Antibiotic prophylaxis in acute childhood leukemia: What is known so far?

ABSTRACT Introduction: The treatment of acute lymphoblastic leukemia (ALL) has evolved in recent decades, reaching an overall survival rate close to 90%. Currently, approximately 4% of patients with ALL die from secondary complications of chemotherapy. Among these complications, the most frequent is febrile neutropenia (FN). The treatment of acute myeloid leukemias (AMLs) is even more aggressive, being consequently related to a considerable amount of treatment-related toxicity with a high risk of severe infection and death. Method: In order to reduce the infection-related risks in these groups of patients, systemic antibacterial prophylaxis has emerged as a possible approach. Results: Antibiotic prophylaxis during neutropenia periods in those undergoing chemotherapy have .already been proven in adults with acute leukemias (ALs). Among the possible available therapeutic options for bacterial prophylaxis in children with cancer, fluoroquinolones emerged with the most amount of evidence. Within this class, levofloxacin became the best choice. Conclusion: Therefore, the use of levofloxacin seems to be indicated in very specific situations: in children who are known to be neutropenic for a long time, secondary to intensive chemotherapy; in children with AL undergoing chemotherapy to induce remission; or in children undergoing hematopoietic stem cell transplantation (HSCT). This article aims to describe recent evidence focusing on antibiotic prophylaxis in children with ALs.

Safety of levofloxacin as an antibiotic prophylaxis in the induction phase of children newly diagnosed with acute lymphoblastic leukemia: an interim analysis of a randomized, open-label trial in Brazil

ABSTRACT Background: Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications. Methods: From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days. Results: Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia. Conclusion: The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.

Synthesis and antibacterial activity of D-glucosamine-fluoroquinolone derivatives / 药学学报

Based on the idea of modification of sugar drugs, or transforming other active substances with sugar molecules, sixteen D-glucosamine-fluoroquinolone (FQ) derivatives were designed by combining D-glucosamine with FQs and synthesized by a multi-step reaction with shared intermediates. The assay results of anti-human pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs, and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2 µg·mL-1, respectively, which all were worthy of further study. In this study, a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time, and super antibacterial molecules were found, which expanded the types and biological activities of D-glucosamine derivatives.

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

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Synthesis and biological activities of three-molecule conjugates with para-aminosalicylic acid as parent nucleus / 药学学报

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

Fluoroquinolonas en aves, huevos, alimentos avícolas y su impacto en la microbiota intestinal de aves / Fluoroquinolone in birds, eggs, poultry feeds and their impact on the intestinal microbiota

Se detectó la presencia de fluoroquinolonas en varios alimentos (huevos, alimentos para aves y pechuga de pollo), así como determinar el perfil de susceptibilidad de ácido nalidíxico y ciprofloxacina de las enterobacterias aisladas del contenido intestinal de pollos de Cumaná. Se estudiaron alimentos iniciadores y de engorde (de cinco marcas comerciales) y uno para gallinas ponedoras, así como pechugas de pollos nacionales y de Brasil. I-2 y E-1 fueron los que tuvieron las concentraciones más altas de enrofloxacina. El alimento para las gallinas ponedoras (AP 2,35 µg/mg) tuvo más enrofloxacina que los de los pollos. En los huevos, la mayor acumulación se vio en las yemas. Los pollos nacionales (0,43-0,56 µg/mg) acumularon más ciprofloxacina que los pollos de Brasil (0,14 µg/mg). De los hisopados rectales de los pollos, E. coli fue la principal especie aislada. Por antibiograma, 48% de las cepas fueron resistentes a las quinolonas probadas (ácido nalidíxico y ciprofloxacina). Cuando se determinó la concentración mínima inhibitoria a ciprofloxacina, todas las cepas fueron resistentes (8-128 µg/ml). Todos los alimentos muestreados exceden los límites máximos de fluoroquinolonas permitidos en humanos, lo cual ejerce una presión selectiva importante en las bacterias de la microbiota intestinal de los pollos

To detect the presence of fluoroquinolones in several foods (eggs, poultry food and chicken breast), as well as to determine the susceptibility profile of nalidixic acid and ciprofloxacin of strains of enterobacterias from chicken's intestinal content from Cumaná. Starter and fattening foods (of five commercial marks), and one for laying hens, were studied, as well as domestic chicken's breast (and Brazil. I-2 and E-1 were the ones with the highest concentrations of enrofloxacin. The food for laying hens (AP 2,35 µg/mg) had more enrofloxacin than those for chickens. In eggs, greatest accumulation was seen in the yolks. Domestic chickens (0,43-0,56 µg/mg) accumulated more ciprofloxacin than Brazilian ones (0,14 µg/mg). E. coli was the main specie from chicken rectal swabs. By antimicrobial susceptibility testing, 48% were resistant to both quinolones (nalidixic acid and ciprofloxacin). When the minimum inhibitory concentration of ciprofloxacin was determined, all strains were resistant (8-128 µg/ml). All sampled foods exceeded the maximum limits of fluoroquinolones allowed in humans, which puts significant selective pressure on the bacteria in the chicken gut microbiota

Development Of Uv-Spectrophotometric Method And Its Validation For Estimating Contents Of Prulifloxacin In Simulated Intestinal Fluid

This study was performed with an objective of developing and validating an UV-spectroscopic method for estimating contents of prulifloxacin in simulated intestinal fluid (SIF) i.e. phosphate- buffer media with a pH of 6.8 as per ICH guidelines. The λmax for prulifloxacin in phosphate- buffer media pH 6.8 was found to be 272 nanometer. The calibration curve of drug followed linearity in-between 1-9 μg/ml concentration range and correlation co-efficient value was found equal to 0.9995. We tested this proposed method onto the bulk and marketed pharmaceutical formulation (tablets) also in order to find out contents of drug. Using developed method for estimation of prulifloxacin in SIF, drug was found to be in-between 101.91 and 104.02 % in marketed tablets which shows a good agreement with that of the claimed level. Accuracy of developed method was established through recovery experimentation, performed for three spiked percent concentrations- 75%, 100%, and 125%. The % recovery was found to be in between 97.27 and 101.82%. Low values of % RSD supported accuracy as well as the reproducibility of developed method. Precision of developed method was established by good in-limit intraday and interday experimental variations and through repeatability tests. Values of % RSD less than 2 confirmed about precision of developed method. The ruggedness of the developed method was validated by performing drug estimation by two different performers. This proposed spectroscopic method has proved to be a rapid and successful method for routine analysis of prulifloxacin in simulated intestinal fluid.

Synthesis and Antitumor Activity of C-3 Arylidene Thiazolotriazolone of Ofloxacin Derivatives / 中国药学杂志

OBJECTIVE: To discover an efficient strategy for a conversion of the antibacterial activity into an antitumor activity. METHODS: Pharmacophore and scaffold hopping-based rational drug design principles, the title fluoroquinolone C-3 thiazolotriazole unsaturated ketones (6a-6l) were designed and synthesized with a S-triazole ring and α,β-unsaturated ketone, respectively, as an isostere and fused modified group from ofloxacin (1), and their structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity against the tested tumor cell lines was evaluated by a MTT assay. RESULTS: Twelve new title compounds were synthesized, and exhibited more significant potency than parent 1. The title compounds with fluorophenyl or O-methoxyphenyl displayed comparable activity to comparasion doxorubicin. CONCLUSION: A fused heterocyclic unsaturated ketone skeleton as an isostere of the C-3 carboxylic acid group are shown to be an alternative route for further design of lead antitumor fluoroquinolone.

A Novel Mismatched PCR-Restriction Fragment Length Polymorphism Assay for Rapid Detection of gyrA and parC Mutations Associated With Fluoroquinolone Resistance in Acinetobacter baumannii

BACKGROUND: Mutations in the quinolone resistance-determining regions (QRDRs) of Acinetobacter baumannii DNA gyrase (gyrA) and topoisomerase IV (parC) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction fragment length polymorphism (RFLP) assay to detect mutations in the gyrA and parC QRDRs associated with FQ resistance in A. baumannii. METHODS: Based on the conserved sequences of A. baumannii gyrA and parC, two primer sets were designed for mismatched PCR-RFLP to detect mutations in gyrA (codons 83 and 87) and parC (codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58 A. baumannii strains and 37 other Acinetobacter strains that have been identified by RNA polymerase β-subunit gene sequence analysis.

Drug resistance profile among multi-drug resistant tuberculosis patients at diagnosis and correlation with history of anti-tubercular treatment in a tertiary care center

Background: Drug Resistant Tuberculosis (DR-TB) is a major threat to the realization of the goal of a TB free world in the near future. It is important to study the reasons for the increasing number of such cases so that effective action can be taken to control this growing epidemic.Methods: Sputum from 36 patients diagnosed with acquired pulmonary Multidrug Resistant Tuberculosis (MDR-TB) were subjected to first- and second-line Drug Sensitivity Testing (DST) after liquid culture in mycobacterium growth Indicator Tube (MGIT). Primary MDR-TB cases were excluded. The relation of the drug sensitivity profile with the history of prior treatment taken was statistically analysed.Results: Majority of the patients had received appropriate treatment, and most had adhered to prescribed treatment. Among the 36 patients, 24(66.7%) were found to be Pre-Extensively Drug Resistant (Pre-XDR-TB) and 4(11.1%) were extensively drug resistant XDR-TB cases. Inappropriate prescription of fluoroquinolone (FQ) was found to be most common. Prior intake of any drug was not found to significantly affect subsequent resistance to that drug.Conclusions: Fluoroquinolone resistance is quite common in patients with DR-TB (66.7%). This study did not find the prior use of FQ or any other drug to significantly affect subsequent resistance to the drug. Primary drug resistance is thus a major concern. 11.1% patients were found to be XDR-TB cases. Hence DST for first- and second-line drugs should be done at the time of diagnosis to avoid failure of treatment with a predesigned regimen.

Mismatch amplification mutation assay-polymerase chain reaction: A method of detecting fluoroquinolone resistance mechanism in bacterial pathogens

The mismatch amplification assay is a modified version of polymerase chain reaction (PCR) that permits specific amplification of gene sequences with single base pair change. The basis of the technique relies on primer designing. The single nucleotide mismatch at the 3' proximity of the reverse oligonucleotide primer makes Taq DNA polymerase unable to carry out extension process. Thus, the primers produce a PCR fragment in the wild type, whereas it is not possible to yield a product with a mutation at the site covered by the mismatch positions on the mismatch amplification mutation assay (MAMA) primer from any gene. The technique offers several advantages over other molecular methods, such as PCR-restriction fragment length polymorphism (RFLP) and oligonucleotide hybridization, which is routinely used in the detection of known point mutations. Since multiple point mutations in the quinolone resistance determining region play a major role in high-level fluoroquinolone resistance in Gram-negative bacteria, the MAMA-PCR technique is preferred for detecting these mutations over PCR-RFLP and sequencing technology.

Antibiotic Resistance Pattern among common Bacterial Uropathogens Isolated in A Tertiary Care Hospital

Introduction: Urinary tract infections (UTI’s) are one of the most common bacterial infections in community and hospital settings and it is important to know the etiology and susceptibility pattern of uropathogens for optimum management of UTI’s.Aim & Objectives:This study was conducted to know the etiologyof UTI and to determine the antibiotic resistance pattern of these isolates.Materials & Methods: A prospective cross sectional study was done on 537 and 486 consecutive urine samples from January to May 2015 and 2016. Isolates obtained were identified by conventional biochemical methods and antimicrobial susceptibility testing was done by Kirby Bauer disk diffusion method as per CLSI guidelines.Results: The prevalence of UTI was 41.71% and 51.85% in 2015 and 2016 respectively. 129 (57.59%) and 148 (58.73%) females and 95(42.41%) and 104(41.27%) males were infected in 2015 and 2016 respectively.Escherichia coli (55.25%) was the predominant organism isolated. An increased resistance to norfloxacin ,ampicillin and cefotaxime were shown in 2016 compared to the antimicrobial resistance pattern obtained in 2015. All the gram negative bacilli studied were sensitive to Imipenem and Piperacillin- Tazobactam. Conclusion:Constant surveillance of resistance rate of uropathogens is necessary to formulate local antibiotic policy and to assist clinicians in the rational choice of antibiotic therapy. KEYWORDS:Urinary Tract Infection, E.coliAntibiogram ,Fluoroquinolone resistance.

Synthesis and antitumor activity of pefloxacin C-3 methylene rhodanine devatives / 中国药科大学学报

@#To further explore an efficient strategy for the construction of antitumor fluoroquinolone molecules from antibacterial fluoroquinolone drugs, twelve new title compounds, 1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-(3-substituted-rhodanin-5-ylidene)methyl-quinolon-4(1H)-ones(6a-6l), was designed and synthesized with α, β-unsaturated ketone scaffold and a rhodanine ring as an isostere and fused modified group, respectively, from pefloxacin(1), and their structures were characterized by elemental analysis and spectral data. The in vitro anti-cell proliferative activity of the title compounds against the tested A549, Hep-3B and HL60 cancer cells exhibited more significant potency than parent 1. In particular, halogenated phenyl title compounds(6d, 6e, 6f)displayed a comparable activity to comparison doxorubicin against A549 cells and low cytotoxicity against normal Vero cells. Thus, a methylene rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group have shown to be beneficial to improving the antitumor activity.

Synthesis and antitumor activity of fluoroquinolone C-3 arylidene thiazolone derivatives from ciprofloxacin / 药学学报

To expand an efficient strategy for the conversion of antibacterial activity of fluoroquinolones into an antitumor activity, sixteen new compounds, 1-cyclopropyl-6- fluoro-7-(4-methyl-piperazin-1-yl)-3-(5-arylidene-thiazol-4(5H)-one-2-yl)-quinolon-4(1H)-ones (7a-7p), were designed and synthesized with a thiazolone ring and an arylidene moiety as an isostere and modified group, respectively, from ciprofloxacin. Their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity of the synthesized compounds were measured using Hep-3B, Capan-1 and HL60 cell lines and were found to be more potent than ciprofloxacin. Meanwhile, the SAR revealed that the halogenated phenyl compounds such as fluorophenyl (7h, 7i), chlorophenyl (7j, 7k) or bromophenyl compounds (7l, 7m), and aromatic heterocyclic substitution such as furyl (6n) or pyridyl compounds (6o, 6p) displayed better activity than the control compounds, especially the IC50 values of pyridyl compounds 6o and 6p against Capan-1 cell growth was comparable to doxorubicin. Thus, an arylidene-modified thiazolone scaffold as the replacement of the C-3 carboxylic acid group appears to be an alternative route for an improved antitumor activity of fluoroquinolones.

Transcriptional response of AcrEF-TolC against fluoroquinolone and carbapenem in Escherichia coli of clinical origin

Introduction: Efflux pump systems constitute a major means of intrinsic resistance in Escherichia coli. AcrEF-TolC pump is known to exhibit higher expression level in quinolone resistant isolates. However, the transcriptional response of this pump is yet to be known when exposed to quinolone and other group of antibiotics. Objective: The present study analyses the transcriptional response of AcrEF-TolC in the presence of quinolones and carbapenems. Methodology: A total of 167 non-duplicate clinical isolates from Silchar medical college and Hospital, Silchar, India were included in this study. Of which 27 were devoid of any carbapenemase activity and among them 13 isolates showed overexpression of AcrE and AcrF gene. Transcriptional response of AcrE was directly proportional to increasing concentration of levofloxacin and ofloxacin. However, the response of AcrE and AcrF was inconsistent with carbapenems. Result: The study isolates showed susceptibility towards amikacin (68.4%), gentamicin (59.6%), cefepime (52.7%) and pipercillin/tazobactam (48.3%). The present investigation highlights that apart from qnr genes and mutational changes in gyr region, AcrEF-TolC plays a major role in fluoroquinolone resistance in this part of the world. Conclusion: Upregulation of AcrE in the presence of levofloxacin and ofloxacin warrants further investigation to establish their active role in efflux of this drug.

Application of statistical process control for spotting compliance to good pharmaceutical practice

ABSTRACT For the release of pharmaceutical products into the drug market; most of the pharmaceutical companies depend on acceptance criteria - that are set internally, regulatory and/or pharmacopeially. However, statistical process control monitoring is underestimated in most quality control in cases; although it is important not only for process stability and efficiency assessment but also for compliance with all appropriate pharmaceutical practices such as good manufacturing practice and good laboratory practice, known collectively as GXP. The current work aims to investigate two tablet inspection characteristics monitored during in-process control viz. tablet average weight and hardness. Both properties were assessed during the compression phase of the tablet and before the coating stage. Data gathering was performed by the Quality Assurance Team and processed by Commercial Statistical Software packages. Screening of collected results of 31 batches of an antibacterial tablet - based on Fluoroquinolone -showed that all the tested lots met the release specifications, although the process mean has been unstable which could be strongly evident in the variable control chart. Accordingly, the two inspected processes were not in the state of control and require strong actions to correct for the non-compliance to GXP. What is not controlled cannot be predicted in the future and thus the capability analysis would be of no value except to show the process capability retrospectively only. Setting the rules for the application of Statistical Process Control (SPC) should be mandated by Regulatory Agencies.

Synthesis and Antitumor Activity Evaluation of C-3 (Rhodanine Unsaturated Ketone) Amides as Ofloxacin Derivatives / 中国药学杂志

OBJECTIVE: To explore an efficient strategy for converting the antibacterial activity of fluoroquinolones to antitumor activity. METHODS: An amide group as an isostere modified by rhodanine unsaturated ketone moiety corresponding to the C-3 carboxylic acid group resulted in 12 new title C-3 (5-arylidene-2-thioxo-1, 3-thiozolidin-2, 4 -dione-3-yl) amides (6a - 6l) from ofloxacin 1. Their structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against three tested cell lines was evaluated by MTT assay. RESULTS: Twelve new title compounds were synthesized from ofloxacin and exhibited significantly higher potency than the parent compound ofloxacin. CONCLUSION: Using a rhodanine unsaturated ketone hybrided amide group as the C-3 bioisostere is favorable to improve antitumor activity.

Synthesis and antitumor activity of 3-(5-benzylidenethuzolo-triazlone)fluoroquinolones / 中国药科大学学报

@#To discover an efficient approach for the conversion of antibacterial fluoroquinolones into an antitumor activity, a fused heterocycle ring core, thiazolo［3, 2-b］［1, 2, 4］triazol-5-one was used as an isostere and further modified with an arylidene group. Then, 12 novel C-3 fused heterocyclic unsaturated ketones, 1- ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-［6-arylidene-thiazolo［3, 2-b］［1, 2, 4］triazol-5(6H)-one-3-yl］- quinolon-4(1H)-ones(6a-6l), were designed and synthesized from pefloxacin(1). The structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against SMMC-7721, Capan-1 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than the parent 1. The compounds with fluorophenyl or o-methoxyphenyl showed comparable activity to the comparasion doxorubicin. Thus, it appears to be an alternative route for a fused heterocyclic unsaturated ketone as an isostere of the C-3 carboxylic group to improve the antitumor activity.

Surveillance of molecular characteristics of gyrA and parC among fluoroquinolone resistant Streptococcus agalatiae isolates in Suzhou hospitals / 国际检验医学杂志

Objective To investigate the molecular characteristic of fluoroquinolone resistant Streptococcus agalactiae (GBS) isolates in Suzhou.Methods Totally 46 fluoroquinolone resistant GBS strains were collected,and then subjected into PCR and two resistance genes were sequenced and their high frequency mutation sites,gyrA and parC were analysed.Results Among these isolates,the most frequent gyrA mutation was gyrA_S81L (TCA→TTA),which displayed 93.4％ (43/46) with substituted at No.81 site of amino acid from Ser to Leu.However,the most frequent parC mutation was mutated at No.79 site of amino acid from Ser to Tyr orPhe,with two mutations parC_S79Y (73.9％,34/46) and parC_S79F(17.4％,8/46).The analysis showed that the major mutation patterns are gyrA_S81L with parC_S79Y (73.9％,34/46),gyrA_S81L with parC(13.0％,6/46).Conclusion The most frequent mutations of fluoroquinolone resistant gene in Suzhou are gyrA and parC and the major mutation patterns are gyrA_S81L/parC_S79Y and gyrA_S81L/parC_S79F.

Comparison of Enterococcus faecium Bacteremic Isolates from Hematologic and Non-hematologic Patients: Differences in Antimicrobial Resistance and Molecular Characteristics

BACKGROUND: Enterococcus faecium, especially vancomycin-resistant E. faecium (VREfm), is a major concern for patients with hematologic diseases. Exposure to antibiotics including fluoroquinolone, which is used as a routine prophylaxis for patients with hematologic (MH) diseases, has been reported to be a risk factor for infection with vancomycin-resistant eneterocci. We compared the characteristics of E. faecium isolates according to their vancomycin susceptibility and patient group (MH vs non-MH patients). METHODS: A total of 120 E. faecium bacteremic isolates (84 from MH and 36 from non-MH patients) were collected consecutively, and their characteristics (susceptibility, multilocus sequence type [MLST], Tn1546 type, and the presence of virulence genes and plasmids) were determined. RESULTS: Among the vancomycin-susceptible E. faecium (VSEfm) isolates, resistance to ampicillin (97.6% vs 61.1%) and high-level gentamicin (71.4% vs 38.9%) was significantly higher in isolates from MH patients than in those from non-MH patients. Notably, hyl, esp, and pEF1071 were present only in isolates with ampicillin resistance. Among the VREfm isolates, ST230 (33.3%) and ST17 (26.2%) were predominant in MH patients, while ST17 (61.1%) was predominant in non-MH patients. Plasmid pLG1 was more prevalent in E. faecium isolates from MH patients than in those from non-MH patients, regardless of vancomycin resistance. Transposon analysis revealed five types across all VREfm isolates. CONCLUSIONS: The antimicrobial resistance profiles and molecular characteristics of E. faecium isolates differed according to the underlying diseases of patients within the same hospital. We hypothesize that the prophylactic use of fluoroquinolone might have an effect on these differences.