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1.
Germs ; 12(4):434-443, 2022.
Article in English | EMBASE | ID: covidwho-20245447

ABSTRACT

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.

2.
Current Drug Therapy ; 18(3):211-217, 2023.
Article in English | EMBASE | ID: covidwho-20243552

ABSTRACT

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.

3.
Pharmaceutical and Biomedical Research ; 6(SpecialIssue1):17-26, 2020.
Article in English | EMBASE | ID: covidwho-20241664

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first discovery in December 2019, in Wuhan, China. Limited data are available on COVID-19 effects during pregnancy;however, information on diseases associated with other highly pathogenic coronaviruses (i.e. Severe Acute Respiratory Syndrome [SARS] and the Middle East respiratory syndrome [MERS]) may provide insight into the effects of COVID-19 during pregnancy. Coronaviruses cause illnesses ranging from the common cold to severe respiratory disease and death. The data indicate an average of 5 days incubation period (range: 2-14 days). The average age range of the hospitalized patients was 49-56 years, and a third to half of them have an underlying illness. Children were rarely mentioned. Within hospitalized cases, men were more frequent (54%-73%). Fever, cough, myalgia, vomiting, and diarrhea are common symptoms. This review aims at giving an in-depth understanding of COVID-19 by comparing its effects with SARS and MERS to evaluate its severity in pregnant women1. The results of varied studies show that COVID-19 affects pregnant women seriously and there is an alarming need to look into this aspect to prevent its harmful effects on the fetus.Copyright © 2020

4.
Asian Journal of Pharmaceutical and Clinical Research ; 16(5):4-6, 2023.
Article in English | EMBASE | ID: covidwho-20241487

ABSTRACT

Burkholderia pseudomallei is soil saprophytic Gram-negative bacilli that cause a fatal disease called melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, and musculoskeletal and central nervous systems. Here, we report rare forms of pulmonary, cerebral, and splenic abscess case series of melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants, and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water;person-to-person transmission is very rare. Melioidosis cases are primarily found in the rainfall season and are usually associated with risk factors such as diabetes, alcoholism, and chronic renal diseases. However, 20-26% of cases were not associated with predisposing conditions. The identification is based on colony morphology, Gram stain, antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect B. pseudomallei. There are two phases, the intensive and eradication phases, in managing melioidosis. In the intensive phase, ceftazidime for 2 weeks showed efficacy in almost 50% of cases, and the eradication phase treatment with co-trimoxazole and doxycycline or amoxicillin/clavulanic acid for 3-6 months showed an excellent response. The improper clinical diagnosis and management of B. pseudomallei can lead to complications. Hence, early diagnosis with microbiological approaches such as culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient quickly without mortality.Copyright © 2023 The Authors.

5.
Pharmacognosy Journal ; 14(6 Supplement):942-947, 2022.
Article in English | EMBASE | ID: covidwho-20240161

ABSTRACT

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.

6.
Ankara Universitesi Eczacilik Fakultesi Dergisi ; 47(1):185-195, 2023.
Article in Turkish | EMBASE | ID: covidwho-20234971

ABSTRACT

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material(s) and Method(s): In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially.Copyright © 2023 University of Ankara. All rights reserved.

7.
ERS Monograph ; 2022(98):241-252, 2022.
Article in English | EMBASE | ID: covidwho-20232317

ABSTRACT

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

8.
Braz. J. Pharm. Sci. (Online) ; 58: e20484, 2022. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-20237571

ABSTRACT

Abstract To evaluate the antibiotic susceptibility patterns in URTIs reporting to tertiary hospitals of Lahore. A cross-sectional study employing 259 culture sensitivity reports obtained from tertiary care hospitals of Lahore. Using SPSS, descriptive statistics were used to estimate frequencies and percentages. In URTIs, S. aureus (5%) was the frequent gram-positive isolate followed by MRSA (1.5%) and MSSA (1.5%), while P. aeruginosa (15.8%) was the prevalent gram-negative isolate followed by Klebsiella (13.1%) and E. coli (6.9%). Against P. aeruginosa, ceftazidime (7.7%), cefuroxime/ceftriaxone (4.6%), amoxicillin (4.3%) and ciprofloxacin (4.2%), were tested resistant, while imipenem (11.2%), ciprofloxacin (9.2%), amikacin (9.2%), meropenem/ levofloxacin/gentamicin (8.1%) and piptaz (6.9%) were found sensitive. Against Klebsiella, carbepenems (7.3%), amikacin (6.5%), ciprofloxacin (5.4%) and gentamicin (5%) were tested sensitive, whereas, ceftazidime (8.5%), ceftriaxone (5.8%), cefaclor (5.5%), ampicillin (4.6%), co-amoxiclave (4.2%) and ciftazidime/ciprofloxacin (3.8%) were found resistant. Overall, imipenem (35%), meropenem (30.8%) and amikacin (31.9%) were the three most sensitive antibiotics, while ceftazidime (25.4%), ceftriaxone (19.2%) and ampicillin (18.5%) were the three most resistant antibiotics. Data suggested that P.aeruginosa and Klebsiella, were the most frequent bacterial isolates in URTIs of Lahore. These isolates were resistant to ampicillin, cefuroxime and ceftazidime, but were sensitive to carbapenem and aminoglycosides


Subject(s)
Patients/classification , Respiratory Tract Infections/pathology , Anti-Bacterial Agents/analysis , Pakistan/ethnology , Pseudomonas aeruginosa/isolation & purification , Ciprofloxacin , Methicillin-Resistant Staphylococcus aureus/classification
9.
China Tropical Medicine ; 23(3):283-288, 2023.
Article in Chinese | GIM | ID: covidwho-2327294

ABSTRACT

Objective: To analyze the distribution and drug resistance of pathogenic bacteria in blood culture specimens of patients with bloodstream infections before and after COVID-19 (2018-2019 and 2020-2021), and to provide scientific basis and reference for rational treatment and effective control of bloodstream infections in the post-epidemic period. Methods: Blood culture specimens were collected from patients in Zhongnan Hospital of Wuhan University in the two years before and after the COVID-19 outbreak (2018-2021). The Automated Blood Culture Systems were used to perform blood culture on blood specimens sent for clinical inspection, and the Vitek MS automatic bacterial identification mass spectrometer was used for strain identification and the Vitek 2 automatic bacterial drug susceptibility analyzer was used for drug susceptibility testing and drug resistance analysis. Results: Blood culture specimens were performed on 28 736 patients with suspected bloodstream infection submitted for inspection from January 2018 to December 2019, and a total of 2 181 strains of pathogenic bacteria were detected after removing duplicate strains, with a positive rate of 7.69%, including 1 046 strains of Gram-negative bacteria, accounting for 47.96%. From January 2020 to December 2021, blood culture specimens from 26 083 patients with suspected bloodstream infection were submitted for inspection, and a total of 2 111 strains of pathogenic bacteria were detected after excluding duplicate strains, with a positive rate of 8.09%, including 1 000 strains of Gram-negative bacteria accounted for 47.37%. The drug resistance of Klebsiella pneumoniae was relatively serious, and the sensitivity rate to ertapenem, polymyxin B and tigecycline was more than 90%. The main non-fermentative bacteria Acinetobacter baumannii was more than 50% sensitive to piperacillin/tazobactam, amikacin and polymyxin B. The sensitivity rates of Pseudomonas aeruginosa to piperacillin/tazobactam, ceftazidime, cefepime, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, piperacillin and meropenem were more than 50%. Conclusions: In the two years before and after COVID-19, there are many types of pathogenic bacteria in bloodstream infection, but the distribution do not differ significantly. The pathogens of bloodstream infection are mainly distributed in ICU, hepatobiliary research institute, and nephrology department. Among them, Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii are the main ones, and different pathogens showed great differences in drug resistance.

10.
Infectious Diseases: News, Opinions, Training ; 10(3):15-22, 2021.
Article in Russian | EMBASE | ID: covidwho-2326598

ABSTRACT

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.

11.
Critical Care Conference: 42nd International Symposium on Intensive Care and Emergency Medicine Brussels Belgium ; 27(Supplement 1), 2023.
Article in English | EMBASE | ID: covidwho-2319092

ABSTRACT

Introduction: Evaluation of prognostic factors in patients with ventilator- associated pneumonia (VAP) due to P. aeruginosa. The effectiveness of novel antipseudomonal antibiotics was reviewed. Method(s): Retrospective, single-center cohort analysis between April 2018 and June 2022. Data were obtained from the ENVIN-HELICS and electronic medical records. Demographic variables, underlying diseases and diagnosis to admission were registered. We considered each treatment appropriate according to Tamma PD et al. [1] criteria. We registered ventilator-associated tracheobronchitis (VAT) and pneumonia (VAP) episodes together with the recurrency of the infection. Result(s): From 61 patients included, 77% were admitted for ARDS due to COVID-19. The mean APACHE-II was 14.3 +/- 6.6. 7 patients required ECMO and 4 required RRT. The median length of stay in the ICU was 52 (ICR 36-84) days. 91 respiratory infections were recorded: 60 VAP and 31 VAT. On the first episode, carbapenem-resistance to meropenem was 40%;rising up to 58% on the second one. 6 patients developed a third episode (VAT) with a 100% of carbapenem- resistance. 13 (14%) respiratory infections showed resistance to the novel beta-lactamase inhibitor cephalosporins (8 to ceftalozanetazobactam and 5 to ceftazidime-avibactam). No resistance to cefiderocol was detected. During ICU stay, 21 patients (34%) developed secondary bacteremia from other foci and 7 (11%) invasive mycoses. Overall mortality was 49.2%. On the univariate analysis we found statistical significant relationships between mortality and COVID-19 admission, SOFA >= 7 points on the first VAP or the development of secondary bacteremia (Table 1). Conclusion(s): COVID-19 admission, SOFA >= 7 points on the first VAP or other secondary bacteremia were associated with mortality. The 14.3% of respiratory infections were resistant to the new beta-lactamase inhibitor cephalosporins. No resistance to cefiderocol was detected.

12.
Anti-Infective Agents ; 21(2):1-17, 2023.
Article in English | EMBASE | ID: covidwho-2315951

ABSTRACT

Antibiotics play an essential role in antimicrobial therapy. Among all the medications in children, the most commonly prescribed therapy is antibiotics and is currently the indispensable means to cure transmissible diseases. Several categories of antibiotics have been introduced into clinical practice to treat microbial infections. Reducing the unnecessary use of antibiotics is a global need and priority. This article aims to provide better knowledge and understanding of the impact of the early use of antibiotics. This article highlights the proper use of antibiotics in chil-dren, detailing how early and inappropriate use of antibiotics affect the gut microbiome during normal body development and consequently affect the metabolism due to diabetes mellitus, obe-sity, and recurrence of infections, such as UTI. Several new antibiotics in their development stage, newly marketed antibiotics, and some recalled and withdrawn from the market are also briefly discussed in this article. This study will help future researchers in exploring the latest information about antibiotics used in paediatrics.Copyright © 2023 Bentham Science Publishers.

13.
Flora ; 28(1):94-103, 2023.
Article in English | EMBASE | ID: covidwho-2293633

ABSTRACT

Introduction: It is important to know the risk factors for death in reducing mortality in patients with Stenotrophomonas maltophilia infections. The purpose of this study was to examine the risk factors associated with mortality in hospitalized patients with S. maltophilia infections. Material(s) and Method(s): Patients with S. maltophilia infections aged 18 years and older who were hospitalized in Haseki Research and Training between January 1, 2017, and April 30, 2022, were included in the study. The patients were divided into two groups, non-survivors and survivors, and the clinical features and laboratory parameters of the groups were compared. Mortality risk factors were analyzed by logistic and Cox regression analyses. Result(s): A total of 75 patients with S. maltophilia infections were included. The mortality rate was 38.6% (n= 29). Advanced age (OR= 1.05, 95% CI= 1.012-1.085, p= 0.009), COVID-19 pneumonia (OR= 9.52, 95% CI= 1.255-72.223, p= 0.029), and presence of central venous catheter (CVC) (OR= 18.25, 95% CI= 2.187-152.323, p= 0.007) were risk factors for death. Conclusion(s): Physicians should be aware of the potential risk of S. maltophilia infections for mortality, particularly in patients with predefined risk factors such as advanced age, the presence of CVC, and COVID-19. Performing CVC care in accordance with infection prevention and control measures and timely removal of CVC may be beneficial in reducing deaths due to S. maltophilia infection.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.

14.
Pharmacia ; 70(1):225-231, 2023.
Article in English | EMBASE | ID: covidwho-2290506

ABSTRACT

Plasmid-mediated quinolone resistance (PMQR) genes confer low resistance to Fluoroquinolones (FQs). This study aims to detect five PMQR genes among FQs-resistant Klebsiella pneumoniae isolated from various clinical specimens. Out of 120 K. pneumoniae isolates, 68 FQs-resistance K. pneumoniae were included in a molecular study. Standard microbiological tests were used for identification and antimicrobial susceptibility. For the detection of PMQR genes, conventional polymerase chain reaction was used. A molecular study revealed that (73.5%) of samples harbored PMQR genes, and among them, 58% were co-carriages of PMQR gene variants. Aac (6')-Ib-cr gene was predominant (47.1%) among samples, and qepA had the lowest percentage (11.8%), qnr genes were (32.4%) (29.4%) (20.6%) qnrS, qnrB, and qnrA respectively. Overall, high percentages of PMQR genes were detected, and almost all of samples were phenotypically resistant to ciprofloxacin. As well, there was a significant statistical relationship between phenotypically ESBL-producers and qnrB and qepA genes.Copyright © Abdulkareem MM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

15.
Antibiotiki i Khimioterapiya ; 67(11-12):16-21, 2022.
Article in Russian | EMBASE | ID: covidwho-2297553

ABSTRACT

Background. The spread of extensive drug-resistance among gram-negative bacteria calls for the search for antimicrobics with new mechanisms of actions. The aim was to assess susceptibility of extensively drug-resistant K.pneumoniae strains to cefiderocol and other new inhibitor-protected beta-lactams, and to determine genetic mechanisms of antibiotic resistance. Methods. This study included 30 extensively drug-resistant K.pneumoniae strains collected in 2016-2021 from 4 regions of Belarus. Carbapenemase genes were detected by real-time PCR. Minimum inhibitory concentrations (MICs) for cefiderocol and other new antibiotics were assessed by microdilution method using the Sensititre system. Whole genome sequencing was performed for 2 resistant and 3 cefiderocol-susceptible strains. Genome assemblies and annotation were performed using UGENE v. 37.0 software. Nucleotide sequences were translated using CLC Sequence Viewer v. 8.0 (QIAGEN) package. The PROVEAN software was used to assess amino asides substitutions and their influence on the functional activity of proteins. Results. KPC carbapenemase-producers were 4 strains, OXA-48 - 17, KPC+OXA-48 - 1, NDM - 7, OXA-48 + NDM - 1. All KPC-producers were susceptible to imipenem/relebactam and meropenem/vaborbactam. Resistance to ceftazidime-avibactam was noted in all NDM producers and OXA-48+NDM co-producer. The study has identified 9 cefiderocol-resistant strains. These were NDM and OXA-48-producers isolated from hospitalized patients with COVID-19 infection from 3 regions of Belarus. Resistant strains had functionally significant nonsynonymous substitutions in the genes of TonB-dependent receptors for catecholate siderophores FepA (F472V, P64S) and Fiu (T92S). Conclusion. The study has shown high efficacy of new inhibitor-protected carbapenems and cephalosporins against certain types of carbapenemase-producers. Strains with mutational resistance to cefiderocol, an antibiotic not previously used in Belarus, have been identified.Copyright © Team of Authors, 2022.

16.
Antibiotics (Basel) ; 12(4)2023 Apr 01.
Article in English | MEDLINE | ID: covidwho-2297567

ABSTRACT

In light of rising antimicrobial resistance and a decreasing number of antibiotics with novel modes of action, it is of utmost importance to accelerate development of novel treatment options. One aspect of acceleration is to understand pharmacokinetics (PK) and pharmacodynamics (PD) of drugs and to assess the probability of target attainment (PTA). Several in vitro and in vivo methods are deployed to determine these parameters, such as time-kill-curves, hollow-fiber infection models or animal models. However, to date the use of in silico methods to predict PK/PD and PTA is increasing. Since there is not just one way to perform the in silico analysis, we embarked on reviewing for which indications and how PK and PK/PD models as well as PTA analysis has been used to contribute to the understanding of the PK and PD of a drug. Therefore, we examined four recent examples in more detail, namely ceftazidime-avibactam, omadacycline, gepotidacin and zoliflodacin as well as cefiderocol. Whereas the first two compound classes mainly relied on the 'classical' development path and PK/PD was only deployed after approval, cefiderocol highly profited from in silico techniques that led to its approval. Finally, this review shall highlight current developments and possibilities to accelerate drug development, especially for anti-infectives.

17.
Ankara Universitesi Eczacilik Fakultesi Dergisi ; 47(1):185-195, 2023.
Article in Turkish | EMBASE | ID: covidwho-2257390

ABSTRACT

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material(s) and Method(s): In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially.Copyright © 2023 University of Ankara. All rights reserved.

18.
Ankara Universitesi Eczacilik Fakultesi Dergisi ; 47(1):185-195, 2023.
Article in Turkish | EMBASE | ID: covidwho-2257389

ABSTRACT

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material(s) and Method(s): In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially.Copyright © 2023 University of Ankara. All rights reserved.

19.
Ankara Universitesi Eczacilik Fakultesi Dergisi ; 47(1):185-195, 2023.
Article in Turkish | Scopus | ID: covidwho-2257388

ABSTRACT

Objective: In recent years, the rapid spread of resistance caused by the production of extended-spectrum beta-lactamase (ESBL) among bacteria has increased the importance of K. pneumoniae bacteria. Regular monitoring of antibiotic resistance rates of bacteria is very important for the treatment of infections and new treatment methods that can be developed. In the study, it was aimed to determine the antibiotic resistance profiles and ESBL positivity rates of K. pneumoniae isolated from patients who applied to Biruni University Hospital between March 2020 and March 2021, covering the COVID-19 Pandemic. Material and Method: In the study, antibiogram test results and ESBL presences of K. pneumoniae bacteria isolated from samples sent from different outpatient clinics and services were evaluated retrospectively. GraphPad InStat V. 3.05 was used for statistical analysis. Result and Discussion: In the study, 423 K. pneumoniae bacteria were isolated from different clinical samples. Of the isolates, 161 (38%) were obtained from the endotracheal aspirate (ETA) sample, and 349 (82.5%) were obtained from the intensive care clinic. In addition, 358 (84.63%) of the isolates were ESBL positive and 65 (15.36%) ESBL negative. It was observed that the majority of the isolates obtained were resistant to ampicillin, and almost all of the ESBL positive isolates were resistant to ceftazidime. Both the studies and the results of the study show that the number of K. pneumoniae strains showing multiple antibiotic resistance has increased over time and this increase continues exponentially. © 2023 University of Ankara. All rights reserved.

20.
Int J Mol Sci ; 24(5)2023 Mar 01.
Article in English | MEDLINE | ID: covidwho-2255591

ABSTRACT

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.


Subject(s)
Anti-Bacterial Agents , Ceftazidime , Drug Combinations , Drug Resistance, Bacterial , Klebsiella Infections , Klebsiella pneumoniae , Meropenem , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , beta-Lactamases/genetics , COVID-19/epidemiology , Intensive Care Units , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Meropenem/pharmacology , Meropenem/therapeutic use , Microbial Sensitivity Tests , Pandemics , Retrospective Studies
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