Comparative In Vitro Activity of Gatifloxacin Against Stenotrophomonas maltophilia and Burkholderia Species Isolates Including Evaluation of Disk Diffusion and E Test Methods

 The in vitro activity of gatifloxacin, a new fluoroquinolone, was compared to that of five other fluoroquinolones against 105 Stenotrophomonas maltophilia isolates and 52 Burkholderia spp. isolates. The gatifloxacin MICs were determined using the broth microdilution method and the E test (AB Biodisk, Sweden); these methods were compared for test accuracy, and 5 μg disk zone diameters were compared for interpretive accuracy using the standardized disk diffusion method. In terms of potency, gatifloxacin was most similar to sparfloxacin and trovafloxacin against Stenotrophomonas maltophilia (MIC50, 0.5–1 mg/l) and Burkholderia spp. (MIC50, 1–2 mg/l). This activity was greater than that of ciprofloxacin, levofloxacin or ofloxacin (MIC50, ≥2 mg/l) against Stenotrophomonas maltophilia isolates but comparable to that of levofloxacin against the Burkholderia spp. (60% susceptible at ≤2 mg/l). The E test results compared well with the reference dilution test results (81–97% at ±1 log₂ dilution). The disk diffusion test using previously suggested breakpoints for other bacteria (≥18 mm or ≤2 mg/l for susceptible and ≤14 mm or ≥8 mg/l for resistant) also performed well, at >90% categorical agreement. The activity of gatifloxacin is comparable to that of other newer quinolones against isolates of Stenotrophomonas maltophilia and Burkholderia spp., and susceptibility testing using simple qualitative and quantitative methods appears to function well with these drug/organism combinations.     

In Vitro Antibacterial Activity and Pharmacodynamics of New Quinolones

This synopsis of published literature summarises data on the in vitro antibacterial activity and pharmacodynamics of fluoroquinolones. Data were compiled for ciprofloxacin, levofloxcin, moxifloxacin, gatifloxacin, grepafloxacin, gemifloxacin, trovafloxacin, sitafloxacin and garenoxacin. All of these quinolones are almost equipotent against gram-negative bacteria but demonstrate improved activity against gram-positive species. The new quinolones are uniformly active against gram-positive species except Streptococcus pneumoniae; against which gemifloxacin, sitafloxacin and garenoxacin are one to two dilution steps more active than moxifloxacin. All of the new quinolones except gemifloxacin demonstrate enhanced activity against anaerobes. Since all the new quinolones show similar activity against the major respiratory tract pathogens except Streptococcus pneumoniae and members of the family Enterobacteriaceae, their pharmacokinetics and pharmacodynamics will be clinically relevant differentiators and determinants of their overall activity and efficacy. In vitro simulations of serum concentrations revealed that (i) gemifloxacin and levofloxacin were significantly and gatifloxacin moderately less active than moxifloxacin against Streptococcus pneumoniae and Staphylococcus aureus, and (ii) resistant subpopulations emerged following exposure to levofloxacin and gatifloxacin (gemifloxacin not yet published) but not to moxifloxacin. The emergence of resistance is a function of drug concentrations achievable in vivo and the susceptibility pattern of the target organisms. Therefore, the use of less potent fluoroquinolones with borderline or even suboptimal pharmacokinetic/pharmacodynamic surrogate parameters will inadvertently foster the development of class resistance. Drugs with the most favourable pharmacokinetic/pharmacodynamic characteristics should be used as first-line agents in order to preserve the potential of this drug class and, most importantly, to provide the patient with an optimally effective regimen. Electronic Publication     

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC₅₀) was 3.59×10^-3 µg/mL in doxycycline-treated group. Whereas in 0.71×10^-3 µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.     

In Vitro Activity of ABT-773 Against Anaerobic Bacteria

 The purpose of the study reported here was to determine the in vitro activity of ABT-773 compared with that of other antimicrobial agents against anaerobic bacteria. The activity of ABT-773 was investigated against 354 clinical isolates of anaerobic bacteria by the agar dilution method and was compared with that of azithromycin, clarithromycin, roxithromycin, erythromycin, cefoxitin, imipenem, clindamycin and metronidazole. ABT-773 and imipenem were the most active antimicrobial agents tested.     

Comparative Activity of Moxifloxacin in Vitro Against Obligately Anaerobic Bacteria

 The antimicrobial activity of moxifloxacin and seven other antibiotics (four of them quinolones) against 292 strains of obligately anaerobic bacteria was assessed employing a broth microdilution technique performed in Wilkens-Chalgren broth. MIC50/MIC90 values (mg/l) for moxifloxacin were as follows: Bacteroides fragilis (n=62) 0.25/2, Bacteroides ovatus (n=70) 1/4, Bacteroides vulgatus (n=29) 0.25/1, Bacteroides thetaiotaomicron (n=17) 2/2, Bacteroides caccae (n=11) 1/2, Prevotella spp. (n=11) 0.25/2, Fusobacterium spp. (n=17) 1/4, Bilophila wadsworthia (n=29) 0.5/1, and Clostridium spp. (n=29) 0.125/0.5, respectively. MIC50 values (mg/l) for Bacteroides distasonis (n=8) and Peptostreptococcus spp. (n=9) were 0.25. The results indicated that moxifloxacin was almost as active as trovafloxacin, as active as gatifloxacin, and more active than levofloxacin and ciprofloxacin against the anaerobes tested.     

Reassessment of Stenotrophomonas maltophilia phenotype

Standard microbiology references describe Stenotrophomonas maltophilia as oxidase negative and variable with respect to utilization of lactose and sucrose. Analysis of a collection of 766 S. maltophilia isolates indicated that approximately 20% are oxidase positive and that this species should be reevaluated for other phenotypes, including oxidative fermentation of lactose and sucrose.     

Activity of colistin in combination with tigecycline or rifampicin against multidrug-resistant Stenotrophomonas maltophilia

The antimicrobial treatment of Stenotrophomonas maltophilia infections is complicated by intrinsic multidrug resistance and a lack of reliable susceptibility data. We assessed the activity of colistin (COL), rifampicin (RIF) and tigecycline (TGC) alone and in combination using a range of in vitro susceptibility testing methodologies and a simple invertebrate model of S. maltophilia infection (Galleria mellonella). Synergy [fractional inhibitory concentration indices (FICIs) ≤0.5] between COL and either RIF or TGC was observed against 92 % and 88 % of 25 S. maltophilia isolates, respectively, despite resistance to one or another of the single agents alone. In time–kill assays, COL combined with either RIF or TGC was superior to single agents, but only the COL/RIF regimen was reliably bactericidal. The in vitro findings correlated with treatment outcomes in G. mellonella, with heightened survival observed for larvae treated with COL/RIF or COL/TGC compared with COL, RIF or TGC alone. COL combined with RIF was the most effective combination overall in both in vitro and in vivo (p?S. maltophilia infections, regimens consisting of COL combined with RIF or TGC could be considered for clinical use.     

头孢他啶/阿维巴坦对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性研究

目的 研究头孢他啶/阿维巴坦(CZA)对耐碳青霉烯类肺炎克雷伯菌(CRKP)的体外抗菌活性并检测其相关耐药基因,为临床治疗CRKP提供参考依据.方法 选取2017年1月至2019年12月北京中医药大学东方医院临床分离的257株CRKP菌株,应用VITEK MS微生物质谱仪和VITEK-2 Compact微生物药敏分析仪进行菌种鉴定和药敏分析,用K-B法检测CZA的药物敏感性.采用碳青霉烯酶抑制剂增强试验对CRKP菌株进行产酶表型检测.通过NG-Test CARBA 5对耐CZA的CRKP菌株进行相关耐药基因检测.结果 257株CRKP菌株对CZA的耐药率为7.8％,对哌拉西林/他唑巴坦、阿莫西林/克拉维酸、头孢哌酮/舒巴坦、头孢呋辛、头孢他啶、头孢曲松、头孢西丁的耐药率均为100％,头孢吡肟97.2％、左氧氟沙星97.1％、阿米卡星48.5％、庆大霉素76.4％、复方新诺明46.5％、替加环素35.5％.碳青霉烯酶抑制剂增强试验结果显示,CRKP菌株耐药主要以产丝氨酸酶为主.20株耐CZA的CRKP菌株中,产KPC 11株,产OXA-481株,产IMP 1株,产NDM 4株,既产KPC又产NDM 2株,不产碳青霉烯酶1株.结论 CZA对CRKP菌株有较强的抗菌效果,抗菌活性明显优于临床常用抗菌药物.CZA体外药敏试验可在临床常规开展,为临床治疗CRKP提供更多的参考.     

42株形成生物被膜的嗜麦芽窄食单胞菌的药物敏感性研究

目的 研究单独及联合使用不同种类抗生素对嗜麦芽窄食单胞菌(Stenotrophomonasmahophilia,SML)体外生物被膜的抗菌活性. 方法 收集从患者分离的非重复SML 42株,分别采用微量接种针和硅胶膜片在水解酪蛋白肉汤中构建细菌生物被膜(bacterial biofilm)的体外模型,经过抗生素(左氧氟沙星、环丙沙星、头孢哌酮/舒巴坦、头孢他啶、哌拉西林、红霉素、磺胺甲噁唑、庆大霉素)作用20 h,超声振荡并测定孵育前后6 h吸光度(A)值的变化,计算相应的细菌生物被膜抑制浓度,进而测定红霉素与左氧氟沙星、头孢哌酮/舒巴坦、哌拉西林对细菌生物被膜的联合作用. 结果 SML对左氧氟沙星、磺胺甲噁唑和哌拉西林敏感率分别为83.33%、66.67%和54.76%,其他抗生素的耐药率均在50%以上.形成生物被膜后,细菌对抗生素的生物被膜抑制浓度大于相应的最小抑菌浓度(MIC)值. 结论 42株SML呈现多重耐药现象,形成生物被膜后耐药性增强.左氧氟沙星的抗菌活性在形成生物被膜前后均优于其他抗生素,联合红霉素与左氧氟沙星有助于增强杀菌效果.     

Role of Stenotrophomonas maltophilia in hospital-acquired infection

Stenotrophomonas maltophilia (previously Pseudomonas maltophilia, Xanthomonas maltophilia) is highly resistant to antibiotics. It causes infections that result in increased morbidity, but not usually mortality, in patients with weakened host defences. The increase in S. maltophilia nosocomial infections is due to the changing nature of the hospital patient population and to changes in antibiotic usage. Detection, identification and susceptibility testing methods require improvement, and this complicates the comparison of published data. Susceptibility testing should be reserved for those isolates that are clearly associated with disease. Treatment can be difficult and may be complicated by biofilm formation. S. maltophilia can both acquire and transfer resistance to antibiotics. Future therapeutic development may be directed against biofilms and efflux mechanisms, in order to render the organism more susceptible to available antimicrobial agents.     

Stenotrophomonas maltophilia: From Trivial to Grievous

Stenotrophomonas maltophilia, once regarded as an organism of low virulence, has evolved as a significant opportunistic pathogen causing severe human infections in both hospital and community settings, especially amongst highly debilitated patients. Globally, S. maltophilia ranks third amongst the four most common pathogenic non-fermenting Gram-negative bacilli (NFGNBs), others being Pseudomonas aeruginosa, Acinetobacter baumannii and Burkholderia cepacia complex (Bcc). The worth of accurate identification of S. maltophilia comes to the forefront as it needs to be differentiated from other NFGNBs such as Acinetobacter, P. aeruginosa and Bcc due to its inherently contrasting antibiotic susceptibility pattern. Consequently, its correct identification is essential as no single drug is amply effective against all NFGNBs, which hinders initiation of appropriate empirical treatment resulting in increased morbidity and mortality.     

Diversity of nosocomialXanthomonas maltophilia (Stenotrophomonas maltophilia) as determined by ribotyping

Seventy-seven clinical isolates ofXanthomonas maltophilia (Stenotrophomonas maltophilia) were consecutively collected from the Rigshospitalet, Copenhagen, ribotyped and compared with the ribotypes of 25 other clinical and reference strains ofXanthomonas maltophilia. Using restriction enzymeEcoRI, 20 different ribotypes were observed, with 78 isolates displaying the five most common types. Using another enzyme,BamHI, these 78 isolates were further subdivided into 16 different ribotypes. Three patients harboured two strains with different ribotypes. No type was found related to only one department and no single-strain outbreak was detected. The origin of this wealth of different strains in hospital patients needs to be established.     

Stenotrophomonas maltophilia genomes: A start-up comparison

The whole DNA sequences of 2 Stenotrophomonas maltophilia strains isolated from the blood of a cancer patient (K279a) and the poplar Populus trichocarpa (R551-3) have been compared. The 2 chromosomes exhibit extensive synteny, but each is punctuated by about 40 genomic islands (GEIs), which vary in size from 3 to 70 kb, and may encode up to about 50 proteins. A large set of smaller DNA sequences, encoding strain-specific ‘solo’ orfs, contributes to genetic heterogeneity in a significant manner. S. maltophilia GEIs potentially encode several proteins mediating interactions with the environment such as transmembrane proteins, haemagglutinins, components of type I and IV secretion systems, and efflux proteins having a role in metal and/or drug resistance. The presence of specific GEIs in the S. maltophilia population was monitored by PCR and slot-blot analyses. Data suggest that some islands are present at sites different from those identified in K279a and that alternative islands may be integrated at mapped sites.     

Immunostimulatory properties of the emerging pathogen Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic pathogen that is being isolated with increasing frequency from patients with health-care-associated infections and especially from patients with cystic fibrosis (CF). While clinicians feel compelled to treat infections involving this organism, its potential for virulence is not well established. We evaluated the immunostimulatory properties and overall virulence of clinical isolates of S. maltophilia using the well-characterized opportunistic pathogen Pseudomonas aeruginosa PAO1 as a control. The properties of CF isolates were examined specifically to see if they have a common phenotype. The immunostimulatory properties of S. maltophilia were studied in vitro by stimulating airway epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was used to determine the rates of pneumonia, bacteremia, and mortality, as well as the inflammatory response elicited by S. maltophilia infection. Respiratory and nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited significant interleukin-8 expression by airway epithelial cells, as well as tumor necrosis factor alpha (TNF-alpha) expression by macrophages. TNF-alpha signaling appears to be important in the pathogenesis of S. maltophilia infection as less than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed pneumonia and bacteremia following intranasal inoculation. The S. maltophilia isolates were weakly invasive, and low-level bacteremia with no mortality was observed. Despite the lack of invasiveness of S. maltophilia, the immunostimulatory properties of this organism and its induction of TNF-alpha expression specifically indicate that it is likely to contribute significantly to airway inflammation.