Comparative effectiveness of gastric bypass versus gastric banding on acute care use for cardiovascular disease in adults with obesity.

BACKGROUND AND AIMS: Gastric bypass is known to have larger effects on weight and metabolism than gastric banding. However, scarce data exist as to whether the differences are translated into differential risks of cardiovascular disease (CVD)-related morbidities. The objective was to examine whether adults with obesity and CVD who underwent gastric bypass have a lower rate of acute care use (emergency department [ED] visit or unplanned hospitalization) for CVD than those with gastric banding. METHODS AND RESULTS: We performed a comparative effectiveness study of gastric bypass versus banding among adults with obesity and CVD who underwent either surgery, using population-based [ED] and inpatient samples in California, Florida, and Nebraska from 2005 through 2011. The primary outcome was acute care use for CVD during a two-year postoperative period. We constructed negative binomial regression models to compare the event rate during sequential 6-month periods, using gastric banding group as the reference. We identified 11,229 adults with obesity and CVD who underwent gastric bypass and 3896 adults who had gastric banding. Patients with gastric bypass had significantly lower rate of the outcome compared to those with banding in the 7-12 months postoperative period (adjusted rate ratio [aRR] 0.77; 95% confidence interval [CI], 0.61-0.98; P = 0.03). The significant reduction in the rate persisted during 13-18 months (aRR 0.71; 95% CI, 0.57-0.90; P = 0.005) and 19-24 months (aRR 0.66; 95% CI, 0.52-0.82; P < 0.001) after bariatric surgery. CONCLUSION: In this population-based comparative effectiveness study of adults with obesity and CVD, the rate of acute care use for CVD was lower after gastric bypass compared to gastric banding.

Development of the EUCAST disk diffusion antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories.

With the support of ESCMID and European countries, EUCAST has developed a disk diffusion test with zone diameter breakpoints correlated with the EUCAST clinical MIC breakpoints. The development of the EUCAST disk diffusion method and quality control criteria are described, together with guidance on quality control and implementation of the method in clinical microbiology laboratories. The method includes the use of Mueller-Hinton agar without supplements for non-fastidious organisms and with 5% mechanically defibrinated horse blood and 20 mg/L ß-NAD for fastidious organisms, a standardized inoculum resulting in confluent growth, an incubation time of 16-20 h, a reading guide on how to read zone diameters on individual species-agent combinations and zone diameter breakpoints calibrated to the EUCAST clinical MIC breakpoints. EUCAST recommendations are described in detail and updated regularly on the EUCAST website (http://www.eucast.org).

EUCAST expert rules in antimicrobial susceptibility testing.

EUCAST expert rules have been developed to assist clinical microbiologists and describe actions to be taken in response to specific antimicrobial susceptibility test results. They include recommendations on reporting, such as inferring susceptibility to other agents from results with one, suppression of results that may be inappropriate, and editing of results from susceptible to intermediate or resistant or from intermediate to resistant on the basis of an inferred resistance mechanism. They are based on current clinical and/or microbiological evidence. EUCAST expert rules also include intrinsic resistance phenotypes and exceptional resistance phenotypes, which have not yet been reported or are very rare. The applicability of EUCAST expert rules depends on the MIC breakpoints used to define the rules. Setting appropriate clinical breakpoints, based on treating patients and not on the detection of resistance mechanisms, may lead to modification of some expert rules in the future.

The role of pharmacokinetics/pharmacodynamics in setting clinical MIC breakpoints: the EUCAST approach.

Clinical breakpoints are used in clinical microbiology laboratories to categorize microorganisms as clinically susceptible (S), intermediate (I) or resistant (R) dependent on the quantitative antimicrobial susceptibility as indicated by the MIC value determined in a well-defined standard test system. The laboratory report, with the designations of S, I or R for each antimicrobial agent, provides guidance to clinicians with respect to the potential use of agents in the treatment of patients, and clinical breakpoints should therefore distinguish between patients that are likely or unlikely to respond to antimicrobial treatment. In Europe, clinical breakpoints are set by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), following a defined procedure. This includes evaluation of efficacy in experimental settings and clinical studies to derive pharmacodynamic targets such as the fAUC/MIC ratio or %fT > MIC required for efficacy, the pharmacokinetic properties of the agent, Monte Carlo simulations to estimate exposures of the antimicrobial agent in the target patient population and commonly used dosing regimens. The probability of target attainment is subsequently determined for a range of pharmacodynamic targets and the results from the Monte Carlo simulations. The breakpoints derived are subsequently evaluated with respect to the wild-type population of the target microorganisms, specific resistance mechanisms and other relevant data. In this paper, we provide an overview of the EUCAST process and considerations for setting pharmacokinetic/pharmacodynamic breakpoints. These are the breakpoints that in the EUCAST breakpoint tables are referred to as 'non-species-related breakpoints'.

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

Guidelines for the control of glycopeptide-resistant enterococci in hospitals.

The increase since the mid 1980s in glycopeptide resistant enterococci (GRE) raised concerns about the limited options for antimicrobial therapy, the implications for ever-increasing numbers of immunocompromised hospitalised patients, and fuelled fears, now realised, for the transfer of glycopeptide resistance to more pathogenic bacteria, such as Staphylococcus aureus. These issues underlined the need for guidelines for the emergence and control of GRE in the hospital setting. This Hospital Infection Society (HIS) and Infection Control Nurses Association (ICNA) working party report reviews the literature relating to GRE prevention and control. It provides guidance on microbiological investigation, treatment and management, including antimicrobial prescribing and infection control measures. Evidence identified to support recommendations has been categorized. A risk assessment approach is recommended and areas for research and development identified.

Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing.

OBJECTIVES: To investigate the variability in antimicrobial susceptibility of Pseudomonas aeruginosa from sputa of patients with cystic fibrosis, to compare testing individual colonies of the same morphotype either separately or combined and to study the reproducibility of testing antimicrobial susceptibility within and between laboratories. METHODS: One hundred and one sputa were cultured. Four colonies of each P. aeruginosa morphotype were suspended. Susceptibility to 12 agents by disc diffusion was tested individually or by pooling the four suspensions. A sputum sample containing four morphotypes of one genotype of P. aeruginosa was used to study reproducibility. Susceptibility was tested in duplicate by eight biomedical scientists in one laboratory and by routine procedures in seven different laboratories. RESULTS: There was a mean of four morphotypes of P. aeruginosa per sputum and three antibiograms per morphotype. In some cases, all four colonies of a single morphotype had different antibiograms. The susceptibility profiles of single isolates of P. aeruginosa correlated poorly with pooled cultures, with the pooled tests missing resistance. Results from one sample tested in duplicate by eight biomedical scientists in one laboratory and in seven other laboratories did not correlate well. The wide range of zone sizes in disc diffusion tests illustrated the variation in susceptibility of 48 colonies from one sputum sample. CONCLUSIONS: The role of conventional antimicrobial susceptibility testing is questionable once P. aeruginosa chronically infects the cystic fibrosis lung. A range of susceptibility patterns is seen, even within a morphotype. Routine test results are not reproducible and underestimate resistance.

The prevalence and implications of incidental findings on ED abdominal CT scans.

We reviewed reports from 321 consecutive emergency department (ED) noncontrast, helical "renal stone" abdominal CT scans obtained at a single medical center between April 1996 to June 1997 for incidental findings. Incidental findings were common (45% of scans), and approximately half were rated of "moderate" or "serious" concern by 2 independent reviewers (kappa = 0.72). ED records indicated that only 21% of incidental findings were documented, and only 11 (18%) of cases with findings of "moderate/severe" concern had evidence of follow-up on hospital chart review. Although work-up of these 11 cases did not yield any serious diagnoses, many potentially serious incidental findings without follow-up remain worrisome.

External quality assessment of antimicrobial susceptibility testing in Europe.

Comparability of results of antimicrobial susceptibility testing is essential for resistance surveillance studies. As different methods may be used in different countries, there may be particular problems with international comparisons of resistance rates. Data from external quality assessment (EQA) surveys participated in by laboratories from several European countries allow comparison of performance between countries. In this study, success rates with organism-antimicrobial agent combinations known to be difficult to test were examined. With penicillin resistance in pneumococci; vancomycin and high-level gentamicin resistance in enterococci; ampicillin, co-amoxiclav and chloramphenicol resistance in Haemophilus influenzae and methicillin resistance in staphylococci there were differences between countries in success rates for discrimination of resistant strains. This study suggests that differences between countries in rates of resistance for some organism-antimicrobial agent combinations should be interpreted with caution. International EQA is useful in the demonstration and clarification of such differences.

Detection of beta-lactamase-mediated resistance.

beta-Lactams are the most widely used antibiotics, and beta-lactamases are the greatest source of resistance to them. An understanding of beta-lactamase detection and identification is therefore valuable. Colorimetric, acidimetric and iodometric tests of beta-lactamase production are good, rapid indicators of penicillin and ampicillin resistance in Haemophilus, Moraxella and Neisseria spp. These methods can also be applied to Gram-negative aerobic bacilli but are less useful, since the usual question is not whether a beta-lactamase is produced by these organisms, but which beta-lactamase? Accurate identification of the beta-lactamases of Enterobacteriaceae demands gene or protein sequencing, but the broad type of enzyme produced by an isolate can often be inferred from antibiotic susceptibility data. Resistance to ceftazidime or cefpodoxime implies extended-spectrum beta-lactamase (ESBL) production in Escherichia coli and Klebsiella spp., especially if susceptibility to cefoxitin is retained. ESBL production can be confirmed with double disc tests or with various commercial kits. Derepression of AmpC beta-lactamases in Enterobacter spp. and Citrobacter freundii is another important mechanism and can be inferred from cross-resistance to beta-lactamase inhibitor combinations and to all cephalosporins except fourth-generation agents. Antagonism between cefoxitin and cefotaxime can be used to infer the presence of inducible AmpC enzymes in these species, indicating the risk of segregation of derepressed mutants, but in general this risk is better predicted from accurate speciation.

Quality assurance of antimicrobial susceptibility testing by disc diffusion.

Quality assurance is essential to ensure the quality of antimicrobial susceptibility tests by diffusion methods. Routine internal quality control testing with a range of control strains is a major part of the quality assurance process, as it facilitates monitoring of the performance of the test. Most standardized methods include tables of acceptable zone size ranges for control strains and, in addition to checking that control zone diameters are within the published ranges, rules or statistical approaches may be applied to indicate deviations from acceptable performance. If control tests indicate unacceptable performance, the source(s) of the error should be investigated and may include problems with media, antimicrobial discs, inoculum and plate reading. Participation in external quality assessment schemes provides an independent assessment of performance although the number of strains distributed in such schemes is limited. Internal quality assessment in which routine tests are repeated with the identity of the organisms blinded is a useful complementary approach to external quality assessment and may detect problem areas not highlighted by other control methods. Education is an important part of the quality assurance process. Knowledge of atypical results for different organism-agent combinations may provide warning of possibly erroneous results, and an understanding of the limitations and sources of error in disc diffusion methods contributes significantly to the recognition, resolution and avoidance of errors.

Detection of methicillin/oxacillin resistance in staphylococci.

Methicillin/oxacillin-resistant staphylococci are heterogeneous in their expression of resistance to beta-lactam agents and the test conditions have a major effect on the expression and therefore the detection of resistance. Conflicting recommendations regarding the most reliable method for routine use are partly related to differences between strains and there may be a variable interaction between the factors affecting the expression of resistance, including the agent tested, the medium, the NaCl concentration, the inoculum, temperature and period of incubation and the reading of endpoints. 'Borderline' resistant strains may have altered PBPs or be penicillinase hyperproducers, and these can be difficult to distinguish from resistant strains that carry the mecA gene. Recommended methods for MIC and disc diffusion testing are described, although it is unlikely that any single method will detect all resistant strains. Some rapid and/or automated methods are also available, including latex agglutination techniques for the detection of PBP2a. The gold standard method for the detection of resistance mediated by mecA is PCR, which is most commonly used as a reference method at present.

Instrumentation in antimicrobial susceptibility testing.

Studies in the 1960s demonstrated the problems of variability in susceptibility testing methods, especially those affecting the performance of disc diffusion procedures. These studies made apparent the need for standardization and resulted in more clearly defined performance limits for growth medium, incubation conditions, inoculum concentration, disc content for diffusion methods, the setting of interpretative MIC breakpoints and the establishment of quality control parameters. More recently, there has been a growing interest in the use of instrumentation for reading disc diffusion tests and the endpoints of agar or broth dilution MIC determinations. Instrumentation ranges in complexity from the simple optical reading of zones of inhibition or growth endpoints, requiring operator interpretation, to more sophisticated devices for reading, recording and 'expert system' analysis of results with interfacing of instruments to laboratory information management systems. Some of the more developed systems are fully automated and can also identify the organisms tested. The pressure to reduce labour costs and provide results earlier favours the use of more automated systems whilst the requirement for resistance surveillance provides impetus for the use of systems that provide quantitative results and electronic data handling.