Introduction
Psittacosis pneumonia is a zoonotic illness brought on by Chlamydia psittaci (C. psittaci).1 Instances primarily happen in sufferers uncovered to respiratory secretions or aerosols from contaminated birds.2 The medical manifestations of psittacosis pneumonia are extremely variable,3,4 usually presenting as community-acquired pneumonia (CAP) with typical signs together with excessive fever, dry cough, headache, myalgia, chills, and gastrointestinal disturbances. Nonetheless, psittacosis accounts for lower than 5% of CAP circumstances.5 In extreme cases, the illness can progress to respiratory failure, endocarditis, jaundice, and neurological problems. Extra essential circumstances might result in acute respiratory misery syndrome (ARDS), septic shock, or multi-organ dysfunction. In China, C. psittaci is acknowledged as a standard pathogen of extreme community-acquired pneumonia (SCAP).6
The medical analysis of psittacosis pneumonia primarily depends on influenza-like atypical pneumonia signs and a historical past of poultry publicity. Suspected circumstances with related epidemiological publicity, medical presentation, and imaging findings might be confirmed in the event that they meet at the least one of many following diagnostic standards:7 (1) Isolation of C. psittaci from respiratory secretions, bronchoalveolar lavage fluid (BALF), or blood samples; (2) Detection of anti-C. psittaci IgM antibodies at a titer of ≥1:16 by way of micro-immunofluorescence (MIF); (3) A ≥4-fold improve in antibody titer between paired serum samples collected two weeks aside, examined by complement fixation or MIF; (4) Identification of C. psittaci nucleic acids in respiratory or blood samples by way of polymerase chain response (PCR), metagenomic next-generation sequencing (mNGS), or focused next-generation sequencing (tNGS). Typical tradition of C. psittaci stays difficult in medical settings as a result of its time-consuming nature and requirement for tissue or egg embryonation. Serological checks and PCR additionally exhibit low sensitivity for C. psittaci detection.8,9 The shortage of extremely delicate and particular diagnostic strategies poses important limitations, contributing to historic estimates, largely derived from research carried out earlier than the widespread availability of molecular diagnostics and focused remedy, counsel a mortality charge of 15%–20% in untreated or delayed-treatment circumstances.10–13 Modern cohorts with well timed analysis and acceptable remedy typically report extra favorable outcomes.
Presently, mNGS has been extensively adopted to detect numerous microbial pathogens, together with viruses, micro organism, fungi, and parasites.14 Notably, mNGS permits analysis of atypical pathogens inside 24–48 hours, far surpassing the extended turnaround time of conventional cultures. This development facilitates early analysis and well timed, efficient remedy, bettering medical outcomes. For critically sick sufferers, mNGS has not too long ago emerged as essentially the most promising software for correct analysis of uncommon infections, significantly SCAP.15
Lately, reported psittacosis circumstances have elevated, with almost all confirmed by way of mNGS or tNGS.16,17 A latest examine analyzed 55 circumstances of C. psittaci pneumonia and in contrast extreme and non-severe illness, offering invaluable insights into medical, laboratory, imaging, mNGS, and remedy traits. The current examine differs from and extends this work within the following points: (i) our cohort is derived from Guangxi, a area with excessive poultry publicity prevalence and distinct epidemiological patterns; (ii) we offer detailed, systematic characterization of bronchoscopic findings — a function not described within the Gao et al examine — which can provide further diagnostic data in suspected psittacosis pneumonia; and (iii) we focus particularly on options differentiating SCAP from non-SCAP circumstances, offering exploratory information for speculation technology relating to severity-associated options.18 Given the absence of routine diagnostic strategies for psittacosis pneumonia, elucidating its medical options is important for early identification and exploration of options related to SCAP development. Though a number of case collection and multicenter research of mNGS-confirmed C. psittaci pneumonia have been reported, information from the Guangxi area — the place poultry publicity is very prevalent — stay restricted. Guangxi is China’s fourth-largest poultry breeding province, with a Chlamydia psittaci an infection charge of 28.20% in poultry, which exceeds the nationwide and Asian common ranges. Furthermore, circulating strains in native poultry are genetically associated to these remoted from human circumstances,19 and epidemiological information counsel greater psittacosis incidence in South China throughout autumn and winter months.20 Regardless of this important regional illness burden, no systematic characterization of mNGS-confirmed C. psittaci pneumonia from this area has been revealed. Moreover, bronchoscopic findings have not often been systematically described in psittacosis pneumonia, and direct comparisons between SCAP and non-SCAP circumstances inside a well-characterized cohort are missing. Nonetheless, direct population-based epidemiological proof on this area is at the moment missing.
The first goal of this retrospective examine was to systematically describe the demographic, medical, laboratory, imaging, and bronchoscopic traits of 40 mNGS-confirmed C. psittaci pneumonia sufferers in Guangxi. The secondary goal was to discover medical and laboratory options related to SCAP by evaluating SCAP and non-SCAP subgroups. This examine doesn’t goal to judge remedy efficacy or establish impartial predictors of outcomes, given the observational design and restricted pattern measurement.
Early identification of sufferers liable to SCAP development is clinically necessary as a result of delayed initiation of efficient antimicrobial remedy is related to worse outcomes in C. psittaci pneumonia. Nonetheless, at the moment out there severity prediction instruments (eg, CURB-65, PSI) had been developed for basic CAP populations and haven’t been particularly validated in C. psittaci pneumonia. Presently, particular person medical and laboratory predictors stay restricted, and bigger multicenter cohorts are wanted to assemble strong illness prediction fashions for early identification of SCAP threat in psittacosis. Within the current examine, we offer exploratory, hypothesis-generating information which will inform the design of such future research.
Supplies and Strategies
Enrolled Sufferers and Research Design
A retrospective evaluation was carried out on 40 hospitalized CAP sufferers on the First Affiliated Hospital of Guangxi Medical College between September 2019 and September 2024, whose bronchoalveolar lavage fluid (BALF), or blood samples examined constructive for C. psittaci by way of mNGS and had been clinically recognized with psittacosis pneumonia. The inclusion standards had been as follows: (1) Detection of C. psittaci in BALF, or blood samples by mNGS; (2) Analysis of CAP primarily based on the Chinese language Pointers for the Analysis and Therapy of Grownup Neighborhood-Acquired Pneumonia (2016 Version)21 and the 2019 joint CAP pointers issued by the Infectious Ailments Society of America/American Thoracic Society (IDSA/ATS);22 (3) Availability of full medical information. The exclusion standards included: (1) Incomplete medical information; (2) Non-CAP sufferers; (3) Age <18 years at admission; (4) CAP sufferers with out C. psittaci detection on mNGS. The key diagnostic standards for SCAP had been: (1) Requirement of invasive mechanical air flow by way of endotracheal intubation; (2) Septic shock necessitating vasopressor remedy regardless of ample fluid resuscitation. The minor standards had been: (1) Respiratory charge ≥30 breaths/min; (2) PaO2/FiO2 ratio ≤250 mmHg (1 mmHg=0.133 kPa); (3) Multilobar infiltrates; (4) Altered psychological standing and/or disorientation; (5) Blood urea nitrogen ≥20 mg/dL (7.14 mmol/L); (6) Systolic blood stress <90 mmHg requiring aggressive fluid resuscitation. Grouping was carried out retrospectively primarily based on essentially the most irregular medical and laboratory values recorded throughout the first 24 hours of admission.
Sufferers assembly both 1 main criterion or ≥3 minor standards had been recognized with extreme pneumonia, requiring shut monitoring, intensive remedy, and ICU admission when possible.
Knowledge Assortment
Scientific information had been extracted from digital medical information, together with: (1) Demographics; (2) Scientific manifestations: Signs, important indicators, endotracheal intubation standing, septic shock, period of mechanical air flow, and PaO2/FiO2 ratio; (3) Laboratory parameters: Inflammatory markers, arterial blood gasoline evaluation, biochemical checks, and microbiological outcomes; (4) Imaging options and bronchoscopic findings; (5) Antimicrobial remedy and outcomes: Very important indicators, hospital size of keep, ICU admission, and ICU period.
mNGS Evaluation
Scientific specimens (39 BALF samples and 1 blood pattern, blood samples had been collected for mNGS testing in a single affected person who had been unable to tolerate bronchoscopy on the time of admission) had been collected following standardized working procedures and instantly transported to WillingMed Know-how (Beijing) Co, Ltd. or Hangzhou Matridx Biotechnology Co, Ltd. for mNGS testing. The samples underwent standardized processing together with nucleic acid extraction and purification, library preparation, high-throughput sequencing, and bioinformatics evaluation to generate pathogen reviews.23,24 Sequencing was carried out on the MGISEQ-200 platform (WillingMed, 50 bp single-end reads, 10–20 million reads per pattern) or the Illumina NextSeq 550 platform (Matridx, 50 bp single-end reads, 10–20 million reads per pattern). Human reads had been subtracted by alignment to the human reference genome (GRCh38) utilizing Bowtie2. Remaining reads had been aligned to custom-curated microbial genome databases, which integrates the RefSeq full genome database and the NCBI non-redundant nucleotide sequence database (NCBI nt), for species-level identification utilizing Kraken2 software program. Turnaround time was roughly 24–48 hours from pattern receipt to report technology. Destructive controls (NTC) had been included in every batch to account for background microbial contamination. Revealed professional consensus has indicated that every testing laboratory ought to set up its personal diagnostic thresholds for various pathogens primarily based on its particular mNGS procedures and for various kinds of infections when issuing reviews, and will validate these thresholds in medical follow.25 For frequent micro organism, fungi, and viruses, Willingmed and Matridx have every established their very own constructive judgment thresholds. The pathogen dedication technique for Willingmed is as follows: The sequence depend for every microorganism is quantified utilizing RPTM (reads per ten million, representing the variety of microorganism-specific reads per ten million complete reads). A virus is taken into account constructive if the RPTM is ≥ 3. The RPTM threshold for micro organism and fungi is ≥ 20. The pathogen dedication technique for Matridx is as follows: Pathogens are reported if: 1) the sequencing information cross high quality management filters (library focus > 50 pM, Q20 > 85%, Q30 > 80%); and a pair of) the unfavourable management (NC) in the identical sequencing run doesn’t comprise the species, or the ratio of RPM(pattern) to RPM(NC) is ≥ 5. Nonetheless, for particular pathogens similar to Chlamydia psittaci, Mycobacterium tuberculosis, and Cryptococcus, and so forth, each the present consensus and the thresholds set by numerous testing laboratories undertake the criterion that the detection of a single particular learn is taken into account constructive.
Co-detected organisms had been categorised by two impartial clinicians as: (i) clinically confirmed co-infection (supportive medical, radiological, and laboratory proof); or (ii) probably colonization (detection with out medical proof of invasive illness). Disagreements had been resolved by consensus with a 3rd reviewer.
Statistical Evaluation
Statistical analyses had been carried out utilizing SPSS 27.0 (IBM, USA). Steady variables with regular distribution had been expressed as imply ± commonplace deviation (X±SD) and in contrast utilizing Pupil’s t-test, non-normal steady variables had been reported as median and interquartile vary (IQR) and in contrast utilizing the Mann–Whitney U-test. Categorical variables had been introduced as counts (percentages) and analyzed utilizing chi-square or Fisher’s precise checks (when any anticipated cell depend was < 5). A two-tailed P < 0.05 was thought of statistically important. Given the restricted pattern measurement (n=40, with 13 SCAP circumstances), formal multivariable logistic regression was not carried out. All analyses must be thought of exploratory and hypothesis-generating.
Outcomes
Baseline Traits of Sufferers
This retrospective examine analyzed 40 sufferers with psittacosis pneumonia, together with 27 non-SCAP and 13 SCAP circumstances. All sufferers had documented poultry publicity (birds, chickens, or geese). Among the many sufferers, 29 had been male (72.50%). The median age was 59 years (vary: 31–85), with SCAP sufferers had a median age of 61 years and Non-SCAP sufferers was 58 years, with no important distinction between teams (P = 0.823). There have been 57.50% (23/40) sufferers with comorbidities, hypertension (n=13) was the most typical. Fever was current in 97.50% (39/40) of sufferers, with 38 circumstances ≥39 C. Different frequent signs included cough (82.50%, 33/40), sputum (75.00%, 30/40), dyspnea (52.50%, 21/40), and digestive tract signs (together with nausea, vomiting, higher belly discomfort, and so forth. 47.50%, 19/40). Much less frequent signs included myalgia (5.00%, 2/40) and headache (10.00%, 4/40). SCAP sufferers exhibited considerably greater charges of dyspnea (76.92% vs, 40.74%, P = 0.046) and headache (30.77% vs, 0%, P=0.008) than Non-SCAP. Among the many 40 sufferers, 12 sufferers had extreme hypoxia (PaO2/FiO2 ≤ 250 mmHg), which was extra frequent in SCAP sufferers. In contrast with non-SCAP sufferers, the oxygenation index of SCAP sufferers was decrease. The chance of loss of life was evaluated in response to the CURB-65 rating:18,19 0–1 level: low threat; 2 factors: average threat; 3–5 factors: excessive threat. All 13 SCAP sufferers had a better threat of loss of life than the Non-SCAP group (Table 1). Among the many 40 sufferers, 6 acquired invasive mechanical air flow, 1 acquired nasal high-flow oxygen remedy, 2 acquired non-invasive air flow, 23 acquired oxygen remedy (nasal cannula oxygen or masks oxygen), and eight didn’t require oxygen remedy. All SCAP sufferers had been admitted to the ICU, with ICU keep starting from 3 to 74 days.
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Desk 1 Demographic Traits of Sufferers
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Laboratory Findings in Psittacosis Pneumonia Sufferers
The vast majority of sufferers exhibited elevated ranges of white blood cells (WBC), absolute neutrophil depend (NEUT), procalcitonin (PCT), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr), and blood urea nitrogen (BUN), whereas confirmed decreased absolute lymphocyte depend (LYM). Furthermore, in comparison with Non-SCAP sufferers, WBC, NEUT, CRP, PCT, and BUN ranges (P < 0.05) had been considerably greater in SCAP sufferers, whereas LYM and CD4⁺ counts had been considerably decrease (P < 0.05) (Table 2). These findings counsel that SCAP sufferers with C. psittaci an infection have elevated inflammatory markers and are extra vulnerable to renal perform impairment.
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Desk 2 Evaluation of Variations in Scientific Indicators Between Teams
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Imaging and Fiberoptic Bronchoscopy Findings
Chest CT scans revealed that 15 circumstances (37.50%) had single lobe pulmonary infiltration, and 25 circumstances (62.50%) had bilateral or a number of lobe infiltration. The commonest manifestations had been consolidation (72.50%, 29/40) and air bronchogram (52.50%, 21/40), adopted by exudates (47.50%, 19/40) and pleural effusion (15.00%, 6/40). In contrast with Non-SCAP sufferers, SCAP sufferers confirmed extra lobe consolidation (Table 3). Consultant chest CT scans from SCAP sufferers are introduced in Figure 1. As proven in Figure 1A, bilateral decrease lobe consolidation was noticed. Figure 1B displays pulmonary infiltrates with bilateral pleural effusion. Moreover, Figure 1C illustrates left-sided opacities and pleural effusion mixed with right-sided consolidation and opacities. All sufferers underwent fiberoptic bronchoscopy. Outcomes confirmed that congestion and edema (75%, 30/40), serous (37.50%, 15/40), mucous (20.00%, 8/40), or purulent secretions (30.00%, 12/40) had been the principle options. In contrast with Non-SCAP sufferers, considerably much less SCAP sufferers had little secretions (15.38% vs, 62.96%, P < 0.05) (Table 4).
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Desk 3 Pulmonary Imaging Manifestations of 40 Sufferers with Psittacosis Pneumonia
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Desk 4 Fiberoptic Bronchoscopy Manifestations of 40 Sufferers with Psittacosis Pneumonia
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Determine 1 Chest CT imaging findings in SCAP sufferers. (A) Case 25, a 33-year-old male, was admitted on February 7, 2024, with a 3-day historical past of cough, sputum, fever, and dyspnea. mNGS was carried out on February 8, and remedy was initiated on February 7. Chest CT on admission confirmed intensive consolidation in each decrease lobes. (B) Case 1, a 69-year-old male, was admitted on September 1, 2022, with a 7-day historical past of cough, sputum, fever, and dyspnea. mNGS was carried out on September 2, and remedy was initiated on September 1. Chest CT revealed faint ground-glass opacities in each lungs and bilateral pleural effusion within the decrease lobes. (C) Case 8, an 85-year-old male, was admitted on November 14, 2024, with a 5-day historical past of cough, sputum, fever, dyspnea, and poor urge for food. mNGS was carried out on November 15, and remedy was initiated on November 14. Chest CT confirmed consolidation and opacities in the proper lung, opacities within the left higher lobe, and pleural effusion within the left decrease lobe.
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mNGS Testing
All sufferers underwent mNGS testing, with 39 circumstances utilizing BALF and 1 circumstances utilizing blood samples. C. psittaci was detected in all circumstances. The detailed pathogen detection outcomes and affected person data for every case are introduced in Supplementary Table S1. Among the many 40 sufferers, mNGS detected a complete of twenty-two pathogen detections categorised as an infection (8 within the SCAP group, 14 within the non-SCAP group) (Table 5) and 27 categorised as colonization (3 within the SCAP group, 24 within the non-SCAP group) (Supplementary Table S2). Within the an infection class, essentially the most regularly detected infecting organisms had been Streptococcus pneumoniae (n = 3, all non-SCAP), Aspergillus fumigatus (n = 3; 2 SCAP, 1 non-SCAP), Aspergillus flavus (n = 2, all non-SCAP), and Haemophilus parainfluenzae (n = 2, all non-SCAP). No statistically important variations within the distribution of particular person pathogens had been noticed between SCAP and non-SCAP teams (all p > 0.05, Fisher’s precise take a look at). Within the colonization class, essentially the most generally colonizing organisms had been Candida albicans (n = 5; 1 SCAP, 4 non-SCAP), Staphylococcus aureus (n = 3, all non-SCAP), Klebsiella pneumoniae (n = 3, all non-SCAP), Human herpesvirus 1 (HSV-1; n = 3, all non-SCAP), and Human herpesvirus 4 (EBV; n = 2, all non-SCAP). Notably, herpesvirus colonization was solely noticed within the non-SCAP group (7 vs, 0 detections, p = 0.074).
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Desk 5 Spectrum of Clinically Related Infectious Pathogens Detected by mNGS
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Therapy and Prognosis of Sufferers with Psittacosis Pneumonia
Among the many 40 sufferers with psittacosis pneumonia on this examine, 3 didn’t obtain empirical anti-infective remedy however had been instantly handled for the recognized pathogen. Two of them had been handled with moxifloxacin, 1 with doxycycline. Among the many 37 sufferers recognized with a selected pathogen, one affected person acquired remedy for the pathogen alone, 25 sufferers acquired mixed antibacterial remedy, one affected person acquired mixed antifungal remedy, seven sufferers acquired mixed antibacterial and antifungal remedy, one affected person acquired mixed antibacterial and antiviral remedy, and two sufferers acquired mixed antibacterial, antifungal, and antiviral remedy. SCAP sufferers had been extra prone to obtain mixed antibacterial and antifungal remedy (Table 6). After remedy, all sufferers on this examine skilled symptom reduction, improved lung imaging, and had been discharged with improved situations (Figure 2).
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Desk 6 Therapy and Outcomes of 40 Sufferers with Psittacosis Pneumonia
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Determine 2 The pulmonary imaging modifications of 1 case of SCAP sufferers. (A) The CT scan on September 10, 2022, after the affected person was admitted and the pathogen was recognized, confirmed consolidation in each lungs. Therapy with doxycycline for psittacosis started. (B) The CT scan on September 16, 2022, after 6 days of remedy for psittacosis, confirmed enchancment with much less exudate in comparison with the earlier scan. (C) The CT scan on September 21, 2022, after 11 days of remedy for psittacosis, confirmed enchancment with much less exudate in comparison with the earlier scan. (D) The CT scan on October 8, 2022, after 28 days of remedy for psittacosis, confirmed a slight exudate in each lungs, which had improved in comparison with the earlier scan. (E) The CT scan on November 2, 2022, after 53 days of remedy for psittacosis, confirmed enchancment with much less exudate in each lungs in comparison with the earlier scan.
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Dialogue
This examine analyzed the medical information of 40 sufferers recognized with C. psittaci CAP by way of mNGS at our hospital. We comprehensively evaluated their demographic traits, medical manifestations, laboratory findings, imaging options, remedy, and outcomes to boost understanding of psittacosis pneumonia in sufferers who underwent bronchoscopy, and to discover medical options and administration of C. psittaci-induced SCAP, finally aiming to enhance affected person prognosis.
All 40 sufferers on this examine had a transparent historical past of poultry publicity (birds, chickens, or geese), in step with earlier reviews on psittacosis transmission in people.3,10,26 Such publicity historical past serves as a vital diagnostic clue. Nonetheless, some sufferers might current with out direct contact with contaminated birds or poultry,11 which considerably complicates medical analysis of psittacosis.
The medical manifestations noticed in our cohort had been nonspecific, primarily together with fever, cough, sputum manufacturing, dyspnea, gastrointestinal signs, myalgia, and headache. Notably, in comparison with non-SCAP sufferers, SCAP sufferers had been extra prone to show dyspnea and headache, along with extra outstanding systemic manifestations and considerably worse oxygenation (decrease PaO2/FiO2 ratios). These distinct medical patterns align with findings reported by Su et al,27 Nonetheless, discrepancies exist with research by Lu2 and Yuan,26 and a multicenter information from 116 psittacosis sufferers in Central-South China,17 which discovered no important symptomatic variations between SCAP and non-SCAP teams, was inconsistent with our outcomes. Given the small pattern measurement, our examine has restricted statistical energy, which can improve the chance of each false-negative (Sort II error, lacking true associations) and false-positive (Sort I error) findings, significantly given the a number of unadjusted comparisons. Due to this fact, all reported associations must be thought of exploratory and interpreted with acceptable warning. However, our findings reinforce essential diagnostic insights: when CAP sufferers with avian publicity current with respiratory signs accompanied by extrapulmonary manifestations – significantly when paired with declining oxygenation indices – clinicians ought to strongly think about psittacosis pneumonia and monitor for potential SCAP development.
Our laboratory outcomes demonstrated that SCAP sufferers exhibited considerably greater ranges of WBC, NEUT, CRP, and PCT in comparison with non-SCAP circumstances, suggesting a extra pronounced inflammatory response in psittacosis-induced SCAP, which aligns with earlier findings by Fang et al,28 It must be famous that elevated WBC, CRP, and PCT ranges in SCAP in comparison with non-SCAP are anticipated findings not particular to psittacosis, as they replicate basic severity markers in community-acquired pneumonia. Nonetheless, decrease LYM and CD4 counts in SCAP sufferers had been related to extra extreme illness, in step with Yuan’s report.26 Whether or not these variations signify a trigger or a consequence of illness severity stays unclear and warrants additional investigation. Elevated Cr and BUN ranges in SCAP circumstances in comparison with non-SCAP circumstances counsel that these markers are related to SCAP development and elevated chance of renal dysfunction. Moreover, elevated ALT, AST, and CK ranges in psittacosis sufferers, as noticed in our examine and different reviews,17,29,30 point out potential gentle liver harm. Notably, CK serves as essentially the most delicate marker for muscle harm,31 implying attainable muscular involvement in psittacosis. These findings spotlight the significance of monitoring and managing hepatic and renal perform in affected sufferers. Given the restricted pattern measurement of the current examine (n=40, with solely 13 SCAP circumstances), formal multivariate logistic regression evaluation couldn’t be carried out with ample statistical energy. Nonetheless, primarily based on univariate analyses, the variables most strongly related to SCAP included PaO2/FiO2 ratio ≤250 mmHg at admission, lymphopenia (LYM <1.0×109/L), elevated CRP (>100 mg/L), elevated BUN (>7.5 mmol/L), and multilobar consolidation on CT. These findings are exploratory and hypothesis-generating; future multicenter potential research with bigger cohorts are wanted to validate these potential SCAP-associated options by way of multivariate evaluation and develop clinically relevant prediction fashions.
Segmental consolidation with air bronchograms emerged as a attribute imaging function of psittacosis pneumonia. Whereas consolidation was the most typical radiological discovering in our cohort, it must be famous that this function is nonspecific and can also happen in CAP brought on by bacterial, viral, or fungal pathogens,32,33 complicating etiological differentiation. Earlier research have additionally documented that C. psittaci an infection can result in meningitis and myocarditis.16,34 Our examine additional revealed that SCAP circumstances exhibited extra intensive consolidation, which possibly an indicator of extreme illness. Whereas pleural effusion has been related to greater mortality in pneumonia sufferers,35,36 our examine discovered no statistically important distinction in pleural effusion between SCAP and non-SCAP teams (P=0.075), which can be attributable to the limitation of the restricted variety of included circumstances. However, the presence of pleural effusion must also be additional investigated as a possible indicator of illness development to extreme kinds.
Our systematic bronchoscopic characterization, together with quantitative evaluation of mucosal options and secretion varieties with SCAP/non-SCAP comparability, extends the restricted bronchoscopic observations within the C. psittaci pneumonia literature. Whereas Gao et al,18 briefly famous bronchial mucosal congestion and edema of their 55-case cohort with out additional characterization or subgroup evaluation, our examine gives the primary detailed, quantitative description of bronchoscopic findings in psittacosis pneumonia and demonstrates that secretion abundance differs considerably between SCAP and non-SCAP sufferers (P < 0.05). These findings counsel that bronchoscopy might present adjunctive data for severity evaluation in suspected C. psittaci pneumonia, though potential validation is required.
Within the present examine, whereas elevated PCT ranges have been related to bacterial co-infection in some research,5 within the context of extreme C. psittaci pneumonia, PCT elevation might primarily replicate the magnitude of the host inflammatory response and illness severity fairly than particularly indicating polymicrobial an infection. Elevated PCT ranges in SCAP sufferers shouldn’t be equated with the presence of bacterial co-infection with out corroborating medical and microbiological proof. Our mNGS outcomes recognized further organisms past C. psittaci in a considerable proportion of sufferers, demonstrating mNGS’s capability for broad respiratory pathogen screening and correct identification of C. psittaci in SCAP sufferers.5,37–42 Based mostly on complete medical adjudication, detected organisms had been categorised as an infection (Table 2) or colonization (Supplementary Table S2). Amongst organisms categorised as an infection, essentially the most regularly detected had been Streptococcus pneumoniae, Aspergillus fumigatus, Aspergillus flavus, and Haemophilus parainfluenzae (Table 2). In distinction, organisms predominantly categorised as colonization included Candida albicans, Staphylococcus aureus, Klebsiella pneumoniae, human herpesvirus 1, and Epstein-Barr virus (Supplementary Table S2). Notably, Acinetobacter baumannii, Klebsiella pneumoniae, and EBV, had been categorised as colonization fairly than an infection in all circumstances after medical adjudication. This distinction underscores that mNGS detection alone can’t decide the pathogenic function of an organism. It must be famous that Candida species and EBV detected by mNGS usually are not usually thought of causative pathogens of pneumonia; their detection might replicate colonization or latent an infection fairly than true co-infection. According to this precept, in our cohort, all EBV and nearly all of Candida detections had been categorised as colonization, and all herpesvirus detections occurred solely within the non-SCAP group, additional suggesting that these viral indicators replicate latent viral shedding fairly than clinically important co-infection. Polymicrobial infections are nicely acknowledged to worsen medical outcomes in extreme pneumonia,5,28 doubtlessly mediated by way of the noticed lymphopenia and diminished CD4⁺ counts. Fu et al,43 reported that decreased CD3+ T lymphocyte percentages and CD4+/CD8+ ratios had been related to pneumonia severity in sufferers co-infected with influenza A virus and Mycoplasma pneumoniae. Equally, Hao et al,44 discovered that dynamic decreases in lymphocyte counts considerably correlated with elevated dangers of ECMO-associated infections and VAP. Relating to the organisms co-detected in our cohort, these overlapping with typical VAP-associated pathogens (together with Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae), had been predominantly categorised as colonization fairly than an infection. Particularly, A. baumannii was categorised as colonization within the sole SCAP case during which it was detected, and Okay. pneumoniae and P. aeruginosa had been categorised as colonization in all circumstances the place they appeared. Due to this fact, the detection of VAP-associated organisms in community-acquired circumstances with out basic VAP threat components warrants cautious interpretation and mustn’t mechanically set off anti-VAP remedy. Critically sick sufferers with SCAP who require invasive mechanical air flow are inherently at elevated threat of growing nosocomial infections, and clinicians ought to assess whether or not newly detected organisms signify true nosocomial superinfection requiring focused remedy versus colonization or contaminant sign, primarily based on complete analysis of the sufferers clinial evolution, together with modifications in fever sample, sputum traits, radiological development, and inflammatory marker traits. In SCAP sufferers with clinically suspected co-infection, individualized antimicrobial choice must be guided by complete medical evaluation, native antibiograms, and antimicrobial stewardship ideas fairly than mNGS co-detection outcomes alone. Broad empiric protection of VAP-associated pathogens will not be really helpful for all SCAP sufferers with out individualized threat evaluation, given the dangers of selling antimicrobial resistance and pointless drug toxicity.
Empirical antimicrobial remedy previous to confirmed analysis of C. psittaci an infection was usually ineffective, because the pathogen is intrinsically proof against beta-lactam antibiotics and aminoglycosides which are generally used as first-line empirical CAP remedy.1,4 On this examine, 92.5% of sufferers initially acquired empirical antibiotics, with 97.30% requiring antibiotic adjustment after definitive analysis (just one case continued unique routine). The best brokers in opposition to psittacosis pneumonia included quinolones, macrolides, and tetracyclines, which signify first-line remedies.21 Our remedy outcomes revealed: 14 sufferers acquired doxycycline, 25 acquired quinolones, 3 acquired mixture remedy with doxycycline and moxifloxacin (together with 2 SCAP circumstances). Notably, SCAP sufferers confirmed choice for doxycycline, in step with earlier reviews of this agent’s efficacy in extreme psittacosis.28,45 Doxycycline must be thought of as a first-line agent, in step with current literature and remedy pointers. All sufferers achieved medical enchancment, aligning with research demonstrating favorable outcomes with tetracycline-class antibiotics.45,46 Nonetheless, the comparative effectiveness of various drug lessons or monotherapy versus mixture remedy can’t be decided from this uncontrolled observational examine and requires additional potential analysis.
There are a number of limitations on this examine. First, this can be a single-center retrospective examine, which limits generalizability. Second, we solely included 40 mNGS-confirmed C. psittaci circumstances and excluded clinically suspected circumstances with out pathogen affirmation. Third, as a retrospective examine relying solely on mNGS, we lacked comparator information from PCR, serology, or tradition strategies, stopping analysis of mNGS sensitivity/specificity for C. psittaci detection. Fourth, the small SCAP pattern measurement (n=13) limits statistical energy and precludes multivariable modeling. Future multicenter potential research ought to incorporate a number of diagnostic modalities, consider utility of medical laboratory parameters, higher differentiate SCAP vs non-SCAP manifestations and optimize remedy methods for extreme circumstances. Fifth, since all enrolled sufferers underwent bronchoscopy previous to mNGS sampling, this cohort is topic to choice bias towards sufferers clinically deemed to require bronchoscopy — usually these with extra extreme or diagnostically unsure shows. This may occasionally account for the comparatively excessive proportion of SCAP circumstances (32.5%) in our cohort in contrast with some population-based estimates, and limits the generalizability of our findings to the broader medical spectrum of C. psittaci pneumonia, together with milder outpatient circumstances. These limitations are inherent to the retrospective, single-center design and might be addressed by way of future multicenter potential research with standardized protocols and bigger pattern sizes. Future research ought to embrace sufferers recognized by way of non-bronchoscopic sampling strategies to supply a extra full medical image.
In conclusion, C. psittaci pneumonia must be suspected in CAP sufferers with poultry or chicken publicity, significantly when presenting with fever, dyspnea, extrapulmonary manifestations (particularly headache), lymphopenia, and appropriate CT findings similar to consolidation with air bronchograms. Pleural effusion on chest CT confirmed a development towards greater frequency in SCAP sufferers however the affiliation didn’t attain statistical significance on this cohort; this discovering warrants additional investigation in bigger research. mNGS of BALF might facilitate well timed identification of C. psittaci when standard diagnostic strategies are unavailable or delayed, though this examine was not designed to judge the diagnostic accuracy of mNGS in opposition to reference requirements. Scientific enchancment was noticed following tetracycline- or quinolone-containing regimens. Doxycycline must be thought of as a first-line agent. The comparative effectiveness of various drug lessons can’t be decided from this observational examine and requires potential analysis. This examine is exploratory and hypothesis-generating; the recognized severity-associated options require validation in bigger, multicenter, potential cohorts.
Knowledge Sharing Assertion
The datasets used and/or analyzed in the course of the present examine can be found from the corresponding creator (Yi Liang, E-mail: [email protected]) upon cheap request.
Moral Approval
The examine was carried out in accordance with the Declaration of Helsinki. All procedures carried out within the examine involving human individuals had been in conformity to the moral requirements of the Ethics Committee of the First Affiliated Hospital of Guangxi Medical College (Approval No. 2025-E0597). The requirement for consent was waived as a result of the examine was a retrospective evaluation and all information had been anonymized previous to evaluation.
Acknowledgments
The authors want to thank the analysis employees and sufferers for his or her participation on this examine.
Creator Contributions
All authors made a big contribution to the work reported, whether or not that’s within the conception, examine design, execution, acquisition of knowledge, evaluation and interpretation, or in all these areas; took half in drafting, revising or critically reviewing the article; gave remaining approval of the model to be revealed; have agreed on the journal to which the article has been submitted; and comply with be accountable for all points of the work. Particular contributions: Tangjuan Liu and Liexiang Liao had been concerned in examine design, information evaluation, and manuscript drafting. Xiaojing Zhang and Yafeng Zheng contributed to manuscript revision and visualization. Chongxi Bao, Yujing Qi and Lu Zhu contributed to information assortment and administration. Yanbin Wu contributed to the revision, and funding. Yi Liang contributed to the oversight and revision of this text.
Funding
This work was supported partially by grants from Guangxi Applicable Medical Well being Know-how Promotion Undertaking (Approval No. S2024023) and a self-funded venture sponsor of Guangxi Well being Fee (Approval No. Z-A20240531).
Disclosure
The authors declare that they haven’t any battle of curiosity.
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