European Journal of Clinical Microbiology & Infectious Diseases

Diagnostic accuracy studies need more informative abstracts

What is the time-to-positivity of blood cultures in infective endocarditis?

Continuous infusion of ceftolozane/tazobactam is associated with a higher probability of target attainment in patients infected with Pseudomonas aeruginosa Abstract Ceftolozane/tazobactam (CTZ/TZ) exhibits time-dependent antimicrobial activity, and prolonged infusion can better achieve the pharmacodynamic target than an intermittent bolus. We aimed to compare the use of prolonged or continuous infusion with intermittent administration of CTZ/TZ for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. We performed a multicentric prospective cohort study to evaluate continuous, prolonged, or intermittent infusion of CTZ/TZ. We assessed the plasma concentration as a function of the duration of infusion and then performed a simulation of the percentage of patients who would reach the PK/PD targets, set at 100% ƒT> MIC or 100% ƒT>4 MIC. Seventy-two patients were enrolled with a median [IQR] age of 48.5 [32.4–63.2] years. Fifty-seven (79%) were hospitalized in an intensive care unit. Thirty-seven (51.4%) were immunosuppressed, and the in-hospital mortality rate was 15.2%. The major site of infection was the respiratory tract (66.7%). The PK/PD objectives (100% ƒT>4 MIC) were achieved for all patients infected with strains with CTZ/TZ MICs < 4 mg/L, regardless of the mode of administration. In contrast, intermittent bolus administration and prolonged infusion did not achieve the PK/PD objectives when the CTZ/TZ MICs were ≥ 4 mg/L. However, the PK/PD objectives (100% ƒT>4 MIC) were achieved for strains with MICs up to 8 mg/L in patients receiving continuous infusion of CTZ/TZ. A dosing regimen of 2 g/1 g CTZ/TZ administered every 8 h as a 1-h intravenous infusion, as currently recommended, did not provided adequate coverage to achieve a sufficient probability of target attainment for P. aeruginosa strains with MICs ≥ 4 mg/L.

Early transthoracic echocardiography has useful prognostic value in left-sided native valve endocarditis despite limited diagnostic performance Abstract To investigate the prognostic implications of findings on early transthoracic echocardiography (TTE) in patients with definite left-sided native valve infective endocarditis (LNVIE). We reviewed a 10-year retrospective cohort of consecutive patients with definite LNVIE treated at a tertiary cardiothoracic centre. TTE studies performed within the first seven days of the index blood culture (for culture-positive cases) or hospital admission (for culture-negative cases) were reviewed for the presence of valvular vegetations, perivalvular abscesses, aortic or mitral regurgitation of moderate or greater severity or a bicuspid aortic valve. Six-week outcomes included all-cause mortality, cardiac surgery for endocarditis or new embolic cerebral infarction. Early TTE was performed in 118 of 151 episodes of definite LNVIE at a median of two days after the index blood culture or hospital admission. Findings on these studies included valvular vegetations or abscesses in 74 patients, moderate or severe aortic or mitral regurgitation in 67 patients and a bicuspid aortic valve in 19 patients. The presence of any of these findings conferred a relative risk of any adverse six-week outcome of 4.80 (95% confidence interval 1.6–17, p = 0.001). The presence of a bicuspid aortic valve appeared particularly predictive of the need for cardiac surgery, including for clinically occult paravalvular abscesses. Early TTE can be used to stratify patients with LNVIE by the risk of major endocarditis-related adverse outcomes occurring within the first six weeks of treatment.

The use of a poster to reduce expectations to receive antibiotics for a common cold Abstract Many doctors prescribe antibiotics for a cold, to meet patient’s expectations. As a result, patient’s education about antibiotics and antibiotic resistance forms a major component of the WHO’s Global Action Plan on Antimicrobial Resistance. However, it is not known whether simple educational material can change a person’s attitudes about antibiotic therapy. We designed three posters about antibiotic treatment for “cold and flu”. Hospital inpatients answered a baseline survey and then were asked to look at one of three randomly selected posters. The posters highlighted the futility of antibiotic treatment for colds (futility), the risk of adverse drug reactions from antibiotics (harm), and the issue of antimicrobial resistance (resistance). Participants then completed a follow-up survey. Participants’ expectations to receive antibiotics for a “bad cold” reduced significantly after viewing a poster (82/299, 27% expected antibiotics in the baseline survey compared with 13% in the follow-up survey, P < 0.01). Continuing expectation to receive antibiotics after viewing one of the posters was associated with expectation to receive antibiotics in the baseline survey and the strong belief that colds were caused by bacteria. Participants who viewed the resistance poster were more likely to continue to expect antibiotics than participants who viewed the futility poster (OR 2.46, 95%CI 1.16–5.20, P = 0.02). Following discussion of the study, viewing a poster reduced participants’ expectations to receive antibiotics for a hypothetical cold. Changing patients’ expectations to receive antibiotics using simple educational material about antibiotic futility could lead to significant reductions in antibiotic prescription for viral upper respiratory tract infections.

Targeting gut microbiota as a possible therapy for mastitis Abstract Mastitis, a disease that affects both dairy herds and humans, is recognized as the most common source of losses in the dairy industry. Antibiotics have been used for years as the primary treatment for mastitis. However, abuse of antibiotics has led to the emergence of resistant strains and the presence of drug residues and has increased the difficulty of curing this disease. In addition, antibiotics kill most of the microbes that are present in the digestive tract, leading to imbalances in the gut microbiome and destruction of the ecosystem that is normally present in the gut. Gut microbiota play an important role in the host’s health and could be considered the “second brain” of the body. In recent years, the gut microbiota and their metabolites, including lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs), have been shown to participate in the development of mastitis. LPS is the main component of the cell walls of gram-negative bacteria. Overproduction of rumen-derived LPS injures the rumen epithelium, resulting in the entry of LPS into the blood and damaged liver function; once in the blood, it circulates into the mammary gland, increasing blood-barrier permeability and leading to mammary gland inflammation. SCFAs, which are produced by gut microbiota as fermentation products, have a protective effect on mammary gland inflammatory responses and help maintain the function of the blood-milk barrier. Recently, increasing attention has been focused on the use of probiotics as a promising alternative for the treatment of mastitis. This review summarizes the effects of the gut microbiome and its metabolites on mastitis as well as the current of probiotics in mastitis. This work may provide a valuable theoretical foundation for the development of fresh ideas for the prevention and treatment of mastitis.

Performance of a new combination of blood culture vials in sepsis detection: a 2-year retrospective comparison Abstract The diagnosis of bloodstream infection requires the optimum combination of media in an automated blood culture system for maximum recovery of pathogens with the earliest time to detection. In a previous work, we showed that for patients admitted to the Emergency Department of our hospital, the combination of BACTEC lytic anaerobic and BACTEC aerobic vials was more efficient than BACTEC anaerobic and BACTEC aerobic vial. In this study, we extended the work including a broader patient population, representative of all hospital. A total of 8629 cultures were collected during the pre-lytic phase, from 01 July 2013 to 30 June 2014 and 7940 cultures during the post-lytic phase, ranged from 01 July 2015 to 30 June 2016. The number of positive blood cultures was higher during the post-lytic phase (19.74%) than in the pre-lytic phase (17.52%), particularly for Escherichia coli, Staphylococcus spp., Enterococcus spp., and anaerobes. We also observed a significant decreased of the time to detection, with the mean and median in the post-lytic phase of 17.68 and 13.05 h compared with 19.49 and 14.47 h in the pre-lytic phase. Whereas the time to detection was the same for organisms recovered in the aerobic Plus bottles for both time periods, time to detection for the anaerobic lytic bottles was significantly faster than with the anaerobic Plus bottles. This study carried out on a long time observation reported that a simple modification of composition of blood culture set could lead to better results in bloodstream infection detection.

Cefazolin versus fluoroquinolones for the treatment of community-acquired urinary tract infections in hospitalized patients Abstract Literature for the treatment of hospitalized patients with community-acquired urinary tract infections (UTI) is limited. Previous outpatient studies do not support the use of oral beta-lactams compared with oral fluoroquinolones (FQ) due to poor clinical cure rates. However, recent studies evaluating intravenous (IV) beta-lactams in more complicated cases demonstrate promising cure rates. In addition, the use of more narrow-spectrum beta-lactams may be preferable when possible, due to a lower incidence of “collateral damage” compared with FQ. This was a retrospective, non-inferiority, single-center, cohort study evaluating the effectiveness of IV cefazolin compared with FQ for the treatment of community-acquired UTI in an inpatient setting. The primary endpoint was clinical failure, defined as the presence of one or more signs or symptoms of UTI that required a change in antibiotics, re-initiation of antibiotics for UTI treatment during the hospital stay, and re-hospitalization with a UTI diagnosis within 30 days after discharge. The secondary endpoints were a microbiological cure, hospital length of stay, inpatient antibiotic duration of treatment, emergence of resistance, and Clostridium difficile infection within 30 days of the end of antibiotic therapy. Overall, 73 patients were treated with either cefazolin (n = 43) or FQ (n = 30) between April 2015 to January 2016. The clinical failure rates were 2% and 7% in the cefazolin and FQ groups, respectively (p = 0.56). Additionally, there were no significant differences between the secondary endpoints. Treatment with cefazolin, a more narrow-spectrum agent with a potential for less “collateral damage,” was non-inferior to FQ for community-acquired UTI in an inpatient setting.

Distribution of carbapenem resistance mechanisms in clinical isolates of XDR Pseudomonas aeruginosa Abstract Our study aims to define the epidemiology of carbapenem resistance mechanisms in clinical isolates of Pseudomonas aeruginosa (PA). We evaluated 11,457 clinical PA strains isolated between 2009 and 2015 at the tertiary care University Hospital in Heidelberg, Germany. Thirty-four percent of the isolates (3867/11,457) were MDR (multidrug-resistant), 16% (1816/11,457) were XDR (extensively drug resistant), and less than 1% (82/11,457) had a PDR (pandrug-resistant) profile. Of those, 23% carried a carbapenemase gene (CPM positive) with 12% VIM-2, 10% VIM-1, and less than 1% IMP-1. Comparing MIC (minimal inhibitory concentration) distributions, the mean rank for meropenem, imipenem, gentamicin, and fosfomycin was significantly higher in the CPM-positive group than in the CPM-negative XDR group (p ≤ 0.004). oprD (outer membrane protein) mutations were found in 19/19 tested strains; 12/19 carried a CPM and had a higher mutation rate. Meropenem resistance was mostly associated with the presence of CPM. Only 1/19 strains was meropenem resistant in the absence of CPM genes; nevertheless, it carried an oprD mutation in a strategic site (loop 2). Of 19 CPM-negative strains tested, 7 (36%) showed EP (efflux pumps) hyperexpression versus 12 in the CPM-positive strains. In our study, nearly 50% of the PA isolates exhibited resistance to the tested first-line antibiotics. Our study also demonstrates that carbapenemase genes can be isolated in approximately 23% of XDR PA strains in our population. This finding supports the clinical relevance of PA driven by the possible presence of multiple resistance mechanisms acquired under exposure to antibiotics or by horizontal transfer of resistance genes.

Central venous catheter unrelated candidemia influences the outcome of infection in patients with solid tumors Abstract Systemic infections due to Candida spp. is common among immunocompromised patients, including those with solid tumors (ST). Clinical characteristics of candidemia in 114 patients with ST were compared with those of 249 candidemic patients without ST (non-ST). Patients with ST were more likely to be hospitalized in medical departments, to have a significantly higher Charlson’s score and to undergo a significantly later central venous catheter (CVC) removal (P < 0.001). Similarly, the use of total parenteral nutrition was more common in ST patients (P = 0.026). Although there was a trend toward a more appropriate use of antifungal therapy in ST (60%) than in non-ST patients (49%), the difference was not statistically significant (P = 0.059). Thirty-day mortality was significantly higher in ST (49%) than in non-ST patients (36%, P = 0.016). Multivariate analysis showed that either higher age or septic shock was an independent risk factor for mortality in both groups of patients. Conversely, a CVC-unrelated candidemia represented an independent risk factor for mortality in ST patients (HR 3.581 [CI 95% 1.412–9.087, P = 0.007]). Overall, these data show that candidemia in ST patients is characterized by an extremely high mortality rate.