Epidemiology and impact of methicillin-sensitive Staphylococcus aureus with ß-lactam antibiotic inoculum effects in adults with cystic fibrosis.

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced ß-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal ß-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥105 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE (P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE (P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.

Differences in outcomes for hospitalizations of systemic and non-systemic infections associated with vascular and cardiac grafts and devices: a population-based study.

BACKGROUND: Use of vascular and cardiac devices has expanded and is associated with a relative, though disproportionate, increase in device-associated infections. AIM: To describe the association between cardiac/vascular device infections and outcomes in those with, and without systemic infections. METHODS: We used the 2016 National Inpatient Sample and the International Classification of Diseases - 10th revision codes to identify hospitalized individuals with vascular and cardiac device infections. Linear and logistic regression models were utilized to compare outcomes of death, length of stay (LOS) and hospitalization costs between individuals with and without systemic infection. FINDINGS: There were a total of 65,110 hospitalizations associated with device infections with a mean age of 61.3 ± 15.9 years (standard deviation); 28,650 (44%) had systemic infections. Elixhauser comorbidity scores of three or greater were observed in 91.2% of individuals with systemic infections along with a higher prevalence of diabetes, renal disease and heart failure. The primary outcome of mortality was observed in 3965 individuals with an odds ratio of 3.97 (95% confidence interval (CI), 2.92-3.95) in those with systemic infections compared with those without. Mean LOS was 3.44 days longer (95% CI, 2.92-3.95) and mean cost was US$11,776 greater (95% CI, US$9826-12,727) in the systemic infection cohort. CONCLUSION: Systemic cardiac and vascular device infections were associated with increased mortality, LOS and costs. Considering the increasing use of these life-saving devices, further work is needed to identify those at risk for infectious complications, particularly systemic infection, in order to enhance preventative strategies and improve health outcomes.

Clinical Outcomes Associated With Escherichia coli Infections in Adults With Cystic Fibrosis: A Cohort Study.

BACKGROUND: Analysis of "emerging" pathogens in cystic fibrosis (CF) lung disease has focused on unique pathogens that are rare in other human diseases or are drug resistant. Escherichia coli is recovered in the sputum of up to 25% of patients with CF, yet little is known about the epidemiology or clinical impact of infection. METHODS: We studied patients attending a Canadian adult CF clinic who had positive sputum cultures for E coli from 1978 to 2016. Infection was categorized as transient or persistent (≥3 positive sputum cultures, spanning >6 months). Those with persistent infection were matched 2:1 with age, sex, and time-period controls without history of E coli infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency, lung function decline, hospitalization, and intravenous antibiotic days. RESULTS: Forty-five patients (12.3%) had E coli recovered from sputum samples between 1978 and 2016, and 18 patients (40%) developed persistent infection. Nine patients (24%) had PEx at incident infection, and increased bioburden was predictive of exacerbation (P = .03). Risk factors for persistent infection included lower nutritional status (P < .001) and lower lung function (P = .009), but chronic infection with Pseudomonas aeruginosa was protective. There was no difference in annual lung function decline, need for hospitalization or intravenous antibiotics, or risk of PEx in patients with persistent infection. CONCLUSIONS: Persistent E coli infection was frequent and was more common in CF patients with low nutritional status and lung function. However, this does not predict clinical decline. Multicenter studies would allow better characterization of the epidemiology and clinical impact of E coli infection.

Duration of antibiotic therapy in non-cystic fibrosis bronchiectasis.

PURPOSE OF REVIEW: a)We conducted a review of the current evidence relating to antibiotic duration in the short and long-term management of non-cystic fibrosis bronchiectasis. RECENT FINDINGS: b)In non-cystic fibrosis pulmonary exacerbations, evidence is primarily based on expert consensus and recent guidelines recommend antibiotic durations of approximately 14 days. Chronic antibiotics (oral or inhaled) are recommended in patients with frequent exacerbations or with chronic Pseudomonas aeruginosa airways infection. Macrolides are the best studied therapies for long-term use with evidence for effect limited to a 12 month duration. Encouragingly, there are increased efforts to develop registries and conduct larger population level studies to improve patient care. SUMMARY: c)There is a paucity of evidence for optimal antibiotic strategies in exacerbations and chronic maintenance in persons with non-cystic fibrosis bronchiectasis. Rationally designed studies which utilize a registry and population-based approach will be critical to build evidence-based strategies to optimize management of non-cystic fibrosis bronchiectasis.

A longitudinal characterization of the Non-Cystic Fibrosis Bronchiectasis airway microbiome.

A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4-16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae. Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥-1 FEV1% predicted. Shannon diversity values <1 were more prevalent in patients with FEV1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.

Prevalence and Outcomes of Achromobacter Species Infections in Adults with Cystic Fibrosis: a North American Cohort Study.

Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian adult CF clinic who had positive sputum cultures for Achromobacter species in the period from 1984 to 2013. Infection was categorized as transient or persistent (≥50% positive cultures for 1 year). Those with persistent infection were matched 2:1 with age-, sex-, and time-matched controls without a history of Achromobacter infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency and lung function decline. Isolates from a biobank were retrospectively assessed, identified to the species level by nrdA sequencing, and genotyped using pulsed-field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8 years), developed Achromobacter infection. Ten patients (29%) developed persistent infection. Persistence did not denote permanence, as most patients ultimately cleared infection, often after years. Patients were more likely to experience PEx at incident isolation than at prior or subsequent visits (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7]; P = 0.03). Following persistent infection, there was no difference in annual lung function decline (-1.08% [95% CI, -2.73 to 0.57%] versus -2.74% [95% CI, -4.02 to 1.46%]; P = 0.12) or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28]; P = 0.70). Differential virulence among Achromobacter species was not observed, and no cases of transmission occurred. We demonstrated that incident Achromobacter infection was associated with a greater risk of PEx; however, neither transient nor chronic infection was associated with a worsened long-term prognosis. Large, multicenter studies are needed to clarify the clinical impact, natural history, and transmissibility of Achromobacter.

Examining Chlamydia trachomatis and Neisseria gonorrhoeae rates between 2010 and 2015: a population-based observational study.

Bacterial sexually transmitted infections including Chlamydia trachomatis and Neisseria gonorrhoeae remain an important public health concern. We aimed to assess the population-based incidence of C. trachomatis and N. gonorrhoeae in an age-standardized cohort over time. A retrospective study of a large Canadian health region was undertaken between 2010 and 2015 using linked census and digital laboratory data. C. trachomatis and N. gonorrhoeae tests were linked to patient data. Sex and age-standardized incidence rates (IR) and ratios (IRR) were calculated for cases and testing rates. The annual mean population was 1,150,556 individuals (50.1% female). A total of 15,109 cases of chlamydia and 981 cases of gonorrhoea occurred. The overall IR for chlamydia ranged from 18.81 to 25.63 cases per 10,000 person-years. The IRR was 1.27 (95% CI 1.20-1.34, p < 0.001) for the comparison of 2015 and 2010 rates. For gonorrhoea, overall rates ranged from 0.92 to 1.86 cases per 10,000 person-years. The IRR for gonorrhoea was 2.02 (95% CI 1.56-2.59, p < 0.001) for 2015 and 2010 rates. In our large population-based study spanning six years, we observed increasing rates of C. trachomatis and N. gonorrhoeae with low testing rates.

Remote transient Lactobacillus animalis bacteremia causing prosthetic hip joint infection: a case report.

BACKGROUND: Lactobacillus spp. are uncommon pathogens in immunocompetent hosts, and even rarer causes of prosthetic device infections. CASE PRESENTATION: A case of chronic hip prosthetic joint infection (PJI) caused by L. animalis is described. This occurred 5 years after a transient bacteremia with the same organism. Whole genome sequencing of both isolates proved this PJI infection resulted from this remote bacteremia. CONCLUSIONS: We document that prosthetic joint infections may be a consequence of bacteremia as much as 3 years before the onset of symptoms.

Human infections due to Staphylococcus pseudintermedius, an emerging zoonosis of canine origin: report of 24 cases.

BACKGROUND: Staphylococcus pseudintermedius has been recently identified as a novel species within the genus Staphylococcus, and is commonly associated with infections in dogs. Currently, there are few reports of human infections due to this bacterium. OBJECTIVE: To use a population-based approach to describe the characteristics of human S. pseudintermedius infections in a large Canadian healthcare region. METHODS: All adult cases aged ≥18 years identified at a large regional laboratory from April 1, 2013 to April 1, 2015 who had at least one positive culture for S. pseudintermedius were retrospectively reviewed. A combination of phenotypic methods, mass spectrometry (i.e., MALDI-TOF), and cpn60 sequencing were used to identify S. pseudintermedius. Chart review was conducted, and cases were analysed descriptively. RESULTS: Twenty-seven isolates of S. pseudintermedius from 24 human cases were included for analysis. 58.3% were male with median age of 61 years (IQR 55-70.5). Most patients [22 (92.1%)] had confirmed contact with dogs at time of infection. S. pseudintermedius was isolated in 18 cases (75.0%) of skin and soft tissue infections (SSTI), and 2 invasive cases (8.3%) including a prosthetic joint and bloodstream infection. The other 4 patients were considered to be colonized (skin - 3; lung - 1). Methicillin resistance was identified in 3 cases with 6 total isolates (22.2%); multi-drug resistance was also demonstrated commonly. CONCLUSION: S. pseudintermedius is most commonly associated with SSTIs in humans. Transmission probably occurs from a pet dog. Species-level identification of S. pseudintermedius is important due to the high prevalence of antibiotic resistance, particularly to methicillin.

Development and Validation of a PCR Assay To Detect the Prairie Epidemic Strain of Pseudomonas aeruginosa from Patients with Cystic Fibrosis.

The monitoring of epidemic Pseudomonas aeruginosa is important for cystic fibrosis (CF) infection control. The prairie epidemic strain (PES) is common in western Canadian CF clinics. Using whole-genome sequencing, we identified a novel genomic island and developed a PCR assay for PES. Against a collection of 186 P. aeruginosa isolates, the assay had 98% sensitivity and 100% specificity.

Infection control knowledge, beliefs and behaviours amongst cystic fibrosis patients with epidemic Pseudomonas aeruginosa.

BACKGROUND: Epidemic P. aeruginosa (ePA) infections are common in cystic fibrosis (CF) and have been associated with accelerated clinical decline. Factors associated with ePA are unclear, and evidence based infection control interventions are lacking. METHODS: We prospectively collect all bacterial pathogens from adult CF patients. We performed PA strain typing on retrospectively collected enrollment samples and recent isolates to identify patients infected with ePA. All patients attending our clinic were approached to complete a survey on infection control knowledge, beliefs and exposures. We analyzed responses of those with ePA relative to the entire cohort without ePA as well as those infected with unique strains of P. aeruginosa to assess for risk factors for ePA and differences in infection control knowledge, beliefs or behaviours. RESULTS: Of 144 participants, 30 patients had ePA (two Liverpool epidemic strain, 28 Prairie epidemic strain), 83 % of which had established infection prior to transition to the adult clinic. Risk of concomitant infecting pathogens was no different between groups although, Staphylococcus aureus and non-tuberculous mycobacteria were less common in those with ePA. Patients with ePA were more likely to have attended CF-camp and have a history of CF fundraising. Patients with ePA did not differ with respect to beliefs regarding pathogens or transmission risk, except they believed indirect contact posed little risk. Furthermore, patients with ePA were more likely to continue to associate with others with CF despite extensive counselling. Use of peer-peer online networking was minimal in both groups. CONCLUSION: Infections with ePA are closely linked to past exposures, now routinely discouraged. As socialization is the greatest risk factor for ePA, infection control strategies for ePA must focus on discouraging face-to-face interactions amongst CF patients. As peer support remains a desire amongst patients, investment in technologies and strategies that enable indirect communication and support are required.