Revistas
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN:
0066-4804
Año:
2023
Vol.:
67
N°:
1
Págs.:
e0126422
Tunneled central venous catheter (TCVC) related infection remains a challenge in the care of hemodialysis patients. We aimed to determine the best antimicrobial lock therapy (ALT) to eradicate coagulase-negative staphylococci (CoNS) biofilms. Tunneled central venous catheter (TCVC) related infection remains a challenge in the care of hemodialysis patients. We aimed to determine the best antimicrobial lock therapy (ALT) to eradicate coagulase-negative staphylococci (CoNS) biofilms. We studied the colonization status of the catheter every 30 days by quantitative blood cultures (QBC) drawn through all catheter lumens. Those patients with a significant culture (i.e.,100 to 1,000 CFU/mL) of a CoNS were classified as patients with a high risk of developing catheter-related bloodstream infections (CRBSI). They were assigned to receive daptomycin, vancomycin, teicoplanin lock solution, or the standard of care (SoC) (i.e., heparin lock). The primary endpoint was to compare eradication ability (i.e., negative QBC for 30 days after ending ALT) rates between different locks and the SoC. A second objective was to analyze the correlation between ALT exposure and isolation of CoNS with antimicrobial resistance. Daptomycin lock was associated with a significant higher eradication success than with the SoC: 85% versus 30% (relative risk [RR] = 14, 95% confidence interval [CI] = 2.4 - 82.7); followed by teicoplanin locks with a 83.3% success (RR = 11.7; 95% CI = 2 - 70.2). We observed CoNs isolates with a higher teicoplanin MIC in patients with repeated teicoplanin locks exposure (coefficient = 0.3; 95% CI = 0.11 - 0.47). However, teicoplanin MICs decreased in patients treated with vancomycin locks (coefficient = -0.56; 95% CI = -0.85 - -0.02). Methicillin-resistance decreased with accumulative ALT (RR = 0.82; 95% CI = 0.69 - 0.98). In this study, daptomycin locks achieve the highest eradication rate of CoNS from hemodialysis catheters in vivo.
Revista:
FRONTIERS IN MICROBIOLOGY
ISSN:
1664-302X
Año:
2023
Vol.:
14
Págs.:
1094929
IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[F-18] fluoro-D-glucose: [F-18]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms. MethodsWe tested two specific radiotracers: 2-deoxy-2-[F-18]-fluoro-D-sorbitol ([F-18]FDS) and 2-[F-18]F-rho-aminobenzoic acid ([F-18]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection. Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [F-18]FDG in vitro. [F-18]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [F-18]FPABA. Furthermore, [F-18]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.
Revista:
ANTIBIOTICS
ISSN:
2079-6382
Año:
2022
Vol.:
11
N°:
3
Págs.:
330
Antimicrobial stewardship programs (ASP) promote appropriate antimicrobial use. We present a 4-year retrospective study that evaluated the clinical impact of the acceptance of the recommendations made by a meropenem-focused ASP. A total of 318 meropenem audits were performed. The ASP team (comprising infectious disease physicians, pharmacists and microbiologists) considered meropenem use in 96 audits (30.2%) to be inappropriate. The reasons to consider these uses inappropriate were the possibility of de-escalating to a narrower-spectrum antibiotic, in 66 (68.7%) audits, and unnecessary meropenem use, in 30 (31.3%) audits. The ASP team recommended de-escalation in 66 audits (68.7%) and discontinuation of meropenem in 30 audits (31.3%). ASP interventions were stratified according to whether or not recommendations were followed. The group in which recommendations were accepted and followed (i.e., accepted audit, AA) included 66 audits (68.7%) and the group in which recommendations were not followed (i.e., rejected audit, RA) included 30 (31.3%) audits. The comorbidity of the AA group (Charlson score) was higher than in the RA group (7.0 (5.0-9.0) vs. 6.0 (4.0-7.0), p = 0.02). Discontinuation of meropenem was recommended in 83.3% of audits in the AA group vs. 62.2% in the RA group (OR 3.05 (1.03-8.99), p = 0.04). Ertapenem de-escalation resulted in a 100% greater rate of follow-up compared with the non-carbapenem option (100% vs. 51.9%, OR 1.50 (1.21-1.860), p = 0.001). Significant differences were observed in the AA group when cultures were taken before antibiotic prescription-98.5% vs. 83.3% (p = 0.01, OR 13.0 (1.45-116.86))-or when screening cultures were taken-45.5% vs. 19.2% (p = 0.03, OR 3.5 (1.06-11.52)). There were no differences between the groups in terms of overall mortality and 30-day mortality, length of stay, Clostridiodes difficile infection, 30-day readmission or hospitalization costs. In conclusion, meropenem ASP recommendations contributed to a decrease in meropenem prescription without worsening clinical and economic outcomes.
Revista:
ANTIBIOTICS
ISSN:
2079-6382
Año:
2022
Vol.:
11
N°:
12
Págs.:
1692
This study aimed to prove that pre-emptive antimicrobial locks in patients at risk of bacteremia decrease infection. We performed a non-randomized prospective pilot study of hemodialysis patients with tunneled central venous catheters. We drew quantitative blood cultures monthly to detect colonization. Patients with a critical catheter colonization by coagulase-negative staphylococci (defined as counts of 100-999 CFU/mL) were at high risk of developing a catheter-related bloodstream infection. We recommended antimicrobial lock for this set of patients. The nephrologist in charge of the patient decided whether to follow the recommendation or not (i.e., standard of care). We compared bloodstream infection rates between patients treated with antimicrobial lock therapy versus patients treated with the standard of care (i.e., heparin). We enrolled 149 patients and diagnosed 86 episodes of critical catheter colonization by coagulase-negative staphylococci. Patients treated with antimicrobial lock had a relative risk of bloodstream infection of 0.19 when compared with heparin lock (CI 95%, 0.11-0.33, p < 0.001) within three months of treatment. We avoided one catheter-related bloodstream infection for every ten catheter-critical colonizations treated with antimicrobial lock [number needed to treat 10, 95% CI, 5.26-100, p = 0.046]. In conclusion, pre-emptive antimicrobial locks decrease bloodstream infection rates in hemodialysis patients with critical catheter colonization.
Revista:
ANTIBIOTICS
ISSN:
2079-6382
Año:
2021
Vol.:
10
N°:
11
Págs.:
1276
According to the search for alternatives to replace antibiotics in animal production suggested in the antimicrobial resistance action plans around the world, the objective of this work was to evaluate the bactericidal effect of kaolin-silver nanomaterial for its possible inclusion as an additive in animal feed. The antibacterial activity of the C3 (kaolin-silver nanomaterial) product was tested against a wide spectrum of Gram-negative and Gram-positive bacteria (including multidrug resistant strains) by performing antibiograms, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), as well as growth inhibition curves against seven strains causing infections in animals. The C3 product generated inhibition halos in all the tested strains, and a higher activity against Gram-negative bacteria was found, with MBC values ranged from 7.8 µg/mL (P. aeruginosa) to 15.6 µg/mL (E. coli and Salmonella). In contrast, it was necessary to increase the concentration to 31.3 µg/mL or 250 µg/mL to eliminate 99.9% of the initial population of S. aureus ATCC 6538 and E. faecium ATCC 19434, respectively. Conversely, the inhibition growth curves showed a faster bactericidal activity against Gram-negative bacteria (between 2 and 4 h), while it took at least 24 h to observe a reduction in cell viability of S. aureus ATCC 6538. In short, this study shows that the kaolin-silver nanomaterials developed in the framework of the INTERREG POCTEFA EFA183/16/OUTBIOTICS project exhibit antibacterial activity against a wide spectrum of bacteria. However, additional studies on animal safety and environmental impact are necessary to evaluate the effectiveness of the proposed alternative in the context of One Health.
Revista:
VIRULENCE
ISSN:
2150-5594
Año:
2021
Vol.:
12
N°:
1
Págs.:
1672 - 1688
Chronic obstructive pulmonary disease (COPD) patients undergo infectious exacerbations whose frequency identifies a clinically meaningful phenotype. Mouse models have been mostly used to separately study both COPD and the infectious processes, but a reliable model of the COPD frequent exacerbator phenotype is still lacking. Accordingly, we first established a model of single bacterial exacerbation by nontypeable Haemophilus influenzae (NTHi) infection on mice with emphysema-like lesions. We characterized this single exacerbation model combining both noninvasive in vivo imaging and ex vivo techniques, obtaining longitudinal information about bacterial load and the extent of the developing lesions and host responses. Bacterial load disappeared 48 hours post-infection (hpi). However, lung recovery, measured using tests of pulmonary function and the disappearance of lung inflammation as revealed by micro-computed X-ray tomography, was delayed until 3 weeks post-infection (wpi). Then, to emulate the frequent exacerbator phenotype, we performed two recurrent episodes of NTHi infection on the emphysematous murine lung. Consistent with the amplified infectious insult, bacterial load reduction was now observed 96 hpi, and lung function recovery and disappearance of lesions on anatomical lung images did not happen until 12 wpi. Finally, as a proof of principle of the use of the model, we showed that azithromycin successfully cleared the recurrent infection, confirming this macrolide utility to ameliorate infectious exacerbation. In conclusion, we present a mouse model of recurrent bacterial infection of the emphysematous lung, aimed to facilitate investigating the COPD frequent exacerbator phenotype by providing complementary, dynamic information of both infectious and inflammatory processes.
Autores:
Cortes-Lara, S.; del Barrio-Tofiño, E.; López-Causapé, C. (Autor de correspondencia); et al.
Revista:
CLINICAL MICROBIOLOGY AND INFECTION
ISSN:
1198-743X
Año:
2021
Vol.:
27
N°:
11
Págs.:
1631 - 1637
Objectives: The aim was to develop and validate a Pseudomonas aeruginosa genotypic resistance score, based on analysis of the whole genome sequence resistome, to predict antimicrobial susceptibility phenotypes. Methods: A scoring system based on the analysis of mutation-driven resistance in 40 chromosomal genes and horizontally acquired resistance (Resfinder) was developed for ceftazidime, ceftolozane/tazobactam, meropenem, ciprofloxacin and tobramycin. Resistance genes/mutations were scored from 0 (no effect) to 1 (EUCAST clinical resistance). One hundred wild-type strains obtained from 51 different hospitals during a 2017 multicentre study were fully sequenced and analysed in order to define a catalogue of natural polymorphisms in the 40 chromosomal resistance genes. The capacity of genotypic score to predict the susceptibility phenotype was tested in 204 isolates randomly selected from the 51 hospitals (four from each hospital). Results: The analysis of the 100 wild-type isolates yielded a catalogue of 455 natural polymorphisms in the 40 genes involved in mutational resistance. However, resistance mutations and high-risk clones (such as ST235) were also documented among a few wild-type isolates. Overall, the capacity of the genotypic score (<0.5) for predicting phenotypic susceptibility (S thorn I in the case of meropenem) was very high (95-10 0%). In contrast, the capacity of the genotypic score to predict resistance (>1) was far more variable depending on the agent...
Autores:
Ceballos, S.; Aspiroz, C.; Ruiz-Ripa, L.; et al.
Revista:
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
ISSN:
0924-8579
Año:
2020
Vol.:
55
N°:
4
Págs.:
105907
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) of lineage CC398 is an emerging clone causing human infections but is mostly found in pigs. The aim of this study was to characterize the antimicrobial resistance phenotypes/genotypes of a collection of 137 MRSA CC398 isolates obtained in a previous study from 17 Spanish hospitals, using tetracycline resistance as marker for selection. A multidrug-resistant (MDR) phenotype was present in 79% of analysed isolates, with 17% of them resistant to at least six different antimicrobial families. All tetracycline-resistant isolates (n = 137) carried the tetM gene and 75% also carried the tetK gene. Almost 50% of MRSA CC398 isolates showed macrolide and/or lincosamide resistance: a) 39% of isolates were ERYR-CLIR (all with constitutive phenotype), with 87% of them carrying the ermC gene, followed by msrA (25%), ermB (21%), vgaA (17%), ermA (6%), lsaB (4%), linA (2%), linB (2%), and ermT (2%, this isolate with the new spa-type t18071); and b) 9% of MRSA CC398 isolates showed the dissociated ERYS-CLIR phenotype carrying the linA, linB, lsaB and vgaA genes. Other antimicrobial resistance phenotypes in these MRSA CC398 isolates included resistance to ciprofloxacin (67%), aminoglycosides (21%), mupirocin (6%), chloramphenicol (4%) or fusidic acid (2%). The more common resistance genes detected for some of these antimicrobials were: aac(6')-Ie-aph(2 '')-Ia (16%) and ant(4')-Ia (12%) for aminoglycosides, and fexA (3%) for chloramphenicol. The high rate of MDR phenotypes with a wide range of antimicrobial resistance genes shown in this study reduce the potential therapeutic options in case of infections. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Autores:
Miqueleiz-Zapatero, A.; Alba-Rubio, C.; Domingo-Garcia, D.; et al.
Revista:
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA
ISSN:
0213-005X
Año:
2020
Vol.:
38
N°:
9
Págs.:
410 - 416
Introduction: The aim of this study was to know, through a national survey, the methods and techniques used for the diagnosis of Helicobacter pylori (Hp) in the different Clinical Microbiology Services/Laboratories in Spain, as well as antibiotic resistance data. Methods: The survey requested information about the diagnostic methods performed for Hp detection in Clinical Microbiology laboratories, including serology, stool antigen, culture from gastric biopsies, and PCR. In addition, the performance of antibiotic susceptibility was collected. Data on the number of samples processed in 2016, positivity of each technique and resistance data were requested. The survey was sent by email (October-December 2017) to the heads of 198 Clinical Microbiology Laboratories in Spain. Results: Overall, 51 centers from 29 regions answered the survey and 48/51 provided Hp microbiological diagnostic testing. Concerning the microbiological methods used to diagnose Hp infection, the culture of gastric biopsies was the most frequent (37/48), followed by stool antigen detection (35/48), serology (19/48) and biopsy PCR (5/48). Regarding antibiotic resistance, high resistance rates were observed, especially in metronidazole and clarithromycin (over 33%). Conclusion: Culture of gastric biopsies was the most frequent method for detection of Hp, but the immunochromatographic stool antigen test was the one with which the largest number of samples were analyzed. Nowadays, in Spain, it concerns the problem of increased antibiotic resistance to 'first-line' antibiotics. (C) 2019 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.
Autores:
López-López, N.; Euba, B.; Hill, J.; et al.
Revista:
ACS INFECTIOUS DISEASES
ISSN:
2373-8227
Año:
2020
Vol.:
6
N°:
3
Págs.:
406 - 421
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and impaired airway immunity, which provides an opportunistic platform for nontypeable Haemophilus influenzae (NTHi) infection. Clinical evidence supports that the COPD airways present increased concentrations of glucose, which may facilitate proliferation of pathogenic bacteria able to use glucose as a carbon source. NTHi metabolizes glucose through respiration-assisted fermentation, leading to the excretion of acetate, formate, and succinate. We hypothesized that such specialized glucose catabolism may be a pathoadaptive trait playing a pivotal role in the NTHi airway infection. To find out whether this is true, we engineered and characterized bacterial mutant strains impaired to produce acetate, formate, or succinate by inactivating the ackA, pflA, and frdA genes, respectively. While the inactivation of the pflA and frdA genes only had minimal physiological effects, the inactivation of the ackA gene affected acetate production and led to reduced bacterial growth, production of lactate under low oxygen tension, and bacterial attenuation in vivo. Moreover, bacterially produced acetate was able to stimulate the expression of inflammatory genes by cultured airway epithelial cells. These results back the notion that the COPD lung supports NTHi growth on glucose, enabling production of fermentative end products acting as immunometabolites at the site of infection. Thus, glucose catabolism may contribute not only to NTHi growth but also to bacterially driven airway inflammation. This information has important implications for developing nonantibiotic antimicrobials, given that airway glucose homeostasis modifying drugs could help prevent microbial infections associated with chronic lung disease.
Revista:
MICROORGANISMS
ISSN:
2076-2607
Año:
2020
Vol.:
8
N°:
9
Págs.:
1425
Due to the global progress of antimicrobial resistance, the World Health Organization (WHO) published the list of the antibiotic-resistant "priority pathogens" in order to promote research and development of new antibiotics to the families of bacteria that cause severe and often deadly infections. In the framework of the One Health approach, the surveillance of these pathogens in different environments should be implemented in order to analyze their spread and the potential risk of transmission of antibiotic resistances by food and water. Therefore, the objective of this work was to determine the presence of high and critical priority pathogens included in the aforementioned list in different aquatic environments in the POCTEFA area (North Spain-South France). In addition to these pathogens, detection of colistin-resistant Enterobacteriaceae was included due its relevance as being the antibiotic of choice to treat infections caused by multidrug resistant bacteria (MDR). From the total of 80 analyzed samples, 100% of the wastewater treatment plants (WWTPs) and collectors (from hospitals and slaughterhouses) and 96.4% of the rivers, carried antibiotic resistant bacteria (ARB) against the tested antibiotics. Fifty-five (17.7%) of the isolates were identified as target microorganisms (high and critical priority pathogens of WHO list) and 58.2% (n= 32) of them came from WWTPs and collectors. Phenotypic and genotypic characterization showed that 96.4% were MDR and resistance to penicillins/cephalosporins was the most widespread. The presence ofblagenes, KPC-type carbapenemases,mcr-1andvanBgenes has been confirmed. In summary, the presence of clinically relevant MDR bacteria in the studied aquatic environments demonstrates the need to improve surveillance and treatments of wastewaters from slaughterhouses, hospitals and WWTPs, in order to minimize the dispersion of resistance through the effluents of these areas.
Revista:
INTERNATIONAL MICROBIOLOGY
ISSN:
1139-6709
Año:
2020
Vol.:
23
N°:
2
Págs.:
171 - 177
Presence of extended-spectrum beta-lactamase (ESBL-E), AmpC-producing and carbapenemase-producing (CPE) Enterobacteriaceae has been observed not only in the clinical environment, but also in the out-of-hospital environment. The objective of this study was to isolate and characterize strains of ESBL, AmpC, and CPE present in feces of healthy carriers in Navarra (n = 125). Despite the fact that no CPE strains were isolated, 16% and 11.2% of the studied population were ESBL-E and AmpC carriers, respectively. No significant differences were found by gender or age; young people (5-18 years old) showed the highest ESBL-E prevalence (31.8%). The isolates corresponded to E. coli (57.1%), Enterobacter spp. (28.6%), and Citrobacter freundii (14.3%), and all strains showed multidrug-resistant profiles. High resistance against cephalosporins, penicillins, and monobactams, and sensitivity to carbapenems, quinolones, and aminoglycosides were observed. With respect to ESBL producers, 52.4% were CTX-M-type (19.0% CTX-M-14, 9.5% CTX-M-1, and 28.6% CTX-M-15) and 47.6% were TEM-type (38.1% TEM-171). These results confirm the extensive dissemination of these resistances among a healthy population and pose the need to implement control measures and strategies according to the One Health approach in order to prevent the increase of severe and untreatable infections in a not far future.
Autores:
Perez-Vazquez, M. (Autor de correspondencia); Campoy, P. J. S. ; Ortega, A.; et al.
Revista:
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
ISSN:
0305-7453
Año:
2019
Vol.:
74
N°:
12
Págs.:
3489 - 3496
Objectives: NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring bla(NDM)-like genes. Methods: High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8year period in Spain. Results: Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three bla(NDM) types were identified: bla(NDM-1), 61.2%; bla(NDM-7), 32.8%; and bla(NDM-5), 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three bla(OXA-48) and two bla(VIM-1)). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding bla(NDM)-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of bla(NDM)-like genes showed a highly variable region upstream of ISAba125. Conclusions: In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried bla(NDM), and the same IncX3 plasmid was detected in K. pneumoniae and E. coli.
Autores:
Ceballos, S.; Aspiroz, C.; Ruiz-Ripa, L.; et al.
Revista:
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
ISSN:
0305-7453
Año:
2019
Vol.:
74
N°:
8
Págs.:
2157 - 2161
Background: Tetracycline resistance (Tet(R)) is a marker of livestock-associated MRSA of lineage CC398. Objectives: To determine the MRSA CC398 prevalence among Tet(R)-MRSA recovered in Spanish hospitals located in regions with different pig-farming densities, and the influence of pig density as a key risk factor for its acquisition. Methods: Tet(R)-MRSA isolates (n = 232) recovered from clinical and epidemiological samples during January-June 2016 in 20 hospitals in 13 regions with different pig-farming densities were analysed. MRSA CC398 identification, detection of spa types, methicillin resistance genes and immune evasion cluster (IEC) genes were performed by PCR/sequencing. Statistical analyses were performed to establish the relationships between MRSA CC398 prevalence and pig density. Results: The global MRSA prevalence was 29.7% (6.9% Tet(R)-MRSA/MRSA), with 137 CC398 isolates recovered, representing 4.1% of total MRSA and 59.1% of Tet(R)-MRSA. Among MRSA CC398, 16 different spa types were recorded (t011: 72.3%), and all but two strains were IEC negative. Higher pig-density regions were associated with significant MRSA CC398 increases in hospitals located in adjacent regions (P<0.001). Linear regression models explained the relationships between MRSA CC398 and pig density (P<0.001), with an increase of 6.6 MRSA CC398 cases per 100 MRSA per increase of 100 pigs/km(2) in a region. Conclusions: High pig density leads to a significant increase in MRSA CC398 in hospitals in Spain, and its combination with a high human population could help its dissemination. In Spain, the prevalence of the zoonotic CC398 lineage is closely related to pig-farming density; therefore, specific tools could be implemented in order to detect its dissemination.
Revista:
PATHOGENS AND DISEASE
ISSN:
2049-632X
Año:
2019
Vol.:
77
N°:
5
Págs.:
ftz051
Non-pigmented rapidly growing mycobacteria (NPRGM) are widely distributed in water, soil and animals. It has been
observed an increasing importance of NPRGM related-infections, particularly due to the high antimicrobial resistance.
NPRGM have rough and smooth colony phenotypes, and several studies have showed that rough colony variants are more
virulent than smooth ones. However, other studies have failed to validate this observation. In this study, we have performed
two models, in vitro and in vivo, in order to assess the different pathogenicity of these two phenotypes. We used collection
and clinical strains of Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium chelonae. On the in vitro model
(macrophages), phagocytosis was higher for M. abscessus and M. fortuitum rough colony variant strains when compared to
smooth colony variants. However, we did not find differences with colonial variants of M. chelonae. Survival of Galleria
mellonella larvae in the experimental model was lower for M. abscessus and M. fortuitum rough colony variants when
compared with larvae infected with smooth colony variants. We did not find differences in larvae infected with M. chelonae.
Results of our in vivo study correlated well with the experimental model. This fact could have implications on the
interpretation of the clinical significance of the NPRGM isolate colonial variants.
Autores:
Fernández-Calver, A.; Euba, B.; Caballero, L.; et al.
Revista:
BIOMOLECULES
ISSN:
2218-273X
Año:
2019
Vol.:
9
N°:
12
Págs.:
891
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammation and impaired airway immunity, providing an opportunistic platform for nontypeable Haemophilus influenzae (NTHi) infection. In this context, therapies targeting not only overactive inflammation without significant adverse effects, but also infection are of interest. Increasing evidence suggests that polyphenols, plant secondary metabolites with anti-inflammatory and antimicrobial properties, may be protective. Here, a Cistus salviifolius plant extract containing quercetin, myricetin, and punicalagin was shown to reduce NTHi viability. Analysis of these polyphenols revealed that quercetin has a bactericidal effect on NTHi, does not display synergies, and that bacteria do not seem to develop resistance. Moreover, quercetin lowered NTHi airway epithelial invasion through a mechanism likely involving inhibition of Akt phosphorylation, and reduced the expression of bacterially-induced proinflammatory markers il-8, cxcl-1, il-6, pde4b, and tnf¿. We further tested quercetin's effect on NTHi murine pulmonary infection, showing a moderate reduction in bacterial counts and significantly reduced expression of proinflammatory genes, compared to untreated mice. Quercetin administration during NTHi infection on a zebrafish septicemia infection model system showed a bacterial clearing effect without signs of host toxicity. In conclusion, this study highlights the therapeutic potential of the xenohormetic molecule quercetin against NTHi infection.
Autores:
Fernandez-Calvet, A. ; Euba, B. ; Caballero, L. ; et al.
Revista:
BIOMOLECULES
ISSN:
2218-273X
Año:
2019
Vol.:
9
N°:
12
Págs.:
891
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammation and impaired airway immunity, providing an opportunistic platform for nontypeable Haemophilus influenzae (NTHi) infection. In this context, therapies targeting not only overactive inflammation without significant adverse effects, but also infection are of interest. Increasing evidence suggests that polyphenols, plant secondary metabolites with anti-inflammatory and antimicrobial properties, may be protective. Here, a Cistus salviifolius plant extract containing quercetin, myricetin, and punicalagin was shown to reduce NTHi viability. Analysis of these polyphenols revealed that quercetin has a bactericidal effect on NTHi, does not display synergies, and that bacteria do not seem to develop resistance. Moreover, quercetin lowered NTHi airway epithelial invasion through a mechanism likely involving inhibition of Akt phosphorylation, and reduced the expression of bacterially-induced proinflammatory markers il-8, cxcl-1, il-6, pde4b, and tnf alpha. We further tested quercetin's effect on NTHi murine pulmonary infection, showing a moderate reduction in bacterial counts and significantly reduced expression of proinflammatory genes, compared to untreated mice. Quercetin administration during NTHi infection on a zebrafish septicemia infection model system showed a bacterial clearing effect without signs of host toxicity. In conclusion, this study highlights the therapeutic potential of the xenohormetic molecule quercetin against NTHi infection.
Revista:
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
ISSN:
0924-8579
Año:
2018
Vol.:
52
N°:
1
Págs.:
123 - 124
Revista:
MEDICINE (ELSEVIER)
ISSN:
0304-5412
Año:
2018
Vol.:
12
N°:
49
Págs.:
2901 - 2909
Corynebacterium, Listeria and Bacillus are ubiquitous gram-positive aerobic bacilli, which colonize environment, animals and human body. Corynebacterium diphtheriae produces diphtheria either cutaneous or respiratory forms, a disease controlled by vaccination only in some countries and with increased incidence due to immigration and vaccine rejection. Listeria monocytgenes is associated with bacteremia and meningitis in pregnant women, neonates, elderly and immunosuppressed patients, although its incidence at a global level remains unknown. Bacillus anthracis is considered a potential bioterrorism agent because of its lethality. Considering that all cutaneous, gastrointestinal and respiratory symptoms of anthrax could be unspecific, diagnostic procedures that allow their detection with greater safety in case of suspicion have been developed. Toxin production, invasiveness and intracellular survival, resistance in the environment and lytic enzymes production are mechanisms of virulence of these species. Other Corynebacterium or Bacillus species are considered opportunistic pathogens and their clinical relevance has increased along the last decades, with the increase of immunosuppressed patients and the use of medical devices and prostheses susceptible of colonization.
Revista:
MEDICINE (ELSEVIER)
ISSN:
0304-5412
Año:
2018
Vol.:
12
N°:
50
Págs.:
2941 - 2951
Revista:
MEDICINE (ELSEVIER)
ISSN:
0304-5412
Año:
2018
Vol.:
12
N°:
50
Págs.:
2963 - 2971
ntroduction: The HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) includes slow-growing gram-negative bacteria that form part of the microbiota of the upper respiratory and genitourinary tracts of humans and animals. Clinical manifestations: These are the slow-growing, gram-negative bacilli that most frequently cause infections in human beings, and can give rise to infections in any location, but fundamentally the skin and soft tissues, and cause bacteraemia and endocarditis. Diagnosis: They are nutritionally demanding bacteria and for visible colonies to develop require blood agar or chocolate agar, an aerobic atmosphere, generally CO2 rich and incubation of at least 42 hours. They are difficult to identify phenotypically as a species and it is not always possible to do so, even using automated systems. However molecular and proteomic techniques have resulted in increased identification and an awareness of their role in human infectious pathology. Treatment: There is limited data on their sensitivity to antimicrobial agents, although from the existing data it is known that amoxicillin-clavulanic acid, second and third generation cephalosporins and fluoroquinolones generally act against them.
Revista:
MEDICINE (ELSEVIER)
ISSN:
0304-5412
Año:
2018
Vol.:
12
N°:
51
Págs.:
2991 - 2999
Introduction.: Tetanus and botulism constitute two life-threating infections caused by spore-forming bacteria, Clostridium tetani and Clostridium botulinum, respectively. Tetanus.: Tetanus is caused by tetanospasmine toxin, which inhibits GABA and glicine neurotransmitters release, causing spastic paralysis followed by respiratory failure and severe impairment of autonomic nervous system. Mortality rate is approximately 8-60%, therefore a prompt clinical diagnosis is essential to transfer the patient to intensive care unit and establish supportive care. In addition, the toxin must be neutralized with specific immunoglobulin, spasms must be controlled with benzodiazepines and cardiovascular instability must be managed with labetalol and magnesium sulphate. Botulism.: Botulism is caused by a thermolabile neurotoxin resulting in flaccid paralysis and respiratory failure, with an observed mortality of 5-10%. There are eight different toxins (A-H) produced by several Clostridium specie, responsible for botulism. Infection can occur following food poisoning with preformed toxin (food-borne botulism), by ingestion of food contaminated with Clostridium botulinum spores (infant botulism), by wound contamination or bacteria inhalation if used as a bioweapon. Early respiratory and airway support must be established together with additional measures (antitoxin and antibiotic).
Revista:
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA
ISSN:
0213-005X
Año:
2017
Vol.:
35
N°:
Supl. 3
Págs.:
29 - 43
Revista:
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
ISSN:
2235-2988
Año:
2017
Vol.:
7
Págs.:
266
Antibacterial treatment with cotrimoxazol (TxS), a combination of trimethoprim and sulfamethoxazole, generates resistance by, among others, acquisition of thymidine auxotrophy associated with mutations in the thymidylate synthase gene thyA, which can modify the biology of infection. The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) is frequently encountered in the lower airways of chronic obstructive pulmonary disease (COPD) patients, and associated with acute exacerbation of COPD symptoms. Increasing resistance of NTHi to TxS limits its suitability as initial antibacterial against COPD exacerbation, although its relationship with thymidine auxotrophy is unknown. In this study, the analysis of 2,542 NTHi isolates recovered at Bellvitge University Hospital (Spain) in the period 2010-2014 revealed 119 strains forming slow-growing colonies on the thymidine low concentration medium Mueller Hinton Fastidious, including one strain isolated from a COPD patient undergoing TxS therapy that was a reversible thymidine auxotroph. To assess the impact of thymidine auxotrophy in the NTHi-host interplay during respiratory infection, thyA mutants were generated in both the clinical isolate NTHi375 and the reference strain RdKW20. Inactivation of the thyA gene increased TxS resistance, but also promoted morphological changes consistent with elongation and impaired bacterial division, which altered H. influenzae self-aggregation, phosphorylcholine level, C3b deposition, and airway epithelial infection patterns. Availability of external thymidine contributed to overcome such auxotrophy and TxS effect, potentially facilitated by the nucleoside transporter nupC. Although, thyA inactivation resulted in bacterial attenuation in a lung infection mouse model, it also rendered a lower clearance upon a TxS challenge in vivo. Thus, our results show that thymidine auxotrophy modulates both the NTHi host airway interplay and antibiotic resistance, which should be considered at the clinical setting for the consequences of TxS administration.
Revista:
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
ISSN:
0305-7453
Año:
2017
Vol.:
72
N°:
2
Págs.:
625 - 628
Revista:
JOURNAL OF PLASTIC, RECONSTRUCTIVE & AESTHETIC SURGERY (ONLINE)
ISSN:
1532-1959
Año:
2016
Vol.:
69
N°:
1
Págs.:
70-76
The difference in thickness between the control capsules and those from the infection group is an indication that bacterial contamination of a capsule from a remote late infection may increase the incidence of capsular contracture suggesting that treating late infections could in fact prevent capsular contracture.
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN:
0066-4804
Año:
2015
Vol.:
59
N°:
12
Págs.:
7581 - 7592
Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae(NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitroand/or in vivoefficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection.
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN:
0066-4804
Año:
2015
Vol.:
59
N°:
5
Págs.:
2700 - 2712
Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.
Autores:
Rojo-Molinero, E.; Alados, J. C.; Gómez G. de la Pedrosa, E.; et al.
Revista:
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA
ISSN:
0213-005X
Año:
2015
Vol.:
33
N°:
6
Págs.:
404 - 410
The normal activity in the laboratory of microbiology poses different risks - mainly biological - that can affect the health of their workers, visitors and the community. Routine health examinations (surveillance and prevention), individual awareness of self-protection, hazard identification and risk assessment of laboratory procedures, the adoption of appropriate containment measures, and the use of conscientious microbiological techniques allow laboratory to be a safe place, as records of laboratory-acquired infections and accidents show. Training and information are the cornerstones for designing a comprehensive safety plan for the laboratory. In this article, the basic concepts and the theoretical background on laboratory safety are reviewed, including the main legal regulations. Moreover, practical guidelines are presented for each laboratory to design its own safety plan according its own particular characteristics.
Revista:
MEAT SCIENCE
ISSN:
0309-1740
Año:
2013
Vol.:
93
N°:
2
Págs.:
316 - 321
Patterns of resistance in ß-lactamase-producing Enterobacteriaceae family were investigated in isolates
from 141 meat products (beef, poultry and pork) purchased in Spain. The strains that grow in ChromID
ESBL agar plates were confirmed using the paired disk diffusion method. Resistance to amoxicillin/clavulanic
acid, ceftazidime, ceftriaxone, aztreonam, cefpodoxime, gentamicin, doxycycline, cotrimoxazol, norfloxacin,
piperacillin/tazobactam, fosfomycin and cefoxitin were tested following CLSI recommendations. Minimum
inhibitory concentrations were determined by the MicroScan® NM37 panel and ß-lactamase genes were
detected using multiplex PCR and sequencing. Results show poultry as the meat product having the highest
prevalence (84%), with Escherichia coli being the predominant bacteria (71.3%). Predominant ß-lactamase
types were CTX-M (37.8%), followed by CTX-M+TEM combination (20.7%), TEM (17%), SHV (12.2%),
TEM+SHV combination (10.9%) and OXA (1.2%). 93.9% of the strains were resistant to one or more
ß-lactam antibiotics. Results indicate a widespread distribution of ESBL-producing Enterobacteriaceae in meat
products, with a high rate of ß-lactam resistance and a low rate of AmpC cephalosporinase-producing strains.
Revista:
JOURNAL OF INFECTION
ISSN:
0163-4453
Año:
2012
Vol.:
65
N°:
4
Págs.:
302-309
The clinical value of information provided by the Microbiology Laboratory may be reduced by the time it takes to generate results for healthcare providers. The aim of this study was to measure the clinical and economic impact associated with rapid reporting of microbiological results. Methods: 574 hospitalized patients with a bacterial clinical infection confirmed by culture were evaluated. 284 hospitalized patients were included in the historical control group (results available the day following the analysis) and 290 in the intervention group (results available the same day of the analysis). The Vitek (R) 2 system (bioMerieux) was used for identification and antimicrobial susceptibility testing in both groups. Results: Faster reporting of microbiological results enabled the clinician to optimize the antibiotic treatment sooner (P < 0.001). This reduction in turnaround time (17.6 h) was associated with improved clinical outcome, a significant reduction in the length of hospitalization and the number of microbiological and biochemical tests performed. Intubation requirements were significantly lower in the intervention group. Mortality rates did not differ significantly between the two groups. Costs incurred for patients in the intervention group were significantly lower than those in the control group, including costs for Microbiology Laboratory testing, antibiotic costs, length of hospitalization and other patient care costs. Conclusions: Rapid microbiological information was associated with quality improvement seen in earlier changes in antibiotic use, an improved clinical outcome and financial benefits. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Revista:
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES
ISSN:
0934-9723
Año:
2012
Vol.:
31
N°:
9
Págs.:
2245-252
Inappropriate antibiotic prescriptions are associated with an increase in healthcare costs and a decrease in the quality of care. The aim of this study was to measure the clinical and economic impact of rapid microbiological reporting on the specimens most frequently processed by the Microbiology Laboratory. The Vitek® 2 system (bioMérieux) was used for identification and susceptibility testing. Only hospitalized patients with bacterial infections were included. Two groups were established, a historical control group (results available the day following the analysis) and an intervention group (results available the same day of the analysis). Specimens studied and the median length of time from the introduction of the microorganism in the Vitek® 2 until microbiological report were as follows: wound and abscess (control¿=¿23.5 h, intervention¿=¿9.5 h, p¿<¿0.001), blood (control¿=¿23.5 h, intervention¿=¿9.2 h, p¿<¿0.001), and urine (control¿=¿23.4 h, intervention¿=¿9.3 h, p¿<¿0.001). Outcome parameters were hospital stay and mortality rates. Hospital costs were calculated. The mortality rates did not differ significantly between the two groups. Faster reporting of identification and antimicrobial susceptibility results was associated with a significant reduction in hospital stay and in overall costs for those patients from whom wound, abscess, and urine specimens were analyzed. However, the antimicrobial results of blood culture isolates did not lead to significant clinical or f
Revista:
International Journal of Antimicrobial Agents
ISSN:
0924-8579
Año:
2011
Vol.:
37
N°:
6
Págs.:
585 - 587
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN:
0066-4804
Año:
2011
Vol.:
55
N°:
1
Págs.:
218 - 228
A subinhibitory concentration of compound P2-15 or P2-27 sensitized P. aeruginosa to most classes of antibiotics tested and counteracted several mechanisms of antibiotic resistance, including loss of the OprD porin and overexpression of several multidrug efflux pump systems. Using a mouse model of lethal infection, we demonstrated that whereas P2-15 and erythromycin were unable to protect mice when administered separately, concomitant administration of the compounds afforded long-lasting protection to one-third of the animals
Revista:
Enfermedades Infecciosas y Microbiologia Clinica
ISSN:
0213-005X
Año:
2010
Vol.:
28
N°:
8
Págs.:
562 - 563