Microbiology of acute bacterial skin and skin-structure infections in Greece: A proposed clinical prediction score for the causative pathogen.

Although clinical definitions of acute bacterial skin and skin-structure infection (ABSSSI) are now well established, guidance of the prediction of likely pathogens based on evidence is missing. This was a large survey of the microbiology of ABSSSIs in Greece. During the period November 2014 to December 2016, all admissions for ABSSSI in 16 departments of internal medicine or surgery in Greece were screened to determine the likely bacterial aetiology. Samples were cultured on conventional media. Expression of the SA442, mecA/mecC and SCCmec-orfX junction genes was assessed. Following univariate and forward logistic regression analysis, clinical characteristics were used to develop scores to predict the likely pathogen with a target of 90% specificity. In total, 1027 patients were screened and 633 had positive microbiology. Monomicrobial infection by Gram-positive cocci occurred in 52.1% and by Gram-negative bacteria in 20.5%, and mixed infection by Gram-positive cocci and Gram-negative bacteria in 27.3%. The most common isolated pathogens were Staphylococcus aureus and coagulase-negative staphylococci. Resistance to methicillin was 57.3% (53.5-61.1%). Three predictive scores were developed: one for infection by methicillin-resistant S. aureus, incorporating recent hospitalisation, atrial fibrillation, residency in long-term care facility (LTCF) and stroke; one for mixed Gram-positive and Gram-negative infections, incorporating localisation of ABSSSI in lumbar area, fluoroquinolone intake in last 6 days, residency in LTCF and stroke; and another for Gram-negative infection, incorporating skin ulcer presentation, peptic ulcer and solid tumour malignancy. In conclusion, methicillin-resistant staphylococci are the main pathogens of ABSSSIs. The scores developed may help to predict the likely pathogen.

The level of endotoxemia in sepsis varies in relation to the underlying infection: Impact on final outcome.

Former studies of our group have shown that the innate and adaptive immune status may differ in relation with the causative infection. To this same end, it was investigated if kinetics of circulating lipopolysaccharide (LPS) leading to inflammatory response may differ. Blood was sampled from 189 patients with sepsis and 206 with severe sepsis/shock starting 24h from advent of sepsis and repeating on day 3. Serum LPS was measured by Limulus Amebocyte Lysate (LAL) assay. From 59 patients, circulating monocytes were isolated and incubated in the absence/presence of LPS. Concentrations of tumor necrosis factor-alpha (TNFα) were measured in supernatants by an enzyme immunoassay. In either category of severity, circulating LPS was greater among sufferers from primary Gram-negative bacteremia (BSI) and from community-acquired pneumonia (CAP) than sufferers from other underlying infections. LPS were greater among patients with BSI compared to patients with secondary Gram-negative bacteremia and patients without bacteremia. Greater decrease of circulating LPS over 48h was recorded for survivors compared to non-survivors only within sufferers from BSI and CAP. Significant endotoxemia was considered for patients with serum LPS within the upper quartile of distribution; their monocytes were less potent for release of TNFα. It is concluded that endotoxemia in sepsis varies greatly with the underlying infection; this is related with immunoparalysis of monocytes with implications on final outcome.

Polymicrobial bloodstream infections: Epidemiology and impact on mortality.

The aim of this study was to investigate the impact of polymicrobial bloodstream infections (pBSIs) on the outcome of sepsis in an area where antimicrobial resistance is of concern. This was a retrospective analysis of data collected prospectively from patients developing BSI outside of an intensive care unit (non-ICU patients) or after ICU admission. Demographics and clinical characteristics were compared for patients with pBSI versus monomicrobial BSI (mBSI) and following stratification by ICU or non-ICU and severity of sepsis status. Possible risk factors for adverse outcome were explored by multivariate analysis, and outcomes were measured by Cox regression analysis. Among 412 patients with BSI, 47 patients (11.4%) with pBSI were recorded; compared with patients with mBSI, they had significantly higher APACHE II scores and presented more frequently with severe sepsis/septic shock. The all-cause 28-day mortality was significantly higher for pBSI versus mBSI (38.3% vs. 24.7%; P=0.033), whereas appropriateness of treatment was comparable (78.7% vs. 86.6%). Primary bacteraemia by combinations of Enterococcus faecalis, Klebsiella pneumoniae and Acinetobacter baumannii was predominant among pBSIs; in mBSIs, urinary tract infections by Escherichia coli, K. pneumoniae or Pseudomonas aeruginosa predominated. Multivariate analysis demonstrated pBSI as a significant contributor to 28-day mortality (HR=1.86; P=0.039), along with presence of two or more co-morbidities (HR=2.35; P=0.004). In conclusion, pBSIs differed epidemiologically from mBSIs, with the emergence of enterococcal species, and portended an almost two-fold increased risk of 28-day mortality. Prospective studies are warranted to elucidate possibly modifiable factors.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

INTRODUCTION: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. RESULTS: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.