Per the GOLD 2021 report, AECOPD can be classified as mild, moderate, and severe, based on the severity of the disease. Patients with mild AECOPD should only be treated with short-acting bronchodilators (SABDs), those with moderate AECOPD are treated with SABDs plus antibiotics and/or oral corticosteroids, while those with severe AECOPD require hospitalization or visits to the emergency room. Our results demonstrate that 86.2% of included AECOPD patients received antibiotic treatment during admission. The median antibiotic therapy duration was 9.0 days. Cephalosporins, penicillin, and quinolones were the most commonly prescribed antibiotics. Furthermore, 56.5% of the included AECOPD patients underwent pathogen examinations. Importantly, a significantly lower proportion of patients receiving pathogen examinations was found in the second hospital group when comparing with the tertiary hospital group. Moreover, the most common bacterial pathogens isolated from the study population were Pneumonia klebsiella, Acinetobacter, Haemophilus influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae isolates.
Prompt treatment improves recovery from exacerbation, reduces the risk of hospitalization, and is associated with a better health-related life quality of AECOPD patients. Antibiotics play an important role in the treatment of AECOPD. However, evidence for the choice of antibiotic type and treatment duration remains insufficient. The GOLD 2021 report suggested that antibiotic choice should be based on the local bacterial resistance pattern, and the initial empirical treatment is usually an aminopenicillin with clavulanic acid, macrolide, or tetracycline; importantly, the report emphasized the potential likelihood of gram-negative bacterial infection (e.g., Pseudomonas species). UK NICE guideline for AECOPD management provides a list of the first-choice oral antibiotics (including amoxicillin, doxycycline, and clarithromycin) and first-choice intravenous antibiotic (including amoxicillin, co-amoxiclav, clarithromycin, co-trimoxazole, and piperacillin with tazobactam); notably, the guideline stresses that clinicians should assess the effects of intravenous antibiotics within 48 hours and consider stepping down to oral antibiotics when possible. In this study, only 1% patients received both intravenous and oral antibiotics, which was inconsistent with stepping-down mode for antibiotic use in NICE guideline; besides, this study suggested that the median antibiotic therapy duration from real-world data was significantly longer than guidelines.(1, 17) Above evidence reflect that there potentially exists insufficient monitoring of respiratory infection symptoms signs, disease prognosis, and pathogens in the clinical practice of AECOPD. Precision medicine has drawn more and more attention recently, and individualized treatment is also necessary for AECOPD patients. In order to dynamically adjust the most suitable antibiotic treatment for AECOPD patients, physicians need to record the infection symptoms of phlegm and fever, and reexamine potential pathogens more timely and comprehensively. As for the Chinese expert consensus for AECOPD, the preferred antibiotic is initially selected based on the results of Pseudomonas aeruginosa infection risk assessment; namely, for those with no risk factors of Pseudomonas aeruginosa infection, antibiotics including amoxicillin/clavulanic acid, levofloxacin, and moxifloxacin are suggested; meanwhile, ciprofloxacin, levofloxacin, or a beta-lactam with anti-Pseudomonas aeruginosa activity combining with aminoglycosides (optional) is suggested for patients with risk factors for Pseudomonas aeruginosa infection, for a recommended duration of 5-10 days. In general, the guidelines and expert consensus all propose the necessity of monitoring Pseudomonas aeruginosa infection. In this study, antibiotic use with a high coverage rate of Pseudomonas aeruginosa was observed, which was consistent with current international guidelines and national expert consensus. Interestingly, we found that anti-pseudomonas cephalosporin and anti-pseudomonas penicillin were main choices for patients in tertiary hospitals, while anti-pseudomonas quinolones were more commonly prescribed in secondary hospitals. We speculate that this may result from physicians’ medication experience varies in different-grade hospitals, and the safety of quinolones is much easier to guarantee than cephalosporin and penicillin.
The lung microbiome, including bacteria, detected in COPD patients, is a dynamic organism, and its composition seems to be dependent upon the heterogeneity of disease, disease progression, and treatment. Patel et al. found that lower airway bacterial colonization in a stable COPD state could modulate the character and frequency of exacerbations. Sanjay et al. clarified that there existed associations between COPD exacerbations and new isolations of bacterial pathogens. Mayhew et al. proved that the stability of the lung microbiome over time was more likely to be decreased in exacerbations and individuals with more frequent exacerbations; additionally, bacterial exacerbations were more likely to be relapse in subsequent exacerbations within a subject. In addition, MAESTRAL study suggested that complete bacteria eradication involved in the exacerbation was of vital importance to the successful treatment of AECOPD. Thus, monitoring the lung microbiome is critical for AECOPD patients. In this study, 61.3% AECOPD patients in tertiary hospitals underwent pathogen examination, while this proportion was significantly lower in secondary hospitals. This suggest that it is necessary to further increase physicians’ awareness of the importance of conducting pathogen examination in AECOPD patients to better guide the treatment, as pathogen examination provides the best evidence for precise antibiotic medication. Herrera et al.  reported that both swab and sputum specimens had good specificity in polymerase chain reaction tests for the diagnosis of community-acquired pneumonia (CAP) caused by atypical bacteria, but there was a significantly lower sensitivity in swab specimens than in sputum specimens. Moreover, a recent French study showed that the diagnostic efficacy of pulmonary samples for Legionella pneumophila was clearly superior to that of nasopharyngeal aspirates in adult patients with CAP or AECOPD. Furthermore, Cho et al. found that sputum was more efficacious than nasopharyngeal swabs for the simultaneous detection of Legionella pneumophila, Chlamydophila pneumoniae, and Mycoplasma pneumoniae using multiplex PCR in CAP. Therefore, specimen type is crucial for accurately detecting bacterial infections, and the sensitivity of sputum specimens may be superior to that of swab specimens. This also suggests the necessity of improving the proportion of sputum specimens collected from AECOPD patients in China, especially in secondary hospitals. Regarding the types of cultured bacterial pathogens, Pneumonia klebsiella isolates, Acinetobacter isolates, Haemophilus influenzae isolates, Pseudomonas aeruginosa isolates, and Streptococcus pneumoniae isolates were commonly detected, which was consistent with the findings of previous studies. Millares et al.  reported that Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera were found by an increase in the relative abundance over 20 % during exacerbations of COPD. In a Chinese study, the predominant bacteria included Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae and Streptococcus pneumoniae. Therefore, monitoring potential bacterial pathogens based on clinical characteristics and territories seems crucial to the management of AECOPD patients in real clinical practice.
This study had some limitations. Firstly, the prescribing of antibiotics according to the international nonproprietary names (INNs), which might cause the absence of a more detailed pharmacotherapeutic approach. Secondly, there were missing data (e.g., duration of antibiotic use) in a portion of the patients. Thirdly, the proportion of patients from secondary hospitals was relatively lower than that from tertiary hospitals; nevertheless, a professional steering committee was employed to monitor the study, and its scientific integrity can be absolutely guaranteed. Future studies focusing on antibiotic use among AECOPD patients in secondary hospitals are needed. Fourthly, due to the limited follow-up duration, no prognostic analysis was performed to investigate the relationship between antibiotic use and long-term clinical outcomes.
To the best of our knowledge, this is the first multicenter retrospective observational study to describe the real-world antibiotic use in AECOPD patients in Chinese hospitals of different grades. This study indicated that antibiotics are extensively prescribed to AECOPD patients in China and demonstrated the limited compliance to the AECOPD guidelines in real-world antibiotic use. More well-designed clinical trials are warranted to further help guide the rational antibiotic use in the treatment of AECOPD.