Community-acquired pneumonia is associated with approximately 740 000 hospitalizations and 41 000 deaths in the US annually. JAMA Review authors Scott A. Flanders, MD, and Valerie M. Vaughn, MD, MSc, discuss diagnosis and treatment of community-acquired pneumonia with JAMA Deputy Editor Mary McGrae McDermott, MD.
Community-acquired pneumonia is associated with approximately 740 000 hospitalizations and 41 000 deaths in the US annually. JAMA Review authors Scott A. Flanders, MD, and Valerie M. Vaughn, MD, MSc, discuss diagnosis and treatment of community-acquired pneumonia with JAMA Deputy Editor Mary McGrae McDermott, MD.
Importance: Community-acquired pneumonia (CAP) results in approximately 1.4 million emergency department visits, 740 000 hospitalizations, and 41 000 deaths in the US annually.
Observations: Community-acquired pneumonia can be diagnosed in a patient with 2 or more signs (eg, temperature >38 °C or ≤36 °C; leukocyte count <4000/μL or >10 000/μL) or symptoms (eg, new or increased cough or dyspnea) of pneumonia in conjunction with consistent radiographic findings (eg, air space density) without an alternative explanation. Up to 10% of patients with CAP are hospitalized; of those, up to 1 in 5 require intensive care. Older adults (≥65 years) and those with underlying lung disease, smoking, or immune suppression are at highest risk for CAP and complications of CAP, including sepsis, acute respiratory distress syndrome, and death. Only 38% of patients hospitalized with CAP have a pathogen identified. Of those patients, up to 40% have viruses identified as the likely cause of CAP, with Streptococcus pneumoniae identified in approximately 15% of patients with an identified etiology of the pneumonia. All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community because their diagnosis may affect treatment (eg, antiviral therapy) and infection prevention strategies. If test results for influenza and COVID-19 are negative or when the pathogens are not likely etiologies, patients can be treated empirically to cover the most likely bacterial pathogens. When selecting empirical antibacterial therapy, clinicians should consider disease severity and evaluate the likelihood of a bacterial infection-or resistant infection-and risk of harm from overuse of antibacterial drugs. Hospitalized patients without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days. Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality.
Conclusions: Community-acquired pneumonia is common and may result in sepsis, acute respiratory distress syndrome, or death. First-line therapy varies by disease severity and etiology. Hospitalized patients with suspected bacterial CAP and without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days.
Importance
The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.
Objective
To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.
Design, Setting, and Participants
Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.
Interventions
Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).
Main Outcomes and Measures
The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.
Results
Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction = .73).
Conclusions and Relevance
Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.
Trial Registration
ISRCTN Identifier: ISRCTN76888927
Description: Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis. This article describes best practices for prescribing appropriate and short-duration antibiotic therapy for patients presenting with these infections.
Methods: The authors conducted a narrative literature review of published clinical guidelines, systematic reviews, and individual studies that addressed bronchitis with COPD exacerbations, CAP, UTIs, and cellulitis. This article is based on the best available evidence but was not a formal systematic review. Guidance was prioritized to the highest available level of synthesized evidence.
Best practice advice 1: Clinicians should limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated bronchitis who have clinical signs of a bacterial infection (presence of increased sputum purulence in addition to increased dyspnea, and/or increased sputum volume).
Best practice advice 2: Clinicians should prescribe antibiotics for community-acquired pneumonia for a minimum of 5 days. Extension of therapy after 5 days of antibiotics should be guided by validated measures of clinical stability, which include resolution of vital sign abnormalities, ability to eat, and normal mentation.
Best practice advice 3: In women with uncomplicated bacterial cystitis, clinicians should prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole (TMP-SMZ) for 3 days, or fosfomycin as a single dose. In men and women with uncomplicated pyelonephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP-SMZ (14 days) based on antibiotic susceptibility.
Best practice advice 4: In patients with nonpurulent cellulitis, clinicians should use a 5- to 6-day course of antibiotics active against streptococci, particularly for patients able to self-monitor and who have close follow-up with primary care.
Objectives
To describe antibiotic prescribing patterns in ambulatory children with community acquired pneumonia, and to assess the relationship between antibiotic selection and clinical outcomes.
Study design
This was a retrospective cohort study of ambulatory Medicaid-enrolled children 0-18 years of age diagnosed with CAP from 2010-2016. The exposure was antibiotic class: narrow-spectrum (aminopenicillins), broad-spectrum (amoxicillin/clavulanate and cephalosporins), macrolide monotherapy, macrolides with narrow-spectrum antibiotics, or macrolides with broad-spectrum antibiotics. The associations between antibiotic selection and the outcomes of subsequent hospitalization and development of severe pneumonia (chest drainage procedure, intensive care admission, mechanical ventilation) were assessed, controlling for measures of illness severity.
Results
Among 252,177 outpatient pneumonia visits, macrolide monotherapy was used in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. A total of 1488 children (0.59%) were subsequently hospitalized and 117 (0.05%) developed severe pneumonia. Compared with children receiving narrow-spectrum antibiotics, the odds of subsequent hospitalization were higher in children receiving broad-spectrum antibiotics (aOR=1.34 [95%CI 1.17-1.52]) and lower in children receiving macrolide monotherapy (aOR=0.64 [95%CI 0.55-0.73]) and macrolides with narrow-spectrum antibiotics (aOR=0.62 [95%CI 0.39-0.97]). Children receiving macrolide monotherapy had lower odds of developing severe pneumonia than children receiving narrow-spectrum antibiotics (aOR=0.56, 95%CI 0.33-0.93). However, the absolute risk difference was <0.5% for all analyses.
Conclusions
Macrolides are the most commonly prescribed antibiotic for ambulatory children with CAP. Subsequent hospitalization and severe pneumonia are rare. Future efforts should focus on reducing broad-spectrum and macrolide antibiotic prescribing.
Abstract
Importance: Pneumonia affects more than 250 000 nursing home (NH) residents annually. A strategy to reduce pneumonia is to provide daily mouth care, especially to residents with dementia.
Objective: To evaluate the effectiveness of Mouth Care Without a Battle, a program that increases staff knowledge and attitudes regarding oral hygiene, changes mouth care, and improves oral hygiene, in reducing the incidence of pneumonia among NH residents.
Design, setting, and participants: This pragmatic cluster randomized trial observing 2152 NH residents for up to 2 years was conducted from September 2014 to May 2017. Data collectors were masked to study group. The study included 14 NHs from regions of North Carolina that evidenced proportionately high rehospitalization rates for pneumonia and long-term care residents. Nursing homes were pair matched and randomly assigned to intervention or control groups.
Intervention: Mouth Care Without a Battle is a standardized program that teaches that mouth care is health care, provides instruction on individualized techniques and products for mouth care, and trains caregivers to provide care to residents who are resistant and in special situations. The control condition was standard mouth care.
Main outcomes and measures: Pneumonia incidence (primary) and hospitalization and mortality (secondary), obtained from medical records.
Results: Overall, the study enrolled 2152 residents (mean [SD] age, 79.4 [12.4] years; 1281 [66.2%] women; 1180 [62.2%] white residents). Participants included 1219 residents (56.6%) in 7 intervention NHs and 933 residents (43.4%) in 7 control NHs. During the 2-year study period, the incidence rate of pneumonia per 1000 resident-days was 0.67 and 0.72 in the intervention and control NHs, respectively. Neither the primary (unadjusted) nor secondary (covariate-adjusted) analyses found a significant reduction in pneumonia due to Mouth Care Without a Battle during 2 years (unadjusted incidence rate ratio, 0.90; upper bound of 1-sided 95% CI, 1.24; P = .27; adjusted incidence rate ratio, 0.92; upper bound of 1-sided 95% CI, 1.27; P = .30). In the second year, the rate of pneumonia was nonsignificantly higher in intervention NHs. Adjusted post hoc analyses limited to the first year found a significant reduction in pneumonia incidence in intervention NHs (IRR, 0.69; upper bound of 1-sided 95% CI, 0.94; P = .03).
Conclusions and relevance: This matched-pairs cluster randomized trial of a mouth care program compared with standard care was not effective in reducing pneumonia incidence at 2 years, although reduction was found during the first year. The lack of significant results in the second year may be associated with sustainability. Improving mouth care in US NHs may require the presence and support of dedicated oral care aides.
Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.]) and a 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). In 2014, the Advisory Committee on Immunization Practices (ACIP)* recommended routine use of PCV13 in series with PPSV23 for all adults aged ≥65 years based on demonstrated PCV13 safety and efficacy against PCV13-type pneumonia among adults aged ≥65 years (1). At that time, ACIP recognized that there would be a need to reevaluate this recommendation because it was anticipated that PCV13 use in children would continue to reduce disease burden among adults through reduced carriage and transmission of vaccine serotypes from vaccinated children (i.e., PCV13 indirect effects). On June 26, 2019, after having reviewed the evidence accrued during the preceding 3 years (https://www.cdc.gov/vaccines/acip/recs/grade/PCV13.html), ACIP voted to remove the recommendation for routine PCV13 use among adults aged ≥65 years and to recommend administration of PCV13 based on shared clinical decision-making for adults aged ≥65 years who do not have an immunocompromising condition,† cerebrospinal fluid (CSF) leak, or cochlear implant, and who have not previously received PCV13. ACIP recognized that some adults aged ≥65 years are potentially at increased risk for exposure to PCV13 serotypes, such as persons residing in nursing homes or other long-term care facilities and persons residing in settings with low pediatric PCV13 uptake or traveling to settings with no pediatric PCV13 program, and might attain higher than average benefit from PCV13 vaccination. When patients and vaccine providers§ engage in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for a particular person, considerations might include both the person's risk for exposure to PCV13 serotypes and their risk for developing pneumococcal disease as a result of underlying medical conditions. All adults aged ≥65 years should continue to receive 1 dose of PPSV23. If the decision is made to administer PCV13, it should be given at least 1 year before PPSV23. ACIP continues to recommend PCV13 in series with PPSV23 for adults aged ≥19 years with an immunocompromising condition, CSF leak, or cochlear implant (2).
Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.
Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.
Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.
Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
Objectives
To estimate associations between long‐term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care.
Design
Longitudinal analyses of electronic medical records.
Setting
England
Participants
Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age‐ and sex‐matched controls (N=75,050).
Measurements
Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures.
Results
During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR‐adjusted hazard ratio=1.82, 95% confidence interval=1.27–2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score– and inverse probability–weighted models.
Conclusion
In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short‐term harms of PPIs should not divert attention from potential long‐term effects of PPI prescriptions on older adults.
