A nested cohort 5-year Canadian surveillance of Gram-negative antimicrobial resistance for optimized antimicrobial therapy.

We analyzed 5 years (2016-2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and antimicrobial resistance (AMR) patterns of adult Gram-negative infections in Canadian health care and to complement other public surveillance programs and studies in Canada. A total of 6853 isolates were analyzed from medical (44%), surgical (18%), intensive care (22%) and emergency units (15%) and from respiratory tract (36%), intra-abdominal (25%), urinary tract (24%) and bloodstream (15%) infections. Overall, E. coli (36%), P. aeruginosa (18%) and K. pneumoniae (12%) were the most frequent isolates and P. aeruginosa was the most common respiratory pathogen. 18% of Enterobacterales species were ESBL positive. Collective susceptibility profiles showed that P. aeruginosa isolates were highly susceptible (> 95%) to ceftolozane/tazobactam and colistin, though markedly less susceptible (58-74%) to other antimicrobials tested. Multi-drug resistance (MDR) was present in 10% of P. aeruginosa isolates and was more frequent in those from respiratory infections and from ICU than non-ICU locations. Of P. aeruginosa isolates that were resistant to combinations of ceftazidime, piperacillin/tazobactam and meropenem, 73-96% were susceptible to ceftolozane/tazobactam over the period of the study. These national data can now be combined with clinical prediction rules and genomic data to enable expert antimicrobial stewardship applications and guide treatment policies to optimize adult patient care.

Differences between a probable and proven BCG infection following intravesical instillations: 16 years experience in a tertiary care hospital.

BACKGROUND: Intravesical instillation of Bacillus Calmette-Guérin (BCG) is an efficient immunotherapy for superficial bladder cancer. BCG infection represents a major yet uncommon adverse event that occurs in 5-10% of the patients treated with BCG instillations, though the pathogenesis of this entity is not clear. METHODS: We report two cases of patients presented at our institution with BCG infection after instillation: one with microbiological BCG isolate and another without, and review all the medical records of patients instilled with BCG in our institution from 1996 until 2012, comparing patients with probable and proven BCG infection. RESULTS: During the study period, a total of 786 patients received BCG intravesical instillations. Of them, 31 (4%) patients had to suspend treatment because of adverse events and, specifically, 11 (1.3%) patients had to interrupt treatment because of suspected BCG infection. The incidence of BCG infection during our study period was 0.87 episodes per 1,000 instilled patients/year and 140 cases per 10,000 instilled patients. Of the 11 patients with suspected BCG infection, 7 (64%) had a probable BCG infection, while 4 (36%) patients had a proven BCG infection. All patients with a proven infection had a previous underlying condition, compared to a high proportion of patients with probable infection (57%) that did not present with underlying diseases. Common findings between both groups of patients were abnormal imaging studies and laboratory tests. Regarding treatment, 8 (73%) of the 11 patients with BCG infection received at least two first line drugs active against M. bovis (isoniazid, rifampicin or ethambutol), four patients (36%) received steroids as part of the treatment and curation was obtained in 10 (91%) patients, while 1 patient with a proven infection had a death related to BCG infection. CONCLUSIONS: We can conclude that BCG infection after intravesical instillations has a low incidence in our institution. Patients with previous underlying conditions seem to have more proven infections. A high proportion of patients do not yield positive microbiological tests; in those cases the diagnosis relies in clinical, radiological and laboratory findings. Treatment for BCG infection should include at least two active drugs against M. bovis and coadjuvant steroid treatment for systemic BCG infections.

Clinical Significance of Clostridium difficile in Children Less Than 2 Years Old: A Case-Control Study.

BACKGROUND: The significance of Clostridium difficile (CD) in the stools of children 2 years old or younger remains unclear. The aim of this study was to investigate risk factors and clinical evolution of diarrheic children ≤2 years old with or without CD in their stools. METHODS: From January 1, 2012 to December 31, 2013, all diarrheic stool samples received in our laboratory were screened for CD. We randomly selected diarrheic children ≤2 years old (n = 100) with an isolation of toxigenic CD in the stools and compared them with diarrheic children (n = 100) without isolation of CD. RESULTS: Cases and controls were appropriately matched for age and sex. We found no significant differences between children with or without CD. Of the CD cases, we compared the patients receiving treatment with metronidazole (19%) versus those that were not prescribed treatment (81%), and found that patients in the first group had used more gastric acid suppressants (P = 0.02), had surgery in the last month (P = 0.03) and also presented with more days with diarrhea (P = 0.03). All the patients, including CD cases, independently of the administration of metronidazole, were cured of the diarrheic episode. Polymerase chain reaction-ribotyping performed in all CD cases showed that the most prevalent ribotype was 014 (25%). CONCLUSIONS: Our study reinforces the nonsignificance of CD in neonates and infants younger than 2 years old. Informing clinicians of CD isolates in this population promotes the use of antibiotics against CD, without evidence of a different outcome than those not receiving treatment.

Coxiella burnetii infection in hemodialysis and other vascular grafts.

Prosthetic arteriovenous (AV) graft infection is the principal cause of morbidity related to chronic hemodialysis AV graft fistula. Coxiella burnetii is a known pathogen that causes fever, pneumonia, and intravascular infections with the limitation of negative cultures. Herein, we report the first case of a patient who presented to the emergency department of our hospital with a prosthetic hemodialysis AV graft infection due to Coxiella burnetii. We also performed a literature search with PubMed to identify studies reporting cases of Coxiella burnetii vascular graft infection. Overall, we reviewed 15 cases of vascular graft infection, including ours. We found a high prevalence of male patients (87%); mean age ± standard deviation (SD) of the entire population was 60.4 ± 9.6 years. The dacron infrarenal aortic and the aortobifemoral bypass were the most common involved grafts. The early diagnosis of infection due to Coxiella burnetii was done by serology or with polymerase chain reaction (PCR), in 12 and 3 cases, respectively. All patients underwent partial or complete resection of the infected grafts; the most common antibiotic treatment for this entity was doxycycline and hydroxycloroquine.Although this is a relatively rare disease, Coxiella burnetii should be included in the differential diagnosis of all patients who present with infection of an endovascular graft of any nature with an inconclusive etiologic diagnosis.

Occult bloodstream infections in adults: a "benign" entity.

BACKGROUND: Patients with septic episodes whose blood cultures turn positive after being sent home from emergency departments (EDs) are recognized as having occult bloodstream infections (BSI). The incidence, etiology, clinical circumstances, and outcome of occult BSI in children are well known, but, to our knowledge, data in adult patients are scarce. We analyzed the episodes of occult BSI in adult patients at our institution. METHODS: This is a retrospective cohort study (September 2010 to September 2012), in adult patients discharged from the ED in whom blood cultures turned positive. Patients were evaluated according to a preestablished protocol. RESULTS: We recorded 4025 cases of significant BSI in the ED and 113 patients with adult occult BSI. In other words, the incidence of occult BSI in the ED was 2.8 per 100 episodes. The predominant microorganisms were gram-negative bacteria (57%); Escherichia coli was the most common (41%), followed by gram-positive bacteria (29%), anaerobes (6.9%), polymicrobial (6.1%), and yeasts (0.8%). The most frequent suspected origin was urinary tract infection (53%), and most infections were community acquired (63.7%). Of the 105 patients that we were able to trace, 54 (42.5%) were asymptomatic and were receiving adequate antibiotic treatment at the time of the call, and 65 (51.2%) had persistent fever or were not receiving adequate antibiotic treatment. CONCLUSIONS: Occult BSI is relatively common in patients in the adult ED. Despite the need for readmission of a fairly high proportion of patients, occult BSI behaves as a relatively benign entity.

Micafungin is more active against Candida albicans biofilms with high metabolic activity.

BACKGROUND: The ability to form biofilm enables Candida spp. to cause catheter-related candidaemia. The use of agents with in vitro activity against Candida albicans biofilms, such as micafungin, could obviate catheter removal. The metabolic activity of C. albicans biofilms is strain-dependent, and cell wall formation is thought to be more prominent in biofilms showing high metabolic activity. METHODS: We studied the antifungal activity of micafungin against 265 C. albicans isolates with different degrees of metabolic activity causing fungaemia in 246 patients admitted to Gregorio Marañón Hospital (January 2007 to June 2013). All strains were classified according to the metabolic activity of their biofilm, which was classified as low, moderate and high using XTT. Micafungin MICs for planktonic and sessile cells were assessed using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. The MIC was defined as a 50% and 80% reduction in metabolic activity compared with the control well. RESULTS: Micafungin was uniformly more active against planktonic cells than against sessile cells (MIC50 ≤ 0.015 versus 8 mg/L), although it was not consistently active against all C. albicans biofilms. Isolates with low metabolic activity biofilms showed the lowest susceptibility to micafungin, followed by moderate and high metabolic activity biofilms (P < 0.001). CONCLUSIONS: Our study suggests that the metabolic activity of biofilm may have a role in future evaluations of micafungin for the eradication of C. albicans biofilms (e.g. the lock therapy approach).