Rates Of Fluoroquinolone Resistance Research Articles

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.

Risk assessment and transmission of fluoroquinolone resistance in drug-resistant pulmonary tuberculosis: a retrospective genomic epidemiology study

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34–20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25–3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.

Genotypic characterization and antimicrobial susceptibility of human Campylobacter jejuni isolates in Southern Spain.

Campylobacter jejuni is the main cause of bacterial gastroenteritis and a public health problem worldwide. Little information is available on the genotypic characteristics of human C. jejuni in Spain. This study is based on an analysis of the resistome, virulome, and phylogenetic relationship, antibiogram prediction, and antimicrobial susceptibility of 114 human isolates of C. jejuni from a tertiary hospital in southern Spain from October 2020 to June 2023. The isolates were sequenced using Illumina technology, and a bioinformatic analysis was subsequently performed. The susceptibility of C. jejuni isolates to ciprofloxacin, tetracycline, and erythromycin was also tested. The resistance rates for each antibiotic were 90.3% for ciprofloxacin, 66.7% for tetracycline, and 0.88% for erythromycin. The fluoroquinolone resistance rate obtained is well above the European average (69.1%). CC-21 (n = 23), ST-572 (n = 13), and ST-6532 (n = 13) were the most prevalent clonal complexes (CCs) and sequence types (STs). In the virulome, the cadF, ciaB, and cdtABC genes were detected in all the isolates. A prevalence of 20.1% was obtained for the genes wlaN and cstIII, which are related to the pathogenesis of Guillain-Barré syndrome (GBS). The prevalence of the main antimicrobial resistance markers detected were CmeABC (92.1%), RE-cmeABC (7.9%), the T86I substitution in gyrA (88.9%), blaOXA-61 (72.6%), tet(O) (65.8%), and ant (6)-Ia (17.1%). High antibiogram prediction rates (>97%) were obtained, except for in the case of the erythromycin-resistant phenotype. This study contributes significantly to the knowledge of C. jejuni genomics for the prevention, treatment, and control of infections caused by this pathogen.IMPORTANCEDespite being the pathogen with the greatest number of gastroenteritis cases worldwide, Campylobacter jejuni remains a poorly studied microorganism. A sustained increase in fluoroquinolone resistance in human isolates is a problem when treating Campylobacter infections. The development of whole genome sequencing (WGS) techniques has allowed us to better understand the genotypic characteristics of this pathogen and relate them to antibiotic resistance phenotypes. These techniques complement the data obtained from the phenotypic analysis of C. jejuni isolates. The zoonotic transmission of C. jejuni through the consumption of contaminated poultry supports approaching the study of this pathogen through "One Health" approach. In addition, due to the limited information on the genomic characteristics of C. jejuni in Spain, this study provides important data and allows us to compare the results with those obtained in other countries.

Assessment of Antibiotic Resistance among Clinical Isolates of Enterobacteriaceae in Nepal.

Clinicians face a global challenge treating infections caused by Enterobacteriaceae because of the high rate of antibiotic resistance. This cross-sectional study from the Nepal Armed Police Force Hospital, Kathmandu, Nepal, characterized resistance patterns in Enterobacteriaceae across different antimicrobial classes and assessed incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections. Enterobacteriaceae from clinical samples were isolated on blood and MacConkey agar, except for urine samples on cysteine lactose electrolyte-deficient agar. To determine antimicrobial susceptibility patterns, including MDR and XDR, the Kirby-Bauer disc diffusion method was used. Statistics were performed using SPSS, v. 17.0. Members of the family were identified in 14.5% (95% CI: 16.2-12.8%) of the total samples (N = 1,617), primarily in urine (54.7%, 128/234), blood (19.7%, 46/234), and sputum (15.0%, 35/234). Escherichia coli (n = 118, 44.2%) was the most predominant bacteria, followed by Citrobacter freundii (n = 81, 30.3%). As much as 95.6% (392/410) of the isolates were penicillin-resistant, whereas only 36.2% (290/801) were carbapenem-resistant. A total of 96 (36.0%) MDR and 98 (36.7%) XDR Enterobacteriaceae were identified. Proteus mirabilis (44.4%, 8/18) predominated MDR cultures, whereas C. freundii (53.1%, 43/81) predominated XDR cultures. Multidrug resistant (38.4%, 71/154) and XDR Enterobacteriaceae (22.7%, 35/154) were chiefly uropathogens. Fluoroquinolone resistance rates in non-MDR, MDR, and XDR isolates were 19.9%, 63.2%, and 96.2%, respectively, whereas cephalosporin resistance rates were 28.6%, 72.9%, and 95.4% and penicillin resistance rates were 67.0%, 97.4%, and 98.0%. One-seventh of patients visiting the hospital were found to be infected with Enterobacteriaceae, and of these patients, at least one-fourth were infected with MDR strains.

Characterization of Beta-Lactamase and Fluoroquinolone Resistance Determinants in Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa Isolates from a Tertiary Hospital in Yola, Nigeria.

Infections due to antimicrobial resistant gram-negative bacteria cause significant morbidity and mortality in sub-Saharan Africa. To elucidate the molecular epidemiology of antimicrobial resistance in gram-negative bacteria, we characterized beta-lactam and fluoroquinolone resistance determinants in Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates collected from November 2017 to February 2018 (Period 1) and October 2021 to January 2022 (Period 2) in a tertiary medical center in north-eastern Nigeria. Whole genome sequencing (WGS) was used to identify sequence types and resistance determinants in 52 non-duplicate, phenotypically resistant isolates. Antimicrobial susceptibility was determined using broth microdilution and modified Kirby-Bauer disk diffusion methods. Twenty sequence types (STs) were identified among isolates from both periods using WGS, with increased strain diversity observed in Period 2. Common ESBL genes identified included blaCTX-M, blaSHV, and blaTEM in both E. coli and K. pneumoniae. Notably, 50% of the E. coli in Period 2 harbored either blaCTX-M-15 or blaCTX-M-1 4 and phenotypically produced ESBLs. The blaNDM-7 and blaVIM-5 metallo-beta-lactamase genes were dominant in E. coli and P. aeruginosa in Period 1, but in Period 2, only K. pneumoniae contained blaNDM-7, while blaNDM-1 was predominant in P. aeruginosa. The overall rate of fluoroquinolone resistance was 77% in Period 1 but decreased to 47.8% in Period 2. Various plasmid-mediated quinolone resistance (PMQR) genes were identified in both periods, including aac(6')-Ib-cr, oqxA/oqxB, qnrA1, qnrB1, qnrB6, qnrB18, qnrVC1, as well as mutations in the chromosomal gyrA, parC and parE genes. One E. coli isolate in Period 2, which was phenotypically multidrug resistant, had ESBL blaCTX-M-15, the serine carbapenemase, blaOXA-181 and mutations in the gyrA gene. The co-existence of beta-lactam and fluoroquinolone resistance markers observed in this study is consistent with widespread use of these antimicrobial agents in Nigeria. The presence of multidrug resistant isolates is concerning and highlights the importance of continued surveillance to support antimicrobial stewardship programs and curb the spread of antimicrobial resistance.

One health transmission of fluoroquinolone-resistant Escherichia coli and risk factors for their excretion by dogs living in urban and nearby rural settings

Rates of fluoroquinolone resistance in Escherichia coli, a key opportunistic human pathogen, are problematic. Taking a One Health approach, we investigated the excretion of fluoroquinolone-resistant (FQ-R) E. coli by 600 dogs (303 from rural and 297 from urban environments) recruited from a 50 × 50 km region where we have also surveyed FQ-R E. coli from cattle and from human urine. FQ-R E. coli were detected in faeces from 7.3% (rural) and 11.8% (urban) of dogs. FQ-R E. coli from rural dogs tended to be of sequence types (STs) commonly excreted by cattle, whilst those from urban dogs tended to carry plasmid-mediated quinolone resistance genes, common in human E. coli in our study region. Phylogenetic evidence was obtained for sharing FQ-R E. coli - particularly for STs 10, 162 and 744 - between cattle, dogs and humans. Epidemiological analysis showed a strong association between feeding dogs uncooked meat and the excretion of FQ-R E. coli, particularly for STs 10, 162 and 744. This practice, therefore, could serve as a transmission link for FQ-R E. coli from farmed animals entering the home so we suggest that dogs fed uncooked meat should be handled and housed using enhanced hygiene practices.

The scope of antimicrobial resistance in residential aged care facilities determined through analysis of Escherichia coli and the total wastewater resistome.

High and often inappropriate antibiotic use has been documented for residential aged care facilities (RACFs). As a result, RACFs represent selective environments favoring the development of antimicrobial resistance (AMR). However, surveillance of the prevalence and scope of AMR in RACFs is limited. Here, wastewater-based epidemiology encompassing culture-based methods in combination with whole genome sequencing and metagenomics allowed for the in-depth analysis of the prevalence of antimicrobial-resistant Escherichia coli in two RACFs and one retirement facility. Wastewater was collected at five different time points over 18 months. From these, E. coli were isolated and assessed for phenotypic and genotypic resistance. The antimicrobial resistome of each wastewater sample was also determined. A comparison of facilities revealed a higher prevalence of AMR and multidrug-resistant E. coli observed in one RACF. The international high-risk E. coli clone, ST131, carrying CTX-M-like extended-spectrum beta-lactamases was exclusively isolated from this facility. A high proportion of these isolates were classified as belonging to phylogroups B2 and D, associated with virulent extra-intestinal E. coli infections. The resistome of this facility also revealed a higher prevalence of mobile resistance genes such as sul1 and sul2, conferring sulfamethoxazole resistance, the plasmid-mediated quinolone-resistance gene qnrS, and qacEdelta1 that confers biocide resistance. High fluoroquinolone resistance rates were observed in all three sample sites despite measures in place limiting the use of this class of antibiotics. The findings of this study illustrate that RACFs are highly selective environments that require measures to limit AMR development, potentially through antimicrobial stewardship. IMPORTANCE Antimicrobial resistance (AMR) is a global threat that imposes a heavy burden on our health and economy. Residential aged care facilities (RACFs), where frequent inappropriate antibiotic use creates a selective environment that promotes the development of bacterial resistance, significantly contribute to this problem. We used wastewater-based epidemiology to provide a holistic whole-facility assessment and comparison of antimicrobial resistance in two RACFs and a retirement village. Resistant Escherichia coli, a common and oftentimes problematic pathogen within RACFs, was isolated from the wastewater, and the phenotypic and genotypic AMR was determined for all isolates. We observed a high prevalence of an international high-risk clone, carrying an extended-spectrum beta-lactamase in one facility. Analysis of the entire resistome also revealed a greater number of mobile resistance genes in this facility. Finally, both facilities displayed high fluoroquinolone resistance rates-a worrying trend seen globally despite measures in place aimed at limiting their use.

Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China.

Multidrug-resistant tuberculosis (MDR-TB) has a severe impact on public health. To investigate the drug-resistant profile, compensatory mutations and genetic variations among MDR-TB isolates, a total of 546 MDR-TB isolates from China underwent drug-susceptibility testing and whole genome sequencing for further analysis. The results showed that our isolates have a high rate of fluoroquinolone resistance (45.60%, 249/546) and a low proportion of conferring resistance to bedaquiline, clofazimine, linezolid, and delamanid. The majority of MDR-TB isolates (77.66%, 424/546) belong to Lineage 2.2.1, followed by Lineage 4.5 (6.41%, 35/546), and the Lineage 2 isolates have a strong association with pre-XDR/XDR-TB (P < 0.05) in our study. Epidemic success analysis using time-scaled haplotypic density (THD) showed that clustered isolates outperformed non-clustered isolates. Compensatory mutations happened in rpoA, rpoC, and non-RRDR of rpoB genes, which were found more frequently in clusters and were associated with the increase of THD index, suggesting that increased bacterial fitness was associated with MDR-TB transmission. In addition, the variants in resistance associated genes in MDR isolates are mainly focused on single nucleotide polymorphism mutations, and only a few genes have indel variants, such as katG, ethA. We also found some genes underwent indel variation correlated with the lineage and sub-lineage of isolates, suggesting the selective evolution of different lineage isolates. Thus, this analysis of the characterization and genetic diversity of MDR isolates would be helpful in developing effective strategies for treatment regimens and tailoring public interventions. IMPORTANCE Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis prevention and control in China. This study provides insight into the drug-resistant characteristics of MDR combined with phenotypic drug-susceptibility testing and whole genome sequencing. The compensatory mutations and epidemic success analysis were analyzed by time-scaled haplotypic density (THD) method, suggesting clustered isolates and compensatory mutations are associated with MDR-TB transmission. In addition, the insertion and deletion variants happened in some genes, which are associated with the lineage and sub-lineage of isolates, such as the mpt64 gene. This study offered a valuable reference and increased understanding of MDR-TB in China, which could be crucial for achieving the objective of precision medicine in the prevention and treatment of MDR-TB.

Changes in prevalence of Mycoplasma genitalium macrolide and fluoroquinolone resistance: notes from a 13-year retrospective survey in Dalarna County, Sweden

ObjectiveMacrolide and fluoroquinolone resistance in Mycoplasma genitalium (MG) is of emerging global concern. Compared with neighbouring countries such as Denmark, Sweden has had lower rates of macrolide resistance while fluoroquinolone...

Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

Association of qnr Genes and OqxAB Efflux Pump in Fluoroquinolone-Resistant Klebsiella pneumoniae Strains.

The aim of this study was to investigate the frequency and relationship between plasmid-mediated quinolone resistance genes and OqxAB pump genes, as well as the genetic linkage in K. pneumoniae strains isolated from Hamadan hospitals in the west of Iran. In this study, 100 K. pneumoniae clinical strains were isolated from clinical samples of inpatients at Hamadan Hospital in 2021. The antimicrobial susceptibility testing was performed using the disk diffusion method. The frequencies of genes encoding OqxAB efflux pumps and qnr were investigated by PCR. Molecular typing of qnr-positive K. pneumoniae isolates was assessed by ERIC-PCR. Antibiotic susceptibility testing showed high resistance (>80%) to fluoroquinolones. The gene encoding the OqxAB efflux pump was detected in more than 90% of K. pneumomiae strains. All K. pneumoniae isolates were negative for qnrA, and 20% and 9% of the isolates were positive for qnrB and qnrS, respectively. The genes encoding oqxA and oqxB were detected in 96% of qnr-positive strains. A qnrB + /qnrS + profile was observed in 16% of qnr-positive K. pneumoniae strains. Ciprofloxacin MIC ≥ 256 μg/ml was detected in 20% of qnr-positive strains. Genetic association analysis by ERIC-PCR revealed genetic diversity among 25 different qnr-positive strains of K. pneumonia. However, no significant correlation was found between the qnr and the OqxAB efflux pump genes in this study. The high rate of fluoroquinolone resistance and determinants of antibiotic resistance among diverse K. pneumoniae strains increase the risk of fluoroquinolone-resistance transmission by K. pneumoniae strains in hospitals.

Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration.

Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX. Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: An alert for empirical treatment

Bacterial resistance to extended-spectrum beta-lactamases (ESBL) is present worldwide. Empirical antibiotic therapy is often needed, and the use of fluoroquinolones, such as ciprofloxacin and norfloxacin, is common. This study aimed to analyze the urine cultures from 2,680 outpatients in January 2019, 2020, 2021, and 2022, with bacterial counts above 100,000 CFU/mL in which Escherichia coli was the etiological agent. We monitored the resistance of ESBL-positive and ESBL-negative strains to ciprofloxacin and norfloxacin and evaluated resistance rates. Significantly higher fluoroquinolone resistance rates were observed among ESBL-positive strains in all years studied. Furthermore, a significant increase in the rate of fluoroquinolone resistance was observed between 2021 and 2022 in ESBL-positive and -negative strains, as well as from 2020 to 2021 among the ESBL-positive strains. The data obtained in the present study showed a tendency towards an increase in fluoroquinolone resistance among ESBL-positive and -negative E. coli strains isolated from urine cultures in Brazil. Since empirical antibiotic therapy with fluoroquinolones is commonly used to treat diverse types of infections, such as community-acquired urinary tract infections, this work highlights the need for continuous monitoring of fluoroquinolone resistance among E. coli strains circulating in the community, which can mitigate the frequency of therapeutic failures and development of widespread multidrug-resistant strains.

1787. County Level Association Between the Rate of Fluoroquinolone-Resistance Gram Negative Bacteria and Fluoroquinolone Utilization in Kansas

Abstract Background Kansas ranks as the 8th-worst state nationally for outpatient antibiotic prescribing, with a rate of 690 antibiotic prescriptions per 1000 population. The statewide rate of fluoroquinolone (FQ) is disproportionately higher than other antibiotic drug classes. Statewide antibiograms can be developed by health departments for antimicrobial stewardship monitoring. The purpose of this study was to investigate the correlation between the FQ resistance rate of gram-negative bacteria to FQ consumption. Methods A retrospective design utilizing 2018-2019 county level FQ-resistant Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was categorized by county level based on the Kansas statewide antibiogram. Outpatient FQ utilization data was obtained from IQVIA and categorized into county level FQ rate based on prescriptions dispensed per 1000 population. Linear regression was used to compare antibiotic resistance (AR) to FQ utilization by county. Results Sixty-six of 123 facilities contacted for antibiogram data responded with results. Of these, 47 were critical access hospitals, and the rest were acute care hospitals or clinics. A total of 31,573 E. coli isolates, 5,942 K. pneumoniae and 5,017 P. aeruginosa isolates were represented. All 106 counties had FQ prescription data. Of the 49 counties with AR reported, FQ rates ranged from 4.6 to 105.6/1000 population. There was no statistical significance associated between counties for FQ-resistant E. coli, K. pneumoniae or P. aeruginosa with FQ-utilization rates (p=0.184, 0.572, 0.352, respectively). Comparing urban and rural regions was also compared for each AR-FQ use combination. There was statistical significance for urban P. aeruginosa FQ-resistance and FQ utilization (p=0.025), but not for urban E. coli (p=0.120) or urban K. pneumoniae (p=0.331). Conclusion A strong correlation was demonstrated between FQ consumption and rates of FQ-resistant P. aeruginosa within urban counties. No significant correlations were found between FQ consumption rates and other organisms. This study demonstrates additional applications for state-level antibiogram data, particularly when paired with antibiotic use data. Disclosures All Authors: No reported disclosures.

High rate of fluoroquinolone resistant Neisseria gonorrhoeae detected by molecular surveillance of antimicrobial resistance determinants in Bulgaria

Antimicrobial-resistant Neisseria gonorrhoeae is a major public health concern. The surveillance of antimicrobial resistance benefits from rapid and accurate molecular techniques in molecular diagnostics to facilitate individualised medicine and antimicrobial stewardship. To support the recommendations for empirical treatment of gonococcal infections in Bulgaria, we investigated N. gonorrhoeae-positive clinical specimens from 2018 to 2021 for the presence of genetic determinants associated with antimicrobial resistance. N. gonorrhoeae-positive samples stored at the National Center of Infectious and Parasitic Diseases during the four-year study period were retrospectively analysed by polymerase chain reaction and DNA sequencing assays for resistance determinants to fluoroquinolones, third-generation cephalosporins and macrolides. The detected determinants indicated a high rate of fluoroquinolone resistance (59%), very low level of decreased susceptibility to third-generation cephalosporins (3%) but no macrolide resistance (0%). These findings validate the utilisation of the international guidelines’ recommendations for empirical dual therapy with ceftriaxone/cefixime and azithromycin in Bulgaria. Because of the high fluoroquinolone resistance rate, ciprofloxacin should only be considered as treatment if phenotypic or molecular antimicrobial susceptibility data indicate susceptibility to ciprofloxacin. For the purposes of surveillance and individualised medicine, molecular assays for resistance determinants could complement culture-based phenotypic gonococcal antimicrobial resistance testing.

Հակամանրէային դեղերի նկատմամբ մանրէային կուլտուրաների զգայունության որոշումը և կայունության մեխանիզմների ուսումնասիրությունը միզուղիների վարակների դեպքում

The uncontrolled and irrational use of antimicrobial drugs in hospitals and outpatient settings (including at home) has led to the emergence of resistance mechanisms of bacterial strains. The increase in fluoroquinolone resistance rates in the 2020-2021 study proves the widespread use of antibiotics (in this case, fluoroquinolones) to treat secondary infections of bacterial origin or to prevent their occurrence during the COVID-19 pandemic. Based on the analysis of the data obtained, the use of fluoroquinolones, cephalosporins of III and IV generations, aminoglycosides of II generation for empirical treatment of urinary tract infections without bacteriological study and the results of sensitivity determination to antimicrobial drugs cannot be justified. Targeted and optimized use of antibiotics, as well as quality laboratory diagnosis and active infection control measures, can prevent the emergence and spread of drugresistant bacteria. The results of the study can be used in healthcare facilities to monitor bacterial resistance, to determine infection control strategies, and to develop policies for their use. Control and monitoring of resistant strains through detection of antibiotic resistance mechanisms, as well as extended analysis (according to the data from healthcare facilities, from regions, according to microbial species and stability mechanisms) requires continued research and long-term studies.

Изучение влияния биологически активного метаболита на нейроны гиппокампа крыс на экспериментальной модели болезни Альцгеймера

The uncontrolled and irrational use of antimicrobial drugs in hospitals and outpatient settings (including at home) has led to the emergence of resistance mechanisms of bacterial strains. The increase in fluoroquinolone resistance rates in the 2020-2021 study proves the widespread use of antibiotics (in this case, fluoroquinolones) to treat secondary infections of bacterial origin or to prevent their occurrence during the COVID-19 pandemic.

High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai Metropolitan Region

BackgroundMultidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains are a serious health problem in India, also contributing to one-fourth of the global MDR tuberculosis (TB) burden. About 36% of the MDR MTBC strains are reported fluoroquinolone (FQ) resistant leading to high pre-extensively drug-resistant (pre-XDR) and XDR-TB (further resistance against bedaquiline and/or linezolid) rates. Still, factors driving the MDR/pre-XDR epidemic in India are not well defined.MethodsIn a retrospective study, we analyzed 1852 consecutive MTBC strains obtained from patients from a tertiary care hospital laboratory in Mumbai by whole genome sequencing (WGS). Univariate and multivariate statistics was used to investigate factors associated with pre-XDR. Core genome multi locus sequence typing, time scaled haplotypic density (THD) method and homoplasy analysis were used to analyze epidemiological success, and positive selection in different strain groups, respectively.ResultsIn total, 1016 MTBC strains were MDR, out of which 703 (69.2%) were pre-XDR and 45 (4.4%) were XDR. Cluster rates were high among MDR (57.8%) and pre-XDR/XDR (79%) strains with three dominant L2 (Beijing) strain clusters (Cl 1–3) representing half of the pre-XDR and 40% of the XDR-TB cases. L2 strains were associated with pre-XDR/XDR-TB (P < 0.001) and, particularly Cl 1–3 strains, had high first-line and FQ resistance rates (81.6–90.6%). Epidemic success analysis using THD showed that L2 strains outperformed L1, L3, and L4 strains in short- and long-term time scales. More importantly, L2 MDR and MDR + strains had higher THD success indices than their not-MDR counterparts. Overall, compensatory mutation rates were highest in L2 strains and positive selection was detected in genes of L2 strains associated with drug tolerance (prpB and ppsA) and virulence (Rv2828c). Compensatory mutations in L2 strains were associated with a threefold increase of THD indices, suggesting improved transmissibility.ConclusionsOur data indicate a drastic increase of FQ resistance, as well as emerging bedaquiline resistance which endangers the success of newly endorsed MDR-TB treatment regimens. Rapid changes in treatment and control strategies are required to contain transmission of highly successful pre-XDR L2 strains in the Mumbai Metropolitan region but presumably also India-wide.

High rates of macrolide and fluoroquinolone resistance in human campylobacteriosis in the Middle East and North Africa.

Campylobacter is one of the main causative agents of bacterial gastrointestinal infections. Recently, a rise in the incidence of campylobacteriosis has been reported worldwide. Despite the clinical importance of this zoonotic disease, its microbiological diagnosis is not systematically performed in clinical laboratories in developing countries such as the Middle East and North Africa region. Multidrug-resistant Campylobacter isolates, particularly against erythromycin and ciprofloxacin, have been highly reported. The findings of this study highlight the critical need to urge clinical laboratories in the Middle East and North Africa region to include screening for Campylobacter in the routine stool culture of diarrheal patients. Although there is apaucity of data regarding the epidemiology of human campylobacteriosis, alarming rates of infection prevalence and antimicrobial resistance were found in Egypt, Iran, Qatar and Lebanon.

Epidemiology and Outcomes of Community-Acquired Escherichia coli Pneumonia.

Background E. coli is an under-recognized cause of bacterial community-acquired pneumonia (CAP). The objective of this study was to describe the epidemiology, risk factors, and outcomes of community-acquired Escherichia coli pneumonia in comparison with other gram-negative and pneumococcal pneumonias.MethodsWe conducted a large retrospective cohort study of adult patients admitted with pneumonia to 173 US hospitals included in the Premier Research database from July 2010 to June 2015. Patients were included if they had a principal diagnosis code for pneumonia or a principal diagnosis of respiratory failure or sepsis with a secondary diagnosis of pneumonia and had a positive blood or respiratory culture obtained on hospital day 1. The primary outcome was in-hospital case fatality. Secondary outcomes included intensive care unit admission, invasive mechanical ventilation, and use of vasopressors.ResultsOf 8680 patients with pneumonia and positive blood or respiratory cultures, 1029 (7.7%) had E. coli CAP. Patients with E. coli pneumonia were older and more likely to have a principal diagnosis of sepsis. Patients with E. coli pneumonia had significantly higher case fatality than patients with pneumococcal pneumonia (adjusted odds ratio, 1.55; 95% CI, 1.23–1.97), but it was not significantly different than other gram-negative pneumonias (adjusted odds ratio, 1.06; 95% CI, 0.85–1.32). Approximately 36% of the isolates were resistant to fluoroquinolones; 9.3% were resistant to ceftriaxone.Conclusions E. coli is an important cause of severe CAP; with mortality that was higher than pneumococcal pneumonia but similar to other gram-negative pneumonias. The rate of fluoroquinolone resistance was high, and empiric fluoroquinolones should be used with caution in these patients.