scholarly journals Antibiotic treatment protocols revisited: The challenges of a conclusive assessment by mathematical modeling

2018 ◽  
Author(s):  
Hildegard Uecker ◽  
Sebastian Bonhoeffer
Keyword(s):  
Combination Therapy ◽  
Bacterial Infections ◽  
Treatment Protocols ◽  
Antibiotic Resistant ◽  
The Past ◽  
Consistent Picture ◽  
Hospital Stays ◽  
Resistant Strains ◽  
Prolonged Hospital ◽  
Hospital Acquired

AbstractHospital-acquired bacterial infections lead to prolonged hospital stays and increased mortality. The problem is exacerbated by antibiotic resistant strains that delay or impede effective treatment. To ensure a successful therapy and to manage antibiotic resistance, treatment protocols that draw on several different antibiotics might be used. This includes the administration of drug cocktails to individual patients (“combination therapy”) but also the random assignment of drugs to different patients (“mixing”) and a regular switch in the default drug used in the hospital from drug A to drug B and back (“cycling”). For the past 20 years, mathematical models have been used to assess the prospects of antibiotic combination therapy, mixing, and cycling. But while tendencies in their ranking across studies have emerged, the picture remains surprisingly inconclusive and incomplete. In this article, we review existing modeling studies and demonstrate by means of examples how methodological factors complicate the emergence of a consistent picture. These factors include the choice of the criterion by which the effects of the protocols are compared, the model implementation, and its analysis. We thereafter discuss how progress can be made and suggest future modeling directions.

scholarly journals Antibiotic treatment protocols revisited: the challenges of a conclusive assessment by mathematical modelling

2021 ◽  
Vol 18 (181) ◽  
pp. 20210308
Author(s):  
Hildegard Uecker ◽  
Sebastian Bonhoeffer
Keyword(s):  
Combination Therapy ◽  
Bacterial Infections ◽  
Treatment Protocols ◽  
Antibiotic Resistant ◽  
Modelling Studies ◽  
Consistent Picture ◽  
Hospital Stays ◽  
Resistant Strains ◽  
Prolonged Hospital ◽  
Hospital Acquired

Hospital-acquired bacterial infections lead to prolonged hospital stays and increased mortality. The problem is exacerbated by antibiotic-resistant strains that delay or impede effective treatment. To ensure successful therapy and to manage antibiotic resistance, treatment protocols that draw on several different antibiotics might be used. This includes the administration of drug cocktails to individual patients (combination therapy) but also the random assignment of drugs to different patients (mixing) and a regular switch in the default drug used in the hospital from drug A to drug B and back (cycling). For more than 20 years, mathematical models have been used to assess the prospects of antibiotic combination therapy, mixing and cycling. But while tendencies in their ranking across studies have emerged, the picture remains surprisingly inconclusive and incomplete. In this article, we review existing modelling studies and demonstrate by means of examples how methodological factors complicate the emergence of a consistent picture. These factors include the choice of the criterion by which the effects of the protocols are compared, the model implementation and its analysis. We thereafter discuss how progress can be made and suggest future modelling directions.

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

scholarly journals Antibiotic resistance in Acinetobacter baumannii as agent of surgery infection and approaches to its overcoming by means of deca-methoxinum antiseptic

2019 ◽  
Vol 1 (2) ◽  
pp. 18-22
Author(s):  
O A Nazarchuk ◽  
V I Nahaichuk
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Sensitivity ◽  
Antibiotic Resistant ◽  
Clinical Strains ◽  
Minimal Inhibitory Concentrations ◽  
Hospital Acquired Infections ◽  
Causative Agents ◽  
Resistant Strains ◽  
Burn Disease ◽  
Hospital Acquired

Introduction. Non-fermenting Gram-negative bacilli are known as one of the most frequent causative agents of hospital-acquired infections. Acinetobacter baumannii, as causative agent of infection complications of different localization, has obtained recently high resistance to anti-biotics and has belonged to ESKAPE group of pathogens. Antimicrobials, recommended for the prophylaxis and therapy of hospital-acquired infections, have been failing in their effectiveness and lead to selection of antibiotic resistant strains of A. baumannii. The aim of this research was to substantiate the way of overcoming of resistance in clinical strains of A. baumannii, by means of synergic antimicrobial activity of antibiotics and antiseptic decamethoxinum®. Material and methods. The research was carried out on 190 clinical strains of A. baumannii, isolated from patients with burn disease during the period 2011–2015. The sensitivity of clinical strains of A. baumannii was determined to such antibiotics as ampicillin/sulbactam, cefoperazone, cefoperazone/sulbactam, meropenem, imipenem, amikacin, ciprofloxacin, gatifloxacin and antiseptic decamethoxinum® (DCM; Registration certificate No UA/14444/01/01 since 24.06.2015. Order of the Ministry of Health of Ukraine No 373). The sensitivity of A. baumannii to antibiotics and DCM was determined by means of disk diffusion test and serial dilution (Order of the Ministry of Health of Ukraine No167 since 05.04.2007; EUCAST expert rules).The study of the influence of antiseptic DCM on the sensitivity of acinetobacteria to antibiotics was studied on 35 clinical strains of A. baumannii, drafted from the general number of isolates enrolled in the research. For this, the sensitivity of A. baumannii to antibiotics in the presence of sub-minimal inhibitory concentrations (subMIC) of DCM was identified. The received experimental data were analyzed by “Statistica 6.0”. Results and discussion. The changes of antibiotic sensitivity profile of A. baumannii for five years were shown. It was found that the sensitivity of A. baumannii to majority of antibiotics, selected for study, decreased significantly. But the only ampicillin/sulbactam was found to have vice versa tendency. We found the rising quantity of antibiotic resistant strains of A. baumannii. At the same time, high resistance of acinetobacteria to fluoroquinolones (ciprofloxacin– 96,1%; gatifloxacin– 95,8%) was found in 2015. The in vitro research of combined activity of DCM antiseptic remedy and early mentioned antibiotics against clinical strains of A. baumannii demonstrated the reveal antibiotic effectiveness. As follows, minimal inhibitory concentrations of antibiotics decreased in 1.5–4 times in the mediums which contained subMIC of DCM. Especially this tendency was found in resistant clinical strains. Conclusion. Under selective influence of antibiotics protected by β-lactamase inhibitors, carbapenems, fluoroquinolones aminoglycosides increase the antibiotic resistance in A. baumannii, causative agents of infectious complications in patients with burn disease. The antiseptic remedy decamethoxinum® helps to improve antibiotic sensitivity in resistant A. baumannii.

scholarly journals Clinical challenges with hypervirulent Klebsiella pneumoniae (hvKP) in China

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yanzhu Chen ◽  
Yi Chen
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Published Data ◽  
Clinical Microbiology Laboratory ◽  
Consensus Definition ◽  
Antibiotic Resistant ◽  
Resistance Determinants ◽  
The Past ◽  
Resistant Strains ◽  
Definition Of

AbstractHypervirulent Klebsiella pneumoniae (hvKp) is an evolving pathotype with higher virulence than classical K. pneumoniae (cKp) and is characterized by community-acquired, multiple sites of infections and young and healthy hosts. hvKP infections were primarily found in East Asia and have been increasingly reported worldwide over the past few decades. To better understand the clinical challenges faced by China with hvKP, this review will provide a summary and discussion focused on recognizing hvKP strains and prevalence of antibiotic-resistant hypervirulent strains in China and the mechanisms of acquiring antimicrobial resistance. Compared with cKP, hvKP is likely to cause serious disseminated infections, leading to a higher mortality. However, sensitive and specific clinical microbiology laboratory tests are still not available. Given the limited published data due to the clinical difficulty in differentiating hvKP from cKP, extrapolation of the previous data may not be applicable for the management of hvKP. A consensus definition of hvKP is needed. Furthermore, an increasing number of reports have described hvKp strains with antimicrobial resistance acquisition, increasing the challenges for management of hvKP. China, as an epidemic country, is also facing these challenges. Quite a number of studies from China have reported antibiotic-resistant hvKP strains, including extended-spectrum β-lactamase (ESBL), and carbapenem-, tigecycline-, and colistin-resistant strains. hvKP infections, especially those of antimicrobial-resistant strains, pose to be a great threat for public health in China. Therefore, an immediate response to recognize the hypervirulent strains and provide optimal treatments, especially those with resistance determinants, is an urgent priority for China.

scholarly journals A Biological Inventory of Prophages in A. baumannii Genomes Reveal Distinct Distributions in Classes, Length, and Genomic Positions

2020 ◽  
Vol 11 ◽  
Author(s):  
Belinda Loh ◽  
Jiayuan Chen ◽  
Prasanth Manohar ◽  
Yunsong Yu ◽  
Xiaoting Hua ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Clinical Importance ◽  
Host Bacterium ◽  
Antibiotic Resistant ◽  
High Prevalence ◽  
Resistant Strains ◽  
Biological Inventory ◽  
Natural Tolerance ◽  
Hospital Acquired

Acinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analyzed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analyzed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined to be approximately 4 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analyzed the existence of genes that are encoded in the prophages, which may confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.

scholarly journals Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections

2015 ◽  
Vol 59 (4) ◽  
pp. 1969-1976 ◽  
Author(s):  
Kimberly C. Claeys ◽  
Jordan R. Smith ◽  
Anthony M. Casapao ◽  
Ryan P. Mynatt ◽  
Lisa Avery ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Case Series ◽  
Signs And Symptoms ◽  
Retrospective Case ◽  
Methicillin Resistant ◽  
Content Type ◽  
Hospital Stays ◽  
Prolonged Hospital

ABSTRACTComplicatedStaphylococcus aureusinfections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistantS. aureus(MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically andin vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidalin vitroto strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, andin vitrosynergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.

scholarly journals A Biological Inventory of Prophages in A. baumannii Genomes Reveal Distinct Distributions in Classes, Length and Genomic Positions

2020 ◽  
Author(s):  
Belinda Loh ◽  
Jiayuan Chen ◽  
Prasanth Manohar ◽  
Yunsong Yu ◽  
Xiaoting Hua ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Clinical Importance ◽  
Host Bacterium ◽  
Antibiotic Resistant ◽  
High Prevalence ◽  
Resistant Strains ◽  
Biological Inventory ◽  
Natural Tolerance ◽  
Hospital Acquired

AbstractAcinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analysed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analysed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined as 3.98 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analysed the existence of genes that are encoded in the prophages, which confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.

scholarly journals Surveillance of surgical site infections to determine incidence, risk factors and microbiologic spectrum following obstetric and gynaecological surgeries

2018 ◽  
Vol 7 (10) ◽  
pp. 4029
Author(s):  
Seetha Panicker ◽  
T. V. Chitra
Keyword(s):  
Risk Factors ◽  
Operating Time ◽  
Surgical Site Infections ◽  
Multidrug Resistant ◽  
E Coli ◽  
Incidence Risk ◽  
Resistant Strains ◽  
Prolonged Hospital ◽  
Drug Resistant Strains ◽  
Hospital Acquired

Background: Surgical site infections (SSI) are one of the major health problems throughout the world with an incidence of 3%-16%. Hospital acquired surgical site infection is further complicated by the emergence of multi drug resistant strains. SSI surveillance is an established monitoring tool and has been shown to reduce infection rates. The importance of preventing surgical site infections is well recognized since they lead to increased morbidity, prolonged hospital stay, need for readmission, high end antibiotic treatment and re-surgery. This study was undertaken to determine the incidence, risk factors, and microbiological spectrum of surgical site infections and to identify the multidrug resistant strains.  Analysis of the effectiveness of the existing surveillance methods was also done.Methods: This retrospective study was done for a period of 1-year form Jan 2016 to Dec 2016. All patients with infection following caesarean section and abdominal and vaginal hysterectomy were included. Laparoscopic surgery and patients with preexisting infection were excluded.Results: Incidence of SSI in present study is 5.27%. The major risk factors identified were obesity, diabetes and prolonged operating time.  The commonest infective organism was Klebsiella Pneumoniae in 37% of which 19% were ESBL producing and 3.8% were carbapenemase producing. E. coli was identified in 20% of isolates. The incidence of ESBL in both isolates was higher.Conclusions: Regular audit of SSIs is a very effective tool to analyse risk factors, identify causes and plan strategies to prevent infection.

scholarly journals Development of coinage metal nanoclusters as antimicrobials to combat bacterial infections

2020 ◽  
Vol 8 (41) ◽  
pp. 9466-9480
Author(s):  
Dan Li ◽  
Beena Kumari ◽  
Jessa Marie Makabenta ◽  
Bailong Tao ◽  
Kun Qian ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Economic Loss ◽  
Resistant Bacteria ◽  
Metal Nanoclusters ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Coinage Metal ◽  
The Past

Infections from antibiotic-resistant bacteria have caused huge economic loss and numerous deaths over the past decades.

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