Mechanism of Plasmid-Mediated Resistance to Cadmium in Staphylococcus aureus

The mechanism of plasmid-mediated resistance to cadmium in Staphylococcus aureus was investigated. Protein synthesis in cell-free extracts from resistant or susceptible bacteria was equally susceptible to inhibition by Cd(2+), but spheroplasts from resistant bacteria retained their resistance. Resistant bacteria did not have a decreased affinity for cations in general, nor was active metabolism required for exclusion of Cd(2+). The kinetics of Cd(2+) uptake into susceptible and resistant bacteria suggested that the conformation of membrane proteins in resistant bacteria may be important in the exclusion of Cd(2+).     

Carbapenem resistance in Enterobacter aerogenes is due to lipopolysaccharide alterations

The extensive characterization of 2 clinical Enterobacter aerogenes isolates resistant to all beta-lactam antibiotics including imipenem revealed that imipenem resistance could not be attributed to overproduction of the chromosomal beta-lactamase; moreover, it was lost after subcultivation and can be thus considered as unstable. The comparison of sensitive and resistant clones revealed that the beta-lactamase in the resistant clones was less inducible in the resistant clones and moreover, there was an altered 2-keto-3-deoxyoctonate/carbohydrate ratio in the resistant clones as compared to the imipenem-sensitive clones, thus suggesting alterations in the lipopolysaccharide (LPS). Neither enzymatic degradation of both imipenem and meropenem nor alterations of the outer membrane proteins could be observed. These findings make it apparent that this type of resistance is likely due to an impaired uptake of the agents due to LPS alterations.     

Chronic osteomyelitis due to Clostridium clostridiiforme

We have reported a case of chronic osteomyelitis due to an unusual anaerobic organism, Clostridium clostridiiforme, a gram-positive rod that often stains gram-negative and that is frequently resistant to such drugs as cefoxitin and clindamycin. Clostridia other than those similar to C perfringens are generally not considered invasive pathogens, but our case and several similar ones show that they can be.     

In vitro susceptibility of Burkholderia vietnamiensis to aminoglycosides

Burkholderia cepacia complex (BCC) bacteria are opportunistic pathogens that can cause severe disease in cystic fibrosis (CF) patients and other immunocompromised individuals and are typically multidrug resistant. Here we observed that unlike other BCC species, most environmental and clinical Burkholderia vietnamiensis isolates were intrinsically susceptible to aminoglycosides but not to cationic antimicrobial peptides or polymyxin B. Furthermore, strains acquired aminoglycoside resistance during chronic CF infection, a phenomenon that could be induced under tobramycin or azithromycin pressure in vitro. In comparing susceptible and resistant B. vietnamiensis isolates, no gross differences in lipopolysaccharide structure were observed, all had lipid A-associated 4-amino-4-deoxy-L-arabinose residues, and all were resistant to the permeabilizing effects of aminoglycosides, a measure of drug entry via self-promoted uptake. However, susceptible isolates accumulated 5 to 6 times more gentamicin than a resistant isolate, and aminoglycoside susceptibility increased in the presence of an efflux pump inhibitor. B. vietnamiensis is therefore unusual among BCC bacteria in its susceptibility to aminoglycosides and capacity to acquire resistance. Aminoglycoside resistance appears to be due to decreased cellular accumulation as a result of active efflux.     

Streptococcus faecium-derived antibacterial substance antagonistic to Bifidobacteria.

An antagonistic strain of Streptococcus faecium was isolated from human feces, and it displayed a marked inhibition of bifidobacteria on agar plates. In liquid culture this isolate produced an antibacterial substance that can be partially purified by ammonium sulfate precipitation followed by gel filtration and ion-exchange chromatography. Its activity was assayed by the inhibition of growth of Bifidobacterium longum. The substance was sensitive to digestion by proteolytic enzymes and alpha-amylase, but was resistant to treatment with 6 M urea, dithiothreitol, 2-mercaptoethanol, ethyl ether, chloroform, and lysozyme. It was also stable to heating at 100 degrees C for 60 min. Its molecular weight was estimated to be about 50,000 by gel filtration.     

Resistance to penicillin-streptomycin synergy among clinical isolates of viridans streptococci

Viridans streptococci are thought to be highly susceptible to penicillin and streptomycin. We recently encountered a unique group of 15 isolates from South Africa epidemiologically related to the isolation of penicillin-resistant pneumococci. These organisms were highly resistant to penicillin (PCN) (minimal inhibitory concentration, 1 to 32 micrograms/ml) and streptomycin (SM) (minimal inhibitory concentration, greater than or equal to 2,000 micrograms/ml). Two additional organisms with high-level streptomycin resistance were identified when 168 clinical isolates from Boston were screened. Time-kill studies with four organisms resistant to high levels of SM demonstrated lack of synergy between PCN and SM but marked synergy between PCN and gentamicin. Adenylylating, acetylating, and phosphorylating activity could not be detected in three organisms studied, and novobiocin failed to cure the SM resistance. Protein synthesis by ribosomes isolated from these organisms was dramatically reduced in the presence of gentamicin but was relatively resistant to inhibition by SM.     

Induction of Murine Acquired Immunodeficiency Syndrome (MAIDS) in Allophenic Mice Generated from Strains Susceptible and Resistant to Disease

To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus.     

Time of Incubation for Antifungal Susceptibility Testing of Aspergillus fumigatus: Can MIC Values Be Obtained at 24 Hours?

A collection of Aspergillus fumigatus isolates was used to check if MICs can be read at 24 h. At 24 h, the geometric mean MIC of itraconazole for resistant isolates was determined to be 5.11 mg/liter, but the MIC was read as 16 mg/liter at 48 h. At 24 h, MICs for 51.5% of resistant strains were determined to be 相似文献   

Differences in Susceptibility of Enterobacteriaceae and Penicillin-Resistant Staphylococcus aureus to Tetracycline and Minocycline

Two hundred strains of penicillin-resistant Staphylococcus aureus and 311 isolates of Enterobacteriaceae were compared for their susceptibility to tetracycline and minocycline. Thirteen and one-half percent of the staphylococcal isolates were resistant to tetracycline but susceptible to minocycline. Similarly, 24% of the enterobacterial isolates were found to be tetracycline resistant but susceptible to minocycline. Of a total of 511 recent clinical isolates, 14.5% were susceptible to minocycline but were tetracycline resistant.     

Multiple resistance to drugs by MRSA]

Most methicillin-resistant Staphylococcus aureus (MRSA) isolates are multiply resistant to various antimicrobial agents. Therefore, MRSA strains have become a serious problem in the clinical setting. However, it should be noted that the frequency of isolation of strains resistant to aminoglycoside and minocycline was not significantly different between low- and high-MRSA isolates and the isolation frequency of high-MRSA strains, less susceptible to not only beta-lactam antibiotics but also to macrolide antibiotics and quinolones, was significantly higher than the corresponding values for low-MRSA strains. These results suggest that high-MRSA strains were selected by antimicrobial agents for the treatment with the patients.     

Characteristics of herpes simplex virus resistance to disodium phosphonoacetate.

Herpes simplex virus (HSV), which was partially resistant to the inhibitory effect of disodium phosphonoacetate (PAA), could be recovered following four virus passages in the presence of 100 microgram/ml PAA. Resistant strains were isolated from both HSV type 1 and HSV type 2. Virus resistance to PAA was not complete, and in most isolations a significant proportion of the virus stock remained susceptible to the drug. Resistance was shown to be heritable and persisted through virus passage and cloning experiments. PAA inhibited the replication of virus-specific DNA in sensitive strains of HSV but not in resistant strains of HSV. In vitro experiments directly demonstrated that PAA inhibited the activity of the virus-specific DNA polymerase 10 times more effectively in PAA-susceptible HSV than in PAA-resistant HSV. The treatment of HSV-infected mice with high levels of PAA did not induce the formation of resistant virus strains.     

阴道光滑念珠菌耐药性及氟康唑耐药相关基因的表达

目的 研究阴道中光滑念珠菌耐药性及氟康唑耐药相关基因的表达.方法 分离、鉴定阴道分泌物中的光滑念珠菌,并进行药敏实验.抽提光滑念珠菌总RNA,通过RT-PCR检测耐药基因CDR1、CDR2和ERG11的相对表达量.结果 光滑念珠菌对制霉菌素、两性霉素B的药物敏感性最好,5-氟胞嘧啶次之,对唑类药物的耐药率(41.00%～67.00%)较高;对氟康唑的耐药率为44.00%.RT-PCR结果显示,光滑念珠菌氟康唑耐药组CDR1、CDR2和ERG11基因高表达.结论 光滑念珠菌对常用抗真菌药物的耐药率呈上升趋势.光滑念珠菌耐药基因CDR1、CDR2和ERG11的高表达,与临床光滑念珠菌对氟康唑耐药有关.     

Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels.

One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime. The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter. Among these strains, 92% were resistant to cefoperazone, 91% were resistant to cefotaxime, 84% were resistant to ceftazidime, and 6% were resistant to cefepime. Of the members of the family Enterobacteriaceae, 57% were resistant to ceftriaxone. The six strains resistant to cefepime were all Pseudomonas aeruginosa and were resistant to both cefotaxime and ceftazidime. Cefepime-resistant P. aeruginosa strains had exceptionally high levels of beta-lactamase activity, higher than the levels found in strains resistant to ceftazidime but susceptible to cefepime. The beta-lactamases from the cefepime-resistant strains were type I (Richmond-Sykes), were constitutively produced, and did not have increased affinity or hydrolytic activity for cefepime. Thus, cefepime was active against most gram-negative bacteria which have developed resistance to the broad-spectrum cephalosporins, and resistance to cefepime in P. aeruginosa appears to be associated with higher beta-lactamase levels than in cefepime-susceptible strains.     

Heteroresistance to Fluconazole and Voriconazole in Cryptococcus neoformans

Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, >/=64 microg/ml) were recovered at a variable frequency (7 x 10(-3) to 4.6 x 10(-2)). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 microg/ml) and voriconazole (1 microg/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 microg/ml) and moderately resistant to voriconazole (1 microg/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35 degrees C and was completely abolished at 40 degrees C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens.     

Resistance of Mycoplasma pneumoniae to macrolides, lincomycin and streptogramin B

Of four strains of Mycoplasma pneumoniae, highly resistant to erythromycin and related antibiotics, three were homogeneously resistant, but the fourth showed heterogeneous resistance, with only 1% of the cells manifesting this property. Stable, homogeneous resistance was generated in this strain in the presence of erythromycin, whereas the heterogeneous resistance was lost spontaneously on passage in the absence of antibiotics, or on treatment with acridine orange. The mechanism of induction of stable resistance appears to be different from that seen in Staphylococcus aureus.     

Susceptibility of Hong Kong isolates of methicillin-resistant Staphylococcus aureus to antimicrobial agents

Two hundred and sixty-six non-replicate Hong Kong isolates of methicillin-resistant Staphylococcus aureus were tested for their susceptibility to various anti-staphylococcal agents. Multiple resistance was common. More than 95% of patient isolates were resistant to both gentamicin and tetracycline, 68% to erythromycin, 37% to chloramphenicol, 10% to trimethoprim, 5% to rifampicin and 2% to fusidic acid. No isolate was resistant to all these agents, but nineteen different patterns of resistance were identified. Selected gentamicin-resistant isolates were tested against other aminoglycosides, and were sensitive to amikacin and netilmicin. The pattern of aminoglycoside resistance indicated that all isolates produced the aminoglycoside-modifying enzymes APH-(2") and AAC-(6')-I. All isolates were sensitive to vancomycin and teicoplanin. A single strain was resistant to three of the five quinolones tested, but resistance to all the quinolones could be induced easily in vitro by exposure to increasing subinhibitory concentrations of norfloxacin in broth.     

氨苄西林预报粪肠球菌和屎肠球菌亚胺培南敏感性的可行性研究

目的 评价氨苄西林预报粪肠球菌和屎肠球菌亚胺培南敏感性的可行性。方法 收集23家医院的127株粪肠球菌和124株屎肠球菌非重复临床分离株。采用微量肉汤稀释法和纸片扩散法测定粪肠球菌和屎肠球菌对青霉素、氨苄西林、亚胺培南的敏感性。结果 纸片扩散法青霉素和氨苄西林均敏感或均耐药的粪肠球菌,微量肉汤稀释法氨苄西林-亚胺培南的分类一致率（CA）均为100.0%,未出现非常重大误差（VME）和重大误差（ME）;纸片扩散法青霉素和氨苄西林均耐药的粪肠球菌,微量肉汤稀释法氨苄西林-亚胺培南的CA为77.8%,ME占22.2%;青霉素耐药、氨苄西林敏感的粪肠球菌,微量肉汤稀释法氨苄西林-亚胺培南的CA为57.1%,纸片扩散法的CA为81.8%。结论 氨苄西林预报粪肠球菌和屎肠球菌亚胺培南敏感性的可靠性优于青霉素,但氨苄西林的敏感性不能用于预报青霉素耐药、氨苄西林敏感表型粪肠球菌和屎肠球菌的亚胺培南敏感性;青霉素敏感可预报粪肠球菌和屎肠球菌对氨苄西林敏感。     

Effect of human blood serum on tissue cultures. II. Development of resistance to toxic human serum in fibroblast-like cells (Earle''s strain L) obtained from a C3H mouse

When NCTC clone 929 (strain L) cells were grown either continuously or at intervals in toxic human serum, they became resistant to the toxic substance or substances. The resistance developed to toxic human serum was passed from one cell generation to another; i.e., it was heritable. The resistance to toxic human serum, developed in strain L cells, was associated with a decrease in their ability to adsorb toxic substances from the serum. This suggests that there is a decrease in the number of loci in the resistant cells where toxic substances can be bound. The resistant cells differed from the sensitive cells in their morphological appearance, the increased frequency of minute chromosomes, and the increased adhesion to glass surfaces. The cells which developed a resistance to a particular toxic serum also resisted the toxic effects of some other sera, but not of all.     

New macrolides active against Streptococcus pyogenes with inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance

Macrolide-resistant bacteria can be classified as inducibly resistant or constitutively resistant. Inducibly resistant bacteria are resistant to 14-membered macrolides, such as erythromycin and clarithromycin (A-56268), but are susceptible to the 16-membered macrolides, such as tylosin and spiramycin, as well as to clindamycin. Constitutively resistant bacteria are resistant to macrolide-lincosamide-streptogramin B antibiotics. In this study, the MICs of several erythromycin and clarithromycin analogs against macrolide-susceptible and macrolide-resistant Streptococcus pyogenes strains were determined. Four 11,12-carbamate analogs of clarithromycin had lower MICs than erythromycin did against S. pyogenes with the inducible or constitutive type of macrolide-lincosamide-streptogramin B resistance. Five 11,12-carbonate analogs of erythromycin with modifications at the 4" position of cladinose had lower MICs than did erythromycin against S. pyogenes with the constitutive type of resistance, and one of these compounds, which had a naphthyl-glycyl substitution at the 4" position, had a lower MIC than erythromycin against both the inducibly resistant and constitutively resistant strains. Two analogs of erythromycin with a modification on the 4" position of cladinose had lower MICs than erythromycin did against the constitutively resistant organisms but not against the inducibly resistant organisms. Thus, 14-membered macrolides can be modified so as to confer a low MIC when tested in vitro.     

Genetic control of resistance to street rabies virus in mice

Resistance to intraperitoneally inoculated street rabies virus (SRV) in mice was shown to be under genetic control. SJL/J, CBA/J, DBA/2J, and BALB/cAn mice were resistant, whereas A/WySn/J and A.SW/SnJ mice were susceptible. In addition, female mice of the resistant BALB/cAn and DBA/2J strains were more resistant than their male counterparts. Resistance was not controlled solely by the major histocompatibility locus because susceptible A.SW/SnJ and resistant SJL/J mice have the same H-2S haplotype. Challenge of F1 hybrids produced by crossing resistant and susceptible strains indicated resistance was dominant (97% survivors). Inoculation of backcross mice produced by mating F1 hybrids with susceptible parents showed that one and/or two genes controlled susceptibility. Furthermore, inoculation of SRV obtained from six different animals indicated that differences in strain susceptibilities were not dependent on the SRV isolate. Genetic control of resistance to SRV was, however, abrogated by intracerebral inoculation of virus. Resistant strains of mice were detected that either remained asymptomatic or, in contrast, developed signs of clinical disease, but disease failed to progress and they survived. The recognition of resistant and susceptible strains of mice, differences in female-male resistance within the same resistant strain, as well as dissimilar clinical responses in different resistant mouse strains to intraperitoneally inoculated SRV provide promising probes for investigation of host resistance and mechanisms for survival after onset of clinical rabies.