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Microbiology Spectrum Aug 2022Antibiotics are widely used for the treatment of bacterial infections. However, injudicious use of antibiotics based on an empirical method may lead to the emergence of...
Antibiotics are widely used for the treatment of bacterial infections. However, injudicious use of antibiotics based on an empirical method may lead to the emergence of resistant strains. Despite appropriate administration of antibiotics, their concentrations may remain subinhibitory in the body, due to individual variations in tissue distribution and metabolism rates. This may promote bacterial virulence and complicate the treatment strategies. To investigate whether the administration of certain classes of antibiotics will induce bacterial virulence and worsen the infection under conditions. Different classes of antibiotics were tested for their ability to induce virulence in a methicillin-resistant S. aureus strain Mu3 and clinical isolates. Antibiotic-induced pathogenicity was assessed using mouse peritonitis and bacteremia models. β-lactam antibiotics and tetracyclines induced the expression of multiple surface-associated virulence factors as well as the secretion of toxins. In peritonitis and bacteremia models, mice infected with MRSA and treated with ampicillin, ceftazidime, or tetracycline showed enhanced bacterial pathogenicity. The release of induced virulence factors was confirmed in a histological examination. Subinhibitory concentrations of antibiotics belonging to β-lactam and tetracycline aggravated infection by inducing staphylococcal virulence . Thus, when antibiotics are required, it is preferable to employ combination therapy and to initiate the appropriate treatment plan, following diagnosis. Our findings emphasize the risks associated with antibiotic-based therapy and underline the need for alternative therapeutic options. Antibiotics are widely applied to treat infectious diseases. Empirically treatment with incorrect antibiotics, or even correct antibiotics always falls into subinhibitory concentrations, due to dosing, distribution, or secretion. In this study, we have systematically evaluated virulence induction effect of antibiotics and exacerbated infection. The major highlight of this work is to prove the β-lactam and tetracyclines antibiotics exacerbated disease is due to their induction effect on staphylococcal virulence. This phenomenon is common and suggests that if β-lactam antibiotics remain the first line of defense during empirical therapy, we either need to increase patient reliability or the treatment approach may improve in the future when paired with anti-virulence drugs.
Topics: Animals; Anti-Bacterial Agents; Bacteremia; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Peritonitis; Reproducibility of Results; Staphylococcal Infections; Tetracycline; Virulence Factors; beta-Lactams
PubMed: 35758685
DOI: 10.1128/spectrum.00640-22 -
Genes Apr 2024Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained... (Review)
Review
INTRODUCTION
Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation.
CONCLUSIONS
This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.
Topics: Humans; Peritoneal Dialysis; Cell-Free Nucleic Acids; DNA, Mitochondrial; Biomarkers; MicroRNAs; DNA, Bacterial; Peritonitis; Peritoneum
PubMed: 38790182
DOI: 10.3390/genes15050553 -
PLoS Computational Biology Jun 2021Cytometry analysis has seen a considerable expansion in recent years in the maximum number of parameters that can be acquired in a single experiment. In response to this...
Cytometry analysis has seen a considerable expansion in recent years in the maximum number of parameters that can be acquired in a single experiment. In response to this technological advance there has been an increased effort to develop new computational methodologies for handling high-dimensional single cell data acquired by flow or mass cytometry. Despite the success of numerous algorithms and published packages to replicate and outperform traditional manual analysis, widespread adoption of these techniques has yet to be realised in the field of immunology. Here we present CytoPy, a Python framework for automated analysis of cytometry data that integrates a document-based database for a data-centric and iterative analytical environment. In addition, our algorithm-agnostic design provides a platform for open-source cytometry bioinformatics in the Python ecosystem. We demonstrate the ability of CytoPy to phenotype T cell subsets in whole blood samples even in the presence of significant batch effects due to technical and user variation. The complete analytical pipeline was then used to immunophenotype the local inflammatory infiltrate in individuals with and without acute bacterial infection. CytoPy is open-source and licensed under the MIT license. CytoPy is available at https://github.com/burtonrj/CytoPy, with notebooks accompanying this manuscript (https://github.com/burtonrj/CytoPyManuscript) and software documentation at https://cytopy.readthedocs.io/.
Topics: Algorithms; Computational Biology; Databases, Factual; Humans; Image Cytometry; Immunophenotyping; Machine Learning; Peritoneal Dialysis; Peritonitis; Programming Languages; Software; T-Lymphocyte Subsets
PubMed: 34101722
DOI: 10.1371/journal.pcbi.1009071 -
EBioMedicine Aug 2022The annual mortality burden of antimicrobial resistant infections exceeds 1.27 million/year. With serious infections, every hour without effective antimicrobial therapy...
BACKGROUND
The annual mortality burden of antimicrobial resistant infections exceeds 1.27 million/year. With serious infections, every hour without effective antimicrobial therapy results in a 6.7% increased risk of death. New technology that delivers actionable pathology results in clinically-relevant timeframes is an urgent priority. We present the development and validation of an acoustic-enhanced flow cytometric (AFC) workflow that provides same-day confirmation of infection and antimicrobial susceptibility, using peritoneal dialysis (PD)-associated peritonitis as a demonstrative example.
METHODS
In this cohort study, we analysed peritoneal dialysis effluent specimens using AFC to confirm the presence of infection and antimicrobial susceptibility of identified organisms. The primary outcome was the performance of the assay compared to conventional microbiology performed by the clinical laboratory. A secondary outcome was time to result.
FINDINGS
AFC confirmed infection from primary specimens (n=116), with a sensitivity of 86% and specificity of 94% in ≤ one hour from arrival, including confirmation of infecting organisms in culture-negative cases. Combined with flow-cytometry-assisted antimicrobial susceptibility testing (FAST), we demonstrate same-day antimicrobial susceptibility profiles with an accuracy equivalent to conventional laboratory-based tests.
INTERPRETATION
Application of AFC based assays to confirm infection and predict antimicrobial susceptibility can deliver actionable results with a performance that meets or exceeds currently utilised microbiological tests in clinically meaningful timeframes, as demonstrated for PD peritonitis. This technology shows potential for broad applicability to other time-critical serious infections.
FUNDING
Government of Western Australia (Department of Health), Government of Australia (National Health and Medical Research Council) and the Forrest Research Foundation.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cohort Studies; Flow Cytometry; Humans; Peritoneal Dialysis; Peritonitis
PubMed: 35864063
DOI: 10.1016/j.ebiom.2022.104145 -
Parasitology Nov 2021Trichomonas vaginalis causes trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to study T. vaginalis infection response...
Trichomonas vaginalis causes trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to study T. vaginalis infection response in a microorganism-free environment, an infection model was established providing a host–parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed on T. vaginalis clearance. Increased viability of T. vaginalis was observed when the NETs inhibitors, metformin and Cl− amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in an in vivo interaction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on the T. vaginalis viability.
Topics: Animals; Kinetics; Mice; Neutrophils; Peritoneum; Trichomonas Infections; Trichomonas vaginalis
PubMed: 35060469
DOI: 10.1017/S0031182021001311 -
Scientific Reports Feb 2022There are considerable differences between males and females regarding the etiology, progression and outcome of liver diseases. Infections are a frequent and severe...
There are considerable differences between males and females regarding the etiology, progression and outcome of liver diseases. Infections are a frequent and severe complication in these patients. This study aimed to examine sex specific differences in the incidence and clinical course of nosocomial infections in patients with decompensated liver cirrhosis. A number of 556 consecutive hospitalized patients with decompensated liver cirrhosis and ascites were analyzed. The patients were followed up for the incidence of nosocomial infections, acute kidney injury (AKI), acute-on-chronic liver failure (ACLF) as well as liver transplantation and death (LTx-free survival). A number of 285 patients (111 women and 174 men) developed a nosocomial infection. Incidence was numerically lower in men (P = 0.076). While the frequency of a nosocomial spontaneous bacterial peritonitis was similar between males and females, the incidence of a nosocomial urinary tract infection was significantly higher in women (P < 0.001). No sex specific differences were documented regarding the outcome of an infection as indicated by a similar incidence of, AKI, ACLF as well as LTx-free survival. There seem to be no major differences in the incidence and outcome of nosocomial infections between male and female patients.
Topics: Acute Kidney Injury; Acute-On-Chronic Liver Failure; Bacterial Infections; Cross Infection; Female; Humans; Liver Cirrhosis; Male; Peritonitis; Prognosis
PubMed: 35228572
DOI: 10.1038/s41598-022-07084-9 -
Journal of Nephrology Sep 2023Peritonitis remains a significant complication of peritoneal dialysis. However, there is limited information on the clinical characteristics and outcomes of...
BACKGROUND
Peritonitis remains a significant complication of peritoneal dialysis. However, there is limited information on the clinical characteristics and outcomes of hospital-acquired peritonitis compared to community-acquired peritonitis in patients undergoing peritoneal dialysis. Furthermore, the microbiology and outcomes of community-acquired peritonitis may vary from hospital-acquired peritonitis. Therefore, the aim was to gather and analyse data to address this gap.
METHODS
Retrospective review of the medical records of all adult patients on peritoneal dialysis within the peritoneal dialysis units in four university teaching hospitals in Sydney, Australia, who developed peritonitis between January 2010 and November 2020. We compared the clinical characteristics, microbiology and outcomes of community-acquired peritonitis and hospital-acquired peritonitis. Community acquired peritonitis was defined as the development of peritonitis in the outpatient setting. Hospital-acquired peritonitis was defined as: (1) developed peritonitis anytime during hospitalisation for any medical condition other than peritonitis, (2) diagnosed with peritonitis within 7 days of hospital discharge and developed symptoms of peritonitis within 3 days of the hospital discharge.
RESULTS
Overall, 904 episodes of peritoneal dialysis-associated peritonitis were identified in 472 patients, of which 84 (9.3%) episodes were hospital-acquired. Patients with hospital-acquired peritonitis had lower mean serum albumin levels compared to those with community-acquired peritonitis(22.95 g/L vs. 25.76 g/L, p = 0.002). At the time of diagnosis, lower median peritoneal effluent leucocyte and polymorph counts were observed with hospital-acquired peritonitis compared to community-acquired peritonitis (1236.00/mm vs. 3183.50/mm, p < 0.01 and 1037.00/mm vs. 2800.00/mm, p < 0.01, respectively). Higher proportions of peritonitis due to Pseudomonas spp. (9.5% vs. 3.7%, p = 0.020) and vancomycin-resistant Enterococcus (2.4% vs. 0.0%, p = 0.009), lower rates of complete cure (39.3% vs. 61.7%, p < 0.001), higher rates of refractory peritonitis (39.3% vs. 16.4%, p < 0.001) and higher all-cause mortality within 30 days of peritonitis diagnosis (28.6% vs. 3.3%, p < 0.001) were observed in the hospital-acquired peritonitis group compared to the community-acquired peritonitis group, respectively.
CONCLUSIONS
Despite having lower peritoneal dialysis effluent leucocyte counts at the time of diagnosis, patients with hospital-acquired peritonitis had poorer outcomes, including lower rates of complete cure, higher rates of refractory peritonitis and higher rates of all-cause mortality within 30 days of diagnosis, compared to those with community-acquired peritonitis.
Topics: Adult; Humans; Retrospective Studies; Peritoneal Dialysis; Peritonitis; Peritoneum; Hospitals
PubMed: 36913080
DOI: 10.1007/s40620-023-01597-w -
Langenbeck's Archives of Surgery Feb 2022In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
BACKGROUND
In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
PURPOSE
This article provides a report on the state-of-the-art of surgery for sigmoid diverticulitis.
CONCLUSION
Acute diverticulitis is the most common reason for colonic resection after cancer; in the last decade, the indication for surgical resection has become more and more infrequent also in emergency. Currently, emergency surgery is seldom indicated, mostly for severe abdominal infective complications. Nowadays, uncomplicated diverticulitis is the most frequent presentation of diverticular disease and it is usually approached with a conservative medical treatment. Non-Operative Management may be considered also for complicated diverticulitis with abdominal abscess. At present, there is consensus among experts that the hemodynamic response to the initial fluid resuscitation should guide the emergency surgical approach to patients with severe sepsis or septic shock. In hemodynamically stable patients, a laparoscopic approach is the first choice, and surgeons with advanced laparoscopic skills report advantages in terms of lower postoperative complication rates. At the moment, the so-called Hartmann's procedure is only indicated in severe generalized peritonitis with metabolic derangement or in severely ill patients. Some authors suggested laparoscopic peritoneal lavage as a bridge to surgery or also as a definitive treatment without colonic resection in selected patients. In case of hemodynamic instability not responding to fluid resuscitation, an initial damage control surgery seems to be more attractive than a Hartmann's procedure, and it is associated with a high rate of primary anastomosis.
Topics: Anastomosis, Surgical; Colostomy; Diverticulitis; Diverticulitis, Colonic; Humans; Intestinal Perforation; Laparoscopy; Peritoneal Lavage; Peritonitis
PubMed: 34557938
DOI: 10.1007/s00423-021-02288-5 -
Internal Medicine (Tokyo, Japan) Nov 2021A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not... (Review)
Review
A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not controlled by one-week intraperitoneal administration of cefazolin and ceftazidime, was cured only after switching to two-week intravenous administration of cefazolin and ceftazidime. The patient had no major dental disease or recent history of dental intervention. This case suggests that S. oralis might cause peritoneal dialysis-related peritonitis with persistent systemic inflammation via an extra-oral infection route. The clinical course is discussed along with a review of the literature.
Topics: Aged; Anti-Bacterial Agents; Humans; Male; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Streptococcus oralis
PubMed: 34024849
DOI: 10.2169/internalmedicine.6234-20 -
BMC Nephrology Dec 2022Peritonitis is one of the major complications of peritoneal dialysis. The most common cause of peritonitis is infection at the catheter exit site. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Peritonitis is one of the major complications of peritoneal dialysis. The most common cause of peritonitis is infection at the catheter exit site. This study aimed to determine the effect of propolis on the incidence of catheter exit site infection and peritonitis in peritoneal dialysis patients.
METHOD
This study was a double-blind clinical trial (2019-2020) with peritoneal dialysis patients. Ninety peritoneal dialysis patients were allocated to three groups (placebo, control, intervention) using block randomization method. Catheter exit site was washed with 0.9% normal saline and dressing was done every other day after the morning peritoneal dialysis exchange by use of normal saline in placebo, mupirocin in control, and propolis in intervention group, for 6 months.
DISCUSSION
10% of the patients in the placebo and 6.7% in the control group developed catheter Exit Site Infection, but none patient in the intervention group developed this infection (P = 0.469). Whereas 6.7% in both the placebo and control groups developed peritonitis, but none patient in the intervention group contracted peritonitis (P = 0.997). No significant differences in the incidence of catheter exit site infection and peritonitis among the three groups were observed. Considering that mupirocin is of chemical origin and may lead to drug resistance whereas propolis is of plant origin and does not produce drug resistance, the use of propolis is recommended.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials [ IRCT20110427006318N10 ] (17/01/2019).
Topics: Humans; Anti-Bacterial Agents; Catheters, Indwelling; Iran; Mupirocin; Peritoneal Dialysis; Peritonitis; Propolis; Saline Solution; Double-Blind Method
PubMed: 36564743
DOI: 10.1186/s12882-022-03036-7