The term "superbugs" refers to microbes with resistance to almost all antibiotics specifically recommended for the treatment. The superbugs disseminating worldwide included methicillinresistant Staphylococcus aureus ; vancomycin-resistant Staphylococcus aureus ; vancomycin-resistant Enterococcus ;carbapenem-resistant Gram-negative bacillus. Due to abuse of antibiotics, novel "superbug"emerged gradually, which demands optimizing antibiotic use, reinforcing surveillance of "superbugs" as well as nosocomial infection control.

The key to improve the clinic antimicrobial therapy results is correct diagnosis of infection,pathogens and antibiotic resistance.To deal with increasingly complex pathogens and drug resistance,the clinic and lab should cooperate and communicate as often as possible,improve the level of pathogen diagnosis,interpretate of the microbiological examination report correctly and explore the mechanisms and treatment of antimicrobial resistant pathogens.Besides,they should make full use of the inflammatory markers to further enhance anti-infective levels.

Community-acquired methicillin-resistant Staphylococcus aureus ( CA-MRSA ) has been increasingly frequently isolated from patients worldwide, and is an emerging threat to public health.CA-MRSA strains differ from hospital-acquired MRSA strains in their epidemiologies, clinical features and genetic backgrounds, and the predominant CA-MRSA strains vary between geographic settings.This paper reviews literatures on the definition, epidemiology, clinical manifestations, treatment and virulent factors of CA-MRSA or CA-MRSA infection, and points out that we should further promote studies on epidemiology, molecular genetic properties of CA-MRSA and clinical management of CA-MRSA infection.

Objective To analyse the encoding gene sequence of extended spectrum ? lactamase produced by Klebsiella pneumoniae E95 strain in Zhejiang Province and identify its ESBLs subtype. Methods The gene of ESBLs produced by E95 strain was amplified by PCR. The purified PCR product was cloned into pGEM Teasy vector and then sequenced by Sanger's dideoxy chain termination composition method. Results The encoded gene of ESBLs was identified as SHV by PCR. Its PCR product had 812 nucleotides. It had the same gene sequence as the gene encoding SHV 12 discovered in Swiss. Conclusions The ESBLs produced by Klebsiella pneumoniae E95 strain isolated from a patient in Zhejiang Province is SHV 12.

Objective To construct the mice pneumonia model with imipenem-resistant Acinetobacter baumannii and provide experimental model in anti-pan-resistant Acinetobacter baumannii therapy study. Methods A total number of 120 4-week-old BALB/C male mice were randomly selected and divided into three groups including micro-intratracheal injection, ultrasonic atomizing and nasal dripping. The mice were treated with methotrexate to induce hypo-immunity in every group. These BALB/C mice of normal immunity and hypo-immunity were infected through Imipenem-resistant Acinetobacter baumannii by microintratracheal injection, ultrasonic atomizing and nasal dripping, respectively. The morbidity, mortality,bacterial clearance rate and histopathology in lung were determined. Results The morbidities of BALB/C mice with hypo-immunity infected by micro-intratracheal injection and ultrasonic atomizing achieved 100%(30/30), while the mortalities were 100% (10/10) and 33.3% (3/10), respectively. Mice in two groups above displayed the influx of neutrophils, lymphocytes and macrophages in the peri-bronchial and alveolar interstitial space 12-24 h after pulmonary infection. In addtion, the mice in micro-intratracheal injection group displayed coUapse of partial alveolar walls, formation of abscesses and bacterial colonies in alveoli. While the lung pathology in mice of ultrasonic atomizing group was characterized by cell degeneration in some regions in the lungs, slight relaxation, congestion in alveolar wall vessels and normal of bronchial and alveolar tissue 24 h after inoculation. Degeneration in peri-tracheal and peri-bronchial areas was observed 24-48 h after inoculation, along with highly expanded pulmonary blood vessels and edems. The inflammation was reduced at 48 hours. There was no obvious pulmonary infection in BALB/C mice with hypo-immunity by nasal dripping with mortality of 0% (0/10) and no significant histopathologic change in lungs. Conclusions BALB/C mice with hypo-immunity pneumonia model with Imipenem-resistant Acinetobacter baumannii can be conducted by micro-intratracheal injection or ultrasonic atomizing, but the latter has the advantages of high-productivity, easy-operation, low-cost, time-saving and usefulness. Mice with normal immunity are not susceptible to imipenem-resistant Acinetobacter baumannii.

Objectives To investigate the properties and distributions of ampC gene among different drug-resistant strains of Serratia marcescens,and the relationship of control gene ampR with AmpC enzymes′ expressions.Methods According to the results of inducting experiment with 1/2 MIC of beta-lactam antibiotics (CTX),three-dimensional testing and isoelectric focusing electrophoresis testing,143 strains of S.marcescens were classified into three groups:including induction group, continuous low-production group and hyperproduction group. In each group, the sequences of ampC and ampR genes were amplified using the method of PCR. The products of PCR were analyzed. The plasmid-mediated beta-lactamases were detected using the method of conjugation experiment.Results Among 143 strains of S.marcescens, the continuous low -production strains, induction strains and hyperproduction strains were 14,103,and 18, respectively.125 and 99 strains were ampC and ampR gene positive, respectively.The detection rate of ampR in hyperproduction group was lower than other groups.5 sites of ampC genes and 4 sites in the Open Reading Frame (ORF) of ampR gene were easily mutated in 5 induction strains and 2 hyperproduction strains.Conclusions The production of inducing drug-resistance of some S.marcescens might be related to mutation of ampC gene encoding AmpC beta-lactamases and the ORF mutation in ampR. The continuous hyperproduction drug-resistance had something to do with deletion mutation in ampR in segmental hyperproduction strains.The plasmid-mediated AmpC enzymes hadn′t been found in S.marcescens.

Objective To observe the effects of Qutantongluo decoction on the expression of TGF-β1 in renal tissue of diabetic nephropathy(DN) rats,which can help to understand the mechanism of action.Methods The rats models of diabetic nephropathy were established by injecting with streptozotocin intraperi-toneally.All Wistar rats were randomly divided into 6 groups:the normal control group,the model control group,Benazepril Hydrochloridec group ( 1 mg/kg ·d-1 ),Qutantongluo decoction low dose group (3 g/kg ·d-1 ),Qutantongluo decoction median dose group (4.5 g/kg · d-1 ),and Qutantongluo decoction high dose group (6 g/kg · d-1 ).Rats in the normal control group and the model control group were given celiac perfusion of distilled water once at the same time and dose.All the rats were gavaged once daily for 8 weeks.The expression of TGF-β1 at the level of gene and protein in renal tissue were tested by immunohistochemistry and RT-PCR methods.Results Compared with the model control group(2.79±0.22),the expression of TGF-β1 at the level of protein in renal tissue of Benazepril Hydrochloridec group (1.55 ±0.12)and the Qutantongluo decoction low dose group ( 1.54± 0.16),Qutantongluo decoction median dose group (1.49 ± 0.17),Qutantongluo decoction high dose group(l.39±0.25) decreased significantly (P＜0.05).Compared with the model control group (0.35±0.07),the expression of TGF-β1 mRNA in renal tissue of Benazepril Hydrochloridec group(0.35± 0.07)and the Qutantongluo decoction low dose group(0.39±0.03),Qutantongluo decoction median dose group (0.35± 0.06),Qutantongluo decoction high dose group (0.32± 0.07) decreased significantly (P＜0.05).Conclusion Qutantongluo decoction can down regulate the expression of TGF-β1 in kidney,which may be one of the mechanisms of Qutantongluo decoction effectiveness in clinical treatment of diabetic nephropathies.

Objective To investigate the resistance-related genes of Shigella sonnei with decreased susceptibility to fluoroquinolones.MethodsA total of 131 strains of Shigella sonnei were analyzed for their antimicrobial susceptibility.Mutations within the quinolone resistance determining regions (QRDR) of gyrA and parC were detected by polymerase chain reaction (PCR) and PCR products were then sequenced. Meanwhile, the plasmid-mediated quinolone resistance (PMQR) genes,qnr and aac(6')-Ib-cr were screened by PCR.ResultsResistance rates of 131 Shigella sonnei isolates to nalidixic acid,tetracycline,ampicillin and trimethoprim-sulfamethoxazole were 100.0％,93.9％,93.2％ and 92.8％,respectively.All strains were susceptible to norfloxacin,ciprofloxacin,levofloxacin,while 94％ nalidixic acid-resistant Shigella sonnei strains showed reduced susceptibilities to fluoroquinolones.All of nalidixic acid-resistant Shigella sonnei strains presented a single mutation at codon 83 (Ser→Leu) of gyrA genes,but no mutations were detected in parC gene.And PMQR genes qnr and aac (6’)-Ib-cr were not detected.Conclusions The nalidixic acid-resistant Shigella sonnei strains with reduced susceptibility to fluoroquinolones are common in the clinical practice,which may mainly due to a single mutation at codon 83 (Ser→Leu) of gyrA genes.

Objective To evaluate the synergy effect of Meropenem and Sulbactam combination against Meropenem-resistant and Meropenem-susceptible A.baumannii in vitro and optimize combination ratio of Meropenem and Sulbactam to achieve best synergy effect.Methods Evaluating the synergy effect of Meropenem and Sulbaetam combination through microdilution checkerboard method against Meropenemresistant and Meropenem-susceptible A.baumannii,isolated from inpatients of Chinese hospitals.Assessing the synergy effect of combination in different ratios of Meropenem to Sulbactam.Results The checkerboard method with the combination of Meropenem and Sulbactam demonstrated 25.0％ ( 10/40 ) synergism,67.5％ (28/40) partial synergism,7.5％ (3/40) additive,no indifference and antagonism in Meropenemsusceptible isolates,and 27.5％ (11/40) synergism,40.0％ (16/40) partial synergism,25.0％(10/40) additive,no indifference and antagonism in Meropenem-resistant isolates.Eleven Meropenemresistant isolates which showed synergism in synergy test were tested for MICs of combination of Meropenem and Sulbactam,using ratios of 4∶ 1,2∶ 1,1∶1 and 1∶2,and the MIC90 were 64∶ 16,64∶ 32,32∶32,32∶64 μg/ml,respectively.Conclusions Meropenem and Sulbactam combination show synergism or partial synergism against most A.baumannii isolates.The optimal ration of combination for clinical use may be 1∶ 1.

Objective To evaluate antimicrobial activity of fosfomycin combined with tigecycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and study the mechanism of drug resistance to fosfomycin. Methods Broth microdilution method was used to independently determine the minimum inhibitory concentrations (MIC)of fosfomycin and tigecycline against 42 Klebsiella pneumoniae isolates (including 20 KPC-producing and 22 KPC non-producing isolates).Checkerboard design method was applied to evaluate combined effect of different concentrations on antimicrobial susceptibility and calculate the fractional inhibitory concentration index (FICI).FICI=MICfosfomycin joint/MICfosfomycin monotherapy +MICtigecycline joint/MICtigecycline monotherapy .Related interpretation criteria were as following:FICI≤0.5 means synergy;0.5 2 means antagonism.The fosfomycin resistant genes in KPC-producing Klebsiella pneumoniae isolates were screened.The data were analyzed by t test.Results Antimicrobial susceptibility testing results indicated the fosfomycin and tigecycline susceptibility rates in KPC-producing isolates were 35 .0%(7/20)and 70.0% (14/20 ),respectively.The susceptibility rates of drug combination increased to 50.0% (10/20 )and 95 .0% (19/20 ),respectively,with both MIC decreased.MIC of tigecycline decreased significantly after combination therapy and showed a statistical significance compared with the MIC of monotherapy (t = - 2.596,P = 0.013 ),whereas there was no significant difference between single and combined therapy of fosfomycin (t=-1 .274,P =0.211).FICI indicated that a total of 60.0%isolates showed synergy and additive effects between two antimicrobial agents,followed by indifference (40.0%),but there was no antagonism effect.Among 22 KPC non-producing isolates,there were 54.5 %showing indifference effects,followed by additive (31 .8%)and synergy (13.6%)effects.No antagonism effect was found.The study also identified two isolates with fosA resistant gene which located on the same plasmid as well as the bla KPC gene.The plasmid sizes in the two isolates were 138.9 kb and 104.5 kb, respectively.Conclusions KPC-producing Klebsiella pneumoniae are more susceptible to tigecycline. Combined use of two antimicrobial agents mainly exerts synergy and additive effect rather than antagonism,which may suggest the combination therapy strategy could inhibit the activity of KPC-producing Klebsiella pneumoniae .