Prevalence of multidrug-resistant Gram-negative bacteria from blood cultures and rapid detection of beta-lactamase-encoding genes by multiplex PCR assay

Introduction This study aimed to determine the prevalence of multidrug-resistant Gram-negative bacteria (GNB) from blood cultures in a tertiary-care hospital and the multiplex PCR assay's ability to detect resistance genes. Methods A total of 388 GNB isolates obtained from hospitalized patients between November 2019 and November 2021 were included in the study. Antimicrobial susceptibility testing was done by VITEK 2 system and broth microdilution method. Beta-lactamase-encoding genes were detected by multiplex PCR assays, BioFire-Blood Culture Identification 2 (BCID2) panel (bioMerieux, France). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically with VITEK AST-GN71 card (bioMerieux, France). The isolates of GNB were classified into multidrug-resistant, extensively-drug-resistant, and pandrug-resistant categories, and their prevalence and distribution in different wards, including coronavirus diseases 2019 (COVID-19) intensive care units (ICU), were calculated. Results Results revealed that all isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were multidrug-resistant as well as 91.6% of Enterobacter cloacae, 80.6% of Proteus mirabilis, and 76.1% of Klebsiella pneumoniae, respectively. In fermentative bacteria, blaOXA-48-like (58.1%), blaNDM (16.1%), blaKPC (9.7%) and blaVIM (6.5%) genes were detected. More than half of Enterobacter cloacae (58.3%) and Klebsiella pneumoniae (53.7%) produced ESBLs. Among non-fermenters, the blaNDM gene was carried by 55% of Pseudomonas aeruginosa and 19.5% of Acinetobacter baumannii. In the COVID-19 ICU, Acinetobacter baumannii was the most common isolate (86.1%). Conclusions This study revealed high proportions of multidrug-resistant blood isolates and various underlying resistance genes in Gram-negative strains. The BCID2 panel seems to be helpful for the detection of the most prevalent resistance genes of fermentative bacteria.Copyright © GERMS 2022.

Evaluation of Microbiological Culture and Antibiogram of the Patient with Corneal Ulcer due to Exposure Keratitis in the Intensive Care Unit in Sina Farshchian Hospital (2019-2020)

Background: Since patients admitted to the intensive care unit have a compromised im-mune system and are more prone to infection than other patients, timely diagnosis and treatment of corneal ulcers among this group of patients can prevent vision loss. Therefore, it is necessary to treat eye infections and corneal ulcers promptly and economize prohibitive costs. Objective(s): Appropriate treatment with the most effective antibiotic before the answer is available to prevent corneal ulcer complications and blindness. Method(s): This study was conducted from November 2019 to November 2020 and after approval by the ethics committee of Hamedan University of Medical Sciences with the code of ethics: IR.UMSHA.REC.1398.716. First, the corneal secretions of 121 patients admitted to the intensive care unit of Sina Hospital are prepared by an ophthalmologist (after anesthetizing the cornea with tetra-caine drops and sterile swabs) and culture in four growth mediums (blood agar, chocolate agar, thio-glycolate, and EMB). Microbial cultures are examined after 48 hours and a fungal culture is examined one week later. Disc diffusions are placed in positive microbial cultures. Antibiotic susceptibility or resistance of the antibiogram was recorded. Other demographic data, including patients' age and sex, are extracted from ICU files. Also, test results and patient identifications are recorded in a checklist designed for this purpose. Result(s): Of all the antibiotics used against common bacteria, vancomycin (84%), colistin (80.43%), cefazolin (80%), and levofloxacin (60%) had the highest sensitivity and gentamicin (93.75%), ceftazidime (86.42%) Erythromycin (85%) had the highest resistance against isolated bacteria. Conclusion(s): The data obtained from this study showed that the most common microorganisms in the age group under the age of 30 years were Acinetobacter Baumannii, in the group of 30-60 years old was Klebsiella pneumonia, and age group over 61 years old was Staphylococcus aureus, and the most sensitive antibiotics in the age group under 30 years were vancomycin and levofloxacin and the age group30-60 were colistin and vancomycin and in the age group over 61 years were vancomycin and cefazolin.Copyright © 2023 Bentham Science Publishers.

Correlation Between the Suitability of Empirical and Definitive Therapies According to Culture Results with the Clinical Outcomes of Patients with Bacteremia Due to Carbapenem- Resistant Acinetobacter baumannii (CRAB) at Dr. Soetomo Tertiary Referral Hospital

Carbapenem administration is an important therapy for nosocomial infections due to MDRO, especially Acinetobacter baumannii. The global increase in carbapenem-resistant A. baumannii (CRAB) that causes this pathogen has significantly threatened public health due to the lack of adequate treatment options due to the very few currently available antimicrobial agents that actively fight CRAB. Antimicrobial resistance is a major negative impact of inappropriate antimicrobial prescribing. Ineffective empiric treatment (initial antibiotic regimen not sensitive to identified pathogens based on in vitro sensitivity test results) is associated with a higher rate of deaths compared to effective empiric treatment. In this study, we analyzed the correlation between the suitability of empiric and definitive antibiotics and the clinical outcomes of patients with bacteremia due to CRAB treated in the inpatient ward of Dr. Soetomo Tertiary Referral Hospital, Surabaya. There were 227 isolates of bacteremia due to CRAB, consisting of 156 carbapenem-resistant A. baumanni and 71 carbapenem-sensitive A. baumannii. There were 88 isolates that met the inclusion and exclusion criteria, and all of them were resistant to ceftriaxone, cefepime, and ciprofloxacin. A total of 29.5% of the isolates were sensitive to cotrimoxazole, 3.4% of the isolates were sensitive to tigecycline, and 2.3% of the isolates were sensitive to amikacin, levofloxacin, and cefoperazone sulbactam. Adequate empirical antibiotics and definitive antibiotics (sensitive based on culture sensitivity test) amounted to 12.5% and 27.3%, respectively. There is no significant correlation between the suitability of empiric and definitive therapies with the patients' clinical outcomes (death and length of stay).Copyright © 2022 Phcogj.Com.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India

Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists

Study of cases of Pseudomonas aeruginosa bacteria in patients with severe COVID-19

Pseudomonas aeruginosa can cause severe nosocomial infections and sepsis, especially in immunocompromised comorbid patients. The purpose of the study was to assess the frequency, clinical course, and the possibility of antimicrobial therapy for bloodstream infections caused by P. aeruginosa in patients with COVID-19. Material and methods. A retrospective single-center uncontrolled study was performed from October 1, 2020 to September 31, 2021 on the basis of a temporary infectious diseases hospital for patients with COVID-19 at the City Clinical Hospital No. 52, Moscow. During the analyzed period, 16 047 patients were admitted to the infectious diseases hospital. The study included 46 patients over 18 years of age with a diagnosis of COVID-19 confirmed by PCR RNA SARS-CoV-2 nasopharyngeal swab (U 07.1) and/or computed tomography (CT) of the lungs (U 07.2). Statistical data processing was carried out using the BioStat, 2009 program (AnalystSoft, USA). Results and discussion. P. aeruginosa has been isolated from the blood of 0.29% of patients with COVID-19. In the structure of bacteremia, P. aeruginosa accounted for 6.1%. In 87% of cases, pathogens were isolated from the blood of patients in the ICU. Most strains are classified as XDR phenotypes - 74% and MDR - 21.7%. The sensitivity of hospital strains of P. aeruginosa was: to colistin - 97%, to amikacin - 39.1%, meropenem - 32.6%. All patients had concomitant diseases: cardiovascular (60%), oncological (27.5%), diabetes mellitus (20%), obesity (22.5%) and others. In 47.5% of cases (19/40), the cause of bloodstream infections was ventilator-associated pneumonia. The mortality rate among patients with COVID-19 with P. aeruginosa bacteremia is 80%. Conclusion. The wide distribution of multidrug-resistant strains of P. aeruginosa limits the number of therapeutic options. In severe bloodstream infections caused by P. aeruginosa XDR, combined antibiotic therapy regimens with the inclusion of polymyxin B are advisable.Copyright © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

Septic Episodes Caused by Acinetobacter Baumannii, Klebsiella Pneumoniae and Pseudomonas Aeruginosa in a Tertiary Hospital in 2018-2020: Trends and Considerations

Intro: This study aimed at evaluating healthcare-related sepses caused by three multi-drug resistant Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa) in a tertiary hospital in 2018-2020, particularly concerning therapy, antibiotic-resistance and outcomes, by also comparing the pre-COVID (2018-2019) and COVID (2020) periods. Method(s): An observational, retrospective-cohort analysis was based on data related to patients admitted to the "SS. Antonio e Biagio e Cesare Arrigo" Hospital in Alessandria (Italy) between 2018 and 2020, with septic episodes from bacteria of the examined species, whose antibiogram proved resistance to >= 2 antimicrobial classes indicated by the European Centre for Disease Prevention and Control. Data were retrieved from patients' medical records and the hospital's computer-based application. Statistics involved Fisher-test comparisons and cumulative incidence analyses. Finding(s): Inclusion criteria led to enrolment of 174 patients. Comparison between 2020 and 2018-2019 showed a relative increase in A. baumannii cases, at the expense of the other species (p<0.0001), and an increasing resistance trend for K. pneumoniae, with a higher proportion of cases resistant to 3-4 classes of antimicrobials (p<0.0001). Overall, most patients were treated with carbapenems (72.4%), although the COVID period saw a significant rise in the use of polymyxins, particularly colistin (62.5% vs 36%, p=0.0005). In both periods, more than half patients recovered (53-57%) and around one third died (27-34%), but with different outcomes according to the infecting bacterium, generally better for P. aeruginosa (70% recovered at 60 days) and worse for A. baumannii (55% recovered). Discussion(s): The study confirmed the importance of the burden connected to healthcare-related sepses. Moreover, since the COVID outbreak, a trend could be spotted towards higher relative incidence of complex cases, caused by antimicrobial-resistant bacteria and thus requiring second-line therapy. Conclusion(s): These findings underline the importance of appropriate antimicrobial stewardship and infection control in view of the evolving healthcare needs.Copyright © 2023

Emergence of Colistin Resistance of Mdr Acinetobacter Spp. In Hospital Sungai Buloh during Covid-19 Pandemic

Intro: Acinetobacter calcoaceticus - A.baumannii complex is an opportunistic pathogen that has emerged as one of the multidrug resistant organism frequently associated with nosocomial infections especially causing ventilator- associated pneumonia (VAP). Colistin and Polymyxin B are currently being used as salvage therapy for treating MDR Acinetobacter spp. However, the emergence of resistance of colistin has been reported and treatment is further complicated by poor lung tissue penetration. Thus, we implied to explore on the prevalence of its resistance in our own facility, being the national COVID-19 referral hospital. Method(s): This is a cross-sectional retrospective analysis of MDR Acinetobacter spp. done for isolates of 2019 and 2021. Only clinically significant isolates were sent to Institute of Medical Research (IMR) for colistin susceptibility testing by broth microdilution. The identification of the isolates was performed by Bruker MALDI-ToF. CLSI breakpoints were used to determine susceptibility, applying the change of breakpoints interpretation in year 2020. Finding(s): In 2021, out of 203 isolates, 195 (96%) were Acinetobacter baumannii. Other spp. isolated were A. nosocomialis (6, 3%) and A. proteolyticus (2, 1%). Out of that, 107 (52.7%) were resistant with MIC of >4 ug/ml and 96 (47.3 %) were intermediate with MIC of <2 ug/ml. Pre-pandemic, resistance rates were compared with 2019 and this showed 47% were resistant with MIC of >4 ug/ml and 52% were susceptible with MIC <2 ug/ml. Clinical characteristics of patients were analysed;previous use of carbapenem, ventilation history, length of stay, and outcome (alive or deceased). Most of patients were severely ill with majority of admissions due to Category 4-5 COVID-19 and required ventilation in critical care unit. Previous carbapenem exposure was not significantly associated with colistin resistance (p=0.936). Conclusion(s): Emergence of colistin resistant MDR Acinetobacter spp. is alarming. Infection control measures are crucial and other therapeutic options need to be explored to improve quality of care.Copyright © 2023

Antibiotic resistance of Klebsiella pneumoniae against the background of the COVID-19 pandemic: experience of the multidisciplinary hospital

Frequency of bacterial co-infections among patients with COVID-19 is not high, and over-prescribing of antibiotics may contribute the selection of resistant strains of enterobacteria and gram-negative non-fermenting bacteria. The aim of the study was to assess the local features of antibiotic resistance of K. pneumoniae and its genetic mechanisms against background of the COVID-19 infection pandemic. Material and methods. There was selected 37 carbapenem-resistant K. pneumoniae strains isolated in 2016, 2017 and 2020 from hospitalized patients, including 15 strains, isolated from patients with COVID-19 infection. Minimal inhibitory concentrations (MICs) of meropenem and colistin were determined by broth microdilution method. Determination of MICs of eravacycline, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam was performed using Sensititre diagnostic system on EUMDROXF plates. Susceptibility to 11 combinations of 2 antibiotics was detected by modified method of multiply combination bactericidal testing. For 4 K. pneumoniae strains high-throughput sequencing was performed, followed with the subsequent search for determinants of antibiotic resistance and virulence, assessment of plasmid profiles. Results. All strains were resistant to meropenem (MIC50 32 mg/l, MIC90 128 mg/l) and produced KPC and OXA-48 carbapenemases. Strains isolated in 2016-2017 were susceptible to colistin (MIC <=2 mg/l), in 2020 only 26.7% of the strains retained their susceptibility (MIC50 64 mg/l, MIC90 256 mg/l). Susceptibility to combinations of two antibiotics with colistin included reduced from 84.6-100% in 2016-2017 till 26.6-66.7% in 2020. The strains isolated in 2020 retained their susceptibility to ceftazidime/avibactam (MIC <=1 mg/l). 5 strains resistant to cefiderocol with a MIC 8 mg/l were identified. Strains 2564 and 3125 isolated in 2020 from sputum of patients with COVID-19 infection belonged to different sequence-types (ST12 and ST23) and contained the blaOXA-48 carbapenemase gene, additionally strain 2564 contained the blaKPC-27carbapenemase gene. Resistance to colistin was caused by inactivation of the mgrB genes due to insertion of IS1 and IS5-like transposons. Conclusion. The performed genetic studies demonstrate a diversity of mechanisms of antibiotic resistance in K. pneumoniae leading to the formation of resistance including to antibiotics that haven't been used in Belarus till now.Copyright © 2021 Geotar Media Publishing Group. All Rights Reserved.

Carbapenem Heteroresistance Mdr Enterobacter Cloacae in a Post-Covid-19 Obese Patient: An Antibiotic Susceptibility Conversion

Intro: Background: Obesity affects drug delivery and clearance owing to the patient's altered pharmacokinetics. In treating infection, this presents as a conundrum antibiotic dosing to achieve optimal antibiotic concentration at the same time avoiding drug toxicity. Particularly in the case of antimicrobial agents, underdosing may lead to antibiotic resistance. Method(s): Case description: We report a case of a morbidly obese (BMI=58) COVID-19 patient infected with carbapenem-sensitive multi-drug resistant (MDR) Enterobacter cloacae bacteremia, treated with ertapenem 1g twice daily and intravenous polymyxin E 9MU stat and 4.5MU twice daily for MDR Acinetobacter baumanii co-infection. He had infected huge grade IV sacral sore one month later in which intraoperative tissue culture grew phenotypically heterogeneous colonies of MDR Enterobacter cloacae with carbapenem-sensitive and carbapenem-intermediate-resistant non-carbapenemase producing colonies. He responded well clinically and biochemically with an increased dose of intravenous ciprofloxacin 800mg BD based on his actual body weight. He was discharged with oral ciprofloxacin 750mg BD for a total of six weeks. Finding(s): Discussion: Obesity is a public health crisis that has reached epidemic proportions. Obesity affects the volume distribution and renal clearance of many drugs including antibiotics. Obese patients are shown to have higher drug clearance than normal-weighted patients resulting in inadequate systemic exposure. This puts patients at risk of developing antibiotic resistant organisms. Our patient, weighing 162kg was given three different beta-lactam antibiotics to treat his infection including ertapenem in which a standard adult dose was given without body weight consideration. Possible underdosing contributed to the conversion of carbapenem susceptibility from sensitive to resistant strain. Conclusion(s): Obese individuals may need a larger ertapenem dose than their non-obese counterparts. Clinical and laboratory assessment may help in monitoring treatment response in this group of patients.Copyright © 2023

Ventilator-associated pneumonia (VAP) and pleural empyema caused by multidrug-resistant Acinetobacter baumannii in HIV and COVID 19 infected patient: A case report

We analyzed the case of a 49-year-old woman with HIV infection off-therapy with poor viro-immunological compensation, not vaccinated for SARS-COV-2, hospitalized for lobar pneumonia and severe COVID19-related respiratory failure in intensive care unit (ICU). The hospitalization was complicated by bacteraemic ventilator-associated pneumonia (VAP) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) isolated on pleural fluid culture, treated with colistin and cefiderocol for about 3 weeks. The molecular research of MDR-AB on transtracheal aspirate was negative following this therapy. The aim is to show the safety, efficacy and tolerability of colistin-based combination therapy with cefiderocol for Acinetobacter baumannii infection in HIV-infected patient. © 2023 The Authors

Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Isolation of Carbapenem and Colistin Resistant Gram-Negative Bacteria Colonizing Immunocompromised SARS-CoV-2 Patients Admitted to Some Libyan Hospitals.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating effect, globally. We describe, for the first time, the occurrence of carbapenem-resistant bacteria colonizing SARS-CoV-2 patients who developed hospital-associated infections with carbapenemase-producing, Gram-negative bacteria at some isolation centers of SARS-CoV-2 in the eastern part of Libya. In total, at first, 109 samples were collected from 43 patients, with the samples being recovered from oral (n = 35), nasal (n = 45), and rectal (n = 29) cavities. Strain identification was performed via matrix assisted laser desorption ionization-time of flight (MALDI-TOF). Antibiotic susceptibility testing was carried out on Mueller-Hinton agar, using the standard disk diffusion method. MIC determination was confirmed via E-TEST and microdilution standard methods. A molecular study was carried out to characterize the carbapenem and colistin resistance in Gram-negative bacterial strains. All of the positive results were confirmed via sequencing. Klebsiella pneumoniae (n = 32), Citrobacter freundii (n = 21), Escherichia coli (n = 7), and Acinetobacter baumannii (n = 21) were the predominant isolated bacteria. Gram-negative isolates were multidrug-resistant and carried different carbapenem resistance-associated genes, including NDM-1 (56/119; 47.05%), OXA-48 (15/119; 12.60%), OXA-23 (19/119; 15.96%), VIM (10/119; 8.40%), and the colistin resistance mobile gene mcr-1 (4/119; 3.36%). The overuse of antimicrobials, particularly carbapenem antibiotics, during the SARS-CoV-2 pandemic has led to the emergence of multidrug-resistant bacteria, mainly K. pneumoniae, A. baumannii, and colistin-resistant E. coli strains. Increased surveillance as well as the rational use of carbapenem antibiotics and, recently, colistin are required to reduce the propagation of multidrug-resistant strains and to optimally maintain the efficacy of these antibiotics. IMPORTANCE In this work, we describe, for the first time, the occurrence of carbapenem-resistant bacteria colonizing COVID-19 patients who developed hospital-associated infections with carbapenemase-producing, Gram-negative bacteria at some isolation centers of COVID-19 in the eastern part of Libya. Our results confirmed that the overuse of antimicrobials, such as carbapenem antibiotics, during the COVID-19 pandemic has led to the emergence of multidrug-resistant bacteria, mainly K. pneumoniae and A. baumannii, as well as colistin resistance.

Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

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.

Secondary bacterial infection caused by ST16 NDM-1 and OXA-48-producing colistin and carbapenem-resistant Klebsiella pneumoniae treated with tigecycline in a pregnant woman with COVID-19.

During the COVID-19 pandemic, the rapid emergence of carbapenem and colistin-resistant Klebsiella pneumoniae has resulted in an alarming situation worldwide. We aimed to describe secondary infections and antimicrobial use, in a pregnant woman admitted to hospital with COVID-19. A 28-year-old pregnant woman was admitted to the hospital due to COVID-19. According to the clinical conditions, the patient was transferred to the ICU on the second day. She was empirically treated with ampicillin and clindamycin. Mechanical ventilation through an endotracheal tube was started on the 10th day. During her hospitalization in the ICU, she was infected with ESBL-producing K. pneumonia, Enterobacter spp and carbapenemase-producing colistin-resistant Klebsiella pneumoniae isolates. Finally, the patient was treated with tigecycline monotherapy that was associated with ventilator-associated pneumonia clearance. Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. Treatment of infections caused by carbapenemase-producing colistin-resistant K. pneumoniae isolates is challenging, with limited antimicrobials available in Iran. In order to prevent the spread of extensively drug-resistant bacteria, infection control programs must be implemented more seriously.

Synergistic Activity of Colistin in Combination with Clofoctol against Colistin Resistant Gram-Negative Pathogens.

Colistin is a bactericidal antibiotic identified decades ago which is active against a number of Gram-negative pathogens. After early elimination from clinical use due to toxicity issues, colistin has been reintroduced as a last-resort treatment for antibiotic-resistant Gram-negative infections lacking other therapeutic options. Inevitably, colistin resistance has emerged among clinical isolates, making the development of colistin adjuvants extremely beneficial. Clofoctol is a synthetic antibiotic active against Gram-positive bacteria, with low toxicity and high tropism for the airways. Interestingly, clofoctol has been found to have multiple biological activities and has been proposed for the treatment of several obstructive lung diseases, including asthma, lung cancer, and SARS-CoV-2 infection. In this study, the activity of clofoctol as a colistin adjuvant was investigated in Gram-negative lung pathogens that are critical for the high prevalence of multidrug-resistant isolates, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Clofoctol potentiated the bactericidal effect of colistin in all tested strains and reduced colistin MICs below the susceptibility breakpoint in nearly all colistin-resistant strains. Overall, this observation supports the development of inhaled clofoctol-colistin formulations for the treatment of difficult-to-treat airway infections caused by Gram-negative pathogens. IMPORTANCE Colistin is used as a last-resort antibiotic against extensively drug-resistant Gram-negative pathogens. However, colistin resistance is on the rise. Clofoctol is an antibiotic used against Gram-positive bacteria, with low toxicity and high penetration and storage in the airways. Here, a strong synergistic activity of the colistin-clofoctol combination against colistin-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii isolates is reported, supporting the development of clofoctol-colistin formulations for the therapy of difficult-to-treat airways infections caused by these Gram-negative pathogens.

The under investigated facet of the COVID-19 pandemic: Molecular analysis of secondary bacterial infections at a COVID dedicated intensive care unit within a tertiary care center in Lebanon.

Background: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Secondary bacterial infections are associated with unfavorable outcomes in respiratory viral infections. This study aimed at determining the prevalence of secondary bacterial infections in COVID-19 patients admitted at a tertiary medical center in Lebanon. Methodology: From May till November, 2020, a total of 26 Gram-negative isolates were recovered from 16 patients during the course of their COVID-19 infection with Escherichia coli being the most prevalent. The isolates were assessed for their antimicrobial susceptibility by broth microdilution against 19 antimicrobial agents from different classes. Whole genome sequencing of 13 isolates allowed the mining of antimicrobial resistance (AMR) determinants as well as mobile genetic elements and sequence types (ST). Finally, broth microdilution with three different efflux pump inhibitors [theobromine, conessine and PheArg-ß-naphthylamide (PAßN)] was done. Results: Antimicrobial susceptibility testing showed that out of the 26 Gram-negative isolates, 1 (4%) was extensively drug resistant and 14 (54%) were multi-drug resistant (MDR). Whole genome sequencing results revealed a plethora of AMR determinants among the 13 sequenced isolates. Moreover, the 9 Enterobacterales and 4 Pseudomonas aeruginosa sequenced isolates belonged to 9 and 2 different ST, respectively. Using a variety of efflux pump inhibitors we demonstrated that only PAßN had a significant effect when combined with levofloxacin, and the latter regained its activity against two P. aeruginosa isolates. Conclusion: The identification of carbapenem and colistin resistant Gram-negative bacilli causing secondary bacterial infections in critical patients diagnosed with COVID-19 should be of high concern. Additionally, it is crucial to monitor and track AMR, post-COVID pandemic, in order to better understand the effect of this disease on AMR exacerbation.

Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study.

Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020-September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.

Emergence of high colistin resistance in carbapenem resistant Acinetobacter baumannii in Pakistan and its potential management through immunomodulatory effect of an extract from Saussurea lappa.

Carbapenem resistant Acinetobacter baumannii has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant A. baumannii infections. Therefore, resistance to colistin is considered as a serious medical threat. The purpose of this study was to assess the current status of colistin resistance in Pakistan, a country where carbapenem resistant A. bumannii infections are endemic, to understand the impact of colistin resistance on virulence in mice and to assess alternative strategies to treat such infections. Out of 150 isolates collected from five hospitals in Pakistan during 2019-20, 84% were carbapenem resistant and 7.3% were additionally resistant to colistin. There were two isolates resistant to all tested antibiotics and 83% of colistin resistant isolates were susceptible to only tetracycline family drugs doxycycline and minocycline. Doxycycline exhibited a synergetic bactericidal effect with colistin even in colistin resistant isolates. Exposure of A. baumannii 17978 to sub inhibitory concentrations of colistin identified novel point mutations associated with colistin resistance. Colistin tolerance acquired independent of mutations in lpxA, lpxB, lpxC, lpxD, and pmrAB supressed the proinflammatory immune response in epithelial cells and the virulence in a mouse infection model. Moreover, the oral administration of water extract of Saussuria lappa, although not showing antimicrobial activity against A. baumannii in vitro, lowered the number of colonizing bacteria in liver, spleen and lung of the mouse model and also lowered the levels of neutrophils and interleukin 8 in mice. Our findings suggest that the S. lappa extract exhibits an immunomodulatory effect with potential to reduce and cure systemic infections by both opaque and translucent colony variants of A. baumannii.

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.