Non-antibiotic Strategies Research Articles

Commensal Neisseria Are Shared between Sexual Partners: Implications for Gonococcal and Meningococcal Antimicrobial Resistance.

Antimicrobial resistance in pathogenic Neisseria parallels reduced antimicrobial susceptibility in commensal Neisseria in certain populations, like men who have sex with men (MSM). Although this reduced susceptibility can be a consequence of frequent antimicrobial exposure at the individual level, we hypothesized that commensal Neisseria are transmitted between sexual partners. We used data from a 2014 microbiome study in which saliva and tongue swabs were taken from 21 couples (42 individuals). Samples were analyzed using 16S rRNA gene sequencing. We compared intimate partners with unrelated individuals and found that the oral Neisseria communities of intimate partners were more similar than those of unrelated individuals (average Morisita–Horn dissimilarity index for saliva samples: 0.54 versus 0.71, respectively (p = 0.005); and for tongue swabs: 0.42 versus 0.63, respectively (p = 0.006)). This similarity presumably results from transmission of oral Neisseria through intimate kissing. This finding suggests that intensive gonorrhea screening in MSM may, via increased antimicrobial exposure, promote, rather than prevent, the emergence and spread of antimicrobial resistance in Neisseria. Non-antibiotic strategies such as vaccines and oral antiseptics could prove more sustainable options to reduce gonococcal prevalence.

Single components of botanicals and nature-identical compounds as a non-antibiotic strategy to ameliorate health status and improve performance in poultry and pigs.

In the current post-antibiotic era, botanicals represent one of the most employed nutritional strategies to sustain antibiotic-free and no-antibiotic-ever production. Botanicals can be classified either as plant extracts, meaning the direct products derived by extraction from the raw plant materials (essential oils (EO) and oleoresins (OR)), or as nature-identical compounds (NIC), such as the chemically synthesised counterparts of the pure bioactive compounds of EO/OR. In the literature, differences between the use of EO/OR or NIC are often unclear, so it is difficult to attribute certain effects to specific bioactive compounds. The aim of the present review was to provide an overview of the effects exerted by botanicals on the health status and growth performance of poultry and pigs, focusing attention on those studies where only NIC were employed or those where the composition of the EO/OR was defined. In particular, phenolic compounds (apigenin, quercetin, curcumin and resveratrol), organosulfur compounds (allicin), terpenes (eugenol, thymol, carvacrol, capsaicin and artemisinin) and aldehydes (cinnamaldehyde and vanillin) were considered. These molecules have different properties such as antimicrobial (including antibacterial, antifungal, antiviral and antiprotozoal), anti-inflammatory, antioxidant, immunomodulatory, as well as the improvement of intestinal morphology and integrity of the intestinal mucosa. The use of NIC allows us to properly combine pure compounds, according to the target to achieve. Thus, they represent a promising non-antibiotic tool to allow better intestinal health and a general health status, thereby leading to improved growth performance.

Anti-inflammatory effects of Lactobacillus johnsonii L531 in a pig model of Salmonella Infantis infection involves modulation of CCR6+ T cell responses and ER stress

Probiotic pretreatment is an effective non-antibiotic strategy for preventing or controlling Salmonella infections. We found that Lactobacillus johnsonii L531, isolated from the colon of a clinically healthy weaned piglet, effectively prevented infection with Salmonella enterica serovar Infantis in a pig model. Newly weaned piglets were intragastrically administered Lactobacillus johnsonii L531 at 1.0 × 1010 CFU/day for 1 week before S. Infantis challenge. Pretreatment with L. johnsonii L531 lessened the severity of diarrhea and ileal inflammation in S. Infantis–infected piglets. Lactobacilli were more abundant in the ileum than jejunum after L. johnsonii L531 pretreatment. Treatment with L. johnsonii L531 reduced the abundance of total bacteria in the ileal mucosa and the production of lipocalin 2 in the jejunum of piglets challenged with Salmonella. Both intestinal morphology and transmission electron microscopy results indicated that L. johnsonii L531 alleviated intestinal tissue damage following S. Infantis challenge, especially in the villus and endoplasmic reticulum (ER). ER stress induced by S. Infantis was attenuated by L. johnsonii L531 treatment. The number of CD4− CCR6+ T cells decreased following S. Infantis challenge, but the percentage of CCR6− IFNγ+ T cells in peripheral blood increased. In intestinal mesenteric lymph nodes, S. Infantis increased the proportion of CCR6+ IFNγ+ T cells, whereas L. johnsonii L531 induced an increase in the proportion of CD4+ CCR6+ T cells in response to S. Infantis infection. Our data thus suggest that L. johnsonii L531 contributes to the maintenance of intestinal homeostasis by modulating T-cell responses and ER stress.

Antibacterial and photocatalytic activities of 5-nitroindole capped bimetal nanoparticles against multidrug resistant bacteria

The emergence of antibiotic resistance to commercially- available antibiotics is becoming a major health crisis worldwide. Non-antibiotic strategies are needed to combat biofilm-associated infectious diseases caused by multidrug resistant (MDR) bacterial pathogens. In this study, MBR1 was isolated from a membrane bioreactor used in wastewater treatment plants, and the resistance profile was explored. 5-Nitroindole (5 N)-capped CuO/ZnO bimetal nanoparticles (5 NNP) were synthesized using a one pot method to improve the antibacterial and antibiofilm activities of 5 N against Gram-negative (Escherichia coli ATCC700376 and Pseudomonas aeruginosa PA01) and positive (Staphylococcus aureus ATCC6538) human pathogens. 5 NNP containing 1 mM of 5 N exhibited strong antibacterial and antibiofilm properties to most MDR bacteria. In addition, the photocatalytic activity of CuO/ZnO reduced bacterial cell growth by 1.8 log CFU/mL maximum when exposed to visible light. Scanning electron microscopy showed that 5 NNP reduced the cell density and biofilm attachment of MBR1 by >90% under static conditions. In addition to the antimicrobial and antibiofilm activities, 5 NNP inhibited the persister cell formation of MDR bacterial strains P. aeruginosa, MBR1, E. coli and S. aureus. Therefore, it is speculated that 5 NNP potentially inhibits biofilm and persister cells; hence, 5 NNP could be an alternative agent to combat MDR infectious diseases using a non-antibiotic therapeutic approach.

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.

Surface display of uropathogenic Escherichia coli FimH in Lactococcus lactis: In vitro characterization of recombinant bacteria and its protectivity in animal model

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are very common, leading to high patient morbidity and substantial medical costs. The development of non-antibiotic strategies such as food-grade lactic acid bacterium can be recognized as an attractive and safe alternative way against UTI. Here, we report the construction of Lactococcus lactis (L. lactis) strain genetically modified to produce FimH virulence factor of UPEC on the cell surface. We showed the FimH inserted into the pT1NX vector is actively synthesized on L. lactis. The L. lactis-pT1NX-FimH exhibited an auto-aggregation phenotype in liquid cultures and formed robust biofilm on abiotic surface compared to vector-only bacteria. Then, we developed protective biofilms with L. lactis strains and examined their inhibitory effect for exclusion of uropathogenic biofilm formation. In the natural protective biofilm assays, L. lactis-pT1NX-FimH resulted in significant reduction in the pathogen load when compared to the L. lactis-pT1NX. Evaluation of the colonization ability in the bladder showed that L. lactis expressing FimH survived better in the mice bladder than L. lactis harboring vector. Protection assay against UPEC infection was investigated using a UTI mouse model. L. lactis-pT1NX-FimH displayed high effectiveness in the protection of the bladder as compared to the control group after UPEC challenge. The results suggest that genetically engineered L. lactis-pT1NX-FimH can be used as a safe alternative way for control of biofilm formation in UPEC. Furthermore, the possibility of using L. lactis-pT1NX-FimH as a new promising strategy against UTIs caused by UPEC strains is proposed.

Antibacterial photodynamic therapy mediated by 5-aminolevulinic acid on methicillin-resistant Staphylococcus aureus.

The emergence of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has brought great difficulties to clinical treatment. Antibacterial photodynamic therapy (aPDT) is a new non-antibiotic treatment strategy for a variety of drug-resistant bacteria. However, there are few studies on the antimicrobial mechanism of a PDT mediated by 5-aminolevulinic acid (ALA-PDT) for MRSA. In this study, we observed the bactericidal effect of ALA-PDT on MRSA. We found that ALA-PDT had the strongest bactericidal effect when ALA was at 0.05 mM, and the bactericidal activity of aPDT increased with the increase of light dose. MRSA was almost completely eliminated at 0.05 mM and 384 Jcm-2. In addition, the bactericidal morphology was also observed under a fluorescence microscope using a LIVE/DEAD® BacLight™ Bacterial Viability Kit and an electron microscope. It was also found that proteins and DNA were damaged by ALA-PDT. Finally, the transcription level of the specific gene of MRSA, nuc, was decreased by 0.74-fold (P < 0.05) after ALA-PDT treatment by qRT-PCR analysis. The findings suggest that ALA-PDT can effectively inhibit MRSA by damaging cell membrane, cytoplasm, proteins and nucleic acid.

Prophylactic Antibiotics in Cirrhosis: Are They Promoting or Preventing Infections?

Prophylactic Antibiotics in Cirrhosis: Are They Promoting or Preventing Infections?

Antimicrobial biomaterials with non‐antibiotic strategy

Biomedical implants have revolutionised medicine, while they also increase the risk of implant-associated infection which is one of the most frequent and severe complications accompanied by the application of biomaterials. Since the widespread usage of antibiotics drives the emergence of multidrug-resistant strains, the orthopaedic implant infections are usually hard to treat due to the antibiotic resistance, tolerance and/or persistence of pathogens. Given the growing impact of multidrug resistance, an urgent need has been triggered to develop new types of antimicrobial strategy other than using antibiotics. In this review, the authors highlight the recent progress on antimicrobial biomaterials with non-antibiotic strategies including chemical strategy, physical strategy, and synergetic strategy. The antimicrobial mechanisms of many kinds of non-antibiotic antimicrobial biomaterials are still not fully understood. Researchers gradually found that welcoming microbial cellular adhesion to a lethal surface was a more effective solution than targeting microbial cellular repulsion when designing antimicrobial surfaces. Moreover, there is a popular tendency to make the antimicrobial biomaterials not only kill pathogenic microbes but also facilitate the adhesion and growth of the healthy cell, which means that the next generation biomaterials should possess dual functions of preventing microbial infection together with promoting tissue regeneration simultaneously for biomedical applications.

Understanding the influence of parent-clinician communication on antibiotic prescribing for children with respiratory tract infections in primary care: a qualitative observational study using a conversation analysis approach

BackgroundAcute respiratory tract infections (RTI) in children are a common reason for antibiotic prescribing. Clinicians’ prescribing decisions are influenced by perceived parental expectations for antibiotics, however there is evidence that parents actually prefer to avoid antibiotics. This study aimed to investigate the influence of parent-clinician communication on antibiotic prescribing for RTI in children in England.MethodsA mixed methods analysis of videoed primary care consultations for children (under 12 years) with acute cough and RTI. Consultations were video-recorded in six general practices in southern England, selected for socio-economic diversity. 56 recordings were transcribed in detail and a subset of recordings and transcripts used to develop a comprehensive interaction-based coding scheme. The scheme was used to examine communication practices between parents and clinicians and how these related to antibiotic or non-antibiotic treatment strategies.ResultsParents’ communication rarely implied an expectation for antibiotics, some explicitly offering a possible viral diagnosis. Clinicians mostly gave, or implied, a viral diagnosis and mainly recommended non-antibiotic treatment strategies. In the minority of cases where parents’ communication behaviours implied they may be seeking antibiotic treatment, antibiotics were not usually prescribed. Where clinicians did prescribe antibiotics, they voiced concern about symptoms or signs, including chest pain, discoloured phlegm, prolonged fever, abnormal chest sounds, or pink /bulging ear drums.ConclusionsWe found little evidence of a relationship between parents’ communication behaviours and antibiotic prescribing. Rather, where antibiotics were prescribed, this was associated with clinicians’ expressed concerns regarding symptoms and signs.

Antimicrobial and antibiofilm activities of prenylated flavanones from Macaranga tanarius

BackgroundThe emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance. Study designIn this study, the antimicrobial and antibiofilm activities of five prenylated flavanones (Okinawan propolins) isolated from fruits of Macaranga tanarius (L.) were investigated against 14 microorganisms including 10 pathogens. ResultsOf these five propolins, propolin D at 5–10 µg/ml significantly inhibited biofilm formation by three Staphylococcus aureus strains, a Staphylococcus epidermidis strain, and a Candida albicans with MICs from 10 to 50 µg/ml, and in C. albicans, propolin D was found to inhibit biofilm formation by reducing cell aggregation and downregulated the expressions of hypha/biofilm-related genes including ECE1 and HWP1. Interestingly, at sub-MIC concentrations (10–50 µg/ml), propolin D significantly inhibited biofilm formation by enterohemorrhagic E. coli O157:H7, uropathogenic E. coli O6:H1, and Acinetobacter baumannii without affecting planktonic cell growth, but did not inhibit biofilm formation by a commensal E. coli K-12 strain, three probiotic Lactobacillus plantarum strains, or two Pseudomonas aeruginosa strains. And, propolin D reduced fimbriae production by E. coli O157:H7 and repressed gene expression of curli fimbriae genes (csgA and csgB). Also, propolin D was minimally toxic in a Caenorhabditis elegans nematode model. ConclusionThese findings show that prenylated flavanones, especially propolin D from Macaranga tanarius (Okinawan propolis), should be considered potential candidates for the development of non-toxic antibacterial and antifungal agents against persistent microorganisms.

Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline.

This document seeks to establish guidance for the evaluation and management of women with recurrent urinary tract infections (rUTI) to prevent inappropriate use of antibiotics, decrease the risk of antibiotic resistance, reduce adverse effects of antibiotic use, provide guidance on antibiotic and non-antibiotic strategies for prevention, and improve clinical outcomes and quality of life by reducing recurrence of urinary tract infection (UTI) events. The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to January Week 1 2018), Cochrane Central Register of Controlled Trials (through December 2017) and Embase (through January 16, 2018). An update literature search was conducted on September 20, 2018. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. Our ability to diagnose, treat, and manage rUTI long-term has evolved due to additional insights into the pathophysiology of rUTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy, rising rates of bacterial antimicrobial resistance (AMR), and better reporting of the natural history and clinical outcomes of acute cystitis and rUTI. As new data continue to emerge in this space, this document will undergo review to ensure continued accuracy.

Application of Porphyrins in Antibacterial Photodynamic Therapy.

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current ‘greener’ methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.

ZnO/Curcumin Nanocomposites for Enhanced Inhibition of Pseudomonas aeruginosa Virulence via LasR-RhlR Quorum Sensing Systems.

The indiscriminate and excessive use of antibiotics has ultimately led to the emergence of bacterial resistant mutants or superbugs. These superbugs are difficult to control with conventional antibiotics. Disabling quorum sensing (QS), a population-density-dependent cell-to-cell communication process used by bacteria to coordinate the expression of virulence genes and biofilm formation, with dietary phytochemicals is emerging as a non-antibiotic strategy to inhibit bacterial pathogenicity. Although curcumin is an anti-QS agent and its delivery to cells has been a challenge due to poor bioavailability, ZnO/curcumin nanocomposites (ZnC-NCs) were fabricated with enhanced delivery of curcumin inside the bacterial superbug Pseudomonas aeruginosa PAO1 for effective inhibition of its QS and biofilm formation. Sustained release of curcumin from ZnC-NCs was observed where 51% curcumin at pH 7.2 and 83% curcumin at pH 5.5 were released within 48 h. ZnC-NCs also decreased the production of virulence factors and biofilm formation without affecting planktonic cell growth. Both LasR and RhlR QS systems were inhibited by ZnC-NCs. ZnC-NCs were also capable of protecting both mice as well as lung epithelial cells from killing by PAO1. The superoxide anions (O2·-) were also found as key players in suppressing PAO1 QS systems by ZnC-NCs. Overall, ZnC-NCs enhanced curcumin bioavailability for effective inhibition of QS signaling in P. aeruginosa via LasR-RhlR suppression and O2·- generation.

Antimicrobial Effects on Swine Gastrointestinal Microbiota and Their Accompanying Antibiotic Resistome.

Antimicrobials are the most commonly prescribed drugs in the swine industry. While antimicrobials are an effective treatment for serious bacterial infections, their use has been associated with major adverse effects on health. It has been shown that antimicrobials have substantial direct and indirect impacts on the swine gastrointestinal (GI) microbiota and their accompanying antimicrobial resistome. Antimicrobials have also been associated with a significant public health concern through selection of resistant opportunistic pathogens and increased emergence of antimicrobial resistance genes (ARGs). Since the mutualistic microbiota play a crucial role in host immune regulation and in providing colonization resistance against potential pathogens, the detrimental impacts of antimicrobial treatment on the microbiota structure and its metabolic activity may lead to further health complications later in life. In this review, we present an overview of antimicrobial use in the swine industry and their role in the emergence of antimicrobial resistance. Additionally, we review our current understanding of GI microbiota and their role in swine health. Finally, we investigate the effects of antimicrobial administration on the swine GI microbiota and their accompanying antibiotic resistome. The presented data is crucial for the development of robust non-antibiotic alternative strategies to restore the GI microbiota functionality and guarantee effective continued use of antimicrobials in the livestock production system.

Non-antibiotic prevention strategies against catheter-associated urinary tract infections

Non-antibiotic prevention strategies against catheter-associated urinary tract infections

Comprehensive Identification of Fim-Mediated Inversions in Uropathogenic Escherichia coli with Structural Variation Detection Using Relative Entropy.

Most urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC), which depends on an extracellular organelle (type 1 pili) for adherence to bladder cells during infection. Type 1 pilus expression is partially regulated by inversion of a piece of DNA referred to as fimS, which contains the promoter for the fim operon encoding type 1 pili. fimS inversion is regulated by up to five recombinases collectively known as Fim recombinases. These Fim recombinases are currently known to regulate two other switches: the ipuS and hyxS switches. A long-standing question has been whether the Fim recombinases regulate the inversion of other switches, perhaps to coordinate expression for adhesion or virulence. We answered this question using whole-genome sequencing with a newly developed algorithm (structural variation detection using relative entropy [SVRE]) for calling structural variations using paired-end short-read sequencing. SVRE identified all of the previously known switches, refining the specificity of which recombinases act at which switches. Strikingly, we found no new inversions that were mediated by the Fim recombinases. We conclude that the Fim recombinases are each highly specific for a small number of switches. We hypothesize that the unlinked Fim recombinases have been recruited to regulate fimS, and fimS only, as a secondary locus; this further implies that regulation of type 1 pilus expression (and its role in gastrointestinal and/or genitourinary colonization) is important enough, on its own, to influence the evolution and maintenance of multiple additional genes within the accessory genome of E. coliIMPORTANCE UTI is a common ailment that affects more than half of all women during their lifetime. The leading cause of UTIs is UPEC, which relies on type 1 pili to colonize and persist within the bladder during infection. The regulation of type 1 pili is remarkable for an epigenetic mechanism in which a section of DNA containing a promoter is inverted. The inversion mechanism relies on what are thought to be dedicated recombinase genes; however, the full repertoire for these recombinases is not known. We show here that there are no additional targets beyond those already identified for the recombinases in the entire genome of two UPEC strains, arguing that type 1 pilus expression itself is the driving evolutionary force for the presence of these recombinase genes. This further suggests that targeting the type 1 pilus is a rational alternative nonantibiotic strategy for the treatment of UTI.

Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets

BackgroundP. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients.ObjectivesTo study the effect of specific polyclonal anti-P. aeruginosa IgY antibodies (Pa-IgY) on colonization of the airways in a porcine model.MethodThe pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 109 CFU nebulized P. aeruginosa (control, n = 6) or 109 CFU nebulized P. aeruginosa + 200 mg Pa-IgY antibodies (intervention, n = 6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured.ResultsAfter nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa-IgY-treated group during the experiment (p = 0.02). Tracheal growth was 4.6 × 103 (9.1 × 102–3.1 × 104) vs. 4.8 × 104 (7.5 × 103–1.4 × 105) CFU/mL in the intervention group vs. the control group at 1 h and 5.0 × 100 (0.0 × 100–3.8 × 102) vs. 3.3 × 104 (8.0 × 103–1.4 × 105) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group.ConclusionIn this porcine model, Pa-IgY antibodies lessen bacterial colonization of the airways.

Antimicrobials Are a Photodynamic Inactivation Adjuvant for the Eradication of Extensively Drug-Resistant Acinetobacter baumannii.

The worldwide emergence of extensively drug resistant (XDR) Acinetobacter baumannii has reduced the number of antimicrobials that exert high bactericidal activity against this pathogen. This is the reason why many scientists are focusing on investigations concerning novel non-antibiotic strategies such as antimicrobial photodynamic inactivation (aPDI) or the use of antimicrobial blue light (aBL). Therefore, the aim of the current study was to screen for antimicrobial synergies of routinely used antibiotics and phototherapies, including both aPDI involving exogenously administered photosensitizing molecules, namely, rose bengal, and aBL, involving excitation of endogenously produced photoactive compounds. The synergy testing was performed in accordance with antimicrobial susceptibility testing (AST) standards, including various methodological approaches, i.e., antibiotic diffusion tests, checkerboard assays, CFU counting and the evaluation of postantibiotic effects (PAEs). We report that combining antimicrobials and aPDI/aBL treatment led to a new strategy that overcomes drug resistance in XDR A. baumannii, rendering this pathogen susceptible to various categories of antibiotics. Sublethal aPDI/aBL treatment in the presence of sub-MIC levels of antimicrobials effectively killed A. baumannii expressing drug resistance to studied antibiotics when treated with only antibiotic therapy. The susceptibility of XDR A. baumannii to a range of antibiotics was enhanced following sublethal aPDI/aBL. Furthermore, 3′-(p-aminophenyl) fluorescein (APF) testing indicated that significantly increased reactive oxygen species production upon combined treatment could explain the observed synergistic activity. This result represents a conclusive example of the synergistic activity between photodynamic inactivation and clinically used antimicrobials leading to effective eradication of XDR A. baumannii isolates and indicates a potent novel therapeutic approach.

The Detection of Bacteria and Matrix Proteins on Clinically Benign and Pathologic Implants.

Bacterial contamination of breast implants causes infection, can lead to capsular contracture, and is implicated in breast implant-associated anaplastic large cell lymphoma. Bacteria, however, also colonize clinically benign breast implants and little is known about the biologic signals that trigger the switch from a benign to pathologic state. Explanted smooth as well as Biocell and Siltex textured breast implants associated with clinically normal and pathologic conditions were analyzed in this observational study. Immunofluorescence and bacterial culture techniques were performed. To avoid sampling bias, implant surfaces >25 sq cm were analyzed. Bacteria were detected on 9 of 22 clinically normal explanted devices or periprosthetic capsules, including 40% of Biocell tissue expanders and 75% of Biocell textured implants. Staphylococcus epidermidis was identified in 67% of the bacteria-positive capsular contractures. Fibrinogen was present on 17 of 18, and collagen on 13 of 18 analyzed breast implants. S. epidermidis co-localized with collagen, while group B streptococci and Klebsiella pneumoniae co-localized with fibrinogen. Bacteria are often detectable on clinically benign breast implants when a multimodal approach is applied to a substantial proportion of the device surface to avoid sampling bias. The impact of bacteria on breast implant pathology should be studied in the presence of an adequate negative control group to account for clinically benign bacteria. Disruption of the interaction of bacteria with matrix proteins coating the surface of breast implants may represent a nonantibiotic strategy for the prevention of breast implant bacterial contamination.