Corticosteroids modulate biofilm formation and virulence of .

Corticosteroids are anti-inflammatory drugs commonly administered to patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis and similar lung pathologies, in which persistent infections with are frequent. However, their therapeutic value is debatable because of their adverse impact on host immunity. The aim of this work was to determine the impact of budesonide and fluticasone propionate on biology.

Collateral susceptibility-guided alternation of ceftolozane/tazobactam with imipenem prevents resistance development in XDR biofilms.

Objectives: New combinations of β-lactams and β-lactamase inhibitors, such as ceftolozane/tazobactam could be useful to combat biofilm-driven chronic infections by extensively resistant (XDR) but resistance development by mutations in the Ω-loop of AmpC has been described. However, these mutations confer collateral susceptibility to carbapenems. Thus we aimed to evaluate the therapeutic efficacy and the prevention of resistance development of regimen alternating ceftolozane/tazobactam and imipenem.

The incidence of HIV-2 infection in Spain is declining - a registry data analysis.

Objectives: HIV-2 infection is a neglected disease caused by a human retrovirus that causes AIDS more slowly than HIV-1. Infection with HIV-2 is endemic in West Africa. Given its differential features, guidelines recommend ruling out HIV-2 infection in all newly diagnosed HIV-seropositive individuals.

Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019-2021.

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM).

To update or not to update the ESCMID guidelines for the diagnosis and treatment of biofilm infections - That is the question! The opinion of the ESGB board.

Background: The work on the ESGB guidelines for diagnosis and treatment of biofilm infections began in 2012 and the result was published in 2014. The guidelines have been and still are frequently cited in the literature proving its usefulness for people working with biofilm infections. At the ESGB Biofilm conference in Mallorca 2022 (Eurobiofilms2022) the board of the ESGB decided to evaluate the 2014-guidelines and relevant publications since 2014 based on a lecture given at the Eurobiofilms2022.

Phenotypic and Genotypic Antimicrobial Susceptibility Testing of Isolates from Patients with Persistent or Clinical Treatment Failure in Spain.

The aim of this multicentre project (seven hospitals across the Spanish National Health Service) was to study the phenotypic and genotypic susceptibility of to the main antimicrobials used (macrolides, doxycycline, and quinolones) in isolates from patients with clinical treatment failure in whom reinfection had been ruled out. During 2018-2019, 73 clinical isolates were selected. Sixty-nine clinical specimens were inoculated onto confluent McCoy cell monolayers for phenotypic susceptibility testing.

Mechanisms of antibiotic resistance in biofilms.

is a major cause of life-threatening acute infections and life-long lasting chronic infections. The characteristic biofilm mode of life in chronic infections severely limits the efficacy of antimicrobial therapies, as it leads to intrinsic tolerance, involving physical and physiological factors in addition to biofilm-specific genes that can confer a transient protection against antibiotics promoting the development of resistance. Indeed, a striking feature of this pathogen is the extraordinary capacity to develop resistance to nearly all available antibiotics through the selection of chromosomal mutations, evidenced by its outstanding and versatile mutational resistome.

Genetic Characterization of Non- Indicates Distinct Infection Transmission Networks in Spain.

infection is an important public health problem. Our objective was to assess the dynamics of the transmission of this infection, analysing the distribution of circulating genotypes and multilocus sequence types of in Spain as a function of clinical and epidemiological variables. During 2018 and 2019, we genetically characterized in tertiary hospitals in six areas in Spain (Asturias, Barcelona, Gipuzkoa, Mallorca, Seville and Zaragoza), with a catchment population of 3.

Prevalence of the fimbrial operon mrkABCD, mrkA expression, biofilm formation and effect of biocides on biofilm formation in carbapenemase-producing Klebsiella pneumoniae isolates belonging or not belonging to high-risk clones.

Background: The role of mrkA adhesin expression, biofilm production, biofilm viability and biocides in the biofilm of carbapenemase-producing Klebsiella pneumoniae isolates was investigated.

Methods: Seventeen isolates representing different sequence types and carbapenemases were investigated. mrkA expression was determined by real-time reverse transcription polymerase chain reaction.

Treatment outcome in dually HIV-1 and HIV-2 coinfected patients living in Spain.

Background: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain.

Methods: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry.

Whole-genome characterization and resistance-associated substitutions in a new HCV genotype 1 subtype.

Hepatitis C virus (HCV) is a highly variable infectious agent, classified into 8 genotypes and 86 subtypes. Our laboratory has implemented an in-house developed high-resolution HCV subtyping method based on next-generation sequencing (NGS) for error-free classification of the virus using phylogenetic analysis and analysis of genetic distances in sequences from patient samples compared to reference sequences. During routine diagnostic, a sample from an Equatorial Guinea patient could not be classified into any of the existing subtypes.

Social Behavior of Antibiotic Resistant Mutants Within Biofilm Communities.

The complex spatial structure and the heterogeneity within biofilms lead to the emergence of specific social behaviors. However, the impact of resistant mutants within bacterial communities is still mostly unknown. Thus, we determined whether antibiotic resistant mutants display selfish or altruistic behaviors in mixed biofilms exposed to antibiotics.

Microbiological diagnosis of biofilm-related infections.

Biofilm-related infections represent a serious health problem, accounting for 65- 80% of all infections. The infections are generally chronic and characterized by the persistence of the microorganism, due to the increased resistance of biofilms to both the immune system and antimicrobials. Biofilms can be located to almost every human body tissue and on exogenous devices such as catheters, pacemakers, prosthetic material, implants, urinary catheters, etc.

Antibiotic treatment of biofilm infections.

Bacterial biofilms are associated with a wide range of infections, from those related to exogenous devices, such as catheters or prosthetic joints, to chronic tissue infections such as those occurring in the lungs of cystic fibrosis patients. Biofilms are recalcitrant to antibiotic treatment due to multiple tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm infections in spite of antibiotic exposure which predisposes to antibiotic resistance development (genetic resistance).

Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections.

Traditional therapeutic strategies to control chronic colonization in cystic fibrosis (CF) patients are based on the use of a single nebulized antibiotic. In this study, we evaluated the therapeutic efficacy and dynamics of antibiotic resistance in Pseudomonas aeruginosa biofilms under sequential therapy with inhaled aztreonam (ATM) and tobramycin (TOB). Laboratory strains PAO1, PAOMS (hypermutable), PAOMA (mucoid), and PAOMSA (mucoid and hypermutable) and two hypermutable CF strains, 146-HSE (Liverpool epidemic strain [LES-1]) and 1089-HSE (ST1089), were used.

The problems of antibiotic resistance in cystic fibrosis and solutions.

Chronic respiratory infection is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. One of the hallmarks of these infections, led by the opportunistic pathogen Pseudomonas aeruginosa, is their long-term (lifelong) persistence despite intensive antimicrobial therapy. Antimicrobial resistance in CF is indeed a multifactorial problem, which includes physiological changes, represented by the transition from the planktonic to the biofilm mode of growth and the acquisition of multiple (antibiotic resistance) adaptive mutations catalyzed by frequent mutator phenotypes.

Alterations of OprD in carbapenem-intermediate and -susceptible strains of Pseudomonas aeruginosa isolated from patients with bacteremia in a Spanish multicenter study.

We investigated the presence of OprD mutations in 60 strains of metallo-ß-lactamase-negative Pseudomonas aeruginosa intermediately susceptible (IS [n = 12]; MIC = 8 μg/ml) or susceptible (S [n = 48]; MICs ≤ 1 to 4 μg/ml) to imipenem and/or meropenem that were isolated from patients with bacteremia in order to evaluate their impact on carbapenem susceptibility profiles. The presence of mutations in oprD was detected by sequencing analysis. OprD expression was assessed by both outer membrane protein (OMP) analysis and real-time PCR (RT-PCR).

Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy.

Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM).

Prevention and correction of oxidative DNA lesions in Pseudomonas aeruginosa is ensured by the DNA oxidative repair system (GO). Single inactivation of mutT, mutY and mutM involved in GO led to elevated mutation rates (MRs) that correlated to increased development of resistance to antibiotics. In this study, we constructed a double mutant in mutY and mutM (PAOMY-Mgm) and characterized the phenotype and the gene expression profile using microarray and RT-PCR.

Dynamics of mutator and antibiotic-resistant populations in a pharmacokinetic/pharmacodynamic model of Pseudomonas aeruginosa biofilm treatment.

Biofilm growth, antibiotic resistance, and mutator phenotypes are key components of chronic respiratory infections by Pseudomonas aeruginosa in cystic fibrosis patients. We examined the dynamics of mutator and antibiotic-resistant populations in P. aeruginosa flow-cell biofilms, using fluorescently tagged PAO1 and PAOMS (mutator [mutS] derivative) strains.

Antagonistic interactions of Pseudomonas aeruginosa antibiotic resistance mechanisms in planktonic but not biofilm growth.

Pseudomonas aeruginosa has an extraordinary capacity to evade the activity of antibiotics through a complex interplay of intrinsic and mutation-driven resistance pathways, which are, unfortunately, often additive or synergistic, leading to multidrug (or even pandrug) resistance. However, we show that one of these mechanisms, overexpression of the MexCD-OprJ efflux pump (driven by inactivation of its negative regulator NfxB), causes major changes in the cell envelope physiology, impairing the backbone of P. aeruginosa intrinsic resistance, including the major constitutive (MexAB-OprM) and inducible (MexXY-OprM) efflux pumps and the inducible AmpC β-lactamase.