Abstract
Background
Vancomycin-resistant enterococci has increased globally in recent decades, with Enterococcus faecium (VREfm) being the most prevalent species. Although the prevalence of VREfm in ...Chile is high (∼70%), its molecular epidemiology is not well-described. Here, we used whole genome sequencing (WGS) to characterize the circulating lineages of VREfm in Chile.
VRE= Vancomycin resistant Enterococcus faecium, SD=Standard deviation, IQR=in˝ter-quartile range; ¥ comorbidities included diagnoses apart from the primary cause for admission such as hypertension, chronic kidney disease and coronary artery disease; *Chi-square or Fisher´s exact were used for categorial variables; T-test for continues variables; P value<0.05 was considered significant.•
Methods
A total of 96 invasive clinical VREfm isolates causing invasive infections were collected from 96 patients admitted to 3 hospitals in Chile as part of an ongoing surveillance program (2018 – 2022). Clinical data including demographics, source of infection, and hospital outcomes were collected. All isolates were subjected to WGS on an Illumina platform. After assembly, in silico MLST and resistome were determined. Further, 5 representative strains were sequenced with Oxford Nanopore Technology (ONT) to further characterize the location of the van gene cluster.
Results
The mean age of the cohort was 62 years, with 61% of males and a mean Charlson Comorbidity Score of 3. All isolates were resistant to vancomycin, ampicillin and ciprofloxacin and remained susceptible to linezolid. Resistance to teicoplanin (16%), high-level resistance to gentamicin (48%) and streptomycin (20%) was also observed. A total of 75 VREfm harbored vanB, with the most common STs being ST17 (23%) and ST656 (25%). Only 7 VREfm isolates carried vanA, 43% of which corresponded to ST17. Surprisingly, 14 VREfm simultaneously carried vanA and vanB (vanA/vanB), most of them belonging to ST233 (50%) or ST2137 (36%). For the VREfm vanA/vanB isolates, the vanB cluster was located on the chromosome, while the vanA gene cluster was harbored on a plasmid (ca. 45Mb) which also contained ermB. A summary of the clinical characteristics of the cohort is shown in Table 1.
Conclusion
vanB was the most frequently observed genotype in Chile, with ST17 and ST656 accounting for most isolates. Importantly, a substantial proportion of VREfm carried both vanA and vanB clusters in Chile, which was mainly observed in two different genomic lineages (ST233 and ST2137). Active surveillance of VREfm is essential to monitor the epidemiology of this critical pathogen in South America.
Disclosures
William R. Miller, M.D., Merck: Grant/Research Support|UpToDate: Honoraria
Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim ...to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile.
We used a large prospective national cohort of about two million children and adolescents 6–16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders.
The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6–16 years was 74.5% (95% CI, 73.8–75.2), 91.0% (95% CI, 87.8–93.4), 93.8% (95% CI, 87.8–93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6–11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7–76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5–87.3) for the prevention of hospitalisation.
Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6–16 years.
Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).
Background: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this ...study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6–16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6–16 years was 74.5% (95% CI, 73.8–75.2), 91.0% (95% CI, 87.8–93.4), 93.8% (95% CI, 87.8–93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6–11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7–76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5–87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6–16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 ...(33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.
Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model ...that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration MIC) in plasma and epithelial lining fluid against C/T-susceptible
. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-
considering the C/T MIC.
This was a multicenter retrospective study of 90 patients with LRI caused by resistant
who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.
The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with
strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%;
= .041). Multivariate analysis identified septic shock (
< .001), C/T MIC >2 mg/L (
= .045), and increasing Charlson Comorbidity Index (
= .019) as independent predictors of mortality.
The effectiveness of C/T in
LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.
Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors ...(ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with
bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with ...septic shock. The presence of solid tumors (33.3% vs. 20.2%,
< 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%;
< 0.001), pneumonia (38% vs. 19.2%
< 0.001), and infection due to multidrug-resistant
(MDRPA) (33.8% vs. 21.1%,
< 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%,
= 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%;
< 0.001), mechanical ventilation (49.1% vs. 5.6%;
< 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%,
< 0.001, and 74% vs. 23.1%,
< 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.
La infección por Bartonella henselae se presenta característicamente con adenopatías regionales y fiebre de intensidad variable, entidad conocida como “enfermedad por arañazo de gato”. Alrededor de 5 ...a 10% de los casos desarrolla compromiso ocular, entre los que destacan el síndrome óculo-glandular de Parinaud, la neuro-retinitis y la retino-coroiditis focal. A continuación se presentan dos pacientes con infección aguda por B. henselae y compromiso ocular. Ambos recibieron tratamiento y evolucionaron con recuperación completa de la visión.
Abstract
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKp) have become an increasing public health problem worldwide. While most CRKp around the world harbour a carbapenemase enzyme, the ...clinical relevance of non-carbapenemase-producing CRKp (non-CP-CRKp) is increasingly recognized. Selective digestive decontamination (SDD) has been proven successful as a decolonization strategy for patients colonized with Gram-negatives in the ICU. However, it is not regularly used to treat invasive infections.
Objectives
To report the use of SDD as a useful strategy for managing recalcitrant CRKp bloodstream infections.
Patients and methods
We present a neutropenic patient with a recalcitrant bloodstream infection with non-CP-CRKp treated with SDD. Besides, genomic analyses of five isolates of non-CP-CRKp was performed.
Results
After 11 days of SDD treatment with oral colistin and gentamicin, bacteraemia was successfully eradicated. Genomic analysis indicates a fully carbapenem-resistant phenotype evolved in vivo and suggests that the mechanism of carbapenem resistance in our strains relates to gene amplification of narrow-spectrum β-lactamases.
Conclusions
Our report highlights that SDD might be a useful strategy to manage CRKp bloodstream infections, when intestinal translocation is the likely source of the bacteraemia. In addition, the development of a resistant phenotype during therapy is worrisome as therapies directed against these organisms are likely to favour the amplification process.
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