A case series and focused review of nocardiosis: clinical and microbiologic aspects

Nocardia species are ubiquitous soil organisms that often infect patients with underlying immune compromise, pulmonary disease, or a history of surgery or trauma. We report 5 cases of nocardiosis representing various aspects of this "great imitator": 1) pneumonia in the setting of underlying malignancy, 2) chronic pneumonia with drug-resistant organism, 3) bacteremia and empyema with chronic hematologic malignancy, 4) primary cutaneous disease, and 5) sternal wound infection. We present a summary of the English literature from 1966 to 2003 with a focus on the teaching points of each of our 5 cases as well as the background epidemiology and microbiology of the Nocardia genus. Isolation of the organism may be achieved with routine media but longer incubation times may be necessary, delaying diagnosis and appropriate therapy. Treatment with a sulfa-containing regimen is standard of care, but resistance testing is warranted given emerging drug resistance, high rates of discontinuation due to adverse reactions, and the potential for nephrotoxicity in transplant recipients on cyclosporine.     

Cardiac magnetic resonance in outpatients in Germany--indications, complications and protocol suggestions from a high-volume center

BACKGROUND: Cardiac magnetic resonance (CMR) has developed into a routine examination in many centers in cardiology. However, there is little knowledge about its applicability in outpatients as a diagnostic tool for cardiovascular diseases. We report about the experiences in a high-volume cardiac imaging center and in a "mobile setting" in Germany and provide routinely used examination protocols. METHODS: 8976 patients referred for CMR from cardiologists, internal medicine practices and from general practitioners and 2200 patients examined in a "mobile" system by outpatient cardiologists were included in the study. Indications were as follows: 7672 (69%) examinations for myocardial ischemia and viability, 1313 (12%) for cardiac and pericardial inflammatory disease and cardiac mass, 976 (9%) for detection and quantification of heart valve disease and 466 (4%) for congenital heart disease. 697 (6%) were referred for other indication. Two independent readers performed image analysis of the 8976 patients in our center. RESULTS: Image quality was rated "excellent" in 90.6%, "good" in 8%, "fair" in 1.2% and "poor" in 0.2%. 0.0002% of all examinations were not assessable due to low image quality. Minor complications (temporarily, asymptomatic AV-blockade; mild chest pain and/or dyspnea; nausea) could be observed in 12% and resolved within few minutes. One patient experienced a grand mal seizure due to hyperventilation. 0.9% examinations had to be terminated untimely due to claustrophobia. CONCLUSION: CMR in outpatients is a widely used imaging modality in cardiology in Germany. A large variety of clinical questions may be answered by CMR with excellent image quality and without major complication. With user-adapted protocols, a rapid diagnosis is achieved even in outpatients in a "mobile" setting. Hence, CMR will increase its applicability as a routine imaging tool.     

Vancomycin-resistant enterococci: mechanisms and clinical observations.

Enterococci are not generally regarded as highly virulent bacterial pathogens. However, resistance to many antimicrobial drugs complicates treatment of enterococcal infections. Acquired resistance to high concentrations of glycopeptide antibiotics, specifically vancomycin, has exacerbated this problem. This article seeks to concisely review the mechanisms of that resistance and its effects on clinical management of enterococcal infections, as well as clinical microbiology and infection control.     

Análisis microbiológico post mórtem

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population.     

Antiplatelet resistance in outpatients with monitored adherence

Abstract

Antiplatelet resistance with aspirin and clopidogrel has been associated with clinical, cellular and pharmacogenetic factors; and non-adherence has been considered as a major contributor to resistance in outpatients. We aimed at assessing factors to resistance when adherence to the antiplatelet drugs and all other oral solid drugs was controlled for. In a pilot study, we tested arachidonic acid and/or ADP-induced in vitro platelet aggregation of 82 outpatients with chronic aspirin and/or clopidogrel treatment before and after a one-week period of measuring the patient’s adherence with the polymedication electronic monitoring system (POEMS). Resistance was found in 20% (aspirin; n?=?69) and 25% (clopidogrel; n?=?32) of the patients after monitored adherence. Mean platelet aggregation was not (aspirin) or non-significantly (clopidogrel) lowered when compared to baseline. Diabetes mellitus and inflammation were consistently associated with resistance to both drugs, but CYP2C19 polymorphisms could not be confirmed as predictors of clopidogrel response. Electronically compiled multidrug dosing histories allowed the concomitant intake of high-dose lipophilic statins to be identified as a risk factor of impaired response to clopidogrel and revealed that exposure to further potential drug–drug interactions (DDIs) was too low for analysis. Multidrug adherence monitoring allowed thus dismissing non-adherence as a major contributor to resistance and inter-individual response variability in an outpatient setting. Additionally, it allowed analysing the impact of DDIs according to the actual exposure to the potentially interfering drugs. Further studies based on this methodology are essential to prevent misleading results due to incomplete adherence and gain additional insight into the impact of timing adherence on antiplatelet drug response.     

Interpretive reading of the antibiogram: Intellectual exercise or clinical need?

Clinical categorisation of susceptibility testing results according to criteria established by different committees is daily performed in clinical microbiology laboratories. By this process clinicians can predict the therapeutic success of antimicrobial treatment in patients infected with susceptible microorganisms. In addition, microbiology laboratories that include a suitable number of antimicrobial agents in susceptibility tests can perform interpretive reading of the antibiogram. With this approach, resistance phenotypes are recognized and allow microbiologist: a) detection of mechanisms of resistance, including low levels of expression; b) modification of clinical classifications that are inconsistent with the inferred resistance mechanism; and c) inference of susceptibility values for antimicrobials that are not included in the antibiogram. In the laboratory, this approach facilitates quality control and validation of susceptibility results. Moreover, it increases the value of the results obtained because new mechanisms of resistance can be characterized and the epidemiology of resistance can be established. From the clinical point of view, this approach contributes to improving the adequacy of treatment (since it is useful for predicting therapeutic failure with the use of antimicrobials in patients with infections due to resistant microorganisms) and to controlling and defining antimicrobial policies. Despite the growing complexity of resistance mechanisms, which makes interpretative reading of the antibiogram difficult, this process should be incorporated into routine practice in microbiology laboratories. Interpretive reading of antibiograms is clinically necessary and not simply a intellectual exercise.     

Value of Cardiac Troponin and sPESI in Treatment of Pulmonary Thromboembolism at Outpatient Setting

Background

Currently, guidelines do not recommend any standard approach for treatment of pulmonary thromboembolism (PTE) at outpatient setting. We investigated the efficacy and safety of a 90-day anticoagulant treatment of outpatients diagnosed with PTE who had negative troponin levels and low-risk simplified pulmonary embolism severity index (sPESI) at presentation.

Methods

This prospective cohort study included a total of 206 patients with objectively confirmed acute symptomatic PTE. Any troponin negative (cTn?) and low sPESI patients (as classified Group-1) were treated in outpatient setting. The primary endpoint was all-cause mortality during the first 90 days, and the secondary endpoint included non-fatal symptomatic recurrent PTE or non-fatal major bleeding. Presence of cancer was excluded from sPESI score.

Results

Fifty-two of 206 patients were eligible for had Group-1, and 31 were treated at outpatients settings. The 90-day all-cause mortality rate was 3.2 % among patients who received outpatient treatment. Otherwise cTn+ and high-risk sPESI 90-day mortality rate was 43.7 %. No difference was found in terms of secondary endpoints between the patients who received outpatient treatment and those who received inpatient treatment in Group-1 (p = NS). In our study, cancer was present in 16 (51.6 %) of the 31 outpatients.

Conclusion

We observed that patients with acute PTE, low-risk sPESI, and negative troponin levels can be safely treated in the outpatient settings. Also the presence of cancer alone does not necessitate hospitalization.

     

Modern chemotherapeutic options for malaria

Unlike HIV disease or tuberculosis, both of which are also major threats to public health throughout the tropics, uncomplicated malaria of whatever species can be cheaply and rapidly cured, usually in outpatients. However, in common with both HIV and tuberculosis, control of malaria is threatened by inadequate resources and by drug resistance. Africa carries the greatest burden of malaria mortality and morbidity; by no coincidence, Africa is also the most resource-limited. The drugs for severe disease (quinine and the artemisinins) are largely unaffected by resistance so far, but the "first-line" drugs, mainly used by outpatients (eg, chloroquine and sulfadoxine-pyrimethamine), are a major cause for concern. Although effective drugs are available they are mostly too expensive for routine use. This article reviews the main drugs for malaria and outlines the therapeutic use of these drugs for uncomplicated and severe disease. The article then examines the challenges faced in the processes of changing policy, and the implementation of that policy shift.     

Análisis de resultados del Programa de Control de Calidad Externo SEIMC. Año 2018

This article provides an analysis of the results obtained in 2018 by the participants inscribed in the External Quality Control Programme of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), which includes controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology, molecular microbiology, and genotypic bacterial resistance. The results obtained in 2018 confirm the excellent skill and good technical standards found in the vast majority of Spanish clinical microbiology laboratories, as shown in previous editions. However, the programme again shows that erroneous results can be obtained in any laboratory and even in clinically relevant determinations. Once again, the results of this programme highlight the need to implement both internal and external controls, as in the SEIMC programme.     

Advances in rapid diagnosis of tuberculosis disease and anti-tuberculous drug resistance

Rapid diagnosis of tuberculosis (TB) and multidrug-resistant (resistance to at least rifampin and isoniazid) Mycobacterium tuberculosis (MDR-TB) is one of the cornerstones for global TB control as it allows early epidemiological and therapeutic interventions. The slow growth of the tubercle bacillus is the greatest obstacle to rapid diagnosis of the disease. However, considerable progress has recently been made in developing novel diagnostic tools, especially molecular methods (commercial and ‘in-house’), for direct detection in clinical specimens. These methods, based on nucleic acid amplification (NAA) of different targets, aim to identify the M. tuberculosis complex and detect the specific chromosome mutations that are most frequently associated with phenotypic resistance to multiple drugs. In general, commercial methods are recommended since they have a better level of standardization, reproducibility and automation. Although some aspects such as cost-efficiency and the appropriate setting for the implementation of these techniques are not yet well established, organizations such as the WHO are strongly supporting the implementation and universal use of these new molecular methods. This chapter summarizes current knowledge and the available molecular methods for rapid diagnosis of TB and anti-tuberculous drug resistance in clinical microbiology laboratories.     

The importance of de-escalating antimicrobial therapy in patients with ventilator-associated pneumonia

The management of ventilator-associated pneumonia (VAP) requires a strategy for antibiotic use that achieves prompt and accurate empirical therapy without overusing antibiotics. Although, efforts at better diagnosis and antibiotic restriction have been attempted, "de-escalation" may be a more useful and effective strategy, and one that can achieve these goals while improving patient outcomes. The centerpiece of this approach is to initiate empirical therapy with a broad-spectrum treatment regimen, based on knowledge of local patterns of microbiology and antimicrobial resistance. Prior to therapy, patients require collection of a lower respiratory tract sample for culture. After 2 to 3 days, the clinical course can be assessed and the culture data reviewed, and in responding patients, efforts can be made to change the initial broad-spectrum therapy. This de-escalation can involve focusing to a more narrow spectrum agent, reducing the number of antibiotics, stopping therapy altogether in patients not likely to have infection, and making efforts to reduce duration of therapy. When this strategy has been used, outcomes such as the frequency of secondary infection, antimicrobial resistance, and mortality have improved. Additional information is needed to apply this approach more widely, especially in patients infected with multidrug-resistant organisms and in those with negative lower respiratory tract cultures.     

Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children

Background

Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited.

Methods

We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013.

Results

Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0·01) was associated with increased risk of hospitalization.

Conclusions

Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting.     

Development of "resistance" in beta-adrenergic receptors of asthmatic patients.

Complete in vitro dose-response curves for (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No "resistance" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors.     

Intrafamilial spreading of Escherichia coli resistant to trimethoprim

Bacterial resistance to trimethoprim has mainly been considered a problem confined to hospitals. The present investigation was undertaken to check for any possible spread of trimethoprim resistance borne by uropathogenic Escherichia coli among families of outpatients. Family members, living in the same household as outpatients with urinary tract infections caused by a trimethoprim-resistant E. coli strain, were asked to deliver faecal specimens. Of a total number of 51 family members 16 were found to be carrying trimethoprim-resistant E. coli in their faecal flora. A comparison of serotypes showed 8 of the 16 family members to have the same E. coli strain in their faeces as originally isolated in the urine of the index patient from the same family. The results indicate that resistance to trimethoprim not only spreads in hospitals with intensive use of antibiotics, but also among the families of trimethoprim-treated outpatients.     

The quinolones

The molecular basis of activity, chemistry, microbiology, and pharmacology of the new fluoroquinolones is reviewed in this article. Areas of clinical use are analyzed with specific reference to efficacy, development of resistance, and potential for toxicity.     

Emergence of Pediatric Melioidosis in Siem Reap, Cambodia

We describe the first cases of pediatric melioidosis in Cambodia. Thirty-nine cases were diagnosed at the Angkor Hospital for Children, Siem Reap, between October 2005 and December 2008 after the introduction of microbiology capabilities. Median age was 7.8 years (range = 1.6–16.2 years), 15 cases were male (38%), and 4 cases had pre-existing conditions that may have pre-disposed the patient to melioidosis. Infection was localized in 27 cases (69%) and disseminated in 12 cases (31%). Eleven cases (28%) were treated as outpatients, and 28 (72%) cases were admitted. Eight children (21%) died a median of 2 days after admission; seven deaths were attributable to melioidosis, all of which occurred in children receiving suboptimal antimicrobial therapy and before bacteriological culture results were available. Our findings indicate the need for heightened awareness of melioidosis in Cambodia, and they have led us to review microbiology procedures and antimicrobial prescribing of suspected and confirmed cases.     

Correlation between serial measurements of N-terminal pro brain natriuretic peptide and ambulatory cardiac filling pressures in outpatients with chronic heart failure

BACKGROUND: Serial measurements of N-terminal pro brain natriuretic peptide (NT-proBNP) have been suggested for the management of outpatients with chronic heart failure (CHF). The relationship between NT-proBNP plasma levels and central haemodynamic parameters in this setting is not known. METHODS: In 19 outpatients with CHF, NT-proBNP was related to central haemodynamic information, continuously measured with an implanted haemodynamic monitor (IHM) during 24 h of daily living activities ("24 h") and during supine rest ("rest"). In 13 patients, three to seven serial measurements were obtained with a mean time interval of 39 days (range 19-113). RESULTS: At the first visit (n=19), NT-proBNP plasma levels were dispersed over a wide range of filling pressures and not correlated with the 24 h median of the right ventricular systolic pressure (RVSP) and the estimated pulmonary artery pressure (ePAD). However, in the individual patient, serial measurements yielded significant positive correlations between NT-proBNP and RVSP (p=0.006) and ePAD (p=0.001). During "24 h" compared with "rest", the median RVSP and ePAD were elevated by 20+/-16% and 32+/-18%, respectively, and corresponded better with NT-proBNP (p<0.05). CONCLUSION: In outpatients with CHF, single measurements of NT-proBNP are not correlated with cardiac filling pressures. However, serial measurements of NT-proBNP in each individual patient show a significant positive correlation with central haemodynamic parameters and reflect changes in the haemodynamic state over time.     

Incidence and Outcomes of Contrast-Induced AKI Following Computed Tomography

Background and objectives: Most studies of contrast-induced acute kidney injury (CIAKI) have focused on patients undergoing angiographic procedures. The incidence and outcomes of CIAKI in patients undergoing nonemergent, contrast-enhanced computed tomography in the inpatient and outpatient setting were assessed.Design, setting, participants, & measurements: Patients with estimated glomerular filtration rates (GFRs) <60 ml/min per 1.73 m² undergoing nonemergent computed tomography with intravenous iodinated radiocontrast at an academic VA Medical Center were prospectively identified. Serum creatinine was assessed 48 to 96 h postprocedure to quantify the incidence of CIAKI, and the need for postprocedure dialysis, hospital admission, and 30-d mortality was tracked to examine the associations of CIAKI with these medical outcomes.Results: A total of 421 patients with a median estimated GFR of 53 ml/min per 1.73 m² were enrolled. Overall, 6.5% of patients developed an increase in serum creatinine ≥25%, and 3.5% demonstrated a rise in serum creatinine ≥0.5 mg/dl. Although only 6% of outpatients received preprocedure and postprocedure intravenous fluid, <1% of outpatients with estimated GFRs >45 ml/min per 1.73 m² manifested an increase in serum creatinine ≥0.5 mg/dl. None of the study participants required postprocedure dialysis. Forty-six patients (10.9%) were hospitalized and 10 (2.4%) died by 30-d follow-up; however, CIAKI was not associated with these outcomes.Conclusions: Clinically significant CIAKI following nonemergent computed tomography is uncommon among outpatients with mild baseline kidney disease. These findings have important implications for providers ordering and performing computed tomography and for future clinical trials of CIAKI.The intravascular administration of iodinated contrast media is a well-recognized cause of acute kidney injury, which in turn, is associated with in-hospital morbidity and mortality (1–4). Clinical factors that increase the risk for contrast-induced acute kidney injury (CIAKI) include preexistent kidney disease, diabetes mellitus in the setting of underlying renal impairment, advanced congestive heart failure, intravascular volume depletion, administration of large volumes of contrast, and the use of high-osmolal contrast media (1,5–8). Much of our understanding of the risk factors for, incidence of, and outcomes associated with CIAKI emanate from clinical studies of patients undergoing angiography, particularly coronary angiography. Moreover, most clinical trials of preventive interventions, such as N-acetylcysteine (NAC) and intravenous (IV) fluids, have been conducted in patients undergoing angiographic procedures (9–15). Despite this, expert recommendations for the prevention of CIAKI make little distinction between patients undergoing cardiac catheterization and other contrast-enhanced procedures, or in the status of the patient at the time of the radiographic procedure (outpatient versus hospitalized) in regard to determining patients’ risk level for CIAKI or implementing preventive measures (6,16–18). Additionally, it remains unclear whether the morbidity and mortality that have been associated with CIAKI among hospitalized patients are present among outpatients.A large proportion of patients who receive intravascular iodinated contrast do so when undergoing outpatient computed tomography. The routine assessment of risk status and implementation of preventive interventions, such as IV fluid, are considerably more difficult in patients who undergo elective computed tomography than coronary angiography. The practical and fiscal challenges to systematically administering preprocedure and postprocedure IV fluid to “at risk” patients are substantial, particularly in the outpatient setting. However, to determine the most effective and practical approach to identifying patients at increased risk for CIAKI following computed tomography and implementing preventive care to those most likely to derive benefit, greater clarity is needed on the incidence and clinical sequelae of CIAKI in this patient population. The primary aim of this study was to assess the incidence and outcomes of CIAKI following nonemergent computed tomography in the inpatient and outpatient setting.     

The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis

Heartburn is a symptom complex that has traditionally been accepted as an acid-mediated event and a reliable indicator of gastroesophageal reflux disease. Recently, however, these concepts have been questioned because patients with endoscopy-negative "heartburn" have lower response rates to acid suppression with proton pump inhibitors than do patients with endoscopy-positive "heartburn," ie, erosive esophagitis. As explanation for this, 3 different mechanisms have been proposed to explain the occurrence of heartburn in the endoscopy-negative setting. They are: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. In this report, we review the observations in support of each concept and propose a means for reconciling them under one hypothesis: abnormal tissue resistance. Essential to this review and to the conclusions drawn about the pathogenesis of heartburn in nonerosive reflux disease is a reaffirmation of the definition of reflux-associated "heartburn" as an acid-mediated event requiring "relief by antacids" as a necessary component of the history.     

提高成教“专升本”医学微生物学教学质量的探索

为改变成教专升本沿袭全日制本科教育模式的现状,提高成教专升本医学微生物学教学质量,本文在分析了临床医学专升本教育与本学科的特点后,对医学微生物学的教学计划、教学内容、教学方法和考核方式等进行了改革与实践,取得了较好的教学效果。