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BioRxiv : the Preprint Server For... Jul 2023Antimicrobial resistance (AMR) has been established to be a significant driver for the persistence and spread of bacterial infections. It is, therefore, essential to...
Antimicrobial resistance (AMR) has been established to be a significant driver for the persistence and spread of bacterial infections. It is, therefore, essential to conduct epidemiological surveillance of AMR in healthy individuals to understand the actual dynamics of AMR in Nigeria. Multi-drug resistant (n=1), (n=1), and (n=3) from stool samples of healthy children were subjected to whole genome sequencing using Illumina Nextseq1000/2000 and Oxford nanopore. Bioinformatics analysis reveals antimicrobial resistance, virulence genes, and plasmids. This pathogenic enteric bacteria harbored more than three plasmid replicons of either Col and/or Inc type associated with outbreaks and AMR resistant gene responsible for colistin resistance. Plasmid reconstruction revealed an integrated gene responsible for tetracycline resistance, and gene responsible for toxin production in two of the isolates, and a gene known to induce neonatal meningitis in the ST3879. The global spread of MDR pathogenic enteric bacteria is a worrying phenomenon, and close surveillance of healthy individuals, especially children, is strongly recommended to prevent the continuous spread and achieve the elimination and eradication of these infections. Molecular epidemiological surveillance using whole genome sequencing (WGS) will improve the detection of MDR pathogens in Nigeria.
PubMed: 37503211
DOI: 10.1101/2023.07.19.549742 -
Journal of Medical Case Reports May 2023Viruses are constantly changing as a result of mutations, and new viral variants are expected to appear over time. The virus that causes coronavirus disease 2019, severe...
BACKGROUND
Viruses are constantly changing as a result of mutations, and new viral variants are expected to appear over time. The virus that causes coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, is not excluded from this condition. Patients with some types of immunodeficiency have been reported to experience symptoms that vary from mild to severe, or even death, after being infected with severe acute respiratory syndrome coronavirus 2. We report a case of a woman with severe hypogammaglobulinemia who developed a prolonged and fatal severe acute respiratory syndrome coronavirus 2 infection.
CASE PRESENTATION
A 60-year-old mestizo female with a previous history of severe hypogammaglobulinemia manifested by recurrent pulmonary infections and follicular bronchiolitis. She received a monthly treatment of intravenous immunoglobulins and was admitted after report of a neurological manifestation related to a left thalamic inflammatory lesion, for a duration of 2 weeks of hospitalization, indicated for the study of her neurological condition, including brain biopsy. Both on admission and 1 week later, nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 were performed and reported negative. In the third week of hospitalization, she developed pulmonary symptoms, and a positive test result for severe acute respiratory syndrome coronavirus 2 was evidenced. On Day 3, the patients' condition worsened as the infection progressed to respiratory failure and required mechanical ventilation. On Day 8 after the coronavirus disease 2019 diagnosis, the polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 showed persistent detection of the virus. Various bacterial coinfections, including Klebsiella pneumoniae and Enterobacter cloacae, were diagnosed and treated. On Day 35, her pulmonary symptoms worsened, and the results of the severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test remained positive. On Day 36, despite all the respiratory support, the patient died. The severe acute respiratory syndrome coronavirus 2 virus was sequenced at the beginning and 8 days after the onset of the disease, and the strain, without obvious mutations in the gene that encodes spike protein, was identified.
CONCLUSIONS
This clinical case showed persistent severe acute respiratory syndrome coronavirus 2 detection after 35 days of infection in a patient with severe hypogammaglobulinemia. The sequencing of the virus showed no mutations on the spike protein at 8 days, indicating that, in this case, the persistence of the viral detection was associated with immunodeficiency instead of changes in the viral components.
Topics: Humans; Female; Middle Aged; COVID-19; Agammaglobulinemia; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Lung
PubMed: 37173711
DOI: 10.1186/s13256-023-03917-x -
Applied and Environmental Microbiology May 2023Contamination of berries and leafy greens with human norovirus (HuNoV) is a major cause of outbreaks of epidemic gastroenteritis worldwide. Using murine norovirus type 1...
Contamination of berries and leafy greens with human norovirus (HuNoV) is a major cause of outbreaks of epidemic gastroenteritis worldwide. Using murine norovirus type 1 (MNV-1) and Tulane virus, we studied the possible extension of HuNoV persistence by biofilm-producing epiphytic bacteria on fresh produce. Nine bacterial species frequently found on the surface of berries and leafy greens (Bacillus cereus, Enterobacter cloacae, Escherichia coli, Kocuria kristinae, Lactobacillus plantarum, Pantoea agglomerans, Pseudomonas fluorescens, Raoultella terrigena, and Xanthomonas campestris) were evaluated for the ability to form biofilms in the MBEC Assay Biofilm Inoculator and in 96-well microplates. The biofilm-forming bacteria were further tested for binding MNV-1 and Tulane virus and the ability to protect them against loss of capsid integrity upon exposure to disinfecting pulsed light at a fluence of 11.52 J/cm. Based on viral reductions, MNV-1 did not benefit from attachment to biofilm whereas Tulane virus was significantly more resistant than the control when attached to biofilms of E. cloacae (0.01), E. coli (0.01), (0.01), (0.05), or P. fluorescens (0.0001). Enzymatic dispersion of biofilm and microscopic observations suggest that the biofilm matrix composition may contribute to the virus resistance. Our results indicate that direct virus-biofilm interaction protects Tulane virus against disinfecting pulsed light, and that HuNoV on fresh produce therefore might resist such treatment more than suggested by laboratory tests so far. Recent studies have shown that bacteria may be involved in the attachment of HuNoV to the surface of fresh produce. Because these foods are difficult to disinfect by conventional methods without compromising product quality, nonthermal nonchemical disinfectants such as pulsed light are being investigated. We seek to understand how HuNoV interacts with epiphytic bacteria, particularly with biofilms formed by bacterial epiphytes, with cells and extracellular polymeric substances, and to determine if it thus escapes inactivation by pulsed light. The results of this study should advance understanding of the effects of epiphytic biofilms on the persistence of HuNoV particle integrity after pulsed light treatment and thus guide the design of novel pathogen control strategies in the food industry.
Topics: Humans; Animals; Mice; Norovirus; Escherichia coli; Disinfectants; Food-Processing Industry; Bacteria
PubMed: 37154750
DOI: 10.1128/aem.00043-23 -
Microbiology Spectrum Jun 2023Clinicians are increasingly confronted with the limitations of antibiotics to clear bacterial infections in patients. It has long been assumed that only antibiotic...
Clinicians are increasingly confronted with the limitations of antibiotics to clear bacterial infections in patients. It has long been assumed that only antibiotic resistance plays a pivotal role in this phenomenon. Indeed, the worldwide emergence of antibiotic resistance is considered one of the major health threats of the 21st century. However, the presence of persister cells also has a significant influence on treatment outcomes. These antibiotic-tolerant cells are present in every bacterial population and are the result of the phenotypic switching of normal, antibiotic-sensitive cells. Persister cells complicate current antibiotic therapies and contribute to the development of resistance. In the past, extensive research has been performed to investigate persistence in laboratory settings; however, antibiotic tolerance under conditions that mimic the clinical setting remain poorly understood. In this study, we optimized a mouse model for lung infections with the opportunistic pathogen Pseudomonas aeruginosa. In this model, mice are intratracheally infected with P. aeruginosa embedded in seaweed alginate beads and subsequently treated with tobramycin via nasal droplets. A diverse panel of 18 P. aeruginosa strains originating from environmental, human, and animal clinical sources was selected to assess survival in the animal model. Survival levels were positively correlated with the survival levels determined via time-kill assays, a common method to study persistence in the laboratory. We showed that survival levels are comparable and thus that the classical persister assays are indicative of antibiotic tolerance in a clinical setting. The optimized animal model also enables us to test potential antipersister therapies and study persistence in relevant settings. The importance of targeting persister cells in antibiotic therapies is becoming more evident, as these antibiotic-tolerant cells underlie relapsing infections and resistance development. Here, we studied persistence in a clinically relevant pathogen, Pseudomonas aeruginosa. It is one of the six ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa, and Enterobacter spp.), which are considered major health threats. P. aeruginosa is mostly known to cause chronic lung infections in cystic fibrosis patients. We mimicked these lung infections in a mouse model to study persistence under more clinical conditions. It was shown that the survival levels of natural P. aeruginosa isolates in this model are positively correlated with the survival levels measured in classical persistence assays . These results not only validate the use of our current techniques to study persistence but also open opportunities to study new persistence mechanisms or evaluate new antipersister strategies .
Topics: Humans; Mice; Animals; Anti-Bacterial Agents; Pseudomonas aeruginosa; Staphylococcal Infections; Enterobacter; Lung; Pseudomonas Infections
PubMed: 37140371
DOI: 10.1128/spectrum.04970-22 -
The Journal of Pediatric Pharmacology... 2023We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age...
We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 mL/kg/hr; however, pharmacokinetic data on cefepime dosing in pediatric CRRT are scant. This case report describes the successful dosing strategy used for this patient while on various rates of continuous veno-venous hemodialysis with CARPEDIEM. Therapeutic drug monitoring of cefepime should be considered in critically ill pediatric patients on CARPEDIEM receiving CRRT.
PubMed: 37139247
DOI: 10.5863/1551-6776-28.2.167 -
Frontiers in Microbiology 2023The Enterobacterales are a group of Gram-negative bacteria frequently exhibiting extended antimicrobial resistance (AMR) and involved in the transmission of resistance...
BACKGROUND
The Enterobacterales are a group of Gram-negative bacteria frequently exhibiting extended antimicrobial resistance (AMR) and involved in the transmission of resistance genes to other bacterial species present in the same environment. Due to their impact on human health and the paucity of new antibiotics, the World Health Organization (WHO) categorized carbapenem resistant and ESBL-producing as critical. Enterobacterales are ubiquitous and the role of the environment in the transmission of AMR organisms or antimicrobial resistance genes (ARGs) must be examined in tackling AMR in both humans and animals under the one health approach. Animal manure is recognized as an important source of AMR bacteria entering the environment, in which resistant genes can accumulate.
METHODS
To gain a better understanding of the dissemination of third generation cephalosporin and fluoroquinolone resistance genes between isolates in the environment, we applied whole genome sequencing (WGS) to Enterobacterales (79 , 1 , 1 , and 1 ) isolated from farm effluents in Ireland before ( = 72) and after ( = 10) treatment by integrated constructed wetlands (ICWs). DNA was extracted using the MagNA Pure 96 system (Roche Diagnostics, Rotkreuz, Switzerland) followed by WGS on a MiSeq platform (Illumina, Eindhoven, Netherlands) using v3 chemistry as 300-cycle paired-end runs. AMR genes and point mutations were identified and compared to the phenotypic results for better understanding of the mechanisms of resistance and resistance transmission.
RESULTS
A wide variety of cephalosporin and fluoroquinolone resistance genes (mobile genetic elements (MGEs) and chromosomal mutations) were identified among isolates that mostly explained the phenotypic AMR patterns. A total of 31 plasmid replicon types were identified among the 82 isolates, with a subset of them ( = 24), identified in isolates. Five plasmid replicons were confined to the isolate and two were confined to the isolate. Virulence genes associated with functions including stress, survival, regulation, iron uptake secretion systems, invasion, adherence and toxin production were identified.
CONCLUSION
Our study showed that antimicrobial resistant organisms (AROs) can persist even following wastewater treatment and could transmit AMR of clinical relevance to the environment and ultimately pose a risk to human or animal health.
PubMed: 37032887
DOI: 10.3389/fmicb.2023.1118264 -
International Journal of Antimicrobial... Jun 2023Bloodstream infections (BSI) caused by Gram-negative bacteria (GNB) in patients with hematological malignancies (HM) have been associated with high mortality rates,...
Bloodstream infections due to Gram-negative bacteria in patients with hematologic malignancies: updated epidemiology and risk factors for multidrug-resistant strains in an Italian perspective survey.
Bloodstream infections (BSI) caused by Gram-negative bacteria (GNB) in patients with hematological malignancies (HM) have been associated with high mortality rates, particularly with infections caused by antibiotic-resistant strains. A multicenter cohort study including all consecutive episodes of GNB BSI in HM patients was conducted to update the epidemiology and antibiotic resistance patterns (compared to our previous survey conducted between 2009 and 2012) and investigate risk factors for GNB BSI due to multidrug-resistant (MDR) isolates. A total of 834 GNB were recovered in 811 BSI episodes from January 2016 to December 2018. Compared to the previous survey, there was a significant reduction in use of fluoroquinolone prophylaxis and a significant recovery in susceptibility rates to ciprofloxacin among Pseudomonas aeruginosa, Escherichia coli and Enterobacter cloacae isolates. In addition, there was a shift to a significantly increased susceptibility of P. aeruginosa isolates to ceftazidime, meropenem, and gentamicin. A total of 256/834 (30.7%) isolates were MDR. In multivariable analysis, MDR bacteria culture-positive surveillance rectal swabs, previous therapy with aminoglycosides and carbapenems, fluoroquinolone prophylaxis, and time at risk were independently associated with MDR GNB BSI. In conclusion, despite the persistence of a high prevalence of MDR GNB, there was a shift to a reduced use of fluoroquinolone prophylaxis and increased rates of susceptibility to fluoroquinolones in almost all isolates and to almost all antibiotics tested among P. aeruginosa isolates, compared to our previous survey. Fluoroquinolone prophylaxis and previous rectal colonization by MDR bacteria were independent risk factors for MDR GNB BSI in the present study.
Topics: Humans; Cohort Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Sepsis; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Fluoroquinolones; Risk Factors; Hematologic Neoplasms; Italy
PubMed: 37030470
DOI: 10.1016/j.ijantimicag.2023.106806 -
Frontiers in Cellular and Infection... 2023Clinical features and severity of the leishmaniasis is extremely intricate and depend on several factors, especially sand fly-derived products. Bacteria in the sand...
Clinical features and severity of the leishmaniasis is extremely intricate and depend on several factors, especially sand fly-derived products. Bacteria in the sand fly's gut are a perpetual companion of parasites. However, consequences of the concomitance of these bacteria and parasite outside the midgut environment have not been investigated in the infection process. Herein, a needle infection model was designed to mimic transmission by sand flies, to examine differences in the onset and progression of infection initiated by inoculation with "low" or "high" doses of and bacteria. The results showed an alteration in the local expression of pro- and anti-inflammatory cytokines in mice receiving different inoculations of bacteria. Simultaneous injection of two bacteria with parasites in the low-dose group caused greater thickness of ear pinna and enhanced tissue chronic inflammatory cells, as well as resulted in multifold increase in the expression of IL-4 and IL-1β and a decrease in the iNOS expression, without changing the burden. Despite advances in scientific breakthroughs, scant survey has investigated the interaction between micro and macro levels of organization of leishmaniasis that ranges from the cellular to macro ecosystem levels, giving rise to the spread and persistence of the disease in a region. Our findings provide new insight into using the potential of the vector-derived microbiota in modulating the vertebrate immune system for the benefit of the host or recommend the use of appropriate antibiotics along with antileishmanial medicines.
Topics: Animals; Mice; Bacteria; Coinfection; Leishmania major; Leishmaniasis; Mice, Inbred BALB C; Phlebotomus; Psychodidae
PubMed: 36779192
DOI: 10.3389/fcimb.2023.1115542 -
JAC-antimicrobial Resistance Feb 2023Temocillin is a β-lactam that is not hydrolysed by ESBLs.
Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.
BACKGROUND
Temocillin is a β-lactam that is not hydrolysed by ESBLs.
OBJECTIVES
To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure.
METHODS
Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure.
RESULTS
Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ± 15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were (49.6%), (44.2%) and (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6).
CONCLUSIONS
The main use of temocillin was UTI due to ESBL-producing and , with a favourable clinical outcome. The main risk factor for failure was neurological disease.
PubMed: 36601547
DOI: 10.1093/jacamr/dlac132 -
The Canadian Journal of Infectious... 2022Cystic fibrosis (CF) is an inherited recessive disorder characterized by recurrent and persistent pulmonary infections, resulting in lung function deterioration and...
BACKGROUND
Cystic fibrosis (CF) is an inherited recessive disorder characterized by recurrent and persistent pulmonary infections, resulting in lung function deterioration and early mortality.
METHODS
A cross-sectional study was conducted on the bacterial profile and antibiotic resistance pattern of 103 respiratory specimens from CF patients with signs of pulmonary exacerbation. Antibiotic susceptibility testing and biofilm formation of and isolates were performed by the Kirby-Bauer disc diffusion method and microtiter plate assay, respectively. Molecular typing of and isolates was carried out by spa typing and repetitive extragenic palindromic element PCR.
RESULTS
In a total of 129 isolates, the most prevalent organisms were (55.3%) and (41.7%). Other less prevalent bacterial isolates include coagulase-negative staphylococci, , , , and . The highest rate of resistance for was observed to azithromycin and erythromycin (80%), ciprofloxacin (52.3%), clindamycin (44.6%) and tetracycline (43%). Twenty percent of isolates were methicillin-resistant (MRSA) and 47.6% were MDR . For isolates the highest resistance was to cefepime (38.3%) and levofloxacin (33.3%) and 20% showed MDR phenotype.
CONCLUSION
Our study demonstrated a significant decline in the prevalence of infections in comparison to previous studies. We found to be more prevalent in younger patients, whereas mucoid showed a shift in prevalence toward older ages. Molecular typing methods showed great diversity between isolates.
PubMed: 36593975
DOI: 10.1155/2022/5831139