Introduction: The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients. Methods: We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene. Results: One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers. Conclusions: Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.

Introduction: In patients with severe sepsis and septic shock as cause of Intensive Care Unit (ICU) admission, we analyze the impact on mortality of adequate antimicrobial therapy initiated before ICU admission. Methods: We conducted a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock from January 2008 to September 2013. The primary end-point was in-hospital mortality. We considered two groups for comparisons: patients who received adequate antibiotic treatment before or after the admission to the ICU. Results: A total of 926 septic patients were admitted to ICU, and 638 (68.8%) had available microbiological isolation: 444 (69.6%) received adequate empirical antimicrobial treatment prior to ICU and 194 (30.4%) after admission. Global hospital mortality in patients that received treatment before ICU admission, between 0-6h ICU, 6–12h ICU, 12–24h ICU and after 24 hours since ICU admission were 31.3, 53.2, 57.1, 50 and 50.8% (p<0.001). The multivariate analysis showed that urinary focus (odds ratio (OR) 0.20; 0.09–0.42; p<0.001) and adequate treatment prior to ICU admission (OR 0.37; 0.24–0.56; p<0.001) were protective factors whereas APACHE II score (OR 1.10; 1.07–1.14; p<0.001), septic shock (OR 2.47; 1.57–3.87; p<0.001), respiratory source (OR 1.91; 1.12–3.21; p=0.016), cirrhosis (OR 3.74; 1.60–8.76; p=0.002) and malignancy (OR 1.65; 1.02–2.70; p=0.042) were variables independently associated with in-hospital mortality. Adequate treatment prior to ICU was a protective factor for mortality in patients with severe sepsis (n=236) or in septic shock (n=402). Conclusions: The administration of adequate antimicrobial therapy before ICU admission is decisive for the survival of patients with severe sepsis and septic shock. Our efforts should be directed to assure the correct administration antibiotics before ICU admission in patients with sepsis.

A potent synergy of a glycopeptide-colistin combination against Acinetobacter baumannii has recently been described. We set out to assess the efficacy and safety of this combination in a retrospective study including episodes of ventilator-associated pneumonia or bacteremia caused by carbapenem-resistant A. baumannii. We compared 29 patients (group I) treated with colistin plus vancomycin with 28 patients treated with colistin alone (group II). Group I received vancomycin (for empirical or targeted therapy) at the onset of colistin administration and both antimicrobials coincided for at least 5 days. Baseline characteristics, clinical cure, microbiological eradication, and mortality were similar in both groups but the rate of acute kidney injury was higher in group I (55.2 vs. 28%; p = 0.04). In critically ill patients with carbapenem-resistant A. baumannii infections, clinical outcomes do not differ in patients treated with colistin plus vancomycin from those receiving colistin without vancomycin. This combination significantly increases the risk of renal failure.

Over the last decade, an exponential increase in bacterial resistance has been observed worldwide [ 1 x 1 Nicolas-Chanoine, MH, Blanco, J, Leflon-Guibout, V et al. Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15. J Antimicrob Chemother. 2008; 61: 273–281 Crossref | PubMed | Scopus (522) | Google Scholar See all References , 2 x 2 Talan, DA, Krishnadasan, A, Gorwitz, RJ et al. Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin Infect Dis. 2011; 53: 144–149 Crossref | PubMed | Scopus (179) | Google Scholar See all References , 3 x 3 Valencia, R, Arroyo, LA, Conde, M et al. Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect Control Hosp Epidemiol. 2009; 30: 257–263 Crossref | PubMed | Scopus (141) | Google Scholar See all References , 4 x 4 Yong, D, Toleman, MA, Giske, CG et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009; 53: 5046–5054 Crossref | PubMed | Scopus (1170) | Google Scholar See all References ]. No new antibacterial agents are expected to be on the market until 2018 at the earliest [ 5 x 5 Bartlett, JG. A call to arms: the imperative for antimicrobial stewardship. Clin Infect Dis. 2011; 53: S4–S7 Crossref | PubMed | Scopus (79) | Google Scholar See all References , 6 x 6 European Centre for Disease Prevention and Control EMA. ECDC/EMEA Joint Technical Report: the bacterial challenge: time to react. Available at: http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf; 2009. ((last accessed 27 February 2013).) Google Scholar See all References ]. Furthermore, the overall societal costs of antibiotic resistance were estimated to be 1.5 billion €/year in the European Union [ 6 x 6 European Centre for Disease Prevention and Control EMA. ECDC/EMEA Joint Technical Report: the bacterial challenge: time to react. Available at: http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf; 2009. ((last accessed 27 February 2013).) Google Scholar See all References 6 ]. Inappropriate use of antibiotics has been shown to be directly related to the increase of bacterial resistances [ 7 x 7 Livermore, DM. Minimising antibiotic resistance. Lancet Infect Dis. 2005; 5: 450–459 Abstract | Full Text | Full Text PDF | PubMed | Scopus (173) | Google Scholar See all References 7 ], as well as to significant increases in morbidity and mortality [ 8 x 8 Davey, PG and Marwick, C. Appropriate vs. inappropriate antimicrobial therapy. Clin Microbiol Infect. 2008; 14: 15–21 Abstract | Full Text | Full Text PDF | PubMed | Scopus (63) | Google Scholar See all References , 9 x 9 Kumar, A, Ellis, P, Arabi, Y et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009; 136: 1237–1248 Crossref | PubMed | Scopus (505) | Google Scholar See all References , 10 x 10 Garnacho-Montero, J, Ortiz-Leyba, C, Herrera-Melero, I et al. Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: a matched cohort study. J Antimicrob Chemother. 2008; 61: 436–441 Crossref | PubMed | Scopus (119) | Google Scholar See all References ]. It is widespread in most health centres, and up to 50% of antibiotic treatments prescribed have been estimated to be incorrect [ 11 x 11 Dellit, TH, Owens, RC, McGowan, JE et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 15: 44 Google Scholar See all References 11 ]. All clinicians are potential antimicrobial prescribers; therefore the generalization of antibiotic misuse is likely to be due to a misbalance between the high level of knowledge required for the appropriate use of antibiotics and the scarce training offered in this respect to the practising clinician.

The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins. Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT–PCR was used to determine the relative expression of genes encoding several efflux pumps and porins. Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan^® was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan^® was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan^®. Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan^® may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).