Bacterial Lower Respiratory Tract Infections Research Articles

Transforming Bacterial Lower Respiratory Tract Infection Diagnosis: A Study on the Efficiency of the FilmArray Pneumonia Panel

Abstract Background: Lower respiratory tract infections (LRTIs) significantly contribute to global morbidity and mortality. Conventional bacterial LRTIs diagnosis relies on microbiological methods, which are time-consuming. The Biofire® FilmArray® Pneumonia Panel (FAPP) offers a faster and more accurate detection of respiratory pathogens but shows conflicting results with conventional cultures. Aim: We assessed the agreement between bacterial organisms and resistance genes identified using FAPP and standard culture techniques. Methods: This single-center retrospective study analyzed 400 patient samples, comparing the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with conventional cultures. The prevalence of bacterial organisms and resistance markers in FAPP and cultures was estimated. Results: In 400 samples, 692 bacterial targets and 216 resistance markers were detected using FAPP. FAPP detection was 3.9 times higher than bacterial culture. The overall PPV, NPV, sensitivity, and specificity were 23.55%, 99.76%, 92.61%, and 90.92%, respectively. Multiple pathogens were found in 177 samples (46.3%) with FAPP. Conclusion: FAPP provides rapid and sensitive detection of respiratory bacterial infections. However, results should be interpreted with the clinical context. Further studies are needed to clarify its clinical impact and cost-effectiveness.

Outcomes of severe lower respiratory tract infection in Mexican children with cancer

Abstract Background Lower respiratory tract infections (LRTI) are a very serious complication in children with cancer, with high morbidity and mortality, due to viral infections, followed by bacterial and fungal organisms. These patients with cancer are undergoing chemotherapy that damages their mucosal barrier and respiratory epithelium, and course with profound or severe neutropenia. Thus, they are high-risk to develop severe respiratory infections acquired from the community. However, the clinical characteristics, etiological agents, finding on computed tomography (CT) and outcomes of the LRTI in immunocompromised patients are not well known, these are necessary in order to start adequate management including empirical antimicrobial therapy and supplementary oxygen therapy. Methods Children with cancer who were attended in the pediatric emergency room due to fever (>38°C) and presence of respiratory symptoms such as increased breath rate, cough, O2Sat <93%, and needed to supplementary oxygen were included. To analyze the cases of children with cancer and LRTI we documented the data regarding to clinical presentation, detection of respiratory virus and findings in the CT. Data such age, sex, oncological diagnosis, absolute neutrophil count. The detection of nucleic acid of respiratory virus was performed by qPCR, whereas the identification galactomannan in serum was done for fungal diagnosis, and clinical presentation was initial used for diagnosis of bacterial LRTI. The findings on TC were included to integrate all the LRTI etiological diagnosis. The outcomes recorded were to need supplementary oxygen therapy (nasal cannula, high-flow nasal cannula or mechanical ventilation), ICU admission, and mortality on the follow for all patient included in the study. A descriptive statistical analysis was performed to estimate frequency of the etiological agents, outcomes, and mortality rate. Results A total of 10 children with cancer and severe LRTI were followed up, 60% female sex, age 5.5 years (range, 1-16 <); 80% had acute leukemias and 20% lymphoma. Seven (70%) children were diagnosed with bacterial LRTI, whereas two (20%) and one (10%) were viral LRTI-diagnosed. The finding in the CT were the follow: bilateral patchy consolidation and ill-defined small nodules for viral infection, centrilobular nodules and bronchial wall thickening for bacterial infection and scattered nodules or patchy focus for fungal infection. In respect to clinical presentation 90% had fever, 100% had cough, and 100% had O2Sat <93%. Of these patients 60% were presented with profound and 20% with severe neutropenia (p<0.05); 30% had required high-flow oxygen and 10% mechanical ventilation; and three (30%) patients required care in ICU. The mortality rate for severe LRTI was 30%. Conclusion Children with cancer and profound or severe neutropenia are in high-risk to develop severe LRTI and they have high mortality. The finding on the CT can help to start on adequate management for LRTI in immunosuppressed pediatric patients.

Electronic Clinical Decision Support Tools: Strategies to Improve the Management of Lower Respiratory Tract Infections in Low-Resource Settings.

Lower respiratory tract infection (LRTI) is a common reason for hospitalization and antibacterial use globally. There is considerable overlap in the clinical presentation of bacterial and viral LRTIs. Low- or middle-income countries (LMICs) face the dual challenge of appropriately targeting antibacterials for bacterial LRTI while reducing inappropriate antibacterials for viral LRTI. We propose a framework by which an electronic clinical decision support tool (eCDST) for diagnosing LRTI and reducing unnecessary antibacterial use may be developed, validated, and prospectively evaluated in an LMIC. The developed tool would be data driven, low-cost, feasible in the local setting, adaptable based on resource availability, and updated in real time, with prospective assessment to identify its clinical impact. We draw upon our team's recent experience developing an eCDST for LRTI management in Sri Lanka. Publicly sharing such processes and data is valuable, such that we can collectively improve clinical care in LMICs and other settings.

Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial-viral differentiation.

Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Antimicrobial resistance patterns of bacterial and fungal lower respiratory tract infections among COVID-19 patients and their impact on Mortality

Antimicrobial resistance patterns of bacterial and fungal lower respiratory tract infections among COVID-19 patients and their impact on Mortality

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Disposable Peptidoglycan-Specific Biosensor for Noninvasive Real-Time Detection of Broad-Spectrum Gram-Positive Bacteria in Exhaled Breath Condensates.

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

Phage therapy: breathing new tactics into lower respiratory tract infection treatments.

Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and evolution of multidrug-resistant bacteria intensifies the urgency for alternative treatments. This review explores bacteriophage (phage) therapy as an innovative solution to combat bacterial LRTIs. Phages, abundant in nature, demonstrate specificity towards bacteria, minimal eukaryotic toxicity, and the ability to penetrate and disrupt bacterial biofilms, offering a targeted approach to infection control. The article synthesises evidence from systematic literature reviews spanning 2000-2023, in vitro and in vivo studies, case reports and ongoing clinical trials. It highlights the synergistic potential of phage therapy with antibiotics, the immunophage synergy in animal models, and the pharmacodynamics and pharmacokinetics critical for clinical application. Despite promising results, the article acknowledges that phage therapy is at a nascent stage in clinical settings, the challenges of phage-resistant bacteria, and the lack of comprehensive cost-effectiveness studies. It stresses the need for further research to optimise phage therapy protocols and navigate the complexities of phage-host interactions, particularly in vulnerable populations such as the elderly and immunocompromised. We call for regulatory adjustments to facilitate the exploration of the long-term effects of phage therapy, aiming to incorporate this old-yet-new therapy into mainstream clinical practice to tackle the looming AMR crisis.

Bacterial pathogens in Xpert MTB/RIF Ultra-negative sputum samples of patients with presumptive tuberculosis in a high TB burden setting: a 16S rRNA analysis.

In patients with presumptive tuberculosis (TB) in whom the diagnosis of TB was excluded, understanding the bacterial etiology of lower respiratory tract infections (LRTIs) is important for optimal patient management. A secondary analysis was performed on a cohort of 250 hospitalized patients with symptoms of TB. Bacterial DNA was extracted from sputum samples for Illumina 16S rRNA sequencing to identify bacterial species based on amplicon sequence variant level. The bacterial pathogen most likely to be responsible for the patients' LRTI could only be identified in a minority (6.0%, 13/215) of cases based on 16S rRNA amplicon sequencing: Mycoplasma pneumoniae (n = 7), Bordetella pertussis (n = 2), Acinetobacter baumanii (n = 2), and Pseudomonas aeruginosa (n = 2). Other putative pathogens were present in similar proportions of Xpert Ultra-positive and Xpert Ultra-negative sputum samples. The presence of Streptococcus (pseudo)pneumoniae appeared to increase the odds of radiological abnormalities (aOR 2.5, 95% CI 1.12-6.16) and the presence of S. (pseudo)pneumoniae (aOR 5.31, 95% CI 1.29-26.6) and Moraxella catarrhalis/nonliquefaciens (aOR 12.1, 95% CI 2.67-72.8) increased the odds of 6-month mortality, suggesting that these pathogens might have clinical relevance. M. pneumoniae, B. pertussis, and A. baumanii appeared to be the possible causes of TB-like symptoms. S. (pseudo)pneumoniae and M. catarrhalis/nonliquefaciens also appeared of clinical relevance based on 16S rRNA amplicon sequencing. Further research using tools with higher discriminatory power than 16S rRNA sequencing is required to develop optimal diagnostic and treatment strategies for this population.IMPORTANCEThe objective of this study was to identify possible bacterial lower respiratory tract infection (LRTI) pathogens in hospitalized patients who were initially suspected to have TB but later tested negative using the Xpert Ultra test. Although 16S rRNA was able to identify some less common or difficult-to-culture pathogens such as Mycoplasma pneumoniae and Bordetella pertussis, one of the main findings of the study is that, in contrast to what we had hypothesized, 16S rRNA is not a method that can be used to assist in the management of patients with presumptive TB having a negative Xpert Ultra test. Even though this could be considered a negative finding, we believe it is an important finding to report as it highlights the need for further research using different approaches.

1269. Prospective Evaluation of a Machine Learning Model that Guides Indication for Antibiotics in Lower Respiratory Tract Infections

Abstract Background Over-prescribing of antibiotics for suspected acute bacterial lower respiratory tract infections (abLRTI) is prevalent. A classification model that can identify instances when antibiotics should be initiated or withheld was previously developed with promising results (80% accuracy). This, however, was based on a retrospective dataset. We conducted a prospective evaluation of this model in the hospital antimicrobial stewardship unit (ASU) to validate its performance and compare its effectiveness against current ASU strategies. Methods Inpatients audited by the hospital ASU between 10 January and 23 March 2023 (twice weekly) were enrolled into this study. Relevant patient information (e.g., clinical notes, radiology reports, vital signs) was extracted from our hospital’s electronic data repository for model inference. The presence of abLRTI as determined by the model, the patient’s primary care team and ASU review were compared. Cases that saw differing opinions between any of the three operators were subsequently reviewed by an independent Infectious Diseases physician, who provided the ground truth for that case. Results A total of 851 cases were included, of which 235 (27.6%) had true abLRTI. The model was most accurate in determining the presence versus absence of abLRTI (734/851, 86.3%), while ASU review and primary care team were correct in only 698 (82.0%) and 677 (79.6%) cases respectively. Primary care team demonstrated greatest sensitivity in the suspicion for abLRTI (91.9%); unfortunately, it also over-diagnosed abLRTI in 155 (42%) patients. Among these false-positive cases, the model rightly rejected presence of abLRTI in 126 (81.3%) patients whereas only 66 (64.1%) of them were identified by ASU. ASU outperformed the model in having a lower false-negative rate when abLRTI is suspected (17.3% vs. 22.0%). Conclusion The model displayed consistent performance in a prospective cohort. Findings support its value in guiding decisions on antibiotic initiation for suspected abLRTI. Deploying this model to augment current ASU capabilities should be strongly considered. Disclosures All Authors: No reported disclosures

2588. Burden of Mortality and Antimicrobial Resistance of Bacterial Pathogens Associated with Lower Respiratory Tract and Other Thorax Infection in United States in 2019: A Systematic Analysis

Abstract Background Detailed information about the impact of bacterial antimicrobial resistance (AMR) on Lower Respiratory Tract and other thorax Infections (LRTIs) is currently unavailable. It is important to have precise data on bacterial AMR to develop effective programs and policies for controlling AMR and to use antibiotics prudently for optimal treatment of LRTI patients. The primary objective of this research is to present extensive estimates of the mortality due to "bacterial pathogens" and its "AMR" of LRTIs in the United States in 2019. Methods Mortality data associated with bacterial antimicrobial resistance and lower respiratory tract infection (LRTI) pathogens were acquired from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) in 2019. Results In United States, there were 88089 deaths (95% uncertainty interval [UI]: 66909-117145) due to bacterial pathogens in LRIT in 2019. Highest number of deaths observed due to Staphylococcus aureus (34.04%), followed by Streptococcus pneumoniae (18.30%), Pseudomonas aeruginosa (12.48%) in LRTI in 2019. There were 10984 deaths attributed to and 46482 deaths associated with bacterial AMR in LRTI in 2019. Conclusion Bacterial pathogens causing LRTIs are a significant cause of mortality in the United States. Moreover, antimicrobial resistance (AMR) among these pathogens has become a growing concern, exacerbating the burden of LRTI-related deaths. The implementation of such measures, along with the promotion of antimicrobial stewardship, can help to mitigate the impact of LRTI-associated deaths and preserve the effectiveness of available antimicrobial agents for the future. Disclosures All Authors: No reported disclosures

Are there differences in the relationship between respiratory rate and oxygen saturation between patients with COVID-19 and those without COVID-19? Insights from a cohort-based correlational study

BackgroundPhysicians have observed patients with COVID-19 without respiratory distress despite marked hypoxaemia and extensive radiographic abnormalities, a controversial phenomenon called ‘silent hypoxaemia’. We aimed to compare the relationship between RR...

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era

BackgroundIn the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making.MethodsAn online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array.ResultsSeventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team.ConclusionsDiagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial.Trial registrationClinicaltrials.gov, NCT04233268. Registered on 18 January 2020.

Host test based on tumor necrosis factor-related apoptosis-inducing ligand, interferon gamma-induced protein-10 and C-reactive protein for differentiating bacterial and viral respiratory tract infections in adults: diagnostic accuracy study

ObjectivesTo assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI). MethodsProspective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed. ResultsOf 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4–100), specificity 88.4% (160/181; 83.7–93.1) and negative predictive value 98.8% (160/162; 97.1–100). DiscussionBV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI.

Quantitative Value of Bacteria Associated with Leukocytes in Differential Diagnosis of Lower Respiratory Tract Infection in Children, in Comparison to Sputum Culture and Procalcitonin.

The mortality and morbidity rates in children with lower respiratory tract infection (LRTI) remain high. To describe the number of bacteria that is associated with leukocytes in differential diagnosis of bacterial, mycoplasma, and viral LRTI in children. Sputum smears were Gram stained for counting single-morphology bacteria associated with leukocytes. The differential diagnostic values of bacterial number were assessed in children with LRTI. The area under the receiver operating characteristic (ROC) curve was 0.95 for bacterial number in the differential diagnosis of bacterial infection from mycoplasma and viral infections. The area under the ROC curve was 0.62 for procalcitonin and 0.94 for bacterial number in the differential diagnosis of bacterial infection from mycoplasma infection. The number of bacteria associated with leukocytes in sputum was valuable and rapid in differential diagnosis of bacterial infection in children with suspected bacterial, mycoplasma, and viral LRTI.

Evaluation of Pathogens and Antibiotic Resistance Profiles Isolated from Lower Respiratory Tract Samples

Objective: In this study, we aimed to guide clinicians in planning empirical treatment and contribute to regional data by presenting bacterial lower respiratory tract infection agents and antibiotic resistance profiles. Methods: All lower respiratory tract samples from patients admitted to our laboratory between January 01 and December 31, 2021 were evaluated retrospectively. Bacterial identification and susceptibility tests were performed using the VITEK 2 automated system and evaluated in accordance with the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Significant growth was detected in 461 of 923 lower respiratory tract samples. Antibiotic susceptibility test results of 340 samples were evaluated after excluding the repeated samples of same patient. Gram negative bacteria was isolated in 309 (90.9%), Staphylococcus aureus in 17 (5%) and Candida albicans in 14 (4.1%) of 340 samples. The most frequently isolated Gram-negative bacteria were Pseudomonas aeruginosa (121, 39.2%), Acinetobacter baumannii (88, 28.5%), Klebsiella pneumoniae (64, 20.7%) and Escherichia coli (36, 11.6%), respectively. Resistance rates of A. baumannii isolates to carbapenems, piperacillin/tazobactam, ceftazidime and fluoroquinolones were found to be over 90%, and higher resistance was observed in intensive care units (ICU) than in wards. Conclusion: The increased antibiotic resistance observed in lower respiratory tract infections from hospitalized patients in ICUs, is remarkable. As a result, knowing the causative agents and current resistance profiles is important, especially for hospitalized patients in ICUs, in order to initiate appropriate empirical treatment and to ensure treatment success. The data obtained from our study will guide clinicians in planning empirical treatment.

In vitro activity of cefpodoxime against Russian clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes

Objective. To determine in vitro activity of oral III generation cephalosporin cefpodoxime against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes isolated from patients with community-acquired respiratory tract infections in different regions of the Russian Federation. Materials and Methods. The study included isolates of bacterial pathogens of community-acquired respiratory tract infections isolated from outpatients and hospitalized patients in different regions of the Russian Federation. A total of 558 isolates were included in the study, including 184 isolates of H. influenzae, 186 isolates of S. pneumoniae and 188 isolates of S. pyogenes. Species identification was performed using the MALDI-TOF mass spectrometry (Bruker Daltonics, Germany), for S. pneumoniae identification was also performed taking into account the morphology of colonies on blood agar, the presence of α-hemolysis, negative catalase reaction, sensitivity to optochin and positive results of latex-agglutination using DrySpot kit (OXOID, UK). Antimicrobial susceptibility to cefpodoxime and comparative antimicrobials was determined using broth microdilution method; interpretation of susceptibility testing results was performed in accordance with the recommendations of EUCAST, v.13.0. Data analysis and visualization were performed using the online platform AMRcloud. Results. Despite the generally low incidence of antibiotic resistance in the tested H. influenzae isolates, cefpodoxime, to which all tested isolates were susceptible, was superior to all other oral antibiotics in terms of in vitro activity: aminophenocillins (R – 8.7%), amoxicillin/clavulanate (R – 1.1%), co-trimoxazole (R – 31.5%), levofloxacin (R – 3.8%), moxifloxacin (R – 3.8%), tetracycline (R – 11%), cefixime (R – 2.2%), ceftibuten (R – 3.3%). Among the studied S. pneumoniae isolates, 81.7% were susceptible to cefpodoxime. All isolates resistant to penicillin, amoxicillin and ceftriaxone were also resistant to cefpodoxime. Cefpodoxime was inferior to levofloxacin (R – 0%), moxifloxacin (R – 0%), linezolid (R – 0%), vancomycin (R – 0%), ertapenem (R – 8.6%), ceftaroline (R – 2.3%), and chloramphenicol (R – 3.2%) in terms of in vitro activity against S. pneumoniae. However, all these drugs are either not available in oral form or have a less favorable safety profile compared to cefpodoxime. When compared with other III generation oral cephalosporins cefixime and ceftibuten, the activity of cefpodoxime against S. pneumoniae was significantly higher based on MIC50/90 values (cefixime – 0.125⁄8 mg/l, ceftibuten – 2/≥ 128 mg/l, cefpodoxime – 0.06/4 mg/l) and MICs range (cefixime – 0.06/≥ 128 mg/l, ceftibuten – 0.06/≥ 128 mg/l, cefpodoxime – 0.03/32 mg/l). No strains resistant to β-lactam antibiotics were detected among the tested S. pyogenes isolates. Based on the MIC50/90 values and the range of MIC values, the in vitro activity of cefpodoxime was higher than that of ceftibuten and comparable to that of cefixime. Conclusions. According to the results of our study, as well as in view of its pharmacokinetic profile, high safety and compliance, cefpodoxime can be considered as one of the options for oral therapy of community-acquired bacterial upper and lower respiratory tract infections.

330. BioFire ® FilmArray® Pneumonia Panel (PN) Results Compared to Standard Microbiologic Testing and Clinical Adjudication in Adults Hospitalized with Respiratory Illness.

Abstract Background Inability to define microbial etiology of lower respiratory tract infection (LRTI) leads to unnecessary antibiotic use. Though multiplex PCR improves viral detection, bacterial LRTI diagnosis remains problematic. We evaluated the clinical utility of BioFire ® FilmArray ® Pneumonia (PN) Panel which detects 8 viruses, 3 atypical and 15 pathogenic bacteria by semi-quantitative PCR to inform bacterial diagnosis. Methods As part of a study to distinguish bacterial from non-bacterial LRTI in hospitalized adults, clinical, laboratory, and X-ray data were collected. Adequate sputa (&amp;lt; 10 Epithelial &amp; &amp;gt;25 PMNs) processed by Gram stain and culture were tested with FilmArray® PN. Microbial LRTI etiology (viral alone, bacterial with or without concomitant viruses, or indeterminate) was adjudicated by a four physician panel using all clinical data except bacterial PCR results. Bacterial PCR was compared to Gram stain and culture and clinical adjudication. Results From 737 illnesses evaluated, 423 sputa were collected and 201 deemed adequate and were tested with FilmArray® PN. Most common discharge diagnoses were pneumonia (24%), AECOPD (21%), viral illness (13%) and asthma exacerbations (9%). FilmArray® PN detected 155 typical bacteria, 9 atypical and 101 viruses. Most bacterial detections were monomicrobial (58%) often with concomitant viruses (43%). Compared to Gram stain and culture, FilmArray® PN detected more bacterial pathogens and was less affected by antibiotics. (Figure) Cases were adjudicated as viral Alone (37), bacterial (93) and indeterminate (71). Bacteria were detected by PCR in 41% of viral and 96% of bacterial cases, p=0.0001 and 76% of indeterminate cases. In cases with no bacteria detected by PCR, only 4 (9%) were adjudicated as bacterial; all deemed caused by anaerobic bacteria which are not included in the PCR panel. Comparing bacterial vs. non-bacterial (Viral + Indeterminate), FilmArray® PN bacterial PCR had 96% sensitivity, 36% specificity, 56% positive predictive value and 91% negative predictive value. Finally, sputum PCR detected 4 mycoplasma and 56 viral infections missed by standard of care testing. FigureRelationship of Gram Stain and Time on Antibiotics to Bacterial Culture and Bacterial PCR Results Conclusion Multiplex PCR testing of sputa for bacteria is useful to rule out bacterial infection with added value to detect viruses and atypical bacteria. Disclosures Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Angela R. Branche, MD, Cyanvac: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Expert Testimony|Pfizer: Grant/Research Support Edward E. Walsh, MD, Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support.

Antimicrobial prescribing for children in China: data from point prevalence surveys in 18 tertiary centres in China in 2016–2017

ObjectivesThe reports on evaluating the classification of antibiotic agents prescribed for Chinese children by combining WHO’s and China’s administrative categories were rare. This study aimed to investigate the pattern of...

Metagenomic prediction of antimicrobial resistance in critically ill patients with lower respiratory tract infections

BackgroundAntimicrobial resistance (AMR) is rising at an alarming rate and complicating the management of infectious diseases including lower respiratory tract infections (LRTI). Metagenomic next-generation sequencing (mNGS) is a recently established method for culture-independent LRTI diagnosis, but its utility for predicting AMR has remained unclear. We aimed to assess the performance of mNGS for AMR prediction in bacterial LRTI and demonstrate proof of concept for epidemiological AMR surveillance and rapid AMR gene detection using Cas9 enrichment and nanopore sequencing.MethodsWe studied 88 patients with acute respiratory failure between 07/2013 and 9/2018, enrolled through a previous observational study of LRTI. Inclusion criteria were age ≥ 18, need for mechanical ventilation, and respiratory specimen collection within 72 h of intubation. Exclusion criteria were decline of study participation, unclear LRTI status, or no matched RNA and DNA mNGS data from a respiratory specimen. Patients with LRTI were identified by clinical adjudication. mNGS was performed on lower respiratory tract specimens. The primary outcome was mNGS performance for predicting phenotypic antimicrobial susceptibility and was assessed in patients with LRTI from culture-confirmed bacterial pathogens with clinical antimicrobial susceptibility testing (n = 27 patients, n = 32 pathogens). Secondary outcomes included the association between hospital exposure and AMR gene burden in the respiratory microbiome (n = 88 patients), and AMR gene detection using Cas9 targeted enrichment and nanopore sequencing (n = 10 patients).ResultsCompared to clinical antimicrobial susceptibility testing, the performance of respiratory mNGS for predicting AMR varied by pathogen, antimicrobial, and nucleic acid type sequenced. For gram-positive bacteria, a combination of RNA + DNA mNGS achieved a sensitivity of 70% (95% confidence interval (CI) 47–87%) and specificity of 95% (CI 85–99%). For gram-negative bacteria, sensitivity was 100% (CI 87–100%) and specificity 64% (CI 48–78%). Patients with hospital-onset LRTI had a greater AMR gene burden in their respiratory microbiome versus those with community-onset LRTI (p = 0.00030), or those without LRTI (p = 0.0024). We found that Cas9 targeted sequencing could enrich for low abundance AMR genes by > 2500-fold and enabled their rapid detection using a nanopore platform.ConclusionsmNGS has utility for the detection and surveillance of resistant bacterial LRTI pathogens.