scholarly journals 2230. Analysis of the Microbiological Data from the Delafloxacin (DLX) Phase 3 Community-acquired Bacterial Pneumonia (CABP) Trial

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S761-S762 ◽  
Author(s):  
Sandra McCurdy ◽  
Kara Keedy ◽  
Laura Lawrence ◽  
Amanda Sheets ◽  
Megan Quintas
Keyword(s):  
Legionella Pneumophila ◽  
Chlamydia Pneumoniae ◽  
Oral Treatment ◽  
Phenotypic Characterization ◽  
Clinical Activity ◽  
Microbiological Analysis ◽  
Culture Methods ◽  
Phase 3 ◽  
Atypical Pathogens

Abstract Background DLX is a novel fluoroquinolone (FQ) antibiotic with Gram-positive/MRSA, Gram-negative and atypical activity. It offers IV and oral treatment with no QT restrictions. In a Phase 3 study in CABP patients, DLX was non-inferior to moxifloxacin (MOX) in the primary endpoint, early clinical response at 96 ± 24 hours (88.9 vs. 89.0; 95% CI: −4.4, 4.1) in the intent-to-treat (ITT) population. A detailed microbiological analysis was conducted. Methods CABP pathogens were identified by culture/non-culture methods. Pathogens identified by non-culture methods included Streptococcus pneumoniae (Sp; culture, urinary antigen [UA], nasopharyngeal [NP] swab lytA PCR), Legionella pneumophila (Lp) (culture, UA, serology), Mycoplasma pneumoniae (Mp; culture, serology), and Chlamydia pneumoniae (Cp; serology). All other pathogens were identified using culture only. For Sp cultured from NP, a concomitant lytA PCR value of ≥ 1000 gene copies/mL was required. All isolates underwent susceptibility testing, and a subset of isolates underwent molecular or phenotypic characterization including whole-genome sequencing for FQ resistance mechanisms, PCR for PVL/mecA genes (S. aureus), β-lactamases (Haemophilus/Moraxella spp), and serotyping (Sp). Results Included in submitted image. Conclusion DLX demonstrated potent in vitro and clinical activity against CABP pathogens, including Sp [MRSP, MDRSP, PRSP], MRSA, Haemophilus species, Enterobacteriaceae, P. aeruginosa, and the atypical pathogens Cp, Mp, and Lp. Disclosures All authors: No reported disclosures.

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

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1489
Author(s):  
Susanne Paukner ◽  
David Mariano ◽  
Anita F. Das ◽  
Gregory J. Moran ◽  
Christian Sandrock ◽  
...  
Keyword(s):  
Clinical Response ◽  
Legionella Pneumophila ◽  
Bacterial Pneumonia ◽  
Chlamydia Pneumoniae ◽  
Diagnostic Methods ◽  
Phase 3 ◽  
Two Phase ◽  
Diagnostic Modality ◽  
Risk Class ◽  
Atypical Pathogens

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.

scholarly journals Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Sandra McCurdy ◽  
Kara Keedy ◽  
Laura Lawrence ◽  
Ashley Nenninger ◽  
Amanda Sheets ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Chlamydia Pneumoniae ◽  
Klebsiella Oxytoca ◽  
Diagnostic Methods ◽  
Multiple Drug ◽  
Phase 3 ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Atypical Pathogens

ABSTRACT Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC90 values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in Streptococcus pneumoniae (penicillin-, macrolide-, and multiple-drug resistant), Haemophilus species (β-lactamase producing and macrolide nonsusceptible), and S. aureus (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible S. aureus [MSSA]). The microbiological success rates were 92.7% for S. pneumoniae (87.5% for penicillin-resistant S. pneumoniae [PRSP]), 92.6% for S. aureus (100% for MRSA), 100% for Escherichia coli, 82.4% for Klebsiella pneumoniae, 100% for Klebsiella oxytoca, 100% for Moraxella catarrhalis, 91.7% for Haemophilus influenzae, 88.6% for Haemophilus parainfluenzae, 96.7% for Mycoplasma pneumoniae, 93.1% for Legionella pneumophila, and 100% for Chlamydia pneumoniae. There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable.

scholarly journals A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia.

1997 ◽  
Vol 41 (9) ◽  
pp. 1965-1972 ◽  
Author(s):  
T M File ◽  
J Segreti ◽  
L Dunbar ◽  
R Player ◽  
R Kohler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Legionella Pneumophila ◽  
Chlamydia Pneumoniae ◽  
Clinical Success ◽  
Clinical Success Rate ◽  
Cefuroxime Axetil ◽  
Community Acquired Pneumonia ◽  
Respiratory Pathogens ◽  
Efficacy And Safety ◽  
Atypical Pathogens

Five hundred ninety patients were enrolled in a prospective, multicenter, randomized trial comparing the efficacy and safety of 7 to 14 days of levofloxacin treatment with that of ceftriaxone and/or cefuroxime axetil in the management of community-acquired pneumonia in adults. Patients received either intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily). Erythromycin or doxycycline could be added to the comparator arm at the investigator's discretion. The decision to use an intravenous or oral antimicrobial agent for initial therapy was made by the investigator. Clinical and microbiological evaluations were completed at the baseline, during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Four hundred fifty-six patients (226 given levofloxacin and 230 administered ceftriaxone and/or cefuroxime axetil) were evaluable for clinical efficacy. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 15 and 12%, respectively, of clinically evaluable patients. One hundred fifty atypical pathogens were identified: 101 were Chlamydia pneumoniae, 41 were Mycoplasma pneumoniae, and 8 were Legionella pneumophila. Clinical success at 5 to 7 days posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and/or cefuroxime axetil group (90%) (95% confidence interval [CI] of -10.7 to -1.3). Among patients with typical respiratory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil group (85%) (95% CI of -21.6 to -4.8). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Both levofloxacin and ceftriaxone-cefuroxime axetil eradicated 100% of the S. pneumoniae cells detected in blood culture. Drug-related adverse events were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients administered ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported in each treatment group. In conclusion, these results demonstrate that treatment with levofloxacin is superior to ceftriaxone and/or cefuroxime axetil therapy in the management of community-acquired pneumonia in adults.

scholarly journals Viability PCR, a Culture-Independent Method for Rapid and Selective Quantification of Viable Legionella pneumophila Cells in Environmental Water Samples

2009 ◽  
Vol 75 (11) ◽  
pp. 3502-3512 ◽  
Author(s):  
Pilar Delgado-Viscogliosi ◽  
Lydie Solignac ◽  
Jean-Marie Delattre
Keyword(s):  
Legionella Pneumophila ◽  
Water Samples ◽  
Environmental Water ◽  
Hot Water ◽  
Culture Methods ◽  
Culture Techniques ◽  
Viability Assay ◽  
Viable Cells ◽  
Wide Range

ABSTRACT PCR-based methods have been developed to rapidly screen for Legionella pneumophila in water as an alternative to time-consuming culture techniques. However, these methods fail to discriminate between live and dead bacteria. Here, we report a viability assay (viability PCR [v-PCR]) for L. pneumophila that combines ethidium monoazide bromide with quantitative real-time PCR (qPCR). The ability of v-PCR to differentiate viable from nonviable L. pneumophila cells was confirmed with permeabilizing agents, toluene, or isopropanol. v-PCR suppressed more than 99.9% of the L. pneumophila PCR signal in nonviable cultures and was able to discriminate viable cells in mixed samples. A wide range of physiological states, from culturable to dead cells, was observed with 64 domestic hot-water samples after simultaneous quantification of L. pneumophila cells by v-PCR, conventional qPCR, and culture methods. v-PCR counts were equal to or higher than those obtained by culture and lower than or equal to conventional qPCR counts. v-PCR was used to successfully monitor in vitro the disinfection efficacy of heating to 70°C and glutaraldehyde and chlorine curative treatments. The v-PCR method appears to be a promising and rapid technique for enumerating L. pneumophila bacteria in water and, in comparison with conventional qPCR techniques used to monitor Legionella, has the advantage of selectively amplifying only viable cells.

scholarly journals Isolation of Legionella pneumophila from a transtracheal aspirate

1979 ◽  
Vol 9 (3) ◽  
pp. 457-458
Author(s):  
P H Edelstein ◽  
S M Finegold
Keyword(s):  
In Vitro Culture ◽  
Legionella Pneumophila ◽  
Body Fluids ◽  
Culture Methods

Isolation of Legionella pneumophila from a transtracheal aspirate was achieved by using simple in vitro culture methods. Clinical microbiologists should routinely culture for this organism from appropriate body fluids obtained from normally sterile areas.

Small Molecules Effective Against Liver and Blood Stage Malarial Infection

2019 ◽  
Vol 18 (23) ◽  
pp. 2008-2021 ◽  
Author(s):  
Snigdha Singh ◽  
Neha Sharma ◽  
Charu Upadhyay ◽  
Sumit Kumar ◽  
Brijesh Rathi ◽  
...  
Keyword(s):  
Drug Targets ◽  
Malaria Parasite ◽  
Blood Stage ◽  
Culture Methods ◽  
Liver Stage ◽  
Malarial Infection ◽  
Dual Stage ◽  
New Treatment ◽  
Global Threat

Malaria is a lethal disease causing devastating global impact by killing more than 8,00,000 individuals yearly. A noticeable decline in malaria related deaths can be attributed to the most reliable treatment, ACTs against P. falciparum. However, the cumulative resistance of the malaria parasite against ACTs is a global threat to control the disease and, therefore the new effective therapeutics are urgently needed, including new treatment approaches. Majority of the antimalarial drugs target BS malarial infection. Currently, scientists are eager to explore the drugs with potency against not only BS but other life stages such as sexual and asexual stages of the malaria parasite. Liver Stage is considered as one of the important drug targets as it always leads to BS and the infection can be cured at this stage before it enters into the Blood Stage. However, a limited number of compounds are reported effective against LS malaria infection probably due to scarcity of in vitro LS culture methods and clinical possibilities. This mini review covers a range of chemical compounds showing efficacy against BS and LS of the malaria parasite’s life cycle collectively (i.e. dual stage activity). These scaffolds targeting dual stages are essential for the eradication of malaria and to evade resistance.

Flavonoids Extracted from Asteriscus graveolens Improve Glucose Metabo-lism and Lipid Profile in Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Fadwa El-ouady ◽  
Fatima Bachir ◽  
Mohamed Eddouks
Keyword(s):  
Glucose Tolerance ◽  
Lipid Profile ◽  
Histopathological Examination ◽  
Oral Treatment ◽  
Hdl Cholesterol ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Traditional Use ◽  
Soxhlet Apparatus

Aim: This study aimed to evaluate the antidiabetic and antihyperlipidemic effects of Asteriscus graveolens. Background: Asteriscus graveolens (Asteraceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes. Objective: This work aimed to assess the capacity of flavonoids extracted from Asteriscus graveolens (FEE) to improve diabetes mellitus and dyslipidemia in normal and STZ-induced diabetic rats. Methods: Flavonoids were extracted from A. graveolens using the Soxhlet apparatus and using different organic solvents. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of A. graveolens at a dose of 10 mg/kg. The oral treatment during 15 days was used to evaluate the effect of the flavonoids extracted from A. graveolens on blood glucose level and lipid profile in normal and diabetic rats. The oral glucose tolerance test as well as the analysis of histopathological examination of liver was performed. The antioxidant activity of FEE was also assessed by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH), in order to estimate the mechanisms of action involved by FEE to improve hyperglycemia and lipid profile in normal and diabetic rats. Results: FEE reduced serum glucose concentrations in both normal and diabetic rats and exhibited in the last group lowering total cholesterol and triglycerides effects as well as improvement of the HDL-cholesterol serum level. In addition, a remarkable influence on glucose tolerance was also noticed after FEE treatment. Moreover, FEE was able to improve histopathological status of liver and possess a potential antioxidant effect in vitro. Conclusion: In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats supporting then its traditional use for the management of diabetes.

Sign in / Sign up

Export Citation Format

Share Document