Pneumonia Pathogens Research Articles

Possibilities of physical therapy and electrophysical modalities in the complex therapy of pneumonia

Pneumonia is one of the most common infectious diseases and the leading infectious cause of death worldwide. High rates of morbidity, frequency of complications, mortality, the emergence of new highly virulent strains of pneumonia pathogens, antibiotic resistance determine the global medical and social problem of community-acquired pneumonia. The economic consequences of pneumonia are represented not only by direct medical costs (the cost of maintaining a patient in a medical institution, the cost of medical services, the cost of medicines, laboratory and instrumental studies, other medical procedures, etc.), but also include non-material costs from pneumonia, which include pain, psycho-emotional experiences of the patient due to a decrease in the quality of life during the illness. One of the directions of increasing the effectiveness of pneumonia therapy is the widespread introduction of physical therapy (PT) and electrophysical modalities (EM) into complex treatment, which are an important part of the medical rehabilitation for pneumonia, aimed at the speedy restoration of the health and working capacity of patients. The effectiveness of EM in the treatment of pneumonia is due to the versatile therapeutic effect of physical factors that have anti-inflammatory, desensitizing, bacteriostatic, broncholytic, mucolytic, immunostimulant effects, improve blood supply to the lungs. PT contributes to the normalization of pulmonary ventilation, has an expectorant effect, strengthens the respiratory muscles, accelerates the resorption of the inflammatory focus, prevents the formation of pleural adhesions, activates blood and lymph circulation. PT and EM are relevant in the comprehensive treatment of community-acquired pneumonia since they accelerate the regression of clinical symptoms, decrease the drug load, reduce the duration of inpatient treatment, that is confirmed by the results of clinical studies. We assume that the inclusion of PT and EM in the comprehensive treatment of pneumonia can lead to minimizing the total cost of the disease while reducing the duration and volume of drug treatment.

Rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by diagnostic bronchoscopy

To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×109/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO2/FiO2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO2/FiO2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Retrospective Analysis of Spectrum of Infections and Antibiotic Resistance Pattern in Chronic Kidney Disease Patients on Maintenance Hemodialysis in a Tertiary Care Centre in North India.

Hemodialysis patients are at risk of infections. This study examines the spectrum of infections and antibiotic resistance patterns. We retrospectively reviewed the records of 586 hemodialysis patients from May 2018 to April 2020 in a tertiary care hospital in North India. The study identified 99 episodes of confirmed infections. Urinary tract infections were the most common type of infections (55.5%), followed by catheter-related bloodstream infections (CRBSI) (definitive 21.2%). Other infections were pneumonia (8.1%), tuberculosis (6.1%), skin and soft tissue infection (4.0%), dengue fever (3.03%), and empyema thoracis (1.0%). Overall, Escherichia coli (33.3%) was the most common organism isolated. The most frequent uropathogens recovered were Escherichia coli (54%). In confirmed CRBSI, P. aeruginosa (23.8%) and MSSA (23.8%) were the most common pathogen isolated. K. pneumonia (37.5%) was the most common pathogen in pneumonia. Uropathogens showed the highest resistance to fluoroquinolones (93.3%-100%). Pathogens isolated in CRBSI showed maximum resistance to ciprofloxacin (100%). In pneumonia, the highest resistance was seen to third-generation cephalosporins (75%-100%). Though the bacterial spectrum remains the same over time, antibiotic resistance is changing in uropathogens. There is a trend of predominance of Gram-negative bacterial infections in CRBSI. Tuberculosis incidence rate was much higher than the general population. There is a need for nationwide and worldwide continuous surveillance.

The Bactericidal Effect of Aloe on Pathogens of Pneumonia

The Bactericidal Effect of Aloe on Pathogens of Pneumonia

The role of hormonal changes in adaptation disorders of young systems in the course of community-acquired pneumonia

Community-acquired pneumoniae are considered as life-threatening infectious diseases and are one of the main causes of morbidity, hospitalization, and mortality. The main goal is to study and assess the role of the hormone imbalance in the adaptation disorders of young organism during the community-acquired pneumonia. To achieve the goals of the research 296 male patients with pneumonia, aged 18-21, were examined. The control group consisted of 63 practically healthy male individuals of the same age. Besides standard examinations, the levels of cortisol, testosterone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, antithyroglobulin and anti-thyroid-peroxidase were determined in the blood serum. The analysis shows that the level of prolactin in all research groups tends to increase; the level of testosterone in all the groups tends to decrease; the level of cortisol in the 18-19 age group tends to decrease; in the 20-21 age group this indicator increases, but it remains below the level of the indicator of the control group. The impact of unfavorable factors of military service, the neuropsychological and physical overstrain, the change in the diet and rations, army-specific conditions, and the unusual situation for some individuals lead to an overstrain and exhaustion of the protective adaptation reactions of the organism, manifested also by hormonal shifts. In the conditions of community-acquired pneumonia, the adaptation process of the organism was accompanied by a similar phasal endocrine shifts, manifested by marginal hyperprolactinemia, a decline in testosterone levels, with no increase in the levels of cortisol detected, regardless of the fact that community-acquired pneumonia was a stress factor for the organism. The main pathogen of the community-acquired pneumonia among the military was mycoplasma pneumoniae and chlamydophila pneumoniae. The course of the pneumonia cases was clinically atypical and rapid, swiftly complicating with hemorrhagic alveolitis. In some cases, the clinical course of the illness lagged behind the findings by X-ray imaging examination results.

Diagnosis and Treatment of Water-Contaminated Severe Legionella Pneumonia with Digestive Symptoms as the First Symptom: A Case Report and Review of the Literature

Although Legionella is not the most common pathogen of community-acquired pneumonia, the epidemiological distribution of pneumonia pathogens has changed in recent years, with a gradual increase in some rare pathogens. For example, pneumonia that occurs after water source contamination is mostly caused by Legionella infection. This paper reports the diagnosis and treatment process of a patient after Legionella infection, who had misdiagnosis at the beginning, rapidly progressed to severe disease and combined with fungal infection. This article focuses on the timely and effective treatment of rapidly progressing Legionella pneumonia, in anticipation of a better understanding of the diagnosis and treatment of the disease. Here, we report a case of legionella infection with the nausea, vomiting as the first symptoms accompanied by weakness, chills, dizziness, abdominal discomfort in a 75-year-old female. The patient had a history of type 2 diabetes for 30 years, diabetic peripheral neuropathy for more than 20 years, arterial hypertension for 10 years, bone hyperplasia for more than 5 years, resection of right-sided thyroid cystadenoma in 1990. The patient had firstly been diagnosed with cholecystitis and gallbladder neck stones, diet abstinence, metronidazole, cefoperazone sulbactam, and rehydration were given. The patient responded poorly to these empiric treatments. The patient was given moxifloxacin in combination with azithromycin after the onset of respiratory symptoms, but the condition continued to deteriorate, and tigecycline was subsequently added. After the mechanical ventilation and the treatment plan adjusting, she improved significantly. Immunocompromised patient combined with underlying diseases are more susceptible to infection in an environment contaminated with Legionella, and the rapid onset and atypical respiratory symptoms make it easy to misdiagnose the disease, thus delaying treatment and leading to further deterioration. Timely diagnosis, early mechanical ventilation and rational drug administration were fundamental to treat Legionella pneumonia.

The role of hormonal changes in adaptation disorders of young systems in the course of community-acquired pneumonia

Community-acquired pneumoniae are considered as life-threatening infectious diseases and are one of the main causes of morbidity, hospitalization, and mortality. The main goal is to study and assess the role of the hormone imbalance in the adaptation disorders of young organism during the community-acquired pneumonia. To achieve the goals of the research 296 male patients with pneumonia, aged 18-21, were examined. The control group consisted of 63 practically healthy male individuals of the same age. Besides standard examinations, the levels of cortisol, testosterone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, antithyroglobulin and anti-thyroid-peroxidase were determined in the blood serum. The analysis shows that the level of prolactin in all research groups tends to increase; the level of testosterone in all the groups tends to decrease; the level of cortisol in the 18-19 age group tends to decrease; in the 20-21 age group this indicator increases, but it remains below the level of the indicator of the control group. The impact of unfavorable factors of military service, the neuropsychological and physical overstrain, the change in the diet and rations, army-specific conditions, and the unusual situation for some individuals lead to an overstrain and exhaustion of the protective adaptation reactions of the organism, manifested also by hormonal shifts. In the conditions of community-acquired pneumonia, the adaptation process of the organism was accompanied by a similar phasal endocrine shifts, manifested by marginal hyperprolactinemia, a decline in testosterone levels, with no increase in the levels of cortisol detected, regardless of the fact that community-acquired pneumonia was a stress factor for the organism. The main pathogen of the community-acquired pneumonia among the military was mycoplasma pneumoniae and chlamydophila pneumoniae. The course of the pneumonia cases was clinically atypical and rapid, swiftly complicating with hemorrhagic alveolitis. In some cases, the clinical course of the illness lagged behind the findings by X-ray imaging examination results.

Rapid Identification of Pathogens in Severe Pneumonia by Species-specific Bacterial Detector (SSBD).

Fast and accurate detection of pathogenic bacterial infection in patients with severe pneumonia is significant to its treatment. The traditional culture method currently used by most medical institutions relies on a time-consuming culture process (over two days) that is unable to meet clinical needs. Rapid, accurate, and convenient species-specific bacterial detector (SSBD) has been developed to provide timely information on pathogenic bacteria. The SSBD was designed based on the fact that Cas12a indiscriminately cleaves any DNA following the binding of the crRNA-Cas12a complex to the target DNA molecule. SSBD involves two processes, starting with PCR of the target DNA using primers specific for the pathogen, followed by detection of the existence of pathogen target DNA in the PCR product using the corresponding crRNA and Cas12a protein. Compared to the culture test, the SSBD can obtain accurate pathogenic information in only a few hours, dramatically shortening the detection time and allowing more patients to benefit from timely clinical treatment.

Antibiotic Resistance of Hemophilus influenzae Isolated from Children in Southwest China.

Hemophilus influenzae (Hi) is one of the major pediatric bacterial pneumonia pathogens that heavily threatens children's lives and global health. With widespread usage as first-line treatment, the prevalence of β-lactam-resistant strains is increasing sharply. In order to treat Hi more effectively, a systematic study on the antibiotic resistance profiles, β-lactamase-negative ampicillin-resistant (BLNAR) strains isolation rate, and potential BLNAR resistance mechanism in our region is needed. This study analyzed antimicrobial susceptibility of Hi, and clinical data of Hi-infected patients retrospectively. BLNAR and β-lactamase-positive ampicillin-clavulanate resistant strains (BLPACR) were confirmed by the Kirby-Bauer method and β-lactamase test. ftsI gene in BLNAR was sequenced to find out whether resistance was induced by penicillin-binding protein mutation. Ampicillin susceptibility test with or without efflux pump inhibitors were done to assess efflux pump contribution in BLNAR. RT-PCR was performed to evaluate the efflux pump genes' transcription levels. A total of 2,561 Hi strains were isolated in our hospital from January 2016 to December 2019. Male to female ratio was 1.52:1. Median age was 10 months. Infant (< 3 years old) infection accounted for 83.72%. Hi resistance rates to sulfamethoxazole-trimethoprim, ampicillin, cefathiamidine, cefaclor, cefuroxime, cephalothin, amoxicillin-clavulanate, tetracycline, chloramphenicol, ofloxacin, cefotaxime, and rifampin were 84.28%, 78.01%, 49.80%, 41.98%, 36.58%, 33.64%, 4.55%, 4.1%, 3.37%, 1.77%, 0.99%, and 0.12%, respectively, while 1.33% were BLNAR. BLNARs were classified into four groups by mutation patterns in ftsI gene and most strains were divided to Group Ⅲ/Ⅲ-like. EmrB, ydeA and norM transcription levels in some ampicillin-resistant strains were higher than their sensitive counterparts. Ampicillin is not sufficiently effective as a first-line Hi infection treatment. However, ampicillin-clavulanate and cefotaxime may be a better choice. Efflux pumps, emrB, ydeA and norM play roles in the high resistance to ampicillin.

Diagnostic Role of FilmArray Pneumonia Panel Compared to Routine Microbiological Methods to Identify Pneumonia Pathogens

Diagnostic Role of FilmArray Pneumonia Panel Compared to Routine Microbiological Methods to Identify Pneumonia Pathogens

Gimap5 promoted RSV degradation through interaction with M6PR.

Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life-threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. RT-qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

2187. Validation of Local Risk Factors for Antibiotic-resistant Pathogens in Community-acquired Pneumonia at an Urban Community-based Medical Center

Abstract Background The 2019 ATS/IDSA community-acquired pneumonia (CAP) guidelines recommend to abandon the term healthcare-associated pneumonia (HCAP) and to base the use of broad-spectrum antibiotics on local epidemiology and risk factors. Jamaica, NY represents a unique population of ethnically diverse, largely immigrant patients. Several nursing homes, an international airport, along with a low socioeconomic status population feed into the hospital. The purpose of this study is to determine prevalent risk factors for drug-resistant pathogens (DRP) in CAP within an urban population. The secondary objective is to validate the Drug Resistance in Pneumonia (DRIP) score in this population. Methods A retrospective study was conducted on adults admitted from August 2018-December 2019 with a diagnosis of CAP, including aspiration pneumonia. Patients with a DRP respiratory culture (collected within 48 hours of admission) were selected, the next consecutively admitted patient with a non-resistant culture was included as a control. Results A total of 227 patients were included (114 in the DRP group and 113 in the control group). The DRP group had more patients with tracheostomies (30% vs 3%, p &amp;lt; .001) and chronic pulmonary disease (37% vs 16%, p &amp;lt; .001) (Table 1). Approximately 40% of the DRP patients were admitted from a long term care (LTC) facility compared to 8.8% in the control group (p &amp;lt; .001). Isolation of P. aeruginosa was not associated with LTC residence (Odds Ratio: 0.75) in our population (Table 2). All DRIP score components were associated with the isolation of DRP in our patient population, except for methicillin-resistant S. aureus (MRSA) colonization (Table 3). In our population 50% of the DRP had a DRIP score &amp;lt; 3. DRIP scores &amp;gt; 2, &amp;gt; 3 and &amp;gt; 4 had low negative predictive values (NPV) for the isolation of DRP in CAP (71.9%, 67.4% and 64.2%, respectively). Conclusion Demographic risk factors may exist for DRP in CAP, e.g. tracheostomy, pulmonary disease. Using a DRIP score cut off of &amp;gt; 4 missed 50% of the DRP in our study population. Despite a DRIP score &amp;gt; 4 having a specificity of 90.3%, with a NPV of 64.2% this scoring tool may underestimate the prevalence of DRP in our patient population. Based on our findings, institutions should consider local validation of the DRIP score prior to implementing use at their site. Disclosures All Authors: No reported disclosures.

2177. Institutional Prevalence of Drug-Resistant Pathogens in Community-Acquired Pneumonia

Abstract Background Community-acquired pneumonia (CAP) is a leading cause of hospitalizations and plays a major role in mortality. The previous Infectious Diseases Society of America (IDSA) definition of healthcare-associated pneumonia (HCAP) was found to be neither sensitive nor specific for identifying drug-resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA) as a cause of CAP, and use is no longer supported by current guidelines. The 2019 IDSA guidelines for CAP management emphasizes the need for clinician understanding of local epidemiology data to guide selection of appropriate treatment. The primary objective of this study was to determine the prevalence of MRSA and PsA CAP at our institution. Methods This was a retrospective observational study of patients admitted to our 870-bed public hospital with a CAP or HCAP diagnosis within 48 hours of admission between March 2016 and March 2021. The primary outcome of prevalence of CAP caused by MRSA or PsA was determined by comparing the number of blood and adequate sputum cultures with MRSA or PsA to total reviewed cases. Secondary outcomes included the percentage of initial antibiotic regimens involving a broad-spectrum agent, percentage of initial broad-spectrum regimens de-escalated within 72 hours if indicated, and duration of CAP antibiotic treatment. Results A total of 220 patients were included. MRSA or PsA was isolated in 1.36% of adequate sputum cultures collected (n=3/35) and in no collected blood cultures (n=0/208). The local prevalence of CAP caused by MRSA or PsA among the analyzed sample was 1.36% (n=3/220) (Table 1). MRSA nares screening tests were completed in 10% of cases, 4.5% of which were positive (n=1/22). Secondary end point results are presented in Table 2.Table 1.Prevalence of MRSA and PsA in CAP Based on Culture DataTable 2.Secondary Outcome Data Conclusion The overall prevalence of CAP caused by MRSA or PsA among admitted patients is low at Parkland Hospital. Further research is needed to identify local risk factors associated with CAP caused by drug-resistant pathogens. Disclosures All Authors: No reported disclosures.

880. Molecular Subtyping and Macrolide-Resistance Determination of Mycoplasma pneumoniae from Children Enrolled in New Vaccine Surveillance Network in the United States during 2015 to 2020

Abstract Background Mycoplasma pneumoniae (MP), a common pediatric pneumonia pathogen, has 2 subtypes based on P1 adhesin gene variation. Macrolide-resistant MP (MRMP), seen since 2000 in many countries, has been subtype associated. Limited U.S. pediatric data exist on MP subtype or MRMP frequency and their clinical importance. Methods During 2015–2020, mid-turbinate nasal swab (MTNS) specimens and/or throat swabs were collected from children with acute respiratory illness (ARI) enrolled in emergency department (ED) or outpatient and inpatient settings at 4 CDC-funded New Vaccine Surveillance Network sites (Cincinnati, Seattle, Houston, and Kansas City). Specimens were tested for MP and common respiratory viruses by singleplex or multiplex polymerase chain reaction assay (PCR). P1-subtyping for MP positive specimens used multiplex TaqMan real-time PCR while MR was assessed by real time PCR with melt curve analysis (Lightmix®, TIBMolbiol). Select demographic/clinical data were analyzed by P1 subtype (P1–1 vs. P1–2). Results Of 208 MTNS specimens from 208 children (median age 5.5 years), 110 (53%) were P1–1, 89 (43%) P1–2, and 9 (4%) untypeable. Of 199 typeable specimens, 111 (56%) came from inpatients while 88 (44%) came from ED/outpatients.Overall MRMP prevalence during 2015–2020 was low (3/208,1.4%); all MRMP (Houston: 1 each in 2016–2017 and 2019–2020, Seattle: 1 in 2018–2019) were P1–1. Differences in P1–2 vs. P1–1 proportions were significant in 2 years: P1–2 dominated in 2015–2016; P1-1 in 2019–2020 (Figure 1). Common clinical symptoms for 199 MP-positive patients were fever (84%, mean 102.5±1.5oF), shortness of breath (82%), wheezing (67%), and cough (60%). Clinical manifestations, hospitalization, and antibiotic use did not differ in P1-1 vs. P1-2 patients. Antibiotics were used in 59/199 (30%) patients overall; amoxicillin was most frequent (48/199, 24%), followed by cefdinir (9/199, 5%) and azithromycin (5/199, 3%). Conclusion MP subtypes co-circulated during 2015–2020; P1-2 dominated in 2015–2016, P1-1 in 2018–2019. Signs/symptoms were similar for P1-1 and P1-2. MRMP detection was uncommon among our pediatric subjects. Ongoing surveillance is important to assess potential changes in MR prevalence and temporal subtype variation. Disclosures Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Mary E. Moffatt, M.D., Becton and Dickinson and Company: Stocks/Bonds|Biogen: Stocks/Bonds|Coloplast B: Stocks/Bonds|Express Scripts: Stocks/Bonds|Novo Nordisk A/S Spons ADR: Stocks/Bonds|Novo Nordisk A/S-B: Stocks/Bonds|Steris PLC: Stocks/Bonds|Stryker Corp: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant.

1689. In Vitro Activity of Lefamulin Against Bacterial Pathogens Collected From Pneumonia Patients in United States and Latin America Medical Centers in 2020-2021

Abstract Background Lefamulin is a novel pleuromutilin protein synthesis inhibitor approved in the US, Canada, and Europe for the oral and intravenous treatment of community-acquired bacterial pneumonia (CABP) in adults due to typical and atypical pathogens. This study evaluated the in vitro activity of lefamulin and comparators against bacterial isolates from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia in the US and Latin America. Methods 1,907 unique isolates were collected within the SENTRY surveillance program from 29 medical centers in the US and 8 medical centers in Latin America (Argentina, Brazil, Chile, Colombia, Mexico, Panama). Isolates were susceptibility tested by CLSI reference broth microdilution methods. CLSI breakpoints (M100, 2022) were applied. Results Lefamulin inhibited 100% of S. pneumoniae isolates at or below its susceptible (S) breakpoint of ≤ 0.5 mg/L, regardless of resistance to other antibiotics used to treat CABP (MIC90 values of 0.12 or 0.25 mg/L, Table). The penicillin-resistant (R; 12.7%), azithromycin-R (43.7%), and tetracycline-R S. pneumoniae (20.4%) displayed reduced susceptibility to the other CABP drugs tested, except moxifloxacin ( &amp;gt; 98.2% S) and lefamulin (100% S). Lefamulin was highly potent against S. aureus, including MRSA, azithromycin-R, and moxifloxacin-R isolates, with 100% of isolates inhibited at or below the lefamulin S breakpoint of ≤ 0.25 mg/L. Susceptibility to azithromycin and moxifloxacin was particularly low for MRSA (13.9% and 25.0%, respectively). The fastidious Gram-negative H. influenzae and M. catarrhalis, of which 24.0% and 98.8%, respectively, were ß-lactamase positive, were S to lefamulin ( &amp;gt; 93%) and the other tested CABP drugs ( &amp;gt; 89%). Table. Susceptibility of pneumonia pathogens from US and Latin America to lefamulin and other CABP drugs Conclusion Lefamulin displayed potent in vitro activity against contemporary CABP pathogens from the US and Latin America. Its activity was unaffected by resistance to other antibiotic classes, including fluoroquinolones, macrolides, β-lactams, and tetracyclines. Lefamulin represents a valuable empiric treatment option for ambulatory and hospitalized patients with CABP, particularly when the causative pathogen is not identified or in settings with high prevalence of resistance. Disclosures Susanne Paukner, PhD, Nabriva Therapeutics: Inventor|Nabriva Therapeutics: Employee|Nabriva Therapeutics: Stocks/Bonds SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Steven P. Gelone, PharmD, Nabriva Therapeutics: Board Member|Nabriva Therapeutics: Inventor|Nabriva Therapeutics: Employee|Nabriva Therapeutics: Stocks/Bonds|Nabriva Therapeutics: Stocks/Bonds Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support.

Insight into the Pathogenic Mechanism of Mycoplasma pneumoniae.

Mycoplasma pneumoniae, an obligate parasitic pathogen without cell wall, can cause severe upper and lower respiratory tract symptoms. It is the pathogen of human bronchitis and walking pneumonia, and named community-acquired pneumonia. In addition to severe respiratory symptoms, there are clinical extrapulmonary manifestations in the skin, brain, kidney, musculoskeletal, digestive system, and even blood system after M. pneumoniae infection. Hereby, we comprehensively summarized and reviewed the intrapulmonary and extrapulmonary pathogenesis of M. pneumoniae infection. The pathogenesis of related respiratory symptoms caused by M. pneumoniae is mainly adhesion damage, direct damage including nutrient predation, invasion and toxin, cytokine induced inflammation damage and immune evasion effect. The pathogenesis of extrapulmonary manifestations includes direct damage mediated by invasion and inflammatory factors, indirect damage caused by host immune response, and vascular occlusion. The intrapulmonary and extrapulmonary pathogenic mechanisms of M. pneumoniae infection are independent and interrelated, and have certain commonalities. In fact, the pathogenic mechanisms of M. pneumoniae are complicated, and the specific content is still not completely clear, further researches are necessary for determining the detailed pathogenesis of M. pneumoniae. This review can provide certain guidance for the effective prevention and treatment of M. pneumoniae infection.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

Host Cell Oxidative Stress Promotes Intracellular Fluoroquinolone Persisters of Streptococcus pneumoniae.

Bacterial persisters represent a small subpopulation that tolerates high antibiotic concentrations without acquiring heritable resistance, and it may be generated by environmental factors. Here, we report the first antibiotic persistence mechanism in Streptococcus pneumoniae, which is induced by oxidative stress conditions and allows the pneumococcus to survive in the presence of fluoroquinolones. We demonstrated that fluoroquinolone persistence is prompted by both the impact of growth arrest and the oxidative stress response induced by H2O2 in bacterial cells. This process protected pneumococci against the deleterious effects of high ROS levels induced by fluoroquinolones. Importantly, S. pneumoniae develops persistence during infection, and is dependent on the oxidative stress status of the host cells, indicating that its transient intracellular life contributes to this mechanism. Furthermore, our findings suggest persistence may influence the outcome of antibiotic therapy and be part of a multistep mechanism in the evolution of fluoroquinolone resistance. IMPORTANCE In S. pneumoniae, different mechanisms that counteract antibiotic effects have been described, such as vancomycin tolerance, heteroresistance to penicillin and fluoroquinolone resistance, which critically affect the therapeutic efficacy. Antibiotic persistence is a type of antibiotic tolerance that allows a bacterial subpopulation to survive lethal antimicrobial concentrations. In this work, we used a host-cell infection model to reveal fluoroquinolone persistence in S. pneumoniae. This mechanism is induced by oxidative stress that the pneumococcus must overcome to survive in host cells. Many fluoroquinolones, such as levofloxacin and moxifloxacin, have a broad spectrum of activity against bacterial pathogens of community-acquired pneumonia, and they are used to treat pneumococcal diseases. However, the emergence of fluoroquinolone-resistant strains complicates antibiotic treatment of invasive infections. Consequently, antibiotic persistence in S. pneumoniae is clinically relevant due to prolonged exposure to fluoroquinolones likely favors the acquisition of mutations that generate antibiotic resistance in persisters. In addition, this work contributes to the knowledge of antibiotic persistence mechanisms in bacteria.

Tigecycline in the treatment of severe pneumonia caused by Chlamydia psittaci: A case report and literature review.

Psittacosis is a zoonotic disease caused by Chlamydia psittaci. Systemic infections are mainly transmitted through the respiratory tract. The most common related disease is human atypical pneumonia, which is a rare pathogen of community-acquired pneumonia. Due to the difficulty of diagnosis, there have been few reports of C. psittaci pneumonia in the past. In recent years, with the widespread application of metagenomic next-generation sequencing (mNGS), the number of reported cases of C. psittaci has increased year by year. However, at present, most hospitals have little understanding of C. psittaci, especially for severe patients, and lack experience in diagnosis and treatment. Herein, we report the case of a 71-year-old woman with severe pneumonia that caused by C. psittaci. This patient was diagnosed through mNGS and was treated with tigecycline successfully. The level of IL-6 in the BALF was significantly increased. We discontinued tigecycline after mNGS of the blood was negative. In this review, we analyzed 53 cases to summarize the etiology, clinical manifestations, diagnosis and treatment strategies of severe C. psittaci pneumonia and hope to raise clinicians' awareness of this disease.

Atypical Pathogens in Adult Community-Acquired Pneumonia and Implications for Empiric Antibiotic Treatment: A Narrative Review.

Atypical pathogens are intracellular bacteria causing community-acquired pneumonia (CAP) in a significant minority of patients. Legionella spp., Chlamydia pneumoniae and psittaci, Mycoplasma pneumoniae, and Coxiella burnetii are commonly included in this category. M. pneumoniae is present in 5-8% of CAP, being the second most frequent pathogen after Streptococcus pneumoniae. Legionella pneumophila is found in 3-5% of inpatients. Chlamydia spp. and Coxiella burnetii are present in less than 1% of patients. Legionella longbeachae is relatively frequent in New Zealand and Australia and might also be present in other parts of the world. Uncertainty remains on the prevalence of atypical pathogens, due to limitations in diagnostic means and methodological issues in epidemiological studies. Despite differences between CAP caused by typical and atypical pathogens, the clinical presentation alone does not allow accurate discrimination. Hence, antibiotics active against atypical pathogens (macrolides, tetracyclines and fluoroquinolones) should be included in the empiric antibiotic treatment of all patients with severe CAP. For patients with milder disease, evidence is lacking and recommendations differ between guidelines. Use of clinical prediction rules to identify patients most likely to be infected with atypical pathogens, and strategies of narrowing the antibiotic spectrum according to initial microbiologic investigations, should be the focus of future investigations.