Fluoroquinolone-resistant Strains Research Articles

High levels of multidrug-resistant isolates of genetically similar Salmonella 1,4, [5],12:I:- from Brazil between 1983 and 2020.

Introduction. Salmonella 1,4, [5],12:i:- strains with different antimicrobial resistance profiles have been associated with foodborne disease outbreaks in several countries. In Brazil, S. 1,4, [5],12:i:- was identified as one of the most prevalent serovars in São Paulo State during 2004-2020.Gap Statement. However, few studies have characterized this serovar in Brazil.Aim. This study aimed to determine the antimicrobial resistance profiles of S. 1,4, [5],12:i:- strains isolated from different sources in Southeast Brazil and compare their genetic diversity.Methodology. We analysed 113 S. 1,4, [5],12:i:- strains isolated from humans (n=99), animals (n=7), food (n=5) and the environment (n=2) between 1983 and 2020. Susceptibility testing against 13 antimicrobials was performed using the disc diffusion method for all the strains. Plasmid resistance genes and mutations in the quinolone resistance-determining regions were identified in phenotypically fluoroquinolone-resistant strains. Molecular typing was performed using enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) for all strains and multilocus sequence typing (MLST) for 40 selected strains.Results. Of the 113 strains, 54.87 % were resistant to at least one antimicrobial. The highest resistance rates were observed against ampicillin (51.33 %), nalidixic acid (39.82 %) and tetracycline (38.05 %). Additionally, 39 (34.51 %) strains were classified as multidrug-resistant (MDR). Nine fluoroquinolone-resistant strains exhibited the gyrA mutation (Ser96→Tyr96) and contained the qnrB gene. The 113 strains were grouped into two clusters using ERIC-PCR, and most of strains were present in one cluster, with a genetic similarity of ≥80 %. Finally, 40 strains were typed as ST19 using MLST.Conclusion. The prevalence of MDR strains is alarming because antimicrobial treatment against these strains may lead to therapeutic failure. Furthermore, the ERIC-PCR and MLST results suggested that most strains belonged to one main cluster. Thus, a prevalent subtype of Salmonella 1,4, [5],12:i:- strains has probably been circulating among different sources in São Paulo, Brazil, over decades.

Multi-drug resistance pattern and genome-wide SNP detection in levofloxacin-resistant uropathogenic Escherichia coli strains.

Antibiotic treatment is extremely stressful for bacteria and has profound effects on their viability. Such administration induces physiological changes in bacterial cells, with considerable impact on their genome structure that induces mutations throughout the entire genome. This study investigated drug resistance profiles and structural changes in the entire genome of uropathogenic Escherichia coli (UPEC) strains isolated from six adapted clones that had evolved under laboratory conditions. Eight UPEC strains, including two parental strains and six adapted clones, with different fluoroquinolone resistance levels originally isolated from two patients were used. The minimum inhibitory concentration (MIC) of 28 different antibiotics including levofloxacin was determined for each of the eight strains. In addition, the effects of mutations acquired with increased drug resistance in the levofloxacin-resistant strains on expression of genes implicated to be involved in drug resistance were examined. Of the eight UPEC strains used to test the MIC of 28 different antibiotics, two highly fluoroquinolone-resistant strains showed increased MIC in association with many of the antibiotics. As drug resistance increased, some genes acquired mutations, including the transcriptional regulator acrR and DNA-binding transcriptional repressor marR. Two strain groups with genetically different backgrounds (GUC9 and GFCS1) commonly acquired mutations in acrR and marR. Notably, acquired mutations related to efflux pump upregulation also contributed to increases in MIC for various antibiotics other than fluoroquinolone. The present results obtained using strains with artificially acquired drug resistance clarify the underlying mechanism of resistance to fluoroquinolones and other types of antibiotics.

CTX-M-55-type ESBL-producing fluoroquinolone-resistant Escherichia coli sequence type 23 repeatedly caused avian colibacillosis in Kagoshima Prefecture, Japan

The production of expanded-spectrum beta-lactamases (ESBLs) and fluoroquinolone resistance in Enterobacteriaceae has become a global concern. The aim of this study was to investigate the spread of ESBL-producing and fluoroquinolone-resistant avian pathogenic Escherichia coli (APEC) in Kagoshima, a prefecture with the largest amount of poultry in Japan. The antimicrobial susceptibility and genetic characteristics of 228 APEC strains isolated from 57 farms in Kagoshima Prefecture, Japan, between 2005 and 2017 were analysed. Information about the companies with hatcheries connected to the farms was also collected, and the epidemiologic relatedness of APEC strains and the processes of adopting chicks were compared. Seven CTX-M-type ESBL genes, blaCTX-M-1, blaCTX-M-2, blaCTX-M-14, blaCTX-M-15, blaCTX-M-25, blaCTX-M-55, and blaCTX-M-65, were found in 60 (26.3%) of the 228 APEC strains. The ciprofloxacin-resistant strains belonged to 10 different sequence types (ST10, ST23, ST93, ST155, ST156, ST350, ST359, ST602, ST648, and ST9479), and the two ST602 strains showed remarkably high ciprofloxacin resistance (MIC: 128 µg/mL) and had amino acid mutations in GyrA (S83L and D87N), ParC (S80I), and ParE (E460A). A CTX-M-55-type ESBL-producing fluoroquinolone-resistant Og78-ST23 strain was isolated multiple times over two years on a farm. Furthermore, epidemiologically closely related strains were isolated from different farms that used the same common hatcheries. APEC is often transferred from hatcheries to farms via healthy chicks, and the prudent use of antimicrobials and careful monitoring of resistant strains on poultry farms and hatcheries are important in preventing the selection and spread of high-risk APEC strains such as CTX-M-55-type ESBL-producing Og78-ST23.

Genetic characterization of plasmid-mediated fluoroquinolone efflux pump QepA among ESBL-producing Escherichia coli isolates in Mexico.

Antimicrobial resistance is a major global public health problem, with fluoroquinolone-resistant strains of Escherichia coli posing a significant threat. This study examines the genetic characterization of ESBL-producing E. coli isolates in Mexican hospitals, which are resistant to both cephalosporins and fluoroquinolones. A total of 23 ESBL-producing E. coli isolates were found to be positive for the qepA gene, which confers resistance to fluoroquinolones. These isolates exhibited drug resistance phenotypes and belonged to specific sequence types and phylogenetic groups. The genetic context of the qepA gene was identified in a novel genetic context flanked by IS26 sequences. Mating experiments showed the co-transfer of qepA1 and chrA determinants alongside blaCTX-M-15 genes, emphasizing the potential for these genetic structures to spread among Enterobacterales. The emergence of multidrug-resistant Gram-negative bacteria carrying these resistance genes is a significant clinical concern for public healthcare systems.

Thoracic limb activity of Simocephalus vetulus and its descendants is shaped by the combination of delafloxacin and calcium

Due to its robust antibacterial activity in acidic environments and effectiveness against old fluoroquinolone-resistant bacterial strains, the use of delafloxacin (DFX) is projected to increase in the coming years. Here, we investigated the effect on the thoracic limb rate (TLR) of the water flea Simocephalus vetulus under the combined exposure of DFX (0, 100, 200, and 400 µg L−1) and calcium (Ca) (26 and 78 mg L−1) using Bayesian statistics-based linear models. The findings showed unexpected increases and decreases in the TLR of maternal S. vetulus exposed to DFX in the 26 mg Ca L−1. In the 78 mg Ca L−1 condition, we found a clearer decrease in TLR during DFX treatments. In addition, in the 26 mg Ca L−1, elusive changes in the TLR of neonatal S. vetulus whose mothers were exposed to DFX were observed, whereas the reduced TLR of the neonate, whose mother was exposed to 400 µg DFX L−1, was apparent in the higher Ca condition. While the elevated Ca content did not appear to have a clear effect on organisms’ TLR, it acted as a synergist in conjunction with DFX, leading to a reduction in TLR, the underlying mechanism of which remains poorly understood. The results of our study indicate that DFX may pose an ecological risk as a xenobiotic; therefore, taking into account the abundance of Ca in specific aquatic environments, a comprehensive ecological risk assessment should be conducted. Moreover, the inclusion of Bayesian statistics in ecotoxicological studies is highly recommended to improve data analysis and interpretation.

Quinolone analogues of benzothiazinone: Synthesis, antitubercular structure-activity relationship and ADME profiling

Mycobacterium tuberculosis (Mtb) has an impermeable cell wall which gives it an inherent ability to resist many antibiotics. DprE1, an essential enzyme in Mtb cell wall synthesis, has been validated as a target for several TB drug candidates. The most potent and developmentally advanced DprE1 inhibitor, PBTZ169, is still undergoing clinical development. With high attrition rate, there is need to populate the development pipeline. Using a scaffold hopping strategy, we imprinted the benzenoid ring of PBTZ169 onto a quinolone nucleus. Twenty-two compounds were synthesised and screened for activity against Mtb, with six compounds exhibiting sub micromolar activity of MIC90 <0.244 μM. Compound 25 further demonstrated sub-micromolar activity when evaluated against wild-type and fluoroquinolone-resistant Mtb strains. This compound maintained its sub-micromolar activity against a DprE1 P116S mutant strain but showed a significant reduction in activity when tested against the DprE1 C387S mutant.

Genomic analysis of fluoroquinolone-resistant Leclercia adecarboxylata carrying the ISKpn19-orf-qnrS1-ΔIS3-blaLAP-2 module in a synanthropic pigeon, Brazil

The aim of this study was to perform a genomic investigation of a multiple fluoroquinolone-resistant Leclercia adecarboxylata strain isolated from a synanthropic pigeon in São Paulo, Brazil. Whole-genome sequencing was performed using an Illumina platform, and in silico deep analyses of the resistome were performed. Comparative phylogenomics was conducted using a global collection of publicly available genomes of L. adecarboxylata strains isolated from human and animal hosts. L. adecarboxylata strain P62P1 displayed resistance to human (norfloxacin, ofloxacin, ciprofloxacin, and levofloxacin) and veterinary (enrofloxacin) fluoroquinolones. This multiple quinolone-resistant profile was associated with mutations in the gyrA (S83I) and parC (S80I) genes and the presence of the qnrS gene within an ISKpn19-orf-qnrS1-ΔIS3-blaLAP-2 module, previously identified in L. adecarboxylata strains isolated from pig feed and faeces in China. Genes associated with arsenic, silver, copper, and mercury resistance were also predicted. Phylogenomic analysis revealed clustering (378-496 single nucleotide polymorphism differences) with two L. adecarboxylata strains isolated from human and fish sources in China and Portugal, respectively. L. adecarboxylata is a Gram-negative bacterium of the Enterobacterales order and is considered an emergent opportunistic pathogen. Since L. adecarboxylata has adapted to human and animal hosts, genomic surveillance is highly recommended, in order to identify the emergence and spread of resistant lineages and high-risk clones. In this regard, this study provides genomic data that can help clarify the role of synanthropic animals in the dissemination of clinically relevant L. adecarboxylata within a One Health context.

Serotype Occurrence, Virulence Profiles, Antimicrobial Resistance and Molecular Characterization of Salmonella Isolated from Hospitalized Patients with Gastroenteritis in Great Tunisia between 2010 and 2020.

Non-typhoid Salmonella is one of the major causes of food-borne infections worldwide. The aim of the current study is to determine the serotype occurrence, virulence factors and antimicrobial resistance patterns of Salmonella isolated from hospitalized patients. The identification of Salmonella strains was performed according to REMIC, 2018. The susceptibility of Salmonella isolates was assessed against 20 antimicrobials using the disk diffusion method. Some virulence and antimicrobial resistance genes were identified using PCR. Among the 61 isolated Salmonella strains, seven serotypes were identified and all were positive for the virulence genes invA, mgtC and sirA. Critical resistance rates (>40%) were detected for tetracycline, nalidixic acid, amoxicillin and fluoroquinolones. However, resistances to ertapenem, ceftazidim, aztreonam and colistin were null. In addition, 33% of the isolated strains were multidrug-resistant (MDR). Moreover, 80% and 60% of S. Kentucky isolates were identified as fluoroquinolone-resistant and MDR strains, respectively. The qnrB gene was amplified in 63.2% of fluoroquinolone-resistant strains. The dfrA1 gene was identified in 20% (4/20) of the trimethoprim-sulfamethoxazole resistant strains and the integrase Class 2 gene was amplified in only 8.2% (5/61) of the isolates. Our findings highlight the emergence of MDR Salmonella isolates. A rationalization of antimicrobial use is urgently recommended in both human and veterinary medicine.

Mycoplasma genitalium infection in the female reproductive system: Diseases and treatment.

Mycoplasma genitalium is a newly emerged sexually transmitted disease pathogen and an independent risk factor for female cervicitis and pelvic inflammatory disease. The clinical symptoms caused by M. genitalium infection are mild and easily ignored. If left untreated, M. genitalium can grow along the reproductive tract and cause salpingitis, leading to infertility and ectopic pregnancy. Additionally, M. genitalium infection in late pregnancy can increase the incidence of preterm birth. M. genitalium infections are often accompanied by co-infection with other sexually transmitted pathogens (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and viral infections (Human Papilloma Virus and Human Immunodeficiency Virus). A recent study suggested that M. genitalium plays a role in tumor development in the female reproductive system. However, few studies endorsed this finding. In recent years, M. genitalium has evolved into a new "superbug" due to the emergence of macrolide-and fluoroquinolone-resistant strains leading to frequent therapy failures. This review summarizes the pathogenic characteristics of M. genitalium and the female reproductive diseases caused by M. genitalium (cervicitis, pelvic inflammatory disease, ectopic pregnancy, infertility, premature birth, co-infection, reproductive tumors, etc.), as well as its potential relationship with reproductive tumors and clinical treatment.

A scoping review of factors associated with antimicrobial-resistant Campylobacter species infections in humans.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

Fluoroquinolone resistance in bacterial isolates from ocular infections: Trend in antibiotic susceptibility patterns between 2005-2020.

To assess the fluoroquinolone resistance pattern and trends among bacterial isolates from ocular infections over a 16-year period and explore alternative antibiotics in fluoroquinolone-resistant strains. In this retrospective, longitudinal study, the microbiology laboratory records of patients with different ocular infections diagnosed at an eye institute in central India from 2005-2020 were reviewed to determine the pattern of fluoroquinolone (ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin) resistance. Antibiotic susceptibility testing was done using the Kirby-Bauer disc diffusion method. In 725 Gram-positive bacteria, the resistance of ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin was 55.9% (95% confidence interval [CI]: 52.2 - 59.6), 42.7% (95% CI: 39.0 - 46.4), 47.6% (95% CI: 43.9 - 51.3), and 45.6% (95% CI: 41.7-49.5), respectively. In 266 Gram-negative bacteria, the resistance of ciprofloxacin, ofloxacin, gatifloxacin, and moxifloxacin was 57.9% (95% CI: 51.9 - 63.9), 56.0% (95% CI: 49.7 - 62.1), 59.9% (95% CI: 53.8 - 66.0), and 74.3% (95% CI: 68.3 - 80.2), respectively. A declining trend in resistance to ciprofloxacin (P < 0.001), ofloxacin (P < 0.001), and moxifloxacin (P < 0.001) was seen in Gram-positive bacteria, whereas a reduction in resistance to only moxifloxacin (P = 0.04) was seen in Gram-negative bacteria. In fluoroquinolone-resistant Gram-positive bacteria, cefuroxime exhibited the highest susceptibility, whereas in fluoroquinolone-resistant Gram-negative bacteria, colistin exhibited the highest susceptibility. Fluoroquinolone resistance was high among bacteria from ocular infections in central India, but a declining trend in resistance to some of the fluoroquinolones was observed in recent times. Cefuroxime and colistin emerged as alternatives in fluoroquinolone-resistant Gram-positive and Gram-negative bacterial infections, respectively.

Host Cell Oxidative Stress Promotes Intracellular Fluoroquinolone Persisters of Streptococcus pneumoniae.

Bacterial persisters represent a small subpopulation that tolerates high antibiotic concentrations without acquiring heritable resistance, and it may be generated by environmental factors. Here, we report the first antibiotic persistence mechanism in Streptococcus pneumoniae, which is induced by oxidative stress conditions and allows the pneumococcus to survive in the presence of fluoroquinolones. We demonstrated that fluoroquinolone persistence is prompted by both the impact of growth arrest and the oxidative stress response induced by H2O2 in bacterial cells. This process protected pneumococci against the deleterious effects of high ROS levels induced by fluoroquinolones. Importantly, S. pneumoniae develops persistence during infection, and is dependent on the oxidative stress status of the host cells, indicating that its transient intracellular life contributes to this mechanism. Furthermore, our findings suggest persistence may influence the outcome of antibiotic therapy and be part of a multistep mechanism in the evolution of fluoroquinolone resistance. IMPORTANCE In S. pneumoniae, different mechanisms that counteract antibiotic effects have been described, such as vancomycin tolerance, heteroresistance to penicillin and fluoroquinolone resistance, which critically affect the therapeutic efficacy. Antibiotic persistence is a type of antibiotic tolerance that allows a bacterial subpopulation to survive lethal antimicrobial concentrations. In this work, we used a host-cell infection model to reveal fluoroquinolone persistence in S. pneumoniae. This mechanism is induced by oxidative stress that the pneumococcus must overcome to survive in host cells. Many fluoroquinolones, such as levofloxacin and moxifloxacin, have a broad spectrum of activity against bacterial pathogens of community-acquired pneumonia, and they are used to treat pneumococcal diseases. However, the emergence of fluoroquinolone-resistant strains complicates antibiotic treatment of invasive infections. Consequently, antibiotic persistence in S. pneumoniae is clinically relevant due to prolonged exposure to fluoroquinolones likely favors the acquisition of mutations that generate antibiotic resistance in persisters. In addition, this work contributes to the knowledge of antibiotic persistence mechanisms in bacteria.

Mutations in the Quinolones Resistance Determining Regions of gyrA in Nosocomial Staphylococcus aureus and Salmonella typhi

In Nigeria, Staphylococcus aureus and Salmonella typhi are common causes of human infections and are also recognized as pathogens of public health significance. This study therefore, sought to determine the incidence and extent of fluoroquinolones resistance of S. typhi and S. aureus isolated from patients in Nigerian Defence Academy Hospital. A total of 60 samples obtained from patients with request for stool microscopy, culture and sensitivity, wound swabs, indoor air of surgical wards and swabbing of working benches were analyzed for the presence of S. aureus and S. typhi. The bacterial isolates were then subjected to antibiotic sensitivity testing using a modified Kirby-Bauer disk diffusion method. The antibiotic susceptibility patterns of S. typhi revealed that some of the isolates were resistant to two or more fluoroquinolones namely: ciprofloxacin, sparfloxacin, ofloxacin and pefloxacin. S. aureus on the other hand, also showed resistance to fluoroquinolones. The isolates that showed resistance to more fluoroquinolones were taken for molecular analysis. The genomic DNA was extracted and amplified using specific primer for gyrA by PCR, visualized using agarose gel electrophoresis and then sequenced. The amplicon sizes were 251bp respectively for each of the isolates. The detection of resistant pattern responsible for fluoroquinolones resistance showed that mutation had occurred. Mutation in nucleotide sequence was detected in gyrA gene of the fluoroquinolone resistant strains.

Fosfomycin in antibiotic prophylaxis of infectious complications after biopsy of the prostate

Introduction. Biopsy of prostate is a routine urologic procedure. More than 1 million biopsies are performed worldwide annually. The frequency of infectious-inflammatory complications remain high, despite the recommended antibiotic prophylaxis schemes.Aim. The evaluation of effectiveness and safety of combined antimicrobial prophylaxis: Fosfomycin and Fluoroquinolones of 3rd generation.Materials and methods. 80 patients underwent prostate biopsy in our study and were divided into 2 groups: the first group of 40 patients received routine prophylaxis: Levofloxacin 500 mg 6 hours before the biopsy and 500 mg per day during 4 days after biopsy. The second group of 40 patients, along with standard prophylaxis as in the first group, additionally after biopsy received Fosfomycin 3 gr single-shot.Results and discussion. In the first group, infectious and inflammatory complications occurred in 8 patients (20%). 12.5% of patients from the first group were hospitalized for paranteral antibiotic therapy. The average length of stay in hospital was 3.4 ± 1.45 days. In all cases, in the first group of patients, E. coli was detected, in 70% of cases fluoroquinolone-resistant strain of the bacterium was received. In the second group of patients now hospitalization was required. One patient out of forty (2.5%) from this group showed signs of urinary tract infection, which was not accompanied by an increase of body temperature, as well as changes in blood and urine tests.Conclusion. Our results show good effectiveness and safety of fosfomicin for antibiotic prophylaxis for transrectal prostate biopsy.

Bacteremia in Hematopoietic Stem Cell Recipients Receiving Fluoroquinolone Prophylaxis: Incidence, Resistance, and Risk Factors.

BackgroundBacteremia is a common complication in hematopoietic stem cell transplant (HSCT) recipients. Prophylactic fluoroquinolone is recommended and used in these individuals. Breakthrough infections can occur with fluoroquinolone-resistant strains. We aimed to identify the incidence, resistance, and risk factors for bacteremia in HSCT recipients receiving fluoroquinolone prophylaxis.Materials and MethodsThis retrospective study was performed on patients who received fluoroquinolone prophylaxis and underwent autologous and allogeneic HSCT between 2015 and 2019. The incidence of bacteremia, comorbidity, treatment, and invasive procedures was compared in these patients with and without bacteremia.ResultsThere were 553 patients included in the study, 68 (12.3%) had bacteremia. The incidence of bacteremia is 8.2% of autologous HSCT recipients and 18.4% of allogeneic HSCT recipients. The significant risk factors associated with bacteremia were steroid-using (odds ratio [OR]:13.83, 95% confidence interval [CI]: 2.88 - 66.40), higher Charlson Comorbidity Index (CCI)-mean (OR: 1.57, 95% CI: 1.15 - 2.16), diabetes mellitus (OR: 4.29, 95% CI: 1.11 - 16.48) in autologous HSCT, steroid-using (OR: 6.84, 95% CI: 1.44 - 32.33), longer duration of neutropenia (OR: 1.05, 95% CI: 1.01 - 1.09) using central venous catheter (OR: 7.81, 95% CI: 1.00 - 61.23) in allogeneic HSCT. Seventy-three pathogens were isolated from a total of 68 bacteremia episodes. The most commonly occurring agents were Escherichia coli, Klebsiella pneumoniae and Enterococcus spp. Resistance to fluoroquinolones was 87.2%, 70.0% and 60.0% among these strains, respectively.ConclusionHigh CCI, diabetes mellitus, use of steroids and long-term neutropenia and use of central venous catheters were significantly associated with the breakthrough bacteremia in HSCT recipients receiving fluoroquinolone prophylaxis. Fluoroquinolone prophylaxis may reduce the incidence of bacteremia but may select strains resistant to fluoroquinolone.

Discovery of antipsychotic loxapine derivatives against intracellular multidrug-resistant bacteria.

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in macrophages and epithelial cells. Moreover, intra-macrophagic Salmonella typhi, Yersinia enterocolitica, and Listeria monocytogenes and methicillin-resistant Staphylococcus aureus are also susceptible to SW14. Overall, our findings suggest that SW14 has a broad-spectrum activity against intracellular bacteria.

Genomic and Transcriptomic Analysis of Bovine Pasteurella multocida Serogroup A Strain Reveals Insights Into Virulence Attenuation.

Pasteurella multocida is one of the primary pathogens of bovine respiratory disease (BRD), and causes huge losses in the cattle industry. The Pm3 strain was a natural isolate, which is a strong form of pathogen and is sensitive to fluoroquinolones antibiotics. A high fluoroquinolone resistant strain, Pm64 (MIC = 64 μg/mL), was formed after continuous induction with subinhibitory concentration (1/2 MIC) of enrofloxacin, with the enhanced growth characteristics and large attenuation of pathogenicity in mice. This study reports the whole genome sequence and the transcription profile by RNA-Seq of strain Pm3/Pm64. The results showed an ineffective difference between the two strains at the genome level. However, 32 genes could be recognized in the gene islands (GIs) of Pm64, in which 24 genes were added and 8 genes were lost. Those genes are involved in DNA binding, trehalose metabolism, material transportation, capsule synthesis, prophage, amino acid metabolism, and other functions. In Pm3 strain, 558 up-regulated and 568 down-regulated genes were found compared to Pm64 strain, from which 20 virulence factor-related differentially expressed genes (DEGs) were screened. Mainly differentially transcribed genes were associated with capsular polysaccharide (CPS), lipopolysaccharide (LPS), lipooligosaccharide (LOS). Iron utilization, and biofilm composition. We speculated that the main mechanism of virulence attenuation after the formation of resistance of Pm64 comes from the change of the expression profile of these genes. This report elucidated the toxicity targets of P. multocida serogroup A which provide fundamental information toward the understanding of the pathogenic mechanism and to decreasing antimicrobial drugs resistance.

Combined antibiotic prophylaxis of infectious complications of prostate biopsy

Introduction. Biopsy of prostate is a routine urologic procedure. Nevertheless the frequency of infectious-inflammatory complications remain high, despite the recommended antibiotic prophylaxis schemes.Purpose. The evaluation of effectiveness and safety of combined antimicrobial prophylaxis: fosfomycin trometamol and fluoroquinolones of 3rd generation.Materials and methods. Our clinical study included 80 patients who underwent prostate biopsy were divided into 2 groups. The first group of 40 patients received routine prophylaxis: levofloxacin 500 mg 6 h before the biopsy and 500 mg per day during 4 days after biopsy. The second group of 40 patients, along with standard prophylaxis as in the first group, additionally after biopsy received fosfomycin trometamol 3 gr single-shot.Results. In the first group, infectious and inflammatory complications occurred in 8 (20 %) patients, 12.5 % of patients from the first group were hospitalized for parenteral antibiotic therapy. The average length of stay in hospital was 3.4 ± 1.45 days. In all cases, in the first group of patients, Escherichia coli was detected, in 70 % of cases fluoroquinolone-resistant strain of the bacterium was received. In the second group of patients no hospitalization was required. One (2.5 %) patient out of forty from this group showed signs of urinary tract infection, which was not accompanied by an increase of body temperature, as well as changes in blood and urine tests.Conclusions. Our results show good effectiveness and safety of combined antibiotic prophylaxis for transrectal prostate biopsy. Since fluoroquinolone resistance grows, it is necessary to introduce alternative schemes, as well as monitoring of nosocomial infection and controlling of antimicrobial therapy.

Genomic Characterization of Fluoroquinolone-Resistant Thermophilic Campylobacter Strains Isolated from Layer Chicken Feces in Gangneung, South Korea by Whole-Genome Sequencing.

Thermophilic Campylobacter species of poultry origin have been associated with up to 80% of human campylobacteriosis cases. Layer chickens have received less attention as possible reservoirs of Campylobacter species. Initially, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of two archived Campylobacter isolates (Campylobacter jejuni strain 200605 and Campylobacter coli strain 200606) from layer chickens to five antimicrobials (ciprofloxacin, nalidixic acid, erythromycin, tetracycline, and gentamicin) were determined using broth microdilution while the presence of selected antimicrobial resistance genes was performed by polymerase chain reaction (PCR) using specific primers. Whole-genome sequencing (WGS) was performed by the Illumina HiSeq X platform. The analysis involved antimicrobial resistance genes, virulome, multilocus sequence typing (MLST), and phylogeny. Both isolates were phenotypically resistant to ciprofloxacin (MIC: 32 vs. 32 µg/mL), nalidixic acid (MIC: 128 vs. 64 µg/mL), and tetracycline (MIC: 64 vs. 64 µg/mL), but sensitive to erythromycin (MIC: 1 vs. 2 µg/mL) and gentamicin (MIC: 0.25 vs. 1 µg/mL) for C. jejuni strain 200605 and C. coli strain 200606, respectively. WGS confirmed C257T mutation in the gyrA gene and the presence of cmeABC complex conferring resistance to FQs in both strains. Both strains also exhibited tet(O) genes associated with tetracycline resistance. Various virulence genes associated with motility, chemotaxis, and capsule formation were found in both isolates. However, the analysis of virulence genes showed that C. jejuni strain 200605 is more virulent than C. coli strain 200606. The MLST showed that C. jejuni strain 200605 belongs to sequence type ST-5229 while C. coli strain 200606 belongs to ST-5935, and both STs are less common. The phylogenetic analysis clustered C. jejuni strain 200605 along with other strains reported in Korea (CP028933 from chicken and CP014344 from human) while C. coli strain 200606 formed a separate cluster with C. coli (CP007181) from turkey. The WGS confirmed FQ-resistance in both strains and showed potential virulence of both strains. Further studies are recommended to understand the reasons behind the regional distribution (Korea, China, and Vietnam) of such rare STs.

Characterization of Human Origin Salmonella Serovar 1,4,[5],12:i:- in Eastern China, 2014 to 2018.

The prevalence of Salmonella serovar 1,4,[5],12:i:- among diarrhea patients has increased considerably in many countries around the world, including China. However, the characterization of this serovar of human origin has been less reported from China. We characterized 76 isolates of Salmonella 1,4,[5],12:i:- gained from diarrhea patients from 2014 to 2018 in the Jiangsu Province of eastern China. These isolates fell into a single-sequence type (ST34) determined by multilocus sequence typing (MLST), and into 44 pulsed-field gel electrophoresis band patterns, with 1 pattern (JSSMM015) comprising 12 isolates (15.9%). By means of PCR-based assays, the seven prophage located virulence genes were detected in our Salmonella 1,4,[5],12:i:- isolates with a high rate of gipA, gtgB, sspH1, sspH2, sodC1, and gtgE (93.4-97.4%), and with a moderate rate of sopE (42.1%). In contrast, none of the five plasmid-borne virulence genes (spvC, pefA, mig5, rck, and srgA) was identified. We tested the isolates' susceptibility to 18 antibiotics of 9 categories using the VITEK 2 system. A high proportion (89.5%) of the isolates were multidrug resistant (MDR) strains with full resistance to cefazolin, cefotetan, amikacin, gentamycin, and tobramycin, followed by resistance to ampicillin (88.2%) and ampicillin/sulbactam (80.3%). The resistance to piperacillin/tazobactam, ceftazidime, cefepime, and levofloxacin was scarce (2.6-9.2%). Notably, an isolate from 2018 was resistant to carbapenems. blaTEM-1B and aac(6')-Ib-cr were the most common drug resistance genes presented in cephalosporin- and fluoroquinolone-resistant strains. All Salmonella 1,4,[5],12:i:- isolates were capable of forming biofilm, with 13.2% of them having strong ability. However, no association was indicated between the scale of biofilm formation ability and MDR. Our results indicate that the combination of these characteristics may together provide a selective and competitive advantage to those Salmonella 1,4,[5],12:i:- isolates, contributing to their increasing prevalence observed worldwide.