Prevalence and characteristics of multidrug-resistant Escherichia coli sequence type ST131 at two academic centers in Boston and Minneapolis, USA.

BACKGROUND: Escherichia coli sequence type (ST) ST131, with its emergent resistance-associated H30Rx, H30R1, and C1-M27 clonal subsets, accounts for the greatest share of extraintestinal E. coli infections and most extended-spectrum ß-lactamase (ESBL)-producing E. coli. METHODS: We characterized and compared consecutive E. coli urine isolates from two geographically distinct medical centers in Minneapolis, Minnesota (n = 172) and Boston, Massachusetts (n = 143) for ESBL phenotype, CTX-M-type ESBL genes, phylogenetic groups, selected ST131 subclones, and 40 extraintestinal virulence genes. RESULTS: Whereas the Boston vs. Minneapolis isolates had a similar prevalence of phylogenetic groups (mainly B2: 79% vs 73%), ST131 (34% vs 28%), H30 (28% vs 21%), and H30Rx (6% vs 5%), the emerging C1-M27 subclone occurred uniquely among Boston (6%) isolates. ESBL production was more prevalent among Boston isolates (15% vs 8%) and among ST131 isolates. Identified ESBL genes included blaCTX-M-27 (Boston only) and blaCTX-M-15. Ciprofloxacin resistance was ST131-associated and similarly prevalent across centers. Boston isolates had higher virulence gene scores. CONCLUSIONS: Despite numerous similarities to Minneapolis isolates, Boston ST131 isolates demonstrated more prevalent ESBL production, higher virulence gene scores, and, uniquely, the C1-M27 subclone and blaCTX-M-27. Broader surveillance is needed to define the prevalence of ST131's globally successful C1-M27 subclone across the U.S.

The antimicrobial peptide DGL13K is active against drug-resistant gram-negative bacteria and sub-inhibitory concentrations stimulate bacterial growth without causing resistance.

Antimicrobial peptides may be alternatives to traditional antibiotics with reduced bacterial resistance. The antimicrobial peptide GL13K was derived from the salivary protein BPIFA2. This study determined the relative activity of the L-and D-enantiomers of GL13K to wild-type and drug-resistant strains of three gram-negative species and against Pseudomonas aeruginosa biofilms. DGL13K displayed in vitro activity against extended-spectrum beta-lactamase (ESBL)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (MICs 16-32 µg/ml), MDR and XDR P. aeruginosa, and XDR Acinetobacter baumannii carrying metallo-beta-lactamases (MICs 8-32 µg/ml). P. aeruginosa showed low inherent resistance to DGL13K and the increased metabolic activity and growth caused by sub-MIC concentrations of GL13K peptides did not result in acquired bacterial resistance. Daily treatment for approximately two weeks did not increase the MIC of DGL13K or cause cross-resistance between LGL13K and DGL13K. These data suggest that DGL13K is a promising antimicrobial peptide candidate for further development.

Performance of Four Fosfomycin Susceptibility Testing Methods against an International Collection of Clinical Pseudomonas aeruginosa Isolates.

Fosfomycin has been shown to have a wide spectrum of activity against multidrug-resistant Gram-negative bacteria; however, breakpoints have been established only for Escherichia coli or Enterobacterales per the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), respectively. A lack of additional organism breakpoints limits clinical use of this agent and has prompted extrapolation of these interpretive categories to other organisms like Pseudomonas aeruginosa without supporting evidence. Further complicating the utility of fosfomycin is the specified method for MIC determination, namely, agar dilution, which is not widely available and is both labor and time intensive. We therefore sought to determine the susceptibility of a large international collection of P. aeruginosa isolates (n = 198) to fosfomycin and to compare testing agreement rates across four methods: agar dilution, broth microdilution, disk diffusion, and Etest. Results were interpreted according to CLSI E. coli breakpoints, with 49.0 to 85.8% considered susceptible, dependent upon the testing method used. Epidemiological cutoff values were calculated and determined to be 256 µg/ml and 512 µg/ml for agar dilution and broth microdilution, respectively. Agreement rates were analyzed using both agar dilution and broth microdilution with a resulting high essential agreement rate of 91.3% between the two susceptibility testing methods. These results indicate that broth microdilution may be a reliable method for fosfomycin susceptibility testing against P. aeruginosa and stress the need for P. aeruginosa-specific breakpoints.

Ceftolozane-tazobactam and ceftazidime-avibactam activity against ß-lactam-resistant Pseudomonas aeruginosa and extended-spectrum ß-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres.

BACKGROUND: Despite availability of ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) for several years, the individual spectrum of activity of each agent may not be widely known. We compared the activity of C/T and CZA against convenience samples of 119 extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales and 60 ß-lactam-resistant Pseudomonas aeruginosa clinical isolates collected from three U.S. institutions. METHODS: Minimal inhibitory concentrations (MICs) for C/T and CZA were determined by broth microdilution. Molecular identification of nine ß-lactamase gene targets was conducted for Enterobacterales and P. aeruginosa isolates with increased MICs to C/T or CZA. RESULTS: More than 90% of Enterobacterales isolates demonstrated susceptibility to both C/T and CZA, in contrast to the other traditional ß-lactam agents tested, which were much less active. The MIC50/90 values were nearly equivalent between agents. The most common ß-lactamase genes identified in Enterobacterales isolates with MIC values ≥2 mg/L were the CTX-M-1 group (85%) and CMY-2-like (23%) ß-lactamases. Both agents were active against >80% of ß-lactam-resistant P. aeruginosa isolates tested, most of which had oprD mutations identified. One P. aeruginosa isolate was positive for a Klebsiella pneumoniae carbapenemase-type gene but remained meropenem-susceptible. The MIC50 values were four-fold lower in favour of C/T (1 mg/L vs. 4 mg/L) against P. aeruginosa. CONCLUSIONS: Our data suggest that either agent may be a reasonable choice for centres with a high proportion of ESBL producers; however, C/T may have improved activity against P. aeruginosa and may be preferred in institutions with a higher frequency of resistant pseudomonal isolates.

Child-directed and nutrition-focused marketing cues on food packaging: links to nutritional content.

OBJECTIVE: We tested whether the presence of both child-targeted and nutrition-focused (i.e. parent-targeted) marketing cues on food packaging was associated with the nutritional content of these products. DESIGN: We conducted a quantitative content analysis of 403 food packages chosen randomly from the supermarket's online portal along with all products (n 312) from the cereal aisle in a supermarket from the Southeastern USA. We examined main and interaction effects for cues on nutritional content (e.g. energy density, sugar, sodium, fibre). SETTING: A regional supermarket chain in the Southeastern USA. RESULTS: Tests of main effects indicated that increased presence of nutritional cues was linked to more nutritious content (e.g. less sugar, less saturated fat, more fibre) while the increased presence of child-targeted cues was uniformly associated with less nutritious content (e.g. more sugar, less protein, less fibre). Among the interaction effects, results revealed that products with increased nutrition-focused and child-targeted cues were likely to contain significantly more sugar and less protein than other products. CONCLUSIONS: Products that seek to engage children with their packaging in the supermarket are significantly less nutritious than foods that do not, while product packages that suggest nutritional benefits have more nutritious content. More importantly, the study provides evidence that those products which try to engage both child and parent consumers are significantly less healthy in crucial ways (e.g. more sugar, less fibre) than products that do not.

Multiple cardiac abnormalities in a case of non-mosaic trisomy 8.

We present a case of complete trisomy 8 in a 40-day-old male infant, who had a number of congenital heart abnormalities.

Coronary cameral fistula occurring in a case of Down syndrome.

This case report describes a coronary cameral fistula, an isolated cardiac defect, in a child with Down syndrome. Although Down syndrome patients are known to have a high incidence of cardiac defects, to the best of our knowledge this particular association has not been described previously.

Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326).

OBJECTIVE: The aim of this study was to evaluate the 2-year survival rate in a group of women in complete clinical remission (cCR) from Stage III ovarian cancer following front-line therapy who were then treated with a 6-month course of altretamine. METHODS: Patients were documented to be in cCR by physical examination, computed tomography or magnetic resonance imaging scan, and serum CA-125. Treatment consisted of altretamine (Hexalen) 260 mg/m(2)/day po divided into four doses taken after meals and at bedtime for 14 of 28 days for six cycles. Based on previous experience in the Southwest Oncology Group, the treatment would be considered promising if the 2-year survival rate was > or = 65% as measured from study registration. RESULTS: From 9/1/93 and 7/1/97, 112 patients were registered and 97 were fully evaluable. The majority of patients had optimally debulked (< or = 1 cm: 63%), high-grade (Grade 3: 82%) tumors. The 2-year survival rate in this study was 75% (95% CI: 66-84%). For those patients with optimal disease, the 2-year survival rate was 82% (95% CI: 72-92%) and for those with suboptimal disease it was 64% (95% CI: 48-79%). Four patients (4%) experienced Grade 4 and 21 patients (22%) experienced Grade 3 toxicities consisting primarily of nausea/vomiting, neutropenia, fatigue, anxiety, and paresthesias. CONCLUSIONS: The 2-year survival rate in this study warrants further evaluation of consolidation therapy for women in clinical complete remission following front-line chemotherapy for Stage III ovarian cancer. Caution is advised in the interpretation of these data, however, because of the nonrandomized nature of the trial and the unknown contribution of front-line use of paclitaxel to the durability of clinical complete response.

Ultrasonographic detection of orbicularis oris defects in first degree relatives of isolated cleft lip patients.

The phenotypic variability of non-syndromic cleft lip (CL) is broad. We demonstrate that the prevalence of orbicularis oris (OO) muscle anomalies, detectable only by ultrasound, is higher in first-degree relatives of individuals with overt CL than in the general population. These findings suggest that occult OO defects may be part of the spectrum of the CL phenotype, that offspring of individuals with such defects are at an increased risk to develop overt CL, and that ultrasound may be a useful tool in future population studies designed to identify CL susceptibility genes.

Community health collaboration models for the 21st century.

The development of partnerships with physicians and other health professionals is a key strategy to improving the community's health. This article reviews the role of nurse leaders as advocates for health care improvement and leading community improvement efforts.

Acquired aortic regurgitation following occlusion of the persistent arterial duct: an echocardiographic assessment.

OBJECTIVE: To document the development of aortic regurgitation following occlusion of a patent arterial duct. DESIGN: Case series involving nine children referred for surgical ligation of an isolated patent arterial duct. SETTING: Academic referral centre. METHODS: A preoperative transthoracic and transoesophageal echocardiogram was performed in theatre to look for aortic regurgitation. Thereafter, aortic flow was monitored throughout the operation by colour flow mapping with the transoesophageal probe in situ. Onset of aortic regurgitation was documented. An immediate postoperative transthoracic echocardiogram was performed on all patients and then daily until discharge on day 5. A follow up clinical and echocardiographic assessment was performed six weeks postoperatively. RESULTS: With ligation of the patient arterial duct, transoesophageal echocardiography showed immediate regurgitation in seven of the nine patients, seen as a small central jet on colour flow mapping. Six of the seven patients continued to have aortic regurgitation on transthoracic echocardiography before leaving theatre. In none was aortic regurgitation audible clinically. At discharge, five patients still had evidence of aortic regurgitation; of four seen at follow up six weeks later, only one had residual regurgitation. CONCLUSIONS: Ligation of the patient arterial duct results in the acute termination of the "run off" in a volume overloaded situation. This, together with a rise in the peripheral vascular resistance and the persistence of increased proximal vascular capacitance, is considered to be the underlying aetiology of the acquired aortic regurgitation.

Reduction of tumor necrosis factor-alpha bioactivity by a human ovarian epithelial cancer cell line in vitro.

OBJECTIVE: Our purpose was to determine the ability of an ovarian epithelial carcinoma cell line, Caov-3, to alter the bioactivity of exogenously added tumor necrosis factor-alpha. STUDY DESIGN: Caov-3 cells were cultured for up to 6 days in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. The control and tumor necrosis factor-alpha-treated cells were analyzed for proliferation, distribution throughout the cell cycle by flow cytometry, their ability to release bioactive tumor necrosis factor-alpha by L929 bioassay, and their ability to release immunoreactive tumor necrosis factor-alpha by a specific double sandwich enzyme-linked immunosorbent assay. RESULTS: Tumor necrosis factor-alpha induced a dose- and time-dependent inhibition of cell proliferation accompanied by accumulation of cells in late S and G2/M phases of the cell cycle. Tumor necrosis factor-alpha bioactivity was undetectable in the media of control Caov-3 cell cultures, but these cells exhibited TNF-alpha messenger ribonucleic acid. After culture of the cells for 2 days in the presence of various doses of TNF-alpha (0.1, 1.0, 10, or 100 ng/ml), a significant decline (p < 0.01) in bioactivity was observed in all groups with the exception of 100 ng of TNF-alpha. Further declines in bioactivity were observed 2 and 4 days later. Addition of TNF-alpha to Caov-3 cells did not affect its immunoactivity, and Western blots of media revealed major bands of immunoactivity at approximately 17 kd, the expected molecular size of TNF-alpha. CONCLUSION: These results indicate that Caov-3 ovarian carcinoma cells reduce the bioactivity of TNF-alpha, an important growth regulator, by a novel yet unknown mechanism to escape the modulatory effects of the normal immune response during cancer cell growth.

Tumor necrosis factor-alpha in the female reproductive tract.

Tumor necrosis factor-alpha (TNF), originally identified as an inflammation-associated cytokine, is synthesized throughout the female reproductive tract as well as in placentas and embryos. Development, female sex steroid hormones, and lipopolysaccharide influence expression of this gene. The functions of TNF may be determined in part by differential expression of the two species of TNF receptors, both of which seem to be regulated by female sex steroid hormones. Evidence has accumulated that supports a role for this potent, pleiotropic cytokine in autocrine and paracrine processes central to reproduction, including gamete and follicle development, steroidogenesis, uterine cyclicity, placental differentiation, development of the embryo, and parturition.

Ineffective hip rotation with Pavlik harness. Prospective study of 35 infant dislocations.

35 hips in 31 infants diagnosed as unstable were treated with a Pavlik harness and followed by weekly clinical and monthly ultrasound evaluation to determine eventual stability. 26 hips became stable within 3 months, and 9 dislocations required reduction with hip spica placement; 1 of these subsequently required open reduction. Of the 7 infants with 9 hips that failed, 2 children had a late onset of treatment, 2 children had problems with brace fit or family acceptance, and 3 other children had no problem with use of the orthosis. Internal rotation of a degree not possible with the Pavlik harness was required to reduce 4 of these 9 hips. The Pavlik harness is ineffective in some patients because of the need for internal rotation.

Peritoneal papillary serous carcinoma in a woman with a history of utero DES exposure.

Antenatal exposure to diethylstilbestrol (DES) has been implicated in the development of clear-cell adenocarcinoma of the vagina and cervix. In addition, there are a handful of case reports of gram cell tumors and other benign ovarian tumors in the offspring of women treated with DES during pregnancy. This the first report of a papillary serous carcinoma of the peritoneum following in utero exposure to DES. As the population of women with a history of in utero exposure to DES is reaching into the fourth decade, these patients need to be closely monitored for the development of gynecologic malignancies, especially epithelial and germ cell ovarian tumors. We also encourage the reporting of these tumors of the DES registry to document the exact incidence of these malignancies.

Local anesthesia for cryosurgery on the cervix.

Forty-five patients were evaluated in a prospective, randomized study to determine the effectiveness of a local injection of lidocaine in reducing pain during cervical cryosurgery. Study patients received a submucosal cervical injection of 1% lidocaine with a 1:100,000 dilution of epinephrine. Control patients did not receive an injection. Both groups received a single dose of naproxen sodium or ketoprofen prior to the procedure. The patient and the observing nurse recorded the pain experienced with a visual analog scale (VAS). Nurse and patient response for the control and study groups showed a high correlation (r = .573 and P < .01, r = .673 and P < .001, respectively). The mean VAS score recorded for the 26 control patients was 4.27, significantly greater than the mean score for the 19 study patients, 1.16 (P < .001). These findings indicate that a submucosal local injection of lidocaine with epinephrine is effective in reducing pain during cervical cryosurgery.

Tumor necrosis factor-alpha alters steroidogenesis and stimulates proliferation of human ovarian granulosal cells in vitro.

OBJECTIVE: To determine if tumor necrosis factor alpha (TNF-alpha) altered human granulosa-luteal cell proliferation and steroidogenesis. DESIGN: Aspirates of follicles from women undergoing in vitro fertilization were subjected to Percoll gradients to collect an enriched population of granulosa-luteal cells. The granulosa-luteal cells were subjected to culture for a period of 10 or 20 days in the presence or absence of various doses of human recombinant TNF-alpha (0.1 to 10.0 ng/mL). PATIENTS: Granulosa-luteal cells from nine patients were evaluated for their response to TNF-alpha in vitro. Patients with three follicles > 16 mm and a serum estradiol (E2) concentration of > 1,836 pmol/L were selected for study. RESULTS: Tumor necrosis factor-alpha increased granulosa-luteal cell number. By day 10 of culture, 10 ng TNF-alpha/mL doubled cell number and > 95% of the cells exhibited 3 beta-hydroxysteroid dehydrogenase. Tumor necrosis factor-alpha at 10 ng/mL increased progesterone (P) accumulation from day 4 through day 20 of culture. Tumor necrosis factor-alpha also increased E2 secretion but in a biphasic manner. During the first 14 days of culture, TNF-alpha increased E2, but thereafter E2 decreased to basal values by day 20. When steroidogenesis was expressed per 1,000 cells per days of culture, TNF-alpha did not increase P beyond controls but significantly increased E2 for the first 14 days of culture after which E2 per 1,000 cells declined. CONCLUSIONS: The results indicate that TNF-alpha stimulates granulosal-luteal cell growth and E2 secretion in vitro, and thus TNF-alpha may promote cellular events associated with formation of the corpus luteum; i.e., granulosa-cell proliferation and steroidogenesis.