Factors associated with lung function response with oral antibiotic treatment of pulmonary exacerbations in cystic fibrosis.

Pulmonary exacerbations treated with oral antibiotics (oPEx) have a significant effect on lung function decline in people with cystic fibrosis (CF). However, factors associated with lung function response with oPExs are not well defined. We performed a retrospective cohort study of pediatric and adult patients with CF followed in the Toronto CF Database. Lung function response was measured both as the change in forced expiratory volume in 1 second (FEV1) from Day 0 of antibiotic therapy to end of treatment as well as from baseline to end of treatment. Drop from baseline to Day 0 FEV1 was strongly associated with lung function response (p<0.001). Greater FEV1 improvements were associated with longer antibiotic treatment durations. Older, female patients had less improvements in FEV1 at end of treatment compared to younger, male patients.

Mitigating healthcare staffing shortages: Should healthcare workers with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) household exposures work?

In a tertiary-care, pediatric healthcare center in Québec, Canada, healthcare workers who reported a household exposure to confirmed coronavirus disease 2019 (COVID-19) cases were allowed to work. On repeated testing, 15% became severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive by reverse-transcription polymerase chain reaction (RT-PCR), with no nosocomial transmission. Being asymptomatic and receiving a booster dose >7 days prior to exposure was protective against becoming SARS-CoV-2-positive by PCR.

Impact of antibiotic eradication therapy of Pseudomonas aeruginosa on long term lung function in cystic fibrosis.

INTRODUCTION: While antibiotic eradication therapy (AET) of early Pseudomonas aeruginosa infection is considered standard of care, its long-term effect on the subsequent course of cystic fibrosis (CF) lung disease remains unclear. METHODS: CF patients who were P. aeruginosa-free for at least a year and had a minimum of 10 years of pulmonary function measurements were included. Subjects were categorized as Never if they never had P. aeruginosa isolated from a respiratory tract sample. Subjects changed to the Eradicated group if they had a P. aeruginosa infection, were treated with AET, and subsequently cleared their infection. Subjects changed to the Chronic group if AET did not clear their P. aeruginosa infection. The primary outcome was absolute FEV1 decline over time, with age as the time variable. Mixed-effects linear regression models were used to account for the repeated lung function measurements over time within each patient. RESULTS: 205 CF subjects (48% female) were included; the median (IQR) age at first infection was 9.6 (5.6, 14.6) years. The median (IQR) follow-up was 10.2 (5.7, 14.7) years for the Eradicated group, 8.8 (4.5, 14.9) years for the Chronic group and 2.8 (1.0, 5.7) years for the Never group was among those patients that had at least one P. aeruginosa infection over the study period, annual lung function decline of FEV1 was significantly less (-1.11% predicted/year; 95% CI: -1.18, -1.04) in the Eradication group compared to the Chronic group (-1.57%; -1.64, -1.50) (p<0.001). CONCLUSIONS: AET against P. aeruginosa improves lung function trajectory in CF patients.

An Infant with Bilateral Keratitis: From Infectious to Genetic Diagnosis.

BACKGROUND Tyrosinemia Type II (TYRII) is a rare autosomal recessive inborn error of metabolism caused by deficiency of tyrosine aminotransferase (TAT), leading to hypertyrosinemia. TYRII patients often present in the first year of life with ocular and cutaneous findings, including corneal ulcers, pseudodendritic keratitis, and palmoplantar hyperkeratosis. The corneal involvement is often mistaken for herpes simplex virus (HSV) keratitis, which is a much commoner condition. CASE REPORT A previously healthy 10-month-old male infant was referred to Ophthalmology for acute onset photophobia. Bilateral dendritiform corneal lesions raised the suspicion for herpetic keratitis. Additionally, a papular, crusted lesion was found on his thumb after a few days of hospitalization, also raising concerns about HSV. The patient's clinical condition seemed to improve under intravenous acyclovir and supportive treatment. A conjunctival swab and crusted lesion on the thumb were tested for HSV using a polymerase chain reaction (PCR) technique, and both were negative. Nevertheless, given the clinical presentation and the favorable course of signs and symptoms, hospital discharge was planned with oral acyclovir. It was halted by an alternative diagnosis of autosomal recessive inborn error of metabolism, tyrosinemia type II, confirmed by elevated plasma tyrosine level and later by molecular analysis requested as a confirmatory investigation by the genetics medical team. CONCLUSIONS The corneal involvement in TYRII is often mistaken for HSV keratitis, and clinical course alone should not halt further investigations to rule out TYRII. Clinicians should suspect TYRII clinically when its characteristic ocular dendritiform lesions are present, namely in infancy or early childhood, and even in the absence of its typical cutaneous palmoplantar hyperkeratosis plaques.

Opportunistic Pathogens in Cystic Fibrosis: Epidemiology and Pathogenesis of Lung Infection.

Cystic fibrosis (CF) is one of the most common life-shortening genetic diseases in Caucasians. Due to abnormal accumulation of mucus, respiratory failure caused by chronic infections is the leading cause of mortality in this patient population. The microbiology of these respiratory infections includes a distinct set of opportunistic pathogens, including Pseudomonas aeruginosa, Burkholderia spp., Achromobacter spp., Stenotrophomonas maltophilia, anaerobes, nontuberculous mycobacteria, and fungi. In recent years, culture-independent methods have shown the polymicrobial nature of lung infections, and the dynamics of microbial communities. The unique environment of the CF airway predisposes to infections caused by opportunistic pathogens. In this review, we will highlight how the epidemiology and role in disease of these pathogens in CF differ from that in individuals with other medical conditions. Infectious diseases (ID) physicians should be aware of these differences and the specific characteristics of infections associated with CF.

Delayed diagnosis of maternal and congenital syphilis: An unrecognized epidemic?

Syphilis is an infection caused by Treponema pallidum spirochetes. The diagnosis of this sexually transmitted disease may be missed, partly due to the painless nature of genital ulcers in its primary stage. Women in Canada are screened for syphilis in their first trimester of pregnancy, but late pregnancy testing is not done in all provinces to date; therefore, undetected vertical transmission of syphilis may occur. This case emphasizes the importance of recognizing congenital syphilis in infants and young children with unexplained growth problems and biochemical and hematological abnormalities. Congenital syphilis remains a rare diagnosis, but in the context of increased syphilis rates in Canada during recent years, clinicians should consider this diagnosis in infants presenting with compatible clinical manifestations.

Evaluation of Real-life Use of Point-of-care Rapid Antigen Testing for SARS-CoV-2 in Schools (EPOCRATES): a cohort study.

BACKGROUND: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts. METHODS: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared with those of other high schools in the same area. RESULTS: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs varied from 99.8% to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR result on days 6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school. INTERPRETATION: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv - doi.org/10.1101/2021.10.13.21264960.

The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide.

BACKGROUND: The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. METHODS: To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0-19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). RESULTS: We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). CONCLUSIONS: The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

Pseudomonas aeruginosa Strain-sharing in Early Infection Among Children With Cystic Fibrosis.

BACKGROUND: We previously identified Pseudomonas aeruginosa isolates with characteristics typical of chronic infection in some early infections in children with cystic fibrosis (CF), suggesting that these isolates may have been acquired from other patients. Our objective was to define the extent of P. aeruginosa strain-sharing in early CF infections and its impact on antibiotic eradication treatment failure rates. METHODS: We performed whole genome sequencing on isolates from early pediatric CF pulmonary infections and from the following comparator groups in the same hospital: chronic CF infection, sink drains, sterile site infections, and asymptomatic carriage. Univariate logistic regression was used to assess factors associated with treatment failure. RESULTS: In this retrospective, observational study, 1029 isolates were sequenced. The CF clones strain B and clone C were present. In 70 CF patients with early infections, 14 shared strains infected 29 (41%) patients over 5 years; 16% (n = 14) of infections had mixed strains. In the 70 children, approximately one-third of shared-strain infections were likely due to patient-to-patient transmission. Mixed-strain infections were associated with strain-sharing (odds ratio, 8.50; 95% confidence interval, 2.2-33.4; P = .002). Strain-sharing was not associated with antibiotic eradication treatment failure; however, nosocomial strain transmission was associated with establishment of chronic infection in a CF sibling pair. CONCLUSIONS: Although early P. aeruginosa CF infection is thought to reflect acquisition of diverse strains from community reservoirs, we identified frequent early CF strain-sharing that was associated with the presence of mixed strains and instances of possible patient-to-patient transmission.

Burkholderia cenocepacia ET12 transmission in adults with cystic fibrosis.

This report describes transmission of a Burkholderia cenocepacia ET12 strain (ET12-Bc) at the Toronto Adult Cystic Fibrosis (CF) Centre occurring from 2008 to 2017. Epidemiological and genomic data from 11 patients with CF were evaluated. Isolates were analysed using whole genome sequencing (WGS). Epidemiological investigation and WGS analysis suggested nosocomial transmission, despite enhanced infection control precautions. This was associated with subsequent deaths in 10 patients. ET12-Bc positive patients are no longer cared for on the same unit as ET12-Bc negative patients.

Microbiology of Cystic Fibrosis Airway Disease.

Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.

Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment.

BACKGROUND: Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients. METHODS: Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS). DNA concentrations were compared in patients in whom AET was successful (Eradicated) to those with persistently positive sputum cultures (Persistent). RESULTS: Forty-seven patients were included. AET was successful in 32 cases (68%), but failed in 15 cases (32%). Median sputum Pa-specific DNA concentration preceding the positive sputum culture was 2.2 × 10-6 µg/mL in Eradicated cases compared to 3 × 10-5 µg/mL in Persistent cases (p = 0.14). There was no significant difference in DNA concentration in the last sputum sample prior to culture positivity, nor in maximal DNA values. There was also no difference in sputum Pa DNA concentrations in patients who had a mucoid (compared to non-mucoid) Pa infection. CONCLUSIONS: Pediatric CF patients with new-onset Pa infections have detectable Pa-specific DNA in the year preceding a positive culture, however, there is no significant difference in Pa DNA concentrations between patients in whom AET is successful compared to those in whom it fails. Therefore, early molecular detection of Pa may not lead to improved eradication success rates.

Scurvy as a mimicker of osteomyelitis in a child with autism spectrum disorder.

A case of scurvy in a 10-year-old boy with autism spectrum disorder is described. His clinical presentation was initially thought to be due to osteomyelitis, for which empirical antimicrobial therapy was initiated. Further invasive and ultimately unnecessary investigations were avoided when scurvy was considered in the context of a restricted diet and classic signs of vitamin C deficiency. Infectious diseases specialists should be aware of scurvy as an important mimicker of osteoarticular infections when involved in the care of patients at risk of nutritional deficiencies.

Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis.

INTRODUCTION: Antibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF. METHODS: A three-step AET protocol which includes: (step 1) 28days of tobramycin inhalation solution (TIS) for new-onset Pa infection; (step 2) a second course of TIS for patients with positive respiratory tract culture after step 1; (step 3) 14days of intravenous antibiotics followed by 28days of TIS for patients with a subsequent positive culture. We conducted a retrospective review of all pediatric CF patients who underwent the eradication protocol between January 2010 and December 2015. The success rate of each step and of the overall protocol was recorded. RESULTS: During the study period, 128 patients had a total of 213 new-onset Pa infections. Of 195 asymptomatic episodes, 150 (76.9%, 95% CI 70.4; 82.6) cleared after step 1 and 12 cleared after step 2 (33.3% (95% CI 18.6; 50.9) stepwise success rate and 87.1% (95% CI 77.1; 88.1) cumulative success rate). Intravenous antibiotics followed by 28days of TIS were administered in 24 episodes; this was successful in 10 episodes (41.7%; 95% CI 22.1; 63.4). The regimen in asymptomatic patients failed in fourteen episodes (7.5%; 95% CI 4.2; 12.3) then considered chronically infected with Pa. Overall, the cumulative success rate of the asymptomatic arm was 88.2% (95% CI 82.8; 92.4). CONCLUSION: The first step of the AET protocol led to the greatest eradication success. Subsequent eradication attempts have a success rate below 50%. Prospective studies of eradication protocols for this population are needed to determine the most effective treatment strategy.

Molecular Epidemiology of a Vancomycin-Intermediate Heteroresistant Staphylococcus epidermidis Outbreak in a Neonatal Intensive Care Unit.

Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV) Staphylococcus epidermidis central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119 S. epidermidis CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling-area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV S. epidermidis seems more common than currently realized in the NICU, and certain hV S. epidermidis clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV S. epidermidis in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS.

Staphylococcal infections in infants: updates and current challenges.

Staphylococci are common pathogens in the neonatal period. Increased survival of premature infants leads to prolonged hospital stay with associated risk factors for developing invasive staphylococcal disease. Challenges of diagnosing coagulase-negative staphylococcal infections result in conflicting definitions and inconsistent clinical practice. Resistance to methicillin influences the choice of empirical therapy.

Central line-associated bloodstream infection in neonatal intensive care units.

OBJECTIVE: Describe the epidemiology of central line-associated bloodstream infections (CLABSIs) in neonatal intensive care units (NICUs) participating in a standardized and mandatory CLABSI surveillance program. DESIGN: Retrospective cohort. Setting. We included patients admitted (April 2007-March 2011) to 7 level II/III NICUs who developed a CLABSI (as defined by the National Healthcare Safety Network). METHODS: CLABSIs/1,000 central line-days and device utilization ratio were calculated; χ(2) test, Student t test, Kruskal-Wallis, and Poisson regression were used. RESULTS: Overall, 191 patients had 202 CLABSI episodes for a pooled mean rate of 4.0 CLABSIs/1,000 central line-days and a device utilization ratio of 0.20. Annual pooled mean CLABSI rates increased from 3.6 in 2007-2008 to 5.1 CLABSIs/1,000 central line-days in 2010-2011 (P - .01). The all-cause 30-day case fatality proportion was 8.9% (n = 17) and occurred a median of 8 days after CLABSI. Coagulase-negative Staphylococcus was identified in 112 (50.5%) cases. Staphylococcus aureus was identified in 22 cases, and 3 (13.6%) were resistant to methicillin. An underlying intra-abdominal pathology was found in 20% (40/202) of CLABSI cases, 50% of which were reported in the last year of study. When adjusted for mean birth weight, annual CLABSI incidence rates were independently associated with the proportion of intra-abdominal pathology (P = .007) and the proportion of pulmonary pathology (P = .016) reported. CONCLUSION: The increase in CLABSI rates in Quebec NICUs seems to be associated with an increased proportion of cases with underlying intra-abdominal and pulmonary pathologies, which needs further investigation.

Management of aboriginal and nonaboriginal people with chronic kidney disease in Quebec: quality-of-care indicators.

OBJECTIVE: To compare quality-of-care indicators for management of patients with chronic kidney disease (CKD) and type 2 diabetes among the James Bay Cree of Northern Quebec with those among residents of Montreal, Que. DESIGN: A cross-sectional survey using medical records from patients seen between 2002 and 2008. SETTING: Predialysis clinics of the McGill University Health Centre in Montreal. PARTICIPANTS: Thirty Cree and 51 nonaboriginal patients older than 18 years of age with type 2 diabetes mellitus and estimated glomerular filtration rates of less than 60 mL/min/1.73 m2. MAIN OUTCOME MEASURES: Rates of anemia, iron deficiency, obesity, and renoprotective medication use among aboriginal and nonaboriginal patients. RESULTS: Overall, the Cree patients were younger (59 vs 68 years of age, P < .0035) and weighed more (101 vs 77 kg,P < .001). The 2 groups were prescribed medication to control blood pressure, lipids, and phosphate levels at similar rates, but the Cree patients were more likely to receive renoprotective agents (87% vs 65%, P = .04). Despite similar rates of erythropoietin supplementation, the Cree patients were at greater risk of anemia, with an adjusted risk ratio of 2.80 (95% CI 1.01 to 7.87). CONCLUSION: Cree patients with CKD were younger, weighed more, and were more likely to receive renoprotective agents. With the exception of the management of anemia, quality of CKD care was similar between the 2 groups.Anemia education for family physicians and continuous monitoring of quality indicators must be implemented in northern Quebec.