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1.
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
2.
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
3.
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
4.
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
5.
Emerg Microbes Infect ; 10(1): 612-618, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1127286

ABSTRACT

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 109 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.


Subject(s)
Acinetobacter Infections/etiology , Acinetobacter Infections/therapy , Acinetobacter baumannii/virology , Bacteriophages/physiology , COVID-19/complications , Coinfection/therapy , Phage Therapy , Podoviridae/physiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/physiology , Aged , Aged, 80 and over , COVID-19/virology , Coinfection/microbiology , Female , Humans , Male , SARS-CoV-2/physiology
6.
MMWR Morb Mortal Wkly Rep ; 69(48): 1827-1831, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-1000679

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Carbapenems/pharmacology , Cross Infection/epidemiology , Drug Resistance, Bacterial , COVID-19/epidemiology , COVID-19/therapy , Female , Hospitals , Humans , Male , Middle Aged , New Jersey/epidemiology , Patient Admission/statistics & numerical data
7.
BMC Infect Dis ; 20(1): 646, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-740368

ABSTRACT

BACKGROUND: COVID-19 is known as a new viral infection. Viral-bacterial co-infections are one of the biggest medical concerns, resulting in increased mortality rates. To date, few studies have investigated bacterial superinfections in COVID-19 patients. Hence, we designed the current study on COVID-19 patients admitted to ICUs. METHODS: Nineteen patients admitted to our ICUs were enrolled in this study. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed. Endotracheal aspirate samples were also collected and cultured on different media to support the growth of the bacteria. After incubation, formed colonies on the media were identified using Gram staining and other biochemical tests. Antimicrobial susceptibility testing was carried out based on the CLSI recommendations. RESULTS: Of nineteen COVID-19 patients, 11 (58%) patients were male and 8 (42%) were female, with a mean age of ~ 67 years old. The average ICU length of stay was ~ 15 days and at the end of the study, 18 cases (95%) expired and only was 1 case (5%) discharged. In total, all patients were found positive for bacterial infections, including seventeen Acinetobacter baumannii (90%) and two Staphylococcus aureus (10%) strains. There was no difference in the bacteria species detected in any of the sampling points. Seventeen of 17 strains of Acinetobacter baumannii were resistant to the evaluated antibiotics. No metallo-beta-lactamases -producing Acinetobacter baumannii strain was found. One of the Staphylococcus aureus isolates was detected as methicillin-resistant Staphylococcus aureus and isolated from the patient who died, while another Staphylococcus aureus strain was susceptible to tested drugs and identified as methicillin-sensitive Staphylococcus aureus. CONCLUSIONS: Our findings emphasize the concern of superinfection in COVID-19 patients due to Acinetobacter baumannii and Staphylococcus aureus. Consequently, it is important to pay attention to bacterial co-infections in critical patients positive for COVID-19.


Subject(s)
Acinetobacter Infections/complications , Acinetobacter baumannii/isolation & purification , Betacoronavirus/physiology , Coinfection/epidemiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Staphylococcal Infections/complications , Staphylococcus aureus/isolation & purification , Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diabetes Complications/epidemiology , Female , Heart Diseases/complications , Humans , Hypertension/complications , Intensive Care Units , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Respiratory System/microbiology , SARS-CoV-2 , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects
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