scholarly journals Spotlight on New Antibiotics for the Treatment of Pneumonia

Author(s):  
Alessandro Russo

In the last years, the presence of multidrug-resistant (MDR) Gram-negative (like Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) and Gram-positive bacteria (mostly methicillin-resistant Staphylococcus aureus) was worldwide reported, limiting the options for an effective antibiotic therapy. For these reasons, inappropriate antimicrobial therapy and delayed prescription can lead to an unfavorable outcome, especially in patients with pneumonia. New antibiotics approved belong to classes of antimicrobials, like beta-lactams with or without beta-lactamase inhibitors, aminoglycosides, oxazolidinones, quinolones, and tetracyclines, or based on new mechanisms of action. These new compounds show many advantages, including a broad spectrum of activity against MDR pathogens, good lung penetration, safety and tolerability, and finally the possibility of intravenous and/or oral formulations. However, the new antibiotics under development represent an important possible armamentarium against difficult-to-treat strains. The safety and clinical efficacy of these future drugs should be tested in clinical practice. In this review, there are reported characteristics of newly approved antibiotics that represent potential future options for the treatment of respiratory tract infections, including those caused by multidrug-resistant bacteria. Finally, the characteristics of the drugs under development are briefly reported.

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2888 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.


2021 ◽  
Vol 23 (06) ◽  
pp. 1489-1509
Author(s):  
VidhyaSri AR ◽  
◽  
Dr. Thamarai Selvi B ◽  
Sanjay Prasad S ◽  
Karkuvelraja R ◽  
...  

The rapid emergence of drug resistance among pathogenic bacteria, especially multidrug-Resistant bacteria, underlines the need to search for new antibiotics. In the present study, actinomycetes were isolated from lichens collected from coconut trees. The actinomycetes were investigated for antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumonia in order to identify the potential antibiotic producers.MIC was determined and the organism was identified using 16s rRNA sequencing. Crude action extracts showed 11mm and 9mm against MRSA and Klebsiella pneumonia. The isolated actinomycetes were found to be Streptomyces hygro scopicus subspecies. GC-MS analysis identified several novel compounds. Thus, the isolated actinomycetes can be used for the development of new antibiotics for the treatment of MDR infection.


2020 ◽  
Vol 66 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Eric Mühlberg ◽  
Florian Umstätter ◽  
Christian Kleist ◽  
Cornelius Domhan ◽  
Walter Mier ◽  
...  

The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been considered as the “last resort” treatment of severe infections caused by Gram-positive bacteria. Since the discovery of the first vancomycin-resistant enterococci strains in the late 1980s, the number of resistances has been steadily rising, with often life-threatening consequences. As an alternative to the generation of completely new substances, novel approaches focus on structural modifications of established antibiotics such as vancomycin to overcome these resistances. Here, we provide an overview of several promising modifications of vancomycin to restore its efficacy against vancomycin-resistant enterococci.


2018 ◽  
Vol 51 (3) ◽  
pp. 1701656 ◽  
Author(s):  
Anne-Sophie Moreau ◽  
Ignacio Martin-Loeches ◽  
Pedro Povoa ◽  
Jorge Salluh ◽  
Alejandro Rodriguez ◽  
...  

The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients.All patients receiving mechanical ventilation for >48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297).The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53–0.80; p<0.0001). Similar results were found regarding ventilator-associated tracheobronchitis (7.3% versus 11.6%; sub-hazard ratio 0.61, 95% CI 0.45–0.84; p=0.002) and ventilator-associated pneumonia (9.3% versus 12.7%; sub-hazard ratio 0.72, 95% CI 0.54–0.95; p=0.019). Among patients with VA-LRTI, the rates of multidrug-resistant bacteria (72% versus 59%; p=0.011) and intensive care unit mortality were significantly higher among immunocompromised than among non-immunocompromised patients (54% versus 30%; OR 2.68, 95% CI 1.78–4.02; p<0.0001). In patients with ventilator-associated pneumonia, mortality rates were higher among immunocompromised than among non-immunocompromised patients (64% versus 34%; p<0.001).Incidence of VA-LRTI was significantly lower among immunocompromised patients, but it was associated with a significantly higher mortality rate. Multidrug-resistant pathogens were more frequently found in immunocompromised patients with VA-LRTI.


2021 ◽  
Vol 5 (8) ◽  
pp. 13-18
Author(s):  
Darija Knežević ◽  
Silvana Trifunović ◽  
Duška Jović ◽  
Jadranka Stanisavić-Šimić

Introduction: Patients in intensive care units (ICUs) are at higher risk of infections due to invasive procedures and antibiotic therapy. Infections caused by multidrug-resistant (MDR) bacteria represent a global problem, limiting the choice of antimicrobial therapy. Objective: To determine the rate of infections in ICUs, as well as the type of MDR bacteria associated with such infections. Material and methods: The study included strains of MDR bacteria isolated from laboratory samples of hospitalized patients in surgical ICUs in a one-year period. All strains of MDR bacteria were isolated and identified by standard microbiological methods for aerobic bacteria according to the recommendations and guidelines are given by the Clinical and Laboratory Standards Institute (CLSI). Results: Infections caused by MDR bacterial isolates were confirmed in 199 (19.17%) patients in ICUs. The frequency of Gram-negative isolates was significantly higher than Gram-positive (88.35% and 11.65%, p <0.001). The most common infections in ICUs caused by MDR bacteria were respiratory tract infections (49%), followed by soft tissue and skin infections. The CDI incidence density 1.13 cases/10,000 patient-days. Conclusion: A high frequency of infections caused by MDR bacteria was found with patients in ICUs, and respiratory tract infections dominated. Information on the types of infections and pathogens can help develop policies for prevention, diagnosis, treatment, and resource allocation.


Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 170
Author(s):  
Urszula Kosikowska ◽  
Monika Wujec ◽  
Nazar Trotsko ◽  
Wojciech Płonka ◽  
Piotr Paneth ◽  
...  

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 218
Author(s):  
Taja Železnik Ramuta ◽  
Larisa Tratnjek ◽  
Aleksandar Janev ◽  
Katja Seme ◽  
Marjanca Starčič Erjavec ◽  
...  

Urinary tract infections (UTIs) represent a serious global health issue, especially due to emerging multidrug-resistant UTI-causing bacteria. Recently, we showed that the human amniotic membrane (hAM) could be a candidate for treatments and prevention of UPEC and Staphylococcus aureus infections. However, its role against multidrug-resistant bacteria, namely methicillin-resistant S. aureus (MRSA), extended-spectrum beta-lactamases (ESBL) producing Escherichia coli and Klebsiella pneumoniae, vancomycin-resistant Enterococci (VRE), carbapenem-resistant Acinetobacter baumannii, and Pseudomonas aeruginosa has not yet been thoroughly explored. Here, we demonstrate for the first time that the hAM homogenate had antibacterial activity against 7 out of 11 tested multidrug-resistant strains, the greatest effect was on MRSA. Using novel approaches, its activity against MRSA was further evaluated in a complex microenvironment of normal and cancerous urinary bladder urothelia. Even short-term incubation in hAM homogenate significantly decreased the number of bacteria in MRSA-infected urothelial models, while it did not affect the viability, number, and ultrastructure of urothelial cells. The hAM patches had no antibacterial activity against any of the tested strains, which further exposes the importance of the hAM preparation. Our study substantially contributes to basic knowledge on the antibacterial activity of hAM and reveals its potential to be used as an antibacterial agent against multidrug-resistant bacteria.


2005 ◽  
Vol 26 (1) ◽  
pp. 13-20 ◽  
Author(s):  
François L'Hériteau ◽  
Corinne Alberti ◽  
Yves Cohen ◽  
Gilles Troché ◽  
Pierre Moine ◽  
...  

AbstractObjectives:To evaluate nosocomial infection (NI) surveillance strategies in French ICUs and to identify similar patterns defining subsets within which comparisons can be made.Design:A questionnaire was sent to all French ICUs, and a random sample of nonresponders was interviewed.Participants:Three hundred ninety-five responder ICUs (69%) in France.Results:In 282 ICUs (71%), a dedicated ICU staff member was responsible for infection control activities. The microbiology laboratory was usually in the hospital (90%) and computerized (94%) but issued regular hospital microbiology records in only 48% of cases. Patients receiving mechanical ventilation, central venous catheterization, and urinary catheterization were 90%, 79%, and 60%, respectively. Patients were screened for carriage of mul-tidrug-resistant bacteria on admission and during the stay in 70% and 60% of ICUs, respectively, most often targeting MRSA. Quantitative cultures were used to diagnose ventilator-associated pneumonia (VAP) in 90% of ICUs, including distal specimens in 80% and bronchoscopy specimens in 60%. Quantitative central venous catheter (CVC)-segment cultures were used in 70% of ICUs. All CVCs were cultured routinely in 53% of the ICUs. Despite wide variations in infection control and surveillance strategies, multiple correspondence analysis identified 13 key points (4 structural variables and 9 variables concerning the diagnosis of VAP, the surveillance and diagnosis of catheter-related and urinary tract infections, and the mode of screening of MRSA carriers) that categorize the variability of French ICUs' approaches to NIs.Conclusion:This study revealed profound differences in N1 surveillance strategies across ICUs, indicating a need for caution when using N1 surveillance data for comparisons and benchmarking.


2021 ◽  
Vol 74 (suppl 6) ◽  
Author(s):  
Monica Taminato ◽  
Richarlisson Borges de Morais ◽  
Dayana Souza Fram ◽  
Rogério Rodrigues Floriano Pereira ◽  
Cibele Grothe Esmanhoto ◽  
...  

ABSTRACT Objectives: to assess the prevalence of colonization and infection by multidrug-resistant bacteria in patients undergoing kidney transplantation and identify the rate of infection, morbidity and mortality and associated risk factors. Methods: a prospective cohort of 200 randomly included kidney transplant recipients. Epidemiological surveillance of the studied microorganisms was carried out in the first 24 hours and 7 days after transplantation. Results: ninety (45%) patients were considered colonized. Female sex, hypertension and diabetes (p<0.005), dialysis time (p<0.004), length of stay after transplantation, delayed renal function, and length of stay were identified as risk factors. The microorganisms were isolated from surgical site, bloodstream and urinary tract infections. Conclusions: colonization by resistant microorganisms in kidney transplant patients was frequent and risk factors associated with infection were identified. The results should guide the care team in order to minimize morbidity and mortality related to infectious causes in this population.


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