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1.
Int J Mol Sci ; 24(11)2023 May 31.
Article in English | MEDLINE | ID: covidwho-20243060

ABSTRACT

The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in Acinetobacter baumannii. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired blaCHDL-genes-carrying A. baumannii clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods. EPIs reduced carbapenem resistance of 14/61 isolates. Upregulation (5-67-fold) of adeB was observed together with mutations in the sequences of AdeRS local and of BaeS global regulators in all 15 selected isolates. Long-read WGS of isolate no. AB96 revealed the presence of AbaR25 resistance island and its two disrupted elements: the first contained a duplicate ISAba1-blaOXA-23, and the second was located between adeR and adeA in the efflux operon. This insert was flanked by two copies of ISAba1, and one of them provides a strong promoter for adeABC, elevating the adeB expression levels. Our study for the first time reports the involvement of the insertion of the ΔAbaR25-type resistance island fragment with ISAba1 element upstream the efflux operon in the carbapenem resistance of A. baumannii.


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Acinetobacter baumannii/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Carbapenems/pharmacology , Carbapenems/metabolism , Mutation , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial/genetics
2.
J Infect Dev Ctries ; 17(1): 129-134, 2023 01 31.
Article in English | MEDLINE | ID: covidwho-20242325

ABSTRACT

INTRODUCTION: Catheter-associated urinary tract infections (CAUTIs) are among the most common nosocomial infections with different clinical and microbiological characteristics. We studied these characteristics in critically ill patients. METHODOLOGY: This research was a cross-sectional study conducted on intensive care unit (ICU) patients with CAUTI. Patients' demographic and clinical information and laboratory data, including causative microorganisms and antibiotic susceptibility tests, were recorded and analyzed. Finally, the differences between the patients who survived and died were compared. RESULTS: After reviewing 353 ICU cases, 80 patients with CAUTI were finally included in the study. The mean age was 55.9 ± 19.1 years, 43.7% were male and 56.3% were female. The mean length of infection development since hospitalisation and hospital stay were 14.7 (3-90) and 27.8 (5-98) days, respectively. The most common symptom was fever (80%). The microbiological identification showed that the most isolated microorganisms were Multidrug-resistant (MDR) Enterobacteriaceae (75%), Pseudomonas aeruginosa (8.8%), Gram-positive uropathogens (8.8%) and Acinetobacter baumannii (5%). Fifteen patients (18.8%) died among whom infections with A. baumannii (75%) and P. aeruginosa (57.1%) were associated with more death (p = 0.005). CONCLUSIONS: Although A. baumannii and P. aeruginosa can be the most important pathogens for death, MDR Enterobacteriaceae are still a serious concern as causes of CAUTIs.


Subject(s)
Acinetobacter baumannii , Cross Infection , Humans , Male , Female , Adult , Middle Aged , Aged , Iran/epidemiology , Cross-Sectional Studies , Critical Illness , Cross Infection/microbiology , Catheters , Pseudomonas aeruginosa , Intensive Care Units , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial
3.
Microbiol Spectr ; 11(3): e0499522, 2023 Jun 15.
Article in English | MEDLINE | ID: covidwho-2313295

ABSTRACT

Colonization and subsequent health care-associated infection (HCAI) with Acinetobacter baumannii are a concern for vulnerable patient groups within the hospital setting. Outbreaks involving multidrug-resistant strains are associated with increased patient morbidity and mortality and poorer overall outcomes. Reliable molecular typing methods can help to trace transmission routes and manage outbreaks. In addition to methods deployed by reference laboratories, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) may assist by making initial in-house judgments on strain relatedness. However, limited studies on method reproducibility exist for this application. We applied MALDI-TOF MS typing to A. baumannii isolates associated with a nosocomial outbreak and evaluated different methods for data analysis. In addition, we compared MALDI-TOF MS with whole-genome sequencing (WGS) and Fourier transform infrared spectroscopy (FTIR) as orthogonal methods to further explore their resolution for bacterial strain typing. A related subgroup of isolates consistently clustered separately from the main outbreak group by all investigated methods. This finding, combined with epidemiological data from the outbreak, indicates that these methods identified a separate transmission event unrelated to the main outbreak. However, the MALDI-TOF MS upstream approach introduced measurement variability impacting method reproducibility and limiting its reliability as a standalone typing method. Availability of in-house typing methods with well-characterized sources of measurement uncertainty could assist with rapid and dependable confirmation (or denial) of suspected transmission events. This work highlights some of the steps to be improved before such tools can be fully integrated into routine diagnostic service workflows for strain typing. IMPORTANCE Managing the transmission of antimicrobial resistance necessitates reliable methods for tracking outbreaks. We compared the performance of MALDI-TOF MS with orthogonal approaches for strain typing, including WGS and FTIR, for Acinetobacter baumannii isolates correlated with a health care-associated infection (HCAI) event. Combined with epidemiological data, all methods investigated identified a group of isolates that were temporally and spatially linked to the outbreak, yet potentially attributed to a separate transmission event. This may have implications for guiding infection control strategies during an outbreak. However, the technical reproducibility of MALDI-TOF MS needs to be improved for it to be employed as a standalone typing method, as different stages of the experimental workflow introduced bias influencing interpretation of biomarker peak data. Availability of in-house methods for strain typing of bacteria could improve infection control practices following increased reports of outbreaks of antimicrobial-resistant organisms during the COVID-19 pandemic, related to sessional usage of personal protective equipment (PPE).


Subject(s)
Acinetobacter baumannii , Anti-Infective Agents , COVID-19 , Cross Infection , Humans , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Acinetobacter baumannii/genetics , Reproducibility of Results , Bacterial Typing Techniques/methods , Pandemics , COVID-19/epidemiology , Molecular Typing , Cross Infection/epidemiology , Cross Infection/microbiology
4.
Biosensors (Basel) ; 13(4)2023 Apr 06.
Article in English | MEDLINE | ID: covidwho-2298134

ABSTRACT

Detection and quantification of DNA biomarkers relies heavily on the yield and quality of DNA obtained by extraction from different matrices. Although a large number of studies have compared the yields of different extraction methods, the repeatability and intermediate precision of these methods have been largely overlooked. In the present study, five extraction methods were evaluated, using digital PCR, to determine their efficiency in extracting DNA from three different Gram-negative bacteria in sputum samples. The performance of two automated methods (GXT NA and QuickPick genomic DNA extraction kit, using Arrow and KingFisher Duo automated systems, respectively), two manual kit-based methods (QIAamp DNA mini kit; DNeasy UltraClean microbial kit), and one manual non-kit method (CTAB), was assessed. While GXT NA extraction kit and the CTAB method have the highest DNA yield, they did not meet the strict criteria for repeatability, intermediate precision, and measurement uncertainty for all three studied bacteria. However, due to limited clinical samples, a compromise is necessary, and the GXT NA extraction kit was found to be the method of choice. The study also showed that dPCR allowed for accurate determination of extraction method repeatability, which can help standardize molecular diagnostic approaches. Additionally, the determination of absolute copy numbers facilitated the calculation of measurement uncertainty, which was found to be influenced by the DNA extraction method used.


Subject(s)
Acinetobacter baumannii , Klebsiella pneumoniae , Pseudomonas aeruginosa , Cetrimonium , DNA
5.
Int J Antimicrob Agents ; 62(1): 106825, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2302838

ABSTRACT

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.


Subject(s)
Acinetobacter baumannii , Bacteremia , COVID-19 , Fosfomycin , Pneumonia, Ventilator-Associated , Humans , Colistin/therapeutic use , Carbapenems/therapeutic use , Carbapenems/pharmacology , Pneumonia, Ventilator-Associated/drug therapy , COVID-19/complications , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy
6.
J Antimicrob Chemother ; 78(4): 1034-1040, 2023 04 03.
Article in English | MEDLINE | ID: covidwho-2262606

ABSTRACT

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Humans , Carbapenems/pharmacology , Carbapenems/therapeutic use , Retrospective Studies , Acinetobacter Infections/drug therapy , Drug Synergism , Anti-Bacterial Agents/therapeutic use , Drug Combinations , Acinetobacter baumannii/genetics , Microbial Sensitivity Tests
7.
Front Immunol ; 13: 1070424, 2022.
Article in English | MEDLINE | ID: covidwho-2215284

ABSTRACT

Acinetobacter baumannii is a nosocomic opportunistic Gram-negative bacteria known for its extensive drug-resistant phenotype. A. baumannii hospital-acquired infections are major contributors to increased costs and mortality observed during the COVID-19 pandemic. With few effective antimicrobials available for treatment of this pathogen, immune-based therapy becomes an attractive strategy to combat multi-drug resistant Acinetobacter infection. Immunotherapeutics is a field of growing interest with advances in vaccines and monoclonal antibodies providing insight into the protective immune response required to successfully combat this pathogen. This review focuses on current knowledge describing the adaptive immune response to A. baumannii, the importance of antibody-mediated protection, developments in cell-mediated protection, and their respective therapeutic application going forward. With A. baumannii's increasing resistance to most current antimicrobials, elucidating an effective host adaptive immune response is paramount in the guidance of future immunotherapeutic development.


Subject(s)
Acinetobacter baumannii , COVID-19 Drug Treatment , Cross Infection , Humans , Pandemics , Antibodies, Monoclonal
8.
BMC Pulm Med ; 23(1): 30, 2023 Jan 20.
Article in English | MEDLINE | ID: covidwho-2214573

ABSTRACT

BACKGROUND: Little is known on the burden of co-infections and superinfections in a specific setting such as the respiratory COVID-19 sub-intensive care unit. This study aims to (i) assess the prevalence of concurrent and superinfections in a respiratory sub-intensive care unit, (ii) evaluate the risk factors for superinfections development and (iii) assess the impact of superinfections on in-hospital mortality. METHODS: Single-center retrospective analysis of prospectively collected data including COVID-19 patients hospitalized in a newly established respiratory sub-intensive care unit managed by pneumologists which has been set up from September 2020 at a large (1200 beds) University Hospital in Rome. Inclusion criteria were: (i) COVID-19 respiratory failure and/or ARDS; (ii) hospitalization in respiratory sub-intensive care unit and (iii) age > 18 years. Survival was analyzed by Kaplan-Meier curves and the statistical significance of the differences between the two groups was assessed using the log-rank test. Multivariable logistic regression and Cox regression model were performed to tease out the independent predictors for superinfections' development and for mortality, respectively. RESULTS: A total of 201 patients were included. The majority (106, 52%) presented severe COVID-19. Co-infections were 4 (1.9%), whereas 46 patients (22%) developed superinfections, mostly primary bloodstream infections and pneumonia. In 40.6% of cases, multi-drug resistant pathogens were detected, with carbapenem-resistant Acinetobacter baumannii (CR-Ab) isolated in 47%. Overall mortality rate was 30%. Prior (30-d) infection and exposure to antibiotic therapy were independent risk factors for superinfection development whereas the development of superinfections was an independent risk factors for in-hospital mortality. CR-Ab resulted independently associated with 14-d mortality. CONCLUSION: In a COVID-19 respiratory sub-intensive care unit, superinfections were common and represented an independent predictor of mortality. CR-Ab infections occurred in almost half of patients and were associated with high mortality. Infection control rules and antimicrobial stewardship are crucial in this specific setting to limit the spread of multi-drug resistant organisms.


Subject(s)
Acinetobacter baumannii , COVID-19 , Coinfection , Superinfection , Humans , Adult , Middle Aged , COVID-19/epidemiology , Superinfection/drug therapy , Retrospective Studies , Coinfection/epidemiology , Coinfection/drug therapy , Rome/epidemiology , Drug Resistance, Multiple, Bacterial , Anti-Bacterial Agents/therapeutic use , Intensive Care Units , Hospitals, University , Risk Factors
9.
J Infect Public Health ; 16(3): 313-319, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2180682

ABSTRACT

BACKGROUND: Acinetobacter baumannii infection is a serious public health problem because it is highly resistant to antimicrobial therapy and causes a high fatality rate in critically ill patients. The aim of the study is to examine the demographics, microbiological findings, clinical presentation, and outcomes of multi-drug-resistant Acinetobacter baumannii respiratory infections in adult ICU intubated patients during COVID-19 pandemic. METHODS: This study included 115 mechanically ventilated adult ICU patients who had multi-drug-resistant Acinetobacter baumannii retrieved from respiratory samples during the COVID-19 pandemic in Albaha, Saudi Arabia. The information was obtained from medical and laboratory files. Univariate analysis was used to compare gender, COVID-19 infection, and outcomes. RESULTS: The rate of Acinetobacter baumanni respiratory infections among adult ICU patients was 6.2 %. Almost 93 % developed ventilator-associated pneumonia, and five of them developed bacteremia. The isolates had significant antibiotic resistance patterns, of which 3 % were pandrug-resistant bacteria. The death rate was 74 %, with major risk factors including sepsis, septic shock, VAP, liver diseases, and the use of inappropriate antibiotic therapy that lacked both colistin and tigecycline. Patients with COVID-19 coinfection had worse outcomes compared to non-COVID-19 patients. CONCLUSIONS: The identification of MDR-AB as a threat highlights the importance of surveillance studies in this region.


Subject(s)
Acinetobacter baumannii , COVID-19 , Respiratory Tract Infections , Adult , Humans , Retrospective Studies , Critical Illness , Pandemics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Drug Resistance, Multiple, Bacterial
10.
BMC Infect Dis ; 23(1): 11, 2023 Jan 06.
Article in English | MEDLINE | ID: covidwho-2196090

ABSTRACT

BACKGROUND: The prevalence of resistant hospital infections in the intensive care unit (ICU) increases mortality and antibiotic resistance. COVID-19 pandemic may have unintended impact on nosocomial infections (NI) and the prevalence of resistant microorganism. METHODOLOGY: The present non-interventional study was performed by a pre and a post survey each lasting 8 months before (March-October 2019) and after (March-October 2020) the onset of COVID-19 pandemic in three ICU's, not allocated to COVID-19 patients, in Nemazee Hospital, Shiraz, Iran. The rates of the following nosocomial infections were compared at pre- and post-pandemic period: ventilator associated pneumonia (VAP), central line associated blood stream infection (CLABSI), catheter-associated urinary tract infections (CAUTI) and incidence of multiple drug resistance (MDR) pathogens. RESULTS: Pre-pandemic and pandemic incidence of VAP was 23.5 and 17.2 cases per 1000 device-days, respectively; an absolute decrease of 27%. The main reason for the decrease in the rate of VAP during the pandemic was a significant decrease in the rate of VAP caused by Acinetobacter baumannii; from 39 to 17% in total VAP episodes. The rate of VAP associated with other microorganisms remained relatively unchanged from 14.2 cases in pre-pandemic period to 14.3 cases per 1000 MV-days during the pandemic (P = 0.801). Pre-pandemic incidence of CLABSI was 7.3 cases and, in pandemic period, was 6.5 cases per 1000 device-days (IRR = 0.88, 95% CI 0.43-1.73, P = 0.703). Pre-pandemic incidence of CAUTI was 2 and in pandemic period, was 1.4 cases per 1000 device-days (IRR = 0.70, 95% CI 0.22-1.98, P = 0.469). CONCLUSION: The results of the present study showed a decrease in the incidence of VAP in critically ill non-COVID-19 patients during the pandemic compared to before the pandemic, especially regarding Acinetobacter baumannii.


Subject(s)
Acinetobacter baumannii , COVID-19 , Catheter-Related Infections , Cross Infection , Pneumonia, Ventilator-Associated , Urinary Tract Infections , Humans , Cross Infection/epidemiology , Pandemics , Incidence , Prospective Studies , COVID-19/epidemiology , Catheter-Related Infections/epidemiology , Intensive Care Units , Pneumonia, Ventilator-Associated/epidemiology , Hospitals, Teaching , Urinary Tract Infections/epidemiology , Drug Resistance, Multiple , Catheters
11.
Sci Rep ; 12(1): 20808, 2022 Dec 02.
Article in English | MEDLINE | ID: covidwho-2151113

ABSTRACT

We aimed to describe the increased rate of Acinetobacter baumannii infections during the COVID-19 pandemic and define its significance within the last five years. This study was performed in a tertiary hospital with 280 beds and included all patients infected with A. baumannii in the intensive care unit between January 1, 2018, and June 30, 2022. A. baumannii-infected patients in the intensive care unit 27 months before the pandemic and 27 months during the pandemic were included. Pulsed-field gel electrophoresis was performed to assess clonal relatedness. The infection control measures were specified based on the findings and targeted elimination. In total, 5718 patients were admitted to the intensive care unit from January 1st, 2018, to June 30th, 2022. A. baumannii infection was detected in 81 patients. Compared to the pre-pandemic era, the rate of A. baumannii infection during the pandemic was 1.90 times higher (OR: 1.90, 95% CI: [1.197, 3.033]). Clonality assessment of multidrug-resistant A. baumannii samples revealed eight clusters with one main cluster comprising 14/27 isolates between 2021 and 2022. The case fatality rate of the pre-pandemic and pandemic era was not different statistically (83.33% vs. 81.48%, p = 0.835). Univariate analysis revealed the association of mechanical ventilation (p = 0.002) and bacterial growth in tracheal aspirate (p = 0.001) with fatality. During the COVID-19 pandemic, potential deficits in infection control measures may lead to persistent nosocomial outbreaks. In this study, the introduction of enhanced and customized infection control measures has resulted in the containment of an A. baumannii outbreak.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Intensive Care Units , Acinetobacter Infections/epidemiology , Tertiary Care Centers
13.
Antimicrob Resist Infect Control ; 11(1): 121, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2053970

ABSTRACT

BACKGROUND: The coronavirus disease 2019 seems to change antibiotic resistance pattern. Certain conditions in the Covid-19 era may be contributing to the rise of antimicrobial resistance (AMR). Due to the limited information on the impact of Covid-19 on antimicrobial resistance (AMR), the purpose of this research was to investigate the trend in antimicrobial resistance changes of E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii in Hasheminezhad hospital. This hospital was a Corona center in Mashhad at the onset of this epidemic. METHODS: 1672 clinical samples were collected between January 21, 2020 and January 30, 2022from patients hospitalized at Hasheminezhad Hospital in Mashhad, Conventional microbiological procedures for identifying gram-negative bacteria and antibiotic susceptibility testing were used, according to the clinical and laboratory standards institute (CLSI) 2021. The two years of the pandemic, from the initial stage of the outbreak until the 6th peak, (January 2020 to and January 2022) were divided into 9 periods according to the seasons. RESULTS: Highest resistance rates were seen in E. coli (615 samples), K. pneumoniae (351 samples), P. aeruginosa (362 samples) and A. baumannii (344 samples) to Ampicillin (89.6%), Ampicillin (98%), Imipenem (91.8%), and Ceftazidime (94.6%), respectively. The largest change in antibiotic resistance was seen between Summer 2020 and Summer 2021 for K. pneumoniae with about a 30% rise in antibiotic resistance to Ceftriaxone. CONCLUSIONS: All 4 species evaluated in this study, have shown rising AMR rates during the first year of the pandemic in the northeast of Iran. This study revealed that E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii strains in Northern Iran have a higher level of antibiotic resistance than what was measured in similar studies conducted before the pandemic. This will further restrict treatment choices and jeopardize global public health.


Subject(s)
Acinetobacter baumannii , COVID-19 , Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Ceftazidime/pharmacology , Ceftriaxone/pharmacology , Drug Resistance, Bacterial , Escherichia coli , Humans , Imipenem/pharmacology , Iran/epidemiology , Klebsiella pneumoniae , Microbial Sensitivity Tests , Pandemics , Pseudomonas aeruginosa
14.
Front Cell Infect Microbiol ; 12: 934671, 2022.
Article in English | MEDLINE | ID: covidwho-2032744

ABSTRACT

Pneumonia is one of the leading causes of morbidity and mortality worldwide and Gram-negative bacteria are a major cause of severe pneumonia. Despite advances in diagnosis and treatment, the rise of multidrug-resistant organisms and hypervirulent strains demonstrates that there will continue to be challenges with traditional treatment strategies using antibiotics. Hence, an alternative approach is to focus on the disease tolerance components that mediate immune resistance and enhance tissue resilience. Adaptive immunity plays a pivotal role in modulating these processes, thus affecting the incidence and severity of pneumonia. In this review, we focus on the adaptive T cell responses to pneumonia induced by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We highlight key factors in these responses that have potential for therapeutic targeting, as well as the gaps in current knowledge to be focused on in future work.


Subject(s)
Acinetobacter baumannii , Pneumonia, Bacterial , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria , Humans , Microbial Sensitivity Tests , Pneumonia, Bacterial/drug therapy , Pseudomonas aeruginosa , T-Lymphocytes
15.
PLoS Pathog ; 18(9): e1010809, 2022 09.
Article in English | MEDLINE | ID: covidwho-2009723

ABSTRACT

Acinetobacter baumannii is an opportunistic pathogen and an emerging global health threat. Within healthcare settings, major presentations of A. baumannii include bloodstream infections and ventilator-associated pneumonia. The increased prevalence of ventilated patients during the COVID-19 pandemic has led to a rise in secondary bacterial pneumonia caused by multidrug resistant (MDR) A. baumannii. Additionally, due to its MDR status and the lack of antimicrobial drugs in the development pipeline, the World Health Organization has designated carbapenem-resistant A. baumannii to be its priority critical pathogen for the development of novel therapeutics. To better inform the design of new treatment options, a comprehensive understanding of how the host contains A. baumannii infection is required. Here, we investigate the innate immune response to A. baumannii by assessing the impact of infection on host gene expression using NanoString technology. The transcriptional profile observed in the A. baumannii infected host is characteristic of Gram-negative bacteremia and reveals expression patterns consistent with the induction of nutritional immunity, a process by which the host exploits the availability of essential nutrient metals to curtail bacterial proliferation. The gene encoding for lipocalin-2 (Lcn2), a siderophore sequestering protein, was the most highly upregulated during A. baumannii bacteremia, of the targets assessed, and corresponds to robust LCN2 expression in tissues. Lcn2-/- mice exhibited distinct organ-specific gene expression changes including increased transcription of genes involved in metal sequestration, such as S100A8 and S100A9, suggesting a potential compensatory mechanism to perturbed metal homeostasis. In vitro, LCN2 inhibits the iron-dependent growth of A. baumannii and induces iron-regulated gene expression. To elucidate the role of LCN2 in infection, WT and Lcn2-/- mice were infected with A. baumannii using both bacteremia and pneumonia models. LCN2 was not required to control bacterial growth during bacteremia but was protective against mortality. In contrast, during pneumonia Lcn2-/- mice had increased bacterial burdens in all organs evaluated, suggesting that LCN2 plays an important role in inhibiting the survival and dissemination of A. baumannii. The control of A. baumannii infection by LCN2 is likely multifactorial, and our results suggest that impairment of iron acquisition by the pathogen is a contributing factor. Modulation of LCN2 expression or modifying the structure of LCN2 to expand upon its ability to sequester siderophores may thus represent feasible avenues for therapeutic development against this pathogen.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Bacteremia , COVID-19 , Pneumonia, Bacterial , Acinetobacter baumannii/genetics , Acinetobacter baumannii/metabolism , Animals , Carbapenems/pharmacology , Humans , Immunity, Innate , Iron/metabolism , Lipocalin-2/genetics , Lipocalin-2/metabolism , Mice , Pandemics , Siderophores/metabolism
16.
J Infect Dev Ctries ; 16(7): 1131-1137, 2022 07 28.
Article in English | MEDLINE | ID: covidwho-1974973

ABSTRACT

INTRODUCTION: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. METHODOLOGY: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. RESULTS: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. CONCLUSIONS: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.


Subject(s)
Acinetobacter baumannii , Bacterial Infections , COVID-19 , Coinfection , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , COVID-19/epidemiology , COVID-19 Testing , Coinfection/drug therapy , Drug Resistance, Multiple, Bacterial , Humans , Klebsiella pneumoniae , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Respiratory System , Staphylococcal Infections/drug therapy
17.
Am J Infect Control ; 50(10): 1182-1184, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1956056

ABSTRACT

This was a prospective observational study performed between January and October 2021. Antimicrobial consumption was classified according to AWaRe and expressed as daily defined doses (DDD/1000 patient-days). Watch group antibiotic consumption demonstrated a strong correlation with carbapenem resistance among both clinical and total isolates, but Acinetobacter baumannii resistance did not correlate with antimicrobial consumption. Efforts to reduce antimicrobial consumption are needed; however, prevention and control guidelines are also a cornerstone to better results.


Subject(s)
Acinetobacter baumannii , Anti-Infective Agents , Antimicrobial Stewardship , COVID-19 , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Hospitals , Humans , Microbial Sensitivity Tests
18.
Medicina (Kaunas) ; 58(7)2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1917622

ABSTRACT

Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical samples were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cultures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected samples, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and ampicillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococcus (VRE) was 3.96%. Conclusions: The results of the current study conclude that empiric antimicrobial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months.


Subject(s)
Acinetobacter baumannii , COVID-19 , Coinfection , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Coinfection/drug therapy , Coinfection/epidemiology , Drug Resistance, Microbial , Escherichia coli , Humans , Pakistan/epidemiology
19.
Sci Rep ; 12(1): 10852, 2022 06 27.
Article in English | MEDLINE | ID: covidwho-1908290

ABSTRACT

The recent outbreak of COVID-19 has increased hospital admissions, which could elevate the risk of nosocomial infections, such as A. baumannii and P. aeruginosa infections. Although effective vaccines have been developed against SARS-CoV-2, no approved treatment option is still available against antimicrobial-resistant strains of A. baumannii and P. aeruginosa. In the current study, an all-in-one antigen was designed based on an innovative, state-of-the-art strategy. In this regard, experimentally validated linear epitopes of spike protein (SARS-CoV-2), OmpA (A. baumannii), and OprF (P. aeruginosa) were selected to be harbored by mature OmpA as a scaffold. The selected epitopes were used to replace the loops and turns of the barrel domain in OmpA; OprF311-341 replaced the most similar sequence within the OmpA, and three validated epitopes of OmpA were retained intact. The obtained antigen encompasses five antigenic peptides of spike protein, which are involved in SARS-CoV-2 pathogenicity. One of these epitopes, viz. QTQTNSPRRARSV could trigger antibodies preventing super-antigenic characteristics of spike and alleviating probable autoimmune responses. The designed antigen could raise antibodies neutralizing emerging variants of SARS-CoV-2 since at least two epitopes are consensus. In conclusion, the designed antigen is expected to raise protective antibodies against SARS-CoV-2, A. baumannii, and P. aeruginosa.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Acinetobacter baumannii/metabolism , Epitopes , Humans , Pseudomonas aeruginosa , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
20.
Sci Rep ; 12(1): 8763, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1873545

ABSTRACT

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to ß-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.


Subject(s)
Acinetobacter baumannii , Albumins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Cephalosporins , Humans , Iron/pharmacology , Microbial Sensitivity Tests , Siderophores , beta-Lactamases/genetics
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