection and timing, and response to antibiotics.

Severity of illness — A retrospective study evaluated 30-day mortality rates using a database of 21,233 Medicare patients with pneumonia aged ≥65 years who had been discharged from hospitals in the United States in 2000 or 2001 [13]. Overall, 2561 patients (12.1 percent) died within 30 days of admission. Among these, 1343 (52.4 percent) died during the hospital stay and 1218 (47.6 percent) died after discharge.

On multivariate analysis, seven factors were associated with death prior to discharge:

●systolic blood pressure <90 mmHg

●respiratory rate >30 breaths/minute

●bacteremia

●arterial pH <7.35

●blood urea nitrogen >11 mmol/L

●arterial PO₂ <60 mmHg or arterial oxygen saturation <90 percent

●need for mechanical ventilation

Additional disease severity indicators that have been associated with increased mortality include hypothermia, multilobar pneumonia, altered mental status, and an abnormal platelet count (ie <100,000 or >400,000/L) [1,9-12,14].

Among severely ill patients, late ICU admission (day 2 or later) was associated with higher 30-day mortality than ICU admission within 24 hours of presentation (47 versus 23 percent) [15]. In a retrospective cohort study of over one million Medicare beneficiaries (aged >64 years) admitted to hospitals in the United States with pneumonia, ICU admission for patients with disease of marginal severity was associated with improved survival and no difference in costs compared with general ward admission, suggesting that ICU admission may benefit such patients [16]. In adjusted analyses, for the 13 percent of patients whose admission appeared to be discretionary (dependent only on distance), ICU admission was associated with a significantly lower adjusted 30-day mortality than patients admitted to a general ward (14.8 versus 20.5 percent). These results suggest a potential benefit of using broader ICU admission criteria but should be confirmed in a randomized trial.

Comorbidities and older age — In general, CAP mortality rises significantly for those ≥65 years old and those with comorbidities [8,17-19]. In an epidemiologic study evaluating 2320 adults hospitalized with CAP in the United States, with an in-hospital mortality rate of approximately 2.2 percent, most deaths (>60 percent) occurred in those ≥65 years old and in those with two or more chronic comorbidities [18,20]. CAP was considered to be the direct cause of death in 52 percent, and a major contributor in an additional 19 percent. In a separate study of over 3000 adults age ≥65 years hospitalized with CAP in China, 60-day mortality was independently associated with age, bedridden status, congestive heart failure, and CAP severity on admission [17].

As an example of the impact of increased age, in a study that included 1349 patients ≥65 years of age, the 30-day mortality rate was 5, 11, and 24 percent in patients 65 to 74 years, 75 to 84 years, and ≥85 years, respectively [9]. Similar trends have been seen in other studies [19].

Pathogen — Mortality rates vary with the cause of pneumonia [1,9,21]. The meta-analysis described above reported mortality rates by pathogen [1]:

●Gram-negative organisms (Pseudomonas aeruginosa, Klebsiella, Escherichia coli; 41 percent)

●Staphylococcus aureus (32 percent)

●Streptococcus pneumoniae and Chlamydia pneumoniae (12 to 15 percent)

●Influenza A (9 percent)

●Mycoplasma pneumoniae (1.4 percent)

However, since the total number of cases of CAP due to Pseudomonas and Enterobacteriaceae is low compared with the number of cases due to Streptococcus pneumoniae, most deaths due to a defined etiology are due to S. pneumoniae.

Mortality also appears to be increased in patients with dual bacterial and viral infection [22,23].

Empiric antibiotic therapy

Timing — The impact of timing of antimicrobial initiation on outcomes is discussed separately. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Antimicrobial initiation'.)

Guideline adherence — A number of studies have evaluated the impact of guidelines on the outcome of CAP, although none were designed to compare specific antibiotic regimens in different guidelines [24-36]. Most found a benefit to guideline-directed care, although the types of benefit (requirement of admission, duration of hospitalization, mortality, and cost) varied among the studies.

Perhaps the best data come from a multicenter controlled trial using cluster randomization in 1743 patients with CAP who presented to the emergency department in 19 hospitals; the trial compared conventional care with a critical pathway algorithm guiding the decision to hospitalize and therapy type, including treatment with intravenous or oral levofloxacin [24]. In comparison, levofloxacin was unavailable to physicians in the conventional treatment hospitals.

Patients treated according to the algorithm had significant reductions in the number of bed days per patient admitted (4.4 versus 6.1 days) and in the proportion of low-risk patients who were admitted (31 versus 49 percent). Although inpatients at critical pathway hospitals had more severe disease, they required significantly fewer days of intravenous therapy and were more likely to be treated with a single class of antibiotic. These reductions in the use of hospital resources were not associated with any adverse clinical effects, as complications, readmission, mortality, and quality of life were not different between the two groups.

An important limitation to observational data in other studies [25-34] is that guideline adherence could represent a surrogate marker for other aspects of clinical care rather than being directly responsible for the improved outcomes [34]. Nevertheless, the available data support a probable benefit from guideline adherence.

Lack of response — It has been estimated that 6 to 15 percent of hospitalized patients with CAP do not respond to initial antibiotic therapy within 72 hours, and the failure rate may be as high as 40 percent in patients initially admitted to an ICU [11,37]. (See "Nonresolving pneumonia".)

Mortality rates are substantially higher in nonresponders. This was illustrated in a review of 1424 hospitalized patients with CAP, 215 of which failed to respond to treatment (15 percent) [11]. Nonresponders had a mortality rate of 25 percent compared with 2 percent in responders. After adjustment for risk class, failure to respond to empiric antibiotic therapy was associated with an 11-fold increase in mortality. A similar mortality difference (27 versus 4 percent in responders) was noted in another series of 1383 nonimmunocompromised hospitalized patients with CAP [37].

One cause of treatment nonresponse is discordant therapy, which refers to treatment of an infection with an antimicrobial agent to which the causative organism has demonstrated in vitro resistance, particularly drug-resistant S. pneumoniae. The available data suggest that the impact of discordant therapy varies with antibiotic class and possibly with specific agents within a class [38-43].

Biomarkers — The use of biomarkers such as procalcitonin to assess the prognosis of CAP is discussed in detail separately. (See "Procalcitonin use in lower respiratory tract infections".)

Other factors — Among nondiabetics with CAP, an elevated serum glucose concentration at hospital admission is a predictor of death at 28 and 90 days [44]. Compared with patients with CAP who had a normal serum glucose on admission, those with mild hyperglycemia (serum glucose 6 to 11 mmol/L [108 to 198 mg/dL]) had an increased risk of death at 90 days (hazard ratio [HR] 1.56, 95% CI 1.22-2.01). The risk was even higher among patients with a serum glucose concentration ≥14 mmol/L (252 mg/d; HR 2.37, 95% CI 1.62-3.46). Patients with preexisting diabetes also had an increased risk of mortality compared with nondiabetics, but this outcome was not significantly affected by serum glucose concentration on admission.

In some observational studies, low vitamin D concentration was an independent predictor of mortality in patients with CAP [45-47]. As an example, in a retrospective study, the 28-day all-cause mortality rate in vitamin D-deficient patients was higher than in nondeficient patients (8.3 versus 2.6 percent) [46]. Serum vitamin D level was negatively associated with risk of 28-day mortality in CAP after adjustment for PSI and serum lactate levels (odds ratio [OR] 0.94, 95% CI 0.90-0.99). However, it is not known whether vitamin D replacement improves outcomes in patients with CAP (see "Vitamin D and extraskeletal health", section on 'Immune system').

Prediction rules — The prognostic factors identified in the studies above have been used to develop prediction rules to assess risk of death and need for hospitalization [1,48-54]. The CURB-65 score and the Pneumonia Severity Index (PSI) are the most commonly used scoring systems.

CURB-65 score — The British Thoracic Society found a 21-fold increase in mortality in patients who had two or more of the following findings [49]:

●Blood urea nitrogen greater than 20 mg/dL (7 mmol/L)

●Diastolic blood pressure less than 60 mmHg

●Respiratory rate above 30 per minute

The predictive value of these findings was validated in 245 patients hospitalized for CAP in the United States, 20 of whom (8.2 percent) died [50]. The presence of all three variables predicted a ninefold greater risk for death, with 70 percent sensitivity and 84 percent specificity.

These three findings plus confusion (based upon a specific mental test or new disorientation to person, place, or time) and age greater than 65 years constitute the five factors at presentation that make up the CURB-65 score, which is a prediction rule for prognosis used to determine whether a patient should be admitted to the hospital (calculator 1). (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care", section on 'The CURB-65 and CRB-65 scores'.)

Among the 718 patients (mean age 64) in the derivation cohort of CURB-65, 30-day mortality was 0.7, 2.1, 9.2, 14.5, and 40 percent for 0, 1, 2, 3, or 4 factors, respectively; only a small number of patients had five factors [55]. These findings were validated in a subsequent cohort of 3181 patients: 30-day mortality was 0.6, 3.0, 6.1, and 14.3 percent for 0, 1, 2, or 3 or more factors, respectively [56].

The authors of the original CURB-65 report suggested that patients with a CURB-65 score of 0 to 1, who comprised 45 percent of the original cohort and 61 percent of the later cohort, were at low risk and could probably be treated as outpatients, those with a score of 2 should be admitted to the hospital, and those with a score of 3 or more should be assessed for care in the intensive care unit (ICU), particularly if the score was 4 or 5 [55].

Pneumonia severity index — The PSI was derived and validated as part of the Pneumonia Patient Outcomes Research Team prospective cohort study to identify patients with CAP at low risk for mortality and to improve decision-making surrounding hospital admission. Points are assigned based upon sex, age, nursing home residence, comorbidities, physical examination findings, and laboratory and radiographic findings. It is widely used for predicting 30-day mortality (calculator 2) (table 1). The PSI is described in detail separately. (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care", section on 'Pneumonia Severity Index'.)

Although the PSI was designed to predict 30-day mortality, it also predicted long-term mortality in a population-based cohort study that followed patients for a median of 3.8 years [57]. It has also been revalidated in the era of endemic COVID-19 [58].

PIRO score in ICU patients — A scoring system based upon PIRO (Predisposition, Insult, Response, and Organ dysfunction) was developed to predict mortality among patients with severe CAP admitted to the ICU and was compared with the APACHE-II score and the ICU admission criteria recommended by the IDSA/ATS [59]. (See "Predictive scoring systems in the intensive care unit" and "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care", section on 'Admission to intensive care'.)

The PIRO score was calculated in 529 patients within 24 hours of ICU admission by giving one point when each of the following variables was present, with a maximum achievable score of 8: comorbidities (chronic obstructive pulmonary disease [COPD], immunocompromise), age >70 years, multilobar opacities on chest radiograph, shock, severe hypoxemia, acute kidney failure, bacteremia, and acute respiratory distress syndrome. The mean PIRO score was significantly higher in non-survivors than survivors (4.6 versus 2.3). Mortality by 28 days increased with the PIRO score as follows:

●Low (0 to 2 points) – 3.6 percent

●Moderate (3 points) – 13 percent

●High (4 points) – 43 percent

●Very high (5 to 8 points) – 76 percent

The PIRO score performed better than the APACHE-II score and ATS/IDSA criteria using the area under the receiver-operating characteristic curve. However, validation of the PIRO score is required in other populations.

IDSA/ATS minor criteria — The Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines for the management of CAP define two major criteria for direct admission to an ICU: septic shock requiring vasopressor support and requirement for mechanical ventilation [60]. The presence of either criterion requires ICU care. The guidelines also note that the need for ICU care is suggested by the presence of at least three minor criteria: respiratory rate ≥30 breaths/minute, PaO₂/FiO₂ ratio ≤250, multilobar infiltrates, confusion, blood urea nitrogen ≥20 mg/dL (blood urea 7 mmol/L), leukopenia, thrombocytopenia, hypothermia, or hypotension requiring fluid support. In a validation study of patients who did not have the major criteria or a contraindication to ICU admission, the minor criteria were equivalent to the PSI for predicting 30-day mortality [61].

The performance of the minor criteria for predicting the need for ICU admission is discussed separately. (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care", section on 'Admission to intensive care'.)

Benefits of vaccination — Prior pneumococcal and influenza vaccination appears to improve outcomes in patients with CAP.

Pneumococcus — The potential efficacy of pneumococcal vaccination in hospitalized or older adults with CAP has been illustrated in several studies.

For example, pneumococcal vaccination was associated with decreased risk of in-hospital mortality or ICU admission in a prospective, multicenter, population-based cohort study that included over 3400 patients [62]. Among these patients, 22 percent had previously been vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). PPSV23 was associated with a significant reduction in the primary outcome (10 versus 21 percent, propensity-adjusted odds of death or ICU admission 0.62, 95% CI 0.42-0.92). Virtually all of the benefit was due to a lower rate of ICU admission. Among over 2400 patients eligible for PPSV23 at hospital discharge, only 9 percent were vaccinated.

Benefit was also noted in a retrospective analysis of 63,000 adults hospitalized with CAP, 12 percent of whom had a record of prior pneumococcal vaccination [63]. The following significant benefits were noted in the vaccination group compared with those who had not received the pneumococcal vaccine:

●A lower rate of all-cause mortality during hospitalization (adjusted OR 0.50; 95% CI 0.43-0.59)

●A lower rate of respiratory failure (adjusted OR 0.67; CI 0.59-0.76)

●A shorter median length of stay (4.5 versus 6.5 days)

In a randomized trial of over 1000 nursing home patients (mean age 85 years), those who were assigned to PPSV23 and developed pneumococcal pneumonia had lower mortality than those who were assigned to placebo (35 versus 0 percent) [64].

The benefit of PPSV23 was also demonstrated in a population-based case-control study of persons 60 years and older (mean age 73) [65]. The study assessed 88 case patients with invasive pneumococcal disease and 176 matched controls. A lower rate of prior PPSV23 was found in the case patients than the controls (39 versus 59 percent).

The efficacy of pneumococcal vaccination for the prevention of pneumococcal infections is discussed separately. (See "Pneumococcal vaccination in adults".)

Influenza — Several studies have suggested that influenza vaccination prevents CAP [66-68]. Prior influenza vaccination also appears to decrease mortality in older adult patients hospitalized for pneumonia. The magnitude of this effect was illustrated in a retrospective review of the medical records of 12,566 randomly selected Medicare beneficiaries who were hospitalized for pneumonia [69]. Patients with a prior vaccination history compared with those with unknown vaccination status had significantly lower rates of mortality (hazard ratio 0.65) and readmission (hazard ratio 0.92).

The efficacy of influenza vaccination is discussed in greater detail separately. (See "Seasonal influenza vaccination in adults".)

LONG-TERM MORBIDITY AND MORTALITY — 

As data on long-term outcomes accumulate, CAP is increasingly recognized as a systemic illness that can impact long-term health [70,71]. Important examples of long-term sequelae include pulmonary fibrosis with decreased lung function (similar to chronic obstructive pulmonary disease) [72] and cardiovascular disease resulting from cardiac stress and hypoxemia. Each appear to correlate with the severity of inflammatory response at the time of initial infection

Morbidity and mortality — Long-term outcomes for both respiratory status and quality-of-life status were assessed in a study of 102 patients with mild to moderate-severe CAP requiring hospital admission [73]. Well-being generally returned to pre-pneumonia status within six months; persistent respiratory symptoms beyond 28 days were more likely to reflect age or comorbidity than the effect of pneumonia.

CAP influences long-term survival of patients admitted to the hospital and subsequently discharged. In one study, one of three patients >65 years of age who survived hospitalization for CAP died in the following year [74]. In a study of Veterans Administration patients with a mean age of 69.9 years, those who were discharged from the hospital after treatment for CAP had a significantly shorter duration of survival compared with patients discharged for nonpneumonia diagnoses (50 percent survival at 34 months, compared with 84 months among patients without CAP) [75]. In a large, population-based cohort study, patients with CAP had an excess risk of death for up to 10 years compared with a matched control group [76].

Similar results have been seen in single-center studies, which have also examined potential risk factors for longer-term mortality. In one single-center cohort study of 255 patients hospitalized for CAP, 30 percent died over a median of 1804 days. The five-year survival was 73 percent. The main causes of death were chronic obstructive pulmonary disease (COPD), vascular disease, and malignancy [77]. In a separate prospective study of 1284 patients discharged from a tertiary hospital after treatment for CAP, 7.2 percent died within one year of discharge, with most of the deaths occurring within the first six months [78]. The major causes of death were infection (mostly pneumonia) and acute cardiovascular events. COPD, diabetes mellitus, cancer, dementia, rehospitalization within 30 days of hospital discharge, and residence in a long-term care facility were independently associated with one-year mortality. The incidence of long-term mortality increased >50 percent when four or more risk factors were present.

Long-term mortality is further increased among patients requiring ICU admission. In a population-based cohort study of 271 CAP patients requiring ICU admission, the 30-day mortality was 11 percent, but the one-year mortality one was 27 percent [79]. Dependent functional status correlated strongly with both short- and long-term mortality. Separately, in a registry study of 3775 patients admitted to the ICU with CAP, one-year mortality was 44 percent [80]. Risk factors included an increased number of comorbidities as well as organ failure, sepsis, or respiratory failure during the ICU admission.

Cardiac complications — CAP has been associated with acute cardiac events that may result from cardiac stress, hypoxemia, and inflammation [81-89]. Compared with CAP patients without acute cardiac events, CAP patients with acute cardiac events have longer time to clinical stability, increased rates of clinical failure, and increased 30- and 90-day mortality [82,90-92].

●Cardiovascular events – In two cohorts of community-dwelling adults, hospitalization for pneumonia was associated with increased short- and long-term risk of new-onset cardiovascular disease (myocardial infarction, cerebrovascular accident, or fatal coronary heart disease), even after adjusting for cardiovascular risk factors such as age, sex, race, diabetes mellitus, smoking, and serum lipid concentrations [87]. One of the cohorts, the Cardiovascular Health Study, included individuals ≥65 years of age. Of 591 pneumonia cases, 206 had cardiovascular events over 10 years after pneumonia admission. The risk of cardiovascular events was highest during the first year after hospitalization and remained higher than among controls through 10 years (adjusted hazard ratio [aHR] from 0 to 30 days after hospitalization: 4.07, 95% CI 2.86-5.27; 31 to 90 days: 2.94, 95% CI 2.18-3.70; 91 days to 1 year: 2.10, 95% CI 1.59-2.60; 9 to 10 years: 1.86, 95% CI 1.18-2.55). In the other cohort, the Atherosclerotic Risk in Communities study, which included individuals 45 through 64 years of age, of 680 pneumonia cases, 112 had cardiovascular events over 10 years after hospitalization. The risk of cardiovascular events was elevated during the first two years following pneumonia hospitalization (aHR from 0 to 30 days: 2.38, 95% CI 1.12-3.63; 31 to 90 days: 2.40, 95% CI 1.23-3.47; 91 days to 1 year: 2.19, 95% CI 2.19, 95% CI 1.20-3.19; 1 to 2 years: 1.88, 95% CI 1.10-2.66), but not thereafter. In a prospective study of 301 consecutive patients admitted with CAP, intra-hospital cardiac complications in the early phase of pneumonia were associated with an enhanced risk of death and cardiovascular events during long-term follow-up [93].

In a systematic review of the association of CAP with cardiovascular diseases that included 39 studies involving 92,188 patients, cardiac complications occurred in 13.9 percent (95% CI 9.6-18.9), acute coronary syndromes in 4.5 percent (95% CI 2.9-6.5), heart failure in 9.2 percent (95% CI 6.7-12.2), arrhythmias in 7.2 percent (95% CI 5.6-9.0), and stroke in 0.71 percent (95% CI 0.1-3.9) of pooled inpatients [94].

●Heart failure – CAP is also associated with heart failure [90,91]. In a large prospective cohort study evaluating 4988 adults, mean age 55 years, patients with CAP showed an increased risk of new-onset heart failure over a median of 9.9 years (11.9 versus 7.4 percent in controls, aHR 1.61, 95% CI 1.44-1.81) [95]. Increased risk was detected across clinical settings and age groups, although those aged ≥65 years had the highest absolute difference in risk (aHR 1.55, 1.36 to 1.77).

The association between pneumococcal pneumonia and acute cardiac events is discussed separately. (See "Pneumococcal pneumonia in patients requiring hospitalization", section on 'Cardiac events and other noninfectious complications'.)

Pulmonary complications — Pulmonary complications of pneumonia, including fatigue, cough, and decreased lung function, can persist for months following acute illness [96]. Declines in functional capacity have been observed and associated with higher re-hospitalization and mortality rates [72]. Permanent lung damage can result from profound inflammatory and subsequent scarring. While not well described for bacterial CAP, long-term lung damage due to pulmonary fibrosis is increasingly recognized with COVID-19. (See "COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness ("long COVID")".)

Other complications — Pneumonia is not only a pulmonary infection and can affect several organ systems. Important systemic complications related to pneumonia include direct progression of the disease in the lungs to involve the pleural space or indirect effects on other organ systems such as the central nervous system, hematologic, cardiac, kidney, endocrine, and/or hepatic systems, and others [97].

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see "Patient education: Community-acquired pneumonia in adults (The Basics)")

●Beyond the Basics topic (see "Patient education: Pneumonia in adults (Beyond the Basics)")

SUMMARY

●Leading cause of morbidity and mortality − Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Traditionally, CAP has been considered an acute respiratory infection that can have short-term complications such as empyema, lung abscess, or sepsis. However, as data on long-term outcomes accumulate, CAP is increasingly recognized as a systemic illness that can impact long-term health. (See 'Introduction' above.)

●Short-term mortality − The mortality rate associated with CAP is very low in most ambulatory patients and higher in patients requiring hospitalization, being as high as 37 percent in patients admitted to the intensive care unit. (See 'Short-term morbidity and mortality' above.)

●Risk factors for short-term mortality – Key factors that predict short-term mortality include severity of illness, older age, and the presence of morbidities (particularly multiple comorbidities). Other factors include the cause of pneumonia, empiric antibiotic selection and timing, and the patient’s response to antibiotics.

●Prediction rules − Several scoring systems have been developed to help predict short-term mortality based on established risk factors. The most commonly used are the Pneumonia severity index (PSI) (calculator 2) and the CURB-65 score (calculator 1). While we prefer the PSI because it is better validated, the CURB-65 score is easier to use. Underlying comorbidity and the cause of pneumonia also affect the mortality risk. (See 'Prognostic factors' above.)

●Improved outcomes among vaccinated patients − Among patients with CAP who require hospitalization, prior pneumococcal and influenza vaccination has been associated with better outcomes. (See 'Benefits of vaccination' above.)

●Adherence to guideline recommendations − Adherence to guideline recommendations has been associated with reductions in the proportion of low-risk patients admitted to the hospital and, for those admitted, the duration of hospitalization. Some observational studies have also noted substantial reductions in mortality but guideline adherence could represent a surrogate marker for other aspects of clinical care. (See 'Guideline adherence' above.)

●Long-term complications − Important examples of long-term sequelae include pulmonary fibrosis with decreased lung function (similar to chronic obstructive pulmonary disease) and cardiovascular disease resulting from cardiac stress and hypoxemia. Each appears to correlate with the severity of inflammatory response at the time of initial infection. (See 'Long-term morbidity and mortality' above.)

ACKNOWLEDGMENT — 

UpToDate gratefully acknowledges John G Bartlett, MD, who contributed on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.