Quinolone Research Articles

The mechanism study of plasmid-mediated quinolone resistance in clinical isolates of Enterobacteriaceae from nine teaching hospitals in China

Objective To investigate the prevalence of plasmid-mediated quinolone resistance qnr and aac(6')-Ib-cr in Enterobacteriaceac in Chiha.Methods A total of 197 clinical isolates with ciprofloxacin≥0.25μg/ml,cefotaxime≥2.0μg/ml and ceftriaxone≥2.0 μg/ml were screened from the 421 non-repetitive clinical isolates of Enterobac teriaceae(Escherichia coli,Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae)from the nine teaching hospitals in China.qnrA,qnrB,qnrS and aac(6')-Ib gene were detected by PCR.aac(6')-Ib-cr gene was further identified by the digestion with BtsCI followed by sequencing.Conjugation experiments were done.The MIC of ciprofloxacin and other antibacterial agents in donor strain and acceptor strain were determined by agar dilution.Results Qnr was present in 42%(83/197)of isolares,and among these,17 isolates carried qnrA(9%),46 isolates carried qnrB(23%),24 isolates carried qnrS(12%),2 isolates carried qnrA and qnrB,and 2 isolates carried qnrB and qnrS.aac(6')-Ib was present in 46%(90/197)of isolates,40%(36/90)of which carried the cr variant responsible for low-level ciprofloxacin resistance.18 isolates carried qnr and aac(6')-Ib-cr.Qnr wag present in 66% of Enterobacter cloacae isolates,66% of Klebsiella pneumoniae isolates,63% of Citrobacter freundii isolates,and 6% of Escheriehia coil isolates,respectively,aac(6')-Ib-cr was present in 9% of Enterobacter cloacae isolates,22% of Klebsiella pneumoniae isolates,27% of Citrohacter freundii isolates,and 17% of Escherichia coil isolates,respectively,qnr and aac(6')-Ib-cr were present in 20% (83/421)and 9% (36/421) of all isolates respectively. The 13 transconjugants showed 16 to 125 fold increases in the MICs of ciprofloxacin and 16 to 31 fold increases in the MICs of levofloxacin relative to that of the recipient Conclusion Transferable plasmid-medlated low level quinolone resistance associated with qnr and aac(6')-Ib-cr widely exists in the enterobacteriaceae strains and perhaps this may contribute to the rapid increase of bacterial resistance to quinolones in China. Key words: Enterobacteriaceae; Bacteriocin plasmids; Quinolones; Drug resistance,bacterial; Escherichia coil proteins; Acetyltransferases

Development of an immunoaffinity column method using broad-specificity monoclonal antibodies for simultaneous extraction and cleanup of quinolone and sulfonamide antibiotics in animal muscle tissues

This paper describes a novel mixed-bed immunoaffinity column (IAC) method. The IAC was produced by coupling anti-quinolone and anti-sulfonamide broad-specificity monoclonal antibodies to Sepharose 4B for simultaneously isolating 13 quinolones (QNs) and 6 sulfonamides (SAs) from swine and chicken muscle tissues, followed by antibiotic determination using liquid chromatography–tandem mass spectrometry (LC–MS/MS). A new broad-specificity Mab (B1A4E8) toward sulfonamides was produced using sulfamethoxazole as hapten that demonstrated cross-reactivities to 6 SAs in the range of 31–112%. IAC optimized conditions were found that allowed the IAC to be reused for selective binding of both SAs and QNs. Recoveries of all 19 antibiotics from animal muscle ranged from 72.6 to 107.6%, with RSDs below 11.3% and 15.4% for intra-day and inter-day experiments, respectively. The limit of quantification ranged from 0.5 to 3.0ng/g. The strategy used here for a mixed-bed IAC may be used to study other compounds and more than two classes of analytes simultaneously.

Plasmid-mediated quinolone resistance due to qnrB5 and qnrS1 genes in Salmonella enterica serovars Newport, Hadar and Saintpaul isolated from turkey meat in Denmark

1. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006; 6: 629–40. 2. Robicsek A, Strahilevitz J, Sahm DF et al. qnr prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. Antimicrob Agents Chemother 2006; 50: 2872–4. 3. Park CH, Robicsek A, Jacoby GA et al. Prevalence in the United States of aac(60)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 2006; 50: 3953–5. 4. Park YJ, Yu JK, Lee S et al. Prevalence and diversity of qnr alleles in AmpC-producing Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Serratia marcescens: a multicentre study from Korea. J Antimicrob Chemother 2007; 60: 868–71. 5. Clinical and Laboratory Standard Institute. Performance Standards for Antimicrobial Susceptibility Testing: Fifteenth Informational Supplement M100-S15. CLSI, Wayne, PA, USA, 2005. 6. Paterson DL, Hujer KM, Hujer AM et al. Extended-spectrum b-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHVand CTX-M-type b-lactamases. Antimicrob Agents Chemother 2003; 47: 3554–60.

Analysis of drug resistance of meticillin-resistant staphylococcus

Objective To analyze distribution and drug resistance of MRSA separated,to probe into a treat method for MRSA infection and offer scientific gist for reasonable use of clinical antibiotic. Methods 568 MRSA separated from clinic were measured and a drug sensitivity test was performed by means of Kirby-Bautr agar diffusion method. Results 370 individual plants were filtered, the rate of inspection was 65.1%. MRSA was 36.2 % among them,MRSCON was 77.5% ,the drug resistance of MRSA to quinolones(21% ～48% ) was below MRSCON(84 %～89 % ). The drug resistance of MRSA and MRSCON obviously excelled MSSA and MSSCON ( P＜0.05 ). VRS was undiscovered. Conclusion Severe infection caused by MRS should choose vancomycin resistant enterococci to cure at fist. Staphylococcus was one of primary pathogenic bacterium caused infection in hospital, MRS had multiple drug resistance and measure range about drug resistance should be extended, which would advance the cognition about the drug resistance of antibiotic and cut off the transmitted path, reduce the drug resistance of bacteria and the infection rate in hospital. Key words: Staphylococcus aureus; Coagulase; Meticillin resistance

Analysis of predisposing factors and drug resistance of urinary tract infection with extended-spectrum beta-lactamase producing Escherichia Coli

Objective To investigate the predisposing factors of urinary tract infection(UTI) with extendedspectrum beta-lactaraase(ESBLs) producing Escherichia Coli(E. coli) and its resistance to antimicrobial agents.Methods 26 cases of UTI patients with ESBLs producing E. coli from 2003 to 2005 in our hospital were analyzed retrospectively and compared with the ESBLs non-producing strains. Results 88.5 % of the patients with UTI in ESBLs producing E. coli had received broad-spectrum antimierobial therapy before the diagnosis, 69.2 % of the patients were complicate UTIS, 42.3 % of the patients experienced invasive operations in urinary tract; the incidence of drug resistance of ESBLs producing bacteria to the second, third-generation cephalosporins and quinolone was significantly higher than that of ESBLs non-producing bacteria, but it was highly sensitive to imipenem. Conclusion The drug resistance of ESBLs producing E. coli is severe gradually. So much attention should be paid to the ESBLs producing bacteria detection in UTIs. Antimicrobial therapy should be initiated under the guidance of drug sensitivity test,it is necessary to rid the predisposing factors of UITs as much as possible in order to decrease ESBLs-producing bacteria infection. Key words: Urinary tract infection; Escherichia; Beta-lactam resistance

Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the β 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.

Plasmid-mediated quinolone resistance

喹诺酮类药物(Quinolones)是一类广谱、强效的化学合成抗细菌药物.长期以来,细菌通过染色体介导的靶位点改变[1]、蓄积减少[2](包括孔蛋白缺失、主动外排增加)等机制逐渐对其形成耐药。

Simultaneous Determination of Trace Levels of 10 Quinolones in Swine, Chicken, and Shrimp Muscle Tissues Using HPLC with Programmable Fluorescence Detection

A HPLC method using a modified sample preparation procedure was optimized and validated for the quantification of 10 quinolones (QNs), including marbofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid, and flumequine, in swine, chicken, and shrimp tissues. In this method, only a small mass (<or=2.0 g) of sample and a relatively small volume of organic reagent (<or=4.6 mL) of a nonchlorinated extraction solvent were required. The QNs were analyzed by liquid chromatography in a single run using a gradient elution program and with a programmable fluorescence detector to obtain optimum detection wavelengths. Mean recoveries of 10 drugs from edible animal tissues at a concentration range of 1-100 ng g-1 were 72.8-106.8% with relative standard deviations below 11.2%. The limits of quantification for each QN in different muscle tissues ranged from 0.3 to 1.0 ng g-1, which were below the lowest maximum residue limits (10 ng g-1) established in many countries. The method was also applied to the measurement of QN residues in commercial muscle samples. The results showed it was rapid, simple, sensitive, and suitable for use in food surveillance programs.

2 Cases of Mycoplasma pneumoniae Infection with Severe Pneumonia

M. pneumoniae는 지역사회폐렴의 중요한 원인균으로 대개 경증의 임상상을 보이지만 급성호흡곤란증후군을 일으킬 정도로 중증의 폐렴을 보이는 경우가 드물게 보고 되고 있다. 저자들은 일반적인 임상적인 경과와 달리 심한 폐침윤과 호흡곤란을 호소한 M. pneumoniae 폐렴 2예를 보고한다. 이들은 M. pneumoniae 폐렴의 전형적인 임상양상을 보이지 않았으나 중증지역사회폐렴의 양상을 보여 처음부터 새로운 퀴놀론이나 마크로라이드가 포함된 경험적 항생제 투여를 시작하였다. 또한 처음부터 M. pneumoniae IgG또는 IgM의 의미있는 상승과 추적검사에서 더욱 상승된 항체가를 보이고 혈청 검사에서 다른 감염증의 가능성을 배제하여 M. pneumoniae 폐렴으로 진단하였으며 합병증을 남기지 않고 치료가 되었다. 두 증례를 통하여 저자들은 M. pneumoniae 감염이 중증의 지역사회폐렴의 원인의 하나로 고려되어야 하며, 중증 폐렴소견을 보이는 경우에도 마크로라이드나 퀴놀론을 포함한 경험적 항생제 치료가 필요할 수 있음을 경험하여 보고한다.

Preventing Bacterial Infections in Cirrhotic Patients with Gastrointestinal Hemorrhage

Bacterial infections are quite common in cirrhotic patients who present with gastrointestinal hemorrhage (GIH) — 25% to 65% of such patients present with infections or develop them during subsequent hospitalization. Currently, cirrhotic patients with GIH usually receive either a quinolone or a cephalosporin; however, recent findings have suggested a rise in quinolone-resistant infections in this population. In this randomized controlled trial, researchers compared the efficacy of oral norfloxacin with intravenous ceftriaxone …

Analysis about epidemic situation of dysentery near upon fourteen years in Beijing

To realize the epidemiological and drug-resistance characteristics of dysentery during 1990 to 2003 in Beijing. The group's characteristics of dysentery were described and analysed by using descriptive study method. Drug sensitivity tests were performed with Kirby-Bauer method recommended by WHO, and data were analyzed with SPSS statistic software. Average incidence rate was 222.24 /100 000 and incidence rate was high in children and in urban areas. The period of high incidence was found in July 16 to August 3. The equation of index-curve forecast model was gained as Y = e (5.816-0.5845x. It showed some value in predicting the tendency of dysentery. Shigella was sensitive to quinolones and cephalosporins, and there was no significant differences between the middle and high grade in these two kinds of antibiotics. It should be taken as a measurement for the period of high incidence of dysentery.

Combination Antibiotic Therapy for Pneumococcal Pneumonia

Current guidelines suggest a β-lactam/macrolide combination or a modern quinolone for empirical treatment of community-acquired pneumonia (CAP). This

Determination of quinolones residues in prawn using high-performance liquid chromatography with Ce(IV)–Ru(bpy)32+–HNO3 chemiluminescence detection

A novel method was developed for the determination of quinolone (QN) residues such as ofloxacin, norfloxacin, ciprofloxacin and lomefloxacin by high-performance liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection. The procedure was based on the chemiluminescent enhancement by QNs of the Ce(SO(4))(2)-Ru(bpy)(3)(2+)-HNO(3) system. The separation was carried out with an isocratic elution using the mobile phase of 3:15:82 (v/v/v) acetonitrile-methanol-ammonium acetate buffer (containing 7.5 x 10(-4)M TBAB, 0.8% (v/v) TEA and 1.0 x 10(-4)M ammonium acetate, pH 3.65) at a flow rate of 1.0 ml/min. For the four QNs, the detection limits at a signal-to-noise of 3 ranged from 0.36 to 2.4 ng/ml. The relative standard deviations for the determination of QNs ranged from 1.6 to 4.5% within a day (n=11) and from 3.7 to 6.2% in three days (n=15), respectively. The method was successfully applied to the determination of QNs in prawn samples. The possible mechanism of the CL reaction was also discussed briefly.

Current infection of Mycoplasma pneumoniae in adults: clinical analysis of 13 hospitalized patients

To investigate the clinical characteristics of Mycoplasma pneumoniae (MP) current infection in adults. The clinical data of 13 patients in Beijing, 7 males and 6 females, aged 21.9 (17 - 34), hospitalized from April 2003 to April 2004, were reviewed retrospectively. Seven of the 13 patients were the schoolmates of the same military school, 3 being in the same class but not living in the same dormitory, 3 being hospitalized with an interval of 5 days and 2 with an interval of 2 days. A 4-fold or higher titer rise was found 16 - 17 days after the onset of symptoms. Six cases showed antibody negative at the first visit (2 - 8 days after the onset). The most common symptoms included fever (13/13), cough (11/13), mild headache (5/13), and sore throat (5/13). No symptoms of sneeze, nasal obstruction, skin rash, and ear pain were found. There was no leukocytosis. Ten patients had pneumonia confirmed by X-ray examination. Appropriate macrolide plus quinolones were effective in the treatment. However, there was no significant difference between the curative effect of erythromycin and that of azithromycin. MP mainly attacks young people and mainly causes pneumonia. Extrapulmonary complication is rare. It is not advisable to use a single high antibody titer as the criterion for diagnosis of MP current infection.

Validity of nalidixic acid screening in fluoroquinolone-resistant typhoid salmonellae.

To validate the screening of low-level fluoroquinolone resistance in typhoid salmonellae by using nalidixic acid (30 mg) disk providing an acceptable zone of inhibition. Quasi-experimental study. The Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan from July 2002 to June 2003. Antimicrobial susceptibility of 225 clinical isolates of S. typhi (n=126) and S. paratyphi A (n=99) against nalidixic acid and ciprofloxacin was determined by the modified Kirby-Bauer disk diffusion and agar dilution techniques of NCCLS. The relationship between the zone sizes and the MICs of the two quinolones was plotted in the form of scattergrams and nalidixic acid MICs and zone of inhibition sizes were correlated with those of ciprofloxacin by regression analysis. One hundred and ninety-five isolates were nalidixic acid-susceptible (MIC <16 microg/mL) and approximately 30 were nalidixic acid-resistant (MIC >32 microg/mL). All the nalidixic acid-susceptible isolates had ciprofloxacin MIC of <0.064 microg/mL. Among the nalidixic acid-resistant isolates approximately 20 had ciprofloxacin MIC > or =0.125 microg/mL and approximately 10 had ciprofloxacin MIC < or =0.03-0.064 microg/mL. The diameter of inhibition zone around a 30 mg nalidixic acid disk of nalidixic acid-resistant isolates was < or =13 mm (range 6-16 mm, mean 10.3 mm + SD 3.5 mm), while among nalidixic acid-susceptible isolates it ranged from 14 to 30 mm (mean 23.8 mm + SD 2.2 mm). The diameter of inhibition zone around a 5mg ciprofloxacin disk of nalidixic acid-resistant isolates ranged from 26 to 35 mm (mean 29.8 mm + SD 3.1 mm), while in nalidixic acid-susceptible isolates it ranged from 32 to 42 mm (mean 36.6 mm + SD 1.9 mm). With ciprofloxacin MIC > or =0.125 microg/mL taken as a breakpoint, a zone of <or =33 mm around a 5 microg ciprofloxacin disk to detect low susceptibility strains had a sensitivity of 100% and a specificity of 82%. Screening for nalidixic acid resistance (inhibition zone diameter of < or =13 mm) in isolates with ciprofloxacin MIC 0.125 microg/mL using a 30 microg nalidixic acid disk yielded a sensitivity of 100% and a specificity of 95%. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method for detection of low-level fluoroquinolone resistance in typhoid salmonellae.

Ciprofloxacin Resistance — It’s in the Feces!

Worldwide, quinolone-resistance rates among gram-negative bacilli are rising rapidly. Widespread use of this class of antibiotics can cause selection of resistant organisms in the gut flora. Because these agents are rarely administered before age 18, children provide an opportunity to investigate the prevalence of quinolone-resistant gram-negative bacilli in individuals not exposed to quinolones. Investigators recently …

Antimicrobial resistance surveillance of gram-positive cocci isolated from 12 teaching hospitals in China in 2008

Objective To investigate antimicrobial resistance among gram-positive cocci in China in 2013. Methods Retrospective study. From June 2013 to December 2013, 1 663 consecutive and non-repetitive gram-positive cocci were collected from 15 teaching hospitals. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. A retrospective study was conducted on rates of resistance to antimicrobial agents. The prevalence of penicillin-resistant Streptococcus pneumoniae (PRSP) between children and adult patients and the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) between elder group and younger adult patients were compared using chi-square test. Results The prevalence of PRSP in children below 3 years old (72.9%, 51/70) was higher than adult patients (55.2%, 106/192) (χ2=6.653, P<0.05). About 94.9% (261/275) and (92.7%, 255/275) of S. pneumonia were resistant to erythromycin and clindamycin. All S. pneumoniae strains were susceptible to teicoplanin, vancomycin, linezolid, tigecycline and daptomycin. Penicillin still showed very high activity against Streptococcus spp. β-Hemolytic group. More than 60% of Streptococcus spp.β-Hemolytic group were resistant to erythromycin, clindamycin and tetracyclines. The prevalence of MRSA and methicillin-resistant coagulase-negative Staphylococci(MRCoNS) was 39.7%(229/576) and 80.6%(224/278), respectively. The MRSA prevalence ranged from 24.2% to 70.0% in different regions. About 52.6% (100/190) of Staphylococcus aureus from respiratory tract specimens, 38.5% (40/104) of Staphylococcus aureus from blood samples, and 29.7%(58/195)of Staphylococcus aureus from wound and pus were resistant to methicillin. The prevalence of MRSA in elder group (48.6%, 84/173) was higher than that in younger adult patients (35.7%, 144/403) (χ2=8.322, P<0.05). The susceptibility rates of MRSA to chloramphenicol and trimethoprim/sulfamethoxazole were 86.4% (244/228) and 94.7% (237/228), respectively. Susceptibility rates to gentamycin, erythromycin, clindamycin, tetracyclines, rifampicin and quinolones were ranged from 15.8% to 59.6%. All Staphylococci isolates were susceptible to teicoplanin, vancomycin, linezolid, daptomycin and tigecycline. All Enterococcus isolates were susceptible to daptomycin and tigecycline. All E. faecalis (158/158) and 96.4% (133/138) of E. faecium were susceptible to teicoplanin. About 98.0% (150/153) of E. faecalis and 97.1% (145/138) of E. faecium were susceptible to linezoild. About 45.8% (70/153) of E. faecalis and 60.9% (84/138) of E. faecium were resistant to gentamycin with a high concentration. The susceptibility of E. faecalis to all the antibiotics tested except chloramphenicol and tetracycline was higher than that of E. faecium. Conclusions Based on different age groups and regions, the resistance rates of Gram-positive cocci are different. Teicoplanin, vancomycin, tigecycline, daptomycin, linezolid and tedizolid showed very high activity against Gram-positive cocci.(Chin J Lab Med, 2015, 38: 373-381) Key words: Gram-positive cocci; Drug resistance, bacterial; Anti-bacterial agents; Microbial sensitivity tests; Multicenter study

Macrolides or Quinolones for Treatment of Legionnaires' Disease?

Macrolides have been standard treatment for Legionnaires' disease (LD) for years. Quinolones show bactericidal instead of bacteriostatic activity

Phosphorus-Containing Quinolone Derived from Phenylaminocrotonate

Phosphorus-Containing Quinolone Derived from Phenylaminocrotonate

Rifaximin Is an Effective Prophylaxis for Travelers’ Diarrhea

Rifaximin is a recently FDA-approved alternative to quinolones for the treatment of travelers’ diarrhea. In this manufacturer-supported study, 219 U.S.