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Early introduction of appropriate antibiotherapy is one of the major prognostic-modifying factors in community acquired pneumonia (CAP). Despite established guidelines for empirical therapy, several factors may influence etiology and, consequently, antibiotic choices. The aims of this study were to analyze the etiology of CAP in adults admitted to a northern Portugal University Hospital and evaluate the yield of the different methods used to reach an etiological diagnosis, as well as analyze of the impact of patient demographic and clinical features on CAP etiology. We retrospectively analyzed 1901 cases of CAP with hospitalization. The diagnostic performance increased significantly when blood and sputum cultures were combined with urinary antigen tests. The most frequent etiological agent was Streptococcus pneumoniae (45.7%), except in August, when it was overtaken by gram-negative bacilli (GNB) and Legionella pneumophila infections. Viral infections were almost exclusive to winter and spring. A negative microbiological result was associated with increasing age, non-smoking and lack of both blood/sputum cultures. Younger age was a predictor for S. pneumoniae, Influenza and L. pneumophila infections. Active smoking without any previously known respiratory disease was a risk factor for legionellosis. COPD was associated with Haemophilus influenzae cases, while dementia was typical in GNB and S. aureus patients. Diabetes mellitus (DM) and heart disease were negative predictors of S. pneumoniae and H. influenzae, respectively. P. aeruginosa was an independent risk factor for mortality (OR 13.02, 95% CI 2.94–57.7). This study highlights the importance of a comprehensive microbiological diagnostic workup and provides clues to predicting the most probable CAP causative agents, based on a patient's clinical profile. These may be taken into account when establishing first line antibiotherapy.

Antimicrobial finishing is increasingly used in textile products to increase their functionality. Antimicrobial properties became extremely important during the COVID-19 situation. The main problems faced by antimicrobial finishing are nontoxicity and durability (wash-resistance) of antibacterial activity. Also, it is important to determine whether the antimicrobial finishing changes comfort properties, such as air permeability. This paper deals with the durability of antimicrobial treatment, that is, resistance to washing, and effect on the structural changes that may have influence on the comfort properties, such as permeability to air. Knits of various raw compositions were antimicrobial-treated with the new commercial antimicrobial product, Si Bactericidal (Smart Inovation, Portugal). After the antimicrobial treatment, knitted specimens were washed 50 times and changes in their structural parameters, air permeability, and antimicrobial activity were measured. It was found that the mentioned antimicrobial treatment gives very good antimicrobial activity to the treated fabric and is wash-resistant and long-lasting. Also, it does not change dimensions and permeability to air of the treated fabrics with some exceptions of cotton-based knitted structures.

RESUMEN Desde un punto de vista microbiológico, tanto en el tratamiento antimicrobiano empírico como el dirigido en la infección respiratoria se fundamenta en el perfil de sensibilidad de los microrganismos aislados y los posibles mecanismos de resistencia que puedan presentar. Estos últimos puedan variar en diferentes áreas geográficas según los perfiles de prescripción y los programas de vacunación. Los antibióticos betalactámicos, las fluoroquinolonas y los macrólidos son los antimicrobianos más empleados en la exacerbación de la enfermedad pulmonar obstructiva crónica y la neumonía adquirida en la comunidad. En su prescripción se deben tener en cuenta aspectos como la actividad intrínseca, el efecto bactericida y su capacidad para evitar el desarrollo de resistencias. Este último está relacionado con los parámetros PK/PD, la concentración preventiva de mutantes y la denominada ventana de selección. Mas reciente ha crecido en importancia el potencial impacto ecológico, no solo sobre la microbiota intestinal, sino también sobre la respiratoria. El mantenimiento del estado de eubiosis requiere el uso de antimicrobianos con bajo perfil de actuación sobre los microorganismos anaerobios. Con ellos se facilita la resiliencia de las poblaciones bacterianas que integran la microbiota, el estado de resistencia de colonización y se limita el daño colateral relacionado con la emergencia de resistencia a los anti-microbianos en los patógenos que producen las infecciones y las poblaciones bacterianas que integran la microbiota.

Introduction: A dramatic increase of infections induced by carbapenemase-producing Enterobacterales (CPE) has been registered worldwide. The aim of this study was to evaluate the molecular epidemiology and the clinical impact of CPE strains isolated from adult inpatients. Material and methods: A one-year, single-center, retrospective observational study including 34 consecutive patients with 37 non-duplicate CPE strains recovered from clinical specimens was accomplished. The Vitek 2 Compact, M.I.C.Evaluator strips, the modified carbapenem inactivation method (mCIM), and the combination disks test (KPC, MBL, OXA-48 Confirm kit, Rosco Diagnostica) were applied as phenotypic tests. A multiplex polymerase chain reaction (PCR) assay was used for detection of blaKPC, blaNDM, and blaOXA-48-like genes. The clonality was assessed with pulsed-field gel electrophoresis (PFGE). Results: Klebsiella pneumoniae (n=25) was the most frequent CPE encountered. The carbapenemase types were NDM (n=13), KPC (n=12), and OXA-48-like (n=12). Two distinct clonal clusters were identified among the 12 KPC positive strains. All CPE isolates exhibited non-susceptibility to carbapenems, cephalosporins, ciprofloxacin. Respiratory tract infections (n=16) and hospitalization in the intensive care unit (ICU) (n=14) were dominant. The most common comorbidity was congestive heart failure (n=11). Monotherapy was the main strategy adopted (n=15). Death occurred in 18 patients. Conclusions: Our analysis underscores the scarcity of antibiotic solutions and high mortality. Monotherapy for urinary tract infections (UTIs) is beneficial. Inter- or intrahospital dissemination of successful epidemic clones is proved. The adequate CPE infections control programs and antimicrobial policies are essential..

Background The matrix assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI-TOF MS) technology has revolutionized the field of microbiology by facilitating precise and rapid species identification. Recently, machine learning techniques have been leveraged to maximally exploit the information contained in MALDI-TOF MS, with the ultimate goal to refine species identification and streamline antimicrobial resistance determination. Objectives The aim was to systematically review and evaluate studies employing machine learning for the analysis of MALDI-TOF mass spectra. Data sources Using PubMed/Medline, Scopus and Web of Science, we searched the existing literature for machine learning-supported applications of MALDI-TOF mass spectra for microbial species and antimicrobial susceptibility identification. Study eligibility criteria Original research studies using machine learning to exploit MALDI-TOF mass spectra for microbial specie and antimicrobial susceptibility identification were included. Studies focusing on single proteins and peptides, case studies and review articles were excluded. Methods A systematic review according to the PRISMA guidelines was performed and a quality assessment of the machine learning models conducted. Results From the 36 studies that met our inclusion criteria, 27 employed machine learning for species identification and nine for antimicrobial susceptibility testing. Support Vector Machines, Genetic Algorithms, Artificial Neural Networks and Quick Classifiers were the most frequently used machine learning algorithms. The quality of the studies ranged between poor and very good. The majority of the studies reported how to interpret the predictors (88.89%) and suggested possible clinical applications of the developed algorithm (100%), but only four studies (11.11%) validated machine learning algorithms on external datasets. Conclusions A growing number of studies utilize machine learning to optimize the analysis of MALDI-TOF mass spectra. This review, however, demonstrates that there are certain shortcomings of current machine learning-supported approaches that have to be addressed to make them widely available and incorporated them in the clinical routine., Clinical Microbiology and Infection, 26 (10), ISSN:1470-9465, ISSN:1198-743X

Background Non-typhoidal Salmonella (NTS) are a frequent cause of invasive infections in sub-Saharan Africa. They are frequently multidrug resistant (co-resistant to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol), and resistance to third-generation cephalosporin and fluoroquinolone non-susceptibility have been reported. Third-generation cephalosporins and fluoroquinolones are often used to treat invasive NTS infections, but azithromycin might be an alternative. However, data on antibiotic treatment efficacy in invasive NTS infections are lacking. In this study, we aimed to assess the spatiotemporal distribution of antimicrobial resistance in invasive NTS infections in sub-Saharan Africa and to describe the available evidence and recommendations on antimicrobial treatment. Methods We conducted a systematic review of all available literature on antimicrobial resistance and treatment in invasive NTS infections. We performed a random effects meta-analysis to assess the temporal distribution of multidrug resistance, third-generation cephalosporin resistance, and fluoroquinolone non-susceptibility. We mapped these data to assess the spatial distribution. We provided a narrative synthesis of the available evidence and recommendations on antimicrobial treatment. Results Since 2001, multidrug resistance was observed in 75% of NTS isolates from all sub-Saharan African regions (95% confidence interval, 70–80% and 65–84%). Third-generation cephalosporin resistance emerged in all sub-Saharan African regions and was present in 5% (95% confidence interval, 1–10%) after 2010. Fluoroquinolone non-susceptibility emerged in all sub-Saharan African regions but did not increase over time. Azithromycin resistance was reported in DR Congo. There were no reports on carbapenem resistance. We did not find high-quality evidence on the efficacy of antimicrobial treatment. There were no supranational guidelines. The “Access group” antibiotics ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol and “Watch group” antibiotics ceftriaxone, cefotaxime, and ciprofloxacin were recommended as the first-choice antibiotics in national guidelines or reviews. These also recommended (a switch to) oral fluoroquinolones or azithromycin. Conclusions In addition to the widespread multidrug resistance in invasive NTS infections in sub-Saharan Africa, resistance to third-generation cephalosporins and fluoroquinolone non-susceptibility was present in all regions. There was a lack of data on the efficacy of antimicrobial treatment in these infections, and supranational evidence-based guidelines were absent.

Purpose Investigation of the current practice of diagnostics and treatment in pediatric cancer patients with febrile neutropenia. Methods On behalf of the German Society for Pediatric Oncology and Hematology and the German Society for Pediatric Infectious Diseases, an Internet-based survey was conducted in 2016 concerning the management of febrile neutropenia in pediatric oncology centers (POC). This survey accompanied the release of the corresponding German guideline to document current practice before its implementation in clinical practice. Results In total, 51 POCs participated (response rate 73%; 43 from Germany, and 4 each from Austria and Switzerland). Identified targets for antimicrobial stewardship concerned blood culture diagnostics, documentation of the time to antibiotics, the use of empirical combination therapy, drug monitoring of aminoglycosides, the time to escalation in patients with persisting fever, minimal duration of IV treatment, sequential oral treatment in patients with persisting neutropenia, indication for and choice of empirical antifungal treatment, and the local availability of a pediatric infectious diseases consultation service. Conclusion This survey provides useful information for local antibiotic stewardship teams to improve the current practice referring to the corresponding national and international guidelines.

Background Chromobacterium violaceum (C. violaceum) is a Gram-negative saprophytic bacterium that is widespread in tropical and subtropical environments, and belongs to conditional pathogenic bacteria. Human infection with C. violaceum is rare, and this can be fatal when the diagnosis and treatment are delayed, especially recurrent infection patients. Since clinicians lack the knowledge for C. violaceum, rapid diagnosis and early appropriate antimicrobial treatment remains challenging. Case presentation A 15-year-old male student was hospitalized for dark abscess, pustules, severe pain in both legs, and fever for 11 days. There were pustules with gray-white pus and red infiltrating plaques on the back, and the subcutaneous nodules could be touched in front of both tibias, with scab, rupture and necrotic tissue of the lower limb. The patient’s condition rapidly progressed. Therefore, next-generation sequencing (NGS), pustular secretion and blood culture were concurrently performed. The final diagnosis for this patient was C. violaceum infection by NGS. However, no bacterial or fungal growth was observed in the pustular secretion and blood culture. After 4 weeks of treatment, the patient was discharged from the hospital without any complications associated with C. violaceum infection. Conclusion Rapid diagnosis and early appropriate antimicrobial treatment is the key to the successful treatment of C. violaceum infection, especially in patients with sepsis symptoms. This case highlights that NGS is a promising tool for the rapid diagnosis of C. violaceum infection, preventing the delayed diagnosis and misdiagnosis of C. violaceum infection in patients who tested negative for pustular secretion and blood culture.

Antimicrobial resistance in Neisseria gonorrhoeae is threatening the treatment and control of gonorrhea globally, and new treatment options are imperative. Utilizing our dynamic in vitro hollow fiber infection model (HFIM), we examined the pharmacodynamics of the first-in-class spiropyrimidinetrione (DNA gyrase B inhibitors), zoliflodacin, against the N. gonorrhoeae reference strains World Health Organization F (susceptible to all relevant antimicrobials) and WHO X (extensively drug resistant, including resistance to ceftriaxone) over 7 days. Dose-range experiments with both strains, simulating zoliflodacin single oral dose regimens of 0.5–8 g, and dose-fractionation experiments with WHO X, simulating zoliflodacin oral dose therapy with 1–4 g administered as q12 h and q8 h for 24 h, were performed. A kill-rate constant that reflected a rapid bacterial kill during the first 6.5 h for both strains and all zoliflodacin doses was identified. In the dose-range experiments, the zoliflodacin 2–8 g single-dose treatments successfully eradicated both WHO strains, and resistance to zoliflodacin was not observed. However, zoliflodacin as a single 0.5 g dose failed to eradicate both WHO strains, and a 1 g single dose failed to eradicate WHO X in one of two experiments. The zoliflodacin 1 g/day regimen also failed to eradicate WHO X when administered as two and three divided doses given at q12 h and q8 h in the dose-fractionation studies, respectively. All failed regimens selected for zoliflodacin-resistant mutants. In conclusion, these data demonstrate that zoliflodacin should be administered at >2 g as a single oral dose to provide effective killing and resistance suppression of N. gonorrhoeae. Future studies providing pharmacokinetic data for zoliflodacin (and other gonorrhea therapeutic antimicrobials) in urogenital and extragenital infection sites, particularly in the pharynx, and evaluation of gonococcal strains with different gyrB mutations would be important.

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

Textile products are an integral part of people’s everyday life. In the process of exploitation of textile products, the human body directly contacts with textile materials throughout life, so the issue of their safety is especially important in the production of textiles and clothing. Creation of innovative formulae of washing compositions allows combining the high efficiency of the washing process with the treatment of textiles with special types of finishing. Studies aimed at the development of effective compositions with polyfunctional action based on surfactants (surface-active biodegradable substances) with the use of antimicrobial preparations are urgent and promising. They also contribute to the development of the market of chemical products, reduce the material consumption of technology and the cost of production and increase the ecological safety of the process. A complex evaluation of changes in the operational properties of textile materials after treatment with compositions of ecologically safe substances was carried out. The results of the study will contribute to reducing the ecological burden on the environment and human health. In addition, this ensures the preservation of the consumer properties of textile products during operation. The complex study of the influence of compositions of ecologically safe substances on the hygienic properties of textile products is presented. The analysis of the effectiveness of the compositions on the technological parameters (washing ability, anti-resorption capacity, composition concentration, treatment time) of the process of removal of contaminations from textile products made of cotton, polyester and their mixtures was carried out. The quantitative indices of capillarity of fabrics are determined, namely, the raising height of the composition of solutions (h, mm), which characterizes the quality of cleaning of pores of textile materials. Experimental data indicate that the treatment of fabrics made of cotton and polyester and mixtures thereof contributes to their hydrophilicity, which is expressed in improving their wettability with aqueous solutions and increasing capillarity from 131 mm to 152 mm due to the presence of adsorbed surfactants on materials. The influence of compositions of ecologically safe substances on the representative of the normal microflora of the human body P. freudenreichii was investigated. It was found that the culture was restored to 104–105cells/ml after 48 hours of fabric sample exposure and in the P. freudenreichii sterility control environment. It was found that treatment of textile products at the concentration of compositions of ecologically safe substances of 2.5 g/l is technologically and ecologically expedient. As the high quality of cleaning of products is achieved (from 80 % to 88 %), the capillarity of textile materials increases, and the healthy microflora of human skin is preserved. The obtained research data allows us to recommend the use of compositions of ecologically safe substances for the treatment of special-purpose textile products (for military, athletes, etc.), as well as home textiles

Antimicrobial treatment during therapeutic plasma exchange (TPE) remains a complex issue. Recommendations based on a limited number of experimental studies should be implemented in clinical practice with caution. Effective management of infections due to plasma or albumin-related interactions, as well as impaired pharmacokinetics, in critical illness is difficult. Knowing the pharmacokinetics of the drugs concerned and the procedural aspects of plasmapheresis should be helpful in planning personalized treatment. In general, possessing a low distribution volume, a high protein-binding affinity, a low endogenous clearance rate, and long distribution and elimination half-lives make a drug more prone to elimination during TPE. A high frequency and longer duration of the procedure may also contribute to altering a drug’s concentration. The safest choice would be to start and finish TPE before antimicrobial agent infusion. If this not feasible, a reasonable alternative is to avoid administering the drug just before TPE and to delay the procedure for the time of the administered drug’s distributive phase. Ultimately, if plasma exchange must be performed urgently or the drug has a very narrow therapeutic index, monitoring its plasma concentration is advised.

Aims Our aim was to summarize the available literature on the effect of short- versus long-course antibiotic therapy on acute cholangitis. Methods A systematic review was performed according to the PRISMA Statement. We searched three databases for papers discussing the length of ABT in acute cholangitis. Long and short therapy groups were defined based on the most recent guideline available at the time of publication of the articles. Primary outcomes were the rate of recurrent cholangitis and mortality; secondary outcomes included length of hospitalization and the duration of fever after ERCP. Data were extracted on these outcomes and on general characteristics. A narrative synthesis was then provided based on collected data. Results Out of 692 articles produced by our search, four met our inclusion and exclusion criteria. These contained 205 acute cholangitis patients, with 137 and 68 patients receiving short and long antibiotic therapy, respectively. No significant difference was observed in any of the studies on the outcomes of mortality and duration of fever after ERCP between the two groups. One out of four studies found the rate of recurrent cholangitis to be significantly lower in the short antibiotic therapy group (0.0% vs. 13.3%, p = 0.036). Length of hospitalization was only compared in the same retrospective article, where it was found to be significantly shorter in the short-term antibiotic therapy group (with a median of 14 vs. 17.5 days, p

Traumatic orthopedic injuries, particularly extremity wounds, are a significant cause of morbidity. Despite prophylactic antibiotic treatment and surgical intervention, persistent infectious complications can and do occur. Persistent bacterial infections are often caused by biofilms, communities of antibiotic tolerant bacteria encased within a matrix. The structural and metabolic differences in this mode of growth make treatment difficult. Herein, we describe both established and novel, experimental treatments targeted at various stages of wound healing that are specifically aimed at reducing and eliminating biofilm bacteria. Importantly, the highly tolerant nature of these bacterial communities suggests that most singular approaches could be circumvented and a multifaceted, combinatorial approach will be the most effective strategy for treating these complicated infections.

Primary peritonitis is a rare infection in healthy children, mainly affecting patients with underlying medical disorders. We report a case of primary pneumococcal peritonitis in an immunocompetent 3-year-old boy. Diagnosis was made at laparotomy and cultures of the intra-abdominal pus yielded Streptococcus pneumoniae. Timely antibiotic treatment administered resulted in complete resolution of the infection.

Ralstonia pickettii is an opportunistic bacillus found in Pseudomonas species, with the ability to induce systemic infections. We report the case of a 69-year-old man, with a clinical history of myeloma, Type IIdiabetes, renal failure (grade IV), and colon cancer, that developed a severe bacterial infection, with acute asthenia and a fever, that appeared at the end of dialysis. Using theMALDI-TOF technology, the bacillus Ralstonia pickettii was identified, and an antimicrobial treatment was quickly started with a rapid microbiological remission.

A 5-year-old male castrated Lhasa Apso cross was evaluated for a 1-month history of inappetence, lethargy, gagging, and progressive right thoracic limb lameness. Synovial fluid analysis revealed nonseptic suppurative inflammation, and a diagnosis of immune-mediated polyarthritis (IMPA) was made. After 3months of treatment with prednisone and later cyclosporine, the dog developed multiple firm cutaneous and subcutaneous masses and a focal mass within the jejunum. Cultures of blood, urine, skin lesions, and the jejunal mass identified Nocardia veterana by matrix-absorption laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and allowed for earlier identification of the organism compared to more traditional secA1 gene sequencing. Immunosuppressive drug treatment was discontinued, and the dog was treated for 3months by administration of trimethoprim-sulfamethoxazole (TMS). No recurrence of clinical signs was reported 1year later. This case report highlights the clinical utility of MALDI-TOF MS, particularly for the rapid identification of slow-growing, fastidious organisms.

Acute inguinal lymphadenitis is usually caused by lower extremity infection and sexually transmitted diseases, such as chancroid, lymphogranuloma venereum, genital herpes, or syphilis. Yersinia pseudotuberculosis is a non-spore forming, pleomorphic, non-lactose fermenting Gram negative bacillus and a member of the family Enterobacteriaceae, which is associated with diarrheal diseases. It also causes mesenteric lymphadenitis at the terminal ileum, which can be clinically indistinguishable from acute appendicitis (pseudoappendicitis). However, lymphadenitis in other regions caused by the organism is rarely reported. Herein, we report a case of a man in his 20s, who presented with unilateral inguinal lymphadenitis caused by Y. pseudotuberculosis, with discussion regarding the pathogenesis of this rare occurrence.

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection SI

Supplementary material associated with this article can be found in the online version available at doi:10.1016/j.pulmoe.2018.09.001. Setting: Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans for which effective treatment is challenging. There is, however, very little information on the prevalence of NTM drug resistance in Portugal. Objective and Design: Our aim was to analyze the drug susceptibility testing (DST) performed in NTM at the Portuguese National Health Institute Dr. Ricardo Jorge from February 2003 to February 2016. A total of 262 DST were included in the analysis. Results: Most (94%) M. avium intracellulare complex isolates showed in vitro susceptibility to clarithromycin. All M. kansasii isolates were susceptible to rifampicin and ethambutol and 97.1% were susceptible to isoniazid. The majority of rapidly-growing mycobacteria (RGM) demonstrated in vitro susceptibility to amikacin, clarithromycin and cefoxitin. However, in RGM there was a marked increase on the relative risk of having sulfamethoxazole resistance in isolates resistant to ciprofloxacin compared to susceptible isolates. Conclusion: Tested NTM in Portugal revealed in vitro susceptibility to most of the antimicrobials currently recommended for treatment. However, our results also suggest that sulfamethoxazole should be avoided in treatment of RGM resistant to ciprofloxacin (or vice versa). Further trials that correlate the in vitro DST results with the clinical outcome are needed in order to reach conclusions on efficient antimicrobial therapy. info:eu-repo/semantics/publishedVersion

The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients.All patients receiving mechanical ventilation for >48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297).The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53–0.80; pversus 11.6%; sub-hazard ratio 0.61, 95% CI 0.45–0.84; p=0.002) and ventilator-associated pneumonia (9.3% versus 12.7%; sub-hazard ratio 0.72, 95% CI 0.54–0.95; p=0.019). Among patients with VA-LRTI, the rates of multidrug-resistant bacteria (72% versus 59%; p=0.011) and intensive care unit mortality were significantly higher among immunocompromised than among non-immunocompromised patients (54% versus 30%; OR 2.68, 95% CI 1.78–4.02; pversus 34%; pIncidence of VA-LRTI was significantly lower among immunocompromised patients, but it was associated with a significantly higher mortality rate. Multidrug-resistant pathogens were more frequently found in immunocompromised patients with VA-LRTI.

Objective: Since dentures can serve as a reservoir for halitosis-causing oral bacteria, halitosis development is a concern for denture wearers. In this study, we surveyed the prevalence of four selected halitosis-related species (Fusobacterium nucleatum, Tannerella forsythia,Veillonella atypicaandKlebsiella pneumoniae) in clinical denture plaque samples, and developed denture biofilm models for these speciesin vitroto facilitate assessment of antimicrobial treatment efficacy.Design:Denture plaque from ten healthy and ten denture stomatitis patients was screened for the presence of aforementioned four species by PCR. Biofilm formation by these halitosis-associated species on the surfaces of denture base resin (DBR) discs was evaluated by crystal violet staining and confocal laser scanning microscopy. The efficacy of denture cleanser treatment on these mono-species biofilms was evaluated by colony counting.Results:80% of the subjects in the denture stomatitis group and 60% in the healthy group contained at least one of the targeted halitosis-related species in their denture plaque. All halitosis species tested were able to form biofilms on DBR disc surfaces to varying degrees. Thesein vitromono-species resin biofilm models were used to evaluate the efficacy of denture cleansers, which exhibited differential efficacies. When forming biofilms on resin surfaces, the halitosis-related species displayed enhanced resistance to denture cleansers compared with their planktonic counterparts.Conclusion:The four selected halitosis-related bacterial species examined in this study are present on the majority of dentures. The mono-species biofilm models established on DBR discs for these species are an efficient screening tool for dental product evaluation.

Background Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia.

Community acquired pneumonia (CAP) is a leading cause of childhood morbidity worldwide. Because of the rising antimicrobial resistance rates and adverse effects of childhood antibiotic use on the developing microbiome, rational prescribing of antibiotics for CAP is important. This review summarizes and critically reflects on the available evidence for the epidemiology, etiology and antimicrobial management of childhood CAP. Larger prospective studies on antimicrobial management derive mostly from low- or middle-income countries as they have the highest burden of CAP. Optimal antimicrobial management depends on the etiology, age, local vaccination policies and resistance patterns. As long as non-rapid surrogate markers are used to distinguish viral- from bacterial pneumonia, the management is probably suboptimal. For a young child with signs of non-severe pneumonia (with or without wheezing), watchful waiting is recommended because of probable viral etiology. For children with more severe CAP with fever, a five-day oral amoxicillin course would be the first choice therapy and dosage will depend on local resistance rates. There is no clear evidence yet for superiority of a macrolide-based regimen for all ages. For cases with CAP requiring hospitalization, several studies have shown that narrow-spectrum IV beta-lactam therapy is as effective as a broad-spectrum cephalosporin therapy. For most severe disease, broad-spectrum therapy with or without a macrolide is suggested. In case of empyema, rapid IV-to-oral switch seems to be equivalent to prolonged IV treatment.

Management practices of complicated skin and skin structure infections (cSSSI) were compared between two areas with similar healthcare structure and low prevalence of antimicrobial resistance.The high affinity to public health-care in the Nordic countries enabled population-based approach used in this retrospective study. The study population (n = 460) consisted of all adult residents from Helsinki (Finland) and Gothenburg (Sweden) treated in hospital due to cSSSI during 2008-2011.The majority of patients in Helsinki (57%) visited more than one ward during their hospital stay while in Gothenburg the majority of patients (85%) were treated in one ward only. Background and disease characteristics were largely similar in both cities but patients in Helsinki were younger [mean(SD) 59(18) versus 63(19) years, p = .0117], and greater proportions had diabetes (50% versus 32%, p .0001) and polymicrobial infections (34% versus 13%, p .0001). Patients in Helsinki received antimicrobials with Gram-negative coverage (in initial therapy 96%) more frequently than in Gothenburg (47%, p .0001), had more treatment modifications (mean 4.3 versus 2.7 antibiotic agents used per patient, p .0001), and longer median duration of antimicrobial therapy (29 versus 12 days, p .0001) and median length of hospital stay (17 versus 11 days, p .0001).This real-life study revealed remarkable differences in the management of cSSSI between the two Nordic cities. Compared to mainly Infectious Disease Specialist guided treatment in Gothenburg, the more frequent transfer from one ward to another in Helsinki was linked to longer antimicrobial therapy and hospital stay and to more frequent changes in antimicrobial treatment.

The aim of this study was to assess changes in antibiotic resistance, epidemiology and outcome among patients with Enterococcus faecalis infective endocarditis (EFIE) and to compare the efficacy and safety of the combination of ampicillin and gentamicin (A+G) with that of ampicillin plus ceftriaxone (A+C). The study was a retrospective analysis of a prospective cohort of EFIE patients treated in our centre from 1997 to 2011. Thirty patients were initially treated with A+G (ampicillin 2 g/4 h and gentamicin 3 mg/kg/day) and 39 with A+C (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) for 4–6 weeks. Increased rates of high-level aminoglycoside resistance (HLAR; gentamicin MIC ≥512 mg/L, streptomycin MIC ≥1024 mg/L or both) were observed in recent years (24% in 1997–2006 and 49% in 2007–2011; p 0.03). The use of A+C increased over time: 1997–2001, 4/18 (22%); 2002–2006, 5/16 (31%); 2007–2011, 30/35 (86%) (p

ObjectivesAssessment of bacterial reduction after chemo-mechanical preparation (using 3% sodium hypochlorite) with or without intracanal dressing (calcium hydroxide paste (Ca(OH)2) or 2% chlorhexidine digluconate gel (CHX)) in necrotic pulps associated or not with apical lesion.MethodsProspective clinical trial, in 69 adult patient's teeth with pulpal necrosis associated or not with apical periodontitis. Microbiological root-canal-sampling occurred before treatment (S1), after chemo-mechanical preparation (S2) and after 14 days intracanal dressing (S3). Colony Forming Units (CFU) were counted after growth in aerobic, anaerobic and microaerofilic cultures. Comparison of the median CFUs treatments and culture media was done with the Friedman test. Comparison of the intracanal dressing effect at S3 was done with the Wilcoxon and the Mann–Whitney tests. Because of the huge differences in bacterial counts variations were expressed as log10 to analyze differences among intracanal medication groups. S2 and S3 counts were expressed as percentage of CFU reduction regarding S1 counts.ResultsSignificant differences were detected between S1, S2 and S3 (Friedman test; p

Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing problem, and current treatment options are suboptimal. Nasal carriage of MRSA is a major risk factor for infection, but nasal eradication strategies are increasingly considered to be insufficiently effective. In this study, a water-in-oil cream formulation was developed for nasal application with an antimicrobial peptide, P60.4Ac, aimed at the eradication of MRSA carriage. Quality control of the cream included the measurement of the content and release of the peptide by a validated high-performance liquid chromatography method. Stability of the peptide in the formulation was investigated including the evaluation of the effect of stress conditions. Preliminary shelf-life study of the drug formulation demonstrated that the peptide is stable in the formulation at least for 5 months. Microbial-killing assays with MRSA LUH14616 as a target demonstrated the dose-dependent antimicrobial activity of the peptide formulation.

Resumen: Introducción: El presente estudio revisa la epidemiología, las manifestaciones clínicas y el manejo de los casos de osteomielitis aguda (OA) ingresados en un hospital pediátrico de tercer nivel. Metodología: Estudio descriptivo de los pacientes menores de 15 años ingresados con el diagnóstico de OA entre 2000 y 2011, retrospectivo hasta 2006, y posteriormente prospectivo. Resultados: Se identificaron 50 pacientes (52% varones) con una mediana de edad de 2 años. La sintomatología preponderante al ingreso fue dolor (94%), impotencia funcional (90%) y fiebre (72%). Las localizaciones más frecuentes fueron el fémur (32%), la tibia (28%) y el calcáneo (22%).Se encontró leucocitosis > 12.000/μl en el 56%, VSG elevada > 20 mm/h en un 26 y un 64% con PCR superior a 20 mg/l. El 20% de los hemocultivos resultó positivo, siendo Streptococcus del grupo A el germen más frecuente (11%).La gammagrafía ósea con 99Tc permitió el diagnóstico de confirmación en todos los casos.El tratamiento antibiótico fue intravenoso (i.v.) durante una media de 10 días ± 3 DE, continuándose por vía oral (v.o.) una media de 18 días ± 6 DE. Tres pacientes requirieron drenaje quirúrgico. La evolución en todos los pacientes fue excelente, salvo 3 excepciones, que se resolvieron con el tiempo. Conclusiones: La actual pauta corta de tratamiento i.v. disminuyó la estancia hospitalaria. Tras su instauración no se encontraron diferencias estadísticamente significativas en la duración de la clínica, ni en la PCR en el momento del alta en comparación con las pautas prolongadas previas a 2006. Abstract: Background and aims: The present study focuses on the epidemiology, clinical and laboratory data, and management of osteomyelitis in a pediatric third level hospital. Methodology: All cases of children under 15 years-old admitted with osteomyelitis between 2000 and 2011 were retrospectively reviewed until July 2006, then prospectively from then until 2011. Results: A total of 50 patients were identified (52% males) with median age at diagnosis of 2 years. Principal onset manifestations were pain (94%), functional impairment (90%) and fever (72%). The femur (32%), fibula (28%) and calcaneus (22%) were most affected bones.Leucocytosis > 12.000/μl was found in 56%, elevated ESR > 20 mm/h in 26%, and elevated CRP > 20 mg/L in 64%. Blood culture was positive in 20%, with group A streptococcus being the most frequently isolated bacteria (11%).All diagnoses were confirmed by a 99Tc scintigraphy bone scan.Antibiotic therapy was initially intravenously (mean time of administration: 10 days ± 3 SD), followed by oral medication (mean time of administration: 18 days ± 6 SD). Surgery was necessary in 3 patients. Evolution of all cases was excellent, despite 3 exceptions that resolved over time. Conclusions: The current short-term intravenous therapy led to shorter hospitalizations. There were no statistically significant differences between time from clinical onset or in CRP levels at discharge compared to long-term therapies prior to 2006.

Rzeżączka jest ważnym problemem zdrowia publicznego na świecie. Szczególnym dylematem jest oporność na cefalosporyny o szerokim spektrum, obserwowana w ostatnich latach. W niniejszych zaleceniach przedstawiono rekomendacje dotyczące diagnostyki i leczenia rzeżączki w Europie. W porównaniu z poprzednimi zaleceniami z 2009 roku zalecenia z 2012 roku zostały uaktualnione; uwzględniają szersze wskazania do przeprowadzania badań; wprowadzają leczenie niepowikłanej rzeżączki dwoma antybiotykami (ceftriakson w dawce 500 mg i azytromycyna w dawce 2 g), gdy nie jest znana wrażliwość na antybiotyki; zalecają wykonanie testu potwierdzającego wyleczenie (ang. test of cure ) we wszystkich przypadkach rzeżączki w celu zapewnienia eradykacji zakażenia i wykrycia możliwej antybiotykooporności oraz identyfikację, weryfikację i zgłaszanie przypadków niepowodzeń po stosowaniu rekomendowanej terapii. Osiągnięcie najwyższej jakości w przeprowadzaniu badań, diagnostyce, leczeniu i kontroli po leczeniu odgrywa podstawową rolę w kontroli nad szerzeniem się rzeżączki opornej na cefalosporyny i na wiele innych leków.

The investigation on antimicrobial mechanisms is a challenging and crucial issue in the fields of food or clinical microbiology, as it constitutes a prerequisite to the development of new antimicrobial processes or compounds, as well as to anticipate phenomenon of microbial resistance. Nowadays it is accepted that a cells population exposed to a stress can cause the appearance of different cell populations and in particular sub-lethally compromised cells which could be defined as viable but non culturable (VBNC). Recent advances on flow cytometry (FCM) and especially on multi-parameter flow cytometry (MP-FCM) provide the opportunity to obtain high-speed information at real time on damage at single-cell level. This review gathers MP-FCM methodologies based on individual and simultaneous staining of microbial cells employed to investigate their physiological state following different physical and chemical antimicrobial treatments. Special attention will be paid to recent studies exploiting the possibility to corroborate MP-FCM results with additional techniques (plate counting, microscopy, spectroscopy, molecular biology techniques, membrane modeling) in order to elucidate the antimicrobial mechanism of action of a given antimicrobial treatment or compound. The combination of MP-FCM methodologies with these additional methods is namely a promising and increasingly used approach to give further insight in differences in microbial sub-population evolutions in response to antimicrobial treatments.

Introduction Buruli ulcer (BU) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy. During the last decade, eight weeks of antimicrobial treatment has become the standard of care. This treatment may be accompanied by transient clinical deterioration, known as paradoxical reaction. We investigate the incidence and the risks factors associated with paradoxical reaction in BU. Methods The lesion size of participants was assessed by careful palpation and recorded by serial acetate sheet tracings. For every time point, surface area was compared with the previous assessment. All patients received antimicrobial treatment for 8 weeks. Serum concentration of 25-hydroxyvitamin D, the primary indicator of vitamin D status, was determined in duplex for blood samples at baseline by a radioimmunoassay. We genotyped four polymorphisms in the SLC11A1 gene, previously associated with susceptibility to BU. For testing the association of genetic variants with paradoxical responses, we used a binary logistic regression analysis with the occurrence of a paradoxical response as the dependent variable. Results Paradoxical reaction occurred in 22% of the patients; the reaction was significantly associated with trunk localization (p = .039 by Χ2), larger lesions (p = .021 by Χ2) and genetic factors. The polymorphisms 3’UTR TGTG ins/ins (OR 7.19, p < .001) had a higher risk for developing paradoxical reaction compared to ins/del or del/del polymorphisms. Conclusions Paradoxical reactions are common in BU. They are associated with trunk localization, larger lesions and polymorphisms in the SLC11A1 gene., Author Summary Buruli ulcer is an infectious disease of skin, subcutaneous fat and sometimes bone, mainly affecting children in West Africa. It is considered as one of the Neglected Tropical Diseases but the disease occurs also in moderate climates like South East Australia and Japan where it may also affect adults. Once a patient has started antibiotic treatment, lesions may increase in size even if the antimicrobial treatment is effective; this is highly confusing for doctors and patients as they may think that treatment actually fails. The cause of Buruli ulcer is Mycobacterium ulcerans, related to other mycobacteria that cause disease in man, like leprosy and tuberculosis. Using data from two different studies in West Africa, we show that these paradoxical reactions are associated with trunk localization and that they occur more often in larger lesions. The chance to develop these reactions appeared partly inherited: carrying the homozygous ins/ins genotype of 3’UTR TGTG 285 polymorphism in the SLC11A1 gene increased the risk of paradoxical reactions. Vitamin D is important for the immune defense against infections by mycobacteria. Vitamin D blood concentrations were not associated with paradoxical reactions; patients generally did well, and we did not need corticosteroid immune suppression to overcome these reactions.

Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-underthe-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bonemarrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe., SCOPUS: ar.j, info:eu-repo/semantics/published

Chronic infection of the respiratory tract is a hallmark of cystic fibrosis (CF). Antibiotic treatment has been used as one of the mainstays of therapy and together with other treatment modalities has resulted in increased survival of CF patients. Increasing resistance of CF-specific pathogens to various classes of antibiotics explains the need for novel antibiotic strategies. This review focuses on the future development of new antibiotic therapies, including: (1) New targets, (2) novel antibiotic regimens in CF, (3) new antibiotics, and (4) other investigational therapies. In addition, we briefly summarize developments in the area of microbial diagnostics and discuss interactions between the complex pulmonary microflora.

Roger Sordé1,2, Albert Pahissa1,2, Jordi Rello3,41Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; 2Spanish Network for Research in Infectious Diseases (REIPI), Spain; 3Department of Critical Care, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; 4CIBER Enfermedades Respiratorias (CIBERES), SpainAbstract: Cystic fibrosis (CF) is the most common life-limiting inherited disease in Caucasian populations. The main cause of death in CF patients is respiratory failure resulting from chronic pulmonary infection. Pseudomonas aeruginosa is the most prevalent organism in the airway colonization of CF patients, and its persistence in the airways has been related to greater morbidity with a more rapid deterioration in lung function. P. aeruginosa has enormous genetic and metabolic flexibility that allows it to adapt and persist within the airways of CF patients, and it has the ability to easily acquire antimicrobial resistance. For these reasons, the management of infections and chronic colonization by P. aeruginosa remains a challenge for physicians. This article reviews the current and future antibacterial chemotherapy options for respiratory pseudomonal infection in CF patients.Keywords: cystic fibrosis, Pseudomonas aeruginosa, respiratory infection, antimicrobial treatment

This study aimed to determine whether prepartum antimicrobial and/or Escherichia coli J5 vaccination in dairy heifers influence the milk production, milk quality, and estimate their economic benefit. Thus, 33 dairy heifers were enrolled in four groups using a split-splot design. Groups were: (G1) prepartum antimicrobial infusion and vaccination with an E. coli J5 bacterin, (G2) prepartum antimicrobial infusion, (G3) vaccination with an E. coli J5 bacterin, and (G4) control heifers. Composite milk samples for somatic cell count, total bacteria count and milk composition were collected 15 days after calving and every 15 days until the end of the experiment. Bacteriological analysis was carried out at the end of study. The milk production and the incidence of clinical cases of mastitis, as well as the costs associated with them were recorded. The results demonstrate a reduction on clinical mastitis rates by preventive strategies, which implicated in lower volume of discarded milk (0.99, 1.01, 1.04 and 3.98% for G1, G2, G3 and G4, respectively) and higher economic benefit. Thus, in well-managed dairy herds the prevention of heifer mastitis by vaccination or antimicrobial therapy can reduce the amount of antimicrobials needed to treat clinical mastitis cases and the days of discarded milk. Resumo: O presente estudo objetivou realizar uma análise econômica do tratamento antimicrobiano no pré-parto e/ou da vacinação com Escherihia coli J5 em novilhas leiteiras, e seu efeito sobre a produção e qualidade de leite. Portanto, utilizou-se o delineamento split-splot em esquema fatorial, no qual 33 novilhas da raça Holandesa foram divididas aleatoriamente em quatro grupos: (G1) antimicroianoterapia no pré-parto e vacinação com E. coli J5, (G2) antimicrobianoterapia no pré-parto, (G3) vacinação com E. coli J5 e (G4) controle. Amostras compostas de leite foram coletadas para contagem de células somáticas, contagem bacteriana total e composição do leite 15 dias após o parto, e a cada 15 dias até o término do experimento. A análise bacteriológica do leite foi realizada ao término do experimento. A produção de leite e a incidência dos casos clínicos de mastite, assim como, os custos associados à antimicrobianoterapia no pré-parto e/ou vacinação com E. coli J5 foram registrados. Os resultados demonstraram redução dos casos clínicos de mastite com a implementação das medidas preventivas resultando no menor volume de leite descartado (0,99, 1,01, 1,04 e 3,98% para os animais dos grupos G1, G2, G3 e G4, respectivemente) e maior benefício econômico. Desta forma, em rebanhos bem manejados, a implementação da antimicrobianoterapia no pré-parto e vacinação com E. coli J5 e novilhas pode reduzir a quantidade de antimicrobianos necessário para o tratamento de casos de mastite clínica durante a lactação, resultando em menor número de dias em que o leite é descartado.

Treatment of mastitis is the most common reason for use of antimicrobial agents in dairy cattle. The responsible use of antimicrobials could be strengthened by knowledge of predictors for cure, which would help to tailor treatment decisions. Ideally, to allow for widespread uptake, this would be achieved using data that are routinely available. To assess whether this is feasible in practice, farmers were invited to submit milk samples from mastitis cases to their veterinary practice for bacteriological culture. Among 624 culture-positive samples, 251 were positive for . Streptococcus uberis. Using cow-level data, cases were classified as severe, first nonsevere, repeat, or subclinical. Additional data were collected at the cow level [somatic cell count (SCC), parity, lactation stage, milk yield, fat and protein contents, treatment] and at the herd level (housing, bedding, premilking teat disinfection, postmilking teat disinfection). Severe cases were overrepresented among heifers and animals in early lactation, and repeat cases were overrepresented in cows with 3 or more lactations. The probability of cure was higher among first- and second-parity animals than among older cows, and was higher in animals with a single elevated cow-level SCC than in animals with multiple high SCC records. Results obtained in the current study are similar to those previously described for . Staphylococcus aureus mastitis. Thus, routinely available cow-level information can help to predict the outcome of antimicrobial treatment of the most common causes of gram-positive mastitis.

Background Antimicrobially pre-treated children with systemic inflammation often pose a diagnostic challenge to the physician. We aimed to evaluate the additional use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative pathogens in children with suspected systemic bacterial or fungal infection. Methods Prospective observational study in 39 children with systemic inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary outcome was the rate of positive blood cultures (BC), compared to the rate of positive SeptiFast (SF) results. Results In total, 14 SF-samples yielded positive results, compared to 4 positive BC (p

International audience; Background : Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Methods and results : Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement.Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively.In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60).Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298).Conclusions :Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

Introduction Ventilator-associated pneumonia (VAP) is a common cause of nosocomial infection, and is related to significant utilization of health-care resources. In the past decade, new data have emerged about VAP epidemiology, diagnosis, treatment and prevention. Results Classifying VAP strictly based on time since hospitalization (early- and late-onset VAP) can potentially result in undertreatment of drug-resistant organisms in ICUs with a high rate of drug resistance, and overtreatment for patients not infected with resistant pathogens. A combined strategy incorporating diagnostic scoring systems, such as the Clinical Pulmonary Infection Score (CPIS), and either a quantitative or qualitative microbiological specimen, plus serial measurement of biomarkers, leads to responsible antimicrobial stewardship. The newly proposed ventilator-associated events (VAE) surveillance definition, endorsed by the Centers for Disease Control and Prevention, has low sensitivity and specificity for diagnosing VAP and the ability to prevent VAE is uncertain, making it a questionable surrogate for the quality of ICU care. The use of adjunctive aerosolized antibiotic treatment can provide high pulmonary concentrations of the drug and may facilitate shorter durations of therapy for multi-drug-resistant pathogens. A group of preventive strategies grouped as a ‘ventilator bundle’ can decrease VAP rates, but not to zero, and several recent studies show that there are potential barriers to implementation of these prevention strategies. Conclusion The morbidity and mortality related to VAP remain high and, in the absence of a gold standard test for diagnosis, suspected VAP patients should be started on antibiotics based on recommendations per the 2005 ATS guidelines and knowledge of local antibiotic susceptibility patterns. Using a combination of clinical severity scores, biomarkers, and cultures might help with reducing the duration of therapy and achieving antibiotic de-escalation.

There are many various diseases in the bone and joint infections, and we tried to make antimicrobial treatment guidelines for common infectious diseases based on available data for microbiology and clinical trials. This guidelines focused on the treatment of osteomyelitis and septic arthritis, which can be experienced by physicians at diverse clinical settings. This guidelines is not applicable to diabetic foot infections, postoperative infections or post-traumatic infections which need special considerations. The guidelines for those conditions will be separately developed later. Surgical treatment of bone and joint infections, pediatric bone and joint infection, tuberculous bone and joint infection, and prophylactic antibiotic use were not included in this guideline.

Background: Outcomes in patients with sepsis are better if initial empirical antimicrobial use is appropriate. Several studies have shown that adherence to guidelines dictating appropriate antimicrobial use positively influences clinical outcome, shortens length of hospital stay and contributes to the containment of antibiotic resistance. Quality indicators (QIs) can be systematically developed from these guidelines to define and measure appropriate antimicrobial use. We describe the development of a concise set of QIs to assess the appropriateness of antimicrobial use in adult patients with sepsis on a general medical ward or Intensive Care Unit (ICU). Methods: A RAND-modified, five step Delphi procedure was used. A multidisciplinary panel of 14 experts appraised and prioritized 40 key recommendations from within the Dutch national guideline on antimicrobial use for adult hospitalized patients with sepsis (www.swab.nl/guidelines). A procedure to select QIs relevant to clinical outcome, antimicrobial resistance and costs was performed using two rounds of questionnaires with a face-to-face consensus meeting between the rounds over a period of three months. Results: The procedure resulted in the selection of a final set of five QIs, namely: obtain cultures; prescribe empirical antimicrobial therapy according to the national guideline; start intravenous drug therapy; start antimicrobial treatment within one hour; and streamline antimicrobial therapy. Conclusion: This systematic, stepwise method, which combined evidence and expert opinion, led to a concise and therefore feasible set of QIs for optimal antimicrobial use in hospitalized adult patients with sepsis. The next step will entail subjecting these quality indicators to an applicability test for their clinimetric properties and ultimately, using these QIs in quality-improvement projects. This information is crucial for antimicrobial stewardship teams to help set priorities and to focus improvement. This work was supported by Zon/MW, the Netherlands Organisation for Health Research and Development, project number 205100003.

Community-acquired pneumonia (CAP) remains a frequent cause of morbidity and mortality worldwide even in industrialised countries, and its incidence is highest among children aged

Frailty is defined as a clinical syndrome in which three or more of the following criteria are present: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed and low physical activity. Sepsis is defined as an inflammatory response to infection, with severe sepsis and septic shock being the most severe forms. The incidence of severe sepsis increases with older age and several studies have shown that there are many risk factors that predispose the elderly to a higher incidence of sepsis. Pre-existing co-morbidities such as cancer, diabetes, obesity, human immunodeficiency virus, and renal or pulmonary disease can cause sepsis, but other factors including poor lifestyle habits (i.e., smoking, drug or alcohol abuse), malnutrition, and endocrine deficiencies, which are frequent in the elderly, may also predispose to severe infections. Other risk factors for sepsis include recurrent hospitalization, especially in the Intensive Care Unit, and nursing home residence, where interventions such as urinary catheterization or multiple drug use are quite frequent and many studies reported that people above 65 years of age are three times more likely to be admitted to hospital than those aged 16-64 years, and have a higher risk of prolonged hospital stays, institutionalization and death. Clinical evaluation of the frail patient with sepsis poses some challenges. The immune response becomes progressively less efficient with increasing age thereby causing an altered response to infection and it is important to know that the clinical evaluation of the so-called fragile patient with severe infection should take into account the sometimes unusual signs and symptoms that, if identified, can lead to early diagnosis. Laboratory diagnostics can also be of great help in this setting. The treatment of sepsis in the fragile patient can be empirical or based on microbiological culture. Moreover, frail patient population presents many clinical problems with numerous comorbidities, therefore anti-infective treatment is difficult, so the physician’s armamentarium must include many antibiotic drugs, of which there are far more available for the treatment of sepsis caused by Gram-positive bacteria than for sepsis caused by Gram-negative ones or fungi.

BACKGROUND: The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. METHODS: In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. RESULTS: The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P < .001). Postantibiogram therapy with a combination of tigecycline, colistin, and meropenem was associated with lower mortality (OR: 0.11; 95% CI: .02-.69; P = .01). CONCLUSIONS: KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.

The purpose of the present study was to evaluate the significance of shortening the antibiotic treatment duration in prosthetic joint infections (PJI) treated with debridement, antibiotics and implant retention (DAIR). In April 2006 we shortened the total antibiotic treatment duration in total knee arthroplasty (TKA) PJIs from 6 months to 3 months and in total hip arthroplasty (THA) PJIs from 3 months to 2 months. All patients with TKA or THA PJI treated with DAIR between February 2001 and August 2009 were reviewed retrospectively. There were 132 patients treated with DAIR, of whom 86 (65%) completed the antibiotic therapy and were therefore eligible for comparison concerning the length of antibiotic treatment. There were 32 (37%) THA and 54 (63%) TKA PJIs in the comparison. The treatment succeeded in 34 (89.5%) patients treated with longer antibiotic treatment and in 42 (87.5%) of those treated with shorter antibiotic treatment (p 0.78). Our conclusion is that if the patient completes the antibiotic therapy, treatment duration of 3 months in TKA PJIs and 2 months in THA PJIs is as good as longer antibiotic treatment of 6 months or 3 months, respectively, in patients treated with DAIR.

Objectives: To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patientswith Gram-positive infections. Methods: MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration(Cmin) for InI and steady-state concentration (Css) for CoI; area under the curve at 24 h (AUC24) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I2 test was calculated to assess heterogeneity across studies. Results: One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P=0.02;I2=0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P=0.9; I2=0). Conclusions: Our meta-analysis suggests that administration of vancomycin for the treatment ofGram-positiveinfections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug.RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Research has demonstrated the need for identifying a novel antimicrobial agent for topical use in the pediatric dental population. The essential oil of Lippia sidoides Cham. (LSO) has been described as having favorable biological properties, and a broad in vitro and in vivo antimicrobial spectrum against bacteria and yeast infections. Our aim was to determine a dose and formulation of LSO, acceptable for clinical testing in a pediatric population with dental caries. Thirty-seven 6–12-year old children were selected to participate in this study, and randomly allocated to receive different concentrations of either a gel (0.8%, 1%, 1.2% and 1.4%) or a mouth rinse (0.6%, 0.8%, 1% and 1.2%) formulation. The highest percentage MS reduction was observed with 0.8% mouth rinse and 1.4% gel. The efficacy of these concentrations was compared with a Thy–Car mixture formulated as a mouth rinse and gel treatments in 11 children. Saliva was collected after a single application of the antimicrobial treatment to establish effectiveness against MS. Both rinse (p