Extensive Drug Resistance Research Articles

The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo.

Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.

Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

The Impact of Fosfomycin on Gram Negative Infections: A Comprehensive Review.

Multidrug-resistant or extended drug resistance has created havoc when it comes to patient treatment, as options are limited because of the spread of pathogens that are extensively or multidrug-resistant (MDR or XDR) and the absence of novel antibiotics that are effective against these pathogens. Physicians have therefore started using more established antibiotics such as polymyxins, tetracyclines, and aminoglycosides. Fosfomycin has just come to light as a result of the emergence of resistance to these medications since it continues to be effective against MDR and XDR bacteria that are both gram-positive and gram-negative. Fosfomycin, a bactericidal analogue of phosphoenolpyruvate that was formerly utilised as an oral medication for uncomplicated urinary tract infections, has recently attracted the interest of clinicians around the world. It may generally be a suitable therapy option for patients with highly resistant pathogenic infections, according to the advanced resistance shown by gram-negative bacteria. This review article aims to comprehensively evaluate the impact of fosfomycin on gram negative infections, highlighting its mechanism of action, pharmacokinetics, clinical efficacy, and resistance patterns.

Predominance of OXA-48 carbapenemase-producingKlebsiella pneumoniaestrains in tertiary hospital in Sarajevo, Bosnia and Herzegovina.

Klebsiella pneumoniae, a member of the Enterobacteriaceae family, demonstrates an increasing trend of resistance to carbapenems and is a common cause of both hospital- and community-acquired infections. The current study provides insights into the genetic characterization of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates circulating during 2022 in a Sarajevo tertiary hospital. Among the 87 CRKP strains analyzed, real-time polymerase chain reaction (rtPCR) results showed that 85 (97.7%) tested positive for the carbapenem resistance gene. The oxacillinase-48 (OXA-48) gene was detected in 83 (95.4%) isolates, while the Klebsiella pneumoniae carbapenemase (KPC) and the New Delhi metallo-beta-lactamase (NDM) genes were detected in one isolate each. No Verona integron-encoded-metallo-beta-lactamase (VIM) or imipenemase-metallo-beta-lactamase 1 (IMP-1) genes were found in any of the tested isolates. The multilocus sequence typing (MLST) analysis of sequence types (STs) revealed that ST101, an emerging high-risk clone exhibiting extensive drug resistance, was the most prevalent, whereas ST307 was detected in only one isolate. Phylogenetic analysis of the ten CRKP isolates indicated the presence of three clusters that could constitute an outbreak. A comparison of the results of the utilized phenotypic test (the combined-disk test [CDT]) and rtPCR showed high concordance, suggesting that the phenotypic assay may be useful for the early detection of resistance mechanisms as part of routine susceptibility testing. With the increased affordability of next-generation sequencing (NGS), its application in hospital settings has proven highly beneficial, aiding in the implementation of infection control and prevention measures. Given the significant resistance demonstrated by the CRKP isolates to most tested antibiotics, it is imperative to establish effective methods to restrict the spread of these isolates, as well as to carefully monitor the use of carbapenems in clinical practice.

Drug Targets, Current and Future Therapeutics for the Treatment of Multi Drug Resistant Tuberculosis with their Clinical Applications: A Critical Review

Abstract: Multi drug-resistant or extensive drug resistance Mycobacterium tuberculosis poses numerous challenges for health care workers and for public health authorities. Treating multidrug resistant or extensive drug resistance tuberculosis continues to be a difficult task, as a longer regimen is associated with a higher number of adverse drug events and economic burden and has a significant negative effect on health care resources. Many trials and observational studies were conducted. Few studies are underway to develop the universal regimen and improve the outcomes related to multi or extensive drug resistance tuberculosis with a shorter regimen duration. The current review will discuss which drug inhibits what target, their synthesis, genetic aspects, repurposed drugs, novel drugs, and extensive trials for the treatment of multi or extensive drug resistance tuberculosis.

Comprehensive Treatment of Generalized Tuberculosis with Endobronchial Valves

The article describes a clinical case of generalized tuberculosis manifested by tuberculous spondylodiscitis and disseminated pulmonary tuberculosis with extensive drug resistance and bilateral multiple destruction. The chemotherapy regimen compiled according to the sensitivity pattern of the pathogen, sequential implantation of two endobronchial valves and their long-term (18 months) synergic effect made it possible to cure pulmonary tuberculosis with healing of all multiple bilateral destruction. The same chemotherapy regimens allowed achieving cure of tuberculous spondylodiscitis. Co-infection of hepatitis C provided no negative impact on the treatment course.

Typhoid Fever: Pakistan's Unique Challenges and Pragmatic Solutions

Typhoid fever is a life-threatening disease caused by gram-negative bacteria Salmonella enteric serotype Typhi. Every year, this disease affects almost 21 million people worldwide, the majority of whom are from South Asia. According to the WHO, almost 11 to 21 million cases of typhoid fever and about 200,000 deaths from typhoid fever occurred all over the world. Pakistan health authorities have confirmed that from 2016 to 2020, almost 22,354 cases of typhoid fever were reported, out of which 15,717 cases were extensive drug-resistant typhoid fever reported from the different regions of Sindh. These calculations are used to measure the disease rate of typhoid fever, ratio is about 15.5/1,000, and the XDR strain of typhoid fever is highly resistant to the antibiotic, also known as extensive drug resistance. The diagnosis of typhoid fever is done by culture tests, serological test, nucleic acid assays, protein markers, and biomarkers. The proper diagnosis is very important to ensure the strain of typhoid fever, so treatment should be started accordingly.

Complete genome sequences and multidrug resistance genotypes of nontuberculous mycobacteria isolates from the Central Tuberculosis Reference Laboratory Muhimbili Tanzania

Background: Nontuberculous mycobacteria (NTM) usually comprise a group of environmental bacteria, with emerging but elusive coinfection with tuberculous mycobacteria, causing pulmonary tuberculosis. Whole genome sequencing may give insight into potential antimicrobial resistance genotypes, giving clinicians and policymakers proper directions in clinical applications and management regimens. Methods: WGS was performed on twenty-four gDNA isolates from archival samples at the Central Tuberculosis Reference Laboratory using the MinION Oxford Nanopore Sequencing approach. Out of twenty-four, two were confirmed to belong to the NTM group. Further analysis was done to resolve the complete genomes of two nontuberculous mycobacteria strains isolated from tuberculosis patients. We then combined phylogenomics, reference-based scaffolding and average nucleotide identity (ANI) analysis to delineate each strain's taxonomic position and corresponding features. Results: Our findings reveal that the two strains fit into the genus Mycolicibacterium, and the closest relative is Mycolicibacterium novocastrense. Coupling BacAnt and CARD-based antibiotic resistance analyses revealed multidrug-resistant genotypes of diverse spectra and mechanisms. While the BC02 strain is genetically resistant to beta-lactams, macrolides and rifamycins, the BC05 strain portrays an extended drug resistance genotype encompassing beta-lactams, macrolides, polyamines, and aminoglycosides. Both strains possess a single nucleotide polymorphism (SNP) of the RNA polymerase beta-subunit (rpoB), representing resistance to the first-line rifampicin. Additionally, the BC05 strain genetically portrays resistance to ethambutol, isoniazid and fosfomycin through mechanisms involving target alteration through SNPs, drug inactivation and efflux. Conclusion: Our findings strongly suggest the potential implication of multidrug-resistant NTM clinical isolates in the pathogenesis of pulmonary tuberculosis.

Global Burden of Tuberculosis in Adolescents and Young Adults: 1990-2019.

Tuberculosis (TB) is a major health threat in adolescents and young adults. However, its burden in this population remains unclear. This study aimed to assess TB burden and changing trends in individuals aged 10 to 24 years from 1990 to 2019. All data were obtained from the Global Burden of Disease Study 2019. We calculated the percentage of relative changes in incident cases, deaths, and disability-adjusted life years (DALYs). The temporal trends of the incidence, mortality, and DALYs were assessed using estimated annual percentage changes (EAPCs). At global level, TB incidence (per 100 000 population) decreased from 144.12 in 1990 to 97.56 in 2019, with average 1.28% (95% confidence interval [CI]: 1.36%-1.19%) of decline per year. Similar decreasing trends occurred across sex, age, sociodemographic index regions, and in most Global Burden of Disease study regions and countries. TB incidence in female adolescents decreased faster than that in male. However, there was an increasing trend in the incidence of extensively drug-resistant TB (EAPC = 11.23, 95% CI: 8.22-14.33) and multidrug-resistant TB without extensive drug resistance (EAPC = 3.28, 95% CI: 1.73-4.86). South Africa had the highest increase in TB incidence (EAPC = 3.51, 95% CI: 3.11-3.92). Global TB incidence, mortality, and DALYs in adolescents and young adults decreased from 1990 to 2019. However, the incidence of drug-resistant TB increased. TB remains a threat in adolescents and young adults worldwide, especially in low- and middle-income countries.

FOLLOW-UP CASES OF BEDAQUILINE IN XDR-TB PATIENTS: A CASE SERIES

Tuberculosis has consistently maintained its lead position in being among the top 10 causes by means of single-cause etiology for death among infectious disease patients. On top of it, now multi-drug resistant cases of tuberculosis (MDR-TB) are raising concern. The vision of tuberculosis eradication gets a major setback with a total of 206,030 million cases being reported worldwide with MDR or rifampicin-resistance MDR-TB in 2019. Bedaquilline a relative recent drug is being made available for the treatment of MDR and extensive drug resistance (XDR) TB under NTEP. It is being provided as a part of 2nd line of drug therapy. Regarding the drug’s efficacy and safety profiling Bedaquiline has been under extensive clinical trials at medical institutes and hospitals of reputation at national level. The treatment options available to treat XDR-TB remain extremely limited at the cost of being less effective, expensive and with more side effects. Even after the availability of potent anti-tubercular drugs, XDR Tuberculosis is proving to be more resistant to all possible drugs available to work against it.

Examining pharmacoepidemiology of antibiotic use and resistance in first-line antibiotics: a self-controlled case series study of Escherichia coli in small companion animals

BackgroundClinicians need to prescribe antibiotics in a way that adequately treats infections, while simultaneously limiting the development of antibiotic resistance (ABR). Although there are abundant guidelines on how to best treat infections, there is less understanding of how treatment durations and antibiotic types influence the development of ABR. This study adopts a self-controlled case study (SCCS) method to relate antibiotic exposure time to subsequent changes in resistance patterns. This SCCS approach uses antibiotic exposure as a risk factor, and the development of ABR as an incidence rate ratio (IRR), which can be considered as the multiplicative change in risk for bacteria to become or maintain resistance.AimTo investigate the IRR of extensive (more than 7 antibiotic classes), revert, persistent, and directed antibiotic resistance according to the duration and type of antibiotic exposures in Escherichia coli (E. coli).Methods and materialWe use anonymized veterinary clinical data from dog and cat patients older than 6 months between 2015 and 2020. Patients were considered suitable cases if they received antibiotics and had a minimum of two urinary antibiograms within a 12-month period (the first prior to antibiotics exposure and the second from 1 week to 6 months after exposure). The first antibiogram is conducted before antibiotic exposure (case n=20).FindingsFrom 20 individuals and 42 paired antibiograms we found that the IRR = 2 for extensive drug resistance in patients who received short-course antibiotic treatment compared to longer treatments. In contrast, multi-drug resistance IRR = 2.6 for long-course compared to short-course antibiotic treatment. The ratio of E. coli isolates that reverted from resistant to sensitive was 5.4 times more likely in patients who received antibiotics for longer than 10 days.

Multidrug Resistance in Bacterial Isolates from Pus Samples: A Hospital-based Descriptive Cross-sectional Study

Introduction: Antimicrobial Resistance (AMR) is a growing public health threat. Multidrug-resistant (MDR) bacteria, initially associated with healthcare-associated infections, have now spread and become a major cause of community-acquired infections, as well. Therefore, there is a need for monitoring MDR bacterial infections in healthcare settings to establish policies for antimicrobial therapy and effective infection prevention strategies. As pyogenic infections were a major burden of infectious diseases in our healthcare setup, the present study was conducted. Aim: To estimate the prevalence of Multidrug Resistance (MDR) and Extensive Drug Resistance (XDR) in bacterial isolates from pus samples. Materials and Methods: The present hospital-based descriptive cross-sectional study was conducted in the Microbiology Laboratory, SMBT Hospital, Nashik, Maharashtra, India, from June 2022 to May 2023. A total of 360 bacterial isolates from pus samples received from the General Surgery, Orthopaedics and Otorhinolaryngology Departments were tested for antimicrobial susceptibility according to the Clinical and Laboratory Standards Institute (CLSI) 2023 guidelines. Isolates were classified as MDR and XDR as per standard definitions. All Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) isolates were tested for Ampicillinase C (AmpCs) production by disk approximation test and double disk synergy test. Microsoft Excel 2013 was used for data analysis. Results: The prevalence of MDR and XDR in Gram-negative bacteria was 175 (68.8%) and 120 (47.2%), respectively. The prevalence of MDR and XDR Staphylococcus aureus (S. aureus) was 59 (67%) and 10 (11.3%), respectively. The prevalence of Methicillin Resistant S. aureus (MRSA) was 45.4% (n=40). Out of the total 111 isolates of E. coli and K. pneumoniae, five isolates were AmpC beta-lactamase producers (4.5%). Conclusion: In the present study, a high prevalence of MDR was observed in both Gram-negative and Gram-positive bacteria isolated from different pus samples. This is an alarming situation, and further in-depth studies need to be conducted to assess the association of MDR bacterial infections with particular sites and types of infections to develop effective therapeutic and infection control policies.

ЭФФЕКТИВНОСТЬ ПРИМЕНЕНИЯ МЕТОДОВ КОЛЛАПСОТЕРАПИИ В КОМПЛЕКСНОМ ЛЕЧЕНИИ БОЛЬНЫХ ТУБЕРКУЛЕЗОМ ЛЕГКИХ С ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ

Objective: to evaluate effectiveness of collapse therapies – artificial pneumoperitoneum (APP) and valve bronchial blockage (VBB) – in the complex treatment of pulmonary TB patients with drug resistance. Materials and methods. We carried out a retrospective analysis of case records of pulmonary TB patients admitted to hospital in 2014–2023. The patients were divided into two groups: group 1 included 181 patients with destructive pulmonary TB and multiple/ extensive drug resistance (MDR/XDR), they received chemotherapy complemented by APP and VBB; group 2 included 84 patients with destructive pulmonary TB and MDR/XDR, they received chemotherapy alone due to different impartial reasons. Chemotherapy regimens for MDR/XDR TB considered individual drug tolerance during the whole observation period. Results. After two months of treatment sputum conversion confirmed by microscopy and cultural studies was observed in 72.9% of group 1 and 57.1% of group 2 (p = 0,01), cavity closure confirmed by X-ray examinations was observed more frequently in group 1 than group 2 (65.7 vs 39.3% respectively, p &lt; 0.001). Additional applications of VBB enabled to increase the incidence of cavity closure in group 1 vs group 2 (71.3 and 54.8%, respectively, p = 0.01). Conclusion. The results demonstrated that applications of collapse therapies in the complex treatment of pulmonary TB patients with MDR/XDR improved treatment effectiveness as confirmed by sputum conversion and cavity closure vs chemotherapy alone.

ПРОЛОНГИРОВАННОЕ ПРИМЕНЕНИЕ БЕДАКВИЛИНА В РЕЖИМЕ ХИМИОТЕРАПИИ У ПОДРОСТКА С ДИССЕМИНИРОВАННЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ И ШИРОКОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ

The article describes a clinical case of delayed diagnosis of bilateral advanced destructive pulmonary TB with extensive drug resistance (XDR) in an adolescent. Effective and safe prolonged use of bedaquiline (Bq) in the complex treatment was demonstrated. A multidisciplinary approach to treatment with two-stage surgery and consultation from a pediatric cardiologist allowed completing the main course of TB treatment and achieving successful treatment outcome.

Cefiderocol susceptibility endows hope in treating carbapenem-resistant Pseudomonas aeruginosa: insights from in vitro and in silico evidence.

'High-risk' hypermutable clones of Pseudomonas aeruginosa disseminating extensive drug-resistance (XDR) have raised global health concerns with escalating mortality rates in immunocompromised patients. Mutations in conventional drug-targets under antibiotic stress necessitate structural understanding to formulate sustainable therapeutics. In the present study, the major β-lactam antibiotic target, penicillin-binding protein-3 (PBP3) with mutations F533L and T91A, were identified in carbapenemase-positive P. aeruginosa isolates (n = 6) using whole genome sequencing. Antibiotic susceptibility tests showed susceptibility to cefiderocol (MIC ≤ 4 μg ml-1) despite pan-β-lactam resistance in the isolates. Both the mutations reduced local intra-chain interactions in PBP3 that marginally increased the local flexibility (∼1%) in the structures to affect antibiotic-interactions. Molecular dynamics simulations confirmed the overall stability of the PBP3 mutants through root-mean square deviations, radius of gyration, solvent-accessibility and density curves, which favored their selection. Docking studies unveiled that the mutations in PBP3 elicited unfavorable stereochemical clashes with the conventional antibiotics thereby increasing their inhibition constants (IC) up to ∼50 fold. It was deciphered that cefiderocol retained its susceptibility despite mutations in PBP3, due to its higher average binding affinity (ΔG: -8.2 ± 0.4 kcal mol-1) towards multiple PBP-targets and lower average binding affinity (ΔG: -6.7 ± 0.7 kcal mol-1) to β-lactamases than the other β-lactam antibiotics. The molecular dynamics simulations and molecular mechanics Poisson Boltzmann surface area calculations further indicated energetically favorable binding for cefiderocol with PBP3 proteins. The study gave structural insight into emerging non-polar amino acid substitutions in PBP3 causing XDR and recommends prioritizing available antibiotics based on multi-target affinities to overcome challenges imposed by target-protein mutations.

Изучение эффективности нового противотуберкулезного препарата тиозонид у пациентов с туберкулезом легких с множественной и широкой устойчивостью M. tuberculosis

Изучение эффективности нового противотуберкулезного препарата тиозонид у пациентов с туберкулезом легких с множественной и широкой устойчивостью M. tuberculosis

Monitoring the Cardiotoxic Effects of Bedaquiline in Older Children and Adolescents with Multiple and Extensive Drug Resistance

The objective: to evaluate expanded monitoring of cardiovascular disorders in older children and adolescents with multiple drug resistant tuberculosis receiving bedaquiline (Bq) as a part of anti-tuberculosis therapy.Subjects and Methods: A cohort retrospective-prospective study (2015-2021) was conducted, which included 36 patients aged 13-17 years old who received Bq. The prospective part included 19 patients (Main Group), they underwent extended monitoring (EM) of cardiotoxic reactions; this extended monitoring program was developed in Central Tuberculosis Research Institute. The retrospective part included 17 patients (Control Group), in whom cardiotoxic reactions were assessed using standard monitoring recommended by the Russian Society of Phthisiologists at that time. The relationship between the studied risk factor (monitoring by standard ECG) and the outcome (Bq discontinuation) was assessed using the Pearson χ2 test.Results. Prolongation of the QTc interval &gt; 0.440 ms was noted in 17.6% of cases in Control Group and it was regarded as a cardiotoxic effect of Bq, the drug was discontinued. In Main Group, prolongation was noted in 47.3% of cases which was considered a functional disorder of the cardiovascular system according to EM, the drug was not discontinued, χ2 = 3.896; p = 0.049. EM can be used in older children and adolescents with multiple drug resistant respiratory tuberculosis, which will make it possible to safely include Bq to chemotherapy regimens.

Drug Resistance Pattern of Salmonella Typhi in Patients Suffering from Enteric Fever - Experience from Tertiary Care Hospital of Peshawar.

Background: Enteric fever is one of the most common infections in Southeast Asia. Over the last decade, increasing drug resistance against salmonella has been documented. Objectives: This study aimed to determine the drug resistance pattern of salmonella typhi at a tertiary care hospital in Peshawar.Material and Methods: A cross-sectional observational study was conducted at Rehman Medical Institute, Peshawar over one year, from June 2022 to June 2023. All the patients who had culture-proven typhoid were included in the study. Antibiotic sensitivity was determined against conventional and latest antibiotics used for typhoid fever. Data was analyzed through SPSS24.Results: Out of 284 patients, 60.6% (n=172) were males and the mean age was 24.07±11.65 years. Only 11.3% (n=32) had non-resistant typhoid fever. Extended Spectrum Beta lactamase resistance was noted in 43.3 % (n=123), Extensive drug resistance (XDR) in 37.3% (n=106), and multidrug resistance (MDR) in 8.1% (n=23) of total cases. Salmonella typhi was sensitive to Azithromycin and Meropenem in 100% and 99.6% of cases respectively. Its sensitivity to cotrimoxazole, Chloramphenicol, and Ampicillin was 48.9%, 17.6%, and 7.70% respectively. Only 2.5% of typhoid cases were sensitive to Ciprofloxacin.Conclusion: Drug-resistant typhoid has shown a rising trend. Conventional antibiotic therapy has developed significant resistance. Azithromycin and Meropenem have shown good sensitivity to Salmonella.Keywords: Drug Resistance, Sensitivity, Typhoid

Evolutionary trends of carbapenem-resistant and susceptible Acinetobacter baumannii isolates in a major tertiary care setting from North India

Emergence of carbapenem-resistant A. baumannii (CRAB) is a global, ongoing healthcare concern. CRAB is among the topmost priority pathogens, with various studies focusing on its global population structure and resistant allelic profiles. However, carbapenem-susceptible A. baumannii (CSAB) isolates are often overlooked due to their sensitivity to beta-lactams, which can provide important insights into origin of CRAB lineages and isolates. In the present study, we report genomic investigation of CRAB and CSAB coexisting in Indian hospital setting. MLST based population structure and phylogenomics suggest they mainly follow distinct evolutionary routes forming two phylogroups. PG-I exclusively for a successful clone (ST2) of CRAB and PG-II comprises diversified CSAB isolates except PG3373, which is CRAB. Additionally, there are few CRAB isolates not belonging to PG-I and sharing clonal relationship with CSAB isolates indicating role of genome plasticity towards extensive drug resistance in the nosocomial environment. Further, genealogical analysis depicts prominent role of recombination in emergence and evolution of a major CRAB lineage. Further, CRAB isolates are enriched in resistomes as compared to CSAB isolates, which were encoded on the genomic island. Such comparative genomic insights will aid in our understanding and localized management of rapidly evolving pandrug resistant nosocomial pathogens.

Ticari buzağı mamalarının mikrobiyolojik analizi ve izole edilen Enterococcus türlerinde antibiyotik dirençliliği

One of the reasons why calf milk replacer is preferred over unpasteurized bulk tank milk or waste milk with antibiotics on farms is that it prevents epidemic diseases and antibiotic resistance that may occur on the farm. In this study analyzed commercial calf milk replacer products (n = 12) obtained from dairy farms around Turkiye by microbiological culture and polymerase chain reaction (PCR). In order to evaluate the microbiological quality of calf milk replacer, total bacteria count, coliform E. coli and E. coli O157-H7, Salmonella spp., Staphylococcus spp., Streptococcus spp., Enterococcus spp. analyses were performed according to microbiological analysis methods determined according to ISO standards. Enterococcus spp. was isolated from all 12 calf milk replacer samples analyzed and molecularly confirmed by PCR with the presence of the gross-Es gene. Salmonella spp., E. coli, Staphylococcus spp. and Streptococcus spp. were not isolated from the samples.&#x0D; Additionally, in the bacterial counts, an average of 5.3x107 Enterococci were counted from all samples in 1 gram of calf milk replacer. Antimicrobial analysis of the isolated bacteria was completed according to CLSI 2022 data, and 11 isolates were defined as multi drug resistance and one isolate was defined as extensive drug resistance. It was also determined that the isolate defined as extensive drug resistance was resistant to Vancomycin and carried the Van A resistance gene. Many proteins used in the preparation of calf milk replacers are of animal origin and may contain pathogenic bacteria. Milk replacers are used on most farms for biosecurity purposes. It is known that milk replacers affect microbiota. It was shown in this study that if calf milk replacers are not prepared under the regulations, they may cause harm rather than benefit to on-farm biosecurity factors. It is concerning that calves are given calf milk replacers containing antibiotic-resistant Enterococcus spp. to sustain their lives when they are most vulnerable to disease during the window of susceptibility. When using calf milk replacer in calf feeding, field veterinarians should be informed about the microbiological certification of the product and provide information about pasteurization and presentation for consumption.