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1.
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
2.
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
4.
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
5.
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
6.
Niger J Clin Pract ; 25(5): 702-709, 2022 May.
Article in English | MEDLINE | ID: covidwho-1863109

ABSTRACT

Background: Epidemiology of nosocomial infections may show variability because of under-estimation of infection control measures (ICMs) in coronavirus disease 19 (COVID-19) outbreak. Aim: To investigate the Acinetobacter bacteremia outbreak developed in an intensive care unit (ICU) between March 20 to May 15, 2020, examine the risk factors, and re-evaluate ICM retrospectively. Material and Methods: A retrospective cohort analysis was conducted to determine the risk factors, pulsed field gel electrophoresis (PFGE) was performed for analysis of the outbreak, ICM practices were observed by a team, and infection control interventions were undertaken. Results: Acinetobacter bacteremia developed in 17 patients (21.5%) within 79 COVID-19 patients included in the study. The mean age of the bacteremic patients was 67.3 (SD = 14.82) years, and 82.4% of them were male; of these, 15 died, leading to 88.2% mortality. The bacteremia rate was higher compared with a 14-month period preceding the COVID-19 pandemic (17/79 versus 12/580 patients, respectively). PFGE revealed that the outbreak was polyclonal. On multi-variate analysis, the bacteremia development rate was 13.7 and 5.06 times higher with central venous catheter (CVC) use and in patients with chronic obstructive pulmonary disease (COPD), respectively. The mortality rate was higher in bacteremic patients (p = 0.0016). It was observed that ICMs were not followed completely, especially change of gloves and hand hygiene. Contamination of A. baumannii was observed in 38% of the gloves. Conclusion: COPD and CVC use were determined as risk factors for Acinetobacter bacteremia development, and failures in ICM may have led to cross-contamination of endemic A. baumannii. The outbreak could be controlled within 3 weeks of interventions.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Bacteremia , COVID-19 , Cross Infection , Pulmonary Disease, Chronic Obstructive , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Aged , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , COVID-19/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Drug Resistance, Multiple, Bacterial , Female , Humans , Intensive Care Units , Male , Pandemics , Pulmonary Disease, Chronic Obstructive/epidemiology , Retrospective Studies
7.
Am J Infect Control ; 50(5): 477-481, 2022 05.
Article in English | MEDLINE | ID: covidwho-1838507

ABSTRACT

BACKGROUND: A carbapenem-resistant Acinetobacter baumannii outbreak in the COVID intensive care unit of a community hospital was contained using multidrug resistant organism guidelines. The purpose of this study is to report on an outbreak investigation and containment strategy that was used, and to discuss prevention strategy. METHODS: A multidisciplinary approach contained the spread of infection. Strategies implemented included consultation with experts, screening, and reversal of personal protective equipment conservation. Ensuring infection control best practices are maintained remain important efforts to reduce the spread of multidrug resistant organisms. RESULTS: Five patients with carbapenem-resistant Acinetobacter baumannii were identified from routine clinical cultures within one week and one patient was identified from active surveillance cultures. DISCUSSION: Personal protective equipment conservation, strategies to prevent health care personnel exposure, and patient surge staffing protocols may have increased the likelihood of multidrug resistant organism transmission. Environmental and behavioral infection control regulations with effective administrative guidance, active surveillance cultures, and antimicrobial stewardship are critical to prevent future outbreaks. CONCLUSIONS: After outbreak containment strategies were implemented, no additional patients were identified with carbapenem-resistant Acinetobacter baumannii. Conventional infection prevention and control strategies were re-instituted. A multidisciplinary approach with continued focus on hand hygiene, environmental cleaning, and correct use of personal protective equipment needs to be put in place to successfully contain and prevent the spread of carbapenem resistant infections.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Carbapenems/pharmacology , Carbapenems/therapeutic use , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple, Bacterial , Humans , Intensive Care Units
8.
Ann Pharmacother ; 56(12): 1299-1307, 2022 12.
Article in English | MEDLINE | ID: covidwho-1820077

ABSTRACT

BACKGROUND: Multidrug-resistant Acinetobacter baumannii remains challenging to treat. Although eravacycline has in vitro activity against this pathogen, there are no studies evaluating outcomes. OBJECTIVE: To assess the efficacy of eravacycline compared with best previously available therapy in adults with difficult-to-treat resistant (DTR) A. baumannii pneumonia. METHODS: This was a retrospective study of adults hospitalized for pneumonia with DTR A. baumannii. Patients receiving eravacycline were compared with those receiving best previously available therapy. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included clinical cure at Day 14, hospital and intensive care unit (ICU) length of stay, microbiologic cure, and readmission within 90 days with a positive A. baumannii respiratory culture. RESULTS: Ninety-three patients were included, with 27 receiving eravacycline. Eravacycline was associated with higher 30-day mortality (33% vs 15%; P = 0.048), lower microbiologic cure (17% vs 59%; P = 0.004), and longer durations of mechanical ventilation (10.5 vs 6.5 days; P = 0.016). At baseline, eravacycline patients had more A. baumannii bacteremia and coinfection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Among bacteremic patients, all 4 receiving eravacycline died by Day 30 and both patients receiving best previously available therapy survived. Upon exclusion of patients with bacteremia and SARS-CoV-2, there were no differences between the groups across any outcomes. CONCLUSIONS: Eravacycline-based combination therapy had similar outcomes to best previously available combination therapy for adults with DTR A. baumannii pneumonia. However, eravacycline should be used with caution in the setting of bacteremia as outcomes were poor in this population.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Bacteremia , COVID-19 , Pneumonia , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Adult , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Drug Resistance, Multiple, Bacterial , Humans , Pneumonia/drug therapy , Retrospective Studies , SARS-CoV-2 , Tetracyclines
9.
J Med Microbiol ; 71(4)2022 Apr.
Article in English | MEDLINE | ID: covidwho-1788579

ABSTRACT

Introduction. Carbapenem-resistant Acinetobacter baumannii (CRAB) is the primary pathogen causing hospital-acquired infections. The spread of CRAB is mainly driven by the dissemination of resistant clones, and in Latin America, International Clones IC-1 (also known as clonal complex CC1), IC-4 (CC15) and IC-5 (CC79) are the most prevalent.Gap Statement. There are no documented outbreaks of CRAB International Clone 2 (IC-2) reported in Brazil.Aim. To describe a large outbreak of CRAB caused by the uncommon IC-2 in a Brazilian COVID-19 hospital.Methodology. From May 2020 to May 2021, 224 patients infected or colonized with CRAB were identified in a single hospital; 92 % of them were also infected with SARS-CoV-2. From these patients, 137 isolates were recovered and subjected to antimicrobial susceptibility testing, PCR analysis and molecular typing. Whole-genome sequencing and downstream analysis were carried out on a representative isolate (the first available isolate).Results. In 76 % of the patients, a single OXA-23-producing CRAB IC-2 was identified. All the isolates were susceptible to polymyxin B, but highly resistant (>95 %) to aminoglycosides, fluoroquinolones and beta-lactams. Genomic analysis revealed that the representative isolate also carried the 16S rRNA Methylase ArmA, which was detected for the first time in this species in Brazil.Conclusion. We report the rapid spread of an emerging CRAB clone responsible for causing a large outbreak in a hospital in Brazil, a country with predominance of other CRAB clones. Continuous and prospective surveillance is warranted to evaluate the impact of this clone in Brazilian hospital settings.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Acinetobacter Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Brazil/epidemiology , COVID-19/epidemiology , Clone Cells , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Pandemics , Prospective Studies , RNA, Ribosomal, 16S , SARS-CoV-2/genetics , beta-Lactamases/genetics
10.
APMIS ; 130(6): 330-337, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1784596

ABSTRACT

Acinetobacter baumannii is known to be an opportunistic pathogen frequently responsible for outbreaks in health-care facilities, particularly in Intensive Care Units (ICU). It can easily survive in the hospital setting for long periods and can be transmitted throughout the hospital in a variety of ways, explored in this review. It can also easily acquire antibiotic resistance determinants rendering several antibiotic drugs useless. In 2019, the US Centre for Disease Control (CDC) considered the organism as an urgent threat. The aim of this review was to raise the awareness of the medical community about the relevance of this pathogen and discuss how it may impact seriously the healthcare institutions particularly in the aftermath of the recent COVID-19 pandemic. PubMed was searched, and articles that met inclusion criteria were reviewed. We conclude by the need to raise awareness to this pathogen's relevance and to encourage the implementation of preventive measures in order to mitigate its consequences namely the triage of specific high-risk patients.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple, Bacterial , Humans , Intensive Care Units , Pandemics/prevention & control
11.
J Antimicrob Chemother ; 77(6): 1676-1684, 2022 05 29.
Article in English | MEDLINE | ID: covidwho-1774396

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, the burden of nosocomial infections caused by MDR pathogens has caused a shortage of polymyxins. Thus, we evaluated the in vitro synergism and antibiofilm activity of antimicrobial combinations and propose a test kit for synergism against carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: Fifty-six CRAB isolates were tested for synergy between meropenem, gentamicin and ampicillin/sulbactam. MICs were determined by broth microdilution. Synergism was tested using chequerboard analysis, followed by a time-kill curve. Additionally, minimum biofilm eradication concentration was determined and the antibiofilm activity of the combinations was evaluated by MTT assay and biomass reduction. A test kit was developed for routine laboratory testing to detect synergism. RESULTS: All CRAB isolates were resistant to gentamicin and ampicillin/sulbactam. Chequerboard synergism occurred against 75% of the isolates. Meropenem + ampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactam + gentamicin (64%) and meropenem + gentamicin (51%). All combinations presented only bacteriostatic activity and no bactericidal or antibiofilm effects. The routine laboratory test showed 100% accuracy compared with other in vitro assays. CONCLUSIONS: Our study demonstrates the potential role of antibiotic combinations against planktonic bacteria. In vitro synergism is possible and can be an alternative treatment for patients with CRAB infection during a polymyxin shortage.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Acinetobacter Infections/microbiology , Ampicillin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Biofilms , Drug Resistance, Multiple, Bacterial , Drug Synergism , Gentamicins/pharmacology , Humans , Meropenem/pharmacology , Microbial Sensitivity Tests , Pandemics , Polymyxins , Sulbactam/pharmacology
13.
Antimicrob Resist Infect Control ; 11(1): 12, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1643184

ABSTRACT

BACKGROUND: Despite the adoption of strict infection prevention and control measures, many hospitals have reported outbreaks of multidrug-resistant organisms (MDRO) during the Coronavirus 2019 (COVID-19) pandemic. Following an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) in our institution, we sought to systematically analyse characteristics of MDRO outbreaks in times of COVID-19, focussing on contributing factors and specific challenges in controlling these outbreaks. METHODS: We describe results of our own CRAB outbreak investigation and performed a systematic literature review for MDRO (including Candida auris) outbreaks which occurred during the COVID-19 pandemic (between December 2019 and March 2021). Search terms were related to pathogens/resistance mechanisms AND COVID-19. We summarized outbreak characteristics in a narrative synthesis and contrasted contributing factors with implemented control measures. RESULTS: The CRAB outbreak occurred in our intensive care units between September and December 2020 and comprised 10 patients (thereof seven with COVID-19) within two distinct genetic clusters (both ST2 carrying OXA-23). Both clusters presumably originated from COVID-19 patients transferred from the Balkans. Including our outbreak, we identified 17 reports, mostly caused by Candida auris (n = 6) or CRAB (n = 5), with an overall patient mortality of 35% (68/193). All outbreaks involved intensive care settings. Non-adherence to personal protective equipment (PPE) or hand hygiene (n = 11), PPE shortage (n = 8) and high antibiotic use (n = 8) were most commonly reported as contributing factors, followed by environmental contamination (n = 7), prolonged critical illness (n = 7) and lack of trained HCW (n = 7). Implemented measures mainly focussed on PPE/hand hygiene audits (n = 9), environmental cleaning/disinfection (n = 9) and enhanced patient screening (n = 8). Comparing potentially modifiable risk factors and control measures, we found the largest discrepancies in the areas of PPE shortage (risk factor in 8 studies, addressed in 2 studies) and patient overcrowding (risk factor in 5 studies, addressed in 0 studies). CONCLUSIONS: Reported MDRO outbreaks during the COVID-19 pandemic were most often caused by CRAB (including our outbreak) and C. auris. Inadequate PPE/hand hygiene adherence, PPE shortage, and high antibiotic use were the most commonly reported potentially modifiable factors contributing to the outbreaks. These findings should be considered for the prevention of MDRO outbreaks during future COVID-19 waves.


Subject(s)
Acinetobacter Infections/prevention & control , Acinetobacter baumannii , COVID-19/complications , COVID-19/epidemiology , Candida auris , Candidiasis/prevention & control , Pandemics , SARS-CoV-2 , Acinetobacter Infections/complications , Acinetobacter baumannii/drug effects , Aged , Candidiasis/complications , Carbapenems/pharmacology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple, Bacterial , Female , Humans , Infection Control/methods , Male , Middle Aged , Retrospective Studies , Switzerland/epidemiology
14.
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
15.
Eur J Clin Invest ; 51(12): e13687, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1443255

ABSTRACT

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.


Subject(s)
COVID-19/prevention & control , Cross Infection/epidemiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Infection Control , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter Infections/transmission , Acinetobacter baumannii , Aged , Cross Infection/microbiology , Cross Infection/transmission , Drug Resistance, Multiple, Bacterial , Enterobacter , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/transmission , Enterococcus faecium , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/transmission , Female , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/transmission , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/transmission , Hand Disinfection , Humans , Intensive Care Units , Interrupted Time Series Analysis , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella Infections/transmission , Klebsiella pneumoniae , Male , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Organizational Policy , Personal Protective Equipment , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas Infections/transmission , Pseudomonas aeruginosa , Retrospective Studies , SARS-CoV-2 , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/transmission , Staphylococcus aureus , Visitors to Patients
16.
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/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 , COVID-19 Drug Treatment
17.
J Hosp Infect ; 116: 78-86, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1404776

ABSTRACT

AIM: To describe the nosocomial transmission of Air, multidrug-resistant, Acinetobacter baumannii, nosocomial, COVID-19 Acinetobacter baumannii (MRAB) in an open-cubicle neurology ward with low ceiling height, where MRAB isolates collected from air, commonly shared items, non-reachable high-level surfaces and patients were analysed epidemiologically and genetically by whole-genome sequencing. This is the first study to understand the genetic relatedness of air, environmental and clinical isolates of MRAB in the outbreak setting. FINDINGS: Of 11 highly care-dependent patients with 363 MRAB colonization days during COVID-19 pandemic, 10 (90.9%) and nine (81.8%) had cutaneous and gastrointestinal colonization, respectively. Of 160 environmental and air samples, 31 (19.4%) were MRAB-positive. The proportion of MRAB-contaminated commonly shared items was significantly lower in cohort than in non-cohort patient care (0/10, 0% vs 12/18, 66.7%; P<0.001). Air dispersal of MRAB was consistently detected during but not before diaper change in the cohort cubicle by 25-min air sampling (4/4,100% vs 0/4, 0%; P=0.029). The settle plate method revealed MRAB in two samples during diaper change. The proportion of MRAB-contaminated exhaust air grills was significantly higher when the cohort cubicle was occupied by six MRAB patients than when fewer than six patients were cared for in the cubicle (5/9, 55.6% vs 0/18, 0%; P=0.002). The proportion of MRAB-contaminated non-reachable high-level surfaces was also significantly higher when there were three or more MRAB patients in the cohort cubicle (8/31, 25.8% vs 0/24, 0%; P=0.016). Whole-genome sequencing revealed clonality of air, environment, and patients' isolates, suggestive of air dispersal of MRAB. CONCLUSIONS: Our findings support the view that patient cohorting in enclosed cubicles with partitions and a closed door is preferred if single rooms are not available.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Cross Infection/epidemiology , Drug Resistance, Multiple, Bacterial , Humans , Microbial Sensitivity Tests , Pandemics , SARS-CoV-2
18.
BMC Infect Dis ; 21(1): 927, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1403227

ABSTRACT

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates. METHODS: From 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme. RESULTS: Eighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene. CONCLUSION: This study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.


Subject(s)
Acinetobacter Infections , COVID-19 , Coinfection , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Aged , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , COVID-19/epidemiology , COVID-19/microbiology , Carbapenems/pharmacology , Coinfection/epidemiology , Humans , Iran/epidemiology , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Pandemics , Tertiary Care Centers , beta-Lactamases/genetics
19.
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
20.
Infection ; 50(1): 83-92, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1281346

ABSTRACT

OBJECTIVES: Superinfections in patients hospitalized in intensive care unit (ICU) are an important and challenging complication, also in COVID-19. However, no definitive data are available about the role of multidrug-resistant Acinetobacter baumannii (MDR-AB) in COVID-19. METHODS: This was a single-center, cross-sectional study including patients with MDR-AB infections admitted to ICU with or without COVID-19, between January 2019 and January 2021. The primary objective of the study was to evaluate risk factor for MDR-AB infections in ICU patients hospitalized for COVID-19 or other etiology. The secondary endpoints were 30-days mortality in all study population and risk factors associated with development of bloodstream infection (BSI). RESULTS: During the study period 32 adults with COVID-19 were enrolled and compared with 115 patients admitted in the same ICU for other reasons. We observed a total of 114 deaths, with a survival rate of 29.3%: 18.8% in COVID-19 and 32.2% in control group. Relative risk for MDR-AB infection in COVID-19 showed that serum lactate levels mmol/l > 2, Acinetobacter baumannii colonization, BSI and steroid therapy were observed more frequently in COVID-19 patients. Cox regression analysis showed that serum lactate levels > 2 mmol/l, Acinetobacter baumannii colonization, BSI, and steroid therapy were associated with 30-days mortality. Finally, patients with COVID-19, white blood cells count > 11,000 mm3, serum lactate levels > 2 mmol/l, infections at time of ICU admission, Acinetobacter baumannii colonization, and steroid therapy were independently associated with development of BSI. CONCLUSIONS: Our data highlight the impact of BSI on outcome, the role of Acinetobacter baumannii colonization and the use of steroids on the risk to develop MDR-AB infections also during COVID-19.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross-Sectional Studies , Drug Resistance, Multiple, Bacterial , Humans , Intensive Care Units , Risk Factors , SARS-CoV-2
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