Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

928. Clinical Characteristics and Microbiology Testing Patterns Among Transplant Recipients Admitted to Acute Care Hospitals for Suspected Infection

Background Solid organ transplant (SOT) is a growing option for patients with end-stage organ diseases. Immunosuppressive therapy (IT) is utilized in this population to minimize risk of allograft rejection, which increases infection risk particularly of atypical pathogens that can complicate the infection-related diagnostic journey. The purpose of this analysis was to evaluate baseline clinical characteristics and microbiological testing utilization patterns among a cohort of patients with a history of SOT and IT. Methods This retrospective cohort study utilized a US hospital-based, service-level database. Patients were selected from a subsample of database facilities utilizing plasma microbial cell-free DNA diagnostic assays. The study period was 1/1/2017-3/21/2020. Eligible patients were identified by 1st observation of SOT status and IT. Subsequent inpatient admissions for suspected infection were analyzed. Results We identified 749 patients with SOT history and use of IT, 56.4% were male, and the mean age was 52.8 (18.7) years. Kidney was the most prevalent transplant category (49.1%), followed by liver (14.1%), lung (10.9%), and heart (10.3%), and 9.7% were multi-organ. Patients experiencing multiple transplants had the most chronic conditions with a mean Elixhauser comorbidity score of 26.3 (14.7). The median length of stay was 4 [3-7] days. The median number of tests per encounter was 6 [IQR=3-11]. Culture was the most utilized test category (2 [1-4]). Blood culture was the highest utilized culture and overall test at 13.5% of all tests observed, while CMV PCR (7.8%) and multi-panel EIA (2.7%) were the most frequent molecular and antigen tests, respectively. Lung transplant recipients had the greatest utilization of tests overall (9 [3.5-17]) versus other transplant categories (6 [3-10]), consistent with the observed test rate in the 1st 48 hours of presentation (4 [1-7] vs. 2 [1-5]). Conclusion This analysis suggests that the infection-related diagnostic journey among patients with a history of SOT involves high utilization of microbiological testing, with greater utilization among lung transplant recipients versus other SOT recipients. Variation in clinical characteristics and microbiological testing patterns were observed across SOT categories. Disclosures T Matthew Hill, PharmD, PhD, Karius, Inc (Employee, Shareholder) Erick R. Scott, MD, MHS, Karius, Inc (Employee, Shareholder) Sivan Bercovici, PhD, Karius (Employee)

Molecular detection of Mycoplasma pneumoniae in Community acquired pneumonia

Community acquired pneumonia (CAP) remains a common and serious illness despite availability of potent anti-microbials and effective vaccine. Two types of CAP are commonly recognised - typical and atypical. Typical pneumonia is usually caused by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catharralis, whereas, atypical pneumonia can be caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneuomophila. Mycoplasma pneumoniae is found to be the most common cause of CAP among atypical pathogens and is called “Walking pneumonia”. It is a common atypical respiratory pathogen that produces diseases of varied severity ranging from mild upper respiratory tract infection to severe atypical pneumonia and is also responsible for producing a wide spectrum of non-pulmonary manifestations like neurological, hepatic, cardiac diseases, hemolytic anemia, polyarthritis and erythema multiforme which occur in as many as 25% of infected persons. As it lacks cell wall they are resistant to β lactam antibiotics, hence accurate and rapid diagnosis of M. pneumoniae infections is critical to initiate appropriate antibiotic treatment. Identification of M pneumoniae allows narrowing of initial empirical regimen which decreases antibiotic selection pressure and may lessen the risk of resistance. In view of this present study will be conducted in a tertiary care hospital for identification of M pneumoniae in cases of CAP by Polymerase chain reaction (PCR). 1. To detect proportion of Mycoplasma Pneumoniae among cases of CAP. 2. Detection of 16SrRNA Mycoplasma pneumoniae by PCR.Clinico-radiologically diagnosed 92 CAP patients were included in the study. Out of which 15 cases were caused by typical CAP pathogens like Streptococcus species, K.pneumoniae & M.tuberculosis. Samples (Sputum Bronchoalveolar lavages) from 77 suspected cases of atypical pneumonia are inoculated on PPLO broth (Difco) followed by identification of genus specific 16S rRNA Mycoplasma pneumoniae using PCR. PCR was found to be positive in 9 (11.68%) out of 77 CAP patients. PCR was found to be positive in 9 (11.68%) out of 77 CAP patients. Detection of M.pneumoniae is essential for prompt diagnosis and start of empirical therapy, thereby reducing antibiotic selection pressure.

Persistent Fever While on Broad-Spectrum Antibiotics in a Patient With Squamous Cell Carcinoma

For solid tumor patients, acute infectious process is often underestimated, especially when caused by fungal, viral, or other atypical pathogens. Providers should perform a comprehensive infectious workup to rule out uncommon pathogen-induced infection before considering tumor fever. Active infection can be life threatening given most patients with cancer are receiving chemotherapy, immunotherapy, or even cellular therapy, as is the case with the patient discussed in this article.

Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis

Objective: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. Materials: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. Results: Escherichia coli (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was <15% for piperacillin/tazobactam and carbapenems (both Gram-negative and -positive pathogens); <5% for glycopeptides against Gram-positive; 7%, 14%, and 20% for aminoglycosides, fosfomycin, and macrolides against Gram-negative pathogens, respectively; 10% for amoxicillin/clavulanate against Gram-positive pathogens; <20% for cephalosporins and fluoroquinolones against to Gram-negative pathogens (higher against Gram-positive pathogens); none for macrolides against atypical pathogens, but 20% and 27% for fluoroquinolones and tetracyclines. In West Africa, the resistance rates were generally higher, although the highest rates for ampicillin, cephalosporins, and fluoroquinolones were observed in the Gulf area. Lower rates were observed in Southeastern Europe. Conclusions: Resistance to antibiotics is a health problem requiring local health authorities to combat this phenomenon. Knowledge of the spectrum of pathogens and antibiotic resistance rates is crucial to assess local guidelines for the treatment of prostatitis.

The differential diagnosis of pneumonia in two patients infected by atypical pathogens

The current study presents two patients who lived in a rural family with close contact and suffered from rapidly progressive pneumonia. Chest computed tomography images and lymphocytopenia indicated the possibility of COVID-19 infection, but antibody and nucleic acid tests excluded this possibility. Negative results were obtained from corresponding tests for pneumococcal, adenovirus, fungal and legionella infection. Metagenomics analysis and subsequent antibody tests confirmed mycoplasma pneumonia. After treating with moxifloxacin, both patients recovered well and left the hospital. In terms of complicated infectious disease, consideration of atypical pathogens and medical and epidemiological history were important for differential diagnosis of COVID-19; metagenomics analysis was useful to provide direct references for diagnosis.

Metabolomic profiling of microbial disease etiology in community-acquired pneumonia

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student’s T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

Clinical utility of serum procalcitonin in adult patients admitted with community-acquired pneumonia in Ilorin, Nigeria

Objectives: The usefulness of biomarkers in community acquired pneumonia (CAP) has been under the research light with limited reports from Africa. This study aimed at evaluating the clinical usefulness of serum procalcitonin (PCT) in patients admitted with CAP in a tertiary hospital in Ilorin, Nigeria. Materials and Methods: This was prospective single center observational study of 102 admitted patients with clinical and radiologic features of CAP. All the patients had serum PCT assay, complete blood count, blood culture, sputum microbiology, and serological evaluation for atypical pathogens. Repeat PCT assay was done following 1 week of antibiotic therapy. The patients were classified into one of two diagnostic groups: Those with microbiologically confirmed bacterial CAP and those without bacterial CAP. Results: Over half (58/102; 56.8%) of the patients had microbiologically confirmed bacterial CAP. The baseline serum PCT concentrations were significantly higher in patients with bacterial CAP when compared to the non-bacterial CAP group (2.55 ± 0.14 vs. 0.94 ± 0.61 ng/ml; P < 0.001). There was also a statistically significant difference between the pre- and post-treatment serum PCT concentrations in the bacterial CAP group (P < 0.001) and the non-bacterial CAP group (P = 0.006). The area under the receiver operating characteristic (AUC) for pre-treatment PCT in diagnosing bacterial CAP was 0.795 (95% confidence level [CI]: 0.709–0.881) with a sensitivity of 67.2% and specificity of 79.5% at an optimal cutoff of 1.5 ng/ml. Overall, the biomarker was independently associated with white cell counts >10 × 109/L (AOR = 6.28; 95% CI: 1.30–30.32, P = 0.02). The baseline mean serum PCT levels were also significantly higher in patients admitted for 7 or more days (P = 0.010). Conclusion: Serum PCT had good diagnostic strength in patients admitted with bacterial CAP in Ilorin. The biomarker can also assist clinicians with predicting the pathogenic group and monitoring clinical progress of CAP.

Seasonality in testing and positive respiratory bacterial infections in the Australian Capital Territory, 1997–2007

Background Chlamydia pneumoniae (Cp) and Mycoplasma pneumoniae (Myco) bacteria are atypical pathogens that can cause pneumonia and exacerbate underlying conditions such as asthma and chronic obstructive pulmonary disease. In the Australian Capital Territory, there is limited information on how seasonal patterns for positive infections and testing may vary, a gap that has implications for control strategies. Methods We examined seasonal patterns of immunoassay results of patients from Canberra Hospital, Australia, who were tested for Cp and/or Myco. Pathology data, collected from August 1997 to March 2007 from 7,275 patients, were analysed with time series additive decomposition and time series regression. Results The proportion of positive Cp infections was highest in March and April (autumn) and lowest in June and August (winter). The proportion of positive Myco infections was highest in December and January (summer) and lowest in August (winter), even though testing for the pathogen peaked in winter with a low in summer. Models with a long-term trend and a variable for month were a better fit for the data than the null models for both infections. Conclusion We found differences in seasonal patterns of testing and in the proportion of positive infections. These findings suggest that preventative measures for common infections need to account for seasonal testing practices so as to build an accurate picture of temporal changes in these infections.