scholarly journals Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii

2021 ◽  
Vol 9 (10) ◽  
pp. 2104
Author(s):  
Sunil Kumar ◽  
Razique Anwer ◽  
Arezki Azzi
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Outer Membrane Proteins ◽  
Multidrug Resistant ◽  
High Rate ◽  
World Health ◽  
Tract Infections

Acinetobacter baumannii is an opportunistic pathogen which is undoubtedly known for a high rate of morbidity and mortality in hospital-acquired infections. A. baumannii causes life-threatening infections, including; ventilator-associated pneumonia (VAP), meningitis, bacteremia, and wound and urinary tract infections (UTI). In 2017, the World Health Organization listed A. baumannii as a priority-1 pathogen. The prevalence of A. baumannii infections and outbreaks emphasizes the direct need for the use of effective therapeutic agents for treating such infections. Available antimicrobials, such as; carbapenems, tigecycline, and colistins have insufficient effectiveness due to the appearance of multidrug-resistant strains, accentuating the need for alternative and novel therapeutic remedies. To understand and overcome this menace, the knowledge of recent discoveries on the virulence factors of A. baumannii is needed. Herein, we summarized the role of various virulence factors, including; outer membrane proteins, efflux pumps, biofilm, penicillin-binding proteins, and siderophores/iron acquisition systems. We reviewed the recent scientific literature on different A. baumannii virulence factors and the effective antimicrobial agents for the treatment and management of bacterial infections.

scholarly journals Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Multi Drug Resistance ◽  
Gram Positive ◽  
Treatment Regimens ◽  
Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

scholarly journals Bacterial infections in cirrhosis: a narrative review and key points for clinical practice

2020 ◽  
Vol 14 (3) ◽  
pp. 126-135
Author(s):  
Mario Mitra ◽  
Andrea Mancuso ◽  
Flavia Politi ◽  
Alberto Maringhini
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Empirical Therapy ◽  
Multidrug Resistant ◽  
High Rate ◽  
First Episode ◽  
Bacterial Peritonitis ◽  
Prophylactic Measures ◽  
Tract Infections ◽  
Healthcare Associated

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.

scholarly journals Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii

2008 ◽  
Vol 52 (8) ◽  
pp. 2898-2904 ◽  
Author(s):  
Tze-Peng Lim ◽  
Kimberly R. Ledesma ◽  
Kai-Tai Chang ◽  
Jing-Guo Hou ◽  
Andrea L. Kwa ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Quantitative Assessment ◽  
Antimicrobial Agents ◽  
Single Agent ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Killing Effect ◽  
Significant Difference ◽  
Objective Basis

ABSTRACT Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r 2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations.

scholarly journals Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 151
Author(s):  
Tatjana Kirtikliene ◽  
Aistė Mierauskaitė ◽  
Ilona Razmienė ◽  
Nomeda Kuisiene
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Essential Information ◽  
Acinetobacter Spp

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.

scholarly journals Prophylaxis and Treatment against Klebsiella pneumoniae: Current Insights on This Emerging Anti-Microbial Resistant Global Threat

2021 ◽  
Vol 22 (8) ◽  
pp. 4042
Author(s):  
Vanessa Arato ◽  
Maria Michelina Raso ◽  
Gianmarco Gasperini ◽  
Francesco Berlanda Scorza ◽  
Francesca Micoli
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Outer Membrane Proteins ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Current Status ◽  
Middle Income ◽  
Health Organization ◽  
Global Threat

Klebsiella pneumoniae (Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections. Here, we review elements of the current status of the epidemiology and the molecular pathogenesis of Kp and explore specific bacterial antigens as potential targets for both prophylactic and therapeutic solutions.

scholarly journals Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Stephanie LaVergne ◽  
Theron Hamilton ◽  
Biswajit Biswas ◽  
M Kumaraswamy ◽  
R T Schooley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Alternative Treatment ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Site Infection ◽  
Bacteriophage Therapy

Abstract In the era of antibiotic resistance, alternative treatment options for multidrug-resistant bacterial infections are being explored. We present a case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages. Clinical trials are needed to further investigate bacteriophage therapy as an option to treat multidrug-resistant bacterial infections.

scholarly journals Acinetobacter baumannii Infections in Times of COVID-19 Pandemic

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1006
Author(s):  
Karyne Rangel ◽  
Thiago Pavoni Gomes Chagas ◽  
Salvatore Giovanni De-Simone
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Secondary Infection ◽  
Immune Dysfunction ◽  
Tract Infections ◽  
Viral Respiratory Infections ◽  
Over Time ◽  
Viral Respiratory

The COVID-19 pandemic has generated an overuse of antimicrobials in critically ill patients. Acinetobacter baumannii frequently causes nosocomial infections, particularly in intensive care units (ICUs), where the incidence has increased over time. Since the WHO declared the COVID-19 pandemic on 12 March 2020, the disease has spread rapidly, and many of the patients infected with SARS-CoV-2 needed to be admitted to the ICU. Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. However, we cannot neglect the increased incidence of antimicrobial resistance, which may be attributed to the excess use of antimicrobial agents during the COVID-19 pandemic. Patients with COVID-19 could be vulnerable to other infections owing to multiple comorbidities with severe COVID-19, prolonged hospitalization, and SARS-CoV-2-associated immune dysfunction. These patients have acquired secondary bacterial infections or superinfections, mainly bacteremia and urinary tract infections. This review will summarize the prevalence of A. baumannii coinfection and secondary infection in patients with COVID-19.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Stephen J. Dollery ◽  
Daniel V. Zurawski ◽  
Elena K. Gaidamakova ◽  
Vera Y. Matrosova ◽  
John K. Tobin ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Protein Profiles ◽  
Vaccine Candidates ◽  
Rich Media ◽  
Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

scholarly journals Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 597
Author(s):  
Luca Pierantoni ◽  
Laura Andreozzi ◽  
Simone Ambretti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metropolitan Area ◽  
Bacterial Infections ◽  
Asymptomatic Bacteriuria ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
First Line ◽  
E Coli ◽  
First Line Therapy ◽  
Tract Infections

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

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