Ciprofloxacin Resistance Research Articles

The role of prokaryotic argonautes in resistance to type II topoisomerases poison ciprofloxacin.

Argonaute proteins are programmable nucleases found in all domains of life. Eukaryotic argonautes (eAgos) participate in genetic regulation, antiviral response, and transposon silencing during RNA interference. Prokaryotic argonautes (pAgos) are much more diverse than eAgos and have been implicated in defense against invading genetic elements. Recently, it was shown that pAgos protect bacterial cells from a topoisomerase poison ciprofloxacin, raising a possibility that they may play a role in DNA replication and/or repair. Here, we discuss possible models of pAgo-mediated ciprofloxacin resistance. We propose that pAgos could (i) participate in chromosome decatenation as a backup to topoisomerases; (ii) participate in the processing of DNA repair intermediates formed after topoisomerase poisoning, or (iii) induce SOS response that generally affects DNA repair and antibiotic resistance. These hypotheses should guide future investigations of the involvement of pAgos in the emergence of resistance to ciprofloxacin and, possibly, other antibiotics.

Antimicrobial Resistance of Environmental V. cholerae Non-O1/O139 Isolates: Systematic Review and Meta-analysis.

The understanding of the antibiotic resistance status of environmental nonO1/nonO139 V. cholerae [NOVC] in relation to other illnesses, which can vary in severity from mild to life-threatening, is limited. However, it is important to note that NOVC-related infections are increasing and serve as a significant illustration of emerging human diseases associated with climate change. The primary objective of the present study was to assess the rates of resistance observed in environmental NOVC isolates across various years, and regions, and their resistance rates. We performed a systematic search of Scopus, PubMed, Web of Science, and EMBASE databases [until May 2024] following PRISMA guidelines. All statistical analyses were carried out using the statistical package R. Our analysis included a total of 34 studies. According to the meta-regression, chlo-ramphenicol, rifampicin, ciprofloxacin, nalidixic acid, cotrimoxazole, kanamycin, trime-thoprim, amoxicillin/clavulanic acid, and tetracycline resistance rate increased over time. The lowest resistance rates were observed in Austria [amoxicillin; 0.6%], the United States [kana-mycin; 0.1% and tetracycline; 0.1%], Morocco [polymyxin B; 12%], and Spain [trimethoprim; 0.3%]. Conversely, the highest resistance rates were found in Spain [amoxicillin; 61%], Indo-nesia [kanamycin and tetracycline; 94.9%], India [polymyxin B; 97.8%], and Morocco [trime-thoprim; 48.9%]. The meta-analysis showed significant variability in antibiotic resistance patterns among environmental NOVC isolates across time and regions, emphasizing the need for tar-geted, time-specific, and country-specific approaches to address antibiotic resistance globally.

Prevalence of sexually transmitted infections and associated risk factors among female sex workers in Guinea-Bissau

ObjectiveTo estimate the prevalence of the curable sexually transmitted infections (STIs) Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and Treponema pallidum, to identify associated risk factors and to assess...

Multidrug-resistant bacteria in healthcare-associated infections among pediatric patients in Lima, Peru: a call for antibiotic stewardship programs

Abstract Background Healthcare-associated infections (HAIs) in children contribute to elevated morbidity and mortality rates. While the surveillance of antibiotic-resistant bacteria involved in HAIs is important, there is limited data available in Latin America. The present study aimed to evaluate the antibiotic resistance levels in bacteria isolated from hospitalized patients with HAIs in a pediatric referral center in Lima – Peru. Methods Surveillance data of HAIs from November 2021 to June 2023 among pediatric patients at Instituto Nacional de Salud del Niño San Borja was prospectively collected and reviewed. The dataset included comprehensive information on the clinical and epidemiological characteristics of patients, bacteria isolation sites and identification, as well as resistance profiles to 13 antibiotics. HAIs included were central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI) and ventilator-associated pneumonia (VAP). Results We included 143 bacterial isolates from pediatric patients hospitalized with HAIs, of which 53.85% were male (n=77). The median age of the patients was 7 months (IQR: 2 -36). A total of 44.76% (n=64) had congenital diseases and 20.28% (n=29) had cancer. Most of the isolates were collected from pediatric Intensive Care Unit (n=104, 72.73%). The median time from the hospital admission to the appearance of HAIs was 17 days (IQR: 7-28). The most frequent isolates were Gram negative bacteria: Klebsiella pneumoniae (n=33), Pseudomonas aeruginosa (n=34) and Escherichia coli (n=24). Among Gram positive bacteria, Staphylococcus epidermidis (n=5) and Staphylococcus aureus (n=5) were the most frequent species. Regarding the site of isolation, the primary etiological agent in CLABSI was K. pneumoniae (n=18); in CAUTI, E. coli (n=13) and in VAP P. aeruginosa (n=9). Multidrug-resistant (MDR) isolates were identified, mainly among K. pneumoniae (62.50%), E. coli (54.55%), and P. aeruginosa (26.74%). Difficult-to-treat resistance was only present in 2.94% of P. aeruginosa isolates. Overall resistance to piperacillin-tazobactam was below 16%. Resistance to cephalosporins was higher than 40% for K. pneumoniae and E. coli isolates, with frequencies exceeding 60% for cefuroxime, ceftazidime, ceftriaxone, cefepime and cefoperazone/sulbactam. E. coli and K. pneumoniae resistance to carbapenems was below than 10%; however, P. aeruginosa resistant isolates were identified in 38.24% and 39.39% for meropenem and imipenem, respectively. Ciprofloxacin resistance was frequent among E. coli (70%) and K. pneumoniae (60.87%), whereas only 26.67% of P. aeruginosa. Amikacin resistance was detected in K. pneumoniae and P. aeruginosa only, with a frequency of 23.08% and 20%, respectively. Conclusion Alarming levels of antibiotic-resistant bacteria were found in HAIs among pediatric patients. Our results highlight the need of supporting initiatives for HAIs control, developing institutional guidelines for prevention and strengthening antibiotic stewardship in pediatric patients. Table 1: Antibiotic resistance profiles of the main microorganisms of healthcare-associated infections (November 2021 – June 2023)

Clonal and resistance profiles of fluoroquinolone-resistant uropathogenic Escherichia coli in countries with different practices of antibiotic prescription.

Antibiotic prescription practices differ between countries, influencing regional antimicrobial resistance prevalence. However, comparisons of clonal diversity among resistant bacteria in countries with different prescribing practices are rare. The rise of fluoroquinolone-resistant Escherichia coli (FQREC), often multidrug-resistant, exacerbates global antibiotic resistance. Unlike in the USA, antibiotics are commonly dispensed in Iraq without prescriptions, leading to widespread overuse and misuse. This study aimed to assess the impact of varying antibiotic use practices on FQREC diversity. We compared FQREC prevalence, multidrug resistance, and clonality of FQREC among E. coli isolated from urine submitted between 2017 and 2018 to three US hospitals and two Iraqi hospitals. All FQREC isolates were analyzed for QRDR mutations and the presence of PMQR genes. A subset of FQREC strains from the ST131-H30R/Rx subgroups underwent whole-genome sequencing (WGS) and phylogenetic analysis. E. coli from Iraq showed significantly higher resistance to all tested antibiotics compared to those from the USA, with 76.2% being FQREC versus 31.2% in the USA (p < 0.01). Iraqi FQREC strains were more frequently multidrug resistant. The predominant subgroup in both countries was ST131-H30, with the notable absence of ST1193 among Iraqi FQREC. Iraqi-origin ST131-H30 strains exhibited higher minimum inhibitory concentrations (MICs) for ciprofloxacin and greater resistance to third-generation cephalosporins (3GC), trimethoprim/sulfamethoxazole (TMP/STX), and imipenem (IMI) than those from the USA. Increased 3GC resistance in Iraqi strains was linked to a higher proportion of bla CTX-M-15-carrying H30Rx subclade isolates. Additionally, Iraqi H30 strains exhibited higher MICs for fluoroquinolones due to more frequent carriage of PMQR determinants compared to US strains. Whole-genome sequencing was performed on 46 Iraqi and 63 US H30 isolates. Phylogenetic analysis revealed two clades-H30R and H30Rx-present in both countries, with isolates from both regions distributed throughout, without the emergence of distinct new major subclones. However, Iraqi isolates tended to cluster in separate subclades, indicating endemic circulation of the strain groups. In regions like Iraq, where antibiotics are overused and misused, resistance among uropathogenic E. coli to various antibiotics is significantly higher. Most Iraqi resistant strains belong to well-known international groups, and no new highly successful strains have emerged. The absence of ST1193 in Iraq may reflect regional, socioeconomic, demographic, or cultural factors that hinder the success of certain strain groups in the country.

Prevalence, antimicrobial resistance, and genomic characterization of Salmonella strains isolated in Hangzhou, China: a two-year study.

This study explored the molecular epidemiology and resistance mechanisms of 271 non-duplicate Salmonella enterica (S. enterica) strains, isolated mainly from adults (209/271) in a tertiary hospital in Hangzhou between 2020 and 2021. Through whole-genome sequencing and bioinformatics, the bacterial strains were classified into 46 serotypes and 54 sequence types (ST), with S. Enteritidis, S. 1,4,[5],12:i:-, and S. Typhimurium being the most prevalent serotypes and ST11, ST34, and ST19 the most common STs. The strains isolated from adults were primarily S. Enteritidis (59/209), while from children were mainly S. 1,4,[5],12:i:- (20/62). Worryingly, 12.55% strains were multi-drug resistant (MDR), with resistance rates to cefepime (FEP), ceftazidime (CAZ), ceftriaxone (CRO) and cefotaxime (CTX) of 7.38%, 9.23%, 15.87% and 16.24%, respectively, and resistance rates to levofloxacin (LEV) and ciprofloxacin (CIP) of 8.49% and 19.19%, respectively. It is worth noting that the resistance rates of CRO and CTX in children reached 30.65%. A total of 34 strains carried extended-spectrum β-lactamase (ESBL) genes, dominated by blaCTX-M-65 (13/34) and blaCTX-M-55 (12/34); it is notable that one strain of S. Saintpaul carried both blaCTX-M-27 and blaCTX-M-55. The resistance mechanism to cephalosporins was mainly due to ESBL genes (20/43), and other genes included AmpC and β-lactamase genes. The strains resistant to quinolones mainly carried qnrS1 (27/53), and others included qnrB6, aac(6')-Ib-cr, and mutations in gyrA and parC. One strain did not carry common quinolone resistance genes but had a parC (p.T57S) mutation to cause CIP resistance. This research provides vital insights into the molecular epidemiology and resistance mechanisms of clinical S. enterica, implicating possible infection control strategies.

Genetic and in-silico approaches for investigating the mechanisms of ciprofloxacin resistance in Salmonella typhi: Mutations, extrusion, and antimicrobial resistance

Salmonella enterica serovar Typhi spreads typhoid infection in humans through the consumption of contaminated food and water. Poor sanitation plays a pivotal role in its dissemination. Over time, the bacterium has acquired resistance to many promising antibiotics, posing a growing global health concern and hindering the achievement of sustainable development goals. This study aims to elucidate the molecular complexity of fluoroquinolone resistance, a first-line treatment for typhoid infection. To achieve this aim, 80 clinical isolates were collected from various diagnostic laboratories. These isolates were confirmed based on morphological characteristics and biochemical tests. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were identified using the Kirby-Bauer disc diffusion method. The mechanism of ciprofloxacin resistance was investigated by sequencing the quinolone resistance-determining region (QRDR) genes and identifying the presence of the qnrS1 gene. As a result of this study, 60 % of isolates showed resistance to ciprofloxacin. At the same time, the qnrS1 gene was present in all the selected strains while mutation analysis identified significant mutation in QRDR of DNA gyrase subunit A (gyrA) and Topoisomerase IV (parC) gene. The combinatorial effect was further investigated by downloading 286 draft genomes. The Mutation analysis reveals significant mutations at gyrA S83F, gyrA D87N, gyrA S83Y, gyrB S464F, parC S80I, and parE L416F. Additionally, docking analysis indicates reduced binding affinity and altered solvent accessibility, which show the structural changes at mutation sites. This study provides crucial insights that mutation reduces the binding affinity while qnrS1 acts as a transport channel to extrude the ciprofloxacin. In the future, further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. Typhi.

Synthesis and evaluation of iron oxide nanoparticles from banana peel (Musa spp.) extract for the delivery of ciprofloxacin against resistant Escherichia coli

Background and objectiveResistance to antimicrobials is one of our most significant worldwide challenges. In Africa, around 31 % of the infections of urinary tract (UTIs) initiated by Escherichia coli (E. coli) have been observed to develop ciprofloxacin (CIP) resistance. As a result, significant efforts have been made to investigate novel and improved antibiotics. This study aimed at synthesizing iron oxide nanoparticles (IONPs) using banana peels (Musa Spp.) extract for delivery of CIP against resistant E. coli. MethodsA green synthesis method was used for the synthesis of IONPs using FeCl3.6H2O as a precursor and banana peel extract as a reducing and stabilizing agent. The physicochemical characteristics of the formed nanoparticles (NPs) were characterized using different methods. ResultsThe formation of hematite (α-Fe2O3) was confirmed with its FTIR characteristic peak at 461 cm−1, 542 cm−1, and 1131 cm−1. The size of synthesized IONPs was found to be 10.4 nm ± 1.98, 48 nm ± 0.9, and 67.3 nm ± 0.9 under XRD, SEM, and DLS measurements respectively. CIP-IONPs had almost the maximum drug loading capacity (33.3 % ± 0.67) with fast and slow drug release patterns at gastric and intestinal or blood pH respectively, and it had a promising resistant reversal with a zone of inhibition (ZOI) 22 mm ± 0.15 against resistance E. coli. ConclusionThe green synthesis of IONP using banana peel extract represents a novel and eco-friendly approach for the delivery of ciprofloxacin, with potential applications in addressing antimicrobial resistance.

A Decade of Antimicrobial Resistance in Human and Animal Campylobacter spp. Isolates.

Objectives: Campylobacter spp. remain a leading cause of bacterial gastroenteritis worldwide, with resistance to antibiotics posing significant challenges to treatment and public health. This study examines profiles in antimicrobial resistance (AMR) for Campylobacter isolates from human and animal sources over the past decade. Methods: We conducted a comprehensive review of resistance data from studies spanning ten years, analyzing profiles in resistance to key antibiotics, ciprofloxacin (CIP), tetracycline (TET), erythromycin (ERY), chloramphenicol (CHL), and gentamicin (GEN). Data were collated from various regions to assess global and regional patterns of resistance. Results: The analysis reveals a concerning trend of increasing resistance patterns, particularly to CIP and TET, across multiple regions. While resistance to CHL and GEN remains relatively low, the high prevalence of CIP resistance has significantly compromised treatment options for campylobacteriosis. Discrepancies in resistance patterns were observed between human and animal isolates, with variations across different continents and countries. Notably, resistance to ERY and CHL showed regional variability, reflecting potential differences in antimicrobial usage and management practices. Conclusions: The findings underscore the ongoing challenge of AMR in Campylobacter, highlighting the need for continued surveillance and research. The rising resistance prevalence, coupled with discrepancies in resistance patterns between human and animal isolates, emphasize the importance of a One Health approach to address AMR. Enhanced monitoring, novel treatment strategies, and global cooperation are crucial for mitigating the impact of resistance and ensuring the effective management of Campylobacter-related infections.

MOLECULAR SURVEILLANCE OF GONOCOCCAL CIPROFLOXACIN SUSCEPTIBILITY/RESISTANCE IN BULGARIA, 2022-2023

Background: The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is a significant public health issue, with Euro-GASP conducting surveillance across the EU-EEA. The advent of molecular diagnostics for N. gonorrhoeae may possibly limit the surveillance data because it is dependent on gonococcal culture for phenotypic susceptibility testing. Ideally, molecular diagnostics should combine identification and resistance detection but the complexity of gonococcal molecular genetics of resistance is a major barrier for test development. Currently, resistance prediction in N. gonorrhoeae is accurate only for fluoroquinolones and there are commercial kits available on the market that allow antimicrobial resistance surveillance and individualized treatment. The study examined Bulgaria's gonococcal fluoroquinolone resistance rate for 2022-2023 by molecular methods and compared it with previous years and EU-EEA trends. Methods: The commercial ResistancePlus® GC assay was used to predict ciprofloxacin susceptibility/resistance in 66 Neisseria gonorrhoeae-positive DNA samples from patients, diagnosed in 2022-2023. Results: The identified fluoroquinolone resistance rate in 2022-2023 was 68.2%. The majority of the cases were males in the age group 20-29 (50.8%), the most common mode of transmission was MSM (77%) and 17% of the cases with known HIV status were positive. Conclusion: This study found a higher than before fluoroquinolone resistance rate (68.2%) in Bulgaria, following the trend in Europe. In the EU-EEA, ciprofloxacin resistance increased to 65.9% in 2022. Molecular testing for predicting susceptibility/resistance is suitable for effective antimicrobial resistance surveillance and individualized treatment decisions.

Characterization of azithromycin-resistant Shigella flexneri serotype 2a isolates using whole genome sequencing in Ontario from 2016 to 2018.

Azithromycin-resistant shigellosis is increasing globally. This retrospective analysis of Shigella flexneri serotype 2a isolates from 2016 to 2018 in Ontario found nearly half were azithromycin (47.7%, 72/151) and ciprofloxacin (50.7%, 77/152) resistant. Moreover, 34.7% (25/72) of azithromycin-resistant isolates were also ciprofloxacin-resistant. Four isolates were ceftriaxone-resistant, although all azithromycin-resistant isolates were ceftriaxone-susceptible. Overall, 83.6% (127/152) of all S. flexneri 2a isolates were recovered from males and 97.2% (70/72) of the azithromycin-resistant cases were males. Among the azithromycin-resistant cases, some (8/72) reported international travel. Phylogenetic analysis of azithromycin-resistant isolates revealed two large male-dominated clusters, and one cluster may have been due to importation of resistant strain. Comparison of plasmids isolated from the clusters in Ontario revealed the presence of incFII plasmid with high percentage of similarity to plasmids present in global outbreaks affecting mostly males including men who have sex with men (MSM). These two large azithromycin-resistant clusters are suggestive of an outbreak among MSM, though disease exposure or sexual orientation of patients was unknown. The presence of plasmid-borne azithromycin resistance in ciprofloxacin-resistant isolates is a public health concern. Antimicrobial surveillance is important for patient management, understanding the spread of novel resistance types in local communities which sometimes is introduced by travel. We found ongoing multidrug-resistant outbreaks spanning multiple years affecting males. Reduction of future outbreaks in high-risk communities like MSM requires consorted information flow between laboratory, public health, and physicians. We impart genomic and antimicrobial characteristics of multidrug S. flexneri 2a which may serve as reference by clinicians and public health.IMPORTANCEOral ciprofloxacin and azithromycin are generally considered as the first-line therapy of shigellosis. Here, we report the emergence and transmission of azithromycin and ciprofloxacin-resistant S. flexneri serotype 2a among male adults in Ontario during 2016-2018. The percentage of azithromycin and ciprofloxacin resistance among S. flexneri 2a is higher compared to previous reports from Canada and United States. Here, we show the genetic basis of the antimicrobial resistance among these unique groups of S. flexneri 2a isolates. We describe a domestically acquired azithromycin-resistant and ciprofloxacin-resistant S. flexneri 2a lineage in Ontario. Combining whole-genome sequencing (WGS) data with travel-associated data helped in understanding dissemination and transmission. We employed WGS, which not only helped us in understanding the genetic-relationship between isolates but also mine information regarding plasmids. In the future, linking WGS, travel-related data, and clinical data can provide enhanced contact tracing and improve public-health management.

Selective increase of antibiotic-resistant denitrifiers drives N2O production in ciprofloxacin-contaminated soils

Agricultural systems significantly contribute to global N2O emissions, which is intensified by excessive fertilization and antibiotic residues, attracting global concerns. However, the dynamics and pathways of antibiotics-induced soil N2O production coupled with microbial metabolism remain controversial. Here, we explored the pathways of N2O production in agricultural soils exposed to ciprofloxacin (CIP), and revealed the underlying mechanisms of CIP degradation and the associated microbial metabolisms using 15N-isotope labeling and molecular techniques. CIP exposure significantly increases the total soil N2O production rate. This is attributed to an unexpected shift from heterotrophic and autotrophic nitrification to denitrification and an increased abundance of denitrifiers Methylobacillus members under CIP exposure. The most striking strain M. flagellatus KT is further discovered to harbor N2O-producing genes but lacks a N2O-reducing gene, thereby stimulating denitrification-based N2O production. Moreover, this denitrifying strain is probably capable of utilizing the byproducts of CIP as carbon sources, evidenced by genes associated with CIP resistance and degradation. Molecular docking further shows that CIP is well ordered in the catalytic active site of CotA laccase, thus affirming the potential for this strain to degrade CIP. These findings advance the mechanistic insights into N2O production within terrestrial ecosystems coupled with the organic contaminants degradation.

Effect of Mentha longifolia essential oil on oqxA efflux pump gene expression and biofilm formation in ciprofloxacin-resistant Klebsiella pneumoniae strains.

Today, medicinal plants and their derivatives are considered to reduce the prevalence of antibiotic resistance. The aim of this study was to investigate the effect of Mentha longifolia essential oil on oqxA efflux pump gene expression and biofilm formation in ciprofloxacin-resistant Klebsiella pneumoniae strains. A total of 50 clinical strains of K. pneumoniae resistant to ciprofloxacin were studied. The minimum inhibitory concentration (MIC) of M. longifolia essential oil and its synergistic effect with ciprofloxacin were determined using the microbroth dilution method and the fractional inhibitory concentration (FIC) method. Minimum biofilm inhibition concentration (MBIC) of M. longifolia essential oil was detected. The effect of essential oils on the expression level of the oqxA gene was detected by Real-time PCR. M. longifolia essential oil showed inhibitory activity against ciprofloxacin-resistant strains of K. pneumoniae. When M. longifolia essential oil was combined with ciprofloxacin, the MIC was reduced 2-4 times. In 28% of the strains, M. longifolia with ciprofloxacin showed a synergistic effect. M. longifolia essential oil reduces the strength of biofilm formation and alters the biofilm phenotype. A significant decrease in oqxA gene expression was observed in all isolates after treatment with M. longifolia essential oil. Based on the results of this study, it was observed that supplementing M. longifolia essential oil can help reduce ciprofloxacin resistance and inhibit biofilm formation in fluoroquinolone-resistant K. pneumoniae strains.

A molecular and phenotypic analysis of the prevalence and patterns of antimicrobial resistance in Neisseria gonorrhoeae isolates from Kwazulu Natal, South Africa

Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented worldwide; however, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance to prevent the emergence of illnesses resistant to multiple treatments. Monitoring antimicrobial susceptibility is crucial to gather data that can inform treatment recommendations, resulting in effective therapy, reduced gonorrhea-related complications and transmission, and efficient treatment. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make decisions about the allocation of STI prevention services and resources, to guide preventive planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The majority of gonococcal isolates (48 %) showed absolute resistance to ciprofloxacin, with penicillin and tetracycline resistance rates of 14 % each. Only one gonococcal isolate tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested.

In vitro evolution of ciprofloxacin resistance in Neisseria commensals and derived mutation population dynamics in natural Neisseria populations.

Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing. 10/16 selected cells lines across the 4 species evolved ciprofloxacin resistance (≥ 1 ug/ml); with resistance-contributing mutations primarily emerging in DNA gyrase subunit A and B (gyrA and gyrB), topoisomerase IV subunits C and E (parC and parE), and the multiple transferable efflux pump repressor (mtrR). Of note, these derived mutations appeared in the same loci responsible for ciprofloxacin reduced susceptibility in the pathogenic Neisseria, suggesting conserved mechanisms of resistance across the genus. Additionally, we tested for zoliflodacin cross-resistance in evolved strain lines and found 6 lineages with elevated zoliflodacin minimum inhibitory concentrations. Finally, to interrogate the likelihood of experimentally derived mutations emerging and contributing to resistance in natural Neisseria, we used a population-based approach and identified GyrA 91I as a substitution circulating within commensal Neisseria populations and ParC 85C in a single gonococcal isolate. Small clusters of gonococcal isolates had commensal-like alleles at parC and parE, indicating recent cross-species recombination events.

Sexually Transmitted Infections in Italian Young and Adult People: A Worrying Positive Trend Hidden by COVID-19 Epidemic.

Recent European data show an increase in sexually transmitted infections (STIs), particularly N. gonorrhoeae, among young heterosexuals, surpassing pre-pandemic numbers. Italy's varied local health restrictions during the COVID-19 pandemic likely affected STI management and reporting. To evaluate COVID-19's impact on STI spread in Italy, we analyzed microbiological data from before and during the pandemic in an area with minimal restrictions on clinical services. This retrospective study (2017-2022) included 5503 subjects: 2586 from STI clinics (STD group) and 3687 diagnosed with primary infertility (ART group). Samples were tested for Mycoplasmas/Ureaplasmas, C. trachomatis, N. gonorrhoeae, and T. vaginalis by a multiplex PCR. During the pandemic, overall STI prevalence increased significantly (p < 0.01). U. parvum was the most frequent microorganism in the STD group (26.1% vs. 23.9%), with a notable increase in women (52.1% vs. 32.7%) (p < 0.001). C. trachomatis and M. hominis positive rates decreased significantly (p < 0.001 and p < 0.01, respectively). N. gonorrhoeae cases rose among young people (19-29), predominantly heterosexual, with high ciprofloxacin resistance. In the ART group, U. parvum was the most common infection, particularly in young infertile women (p = 0.01). This study indicates a notable rise in STIs among young people, including heterosexuals, despite social restrictions. The long-term impact of this trend requires further evaluation.

Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC50 = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics—tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)—compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Occurrence and characterization of plasmid-encoded qnr genes in quinolone-resistant bacteria across diverse aquatic environments in southern Ontario.

Antimicrobial resistance is an ever-increasing threat. The widespread usage of ciprofloxacin has led to the manifestation of resistance due to chromosomal mutations or the acquisition of plasmid-mediated quinolone resistance (PMQR) traits. Some particular PMQR traits, qnr genes, have been identified globally in clinical and environmental isolates. This study aimed to determine the prevalence of ciprofloxacin-resistant bacteria in aquatic environments in southern Ontario and investigate the extent of dissemination of ciprofloxacin resistance traits among the bacterial communities. We surveyed the prevalence of plasmid encoding qnr genes using a multiplex PCR assay of associated PMQR genes, qnrA, qnrB, and qnrS, on 202 isolates. Despite the absence of significant impacts on minimum inhibitory concentration levels, the presence of qnr genes correlates with heightened resistance to quinolones and nalidixic acid in some isolates. Taxonomic analysis highlights distinct differences in the composition and diversity of ciprofloxacin-sensitive (CipS) and ciprofloxacin-resistant (CipR) populations, with Proteobacteria dominating both groups. Importantly, CipR populations exhibit lower genetic diversity but higher prevalence of multiple antibiotic resistances, suggesting co-selection mechanisms. Co-occurrence analysis highlights significant associations between ciprofloxacin resistance and other antibiotic resistances, implicating complex genetic linkages. The results of our study signified the critical role of environmental monitoring in public health.

Ciprofloxacin and Imipenem Resistance in Bathing Waters—Preliminary Studies of Great Rudnickie Lake

Ciprofloxacin and Imipenem Resistance in Bathing Waters—Preliminary Studies of Great Rudnickie Lake

An Investigation of Ciprofloxacin-resistant Neisseria Meningitidis Serogroup B Infection Outbreak in a Provincial Prison, Nan Province, Thailand, October 2023

Meningococcal infection is a severe illness that can result in organ damage or death. On 23 Oct 2023, a joint investigation team was notified about two inmates diagnosed with meningococcal infection in a provincial prison. The investigation aimed to confirm the outbreak, describe epidemiological characteristics, determine possible source and risks of infection, and provide recommendations and control measures. This study reviewed the situation using surveillance databases. Active case finding was conducted among inmates and prison staff. Close contacts were identified and assessed. Drug sensitivity and serogroup identification were done in the cultured-growth specimens. Surveying inmate rooms, observing inmates' behaviors, and interviewing inmates and prison staff were performed. There were 7 laboratory-confirmed cases identified (attack rate 0.5%). All cases were male inmates with a median age of 46 years (interquartile range 38.5–49.5 years). Common symptoms were fever (100%) and headache (71%). Eight cases required hospital admission and one dead case was found (CFR 14%). Among 609 close contacts, 99% were inmates. All cultured-growth specimens were Neisseria meningitidis serogroup B with ciprofloxacin resistance. Crowded inmates and sharing water cups were risk factors for intra-room spreading. Daily activities and the previous influenza outbreak promoted inmates' inter-room contact. This is the ciprofloxacin-resistant serogroup B meningococcal disease outbreak in a provincial prison revealing multiple factors, including environmental, behaviors and daily activities, that promoted the disease's spread. Rifampicin chemoprophylaxis, active surveillance, and limited inmate activities could help reduce disease spread.