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1.
Int J Mol Sci ; 22(22)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1534089

ABSTRACT

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Drug Resistance, Bacterial/genetics , Peptides/pharmacology , Acinetobacter Infections/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/pathogenicity , Anti-Infective Agents, Local/pharmacology , Biofilms/drug effects , Carbapenems/adverse effects , Carbapenems/pharmacology , Humans , Microbial Sensitivity Tests
2.
Microb Drug Resist ; 27(9): 1167-1175, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1406451

ABSTRACT

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.


Subject(s)
Acinetobacter Infections/mortality , COVID-19/mortality , Drug Resistance, Multiple, Bacterial , Klebsiella Infections/mortality , Opportunistic Infections/mortality , Pneumonia/mortality , SARS-CoV-2/pathogenicity , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter Infections/virology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/pathogenicity , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Carbapenems/therapeutic use , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella Infections/virology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Length of Stay/statistics & numerical data , Male , Middle Aged , Opportunistic Infections/drug therapy , Opportunistic Infections/microbiology , Opportunistic Infections/virology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Pneumonia/drug therapy , Pneumonia/microbiology , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Steroids/therapeutic use , Survival Analysis , Treatment Outcome
3.
Jpn J Infect Dis ; 74(4): 367-368, 2021 Jul 21.
Article in English | MEDLINE | ID: covidwho-1380103

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major worldwide concern. Guidelines have been issued regarding precautions for healthcare workers caring for SARS-CoV-2-infected patients. Despite accurate observance of infection control measures, including contact precautions, we encountered an OXA-23-producing Acinetobacter baumannii outbreak in 5 intensive care units of 10 beds each in our tertiary care teaching hospital.


Subject(s)
Acinetobacter Infections/epidemiology , COVID-19/epidemiology , Acinetobacter baumannii/pathogenicity , Adult , Aged , Disease Outbreaks , Female , Health Personnel , Humans , Infection Control/methods , Male , Middle Aged , SARS-CoV-2/pathogenicity , Tertiary Care Centers
4.
J Infect Dev Ctries ; 15(1): 58-68, 2021 Jan 31.
Article in English | MEDLINE | ID: covidwho-1079734

ABSTRACT

INTRODUCTION: SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico. METHODOLOGY: Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done. RESULTS: Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus. CONCLUSIONS: Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients.


Subject(s)
Acinetobacter Infections/transmission , Acinetobacter baumannii/isolation & purification , COVID-19/prevention & control , Cross Infection/prevention & control , Intensive Care Units , Acinetobacter baumannii/pathogenicity , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Cross Infection/microbiology , Drug Resistance, Bacterial/genetics , Equipment and Supplies/microbiology , Genotype , Humans , Interspersed Repetitive Sequences , Mexico , Pneumonia, Ventilator-Associated/microbiology
5.
IUBMB Life ; 72(10): 2097-2111, 2020 10.
Article in English | MEDLINE | ID: covidwho-696287

ABSTRACT

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Bacterial Infections/epidemiology , COVID-19/epidemiology , Pandemics , Pneumonia, Bacterial/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/pathogenicity , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Infections/virology , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Coinfection , Haemophilus influenzae/drug effects , Haemophilus influenzae/pathogenicity , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Legionella pneumophila/drug effects , Legionella pneumophila/pathogenicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/virology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , Respiratory System/drug effects , Respiratory System/microbiology , Respiratory System/pathology , Respiratory System/virology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/pathogenicity , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/pathogenicity
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