Does Online Search Behavior Coincide with Candida auris Cases? An Exploratory Study

Candida auris is an emerging multidrug resistant infectious yeast which is challenging to eradicate and despite available laboratory methods is still difficult to identify especially in less developed countries. To limit the rapid spread of C. auris, quick and accurate detection is essential. From the perspective of disease surveillance, additional methods of tracking this yeast are needed. In order to increase global preparedness, we explored the use of online search behavior to monitor the recent global spread of C. auris. We used Google Trends to assess online search behavior on C. auris from January 2016 until August 2018. Weekly Google Trends results were counted as hits and compared to confirmed C. auris cases obtained via publications and a global expert network of key opinion leaders. A total of 44 countries generated a hit, of which 30% (13/44) were confirmed known cases, 34% (15/44) were missed known cases, 34% (15/44) were hits for unknown cases, and 2% (1/44) were confirmed unknown cases. Conclusions: Google Trends searches is rapidly able to provide information on countries with an increased search interest in C. auris. However, Google Trends search results do not generally coincide with C. auris cases or clusters. This study did show that using Google Trends provides both insight into the known and highlights the unknown, providing potential for surveillance and tracking and hence aid in taking timely precautionary measures

Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies

Objectives: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. Methods: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results: The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.Junta de Andalucía PI 0185/201

CON: carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant enterobacterales

Carbapenems are considered the drugs of choice for the treatment of serious infections caused by ceftriaxone resistant Enterobacterales. However, because of the dramatic increase in carbapenem-resistant organisms worldwide, finding alternatives to carbapenems is a must. The potential options include b-lactam/b-lactamase inhibitor combinations, temocillin, cephamycins and some non-b-lactam drugs. The most controversial is pipera cillin/tazobactam; the results of the MERINO trial are challenged because the isolates of patients with worse out comes were frequently not susceptible to piperacillin/tazobactam when studied by reference methods, and also because the drug was not administered in extended infusion. Other potential options are briefly discussed. We conclude that carbapenems are not necessary for all patients with infections caused by ceftriaxone-resistant Enterobacterales

Duration of Colonization by Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in Healthy Newborns and Associated Risk Factors: a Prospective Cohort Study

Duration of colonization by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) and factors associated with it were studied in 20 newborns in Seville, Spain. Median duration of colonization was 7.5 months; factors associated with prolonged colonization were delivery by caesarean section, colonization of the mother and phylogroup B2 Eschericha coli isolate.Ministerio de Economía, Industria y Competitividad REIPI RD12/0015/0010Ministerio de Economía, Industria y Competitividad REIPI RD16/0016/0001Instituto de Salud Carlos III Grants 070190, 10/01955, y 10/00795Junta de Andalucía Grants CTS-5259 y CTS21

Pharmacodynamics of fosfomycin: Insights into clinical use for antimicrobial resistance

The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing E. coli strains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycinresistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [for E. coli urinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (fAUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically against E. coli strains in preventing the emergence of fosfomycin resistance.Consejería de Igualdad, Salud y Políticas Sociales Junta de Andalucía PI-0044-2013FEDER REIPI RD12/001

Virulence Profiles of Bacteremic Extended-Spectrum β-Lactamase-Producing Escherichia coli: Association with Epidemiological and Clinical Features

There is scarce data about the importance of phylogroups and virulence factors (VF) in bloodstream infections (BSI) caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC). A prospective multicenter Spanish cohort including 191 cases of BSI due to ESBLEC was studied. Phylogroups and 25 VF genes were investigated by PCR. ESBLEC were classified into clusters according to their virulence profiles. The association of phylogropus, VF, and clusters with epidemiological features were studied using multivariate analysis. Overall, 57.6%, 26.7%, and 15.7% of isolates belonged to A/B1, D and B2 phylogroups, respectively. By multivariate analysis (adjusted OR [95% CI]), virulence cluster C2 was independently associated with urinary tract source (5.05 [0.96-25.48]); cluster C4 with sources other than urinary of biliary tract (2.89 [1.05-7.93]), and cluster C5 with BSI in non-predisposed patients (2.80 [0.99-7.93]). Isolates producing CTX-M-9 group ESBLs and from phylogroup D predominated among cluster C2 and C5, while CTX-M-1 group of ESBL and phylogroup B2 predominantes among C4 isolates. These results suggest that host factors and previous antimicrobial use were more important than phylogroup or specific VF in the occurrence of BSI due to ESBLEC. However, some associations between virulence clusters and some specific epidemiological features were foundSpanish Network for Research in Infectious Diseases REIPI RD06/0008Fondo de Investigación Sanitaria 070190, 10/02021, 10/01955, y 10/00795Junta de Andalucía 0048/2008 y CTS-525

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM"Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation.In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de IþDþi 2013-2016 and Instituto de Salud Carlos III, Subdirecci on General de Redes y Centros de Investigaci on Cooperativa, Ministerio de Ciencia, Innovaci on y Universidades e co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014e2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/ 0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP)

Combined use of the Ab105-2фΔCI lytic mutant phage and different antibiotics in clinical isolates of multiresistant Acinetobacter baumannii

Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) showing antimicrobial activity against A.baumannii clinical strains(such as Ab177_GEIH-2000 which showed MICs to meropenem and imipenem of 32 μg/ml and 16 μg/ml, respectively as well as belonging to GEIH-REIPI Spanish MulticenterA. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585).We observed in vitro, an antimicrobial synergistic effect(from 4 log to 7 log CFU/ml) with meropenem plus lytic phage in all combinations analysed(0.1, 1 and 10 MOI of Ab105-2phiΔCI mutant as well as 1/4 and 1/8 MIC of meropenem). Moreover, we had a decrease in bacterial growth of 8 log CFU/ml for the combination of imipenem at 1/4 MIC plus lytic phage(Ab105-2phiΔCI mutant) and of 4 log CFU/ml for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) in both MOI 1 and 10.These results were confirmed in in vivo(G. mellonella) obtaining a higher effectiveness in thecombination of imipenem and Ab105-2phiΔCI mutant(P<0.05). This approach could help to reducethe emergence of phage resistant bacteria and restore sensitivity to the antibiotics when used tocombat multiresistant strains of Acinetobacter baumannii

Impact of the MIC of Piperacillin-Tazobactam on the Outcome of Patients with Bacteremia Due to Extended-Spectrum-B-Lactamase- Producing Escherichia coli

We investigated the impact of the piperacillin-tazobactam MIC in the outcome of 39 bloodstream infections due to extended- spectrum-B-lactamase-producing Escherichia coli. All 11 patients with urinary tract infections survived, irrespective of the MIC. For other sources, 30-day mortality was lower for isolates with a MIC of <2 mg/liter than for isolates with a higher MIC (0% ver- sus 41.1%; P = 0.02