Antimicrobial Susceptibility Breakpoints and First-Step parC Mutations in Streptococcus pneumoniae: Redefining Fluoroquinolone Resistance

Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae. To determine whether levofloxacin breakpoints can identify isolates that harbor recognized resistance mechanisms, we examined 115 S. pneumoniae isolates with a levofloxacin MIC of >2 μg/mL for first-step parC mutations. A total of 48 (59%) of 82 isolates with a levofloxacin MIC of 2 μg/mL, a level considered susceptible by NCCLS criteria, had a first-step mutation in parC. Whether surveillance programs that use levofloxacin data can effectively detect emerging resistance and whether fluoroquinolones can effectively treat infections caused by such isolates should be evaluated

Antimicrobial Susceptibility Breakpoints and First-Step parC Mutations in Streptococcus pneumoniae: Redefining Fluoroquinolone Resistance

Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae. To determine whether levofloxacin breakpoints can identify isolates that harbor recognized resistance mechanisms, we examined 115 S. pneumoniae isolates with a levofloxacin MIC of >2 μg/mL for first-step parC mutations. A total of 48 (59%) of 82 isolates with a levofloxacin MIC of 2 μg/mL, a level considered susceptible by NCCLS criteria, had a first-step mutation in parC. Whether surveillance programs that use levofloxacin data can effectively detect emerging resistance and whether fluoroquinolones can effectively treat infections caused by such isolates should be evaluated

Stereotactically guided breast biopsy: a review

The aims of this review are to compare and contrast the available stereotactic equipment, and to describe the variety of needle types used and their affect on pathological results and subsequent patient management. Initial stereotactic devices were “added-on” to analogue mammography units and have been replaced by prone or ducubitus equipment using digital image acquisition. Biopsies use either 14-G core biopsy (CB) needles or vacuum-assisted biopsies (VAB). Vacuum-assisted biopsy systems consistently out-perform 14-G CB with reduced need for diagnostic or multi-treatment surgery. The false-negative rate is 8% for 14-G CB compared with 0.7% for VAB. There is a risk of underestimating the disease present for lesions of uncertain malignant potential (Cat B3) and suspicious of malignancy (Cat B4) results with 25% of patients with a B3 biopsy found to have cancer at subsequent surgery and 66% of those with a B4 biopsy. A CB diagnosis of in situ malignancy is upgraded to invasive disease at surgery in 15-36% of patients undergoing CB and of the order of 10% with VAB. A high degree of diagnostic accuracy and hence safe patient care can only be achieved by meticulous attention to technique and multi-disciplinary cooperation

Percutaneous stereotactic en bloc excision of nonpalpable breast carcinoma: a step in the direction of supraconservative surgery

peer reviewedRecently, the advanced breast biopsy instrumentation (ABBI) system has been introduced as an alternative to conventional breast biopsy techniques. This study was prospectively conducted to evaluate the potential of the ABBI method in locoregional management of a consecutive series of patients with nonpalpable mammographically detected breast carcinomas. Sixty-one consecutive patients underwent an ABBI procedure as a first step before possible surgery for nonpalpable breast lesions that would in any case require complete excision. For the 27 patients in whom the ABBI biopsy revealed malignancy further surgery was recommended, including re-excision of the biopsy site and axillary dissection in cases of infiltrating carcinoma. We calculated the probabilities that the ABBI specimen would have tumor-free margins and that a definitely complete excision had been achieved as a function of the mammographic or pathological diameter of the cancer. For cancer with a pathological diameter less than 10 mm, measured on the ABBI specimen, the probability (92%) of obtaining complete resection was significantly better than for larger lesions (P = 0.01, Fisher's exact test). Although the therapeutic perspectives for the ABBI method are limited at present, we suggest that this approach is a first step in the direction of a surgical strategy that is better adapted to the pathological characteristics peculiar to these small tumors, whose incidence is increasing. (C) 2002 Elsevier Science Ltd. All rights reserved

Group B streptococcus serotype prevalence in reproductive-age women at a tertiary care military medical center relative to global serotype distribution

<p>Abstract</p> <p>Background</p> <p>Group B <it>Streptococcus </it>(GBS) serotype (Ia, Ib, II-IX) correlates with pathogen virulence and clinical prognosis. Epidemiological studies of seroprevalence are an important metric for determining the proportion of serotypes in a given population. The purpose of this study was to evaluate the prevalence of individual GBS serotypes at Madigan Healthcare System (Madigan), the largest military tertiary healthcare facility in the Pacific Northwestern United States, and to compare seroprevalences with international locations.</p> <p>Methods</p> <p>To determine serotype distribution at Madigan, we obtained GBS isolates from standard-of-care anogenital swabs from 207 women of indeterminate gravidity between ages 18-40 during a five month interval. Serotype was determined using a recently described molecular method of polymerase chain reaction by capsular polysaccharide synthesis (cps) genes associated with pathogen virulence.</p> <p>Results</p> <p>Serotypes Ia, III, and V were the most prevalent (28%, 27%, and 17%, respectively). A systematic review of global GBS seroprevalence, meta-analysis, and statistical comparison revealed strikingly similar serodistibution at Madigan relative to civilian-sector populations in Canada and the United States. Serotype Ia was the only serotype consistently higher in North American populations relative to other geographic regions (p < 0.005). The number of non-typeable isolates was significantly lower in the study (p < 0.005).</p> <p>Conclusion</p> <p>This study establishes PCR-based serotyping as a viable strategy for GBS epidemiological surveillance. Our results suggest that GBS seroprevalence remains stable in North America over the past two decades.</p

Contribution of Exogenous Genetic Elements to the Group A Streptococcus Metagenome

Variation in gene content among strains of a bacterial species contributes to biomedically relevant differences in phenotypes such as virulence and antimicrobial resistance. Group A Streptococcus (GAS) causes a diverse array of human infections and sequelae, and exhibits a complex pathogenic behavior. To enhance our understanding of genotype-phenotype relationships in this important pathogen, we determined the complete genome sequences of four GAS strains expressing M protein serotypes (M2, M4, and 2 M12) that commonly cause noninvasive and invasive infections. These sequences were compared with eight previously determined GAS genomes and regions of variably present gene content were assessed. Consistent with the previously determined genomes, each of the new genomes is ∼1.9 Mb in size, with ∼10% of the gene content of each encoded on variably present exogenous genetic elements. Like the other GAS genomes, these four genomes are polylysogenic and prophage encode the majority of the variably present gene content of each. In contrast to most of the previously determined genomes, multiple exogenous integrated conjugative elements (ICEs) with characteristics of conjugative transposons and plasmids are present in these new genomes. Cumulatively, 242 new GAS metagenome genes were identified that were not present in the previously sequenced genomes. Importantly, ICEs accounted for 41% of the new GAS metagenome gene content identified in these four genomes. Two large ICEs, designated 2096-RD.2 (63 kb) and 10750-RD.2 (49 kb), have multiple genes encoding resistance to antimicrobial agents, including tetracycline and erythromycin, respectively. Also resident on these ICEs are three genes encoding inferred extracellular proteins of unknown function, including a predicted cell surface protein that is only present in the genome of the serotype M12 strain cultured from a patient with acute poststreptococcal glomerulonephritis. The data provide new information about the GAS metagenome and will assist studies of pathogenesis, antimicrobial resistance, and population genomics

Diagnostic value of fine-needle aspiration biopsy for breast mass: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Fine-needle aspiration biopsy (FNAB) of the breast is a minimally invasive yet maximally diagnostic method. However, the clinical use of FNAB has been questioned. The purpose of our study was to establish the overall value of FNAC in the diagnosis of breast lesions.</p> <p>Methods</p> <p>After a review and quality assessment of 46 studies, sensitivity, specificity and other measures of accuracy of FNAB for evaluating breast lesions were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall accuracy. The sensitivity and specificity for the studies data (included unsatisfactory samples) and underestimation rate of unsatisfactory samples were also calculated.</p> <p>Results</p> <p>The summary estimates for FNAB in diagnosis of breast carcinoma were as follows (unsatisfactory samples was temporarily exluded): sensitivity, 0.927 (95% confidence interval [CI], 0.921 to 0.933); specificity, 0.948 (95% CI, 0.943 to 0.952); positive likelihood ratio, 25.72 (95% CI, 17.35 to 28.13); negative likelihood ratio, 0.08 (95% CI, 0.06 to 0.11); diagnostic odds ratio, 429.73 (95% CI, 241.75 to 763.87); The pooled sensitivity and specificity for 11 studies, which reported unsatisfactory samples (unsatisfactory samples was considered to be positive in this classification) were 0.920 (95% CI, 0.906 to 0.933) and 0.768 (95% CI, 0.751 to 0.784) respectively. The pooled proportion of unsatisfactory samples that were subsequently upgraded to various grade cancers was 27.5% (95% CI, 0.221 to 0.296).</p> <p>Conclusions</p> <p>FNAB is an accurate biopsy for evaluating breast malignancy if rigorous criteria are used. With regard to unsatisfactory samples, futher invasive procedures are required in order to minimize the chance of a missed diagnosis of breast cancer.</p

Early detection of breast cancer rectifies inequality of breast cancer outcomes

Objectives To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome.Methods We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.Results All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range.Conclusions Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.</div

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women

Background It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.Methods Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.Results Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]).Conclusions Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens