Evaluation of vancomycin MIC creep in methicillin-resistant Staphylococcus aureus infections—a systematic review and meta-analysis

ObjectivesVancomycin is currently the primary option treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing number of MRSA isolates with high MICs, within the susceptible range (vancomycin MIC creep), are being reported worldwide. Resorting to a meta-analysis approach, this study aims to assess the evidence of vancomycin MIC creep.MethodsWe searched for studies in the PubMed database. The inclusion criteria for study eligibility included the possibility of retrieving the reported data values of vancomycin MIC and information concerning the applied MIC methodology.ResultsThe mean values of vancomycin MICs, of all 29 234 S. aureus isolates reported in the 55 studies included in the meta-analysis, were 1.23 mg/L (95% CI 1.13–1.33) and 1.20 mg/L (95% CI 1.13–1.28) determined by Etest and broth microdilution method, respectively. No significant differences were observed between these two methodologies. We found negative correlation between pooled mean/pooled proportion and time strata.ConclusionsWe have found no evidence of the MIC creep phenomenon.     

Etiology,clinical features,management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review

PurposeThis study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA).MethodsWe reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0–18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs.ResultsA total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0–1 month (OR, 6.52; 95% CI 1.09–38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004–6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P < 0.001).ConclusionS. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.     

Relationship between pathogenic,clinical, and virulence factors of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> in infective endocarditis versus uncomplicated bacteremia: a case–control study

Pathogenic factors of Staphylococcus aureus (SA) in the development of infective endocarditis (IE) have not been sufficiently investigated. The purpose of this study was to analyze the pathogenesis and virulence factors of SA in patients with IE as compared to patients with uncomplicated bacteremia (un-BAC). This is a retrospective case–control study (2002–2014) performed at a tertiary hospital in Spain. Clinical and epidemiological factors were analyzed. We assessed the presence of toxin genes [toxic shock syndrome toxin 1 (tst-1) and enterotoxins A (etA), B (etB), and D (etD)] and the potential relationship between accessory gene regulator (agr) groups and the development of IE confirmed by polymerase chain reaction (PCR). Twenty-nine patients with IE were compared with 58 patients with uncomplicated S. aureus bacteremia (SAB). As many as 75.9 % of patients had community-acquired IE (p?<?0.005). Multivariate analysis revealed that there is a significant relationship between community-acquired infection and severe sepsis or septic shock and IE. Also, a minimum inhibitory concentration (MIC) of vancomycin?≥1.5 μg/ml was found to be associated with IE. The agr group I was prevalent (55.2 % vs. 31.0 %; p?=?0.030). No association was observed between toxin genes (tst-1, etA, etB, and etD) and IE. The superantigen (SAg) most frequently found in SA isolates was tst-1 (12.6 %). We found no association between toxin genes and IE, probably due to the small sample size. However, a direct relationship was found between agr I and the development of IE, which suggests that agr I strains may have more potential to cause IE.     

Factors associated with local invasion in infective endocarditis: a nested case–control study

ObjectiveA substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients.MethodsThis was a nested case–control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model.ResultsAmong 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55–11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36–6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60–9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87–7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42–24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13–3.04) were associated with local invasion.DiscussionIntracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE.     

Panton-Valentine leukocidin–positive Staphylococcus aureus in skin and soft tissue infections from primary care patients

ObjectivesTo characterize deep skin and soft tissue infections (dSSTI) caused by Panton-Valentine leukocidin (PVL)-positive versus PVL-negative Staphylococcus aureus isolates.MethodsWe performed a retrospective analysis of patients' records including S. aureus isolates from outpatients with dSSTI. Samples had been submitted by primary care physicians, i.e. general practitioners, surgeons, dermatologists and paediatricians, located in Berlin, Germany, in 2007–2017. Bacterial isolates were identified and tested for antimicrobial susceptibility by VITEK 2; PVL was detected by PCR.ResultsIn total, 1199 S. aureus isolates from 1074 patients with dSSTI were identified, and 613 (51.1%) of 1199 samples were PVL⁺. The median age of patients with PVL⁺ S. aureus was lower than in patients with PVL− S. aureus (34 years, range 0–88 years, vs. 44 years, range 0–98 years; p < 0.0001). PVL was associated with repeated/multiple samples compared to single sample submission (69/92, 75% vs. 448/982, 45.6%, p < 0.0001; odds ratio (OR), 3.6; 95% confidence interval (CI), 2.2–5.8). Interestingly, the highest PVL positivity rate was found in isolates from gluteal (82/108, 75.9%; OR, 3.6; 95% CI, 2–5) or axillary (76/123, 61.8%; OR, 2; 95% CI, 1.1–3.3) localizations compared to isolates from the arm. The PVL positivity rate did not increase over time. Yet we noticed an increase in the trimethoprim/sulfamethoxazole (SXT) resistance rate in PVL⁺ isolates, mainly methicillin-sensitive S. aureus, when considering SXT resistance rates of 2007–2012 versus 2013–2017 (35/226, 15.5% vs. 74/289, 25.6%; p 0.01).ConclusionsIn outpatients, gluteal and axillary dSSTI are indicative of PVL⁺ S. aureus. Providing SXT as a complementary treatment for dSSTI should be based on susceptibility testing.     

Microbiological features,clinical characteristics and outcomes of infective endocarditis in adults with and without hemodialysis: A 10-year retrospective study in Northern Taiwan

Background/purposesInfective endocarditis (IE) is an important cause of morbidity and mortality in hemodialysis (HD) patients. Data on the differences in the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE are limited.MethodsMedical records of patients (aged over 20 years) with IE were retrospectively reviewed from January 2008 to June 2017 in a tertiary care center in Northern Taiwan. Those with definite or possible IE were included in the study. The clinical characteristics, microbiological results, echocardiographic findings and outcomes of patients were analyzed.ResultsOf the 183 patients with definite or possible IE, 47 had undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson comorbidity index, 8.17 vs. 4.21, p < 0.001), diabetes mellitus (68.1% vs. 35.3%, p < 0.001), and hypertension (85.1% vs. 53.7%, p < 0.001) were commonly observed in HD patients than in non-HD patients. The yield rate of the blood cultures was higher in HD group than in non-HD group (89.4% vs. 72.8%, p = 0.02). The proportion of methicillin-resistant Staphylococcus aureus was significantly higher in HD group than in non-HD group (31.9% vs. 5.9%, p < 0.001). HD patients versus non-HD patients had higher cardiac complication rates (38.3% vs. 14%, p < 0.001).ConclusionAdvanced age, sex (female), comorbidities, diabetes mellitus, and hypertension were more common in HD patients than in non-HD patients with IE. HD patients had higher proportion of methicillin-resistant S. aureus and cardiac complication rates than non-HD patients with IE. Culture-negative IE was more common in non-HD patients.     

In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections

ObjectivesMortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections.MethodsIsolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 10⁵ CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes.ResultsThe sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25).ConclusionsIn vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.     

Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis

BackgroundPrecise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies.ObjectivesWe performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time.Data sourcesThe MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021.Study eligibility criteriaHuman observational studies on patients with S. aureus bloodstream infection were included.ParticipantsThe study analyzed data of patients with a positive blood culture for S. aureus.MethodsTwo independent reviewers extracted study data and assessed risk of bias using the Newcastle–Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates.ResultsA total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%–12.1%) at 7 days, 13.3% (95% CI, 11.1%–15.8%) at 2 weeks, 18.1% (95% CI, 16.3%–20.0%) at 1 month, 27.0% (95% CI, 21.5%–33.3%) at 3 months, and 30.2% (95% CI, 22.4%–39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02–1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75–1.03 for 2001–2010; aOR: 0.82; 95% CI, 0.69–0.97 for 2011 onward).ConclusionsSAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.     

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection

ObjectivesTo assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients.MethodsSingle-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004–2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk.ResultsOf 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15–9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32–18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74–7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64–28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04–5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15–15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87–17.67), haematological malignancy (OR 3.44; 95% CI 1.07–10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42–10.22) and quinolones (OR 3.97; 95% CI 1.37–11.48), corticosteroids (OR 2.92; 95% CI 1.15–7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58–15.05) and β-lactam other than ertapenem (OR 4.51; 95% CI 1.45–14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI.ConclusionsA simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.     

Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates

An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.     

The level of thymic stromal lymphopoietin and its gene polymorphism are associated with rheumatoid arthritis

ObjectiveTo study the correlation between TSLP gene SNPs and RA in a Han Chinese population.MethodsThe genotypes of TSLP genes rs11466749, rs11466750 and rs10073816 among 197 RA patients and 197 controls were analysed by direct sequencing. ELISA was used to detect the plasma TSLP level. Logistic regression analysis was also conducted to identify risk factors for RA.ResultsThe rs11466749 locus GG genotype (OR = 5.30, 95% CI: 1.76–15.95, P < 0.01), dominant model (OR = 1.68, 95% CI: 1.03–2.73, P = 0.04), recessive model (OR = 5.15, 95% CI: 1.72–15.43, P < 0.01), and G allele (OR = 2.02, 95% CI: 1.33–3.09, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus AA genotype (OR = 4.58, 95% CI: 1.49–14.01, P < 0.01), dominant model (OR = 1.75, 95% CI: 1.09–2.79, P = 0.03), recessive model (OR = 4.27, 95% CI: 1.40–13.00, P = 0.03) and A allele (OR = 1.94, 95% CI: 1.29–2.91, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus GA genotype (OR = 0.29, 95% CI: 0.18–0.45, P < 0.01), dominant model (OR = 0.32, 95% CI: 0.21–0.49, P < 0.01) and A allele (OR = 0.45, 95% CI: 0.32–0.63, P < 0.01) were related to a decreased risk of RA susceptibility. The rs1466749 locus GG genotype, rs11466750 AA genotype, and rs10073816 GG genotype were independent risk factors for RA (P < 0.05). The AUC of plasma TSLP level in the diagnosis of RA was 0.8661 (95% CI: 0.8301–0.9002, P < 0.001). There were statistically significant differences in plasma TSLP levels among subjects with different genotypes at rs11466749, rs11466750, and rs10073816 in the TSLP gene (P < 0.05).ConclusionPlasma TSLP levels are a potential molecular marker of RA. SNPs at rs11466749, rs11466750 and rs10073816 of the TSLP gene are related to the susceptibility of the Han Chinese population to RA.     

Community-acquired bacterial meningitis in adults: in-hospital prognosis,long-term disability and determinants of outcome in a multicentre prospective cohort

ObjectivesTo identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM).MethodsIn a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed.ResultsAmong the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93–11.15), male gender (aOR 2.11; 95% CI 1.25–3.57), chronic renal failure (aOR 6.65; 95% CI 1.57–28.12), purpura fulminans (aOR 4.37; 95% CI 1.38–13.81), localized neurological signs (aOR 3.72; 95% CI 2.29–6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16–8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/μL (aOR 2.40; 95% CI 1.42–4.03), CSF glucose concentration (0.1–2.5 g/L: aOR 1.92; 95% CI 1.01–3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01–4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03–1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32–6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98–12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68–12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001).ConclusionsThe burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis.ClinicalTrialGov identification number: NCT01730690.     

Repeat endocarditis: analysis of risk factors based on the International Collaboration on Endocarditis – Prospective Cohort Study

Repeat episodes of infective endocarditis (IE) can occur in patients who survive an initial episode. We analysed risk factors and 1-year mortality of patients with repeat IE. We considered 1874 patients enrolled in the International Collaboration on Endocarditis – Prospective Cohort Study between January 2000 and December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year follow-up. Multivariable analysis was used to determine risk factors for repeat IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single-episode IE and 91 (4.8%) had repeat IE: 74/91 (81%) with new infection and 17/91 (19%) with presumed relapse. On bivariate analysis, repeat IE was associated with haemodialysis (p 0.002), HIV (p 0.009), injection drug use (IDU) (p < 0.001), Staphylococcus aureus IE (p 0.003), healthcare acquisition (p 0.006) and previous IE before ICE enrolment (p 0.001). On adjusted analysis, independent risk factors were haemodialysis (OR, 2.5; 95% CI, 1.2–5.3), IDU (OR, 2.9; 95% CI, 1.6–5.4), previous IE (OR, 2.8; 95% CI, 1.5–5.1) and living in the North American region (OR, 1.9; 95% CI, 1.1–3.4). Patients with repeat IE had higher 1-year mortality than those with single-episode IE (p 0.003). Repeat IE is associated with IDU, previous IE and haemodialysis. Clinicians should be aware of these risk factors in order to recognize patients who are at risk of repeat IE.     

Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis

ObjectivesPatients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems.MethodsThis retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores.ResultsA total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7–10.6) hours compared to those without, at 13.3 (10.5–16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91–100) and specificity of 52% (95% CI, 47–57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76–99) and a specificity of 70% (95% CI, 66–74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA.ConclusionsTTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors.     

Molecular epidemiology of the nasal colonization by methicillin-susceptible Staphylococcus aureus in Swiss children

Nasal carriage of Staphylococcus aureus contributes to an increased risk of developing an infection with the same bacterial strain. Genetic regulatory elements and toxin-expressing genes are virulence factors associated with the pathogenic potential of S. aureus. We undertook an extensive molecular characterization of methicillin-susceptible S. aureus (MSSA) carried by children. MSSA were recovered from the nostrils of children. The presence of Panton-Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic-shock staphylococcal toxin (TSST-1) and agr group typing were determined by quantitative PCR. A multiple-locus variable-number of tandem repeat analysis (MLVA) assay was also performed for genotyping. Five hundred and seventy-two strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0–100.8). MLVA analysis revealed a large diversity of genetic content and no clonal relationship was demonstrated among the analysed MSSA strains. Multilocus sequence typing confirmed this observation of diversity and identified ST45 as a frequent colonizer. This broad diversity in MSSA carriage strains suggests a limited selection pressure in our geographical area.     

Incidence and outcomes of infective endocarditis after transcatheter aortic valve implantation versus surgical aortic valve replacement

ObjectivesTranscatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in aortic stenosis (AS). Infective endocarditis (IE) in patients with prosthetic heart valves is associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after TAVI are conflicting. We evaluated these issues in patients with percutaneous TAVI vs. isolated surgical AVR (SAVR) at a nationwide level.MethodsBased on the administrative hospital discharge database, the study collected information for all patients with aortic stenosis treated with AVR in France between 2010 and 2018.ResultsA total of 47 553 patients undergoing TAVI and 60 253 patients undergoing isolated SAVR were identified. During a mean follow-up of 2.0 years (median (25th to 75th percentile) 1.2 (0.1–3.4) years), the incidence rates of IE were 1.89 (95% confidence interval (CI) 1.78–2.00) and 1.40 (95% CI 1.34–1.46) events per 100 person-years in unmatched TAVI and SAVR patients, respectively. In 32 582 propensity-matched patients (16 291 with TAVI and 16 291 with SAVR), risk of IE was not different in patients treated with TAVI vs. SAVR (incidence rates of IE 1.86 (95% CI 1.70–2.04) %/year vs 1.71 (95% CI 1.58–1.85) %/year respectively, relative risk (RR) 1.09, 95% CI 0.96–1.23). In these matched patients, total mortality was higher in TAVI patients with IE (43.0% 95% CI 37.3–49.3) than in SAVR patients with IE (32.8% 95% CI 28.6–37.3; RR 1.32, 95% CI 1.08–1.60).DiscussionIn a nationwide cohort of patients with AS, treatment with TAVI was associated with a risk of IE similar to that following SAVR. Mortality was higher for patients with IE following TAVI than for those with IE following SAVR.     

Timing of antibiotics in septic patients: a prospective cohort study

ObjectivesTo evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition.MethodsThis prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality.ResultsOf 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093–1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034–1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027–1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027–1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013–1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates.ConclusionsTime to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.     

Obesity,diabetes, hypertension and severe outcomes among inpatients with coronavirus disease 2019: a nationwide study

ObjectivesInitial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death.MethodsAll French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account.ResultsA total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9–2.1 and aOR 1.5, 95% CI 1.4–1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0–2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8–3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5–18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1–1.2) and diabetes (aOR 1.2, 95% CI 1.1–1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8–2.0), diabetes (aOR 1.4, 95% CI 1.3–1.4) and hypertension (aOR 1.7, 95% CI 1.6–1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3–3.7), diabetes (aOR 2.0, 95% CI 1.8–2.1) and hypertension (aOR 2.5, 95% CI 2.4–2.6).ConclusionsAmong 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.     

High incidence of acquiring methicillin-resistant Staphylococcus aureus in Brazilian children with Atopic Dermatitis and associated risk factors

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) colonization in Atopic Dermatitis (AD) patients can contribute to worsening their clinical condition.ObjectiveA cohort study was carried out to determine the incidence of MRSA acquisition and its risk factors in AD children.MethodsPatients with AD (2 months–14 years old) were followed up for about 1 year at a reference center for AD treatment in Rio de Janeiro, Brazil, from September 2011 to February 2014. Nasal swabs from patients and contacts were collected every 2 months. The SCORAD system assessed the severity of the AD. S. aureus isolates were evaluated to determine the methicillin resistance and the clonal lineages.ResultsAmong 117 AD patients, 97 (82.9%) were already colonized with S. aureus and 26 (22.2%) had MRSA at the first evaluation. The incidence of MRSA acquisition in the cohort study was 27.47% (n = 25). The SCORAD assessments were: mild (46.15%), moderate (37.36%) or severe (16.48%). Risk factors were: colonized MRSA contacts (HR = 2.27; 95% CI: 1.16–7.54), use of cyclosporine (HR = 5.84; 95% CI: 1.70–19.98), moderate or severe AD (HR = 3.26; 95% CI: 1.13–9.37). Protective factors were: availability of running water (HR = 0.21; 95% CI: 0.049–0.96) and use of antihistamines (HR = 0.21; 95% IC: 0.64–0.75). MRSA isolates carried the SCCmec type IV and most of them were typed as USA800/ST5.ConclusionsThe high incidence of MRSA acquisition found among AD patients and the risk factors associated show that an effective surveillance of MRSA colonization in these patients is needed.     

Clinical outcome and predictors of mortality in children with sepsis,severe sepsis,and septic shock from Rohtak,Haryana: A prospective observational study

Background:

Information regarding early predictive factors for mortality and morbidity in sepsis is limited from developing countries.

Methods:

A prospective observational study was conducted to determine the clinical outcome and predictors of mortality in children with sepsis, severe sepsis, and septic shock. Children aged 1 month to 14 years admitted to a tertiary care pediatric intensive care unit (PICU) with a diagnosis of sepsis, severe sepsis, or septic shock were enrolled in the study. Hemodynamic and laboratory parameters which discriminate survivors from nonsurvivors were evaluated.

Results:

A total of 50 patients (30 [60%] males) were enrolled in the study, of whom 21 (42%) were discharged (survivors) and rest 29 (58%) expired (nonsurvivor). Median (interquartile range) age of enrolled patients were 18 (6, 60) months. Mortality was not significantly predicted individually by any factor including age (odds ratio [OR] [95% confidence interval [CI]]: 0.96 [0.91-1.01], P = 0.17), duration of PICU stay (OR [95% CI]: 1.18 [0.99-1.25], P = 0.054), time lag to PICU transfer (OR [95% CI]: 1.02 [0.93-1.12], P = 0.63), Pediatric Risk of Mortality (PRISM) score at admission (OR [95% CI]: 0.71 [0.47-1.04], P = 0.07) and number of organ dysfunction (OR [95% CI]: 0.03 [0.01-1.53], P = 0.08).

Conclusion:

Mortality among children with sepsis, severe sepsis, and septic shock were not predicted by any individual factors including the time lag to PICU transfer, duration of PICU stay, presence of multiorgan dysfunction, and PRISM score at admission.