Empirical treatment selection for CAP in the Emergency Department

28 September, 2020

Professor Zhao Bin

Director and Chief Physician of the Emergency Department of Beijing Jishuitan Hospital, Professor of Peking University Health Science Centre and tutor for postgraduate students.

Graduated from the Medical department of Peking Medical College with a Master’s degree. Committee member of Chinese Society of Emergency Medicine, Chinese Medical Association; Standing committee member and academic secretary of Emergency Medicine Branch, Beijing Medical Association; Vice-chairman of Emergency Medicine Branch, Chinese Association for Disaster & Emergency Rescue Medicine; Vice-chairman of Association of First Aid and Resuscitation, Chinese Society of Cardiothoracic and Vascular Anesthesiology; Standing committee member and Secretary-General of Emergency Medicine Expert Committee, Cross-straits Medical Exchange Association; Committee member of Association of Emergency Physicians, Chinese Medical Doctor Association; Committee member of Emergency Medicine Branch, First Aid and Recovery Committee, Chinese Medical Doctor Association; Standing committee member of Emergency Expert Committee of Beijing Association of Chinese Medicine; Committee member of Beijing Quality Control and Improvement Centre of Emergency Medicine; Council member of Emergency Medicine Specialist Physician Branch , Beijing Medical Doctor Association; Member of the Editorial Board of China Journal of Emergency Resuscitation and Disaster Medicine; Member of the Editorial Board of Chinese Journal of Emergency Medicine; Member of the Editorial Board of Chinese Journal of Medicine.


Q1: What are the clinical characteristics of patients with community-acquired pneumonia (CAP) who present at the emergency department (ED)?

All physicians are familiar with pneumonia – one of the most commonly observed infectious diseases encountered in the ED. In the past, pneumonia was categorised according to the anatomic appearance of the lung: lobar, lobular, and interstitial pneumonia; pneumonia was also categorised based on the causative pathogen such as bacteria, virus, Mycoplasma pneumonia, and fungal pneumonia. However, findings from imaging studies of pneumonia in the early stages may not be apparent and clear aetiological evidence may not be obtained – making the diagnosis of pneumonia based on anatomical classification or pathogen-typing difficult. Pneumonia is now categorised into CAP and hospital-acquired pneumonia (HAP) according to the time of onset. This categorisation considers information such as the patient’s condition, the environment, and the causative pathogen. This method is also more scientific and more convenient for doctors to apply in the clinical setting.

Infectious diseases are the most common ED diagnoses, with 60% to 70% of ED visits attributed to infections. CAP causes acute fever and respiratory symptoms, as well as haemodynamic instability in more severe diseases. As such, patients with acute and severe CAP are typically admitted to the ED in the first instance. Although there are no nationwide statistics on the incidence rate of CAP in the ED, respiratory disease is one of the top three diseases diagnosed in the ED, with infection as the primary cause. CAP and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are the most common respiratory diseases affecting patients in the ED. In other countries, researchers have reported that CAP patients make up 271/10,000 of inpatients from the ED, and this figure increases with age.

The management of patients in the ED is time critical. This is where treatment stratification and the prioritisation of patients with severe conditions are typically carried out. Doctors often categorise patients into four levels based on the severity of their condition: category 1 represents critically ill patients, category 2 represents severe acute patients, category 3 represents patients with potentially critical illnesses, and category 4 covers patients with stable vital signs. The patients’ condition, treatment locations, and treatment strategies often influence treatment outcomes. The management of CAP in the ED thus requires similar stratified management. Previously, CAP patients were subjectively sorted by doctors based on their symptoms. This often led to clinicians having differing opinions. The utilisation of the CURB-65 tool or pneumonia severity index (PSI) score has now facilitated the sorting of CAP patients in the ED, therefore refining the management of patients with severe CAP.

From the patients’ perspective, CAP is a medical specialty – thus patients with respiratory symptoms would first consult the respiratory department. As such, young and healthy patients with mild CAP and without underlying diseases are not seen in the ED. These patients who have CURB-65 score of <2 or PSI risk class I or II, usually seek community or outpatient treatment. However, elderly CAP patients with comorbidity, weakened immunity or haemodynamic instability, i.e. CURB-65 score of >2 or PSI score above risk class III, are always admitted to the ED.  As a result, there are more severe CAP patients or CAP patients with comorbidities at the ED than at specialist departments.

This situation is due to an ageing population, the delay in seeking medical care, as well as the inadequate distribution of medical resources. Older adults with comorbidities and weakened organ function and immunity are more vulnerable to infections. Timely management of upper respiratory tract infection is crucial to prevent infection of the lower respiratory tract. Furthermore, the weakening of organ functions, antimicrobial resistance, repeated treatment, and malnutrition may lead to CAP developing into complex multiorgan failure. As the bed space in specialist departments are limited, patients with multiple diseases may also have difficulty receiving specialist treatment. These are the differences between CAP presented at the ED and outpatient CAP.


Q2: The causative pathogens of CAP are diverse and complex. What are the commonly observed CAP pathogens in the EDs in China?

Research on pneumonia has been receiving attention since 1800. Before the discovery of antibiotics, 95% of pneumonia cases were caused by Streptococcus pneumoniae. Currently, although S. pneumoniae remains the most common cause of CAP and the incidence rate has decreased. In the US, only approximately 10% to 15% of hospitalisations are due to S. pneumoniae infection. Other causative pathogens of CAP include Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Pseudomonas aeruginosa, and other Gram-negative bacteria. COPD patients are at greater risk of CAP caused by H. influenzae and M. catarrhalis. P. aeruginosa and Gram-negative bacteria may also cause CAP in COPD patients or patients with bronchiectasis, especially those who are using glucocorticoid. In recent years, the incidence rate of Mycoplasma pneumoniae and Chlamydia pneumoniae (also known as atypical CAP) has increased, mainly due the improvements in PCR technology that provides clear diagnosis. In elderly patients with complications of cerebrovascular disease, microaerophiles and anaerobes (oral flora) – are often isolated in the sputum, suggesting that these microorganisms are the causative pathogens of CAP for this group of patients. During the flu season, influenza virus is the main cause of CAP. Respiratory syncytial virus, parainfluenza virus, adenovirus, coronavirus, and rhinovirus are other common CAP pathogens; however, it is unclear to what extent these pathogens cause diseases or cause the patient to be more susceptible to secondary bacterial infection. The Middle East respiratory syndrome coronavirus (MERS-CoV), which appeared in the Arabian peninsula recently, and H7N9 virus ,which is epidemic in China, are also causes of CAP.

Overall, there are many CAP-causing pathogens, including bacteria, atypical bacteria, and viruses. However, in the past 200 years, the order of CAP-causing pathogens has not changed much in China or overseas, be it in community, outpatient, or EDs. According to a 2013 multicentre analysis done by a Beijing Grade 3A general hospital on severe CAP in the ED, the most common causes of CAP are H. influenzae, followed by S. pneumoniae, and Klebsiella pneumoniae – and screening for atypical pathogens has yet to be performed. While the types of causative pathogens remain for CAP, antimicrobial resistance has developed rapidly. The treatment location of patients and the presence of comorbidities often impact the development of antimicrobial resistance. The rate of resistance of S. pneumoniae to macrolides has been quite high in China in recent years – with resistance rates of more than 90%. At the standard breakpoint of oral penicillin used for S. pneumoniae, 56.7% of S. pneumoniae were insensitive to penicillin; 39.9% to 50.7% S. pneumoniae were resistant to oral cephalosporin; 27.7% H. influenzae resistant to ampicillin and sulbactam, and 31.6% resistant to cefuroxime. As such, ED doctors should be cautious when prescribing antimicrobials for the treatment of CAP.


Q3: CAP patients in the ED are often presented with urgent conditions and are treated with empirical anti-infective therapy. What are the main recommendations and strategies for empirical anti-infective therapy? (i.e. what are the key considerations when administering the first dose of antibiotics? What patient factors should be taken into consideration? E.g., age, underlying diseases, flu season, etc.)

CAP, especially severe CAP, is an acute illness. Treatment time and prognosis are closely related, i.e. patients benefit from early treatment. All physicians understand that the best treatment option is based on aetiology results. However, it is time-consuming to obtain aetiology results. Empirical antibiotics selection at the ED is often evidence-based. Subsequent treatment is given upon receiving a diagnosis to manage CAP. ED physicians cannot afford to be hesitant and cannot delay the empirical antibiotics due to concerns about other diseases; for severe CAP patients, empirical antibiotics must be administered within an hour of admission. Empirical anti-infective therapy should adhere to a certain scientific method and clinical thinking.

The treatment strategy for empirical anti-infective therapy is to: 1. Confirm the CAP diagnosis and severity using CURB-65 tool or PSI score; 2. Understand the patient’s general condition, including age, underlying diseases, immune function, nutrition, compliance, smoking and drinking habits, mental state (patients with mental illnesses are susceptible to exacerbation of the infection), swallowing function, mobility, and history of antibiotic use; 3. Ascertain the possibility of a viral infection, especially during winter; 4. Note that young adults with CAP tend to have bacterial infection that are drug sensitive, whereas antibiotics against Gram-negative bacteria and drug-resistant bacteria should not be used for elderly CAP patients, and that atypical bacteria is often found in children with CAP; 5. Understand the region, medical organisation, and the situation regarding antibacterial drug resistance; and 6. Weigh up the benefits to the patient, i.e. the most suitable treatment.


Q4: Based on the abovementioned anti-infective therapy strategies, what are the factors that influence empirical antibiotics therapy?

The three aspects of anti-infective therapy are the patient, the pathogenic bacteria, and the antibiotics. The former two are living organisms that are constantly changing and difficult to understand. Once an antibiotic is produced, however, as long as there is no issue with storage, it is constant and never changes. So, doctors must exert the effort to fully and clearly understand all the aspects of the antibiotic used.

The role of the antibacterial spectrum of each antibiotic, pharmacokinetic properties, and toxicity and side effects of anti-infective therapy are important considerations. The antibacterial spectrum directly informs doctors of the effectiveness of an antibacterial against certain bacteria. The understanding of the antibacterial spectrum prevents antibacterial misuse. When prescribing and administering the empirical antibiotic, a broad-spectrum antibiotic should be used, i.e. one with lower antimicrobial resistance rate and more potent. The pharmacokinetic properties are also important as they explain how the antibiotic works in the body and how it fights the bacteria. However, ED doctors often neglect these factors and end up with clinical misuse of the antibiotics, including dosage, solvent used, and frequency of use per day. These cases common in the clinical setting and must be avoided; all drugs, including antibiotics, have side effects. ED doctors must always evaluate the benefit-risk balance.


Q5: In the treatment of patients with CAP presenting at the ED, which patients should be prioritised for the use of quinolones? (According to guideline recommendations, which CAP patients should doctors prioritise for the use of quinolones such as levofloxacin? What are the characteristics of quinolones?)

For CAP treatment in the ED, whether the benefits of anti-infective therapy outweigh the risk depends on many factors. The selection of antibiotics is undeniably an important step. To allow ED doctors to be able to choose the antibiotics under a framework with reasonable scope in addition to concrete analysis of each and every patient’s issues, specialists and emergency medicine associations within and outside China have published several CAP diagnosis and treatment consensus papers and guidelines. The aim of these guidelines is to prescribe appropriate antibiotics for CAP treatment. Thus, ED doctors should follow these guidelines closely for the benefits of patients.

The IDSA/ATS “Guidelines for CAP in Adults” recommend using levofloxacin or moxifloxacin alone or using a β-lactam (such as amoxicillin-clavulanate) plus a macrolide for outpatients with underlying diseases or patients who have recently used antimicrobials. If ED doctors are unable to confirm the antibiotic resistance of S. pneumoniae towards macrolides in the region, they should use levofloxacin or moxifloxacin alone, or a β-lactam (such as amoxicillin-clavulanate) plus macrolide antibiotics.

For inpatient CAP, the IDSA/ATS guidelines recommend a β-lactam plus a macrolide, or a quinolone in empirical therapy. For inpatient ICU CAP, the guidelines recommend a minimal dosage of a β-lactam plus either a macrolide or a quinolone antibiotic. When patients with structural lung diseases such as COPD or bronchiectasis (especially when they are directly receiving glucocorticoid or other immunosuppressive therapy) are infected with P. aeruginosa, an antipseudomonal β-lactam plus either ciprofloxacin or levofloxacin (500mg) should be used. For patients with Legionella infection, the IDSA/ATS guidelines recommend fluoroquinolones or azithromycin.

According to the guidelines, quinolones are indispensable in treating ED patients with CAP caused by bacteria. Also, quinolones are known for their once-daily dosing with good permeability into the lung tissues, as well as less adverse reactions. For the past few years, quinolones have been used frequently by ED doctors for CAP treatment, and the drug has become the most considered antibiotic for ED CAP patients.

The IDSA/ATS guidelines standardise an appropriate antibiotic treatment for CAP patients. However, the clinical success depends on the patient’s condition, the causative microorganisms, and the antibiotic. Thus, empirical therapy is not a one-size-fits-all approach but an individualised approach. However, practical applications in the clinical setting may be difficult – there are many problems such as misdiagnosis, inability to identify aetiological evidence, and the worst being problems due to antibiotic use.

Thus, other than taking note of the causes of CAP, its diagnosis, and the use of antibiotics, the CAP patient’s overall condition is a key consideration. ED doctors should take note of the patient’s age, medical history, nutrition condition, diet, as well as other health indicators. Clinicians should understand the biological characteristics of pathogenic bacteria and know how it manifests differently in different environments such as inside and outside the body. They should also be clear about which antibiotics work against which pathogenic bacteria, the pharmacokinetics of the antibiotic, and how to administer time-dependent antibiotics and concentration-dependent antibiotics. At the same time, ED doctors must always observe and analyse any micro-changes in the patient’s body during the CAP treatment process, including post-treatment, clinical symptoms, physical signs, inflammation indices, and changes in radiographic images. Naturally, they should also not neglect the immunity of the patient. With a holistic perspective, emphasis on details, and continuous accumulation of CAP case studies, I believe that the treatment of CAP by ED doctors will improve.



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