scholarly journals Design of clinical trials of antibacterial agents for community-acquired bacterial pneumonia

2011 ◽  
Vol 1 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Brad Spellberg ◽  
Roger J Lewis ◽  
Helen W Boucher ◽  
Eric P Brass
Keyword(s):  
Clinical Trials ◽  
Bacterial Pneumonia ◽  
Antibacterial Agents

scholarly journals Systematic Literature Review of Real-World Evidence of C Eftolozane/Tazobactam for the Treatment of Respiratory Infections

2021 ◽  
Author(s):  
Laura Puzniak ◽  
Ryan Dillon ◽  
Thomas Palmer ◽  
Hannah Collings ◽  
Ashley Enstone
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Real World ◽  
Bacterial Pneumonia ◽  
Respiratory Infections ◽  
Clinical Success ◽  
Multidrug Resistant ◽  
Success Rates ◽  
Gram Negative

Abstract Background: Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa are highly prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes and higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aimed to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice. Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative respiratory tract infections (RTIs) up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.Results: Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection C/T was used to treat (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. Data on severity of illness and comorbidity were inconsistently reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant (including extensively drug-resistant or pandrug-resistant). Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4–100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of >70%; microbiological success rates ranged from 57.0–100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of >70%. Thirty-day mortality ranged from 0.0–33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of <30%. Conclusions: The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities/conditions that may have been excluded from the trials.

Lefamulin: A Novel Semisynthetic Pleuromutilin Antibiotic for Community-acquired Bacterial Pneumonia

2020 ◽  
Vol 71 (10) ◽  
pp. 2757-2762 ◽  
Author(s):  
Richard R Watkins ◽  
Thomas M File
Keyword(s):  
Clinical Trials ◽  
Protein Synthesis ◽  
Antimicrobial Resistance ◽  
Bacterial Pneumonia ◽  
Potential Role ◽  
Phase Iii ◽  
In Vitro Activity ◽  
Phase Iii Clinical Trials ◽  
Unique Mechanism

Abstract Community-acquired bacterial pneumonia (CABP) remains a significant cause of morbidity and mortality worldwide. Antimicrobial resistance, including in pathogens that cause CABP, continues to spread at an alarming rate. Because of these factors, the development of new antibiotic classes is urgently needed. Lefamulin, previously known as BC-3781, is a semisynthetic pleuromutilin antibiotic that was approved by the Food and Drug Administration for the treatment of CABP in adults. Available in both oral and intravenous formulations, lefamulin has potent in vitro activity against both typical and atypical CABP pathogens. The first pleuromutilin to be used systemically in humans, lefamulin has a unique mechanism of action that inhibits protein synthesis by preventing the binding of tRNA for peptide transfer. This review summarizes the available data on lefamulin, including recent evidence from 2 phase III clinical trials (LEAP 1 and LEAP 2), and discusses its potential role in the treatment of CABP.

Changes in the oropharyngeal microbiome in patients with viral-bacterial pneumonia associated with сovid-19 on the background of antibiotic therapy and monitoring of antibioticaresistentie strains

2021 ◽  
Vol 43 (3-4) ◽  
pp. 37-41
Author(s):  
L. B. Romanyuk ◽  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Pneumonia ◽  
Antibacterial Agents ◽  
Cost Of Treatment ◽  
E Coli ◽  
Intestinal Dysbiosis ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Clinically Significant ◽  
The Cost

The relevance of the infection caused by COVID-19 today is beyond doubt. According to the Protocol “Provision of medical care for the treatment of coronavirus disease (COVID-19)” approved by the order of the Ministry of Health of Ukraine dated April 2, 2020 № 762, antibacterial drugs are prescribed only in the presence of confirmed bacterial co-infection ( after receiving positive bacteriological results) blood and / or sputum analysis). But given that the results of the analysis must wait a few days, antibiotics, under certain indications, can be prescribed empirically. The aim of our work was to analyze the structure of the oropharyngeal microbiome, patients with viral and bacterial pneumonia who received antibiotics, to determine clinically significant strains and their sensitivity to antibacterial agents. In the structure of the oropharyngeal microbiome, fungi of the genus Candida significantly prevailed, which were found in 50 (45.6%) subjects, in second place in terms of frequency of detection were S. pneumoniae – 29 (26.4%). Much less often from the oropharynx of patients with viral-bacterial pneumonia associated with COVID-19 were isolated K. pneumoniae – 13 (11.8%), S. aureus – 11 (10.0%) and E. coli – 7 (6.4 %). Among the isolated S. pneumoniae, the maximum number of resistant strains was detected for such fairly new antibiotics as ceftriaxone – 37.9% and azithromycin – 31.0%. Among fungi of the genus Candida resistant to nystatin and amphotericin were 38.5% and 26.9%, respectively. Therefore, the administration of antibacterial agents, taking into account the sensitivity of clinically significant strains, will guarantee effective treatment, prevent the development of antibiotic resistance, prevent the development of oropharyngeal and intestinal dysbiosis, and thus reduce the cost of treatment of antibiotic side effects, including probiotics.

Discovery and Development of Antibacterial Agents: Fortuitous and Designed

2021 ◽  
Vol 22 ◽  
Author(s):  
Ravleen Kaur ◽  
Pooja Rani ◽  
Atanas G Atanasov ◽  
Qushmua Alzahrani ◽  
Reena Gupta ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antibacterial Agents ◽  
Public Health Issue ◽  
Antibacterial Drug ◽  
Phase 3 ◽  
New Agents ◽  
Critical Elements ◽  
Significant Public Health ◽  
Conventional Antibiotics ◽  
Antibacterial Drug Resistance

Abstract: Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

scholarly journals Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Elizabeth L. Alexander ◽  
Jeffery Loutit ◽  
Mario Tumbarello ◽  
Richard Wunderink ◽  
Tim Felton ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Population ◽  
Bacterial Pneumonia ◽  
Complicated Urinary Tract Infection ◽  
Clinical Trial Design ◽  
New Drugs ◽  
External Control ◽  
Phase 3 ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials. Methods This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE. Results Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis. Conclusions The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.

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