Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability ...to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia.
We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%).
A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68–0.89, optimism-corrected AUCs 0.63–0.85) and pathogen-guided (12 models, AUCs 0.75–0.98, optimism-corrected AUCs 0.64–0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy.
Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires further prospective evaluation.
Readily available epidemiologic risk factors can be used to predict susceptibility of Gram-negative organisms among patients with bacteraemia, using automated decision-making models.
Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding ...empiric treatment in Gram-negative bloodstream infections.
We conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015.
Among 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91–0.93), and positive predictive value was 0.66 (95% CI 0.61–0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five.
In patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.
Mumps in a 27-year-old man Wiggers, J. Brad, MD; Chan, Tiffany, MD; Gold, Wayne L., MD ...
Canadian Medical Association journal (CMAJ),
04/2017, Letnik:
189, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Laboratory investigations showed that the patient had a normal complete blood cell count and a serum lipase level of 22 U/L (normal < 60 U/L). Initial investigations included a throat swab for group ...A streptococcus and a nasopharyngeal swab to detect respiratory viruses using multiplex polymerase chain reaction testing. He had blood taken for cytomegalovirus immunoglobulin M (IgM) antibody, a monospot test, parvovirus B19 IgM antibody and testing for HIV. He also had nucleic acid amplification testing of urine and testing of pharyngeal swabs for both Neiserria gonorrhoeae and Chlamydia trachomatis. Scrotal ultrasonography showed an enlarged hyperemic right testicle (measuring 5.1 x 3.3 x 3.3 cm3) and an edematous hyperemic epididymis. Given the constellation of fever, prior neck swelling, right epididymo-orchitis and history of bilateral parotid swelling in his partner, serum mumps serologic testing and polymerase chain reaction testing of both urine and buccal samples for mumps virus were requested. The presence of parotitis should prompt physicians to consider a diagnosis of mumps. Although the diagnosis may be clear in an outbreak setting, a variety of other infectious and noninfectious etiologies can cause parotid enlargement (Box 1). Features of these conditions should be obtained through a detailed history, physical examination and directed investigations. Historical features supporting an alternate diagnosis include radiation exposure (primary salivary neoplasm), known primary malignant disease (metastasis), symptoms of a systemic autoimmune condition (Sjögren syndrome or sarcoidosis), unilateral suppurative parotitis (bacterial) or use of drugs known to cause parotid enlargement/parotitis.3"6 Many other viruses are associated with parotitis. Epstein-Barr virus is a common cause of mumps-like illness in nonoutbreak settings.3 Mumps orchitis should be considered in acute testicular pain, which can also be caused by testicular torsion, epididymitis, Fournier gangrene and appendiceal torsion. Mumps is a self-limited illness for which no specific treatment is required. Supportive care with analgesics for parotitis or orchitis may be required. Immunization with a vaccine containing a live attenuated mumps component is the main strategy for preventing infection and clinical disease. Since the introduction of the single-dose mumps vaccine in 1969, there has been a 99% decline in mumps cases, with a further decrease seen after the introduction of the two-dose vaccine schedule in 1996/97.1 The current Canadian immunization schedule recommends administration of the first mumps-containing vaccine dose at 12 to 15 months and the second at 18 months.1 However, provincial schedules and vaccine usage vary and should be confirmed with local authorities. Pregnancy, prior anaphylaxis to the vaccination, anaphylaxis to any component of the vaccine with the exception of eggs and immunocompromised status are contraindications to immunization.1
A biopsy sample of the skin lesions showed broad-based budding yeast with Gömöri methenamine silver stain in the dermis consistent with blastomycosis (figure, appendix).
Persistent epigastric pain in an 80-year-old man MacFadden, Derek R; Penner, Todd P; Gold, Wayne L
Canadian Medical Association journal (CMAJ),
2011-May-17, 2011-05-17, 20110517, Letnik:
183, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The annual incidence of pyogenic liver abscess has been estimated at 1.1-2.3 cases per 100 000 population.1,2 Incidence increases with age: people aged 65 years or older are 10 times more likely than ...younger people to develop pyogenic liver abscesses.1 This parallels the increased incidence of biliary tract disease in older populations. 3,4 Risk factors for pyogenic liver abscess include male sex, advanced age, biliary tract disease, diabetes mellitus, liver transplantation, malignancy and percutaneous treatments for hepatocellular carcinoma, including radiofrequency ablation.1,5 The most common clinical features include fever (73%), chills (45%) and right upper quadrant pain (38%). The most frequent laboratory abnormalities include hypoalbuminemia (96%), elevated γ-glutamyl transferase (81%), elevated alkaline phosphatase (71%) and leukocytosis (69%).1 Liver abscesses resulting from foreign-body migration most commonly occur in the left lobe of the liver, often as a result of perforation through the gastric antrum or proximal small bowel. Common foreign bodies include fishbones (44%), toothpicks (29%), chicken bones (8%), metallic objects (14%) and unidentified bones (5%).11 Clinical and laboratory features of liver abscess secondary to foreign-body migration are similar to those related to other mechanisms of infection.11 A systematic review of the literature that identified 60 instances of pyogenic liver abscess related to foreign-body migration suggested improved sensitivity of CT over ultrasonography for visualization of foreign bodies; however, imaging may be nondiagnostic in more than 50% of instances.11 A thickened gastrointestinal wall in contact with a liver abscess may suggest a migrated foreign body as the mechanism of infection. For instances in which a foreign-body mechanism is suspected and the foreign body is not seen on imaging, esophagogastroduodenoscopy is recommended.11 Findings at endoscopy may include direct visualization of the foreign body, mucosal inflammation and the presence of a fistulous tract. Endoscopy may assist with foreign-body removal. In some instances, exploratory laparotomy or laparoscopy may be needed to arrive at the diagnosis.11 In instances of liver abscess related to foreign- body migration, rates of cure without foreign- body removal are low (9.5%).11 Removal of the foreign body is critical to permitting resolution of the abscess and closure of fistulous tracts. Surgical drainage of the abscess at the time of removal of the foreign body appears to be an adequate means of source control (i.e., eradicating the focus of infection).11 There are limited data addressing the need for ongoing catheter drainage following surgical drainage in this situation. Surgical drainage is in principle similar to needle drainage, which has shown comparable efficacy to catheter drainage in instances of pyogenic liver abscess due to all causes.13
The COVID-19 pandemic has had an effect on the incidence of infectious diseases and medical care. This study aimed to describe the impact of the COVID-19 pandemic on community-level antibiotic use.
...Using national antibiotic dispensing data from IQVIA's CompuScript database, this ecological study investigated antibiotic dispensing through community retail pharmacies in Canada from November 2014 to October 2020. Analyses were stratified by age, sex, prescription origin and approximate indication.
Adjusting for seasonality, the national rate of antibiotic dispensing in Canada decreased by 26.5% (50.4 to 37.0 average prescriptions per 1000 inhabitants) during the first 8 months of the Canadian COVID-19 period (March to October 2020), compared with the pre-COVID-19 period. Prescribing rates in children ≤18 years decreased from 43.7 to 12.2 prescriptions per 1000 inhabitants in males (–72%) and from 46.8 to 14.9 prescriptions per 1000 inhabitants in females (–68%) in April 2020. Rates in adults ≥65 decreased from 74.9 to 48.8 prescriptions per 1000 inhabitants in males (–35%) and from 91.7 to 61.3 prescriptions per 1000 inhabitants in females (–33%) in May 2020. Antibiotic prescriptions from family physicians experienced a greater decrease than from surgeons and infectious disease physicians. Prescribing rates for antibiotics for respiratory indications decreased by 56% in May 2020 (29.2 to 12.8 prescriptions per 1000 inhabitants), compared with prescribing rates for urinary tract infections (9.4 to 7.8 prescriptions per 1000 inhabitants; –17%) and skin and soft tissue infections (6.4 to 5.2 prescriptions per 1000 inhabitants; –19%).
The first 8 months of the COVID-19 pandemic reduced community antibiotic dispensing by 26.5% in Canada, compared with the marginal decrease of 3% in antibiotic consumption between 2015 and 2019. Further research is needed to understand the implications and long-term effects of the observed reductions on antibiotic use on antibiotic resistance in Canada.
A breast mass in a 56-year-old man MacFadden, Derek R; Gold, Wayne L; Richardson, Susan E ...
Canadian Medical Association journal (CMAJ),
2011-Nov-08, 2011-11-08, 20111108, Letnik:
183, Številka:
16
Journal Article
Our objective was to evaluate whether patients with bacteraemic urinary tract infection (UTI) who receive inadequate empirical therapy have worse outcomes than those with adequate therapy. This was a ...retrospective cohort study of patients with bacteraemic UTI. The exposure variable was adequate versus inadequate empirical antibiotic therapy (AEAT versus IEAT) within 24 h of culture collection. Primary endpoint was time to cure. The primary analysis used propensity score models with inverse probability of treatment weights. A secondary Cox proportional hazards modelling approach was used to test the robustness of this finding, and to evaluate other patient and pathogen predictors of time to cure. Of 469 patients with bacteraemic UTI, 368 (78.5%) received AEAT. There was no significant difference in mortality between those receiving AEAT and those receiving IEAT (adjusted OR 0.86, 95%CI 0.47–1.58). Receipt of AEAT had no association with time to cure (HR 0.93, 95%CI 0.73–1.19, p 0.55) or time to normalization of individual clinical variables. Cox proportional hazards modelling revealed that longer time to cure was associated with liver disease (HR 0.25, 95%CI 0.08–0.76, p 0.015), prior stroke (HR 0.73, 95%CI 0.54–0.99, p 0.044), empirical receipt of piperacillin–tazobactam (HR 0.77, 95%CI 0.59–0.99, p 0.044), qSOFA score >1 (HR 0.68, 95%CI 0.55–0.84, p < 0.001), and hospital-onset UTI (HR 0.53, 95%CI 0.39–0.71, p < 0.001). In conclusion, we found no association between AEAT and time to cure for patients with bacteraemic UTI. It may be appropriate to accept a higher risk threshold when choosing empirical antibiotic regimens, even in centres with high rates of resistant uropathogens.
New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular ...divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants. Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.
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