[Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023].

Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

[Epidemiological investigation on the local epidemic situation in Zhengzhou High-Tech Zone caused by SARS-CoV-2 Delta variant].

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.

[Effects of ambient particulate matter (PM10) on prevalence of diabetes and fasting plasma glucose].

Objective: To explore the effect of long-term exposure to ambient particulate matter (PM10) on the prevalence of diabetes and fasting plasma glucose (FPG). Methods: The subjects of the study were from the baseline population of "Jinchang Cohort", and 24 285 subjects were finally included after excluding incomplete home address information and diabetic diagnosis information. The demographic characteristics, lifestyle and health status of the survey subjects were collected through questionnaire, physical examination and laboratory tests. ArcGIS software was used to match the nearest environmental monitoring stations for each subject according to residential address. Two-year average concentrations of PM10 were calculated to estimate exposure level. The logistic regression and the multiple linear regression were conducted to assess the effects of ambient PM10 on the prevalence of diabetes and FPG. The restricted cubic spline was used to quantify the dose-response relationship. Stratified analysis and effect modification analysis were also performed. Results: The age of 24 285 participants was (49.32±8.60) years, and the BMI was (24.22±6.09) kg/m2. There were 13 950 (57.44%) males and 2 066 (8.51%) diabetic patients. After adjusting for confounders, for every 10 µg/m3 increase in the average PM10 concentration in the first two years of the survey, the prevalence of diabetes increased [OR (95%CI) =1.05 (1.01-1.09)]and the FPG level elevated [ß (95%CI) = 0.061 (0.047-0.076) mmol/L]. The results of the restricted cubic spline analysis showed a nonlinear relationship between PM10 concentration and FPG level (P<0.001). Further subgroup analysis showed that female [OR (95%CI) =1.10 (1.03-1.18)], people over 50 years old [OR (95%CI) =1.06 (1.02-1.11) ], subjects with family history of diabetes [OR (95%CI) = 1.13 (1.04-1.23) ], and with hypertension [OR (95%CI) = 1.07 (1.02-1.12) ] had a stronger association between the prevalence of diabetes and PM10 exposure (all P interaction values were<0.05). The effects of PM10 on FPG were more significant in people older than 50 years[ß (95%CI) = 0.080 (0.050-0.109) mmol/L], with family history of diabetes [ß (95%CI) = 0.087 (0.036-0.137) mmol/L], and hypertension [ß (95%CI) = 0.077 (0.046-0.108) mmol/L] (all P interaction values were<0.05). Conclusions: Long-term exposure to ambient PM10 increases the diabetes prevalence and FPG. People older than 50 years old, with family history of diabetes and hypertension could be more sensitive to the effects of PM10 exposure.

[Preliminary analysis on COVID-19 case spectrum and spread intensity in different provinces in China except Hubei province].

Objective: To analyze the characteristics of COVID-19 case spectrum and spread intensity in different provinces in China except Hubei province. Methods: The daily incidence data and case information of COVID-19 were collected from the official websites of provincial and municipal health commissions. The morbidity rate, severity rate, case-fatality rate, and spread ratio of COVID-19 were calculated. Results: As of 20 March, 2020, a total of 12 941 cases of COVID-19 had been conformed, including 116 deaths, and the average morbidity rate, severity rate and case-fatality rate were 0.97/100 000, 13.5% and 0.90%, respectively. The morbidity rates in Zhejiang (2.12/100 000), Jiangxi (2.01/100 000) and Beijing (1.93/100 000) ranked top three. The characteristics of COVID-19 case spectrum varied from province to province. The first three provinces (autonomous region, municipality) with high severity rates were Tianjin (45.6%), Xinjiang (35.5%) and Heilongjiang (29.5%). The case-fatality rate was highest in Xinjiang (3.95%), followed by Hainan (3.57%) and Heilongjiang (2.70%). The average spread ratio was 0.98 and the spread intensity varied from province to province. Tibet had the lowest spread ratio (0), followed by Qinghai (0.20) and Guangdong (0.23). Conclusion: The intervention measures were effective in preventing the spread of COVID-19 and improved treatment effect in China. However, there were significant differences among different regions in severity, case-fatality rate and spread ratio.

ANXA3 deletion inhibits the resistance of lung cancer cells to oxaliplatin.

OBJECTIVE: The purpose of this study was to explore the role of ANXA3 in lung cancer cell resistance to oxaliplatin (OXA). MATERIALS AND METHODS: After adding different concentrations of Ox, A549, and A549/Ox cell viability were examined using cell counting kit-8 (CCK-8) assay, and the mRNA and protein expressions of ANXA3 were analyzed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. After treating cells with 5 µg/mL and 15 µg/mL Ox for 24 hours and knocking down ANXA3, qRT-PCR, CCK8, flow cytometry, transwell, and BrdU assays were performed to examine ANXA3 expression level, cell viability, apoptosis, migration, and proliferative capacities, respectively. In addition, Western blot was performed to detect the protein expression of c-caspase 3. RESULTS: The higher the concentration of Ox added, the worse the cell viability. Meanwhile, ANXA3 expression in A549/Ox cells was found remarkably higher than that in normal A549 cells. After treated with different concentrations of Ox for 24 hours, the cell viability, migration capacity and cell proliferation of A549 cells were found remarkably decreased, while the opposite results were observed in cell apoptosis and C-caspase 3 protein expression, and the Ox treatment group was evidently lower than control group. CONCLUSIONS: Knockdown of ANXA3 may be able to inhibit the resistance of LCa cells to OXA.

[The preliminary analysis on the characteristics of the cluster for the COVID-19].

Since December 2019, COVID-19, a new emerging infection disease, has spread in 27 countries and regions. The clusters of many cases were reported with the epidemic progresses. We collected currently available information for 377 COVID-19 clusters (1 719 cases), excluded the hospital clusters and Hubei cases, during the period from January 1 to February 20, 2020. There were 297 family clusters (79%), case median was 4; 39 clusters of dining (10%), case median was 5; 23 clusters of shopping malls or supermarkets (6%), case median was 13; 12 clusters of work units (3%), case median was 6, and 6 clusters of transportation. We selected 325 cases to estimate the incubation period and its range was 1 to 20 days, median was 7 days, and mode was 4 days. The analysis of the epidemic situation in a department store in China indicated that there was a possibility of patients as the source of infection during the incubation period of the epidemic. From February 5 to 21, 2020, 634 persons were infected on the Diamond Princess Liner. All persons are susceptible to the 2019 coronavirus. Age, patients during the incubation period and the worse environment might be the cause of the cases rising. The progress of the two typical outbreaks clearly demonstrated the spread of the early cases in Wuhan. In conclusion, screening and isolating close contacts remained essential other than clinical treatment during the epidemic. Especially for the healthy people in the epidemic area, isolation was the key.

PCAT6 participates in the development of gastric cancer through endogenously competition with microRNA-30.

OBJECTIVE: To investigate the role of lncRNA PCAT6 in the progression of gastric cancer and its underlying mechanism. PATIENTS AND METHODS: Expression levels of PCAT6 in 72 gastric cancer tissues and paracancerous tissues were detected by qRT-PCR (Quantitative Real-Time Polymerase Chain Reaction). The correlation between PCAT6 expression and clinical data of gastric cancer patients was analyzed by the chi-square test. After lentivirus transfection of PCAT6 in gastric cancer cells, proliferation, apoptosis, and invasion were detected by CCK-8 (cell counting kit-8), flow cytometry, and transwell assay, respectively. Western blot was utilized to detect protein expressions of apoptosis-related and EMT-related (epithelial-mesenchymal transition) genes in gastric cancer cells. Furthermore, target genes of PCAT6 were predicted via bioinformatics method and verified by luciferase reporter gene assay. The effects of target genes on biological functions of gastric cancer cells were determined as well. RESULTS: PCAT6 was overexpressed in gastric cancer tissues than those of paracancerous tissues. PCAT6 expression was negatively correlated to prognosis, tumor size, TNM (tumor node metastasis) stage and metastasis of gastric cancer. For in vitro experiments, overexpression of PCAT6 increased proliferation, migration, and invasion, whereas decreased apoptosis of gastric cancer cells. MicroRNA-30 was predicted as the target gene of TCAT6. Furthermore, microRNA-30 was found to bind to TCAT6 via targeting MKRN3. Either microRNA-30 knockdown or PCAT6 overexpression could remarkably promote MKRN3 expression. CONCLUSIONS: PCAT6 is overexpressed in gastric cancer, which promotes the development of gastric cancer by endogenously competition with microRNA-30 via targeting MKRN3.

[Bilateral laryngocele:a case report].

A 71 years old male with throat discomfort, shortness of breath, irritating cough admission. Fiberoptic laryngoscope: bilateral glottis ventricular zone with about quail egg size smooth cystic masses. Throat enhanced CT: infrahyoid margin level about bilateral aryepiglottic fold inside have package containing gas shadow, communicated with the laryngeal chamber. Support laryngoscope under coblation radiofrequency ablation assisted laryngeal cyst excision were done and postoperative pathology consistent with laryngocele.

[Cloning and characterization of a chromosome-encoded catechol 2,3-dioxygenase gene from Pseudomonas aeruginosa ZD 4-3]. / Klonirovanie i kharakteristika gena katekhol-2,3-dioksigenazy, lokalizovannogo v khromosome Pseudomonas aeruginosa ZD 4-3.

Catechol 2,3-dioxygenase (C23O), one of extradiol-type dioxygenases cleaving the aromatic C-C bond at the meta-position of dihydroxylated aromatic substrates, catalyzes the conversion of catechol to 2-hydroxymuconic semialdehyde. Based on curing experiment, PCR identification, and Southern hybridization, the gene responsible for C23O was localized on a 3.5-kb EcoRI/BamHI fragment and cloned from P. aeruginosa ZD 4-3 able to degrade both single and bicyclic compounds via the meta-cleavage pathway. A complete nucleotide sequence analysis of the C23O revealed that it had one ORF, which showed a strong amino acid sequence similarity to the known C23Os of mesophilic gram-negative bacteria. The alignment analysis indicated that distinct difference existed between the C23O in this study and the 2,3-dihydroxybiphenyl dioxygenases cleaving bicyclic aromatic compounds. The heterogenous expression of the pheB gene in Escherichia coli BL21(DE3) demonstrated that this C23O possessed a meta-cleavage activity.

Effect of hydrophobicity and molecular mass on the accumulation of fluoroquinolones by Staphylococcus aureus.

Ten novel fluoroquinolones, with similar chemical structures but differing antibacterial activities and hydrophobicities, were studied to evaluate the role of the physical properties of quinolones on their accumulation and antibacterial activity for Staphylococcus aureus. Six of the 10 agents and tosufloxacin were more active against quinolone-susceptible and -resistant S. aureus than the remaining four agents and several piperazinyl fluoroquinolones. Changes to the side chains of the pyrollidinyl substituent at the R7 position alone made little difference to the MICs. Comparison of MICs of agents that were structurally identical apart from the R1 substituents, confirmed that a t-butyl group confers enhanced activity against S. aureus over a cyclopropyl or ethyl group at this position. The steady-state concentrations (SSCs) of the 10 novel quinolones accumulated by wild-type S. aureus did not correlate with their MICs or chemical structures. There was no apparent relationship between logP of the quinolone and accumulation by S. aureus F77; however, accumulation was positively correlated with molecular mass for 9/10 agents (r = 0.745) confirming that high molecular mass is not a barrier to accumulation in S. aureus. For all 10 agents, the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) increased the concentration of quinolone accumulated by SA-1199, suggesting that NorA was inhibited. The fold increase of the SSC in the presence of CCCP did not correlate with hydrophobicity, but the SSC of agents with either an ethyl or cyclopropyl group at R1 was increased two- to three-fold in the presence of CCCP, suggesting that affinity for the NorA efflux pump may be influenced by quinolone structure.

Antimicrobial activity and accumulation of moxifloxacin in quinolone-susceptible bacteria.

The antibacterial activity of moxifloxacin, compared with that of ciprofloxacin, was determined for five strains of Staphylococcus aureus, including one NorA-overproducing strain, two quinolone-susceptible strains of Streptococcus pneumoniae, four quinolone-susceptible strains of Haemophilus influenzae, and one strain each of quinolone-susceptible Escherichia coli, Pseudomonas aeruginosa and Moraxella catarrhalis. In addition, the accumulation of moxifloxacin and ciprofloxacin by the NCTC type strain of S. pneumoniae, H. influenzae, S. aureus, E. coli and P. aeruginosa was determined by a fluorescence method. For all strains, moxifloxacin accumulated to a lower concentration than ciprofloxacin. The concentrations of moxifloxacin accumulated ranged from 12 to 44 ng/mg dry cells. The lowest concentration was accumulated by S. pneumoniae NCTC 7465 and the highest concentration by S. aureus NCTC 8532. Increased expression of norA in S. aureus had no effect on the accumulation of moxifloxacin. Despite differences in the concentration of moxifloxacin accumulated by the different species, there was little difference between the MICs of this agent for each strain (0.06-0.5 mg/L), suggesting that the concentration accumulated by wild-type bacteria has little effect on the MIC.

Quinolone accumulation by Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.

The accumulation of nalidixic acid and 14 fluoroquinolones over a range of external drug concentrations (10-100 mg/L; c. 25-231 microM) into intact cells of Escherichia coli KL-16, Staphylococcus aureus NCTC 8532, Pseudomonas aeruginosa NCTC 10662 and spheroplasts of E. coli was investigated. The effect of 100 microM carbonyl cyanide m-chlorophenyl hydrazone (CCCP) upon the concentration of quinolone accumulated by intact cells and spheroplasts of E. coli was also determined. Except for pefloxacin, there was an increase in the concentration of the six quinolones examined accumulated by E. coli, despite a reduction in fluorescence at alkaline pH. For ciprofloxacin the partition coefficient (P(app)) was constant despite an increase in the pH; however, the P(app) for nalidixic acid decreased significantly with an increase in pH. The concentration of nalidixic acid, ciprofloxacin and enrofloxacin accumulated by E. coli and S. aureus increased with an increase in temperature up to 40 degrees C and 50 degrees C, respectively. Above these temperatures the cell viability decreased. With an increase in drug concentration there was, for intact E. coli and 12/15 agents, and for S. aureus and 10/15 agents, a linear increase in the concentration of drug accumulated. However, for P. aeruginosa and 13/15 agents there was apparent saturation of an accumulation pathway. Assuming 100% accumulation into intact cells of E. coli, for 10/14 fluoroquinolones < or = 40% was accumulated by spheroplasts. CCCP increased the concentration of quinolone accumulated but the increase varied with the agent and the bacterial species. The variation in the effect of CCCP upon accumulation of the different quinolones into E. coli could result from chemical interactions or from different affinities of the proposed efflux transporter for each quinolone. Overall, these data suggest that accumulation of most quinolones into E. coli and S. aureus proceeds by simple diffusion, but that P. aeruginosa behaves differently.

Non-gyrA-mediated ciprofloxacin resistance in laboratory mutants of Streptococcus pneumoniae.

Two strains of Streptococcus pneumoniae, M4 (NCTC 7465, type strain) and M5 (clinical isolate), and their respective ciprofloxacin-resistant mutants, M4/C1, M5/C1 and M5/C3, were evaluated. All mutants were stable after one year's storage and all grew more slowly in Brain Heart Infusion broth than the parent. The MICs of ciprofloxacin, sparfloxacin and tosufloxacin were increased for the mutants of M4, whereas the mutants of M5 were less susceptible to ciprofloxacin only. The optimal bactericidal concentration (OBC) of each quinolone for all the strains was approximately ten-fold greater than the MIC. The OBCs for the mutants were increased for ciprofloxacin, but not for the other two quinolones. The DNA synthesis IC50 values of all quinolones correlated well with the MIC of each drug. All quinolones accumulated rapidly within all five strains; 10 mM magnesium chloride decreased the concentration of quinolone accumulated, but carbonyl cyanide m-chlorophenyl hydrazone had no effect. Mutant strains M4/C1, M5/C1 and M5/C3 accumulated less quinolone than their respective parent strains. DNA sequencing of those regions of gyrA and gyrB corresponding to the quinolone resistance-determining region in other bacteria did not reveal any differences between the parent and mutant strains.

Prevalence and mechanism of resistance to 'third-generation' cephalosporins in clinically relevant isolates of Enterobacteriaceae from 43 hospitals in the UK, 1990-1991.

In a UK survey of the occurrence of extended spectrum beta-lactamases, 96 hospitals submitted a total of 3951 non-selected, non-duplicate isolates of Enterobacteriaceae from 100 patients in each hospital, 206 of these cultures being mixed and, therefore, discarded. These isolates were initially screened for strains likely to produce extended-spectrum beta-lactamases (ESBLs) by MIC determination of beta-lactams followed by a bioassay, then disc approximation test and isoelectric focusing (IEF). Isolates were further examined using two pairs of PCR primers for both blaTEM and blaSHV genes. The ability of isolates to transfer resistance to both cefotaxime and ceftazidime by conjugation and transformation were examined. Four hundred and nine cefotaxime/ceftazidime-resistant isolates (10.9%) were identified from the 3745 submitted isolates, of which 338 (9.0%) were Enterobacteriaceae, 29 Escherichia coli, 35 Klebsiella spp. and seven Hafnia alveii. IEF suggested that 17 isolates produced an ESBL, which was confirmed in most cases by PCR and hydrolysis, five isolates produced an SHV enzyme by IEF, but not confirmed by PCR, and 11 had isoelectric points in the range 8-9 suggesting a possible AmpC enzyme. Only two isolates transferred the determinants. In the case of the Klebsiella spp., 19 of the 24 ceftazidime-resistant/clavulanate-sensitive isolates were positive by PCR for a blaSHV gene. No isolates were identified as carrying blaTEM, although eight isolates had isoelectric points of 5-6.3, suggesting the presence of a possible TEM beta-lactamase. The results for the H. alveii isolates suggest that either an AmpC-like enzyme or a transferable beta-lactamase which is not TEM/SHV is present. This study shows that a wide range of genotypically and phenotypically different isolates of Enterobacteriaceae producing ESBL-like enzymes is present throughout the UK at a frequency of about 1% of unselected isolates. It is important that surveillance of resistance to these clinically important antibiotics is maintained as the occurrence of localized or more widespread outbreaks caused by bacteria producing ESBLs is to be expected.

Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals.

Twenty-eight human isolates of Escherichia coli from Argentina and Spain and eight veterinary isolates received from the Ministry of Agriculture Fisheries and Foods in the United Kingdom required 2 to > 128 micrograms of ciprofloxacin per ml for inhibition. Fragments of gyrA and parC encompassing the quinolone resistance-determining region were amplified by PCR, and the DNA sequences of the fragments were determined. All isolates contained a mutation in gyrA of a serine at position 83 (Ser83) to an Leu, and 26 isolates also contained a mutation of Asp87 to one of four amino acids: Asn (n = 14), Tyr (n = 6), Gly (n = 5), or His (n = 1). Twenty-four isolates contained a single mutation in parC, either a Ser80 to Ile (n = 17) or Arg (n = 2) or a Glu84 to Lys (n = 3). The role of a mutation in gyrB was investigated by introducing wild-type gyrB (pBP548) into all isolates; for three transformants MICs of ciprofloxacin were reduced; however, sequencing of PCR-derived fragments containing the gyrB quinolone resistance-determining region revealed no changes. The analogous region of parE was analyzed in 34 of 36 isolates by single-strand conformational polymorphism analysis and sequencing; however, no amino acid substitutions were discovered. The outer membrane protein and lipopolysaccharide profiles of all isolates were compared with those of reference strains, and the concentration of ciprofloxacin accumulated (with or without 100 microM carbony cyanide m-chlorophenylhydrazone [CCCP] was determined. Twenty-two isolates accumulated significantly lower concentrations of ciprofloxacin than the wild-type E. coli isolate; nine isolates accumulated less then half the concentration. The addition of CCCP increased the concentration of ciprofloxacin accumulated, and in all but one isolate the percent increase was greater than that in the control strains. The data indicate that high-level fluoroquinolone resistance in E. coli involves the acquisition of mutations at multiple loci.

Activity of biapenem (LJC 10627) against 51 imipenem-resistant bacteria and selection and characterisation of biapenem-resistant mutants.

For wild-type bacteria the activity of biapenem was similar to that of imipenem, but for 51 imipenem-resistant strains meropenem was more active than either. When penicillin-binding protein 2a (PBP 2a) was expressed in Staphylococcus aureus biapenem had reduced activity. Mutant bacteria with decreased susceptibility to biapenem were selected in agar. Most of the mutant Gram negative bacteria were unstable and readily reverted to susceptible. The mutant Proteus vulgaris and Pseudomonas aeruginosa lacked an outer membrane protein. Biapenem-resistant S. aureus could be selected only from MRSA.

A novel gyrB mutation in a fluoroquinolone-resistant clinical isolate of Salmonella typhimurium.

In order to study the role of gyrB in antibiotic resistance in post-ciprofloxacin therapy fluoroquinolone-resistant clinical isolates of Salmonella typhimurium, plasmid pBP548, which contains the Escherichia coli gyrB gene, was used in complementation studies. In a heterodiploid strain, the wild-type (quinolone sensitive) allele is dominant over the resistant allele therefore, eleven clinical isolates were complemented with gyrB encoded on pBP548. Only one transformant, L18pBP548, exhibited increased susceptibility to the quinolones nalidixic acid, ciprofloxacin and sparfloxacin. The amino acid sequence of the gyrase B protein from a wild-type and the pre-therapy S. typhimurium (deduced from the nucleotide sequence) was identical to that of E. coli from codons 436 to 470; however, a point mutation was identified in codon 463 of gyrB of the quinolone-resistant post-therapy isolate L18, giving rise to an amino acid substitution of serine to tyrosine.

Quinolone resistance in veterinary isolates of Salmonella.

Twenty-seven nalidixic acid-resistant (MIC > or = 256 mg/L) isolates of salmonella from veterinary sources were also less susceptible to fluoroquinolones (range of MICs of ciprofloxacin, 0.12-2 mg/L). Six isolates were cross-resistant to one or more chemically unrelated antibacterial agents. The concentrations of enrofloxacin that inhibited DNA synthesis by 50% were similar to the MIC values for 23 of 27 isolates, suggesting a mutation in gyrA. Insertion of pNJR3-2 (gyrA) in nine of 20 isolates increased susceptibility to quinolones, suggesting that resistance was due to mutation in gyrA. Five of 27 isolates had reduced levels of accumulation of enrofloxacin. Two of the five also had increased susceptibility to quinolones when pNJR3-2 was introduced. None of the outer membrane protein profiles of the resistant isolates differed from those of sensitive control strains. Three of 27 isolates had differences in lipopolysaccharide profiles compared to control strains. Although the MIC of ciprofloxacin was less than the recommended UK break point concentrations for most isolates, the increasing incidence of quinolone-resistance in salmonella from veterinary sources is a matter of concern.

Activity of Bay y3118 against quinolone-susceptible and -resistant gram-negative and gram-positive bacteria.

The activity of Bay y3118 against laboratory strains of bacteria, including those with mutations in gyrA, with decreased expression of outer membrane proteins, and/or that are multiply resistant, and 121 selected clinical isolates, including highly fluoroquinolone-resistant bacteria from Spain and Argentina, was determined. Bay y3118 was extremely active (MICs, < or = 1 microgram/ml) against all bacteria, including quinolone-resistant laboratory strains. However, Bay y3118 was less active against 46 of 121 quinolone-resistant clinical isolates, such that > or = 16 micrograms of Bay y3118 per ml was required to inhibit 3 isolates. The concentration of Bay y3118 required to inhibit DNA synthesis by 50% correlated well with the MIC. Bay y3118 had accumulation kinetics similar to those of previously studied fluoroquinolones, e.g., ciprofloxacin, and there was a 50% decrease in the steady-state concentration in those members of the family Enterobacteriaceae that lacked porin proteins. Magnesium chloride at 20 mM apparently abolished the accumulation of Bay y3118 into Escherichia coli and reduced the level of accumulation into other gram-negative bacteria and Staphylococcus aureus. Carbonyl cyanide m-chlorophenylhydrazone at 100 microM enhanced the accumulation of Bay y3118 into E. coli, but it had a minimal effect on accumulation into S. aureus.