scholarly journals Clinically relevant infections in hematology and oncology: bacterial infections and the role of novel antibiotics in times of multidrug resistance

Author(s):  
Gernot Fritsche

SummaryMultidrug resistance of bacterial pathogens is an increasing problem wordwide, especially treatment of multidrug resistant (MDR) gramnegative bacteria is challenging. In the recent past, several new antibiotics as well as new betalactamase inhibitors have been introduced. These novel drugs are valuable new tools for the therapy of infectious complications in cancer patients once there is a high risk for infections due to multidrug-resistant pathogens. While it is necessary to start empirical antibiotic therapy immediately, novel antibiotics only provide benefits in certain situations, depending on the underlying pathogens. Thus, these new antibiotics are best used guided by microbiological testing, since the exact mechanism of resistance determines susceptibility or resistance to certain antibiotics. For empirical therapy, previous culture results and/or colonization with MDR pathogens can help to choose from conventional antibiotics or novel drugs. In clinical practice, optimal antibiotic therapy can be achieved by close collaboration of specialists in hematooncology, infectious diseases and microbiology.

2021 ◽  
Vol 18 (2) ◽  
pp. 239-250
Author(s):  
Nabanita Giri

Current emergence of multidrug resistance and limitations in the development of the new antibiotics has proposed the problem of treating bacterial infections more challenging. This scenario may lead to the fear of failure in treating the multidrug resistant (MDR) bacterial infections and fuelled the uses of bacteriophages as an alternative of the conventional antibiotics in the post antibiotic era.So it is very much essential to know about the details of phage life cycle, assembly of phage complete structure, configuration and function of phage associated proteins etc. Although phages have been discovered a century ego, detailed study about lytic phages are gaining more interest in global fight against MDR bacterial species. This review has highlighted the basic knowledge of bacteriophage with the past and present scenario of several clinical studies targeting the MDR bacterial species. On the other hand it also discussed about the other uses of phages except human clinical trials.


2012 ◽  
Vol 56 (9) ◽  
pp. 4833-4837 ◽  
Author(s):  
Laura Morata ◽  
Nazaret Cobos-Trigueros ◽  
José A. Martínez ◽  
Álex Soriano ◽  
Manel Almela ◽  
...  

ABSTRACTInfections due to multidrug-resistant (MDR)Pseudomonas aeruginosaare increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due toP. aeruginosa(PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n= 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.


Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Author(s):  
Silpak Biswas ◽  
Mohammed Elbediwi ◽  
Guimin Gu ◽  
Min Yue

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.


Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 522 ◽  
Author(s):  
Paula Segura-Ramírez ◽  
Pedro Silva Júnior

The remarkable ability of microorganisms to develop resistance to conventional antibiotics is one of the biggest challenges that the pharmaceutical industry currently faces. Recent studies suggest that antimicrobial peptides discovered in spider venoms may be useful resources for the design of structurally new anti-infective agents effective against drug-resistant microorganisms. In this work, we found an anionic antibacterial peptide named U1-SCRTX-Lg1a in the venom of the spider Loxosceles gaucho. The peptide was purified using high-performance liquid chromatography (HPLC), its antimicrobial activity was tested through liquid growth inhibition assays, and its chemical properties were characterized using mass spectrometry. U1-SCRTX-Lg1a was found to show a monoisotopic mass of 1695.75 Da, activity against Gram-negative bacteria, a lack of hemolytic effects against human red blood cells, and a lack of cytotoxicity against human cervical carcinoma cells (HeLa). Besides this, the sequence of the peptide exhibited great similarity to specific regions of phospholipases D from different species of Loxosceles spiders, leading to the hypothesis that U1-SCRTX-Lg1a may have originated from a limited proteolytic cleavage. Our data suggest that U1-SCRTX-Lg1a is a promising candidate for the development of new antibiotics that could help fight bacterial infections and represents an exciting discovery for Loxosceles spiders.


2018 ◽  
Vol 14 ◽  
pp. 2881-2896 ◽  
Author(s):  
Laura Carro

Antibiotics are potent pharmacological weapons against bacterial infections; however, the growing antibiotic resistance of microorganisms is compromising the efficacy of the currently available pharmacotherapies. Even though antimicrobial resistance is not a new problem, antibiotic development has failed to match the growth of resistant pathogens and hence, it is highly critical to discover new anti-infective drugs with novel mechanisms of action which will help reducing the burden of multidrug-resistant microorganisms. Protein–protein interactions (PPIs) are involved in a myriad of vital cellular processes and have become an attractive target to treat diseases. Therefore, targeting PPI networks in bacteria may offer a new and unconventional point of intervention to develop novel anti-infective drugs which can combat the ever-increasing rate of multidrug-resistant bacteria. This review describes the progress achieved towards the discovery of molecules that disrupt PPI systems in bacteria for which inhibitors have been identified and whose targets could represent an alternative lead discovery strategy to obtain new anti-infective molecules.


Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1009 ◽  
Author(s):  
Priyanka Singh ◽  
Abhroop Garg ◽  
Santosh Pandit ◽  
V. Mokkapati ◽  
Ivan Mijakovic

Infectious diseases pose one of the greatest health challenges in the medical world. Though numerous antimicrobial drugs are commercially available, they often lack effectiveness against recently developed multidrug resistant (MDR) microorganisms. This results in high antibiotic dose administration and a need to develop new antibiotics, which in turn requires time, money, and labor investments. Recently, biogenic metallic nanoparticles have proven their effectiveness against MDR microorganisms, individually and in synergy with the current/conventional antibiotics. Importantly, biogenic nanoparticles are easy to produce, facile, biocompatible, and environmentally friendly in nature. In addition, biogenic nanoparticles are surrounded by capping layers, which provide them with biocompatibility and long-term stability. Moreover, these capping layers provide an active surface for interaction with biological components, facilitated by free active surface functional groups. These groups are available for modification, such as conjugation with antimicrobial drugs, genes, and peptides, in order to enhance their efficacy and delivery. This review summarizes the conventional antibiotic treatments and highlights the benefits of using nanoparticles in combating infectious diseases.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Oumer Abdu Muhie

Background. In the last decades, medicines have had an unprecedented positive effect on health, leading to reduced mortality and disease burden and consequently to an improved quality of life. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. In the absence of the development of new generations of antibiotic drugs, appropriate use of existing antibiotics is needed to ensure the long-term availability of effective treatment for bacterial infections. Irrational use of antibiotics is an ongoing global public health problem that deserves more attention. This review is conducted to evaluate the prevalence of inappropriate antibiotic utilization and resistance to antibiotics in Ethiopia. Methods. Electronic search in PubMed/MEDLINE and Google was used to find published literature with reference lists of relevant articles searched manually. Titles and abstracts were initially screened for eligibility. The full texts of articles judged to be eligible were reviewed if they meet the inclusion criteria. Data were extracted on important variables like the sample size, region of the study, the inappropriate antibiotic use, bacterial detection rate, multidrug resistance pattern, and more other variables. Microsoft Excel was used for data extraction. Quantitative analysis was performed using STATA version 11. Results. The electronic searches identified 193 articles of which 33 were found eligible. The random-effects model was used to provide point estimates (with 95% confidence interval (CI)) of bacterial detection rate, inappropriate antibiotic use, and multidrug resistance rate to account for heterogeneity. The pooled bacteria detection rate was 29.1 with 95% CI (16.6–41.7). The pooled prevalence of multidrug resistant strains identified was 59.7% (95% CI: 43.5–75.9). The pooled estimate of inappropriate antibiotic use was 49.2% (95% CI: 32.2–66.2). The pooled proportion of self-antibiotic prescription was 43.3% (95% CI: 15.7–70.9). Other reasons for inappropriate antibiotic use included a wrong indication, wrong duration, improper route of administration, use of leftover antibiotics from a family member, and immature discontinuation of antibiotics. Conclusion and Recommendations. Inappropriate antibiotic use is a huge problem in Ethiopia, and many bacteria were resistant to commonly used antibiotics and similarly, multidrug-resistant bacterial strains are numerous. Appropriate antibiotic use should be ensured by prohibiting over-the-counter sale of antibiotics and strengthening antimicrobial stewardship.


mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Sabrina Sabino ◽  
Silvia Soares ◽  
Fabiano Ramos ◽  
Miriane Moretti ◽  
Alexandre P. Zavascki ◽  
...  

ABSTRACT The objective of this study is to evaluate the impact of carbapenem-resistant Enterobacteriaceae (CRE) infection on sepsis 30-day mortality. A retrospective cohort of patients >18 years old with sepsis and organ dysfunction or septic shock was conducted. Univariate analysis was done for variables potentially related to 30-day mortality, and the ones with P values of <0.05 were included in a backward stepwise hierarchic Cox regression model. Variables that remained with P values of <0.05 were retained in the model. A total of 1,190 sepsis episodes were analyzed. Gram-negative bacterial infections occurred in 391 (68.5%) of 571 patients with positive cultures, of which 69 (17.7%) were caused by a CRE organism. Patients with CRE infections had significantly higher 30-day mortality: 63.8% versus 33.4% (P < 0.01). CRE infection was also associated with a lower rate of appropriate empirical therapy (P < 0.01) and with the presence of septic shock (P < 0.01). In the hierarchic multivariate model, CRE remained significant when controlling for demographic variables, comorbidities, and infection site but lost significance when controlling for septic shock and appropriate empirical therapy. Older age (P < 0.01), HIV-positive status (P < 0.01), cirrhosis (P < 0.01), septic shock (P < 0.01), higher quick sepsis-related organ failure assessment (quick-SOFA) (P < 0.01), and appropriate empirical therapy (P = 0.01) remained in the final model. CRE infections were associated with higher crude mortality rates. A lower rate of appropriate empirical therapy and late diagnosis were more frequent in this group, and improvement of stewardship programs is needed. IMPORTANCE The importance of this work relies on exploring the impact of multidrug-resistant bacterial infections such as those with carbapenem-resistant Enterobacteriaceae (CRE) on sepsis mortality. These infections are growing at alarming rates worldwide and are now among the most frequent and difficult-to-treat bacteria due to the very few options for susceptible antimicrobials available. This study examined 1,190 sepsis episodes, and the main findings were as follows: (i) the prevalence of CRE infections significantly increased over time, (ii) CRE infection was associated with higher 30-day mortality than that of patients with other infections (63.8% versus 33.4%), and (iii) the effect of CRE on mortality was probably influenced by the fact that those patients received lower rates of empirical therapy with active antibiotics and were also diagnosed in more advanced stages of sepsis (septic shock). Those findings point to the need for rapid diagnostic methods to identify these bacteria and the need to adjust therapeutic guidelines to this worrisome epidemiological scenario.


2020 ◽  
Vol 14 (3) ◽  
pp. 126-135
Author(s):  
Mario Mitra ◽  
Andrea Mancuso ◽  
Flavia Politi ◽  
Alberto Maringhini

Bacterial infections are frequent complications of liver cirrhosis, accounting for severe clinical courses, and increased mortality. The reduction of the negative clinical impact of infections may be achieved by a combination of prophylactic measures to reduce the occurrence, early identification, and management. Spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, cellulitis, and spontaneous bacteremia are frequent in cirrhosis. The choice of initial empirical antimicrobial therapy should be based on both site, severity, and origin of infection (community-acquired, nosocomial, or healthcare-associated) and on antibiotic resistance patterns. 3rd generation cephalosporins are generally indicated as empirical therapy in most community-acquired cases. However, for nosocomial and healthcare-associated infections, due to a high rate of multidrug-resistant (MDR) pathogens, a broader spectrum treatment is appropriate. In order to prevent antibiotic resistance emergence, microbiological cultures should be collected, and a de-escalation applied when antimicrobial susceptibility tests are available. Standard measures to prevent infections and the identification of carriers of MDR bacteria are essential strategies to prevent infections in cirrhosis. Antibiotic prophylaxis should be applied only to gastrointestinal bleeding, SBP recurrence prevention, and cirrhotics at high risk of a first episode of SBP.


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