Characterization of Ceftriaxone-Resistant Haemophilus influenzae Among Korean Children.

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.

Identification of ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone and isolates harboring a novel mosaic penA gene in Chengdu in 2019-2020.

BACKGROUND: Antimicrobial resistance in gonorrhea has become a growing global public health burden. Neisseria gonorrhoeae isolates with resistance to ceftriaxone, the last remaining first-line option, represent an emerging threat of untreatable gonorrhea. METHODS: A total of ten ceftriaxone-resistant N. gonorrhoeae FC428 isolates and two isolates harboring a novel mosaic penA-232.001 allele from 160 gonococcal isolates in Chengdu in 2019-2020 was described in the present study. Multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed to characterize the isolates. Whole genome sequencing and maximum-likelihood method were performed to infer how the genetic phylogenetic tree of these isolates looks like. Recombination analysis was performed using the RDP4 software. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100048771, registration date: 20210716). RESULTS: The genetic phylogeny showed that the ten FC428 isolates sporadically clustered into different phylogenetic clades, suggesting different introductions and local transmission of FC428. Two isolates showed close genetic relatedness to ceftriaxone-resistant clone A8806, which was only reported from Australia in 2013. Homologous recombination events were detected in penA between Neisseria gonorrhoeae and commensal Neisseria species (N. perflava and N. polysaccharea), providing evidence of commensal Neisseria species might serve as reservoirs of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. CONCLUSIONS: Our results demonstrate further dissemination of FC428 in China and resurgence risks of sporadic ceftriaxone-resistant A8806 to become the next clone to spread.

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.

Spatial, Ecologic, and Clinical Epidemiology of Community-Onset, Ceftriaxone-Resistant Enterobacteriaceae, Cook County, Illinois, USA.

We performed a spatial and mixed ecologic study of community-onset Enterobacteriaceae isolates collected from a public healthcare system in Cook County, Illinois, USA. Individual-level data were collected from the electronic medical record and census tract-level data from the US Census Bureau. Associations between individual- and population-level characteristics and presence of ceftriaxone resistance were determined by logistic regression analysis. Spatial analysis confirmed nonrandom distribution of ceftriaxone resistance across census tracts, which was associated with higher percentages of Hispanic, foreign-born, and uninsured residents. Individual-level analysis showed that ceftriaxone resistance was associated with male sex, an age range of 35-85 years, race or ethnicity other than non-Hispanic Black, inpatient encounter, and percentage of foreign-born residents in the census tract of isolate provenance. Our findings suggest that the likelihood of community-onset ceftriaxone resistance in Enterobacteriaceae is influenced by geographic and population-level variables. The development of effective mitigation strategies might depend on better accounting for these factors.

Molecular characterization of a ceftriaxone-resistant Neisseria gonorrhoeae strain found in Switzerland: a case report.

BACKGROUND: The resistance of Neisseria gonorrhoeae to ceftriaxone is unusual in Switzerland. The underlying genotype responsible for resistance is suspected to be novel. Generally, resistance in Neisseria gonorrhoeae (Ng) involves a comprehensive set of genes with many different mutations leading to resistance to different ß-lactams and fluoroquinolones. CASE PRESENTATION: A patient had a positive result from specific PCR for Ng. We routinely culture all clinical specimens with a positive NG-PCR. In this particular case, we isolated a strain with resistance to ceftriaxone in Switzerland. A total of seven different genes (penA, ponA, porinB, mtr, gyrA, parC, 23S rRNA gene) in this strain were partially sequenced for comparison with phenotypic susceptibility testing. Interestingly, two different mutations in the porinB gene were observed, and data on this gene are limited. Information on the identified allele type of the penA gene is very limited as well. Three different mutations of parC and gyrA that correlate with ciprofloxacin resistance were found. The combination of ceftriaxone and ciprofloxacin resistance makes an appropriate treatment difficult to obtain due to multidrug resistance. CONCLUSION: The combined results for all genes show the appearance of new mutations in central Europe either due to worldwide spread or the emergence of new genetic combinations of mutations.

A Novel Lineage of Ceftriaxone-resistant Salmonella Typhi From India That Is Closely Related to XDR S. Typhi Found in Pakistan.

Two MDR Salmonella Typhi isolates from India were found by whole genome sequencing to be closely related to the 2016 XDR S. Typhi outbreak strain from Pakistan. The Indian isolates have no chromosomal antimicrobial resistance cassette but carry the IncY plasmid p60006. Both isolates are susceptible to chloramphenicol, azithromycin, and carbapenems.

Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. METHODS: We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. FINDINGS: We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. INTERPRETATION: Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. TRIAL REGISTRATION: PROSPERO CRD42018029432.

Ceftriaxone-resistant Salmonella Typhi Outbreak in Hyderabad City of Sindh, Pakistan: High Time for the Introduction of Typhoid Conjugate Vaccine.

BACKGROUND: The Aga Khan University clinical microbiology laboratory identified an outbreak of ceftriaxone-resistant Salmonella Typhi in Hyderabad, Pakistan, through antimicrobial resistance surveillance. An outbreak investigation was carried out to identify the risk factors and institute control measures. Here we report the preliminary findings of this outbreak investigation, using data collected from 30 November 2016 to 28 March 2017. METHODS: The design for the investigation was a case-control study that included identification of culture-proven ceftriaxone-resistant S. Typhi cases, suspected cases from the households or neighborhood of the confirmed cases, and enrollment of controls matched by age to identify the risk factors. Data were collected through face-to-face interviews using a structured questionnaire. Blood cultures were obtained from all suspected cases. Drinking water samples from each household of cases and controls were obtained for microbiological testing. Geographic Information System coordinates were obtained for all cases and controls. RESULTS: Only 2 subdistricts of Hyderabad (Latifabad and Qasimabad) were affected. A total of 101 confirmed cases of ceftriaxone-resistant S. Typhi had been reported in 4 months with the first case reported on 30 November 2016. Median age was 48 (interquartile range, 29-84) months. The majority (60% [61/101]) of the cases were 6-60 months old. More than half (56% [57/101]) of the cases were male. About 60% of the cases were admitted to hospital and treated as inpatient. More than half (57/101) of the patients developed complications related to typhoid. CONCLUSIONS: Community awareness was raised regarding chlorination of drinking water and sanitation measures in Hyderabad. These efforts were coordinated with the municipal water and sewage authority established to improve chlorination at processing plants and operationalize fecal sludge treatment plants. Outbreak investigation and control efforts have continued. Immunization of children with typhoid conjugate vaccine within Hyderabad city is planned.

Identification of Internationally Disseminated Ceftriaxone-Resistant Neisseria gonorrhoeae Strain FC428, China.

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.

CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress.

It has been proposed that some antibiotics exert additional damage through reactive oxygen species (ROS) production. Since H2S protects neurons and cardiac muscle from oxidative stress, it has been hypothesized that bacterial H2S might, similarly, be a cellular protector against antibiotics. In Enterobacteriaceae, H2S can be produced by the cysJIH pathway, which uses sulfate as the sulfur source. CysB, in turn, is a positive regulator of cysJIH. At present, the role of S. Typhimurium cysJIH operon in the protection to reactive oxygen species (ROS) induced by antimicrobial compounds remains to be elucidated. In this work, we evaluated the role of cysJIH and cysB in ROS accumulation, superoxide dismutase (SOD) activity, reduced thiol accumulation, and H2S accumulation in S. Typhimurium, cultured in either sulfate or cysteine as the sole sulfur source. Furthermore, we assessed the effects of the addition of ceftriaxone (CEF) and menadione (MEN) in these same parameters. In sulfate as the sole sulfur source, we found that the cysJIH operon and the cysB gene were required to full growth in minimal media, independently on the addition of CEF or MEN. Most importantly, both cysJIH and cysB contributed to diminish ROS levels, increase the SOD activity, increase the reduced thiols, and increase the H2S levels in presence of CEF or MEN. Moreover, the cysJIH operon exhibited a CysB-dependent upregulation in presence of these two antimicrobials compounds. On the other hand, when cysteine was used as the sole sulfur source, we found that cysJIH operon was completely negligible, were only cysB exhibited similar phenotypes than the described for sulfate as sulfur source. Unexpectedly, CysB downregulated cysJIH operon when cysteine was used instead of sulfate, suggesting a complex regulation of this system.

Complete reference genomes of two ceftriaxone-resistant Neisseria gonorrhoeae strains identified in routine surveillance in Bangkok, Thailand, using Nanopore Q20+ chemistry, VolTRAX V2b, and Illumina sequencing.

Ceftriaxone-resistant Neisseria gonorrhoeae strains, mostly associated with Asia, threaten gonorrhea treatment. We report the reference genomes of two ceftriaxone-resistant isolates found in routine surveillance in Bangkok, Thailand. The genomes belonged to the more antimicrobial-susceptible genomic lineage B, illustrating that both ceftriaxone-resistant strains and the mosaic penA-60.001 ceftriaxone-resistance determinant are spreading.

Ceftriaxone-resistant Salmonella enterica serovar Newport: a case report from South India.

Salmonella enterica serovar Newport is a human pathogen underreported in most developing countries. It is known for causing gastroenteritis and extraintestinal infections. In this case report, we report the case of ceftriaxone-resistant Salmonella enterica serovar Newport from South India, causing acute gastroenteritis in a sixty-year-old female patient having a history of antimicrobial therapy and recent hospital admission. Serovar Newport, especially among antibiotic-exposed patients, poses a significant public health threat due to its ability to acquire multidrug resistance. This emphasizes the necessity for robust surveillance and monitoring of nontyphoidal Salmonella infections, particularly given the limited data on serovar Newport in India. Vigilance in clinical practice and public health initiatives is crucial to effectively address the emergence and spread of multidrug-resistant strains.

Ceftriaxone-resistant Salmonella Typhi isolated from paediatric patients in north India: Insights into genetic profiles and antibiotic resistance mechanisms.

PURPOSE: To investigate the antibiotic resistance and genetic profile of ceftriaxone-resistant Salmonella Typhi isolated from the blood culture of two paediatric cases of typhoid fever and one from the stool culture of their household contact, in North India. METHODS: In this study, whole-genome sequencing was carried out with paired-end 2 â€‹× â€‹150 bp reads on Illumina MiSeq (Illumina, USA) employing v2 and v3 chemistry. To check data quality, adapters and low-quality sequences were removed through Trimmomatic-v0.36. High quality reads were then assembled de novo using A5-miseq pipeline. For further refinement, reference-guided contig ordering and orienting were performed on the scaffold assemblies using ABACAS (http://abacas.sourceforge.net/). The assembled genome was annotated using Prokka v1.12 to identify and annotate the gene content. Plasmid replicons in bacterial isolates were identified by PlasmidFinder, whereas mobile genetic elements were predicted using Mobile Element Finder. Referenced-based SNP tree with maximum likelihood method was built with CSI phylogeny v1.4. RESULTS: All three isolates exhibited resistance to ceftriaxone, cefixime, ciprofloxacin, ampicillin, and co-trimoxazole, while demonstrating sensitivity to azithromycin and chloramphenicol. The whole-genome sequencing of these strains revealed the presence of blaCTX-M-15 gene for cephalosporin resistance in addition to gyrA, qnr and IncY plasmid replicon. A 5 â€‹kb IS91 Sbo1 gene cassette (IncY plasmid) was identified which carried extended spectrum ß-lactamase blaCTX-M-15, blaTEM-1D (resistance to ampicillin and cephalosporin), sul2, dfrA14 (resistant to trimethoprim-sulfamethoxazole) and qnrS (resistant to ciprofloxacin). These isolates belong to H58 lineage and grouped as sequence type 1 (ST1) on multilocus sequence typing (MLST) analysis. CONCLUSION: In the present study we report the isolation of blaCTX-M-15 positive S. Typhi from two paediatric patients presenting with fever and one from stool culture of their contact from North India and highlight the need for further investigations to understand the different factors contributing to ceftriaxone resistance in Salmonella Typhi.

Increase in Multidrug Resistant Neisseria gonorrhoeae FC428-Like Isolates Harboring the Mosaic penA 60.001 Gene, in Nanjing, China (2017-2020).

Background: Since the first Chinese report of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in 2016, additional FC428-like, penA 60.001 isolates have been identified in China. Objective: To document the rise in penA 60.001 isolates in Nanjing, China, and characterize their molecular and epidemiological features. Methods: N. gonorrhoeae minimum inhibitory concentrations (MICs, mg/L) for ceftriaxone, cefixime, penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, gentamicin and zoliflodacin were determined by agar dilution. MICs for ertapenem were measured by E-test. N. gonorrhoeae antimicrobial sequence typing (NG-STAR) of seven loci (penA, mtrR, porB, ponA, gyrA, parC and 23S rRNA) was analyzed together with N. gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST). Phylogenetic analysis was also performed using whole genomic sequencing (WGS). Results: Fourteen FC428-related penA 60.001 N. gonorrhoeae infections were identified out of 677 infections from 2017 to 2020, in Nanjing, representing an incremental yearly rise in the percentage of the city's N. gonorrhoeae isolates that were FC428-related. Seven FC428-related N. gonorrhoeae infections were acquired in Nanjing, proper; four others in eastern Chinese cities and three from unknown locations. All FC428-related isolates were resistant to ceftriaxone, cefixime, ciprofloxacin, tetracycline and penicillin but susceptible to spectinomycin, gentamicin, ertapenem and zoliflodacin; three strains were resistant to azithromycin. penA 60.001 isolates displayed closely related MLST types and NG-STAR types but relatively distant NG-MAST types. WGS showed a phylogenetic analysis that intermingled with other international isolates. Conclusion: penA 60.001 N. gonorrhoeae isolates emerged in Nanjing, China, beginning in 2017, and have continued to rise.

Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance.

OBJECTIVES: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). METHODS: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. RESULTS: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. CONCLUSIONS: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae.

Ceftriaxone Resistance in Campylobacter Gastroenteritis.

Annually, millions of people worldwide are exposed to Campylobacter, a species of bacteria that commonly causes gastroenteritis and in cases of immunocompromised individuals, can also lead to life-threatening complications. After stool cultures are obtained, the usual treatment for infectious diarrhea involves metronidazole and quinolones such as ciprofloxacin or levofloxacin. Quinolones are a family of broad-spectrum antibiotics known to be effective against various gram-negative infections that also include Campylobacter jejuni (C. jejuni). However, due to adverse side effects and bacterial resistance risks that may exist with medication use, they are no longer used as a first line. Our patient, initially treated with ceftriaxone for symptoms resembling bacterial meningitis, pneumonia, and infectious diarrhea, showed minimal to no improvement. Subsequent cerebral spinal fluid (CSF) ruled out meningitis while stool studies confirmed C. jejuni as the causative agent. A switch to levofloxacin resulted in a noticeable improvement in the patient's condition. This case emphasizes the importance of considering changes in antibiotic regimen from ceftriaxone to quinolones when faced with persistent infectious diarrhea, due to the high prevalence of ceftriaxone resistance in C. jejuni infections.

Phylogenomic Analysis of Salmonella enterica Serovar Indiana ST17, an Emerging Multidrug-Resistant Clone in China.

Salmonella enterica serovar Indiana (S. Indiana) is an extremely expanded foodborne pathogen in China in recent years. This study aimed to elucidate the national prevalence and phylogenomic characterization of this pathogen in China. Among 5, 287 serotyped Salmonella isolates collected during 2002 to 2018, 466 S. Indiana isolates were found in 15 provinces, and 407 were identified to be ST17, and the rest were ST2040. Among 407 ST17 isolates, 372 (91.4%) were multidrug resistant, and 366 (89.9%) were resistant to ciprofloxacin, 235 (57.7%) were further resistant to ceftriaxone. Phylogenomic analysis revealed that ST17 isolates were classified into four clades (I, II, III and IV), which appeared in international clonal dissemination. ST17 isolates from China fell into Clade IV with part of isolates from the United Kingdom, the United States, South Korea, and Thailand, suggesting their close genetic relationship. Mutations in quinolone resistance-determining regions (QRDR) of GyrA and ParC, and plasmid-mediated quinolone resistance (PMQR) genes aac(6')-Ib-cr, oqxAB, and qnrS as well as extended spectrum ß-lactamases (ESBL) genes blaCTX-M, blaOXA, and blaTEM in isolates from Clade IV were much higher than those from other three clades. Various blaCTX-M subtypes (blaCTX-M-65, blaCTX-M-55, blaCTX-M-27, blaCTX-M-14, and blaCTX-M-123) with ISEcp1, IS903B, ISVsa5, and IS1R were found in ST17 isolates, especially Tn1721 containing ΔISEcp1-blaCTX-M-27-IS903B in P1-like bacteriophage plasmids. These findings on the prevalent and genomic characterization for the S. Indiana multidrug-resistant ST17 clone in China, which have not been reported yet, provide valuable insights into the potential risk of this high-resistant clone. IMPORTANCE Fluoroquinolones and cephalosporins are the primary choices for severe salmonellosis treatment. S. Indiana has become one of the most prevalent serovars in breeding poultry and poultry meats in China in recent years. ST17 was recognized as the leading epidemiological importance in S. Indiana because of its high-level resistance to the most of common antibiotics, including ciprofloxacin and ceftriaxone. However, the prevalence and phylogenomic characterization of ST17 isolates are unclear. Here, we did a retrospective screening on a large scale for S. Indiana in China, and performed its phylogenomic analysis. It was found that ST17 isolates had extensive spread in 15 provinces of China and became a multidrug-resistant clone. The international spread of the ST17 isolates was observed among several countries, especially China, the United Kingdom, and the United States. Our study emphasized the importance of surveillance of a high-resistant S. Indiana ST17 clone to combat its threat to public health.

Prevalence and Trends in Antimicrobial Susceptibility Patterns of Multi-Drug-Resistance Non-Typhoidal Salmonella in Central Thailand, 2012-2019.

Purpose: Multi-drug resistance of non-typhoidal Salmonella (MDR-NTS) is an increasing threat worldwide. In Thailand, data for the past decade is limited. This research is to determine the prevalence and trends of nonsusceptibility patterns of the bacteria, especially to ciprofloxacin and ceftriaxone. Methods: This retrospective study was extracted data of patients who had non-typhoidal Salmonella (NTS) infection, from 10 hospitals between June 2011 and June 2020. Demographic data, culture reports, and antimicrobial susceptibility were included in the analysis. Results: A total of 433 patients were identified. The most common age group was less than 15 years old (53.6%), with a median age of 12 years (IQR 57-4). Of these people, 61.1% had gastroenteritis and 36.7% had bacteremia. The most prevalent serogroups was C (28.6%). MDR-NTS rate was 52.8% (95% CI 39-44). The resistant rates were 43%, 32.8%, 22.8%, 6.7%, 4%, 0.45%, 0.45% for sulfamethoxazole/trimethoprim, amoxicillin-clavulanic acid, cefotaxime, ampicillin/sulbactam, piperacillin/tazobactam, imipenem and meropenem retrospectively. Resistant rates have been increasing, especially for ciprofloxacin (30%), which rose from 16.6% in 2011-2015 to 39.5% in 2016-2020 (prevalence rate ratio (PRR) 2.4,95% CI 1.51-3.72) and for ceftriaxone 25.4% which rose from 16.1% to 32% (PRR 2 95% CI 1.24-3.16). Ampicillin, norfloxacin, tetracycline, amikacin, gentamicin, and ceftazidime remained static at 62.3%, 49.5%, 33.2%, 15.2%, 8.8%, 2.8%, respectively. Conclusion: The prevalence of MDR-NTS has been increasing over the past decade, particularly those strains which demonstrate resistance to ciprofloxacin and ceftriaxone. Finding successful treatment requires a comprehensive selection of proper antimicrobials as well as close monitoring, especially in cases with severe infection.

The contribution of nano-based strategies in overcoming ceftriaxone resistance: a literature review.

Antimicrobial drug resistance, including resistance to multiple antibiotics, is continuously increasing. According to research findings, many bacteria resistant to other antibiotics were susceptible to ceftriaxone. However, over the last few years, ceftriaxone resistance has become growing and extremely worrisome challenge to the global healthcare system and several strategies have been initiated to contain the spread of antimicrobial drug resistance. Its extended use for therapeutic or preventative measures in humans and farm animals resulted in the development and spread of resistance. Recent advances in nanotechnology also offer novel formulations based on distinct types of nanostructure particles with different sizes and shapes, and flexible antimicrobial properties. For ceftriaxone, several nanostructured formulations through conjugation, intercalation, encapsulation with lipid carrier, and polymeric films have been investigated by different groups with promising results in combating the development of resistance. This review addressed the existing knowledge and practice on the contribution of nano-based delivery approaches in overcoming ceftriaxone resistance. Evidences have been generated from published research articles using major search electronic databases such as PubMed, Medline, Google Scholar, and Science Direct.