Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant Helicobacter pylori.

Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of Helicobacter pylori infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in H. pylori are associated with point mutations in 23S ribosomal RNA (rRNA), the relationships of other mutations with resistance remain unclear. We examined possible new macrolide resistance mechanisms in resistant strains using next-generation sequencing. Two resistant strains were obtained from clarithromycin-susceptible H. pylori following exposure to low clarithromycin concentrations using the agar dilution method. Sanger sequencing and whole-genome sequencing were performed to detect resistance-related mutations. Both strains carried the A2142G mutation in 23S rRNA. Candidate mutations (T1495A, T1494A, T1490A, T1476A, and G1472T) for clarithromycin resistance were detected in the Mutant-1 strain. Furthermore, a novel mutation in the gene encoding for the sulfite exporter TauE/SafE family protein was considered to be linked to clarithromycin resistance or cross-resistance, being identified as a target for further investigations. In the Mutant-2 strain, a novel mutation in the gene that encodes DUF874 family protein that can be considered as relevant with antibiotic resistance was detected. These mutations were revealed in the H. pylori genome for the first time, emphasizing their potential as targets for advanced studies.

Antibiotic Resistance of Helicobacter pylori in Turkey: A Systematic Review and Meta-Analysis.

Turkey presents both a high prevalence of Helicobacter pylori infection and high prevalence of antibiotic resistance. In this study, we aimed to summarize recent data on H. pylori antibiotic resistance rates in this nation. After conducting searches in two national and international databases (ULAKBIM, EKUAL, and PubMed), a systematic review was conducted. A total of 197 original articles on antibiotic resistance of H. pylori in Turkey were collected. After screening for inclusion and exclusion criteria, to evaluate the H. pylori antibiotic resistance for the period 2005-2020, 20 eligible articles were included in the meta-analysis. Data analysis was performed using MedCalc 12.7.0. The number of isolated H. pylori strains in each study was weighted, and pooled proportion analysis was performed. This review included 20 Turkish studies, including 1,556 H. pylori strains. The overall resistance rates were as follows: clarithromycin (CLA), 26.7% (95% confidence interval [CI]: 20.5-33.5); metronidazole (MTZ), 28.4% (95% CI: 19.7-38.1); levofloxacin (LVX), 19.6% (95% CI: 9.9-31.7); tetracycline (TET), 0.7% (95% CI: 0.1-1.8); and amoxicillin (AMO), 1.3% (95% CI: 0.3-3.1). The reported results showed that Turkish H. pylori isolates are highly resistant to CLA, MTZ, and LVX, while exhibiting a low level of resistance toward AMO and TET.

Development of preschool refugee children living under temporary protection status.

BACKGROUND: The conflict in Syria following the anti-regime demonstrations that started in March 2011 created one of the greatest humanitarian crises. The United Nations High Commissioner for Refugees (UNHCR) reports that refugee and resettlement experiences can influence the critical stages of intellectual, social, emotional and physical development of children. There is a lack of sufficient information about the prevalence of developmental delay in forcibly displaced children. In this study, we aimed to describe the impact of the Syrian crisis on the development of children after resettlement, factors that are associated with developmental problems and domains in which developmental delays are more likely to occur. METHODS: Refugee children (n=60) between the ages of 18-72 months admitted to the Yenimahalle Community Health Center Immigrant Health Unit to receive primary health care services between 1 November 2018- 1 March 2019 were included in this study. The control group included 60 Turkish children between 18-72 months admitted to the Ismail Ulucan Family Health Center which is in the same building. Developmental assessments were conducted by the researchers using the Denver II Developmental Screening Test (DDST-II). Sociodemographic characteristics of the child, family and caregivers as well as risk factors related to development were collected using a questionnaire. The interviews with refugee families were conducted with an interpreter. RESULTS: Developmental delay was more frequent in refugee children compared to Turkish children. The DDST-II were normal in 82.1%, questionable in 10.7% and abnormal in 7.1% of Turkish children; in the study group, 22.2% of the patients were found to be normal, 33.3% were questionable and 44.4% were abnormal. The differences were statistically significant (p < 0.05). Multiple logistic regression analysis revealed that, being a forcibly displaced refugee was the single significant risk factor for developmental delay alone. In the DDST II subdomain analysis, it was seen that high monthly income reduces the risk of caution-delay in personal-social domain. It was found that birth weight below 2500 g increased the risk of caution-delay in the fine-motor and gross-motor domain and being a forcibly displaced refugee and consanguinity increased the risk of caution -delay in the language domain. CONCLUSIONS: This study showed that being a forcibly displaced refugee was the most important risk factor for developmental delay. We emphasized the importance of surveillance and screening development in these highrisk children as well as early intervention services.

Investigation of ceftazidime-avibactam susceptibility in clinical isolates of gram-negative bacteria.

BACKGROUND: Our study investigated the susceptibility rate of ceftazidime-avibactam and the risk factors associated with its resistance by analyzing gram-negative bacteria isolated from various patient samples. METHODS: Between March and November 2020, 1119 gram-negative bacteria strains were isolated from patient samples in Acibadem Healthcare Group hospitals; ceftazidime-avibactam susceptibility results were evaluated using a 10/4µg (Oxoid, UK) disc and evaluated according to Eucast 2020 recommendations. Patient and isolate characteristics that could be risk factors were retrospectively investigated and statistically analyzed using SPSS 25.0. RESULTS: Male patients made up 52% (n = 581) of the study's total patient population, and they averaged 55.5 ± 24.9 years old. Of 1119 gram-negative strains culture and antibiogram, 1023 (91.4%) were sensitive to ceftazidime-avibactam. An increased risk of resistance was observed with female gender (OR = 2.29; CI 95% [1.45-3.61]; p < 0.05), Pseudomonas aeruginosa (OR = 1.67, CI 95% [1.03-2.7]; p < 0.05), the presence of multidrug-resistance (MDR) (OR = 4.07, CI 95% [2.47-6.7]; p < 0.05) pandrug-resistance (PDR) (OR = 12, (CI) 95% [9.9-14.7] ]; p < 0.05) and admission to intensive care unit (ICU) (OR = 1.89, CI 95% [1.22-2.93]; p < 0.05). DISCUSSION: The resistance rate of ceftazidime-avibactam was found to be 8.6%, and it was thought that resistant strains produced metallo-ß-lactamase (MBL) type carbapenemase. Risk factors were female gender, Pseudomonas aeruginosa, MDR, PDR, and admission to ICU. Therefore, studying the ceftazidime-avibactam susceptibility test together with gram-negative bacteria identification, especially in groups at risk for resistance, is one of the important factors that can positively affect the success of treatment.

Performance Evaluation of MALDI-TOF MS MBT STAR-BL Versus In-House Carba NP Testing for the Rapid Detection of Carbapenemase Activity in Escherichia coli and Klebsiella pneumoniae Strains.

There is an urgent need to be able to identify carbapenemase-producing Enterobacterales. In this study we aimed to compare the performance of the MALDI Biotyper Selective Testing of Antibiotic Resistance-ßLactamase (MBT STAR-BL) test with the in-house Carba NP test in their ability to rapidly detect carbapenemase production in Escherichia coli and Klebsiella pneumoniae strains. MBT STAR-BL and Carba NP testing were performed in parallel. One hundred sixty-nine isolates in total were tested. K. pneumoniae (n = 139) and E. coli (n = 14) strains with previously characterized carbapenemase types, and non-carbapenemase-producing strains of K. pneumoniae (n = 8) and E. coli (n = 8), were included in the study. When the results of the ertapenem and meropenem hydrolysis assays were evaluated together, MBT STAR-BL correctly identified 151 out of 153 (99%) carbapenemase producers as positive, while giving false-negative results for OXA-48 and OXA-48+NDM-1 producers in two K. pneumoniae isolates. The specificity and sensitivity of MBT STAR-BL were 100% and 98.69%, respectively. For the Carba NP test we confirmed 100% specificity, but sensitivity was 96.7%, although increasing to 100% when using prolonged incubation timing (4 hours). False-negative results were associated with enzymes with low carbapenemase activity, particularly OXA producers, which are common in Enterobacterales.

Evaluation of the performance of MALDI-TOF MS and DNA sequence analysis in the identification of mycobacteria species

Background/aim: Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is an alternative way of identifying mycobacteria via the analysis of biomolecules. It is being increasingly used in routine microbiology practice since it permits early, rapid, and cost-effective identification of pathogens of clinical importance. In this study, we aimed to evaluate the efficacy of phenotypic identification of mycobacteria by the MALDI-TOF MS MBT Mycobacteria Library (ML) 4.0 (Bruker, Daltonics) compared to standard sequence analysis. Materials and methods: A total of 155 Mycobacterium clinical and external quality control isolates, comprising nontuberculous mycobacteria (NTM) (n = 95) and the Mycobacterium tuberculosis complex (MTC) (n = 60), were included in the study. Results: Identification by MBT ML4.0 was correctly performed in 100% of MTC and in 91% of NTM isolates. All of the MTC isolates were correctly differentiated from NTM isolates. Conclusion: Based on our results, MBT ML4.0 may be used reliably to identify both NTM and MTC.

Evaluation of the Carba NP Test for the Detection of Carbapenemase Activity in Bacteroides Species.

We evaluated the usefulness of the Carba NP test for rapid detection of carbapenemase activity in Bacteroides spp. The minimum inhibitory concentration (MIC) for imipenem was determined with gradient test strips, and cfiA gene was investigated by polymerase chain reaction for 27 clinical Bacteroides spp. isolates. Carba NP test was performed according to recommendations of the Clinical and Laboratory Standards Institute. Among three cfiA gene harboring clinical isolates, two imipenem resistant isolates were Carba NP test positive, while the imipenem intermediate isolate was negative. Our preliminary results suggest that the Carba NP test can be useful as a rapid test to detect carbapenemases in Bacteroides species.

Does Low Dose Lidocaine Cause Convulsions?

In anaesthesiology practice, lidocaine is commonly used for local and regional anaesthesia as well as to decrease haemodynamic response to intubation. Lidocain usage within the safe dose range is suggested and in case of overdose; systemic intoxication, central nervous system and cardiovascular system toxicity may occur. Convulsions, cardiac collapse and coma are reported in relation to overdoses of lidocain. In this report; the convulsion event, which occurred after injection of intravenous 1 mg kg(-1) 1% lidocaine to inhibit intubation-related hemodynamic side effects in patients scheduled for vitrectomy under general anaesthesia due to retinal detachment, is presented.