scholarly journals Efficacy of Lysophosphatidylcholine as Direct Treatment in Combination with Colistin against Acinetobacter baumannii in Murine Severe Infections Models

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 194
Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Manuel Enrique Jiménez-Mejías ◽  
Jerónimo Pachón ◽  
Younes Smani
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Experimental Models ◽  
Antimicrobial Treatment ◽  
Clinical Settings ◽  
Monotherapy Group ◽  
Bacterial Concentration ◽  
Sepsis Model ◽  
Severe Infections ◽  
Stimulation Of

The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by Acinetobacter baumannii. We used the A. baumannii Ab9 strain, susceptible to colistin and most of the antibiotics used in clinical settings, and the A. baumannii Ab186 strain, susceptible to colistin but presenting a multidrug-resistant (MDR) pattern. The therapeutic efficacies of one and two LPC doses (25 mg/kg/d) and colistin (20 mg/kg/8 h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. One and two LPC doses combined with colistin and colistin monotherapy enhanced Ab9 and Ab186 clearance from spleen, lungs and blood and reduced mice mortality compared with those of the non-treated mice group in both experimental models. Moreover, one and two LPC doses reduced the bacterial concentration in tissues and blood in both models and increased mice survival in the peritoneal sepsis model for both strains compared with those of the colistin monotherapy group. LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the MDR A. baumannii infection.

scholarly journals Efficacy of lysophosphatidylcholine as direct treatment in combination with colistin against Acinetobacter baumannii in murine severe infections models

2020 ◽  
Author(s):  
A Miró-Canturri ◽  
R Ayerbe-Algaba ◽  
ME Jiménez-Mejías ◽  
J Pachón ◽  
Y Smani
Keyword(s):  
Acinetobacter Baumannii ◽  
Experimental Models ◽  
Antimicrobial Treatment ◽  
Clinical Settings ◽  
Bacterial Clearance ◽  
Bacterial Concentration ◽  
Direct Treatment ◽  
Sepsis Model ◽  
Severe Infections ◽  
Stimulation Of

ABSTRACTObjectivesThe stimulation of the immune response to prevent the progression of the infection may be an adjuvant to antimicrobial treatment. Previously, we showed that preemptive treatment with lysophosphatidylcholine (LPC) in combination with colistin improved the therapeutic efficacy of colistin against MDR Acinetobacter baumannii. In this study, we aimed to evaluate the efficacy of direct treatment with LPC in combination with colistin in murine experimental models of severe infections by A. baumannii.MethodsWe used A. baumannii strain Ab9, which is susceptible to colistin and most of the antibiotics used in clinical settings, and A. baumannii strain Ab186, which is susceptible to colistin but presents a MDR pattern. The therapeutic efficacies of one and two doses of LPC (25 mg/kg/d) and colistin (20 mg/kg/8h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models.ResultsOne and two doses of LPC in combination with colistin and colistin monotherapy enhanced bacterial clearance of Ab9 and Ab186 from spleen, lungs and blood and reduced mortality rates compared with those of the non-treated mice group in both experimental models (P<0.05). Moreover, one and two doses of LPC reduced the bacterial concentration in tissues and blood in both models, and increased mice survival in peritoneal sepsis model for both strains compared with those of colistin monotherapy group.ConclusionsLPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the infection by MDR A. baumannii.

scholarly journals In Vitro Activity of Sulbactam-Durlobactam against Acinetobacter baumannii-calcoaceticus Complex Isolates Collected Globally in 2016 and 2017

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sarah M. McLeod ◽  
Samir H. Moussa ◽  
Meredith A. Hackel ◽  
Alita A. Miller
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Single Amino Acid ◽  
Content Type ◽  
Level Of Activity ◽  
Severe Infections ◽  
Sources Of Infection

ABSTRACT Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due to preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam–β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined by broth microdilution against 1,722 clinical isolates of ABC organisms collected in 2016 and 2017 from 31 countries across Asia/South Pacific, Europe, Latin America, the Middle East, and North America. Over 50% of these isolates were resistant to carbapenems. Against this collection of global isolates, SUL-DUR had a MIC50/MIC90 of 1/2 μg/ml compared to a MIC50/MIC90 of 8/64 μg/ml for sulbactam alone. This level of activity was found to be consistent across organisms, regions, sources of infection, and subsets of resistance phenotypes, including MDR and extensively drug-resistant isolates. The SUL-DUR activity was superior to those of the tested comparators, with only colistin having similar potency. Whole-genome sequencing of the 39 isolates (2.3%) with a SUL-DUR MIC of >4 μg/ml revealed that these strains encoded either the metallo-β-lactamase NDM-1, which durlobactam does not inhibit, or single amino acid substitutions near the active site of penicillin binding protein 3 (PBP3), the primary target of sulbactam. In summary, SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC organisms, including MDR isolates.

scholarly journals Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 119 ◽  
Author(s):  
Carole Ayoub Moubareck ◽  
Dalal Hammoudi Halat
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Efflux Pump ◽  
Iron Acquisition ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Biofilm Production ◽  
Resistant Phenotype ◽  
Severe Infections ◽  
Hydrolyzing Enzymes

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

scholarly journals Insights into the Resistome and Phylogenomics of a ST195 Multidrug-Resistant Acinetobacter baumannii Clinical Isolate from the Czech Republic

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1079
Author(s):  
Patrik Mlynarcik ◽  
Monika Dolejska ◽  
Iva Vagnerova ◽  
Jana Petrzelova ◽  
Iva Sukkar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Isolate ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Clinical Settings ◽  
Sequencing Analysis ◽  
Pump System ◽  
The Czech Republic

Increasing antimicrobial resistance in nosocomial pathogens, such as Acinetobacter baumannii, is becoming a serious threat to public health. It is necessary to detect β-lactamase-producing microorganisms in clinical settings to be able to control the spread of carbapenem resistance. This study was conducted to evaluate the presence of β-lactamases in a selected clinical isolate of A. baumannii of ST2P/ST195Ox and to characterize possible enzymes, as well as its β-lactam resistome, using PCR and whole-genome sequencing analysis. PCR and sequencing confirmed that the isolate harbored five bla gene alleles, namely, blaADC-73, blaTEM-1, blaOXA-23, blaOXA-58 and blaOXA-66, as well as aminoglycosides, macrolides, sulfonamides and tetracyclines resistance determinants, which were either chromosomally and/or plasmid located. Furthermore, a gene order comparison using MAUVE alignment showed multiple changes compared with the clinical isolate of Malaysian A. baumannii AC30 genome and 76 regions with high homology. This study suggests that resistance to β-lactams in this A. baumannii isolate is mainly due to an overproduction of β-lactamases in combination with other resistance mechanism (efflux pump system).

scholarly journals Molecular characterization of a multidrug-resistant/pandrug-resistant nosocomial polymicrobial infection with Klebsiella pneumoniae, Providencia rettgeri, and Acinetobacter baumannii from Rural Maharashtra, India

2020 ◽  
Author(s):  
Dilip D Karad ◽  
Yogesh Somani ◽  
Hemant Khande ◽  
Bipin Yadav ◽  
Arun S Kharat
Keyword(s):  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Bacterial Infections ◽  
Rapid Development ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Polymicrobial Infection ◽  
Multiple Drug ◽  
Providencia Rettgeri

The emergence of resistance against commonly used antibiotics has become a serious global concern. The rapid development of antibiotic resistance exhibited by Enterobacteriaceae has caused an increasing concern regarding untreatable bacterial infections. Here, we isolated four pathogens from a geriatric female patient who was hospitalized for a month with ventilator-associated pneumonia (VAP) and fever. The organisms isolated from the tracheal aspirates and urine included Klebsiella pneumoniae, pandrug-resistant Providencia rettgeri, and Acinetobacter baumannii. Resistome analysis indicated that the bacterial isolates from the polymicrobial infection were multiple-drug resitnat and pandrug resistant clones. Molecular characterization revealed presence of blaTEM-1 in K. pneumonaie, P. rettgeri and A. baumannii. The blaTEM-1 and blaNDM-1 genes were present in P. rettgeri and A. baumannii, whereas the blaTEM-1, blaNDM-1 and blaOXA-23 traits were present in A. baumannii isolates. The patient has died due to the unavailability of effective antimicrobial treatment for this drug-resistant polymicrobial infection.  

scholarly journals The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

2021 ◽  
Vol 11 ◽  
Author(s):  
Yasaman Taheri ◽  
Nataša Joković ◽  
Jelena Vitorović ◽  
Oliver Grundmann ◽  
Alfred Maroyi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antimicrobial Treatment ◽  
Bacterial Cells ◽  
Gram Negative ◽  
Pubmed Database ◽  
Severe Infections ◽  
Unique Cell

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

scholarly journals Therapeutic Efficacy of Lysophosphatidylcholine in Severe Infections Caused by Acinetobacter baumannii

2015 ◽  
Vol 59 (7) ◽  
pp. 3920-3924 ◽  
Author(s):  
Younes Smani ◽  
Juan Domínguez-Herrera ◽  
José Ibáñez-Martínez ◽  
Jerónimo Pachón
Keyword(s):  
Acinetobacter Baumannii ◽  
Therapeutic Efficacy ◽  
Immune Cell ◽  
Early Time ◽  
Experimental Models ◽  
Antimicrobial Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Preemptive Therapy ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACTDue to the significant increase in antimicrobial resistance ofAcinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused byA. baumannii. A. baumanniiATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml ofA. baumannii. The therapeutic efficacy of LPC againstA. baumanniiin murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused byA. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused byA. baumannii.

scholarly journals RND-Type Efflux Pumps in Multidrug-Resistant Clinical Isolates of Acinetobacter baumannii: Major Role for AdeABC Overexpression and AdeRS Mutations

2013 ◽  
Vol 57 (7) ◽  
pp. 2989-2995 ◽  
Author(s):  
Eun-Jeong Yoon ◽  
Patrice Courvalin ◽  
Catherine Grillot-Courvalin
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Regulatory System ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Two Component System ◽  
Content Type ◽  
High Incidence ◽  
Two Component

ABSTRACTIncreased expression of chromosomal genes for resistance-nodulation-cell division (RND)-type efflux systems plays a major role in the multidrug resistance (MDR) ofAcinetobacter baumannii. However, the relative contributions of the three most prevalent pumps, AdeABC, AdeFGH, and AdeIJK, have not been evaluated in clinical settings. We have screened 14 MDR clinical isolates shown to be distinct on the basis of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) for the presence and overexpression of the three Ade efflux systems and analyzed the sequences of the regulators AdeRS, a two-component system, for AdeABC and AdeL, a LysR-type regulator, for AdeFGH. GeneadeBwas detected in 13 of 14 isolates, andadeGand the intrinsicadeJgene were detected in all strains. Significant overexpression ofadeBwas observed in 10 strains, whereas only 7 had moderately increased levels of expression of AdeFGH, and none overexpressed AdeIJK. Thirteen strains had reduced susceptibility to tigecycline, but there was no correlation between tigecycline MICs and the levels of AdeABC expression, suggesting the presence of other mechanisms for tigecycline resistance. No mutations were found in the highly conserved LysR regulator of the nine strains expressing AdeFGH. In contrast, functional mutations were found in conserved domains of AdeRS in all the strains that overexpressed AdeABC with two mutational hot spots, one in AdeS near histidine 149 suggesting convergent evolution and the other in the DNA binding domain of AdeR compatible with horizontal gene transfer. This report outlines the high incidence of AdeABC efflux pump overexpression in MDRA. baumanniias a result of a variety of single mutations in the corresponding two-component regulatory system.

scholarly journals In VitroActivities of Combinations of Rifampin with Other Antimicrobials against Multidrug-Resistant Acinetobacter baumannii

2014 ◽  
Vol 59 (3) ◽  
pp. 1466-1471 ◽  
Author(s):  
Yan Bai ◽  
Bin Liu ◽  
Tianlin Wang ◽  
Yun Cai ◽  
Beibei Liang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Clinical Isolates ◽  
Content Type ◽  
Synergistic Interactions ◽  
Therapeutic Alternatives ◽  
Concentration Indices

ABSTRACTThe antimicrobial treatment of multidrug-resistant (MDR)Acinetobacter baumanniiinfections has become a great challenge for medical staff all over the world. Increasing numbers of MDRA. baumanniiinfections have been identified and reported, but effective clinical treatments for them are decreasing. The objective of this study was to investigate thein vitroactivities of combinations of rifampin (an established antimicrobial) and other antimicrobials, including biapenem, colistin, and tigecycline, against 73 clinical isolates of MDRA. baumannii. In total, 73 clinical isolates of MDRA. baumanniiwere collected from two A-level general hospitals in Beijing, and the MICs of rifampin, biapenem, colistin, and tigecycline were determined. The checkerboard method was used to determine the fractional inhibitory concentration indices (FICIs), that is, whether the combinations acted synergistically against these isolates. The MIC50, MIC90, and MICrangeof rifampin combined with biapenem, colistin, and tigecycline against the isolates were clearly lower than those for four antimicrobials (rifampin, biapenem, colistin, and tigecycline) that were used alone. Combinations of rifampin with biapenem, colistin, and tigecycline individually demonstrated the following interactions: synergistic interactions (FICI ≤ 0.5) for 31.51%, 34.25%, and 31.51% of the isolates, partially synergistic interactions (0.5 < FICI < 1) for 49.31%, 43.83%, and 47.94% of the isolates, and additive interactions (FICI = 1) for 19.18%, 21.92%, and 20.55% of the isolates, respectively. There were no indifferent (1 < FICI < 4) or antagonistic (FICI ≥ 4) interactions. Therefore, combinations of rifampin with biapenem, colistin, or tigecycline may be future therapeutic alternatives for the treatment of MDRA. baumanniiinfections.

scholarly journals Efficacy of Rifampin and Its Combinations with Imipenem, Sulbactam, and Colistin in Experimental Models of Infection Caused by Imipenem-Resistant Acinetobacter baumannii

2010 ◽  
Vol 54 (3) ◽  
pp. 1165-1172 ◽  
Author(s):  
María E. Pachón-Ibáñez ◽  
Fernando Docobo-Pérez ◽  
Rafael López-Rojas ◽  
Juan Domínguez-Herrera ◽  
Manuel E. Jiménez-Mejias ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Combined Treatment ◽  
Multidrug Resistant ◽  
Experimental Models ◽  
Blood Cultures ◽  
Control Group ◽  
Group I ◽  
Time Kill ◽  
Bacterial Concentrations

ABSTRACT There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.

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