Postoperative Staphylococcus aureus Infections in Patients With and Without Preoperative Colonization.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. Exposure: Preoperative S aureus colonization. Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia.

BACKGROUND: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). METHODS: We performed a nested case-control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and-in cases-on the day of pneumonia diagnosis. RESULTS: Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n = 632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (< 5 days, n = 105) or late (> 10 days, n = 68) after ICU admission. CONCLUSIONS: Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02413242, posted April 9th, 2015.

Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial.

OBJECTIVES: To determine the susceptibility profiles and the resistome of Pseudomonas aeruginosa isolates from European ICUs during a prospective cohort study (ASPIRE-ICU). METHODS: 723 isolates from respiratory samples or perianal swabs of 402 patients from 29 sites in 11 countries were studied. MICs of 12 antibiotics were determined by broth microdilution. Horizontally acquired ß-lactamases were analysed through phenotypic and genetic assays. The first respiratory isolates from 105 patients providing such samples were analysed through WGS, including the analysis of the resistome and a previously defined genotypic resistance score. Spontaneous mutant frequencies and the genetic basis of hypermutation were assessed. RESULTS: All agents except colistin showed resistance rates above 20%, including ceftolozane/tazobactam and ceftazidime/avibactam. 24.9% of the isolates were XDR, with a wide intercountry variation (0%-62.5%). 13.2% of the isolates were classified as DTR (difficult-to-treat resistance). 21.4% of the isolates produced ESBLs (mostly PER-1) or carbapenemases (mostly NDM-1, VIM-1/2 and GES-5). WGS showed that these determinants were linked to high-risk clones (particularly ST235 and ST654). WGS revealed a wide repertoire of mutation-driven resistance mechanisms, with multiple lineage-specific mutations. The most frequently mutated genes were gyrA, parC, oprD, mexZ, nalD and parS, but only two of the isolates were hypermutable. Finally, a good accuracy of the genotypic score to predict susceptibility (91%-100%) and resistance (94%-100%) was documented. CONCLUSIONS: An overall high prevalence of resistance is documented European ICUs, but with a wide intercountry variability determined by the dissemination of XDR high-risk clones, arguing for the need to reinforce infection control measures.

Association of Staphylococcus aureus Colonization and Pneumonia in the Intensive Care Unit.

Importance: Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective: To quantify associations of patient-related and contextual factors, including S aureus colonization status, with the occurrence of SAIP. Design, Setting, and Participants: This cohort study was conducted in ICUs of 30 hospitals in 11 European countries, geographically spread across 4 regions. Among patients with an anticipated length of stay 48 hours or longer who were undergoing mechanical ventilation at ICU admission, S aureus colonization was ascertained in the nose and lower respiratory tract. From this group, S aureus-colonized and noncolonized patients were enrolled into the study cohort in a 1:1 ratio. Data analysis was performed from May to November 2019. Main Outcomes and Measures: SAIP was defined as any pneumonia during the ICU stay developing 48 hours or more after ICU admission with S aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account. Weighted risk factor analysis was performed using Cox multivariable regression. Results: The study cohort consisted of 1933 patients (mean [SD] age, 62.0 [16.0] years); 1252 patients (64.8%) were men, and 950 patients (49.1%) were S aureus carriers at ICU admission. In all, 304 patients (15.7%) developed ICU-acquired pneumonia, of whom 131 patients (6.8%) had SAIP. Weighted SAIP incidences were 11.7 events per 1000 patient-days in the ICU for S aureus-colonized patients and 2.9 events per 1000 patient-days in the ICU for noncolonized patients (overall incidence, 4.9 events per 1000 patient-days in the ICU). The only factor independently associated with SAIP was S aureus colonization status at ICU admission (cause-specific hazard ratio, 3.6; 95% CI, 2.2-6.0; P < .001). There were marked regional differences in SAIP incidence and cause-specific hazard ratios for colonization status. Conclusions and Relevance: SAIP incidence was 4.9 events per 1000 ICU patient-days for patients undergoing mechanical ventilation at ICU admission (or shortly thereafter). The daily risk of SAIP was 3.6 times higher in patients colonized with S aureus at ICU admission compared with noncolonized patients.

Risk prediction for Staphylococcus aureus surgical site infection following cardiothoracic surgery; A secondary analysis of the V710-P003 trial.

BACKGROUND: Identifying patients undergoing cardiothoracic surgery at high risk of Staphylococcus aureus surgical site infection (SSI) is a prerequisite for implementing effective preventive interventions. The objective of this study was to develop a risk prediction model for S. aureus SSI or bacteremia after cardiothoracic surgery based on pre-operative variables. MATERIALS/METHODS: Data from the Merck Phase IIb/III S. aureus vaccine (V710-P003) clinical trial were analyzed. In this randomized placebo-controlled trial, the effect of preoperative vaccination against S. aureus was investigated in patients undergoing cardiothoracic surgery. The primary outcome was deep/superficial S. aureus SSI or S. aureus bacteremia through day 90 after surgery. Performance, calibration, and discrimination of the final model were assessed. RESULTS: Overall 164 out of 7,647 included patients (2.1%) developed S. aureus infection (149 SSI, 15 bacteremia, 28 both). Independent risk factors for developing the primary outcome were pre-operative colonization with S. aureus (OR 3.08, 95% confidence interval [CI] 2.23-4.22), diabetes mellitus (OR 1.87, 95% CI 1.34-2.60), BMI (OR 1.02 per kg/m2, 95% CI 0.99-1.05), and CABG (OR 2.67, 95% CI 1.91-3.78). Although vaccination had a significant (albeit modest) protective effect, it was omitted from the model because its addition did not significantly change the coefficients of the final model and V710-vaccine development has been discontinued due to insufficient efficacy. The final prediction model had moderate discriminative accuracy (AUC-value, 0.72). CONCLUSION: Pre-operative S. aureus colonization status, diabetes mellitus, BMI, and type of surgical procedure moderately predicted the risk of S. aureus SSI and/or bacteremia among patients undergoing cardiothoracic surgery.

Rationale and design of ASPIRE-ICU: a prospective cohort study on the incidence and predictors of Staphylococcus aureus and Pseudomonas aeruginosa pneumonia in the ICU.

BACKGROUND: The epidemiology of ICU pneumonia caused by Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) is not fully described, but is urgently needed to support the development of effective interventions. The objective of this study is to estimate the incidence of S. aureus and P. aeruginosa ICU pneumonia and to assess its association with patient-related and contextual risk factors. METHODS: ASPIRE-ICU is a prospective, observational, multi-center cohort study nested within routine surveillance among ICU patients in Europe describing the occurrence of S. aureus and P. aeruginosa ICU pneumonia. Two thousand (2000) study cohort subjects will be enrolled (50% S. aureus colonized) in which specimens and data will be collected. Study cohort subjects will be enrolled from a larger surveillance population, in which basic surveillance data is captured. The primary outcomes are the incidence of S. aureus ICU acquired pneumonia and the incidence of P. aeruginosa ICU acquired pneumonia through ICU stay. The analysis will include advanced survival techniques (competing risks and multistate models) for each event separately as well as for the sub-distribution of ICU pneumonia to determine independent association of outcomes with risk factors.. A risk prediction model will be developed to quantify the risk for acquiring S. aureus or P. aeruginosa ICU pneumonia during ICU stay by using a composite score of independent risk factors. DISCUSSION: The diagnosis of pathogen-specific ICU pneumonia is difficult, however, the criteria used in this study are objective and comparable to those in the literature. TRIAL REGISTRATION: This study is registered on clinicaltrials.gov under identifier NCT02413242 .

P. aeruginosa colonization at ICU admission as a risk factor for developing P. aeruginosa ICU pneumonia.

OBJECTIVE: To determine the incidence of P. aeruginosa (PA) ICU pneumonia and its independent association with PA colonization at ICU admission. METHODS: This was a post-hoc analysis of a prospectively collected cohort study. Adult ICU patients with a length of stay of ≥48 h were included and assessed for microbiologically confirmed PA ICU pneumonia. Multivariate survival analysis was performed, including the covariates age, gender, PA colonization at ICU admission, ICU admission specialty and mechanical ventilation at ICU admission, while taking into account the effect of competing risks. RESULTS: We included 5093 patients, 2447 (48%) were tested for colonization; of those 226 (9.2%) were PA colonized at ICU admission. The incidence of PA ICU pneumonia was 1.34% (n = 68). PA colonization was an independent risk factor (subdistribution hazard ratio [SHR] 8.8; 95% confidence interval [CI] 4.9-15.7), as was mechanical ventilation (SHR 5.3, 95% CI 2.7-10.6). CONCLUSION: In this study the incidence of P. aeruginosa ICU pneumonia was 1.34%. Hazard ratios for PA colonized patients compared to non-colonized to develop PA ICU pneumonia were 8.8. The high risk associated with P. aeruginosa colonization for subsequent infection may offer a target for future interventions.

The scrutiny of identifying community-acquired pneumonia episodes quantified bias in absolute effect estimation in a population-based pneumococcal vaccination trial.

OBJECTIVES: To determine the accurateness of detecting community-acquired pneumonia (CAP) in the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a community-based, double-blind, randomized placebo-controlled trial in which the needed to treat (NNT) for prevention of vaccine-type pneumococcal CAP was 1,007 [95% confidence interval (CI): 613, 2,646]. STUDY DESIGN AND SETTING: Study participants developing pneumonia were identified in 58 participating hospitals by research nurses (RNs) using local-adapted protocols. In addition, general practitioner (GP) records were screened for hospital referrals for suspected pneumonia. Two independent reviewers determined reasons for not identifying pneumonia episodes, and the NNT adjusted for missed episodes was estimated. RESULTS: Of 2,183 hospital referrals with suspected pneumonia detected in GP records, 232 (11%) were admitted outside established screening routes and 102 (5%) were not suspected of pneumonia on admission. Of the remaining 1,849 episodes, 1,374 (63% of all episodes and 74% of identifiable episodes) were identified by RNs. Several causes of missing episodes were identified. After adjustment for missed episodes, the NNT reduced to 634 (95% CI: 386, 1,675). CONCLUSION: With the screening procedure, 63% of suspected pneumonia episodes were identified, and the estimated NNT reduced from 1,007 to 634. Root cause analysis of unidentified episodes provides guidance for improving pneumonia detection in future trials.