Antibiotics, Volume 13, Issue 1 (January 2024) – 109 articles

Foodborne diseases are one of the main issues for human health, and antibacterial packaging plays a major role in food security assurance. Silver ultra nanoparticles (Argirium SUNc) are antimicrobial agents that have a wide spectrum of action, including against pathogenic bacteria and spoilage fungi. The aim of the present study was to evaluate the antibacterial activity of Argirium SUNc on the bacteria most commonly found in food: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Listeria monocytogenes, and Salmonella typhimurium. In this regard, an in vitro study was carried out by assessing the Argirium SUNc effectiveness on different concentrations of each tested microbial strain and at different time intervals. The data showed that the antimicrobial activity of Argirium SUNc was directly related to the microbial concentration and varied depending on the microbial species. Moreover, a greater effectiveness against Gram-negative bacteria than Gram-positive bacteria was observed. These preliminary results provided important information on the silver nanoparticles spectrum of action, and this is an aspect that appears particularly promising for obtaining a viable alternative to traditional antimicrobials to be used against the pathogens and spoilage agents most commonly found in the food chain, harmful both to health and quality aspects. Full article

This study investigated the potential of pulsed electric field (PEF) extraction in enhancing the antimicrobial properties related to anti-acne and deodorant properties of Hedychium coronarium extract. The dried leaf and rhizome of H. coronarium were extracted using 95% v/v ethanol through both conventional solvent extraction and PEF extraction techniques (10, 14, and 20 kV/cm). The chemical composition of the extracts was analyzed. The antimicrobial activities, specifically in relation to acne treatment against Cutibacterium acnes and deodorant properties against Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa, and Escherichia coli, were determined. The irritation profile of was evaluated using the hen’s egg chorioallantoic membrane test. The results showed that PEF extraction increased the extract yield, particularly at an electric field strength of 20 kV/cm. Furthermore, PEF extraction significantly enhanced the ellagic acid content, particularly in the leaf extract. Furthermore, the leaf extract demonstrated stronger inhibitory effects against microorganisms associated with body odor and acne compared to the rhizome extract. Notably, all extracts exhibited no signs of irritation, indicating their safety. Overall, the findings suggest that PEF extraction from H. coronarium enhances yield, bioactive compound content, and antimicrobial effects. This indicates the potential of the extract for acne treatment and deodorant use. Full article

Aquaculture located in urban river estuaries, where other anthropogenic activities may occur, has an impact on and may be affected by the environment where they are inserted, namely by the exchange of antimicrobial resistance genes. The latter may ultimately, through the food chain, represent a source of resistance genes to the human resistome. In an exploratory study of the presence of resistance genes in aquaculture sediments located in urban river estuaries, two machine learning models were applied to predict the source of 34 resistome observations in the aquaculture sediments of oysters and gilt-head sea bream, located in the estuaries of the Sado and Lima Rivers and in the Aveiro Lagoon, as well as in the sediments of the Tejo River estuary, where Japanese clams and mussels are collected. The first model included all 34 resistomes, amounting to 53 different antimicrobial resistance genes used as source predictors. The most important antimicrobial genes for source attribution were tetracycline resistance genes tet(51) and tet(L); aminoglycoside resistance gene aadA6; beta-lactam resistance gene blaBRO-2; and amphenicol resistance gene cmx_1. The second model included only oyster sediment resistomes, amounting to 30 antimicrobial resistance genes as predictors. The most important antimicrobial genes for source attribution were the aminoglycoside resistance gene aadA6, followed by the tetracycline genes tet(L) and tet(33). This exploratory study provides the first information about antimicrobial resistance genes in intensive and semi-intensive aquaculture in Portugal, helping to recognize the importance of environmental control to maintain the integrity and the sustainability of aquaculture farms. Full article

This study aimed to investigate the effects of dental coating materials on Streptococcus mutans biofilm formation. The test materials were PRG Barrier Coat (PRG), BioCoat Ca (BioC), and FluorDental Jelly (FluorJ). Bovine enamel specimens were demineralized to mimic early enamel lesions. The biofilm was developed on a specimen treated with one of the materials by using a modified Robbins device flow-cell system. Scanning electron and fluorescence confocal laser scanning microscopy, viable and total cell counts, and gene expression assessments of the antibiofilm were performed. Ion incorporation was analyzed using a wavelength-dispersive X-ray spectroscopy electron probe microanalyzer. All materials allowed biofilm formation but reduced its volume. FluorJ was the only material that inhibited biofilm accumulation and had a bactericidal effect, revealing 0.66 log CFU in viable cells and 1.23 log copy reduction in total cells compared with the untreated group after 24 h of incubation. The ions released from PRG varied depending on the element. BioC contributed to enamel remineralization by supplying calcium ions while blocking the acid produced from the biofilm. In summary, the dental coating materials physically prevented acid attacks from the biofilm while providing ions to the enamel to improve its mechanical properties. Full article

Anatomical or functional asplenia constitutes a risk factor for Streptococcus pneumoniae (SP) infection, being more frequent in children and the elderly and in people with multiple comorbidities. We aimed to describe the impact of invasive pneumococcal disease (IPD) on the clinical features and outcomes of patients hospitalized for asplenia in Spain. Discharge reports from the Spanish Minimum Basic Data Set were used to retrospectively analyze hospital discharge data with a diagnosis of asplenia from 1997 to 2021. A total of 132,257 patients with asplenia (splenectomized/non-splenectomized) were identified from the Spanish database. Among the cases, 177 (37.5%) patients with splenectomy and 295 (62.5%) patients without splenectomy developed IPD. The clinical presentations (non-infection vs. infection) did not significantly differ between the two reference groups, except for patients with COPD, rheumatoid disease, AIDS, other neurological disorders, metastatic cancer, and drug abuse. The risk factors for IPD were also more frequently reported in patients without splenectomy (p < 0.001) and with comorbidities (p = 0.005). The study of patients with asplenia provides relevant information about the state of SP infection. This epidemiological tracking can serve to better understand the comorbidities that affect them, the risk factors for the disease, the prediction of antibiotic use, and vaccination in public health, among other factors. Full article

Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS data from 1449 E. coli isolates were evaluated for isolation source (humans, animals, food, or the environment) and the presence of antibiotic resistance genes (ARGs). We performed sequence typing using PubMLST and used ResFinder to identify ARGs. We categorized isolates as being pan-susceptible, resistant, or multidrug-resistant (MDR), defined as carrying resistance genes for at least three or more antimicrobial drug classes. In total, 60% of isolates were pan-susceptible, while 18% were resistant, and 22% exhibited MDR. The proportion of resistant isolates varied significantly according to the source of the isolates (p < 0.001). The greatest resistance was detected in isolates from humans and then animals, while environmental isolates showed the least resistance. This study demonstrates the feasibility of comparing AMR across various sectors in Washington using WGS and a One Health approach. Such analysis can complement other efforts for AMR surveillance and potentially lead to targeted interventions and monitoring activities to reduce the overall burden of AMR. Full article

The aim of this study was to assess antibiotic use in the Hungarian hospital care sector during and before the pandemic. Aggregated systemic antibiotic (ATC: J01) utilisation data were obtained for the 2010–2021 period. Classifications and calculations were performed according to the WHO ATC/DDD index and expressed as DDD per 1000 inhabitants and per day (DID), DDD per 100 patient-days (DHPD) and DDD/discharge. A linear regression (trend analysis) was performed for the pre-COVID years (2010–2019) and a prediction interval was set up to assess whether the pandemic years’ observed utilisation fit in. Antibiotic utilisation was constant in DID before and during the pandemic (2019: 1.16; 2020: 1.21), while we observed a substantial increase in antibiotic use when expressed in DDD per 100 patient-days (2019: 23.3, 2020: 32.2) or DDD/discharge (2019: 1.83, 2020: 2.45). The observed utilisation level of penicillin combinations; first-, third- and fourth-generation cephalosporins; carbapenems; glycopeptides; nitroimidazoles and macrolides exceeded the predicted utilisation values in both pandemic years. Before the pandemic, co-amoxiclav headed the top list of antibiotic use, while during the pandemic, ceftriaxone became the most widely used antibiotic. Azithromycin moved up substantially on the top list of antibiotic use, with a 397% increase (2019: 0.45; 2020: 2.24 DHPD) in use. In summary, the pandemic had a major impact on the scale and pattern of hospital antibiotic use in Hungary. Full article

The average American today undergoes three inpatient and two outpatient surgical procedures during one’s life, each of which carries with it a risk of post-operative infection. It has long been known that post-operative infections cause significant morbidity in the immediate peri-operative period, but recent evidence suggests that they can have long-term consequences as well, increasing a patient’s risk of infectious complications in unrelated surgeries performed months or even years later. While there are several theories on the origin of this association, including bacterial colonization of a post-operative infectious wound site, antimicrobial resistance from curative courses of antibiotics, subclinical immunosuppression, or the creation of an inflammatory “pathobiome” following an infectious insult, it is ultimately still unclear why patients who experience a single post-operative infection seem to be at a significantly higher risk of experiencing subsequent ones. Regardless, this association has significant implications for the routine use of pre-operative antibiotic prophylaxis. Indeed, while the prescription of antibiotics pre-operatively has dramatically reduced the rate of post-operative infections, the chosen prophylaxis regimens are typically standardized according to national guidelines, are facing increasing antimicrobial resistance patterns, and have been unable to reduce the risk of post-operative infection to acceptably low levels for certain surgeries. As a result, some clinicians have speculated that tailoring pre-operative antibiotic prophylaxis according to a patient’s prior infectious and operative history could improve efficacy and further reduce the rate of post-operative infections. The purpose of this review is to describe the evidence for the link between multiple post-operative infections and explore the efficacy of individualized pre-operative prophylaxis. Full article

Antibiotic self-medication, which refers to acquisition and using antibiotics to treat infections based on personal experience and/or without a doctor’s advice or prescription, is a significant public health issue jeopardizing patient health outcomes. The purpose of the present cross-sectional online survey was to assess the frequency of self-medication among the general public in various geographical locations in southern Jordan, as well as to examine the determinants to self-medication. The survey was distributed through several social media networks over the period November–December 2022, and included demographic information as well as items related to the use and abuse of antibiotics, information sources about antibiotics, the duration of use of antibiotics, and assessment of the public knowledge about appropriate antibiotic use. Inferential analysis, such as the Chi-Square test and logistic regression, were adopted to assess the associations between the different variables with self-medication. A total of 984 respondents were enrolled in the study. Of these, 752 had been using antibiotics during the last year. However, the self-medicating cases were 413 of the 752. The main source of information about the utilization of antibiotics among participants in the survey was pharmacists. The participants commonly (36.0%) tended to use antibiotics until the symptoms disappeared. Nearly half of the respondents reported usually taking antibiotics for treating a runny nose (rhinorrhea). The logistic regression analysis indicated that self-medication with antibiotics was significantly associated with female gender (p-value < 0.001), low educational level (p-value = 0.014), rural living location (p-value 0.003), no health insurance (p-value = 0.001) and occupation (p-value = 0.005). Meanwhile age had no significant relationship to self-medication. Finally, the results revealed poor understanding of key appropriate antibiotic usage, which inevitably influences self-medication practice. It is crucial to come up with several programs and governmental policies to suppress widespread antibiotic self-medication as it will affect the health of future generations of Jordanian citizens. Full article

The National Reference Centre for Enterococci receives an increasing number of linezolid-resistant Enterococcus isolates. Linezolid (LIN) resistance is mediated by G2576T 23S rDNA gene mutations and/or acquisition of resistance genes (cfr, optrA, poxtA). There are anecdotal reports that those resistance traits may be present in phenotypically linezolid-susceptible isolates. We aimed to determine the prevalence of LIN resistance genes and mutations in enterococci with a LIN MIC of 4 mg/L in broth microdilution (EUCAST = susceptible) isolated from German hospital patients 2019–2021. LIN MICs were additionally determined by ETEST^® and VITEK2. Selected strains were subjected to LIN selective pressure and growth was monitored with increasing antibiotic concentrations. We received 195 isolates (LIN MIC = 4 mg/L). In total, 78/195 (40%) isolates contained either a putative resistance gene, the G2576T mutation, or a combination thereof. Very major error was high for broth microdilution. The ability to predict phenotypic resistance from genotypic profile was highest for G2576T-mediated resistance. Selection experiments revealed that, in particular, E. faecium isolates with resistance gene mutations or poxtA rapidly adapt to MICs above the clinical breakpoint. In conclusion, LIN resistance genes and mutations can be observed in phenotypically linezolid-susceptible enterococci. Those isolates may rapidly develop resistance under LIN selective pressure potentially leading to treatment failure. Full article

In the multimodal strategy context, to implement healthcare-associated infection prevention, bundles are one of the most commonly used methods to adapt guidelines in the local context and transfer best practices into routine clinical care. One of the most important measures to prevent surgical site infections is surgical antibiotic prophylaxis (SAP). This narrative review aims to present a bundle for the correct SAP administration and evaluate the evidence supporting it. Surgical site infection (SSI) prevention guidelines published by the WHO, CDC, NICE, and SHEA/IDSA/APIC/AHA, and the clinical practice guidelines for SAP by ASHP/IDSA/SIS/SHEA, were reviewed. Subsequently, comprehensive searches were also conducted using the PubMed^®/MEDLINE and Google Scholar databases, in order to identify further supporting evidence-based documentation. The bundle includes five different measures that may affect proper SAP administration. The measures included may be easily implemented in all hospitals worldwide and are based on minimal drug pharmacokinetics and pharmacodynamics knowledge, which all surgeons should know. Antibiotics for SAP should be prescribed for surgical procedures at high risk for SSIs, such as clean–contaminated and contaminated surgical procedures or for clean surgical procedures where SSIs, even if unlikely, may have devastating consequences, such as in procedures with prosthetic implants. SAP should generally be administered within 60 min before the surgical incision for most antibiotics (including cefazolin). SAP redosing is indicated for surgical procedures exceeding two antibiotic half-lives or for procedures significantly associated with blood loss. In principle, SAP should be discontinued after the surgical procedure. Hospital-based antimicrobial stewardship programmes can optimise the treatment of infections and reduce adverse events associated with antibiotics. In the context of a collaborative and interdisciplinary approach, it is essential to encourage an institutional safety culture in which surgeons are persuaded, rather than compelled, to respect antibiotic prescribing practices. In that context, the proposed bundle contains a set of evidence-based interventions for SAP administration. It is easy to apply, promotes collaboration, and includes measures that can be adequately followed and evaluated in all hospitals worldwide. Full article

The Australian roadside soil-derived fungus Penicillium shearii CMB-STF067 was prioritized for chemical investigation based on an SDA cultivation extract exhibiting both antibacterial properties and natural products with unprecedented molecular formulae (GNPS). Subsequent miniaturized 24-well plate cultivation profiling (MATRIX) identified red rice as optimal for the production of the target chemistry, with scaled-up cultivation, extraction and fractionation yielding four new xanthone–anthraquinone heterodimers, jugiones A–D (1–4), whose structures were assigned by detailed spectroscopic analysis and biosynthetic considerations. Of note, where 1–2 and 4 were active against the Gram-positive bacteria vancomycin-resistant Enterococcus faecalis (IC₅₀ 2.6–3.9 μM) and multiple-drug-resistant clinical isolates of Staphylococcus aureus (IC₅₀ 1.8–6.4 μM), and inactive against the Gram-negative bacteria Escherichia coli (IC₅₀ > 30 μM), the closely related analog 3 exhibited no antibacterial properties (IC₅₀ > 30 μM). Furthermore, where 1 was cytotoxic to human carcinoma (IC₅₀ 9.0–9.8 μM) and fungal (IC₅₀ 4.1 μM) cells, 2 and 4 displayed no such cytotoxicity (IC₅₀ > 30 μM), revealing an informative structure activity relationship (SAR). We also extended the SAR study to other known compounds of this heterodimer class, which showed that the modification of ring G can reduce or eliminate the cytotoxicity while retaining the antibacterial activity. Full article

Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin—1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. Staphylococcal TSS can be menstrual or nonmenstrual. Streptococcal TSS is linked to a severe group A streptococcal infection and, most frequently, to a necrotizing soft tissue infection. Management of TSS is a medical emergency and relies on early detection, immediate resuscitation, source control and eradication of toxin production, bactericidal antibiotic treatment, and protein synthesis inhibiting antibiotic administration. The interest of polyclonal intravenous immunoglobulin G administration as an adjunctive treatment for TSS requires further evaluation. Scientific literature on TSS mainly consists of observational studies, clinical cases, and in vitro data; although more data on TSS are required, additional studies will be difficult to conduct due to the low incidence of the disease. Full article

Pneumonia is a common and severe illness that requires prompt and effective management. Advanced, rapid, and accurate tools are needed to diagnose patients with severe bacterial pneumonia, and to rapidly select appropriate antimicrobial therapy, which must be initiated within the first few hours of care. Two multiplex molecular tests, Unyvero HPN and FilmArray Pneumonia+ Panel, have been developed using the multiplex polymerase chain reaction (mPCR) technique to rapidly identify pathogens and their main antibiotic resistance mechanisms from patient respiratory specimens. Performance evaluation of these tests showed strong correlations with reference techniques. However, good knowledge of their indications, targets, and limitations is essential. Collaboration with microbiologists is, therefore, crucial for their appropriate use. Under these conditions, and with standardized management, these rapid tests can improve the therapeutic management of severe pneumonia faster, more precisely, and with narrow-spectrum antibiotic therapy. Further randomized controlled trials are needed to address the many unanswered questions about multiplex rapid molecular testing during the diagnosis and the management of severe pneumonia. This narrative review will address the current knowledge, advantages, and disadvantages of these tests, and propose solutions for their routine use. Full article

Laboratory evolution studies, particularly with Escherichia coli, have yielded invaluable insights into the mechanisms of antimicrobial resistance (AMR). Recent investigations have illuminated that, with repetitive antibiotic exposures, bacterial populations will adapt and eventually become tolerant and resistant to the drugs. Through intensive analyses, these inquiries have unveiled instances of convergent evolution across diverse antibiotics, the pleiotropic effects of resistance mutations, and the role played by loss-of-function mutations in the evolutionary landscape. Moreover, a quantitative analysis of multidrug combinations has shed light on collateral sensitivity, revealing specific drug combinations capable of suppressing the acquisition of resistance. This review article introduces the methodologies employed in the laboratory evolution of AMR in bacteria and presents recent discoveries concerning AMR mechanisms derived from laboratory evolution. Additionally, the review outlines the application of laboratory evolution in endeavors to formulate rational treatment strategies. Full article

Antimicrobial resistance of Escherichia coli is a growing problem in both developed and developing countries. This study aimed to investigate the phenotypic antimicrobial resistance of E. coli isolates (n = 260) isolated from the stool specimen of patients attending public health facilities in Addis Ababa and Hossana. This study also aimed to characterize phenotypically confirmed extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (n = 22) using whole-genome sequencing. Resistance to 18 different antimicrobials was assessed using the disc diffusion method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The highest resistance rate among the E. coli isolates was found for ampicillin (52.7%), followed by trimethoprim-sulfamethoxazole (29.6%). Of all isolates, 50 (19.2%) were multidrug-resistant and 22 (8.5%) were ESBL producers. ESBL genes were detected in 94.7% of the sequenced E. coli isolates, and multiple β-lactamase genes were detected in 57.9% of the isolates. The predominant ESBL gene identified was bla_CTX-M-15 (78.9%). The bla_TEM-1B gene was detected in combination with other ESBL genes in 57.9% of the isolates, while only one of the sequenced isolates contained the bla_TEM-1B gene alone. The bla_CTX-M-3 gene was detected in three isolates. The genes bla_CTX-M-15 and bla_TEM-1B as well as bla_CTX-M-15 and bla_TEM-169 were confirmed to coexist in 52.6% and 10.5% of the sequenced E. coli isolates, respectively. In addition, bla_OXA-1 was identified together with bla_CTX-M-15 and bla_TEM-1B in one isolate, and in one isolate, bla_TEM-169 together with bla_CTX-M-15 and bla_TEM-1B was found. The results obtained show that measures need to be taken to reduce the spread of drug resistance and ensure the long-term use of available antimicrobials. Full article

Primary care antimicrobial stewardship program (ASP) interventions can reduce the over-prescription of unnecessary antibiotics, but the impact on the reduction in bacterial resistance is less known, and there is a lack of available data. We implemented a prolonged educational counseling ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, which was compared to a pre-intervention period, a significant reduction in antibiotic prescriptions occurred, particularly those associated with greater harmful effects and resistance selection. There was also a decrease in methicillin-resistant Staphylococcus aureus (MRSA) strains and in their co-resistance to other antibiotics, particularly those with an ecological impact. Full article

The objective of this study was to compare the minimum inhibitory concentrations of antimicrobials included in a commercial broth microdilution panel among Gram-positive pathogens that caused non-severe clinical mastitis on three Michigan dairy farms. Duplicate quarter milk samples were collected from eligible quarters of cows enrolled in a randomized clinical trial, cultured in a university laboratory, and identified using MALDI-TOF. Etiologies were grouped by genus as Enterococcus species (n = 11), Lactococcus species (n = 44), non-aureus Staphylococcus species (n = 39), or Streptococcus species (n = 25). Minimum inhibitory concentrations (MICs) were determined using the mastitis panel of a commercially available broth microdilution test. In vitro susceptibility was determined using approved guidelines and included breakpoints for mastitis pathogens, or when not available, breakpoints from other species. Most isolates were inhibited at or below breakpoints that demonstrated in vitro susceptibility. The proportions of susceptible isolates varied among pathogens for pirlimycin, penicillin, and tetracycline. The greatest proportion of resistance was observed for pirlimycin, tetracycline, and sulfadimethoxine. Survival analysis was performed to evaluate differences in MICs among pathogen groups. MIC values varied among pathogens for ceftiofur, cephalothin, erythromycin, penicillin, pirlimycin, and tetracycline. However, nearly all isolates were susceptible to ceftiofur and cephalothin, indicating that pathogen differences in MIC are not likely clinically relevant, as these are the two most commonly administered mastitis treatments in the United States. While differences in vitro susceptibility were observed for some antimicrobials, susceptibility was high to cephalosporin-based IMM treatments that are most commonly used and did not vary among pathogens. Full article

Background: Managing Pseudomonas aeruginosa bloodstream infections (BSIs) is challenging due to increasing antimicrobial resistance, limited therapeutic options, and high mortality rates. In this study, we aimed to identify 30-day mortality risk factors and assess infectious diseases consultants’ preferences for combination or monotherapy. Methods: The study was conducted in four hospitals in Istanbul, Turkey, involving 140 adult ICU beds and 336,780 ICU-bed-days between 1 January 2014, and 31 December 2021. A total of 157 patients were included in the study. Cox proportional hazard regression was performed to assess the factors on 30-day mortality. Results: The 30-day mortality rate was 44.6% (70/157). Higher Charlson Comorbidity Index (CCI) score, severe sepsis, primary bloodstream infection, being in COVID-19 pandemic period, and infection caused by MDR strain were associated with higher hazard of 30-day mortality. Combination therapy was more commonly used in patients with BSIs with MDR or DTR (difficult-to-treat) strains but did not significantly improve the hazard of 30-day mortality. Conclusions: Targeted interventions and vigilant management strategies are crucial for patients with defined risk factors. While infectious disease consultants tended to favor combination therapy, particularly for drug-resistant strains, our analysis revealed no significant impact on 30-day mortality hazard. The increased incidence of P. aeruginosa BSIs during the pandemic emphasizes the need for infection control measures and appropriate antibiotic prescribing practices. Full article

Background: The use of peripherally inserted central catheters (PICCs) as an alternative to central venous catheters (CVCs) has steadily risen over the last two decades. However, there is an ongoing debate regarding research evidence that supports any clear advantages or disadvantages of them compared to traditional central venous lines. The present study was conducted to compare the indwelling time of CVC and PICC placements leading to microbial colonization by multidrug-resistant microorganisms (MDROs) in critically ill patients. Methods: A single-center retrospective descriptive study was performed that reviewed the medical records of critically ill patients with colonized CVCs and PICCs who were hospitalized during a 24-month period (May 2019–May 2021). To evaluate the association between indwelling time of catheter placement and colonization rates, events were categorized into three groups, each representing a one-week time interval of catheter indwelling time: group 1: ≤7 days, group 2: 8–14 days, and group 3: >14 days. Results: A total of 207 hospitalized patients with colonized PICCs or CVCs were included in the study. Of these, 144 (69.5%) had a CVC placement and 63 (30.5%) had a PICC placement. The overall colonization rate (per 1.000 catheter/days) was 14.73 in the CVC and 5.67 in the PICC cohort (p = 0.003). In the group of PICCs, 12/63 (19%) of the pathogens were MDROs and 51/63 (81%) were non-MDROs, while in the group of CVCs, 86/144 (59.7%) were MDROs and 58/144 (40.3%) were non-MDROs (p < 0.001). The colonization rate in the CVC cohort, was 6.98 for group 1, 21.57 for group 2, and 21.6 for group 3 (p = 0.019). The colonization rate of MDROs was 3.27 for group 1, 14.47 for group 2, and 12.96 for group 3 (p = 0.025). Regarding the PICC cohort, the colonization rate was 1.49 for group 1, 3.19 for group 2, and 8.99 for group 3 (p = 0.047). No significant difference existed between the three groups in terms of MDRO pathogens, with the colonization rate being 0 for group 1, 0.8 for group 2, and 1.69 for group 3 (p = 0.78). Within the CVC cohort, the most common isolated microorganism was MDR Acinetobacter baumannii (n = 44; 30.6%), followed by MDR Klebsiella pneumoniae (n = 27; 18.7%). In the PICC cohort, the predominant isolated microorganism was Candida non-albicans (n = 15; 23.8%), followed by Candida albicans, coagulase-negative staphylococci, and MDR Klebsiella pneumoniae in equal numbers (n = 6; 9.5%). Conclusions: Our findings show that while the indwelling time of PICC placement was longer compared to CVCs, its colonization rate was considerably lower. Furthermore, high colonization rates by microorganisms, especially MDROs, arose later during catheterization in PICCs compared to CVCs, suggesting that in terms of vascular infections, PICCs may be a safer alternative to conventional CVCs for long-term intravenous access. Full article

Febrile infants under three months of age pose a diagnostic challenge to clinicians. Unlike in older children, the rates of invasive bacterial infections (IBIs), such as bacteraemia or meningitis, are high. This greater risk of IBI combined with the practical challenges of assessing young infants results in a cautious approach with many febrile infants receiving parenteral antibiotics “just in case”. However, there is a range of validated tailored care guidelines that support targeted investigation and management of febrile infants, with a cohort identified as lower risk suitable for fewer invasive procedures and observation without parenteral antibiotics. This manuscript outlines five common conundrums related to the safe application of tailored-care guidelines for the assessment and management of febrile infants under three months of age. It also explores future research which aims to further refine the management of febrile infants. Full article

Waterborne faecal contamination is a major public health concern. The main objectives of this study were to investigate faecal contamination and Escherichia coli (E. coli) antibiotic resistance in recreational fresh water from Guadeloupe and to characterise the microbiome and resistome composition in biofilms from submerged rocks. Significant faecal contamination was observed at 14 freshwater sites. E. coli predominated (62%), followed by Enterobacter cloacae (11%) and Acinetobacter spp. (11%). Of 152 E. coli isolated, none produced extended-spectrum beta-lactamases (ESBLs), but 7% showed resistance to streptomycin and 4% to tetracycline. Biofilm resistome analysis revealed clinically significant antibiotic-resistance genes (ARGs), including those coding for resistance to sulfonamides (sul1), carbapenems (bla_KPC), and third-generation cephalosporins (bla_CTX-M). Mobile genetic elements (MGEs) (intI1, intI2, intI3) linked to resistance to aminoglycosides, beta-lactams, tetracycline, as well as heavy metal resistance determinants (copA, cusF, czcA, merA) conferring resistance to copper, silver, cadmium, and mercury were also detected. Diverse bacterial phyla were found in biofilm samples, of which Proteobacteria, Bacteroidetes, Planctonomycetes, and Cyanobacteria were predominant. Despite the frequent presence of E. coli exceeding regulatory standards, the low levels of antibiotic-resistant bacteria in freshwater and of ARGs and MGEs in associated biofilms suggest limited antibiotic resistance in Guadeloupean recreational waters. Full article

The absence of effective therapy against Escherichia coli O157:H7 infections has led to the need to develop new antimicrobial agents. As the use of synergistic combinations of natural antimicrobial compounds is growing as a new weapon in the fight against multidrug-resistant bacteria, here, we have tested new synergistic combinations of natural agents. Notably, we investigated a possible synergistic effect of combinations of essential oils and natural peptides to counteract the formation of biofilm. We chose three essential oils (i.e., Cymbopogon citratus, C. flexuosus and C. martinii) and one peptide already studied in our previous works. We determined the fractional inhibitory concentration (FIC) by analyzing the combination of the peptide derived from esculentin-1a, Esc(1–21), with the three essential oils. We also studied the effects of combinations by time–kill curves, scanning electron microscopy on biofilm and Sytox Green on cell membrane permeability. Finally, we analyzed the expression of different genes implicated in motility, biofilm formation and stress responses. The results showed a different pattern of gene expression in bacteria treated with the mixtures compared to those treated with the peptide or the single C. citratus essential oil. In conclusion, we demonstrated that the three essential oils used in combination with the peptide showed synergy against the E. coli O157:H7, proving attractive as an alternative strategy against E. coli pathogen infections. Full article

Streptococcus agalactiae (Group B Streptococcus; GBS) is a leading cause of neonatal invasive disease worldwide. GBS can colonize the human gastrointestinal and genitourinary tracts, and the anovaginal colonization of pregnant women is the main source for neonatal infection. Streptococcus anginosus, in turn, can colonize the human upper respiratory, gastrointestinal, and genitourinary tracts but has rarely been observed causing disease. However, in the last years, S. anginosus has been increasingly associated with human infections, mainly in the bloodstream and gastrointestinal and genitourinary tracts. Although anovaginal screening for GBS is common during pregnancy, data regarding the anovaginal colonization of pregnant women by S. anginosus are still scarce. Here, we show that during the assessment of anovaginal GBS colonization rates among pregnant women living in Rio de Janeiro, Brazil, S. anginosus was also commonly detected, and S. anginosus isolates presented a similar colony morphology and color pattern to GBS in chromogenic media. GBS was detected in 48 (12%) while S. anginosus was detected in 17 (4.3%) of the 399 anovaginal samples analyzed. The use of antibiotics during pregnancy and history of urinary tract infections and sexually transmitted infections were associated with the presence of S. anginosus. In turn, previous preterm birth was associated with the presence of GBS (p < 0.05). The correlation of GBS and S. anginosus with relevant clinical features of pregnant women in Rio de Janeiro, Brazil, highlights the need for the further investigation of these important bacteria in relation to this special population. Full article

(1) Background. Antimicrobial resistance (AMR) poses a substantial global health threat with profound economic implications. Acknowledging the imperative for a One Health (OH) strategy to combat this menace, Belgium introduced an annual national OH report, known as the “BELMAP report,” encompassing antimicrobial use (AMU) and AMR, with the first edition completed in 2021. The integration of innovations for the healthcare system demands a meticulously planned process. (2) Methods. We introduced a three-step stakeholder analysis (SA) as a prospective framework for navigating this new report process, fostering complementary collaboration, pinpointing obstacles, suggesting approaches to overcome them, and facilitating national policy development. The SA unfolds in three steps: stakeholders identify and list their relevant activities, assess their positions regarding the BELMAP report, and complete “actor mapping” of national AMR and AMU stakeholders. (3) Results. Stakeholder identification reveals a fragmented landscape of AMR and AMU activities across Belgium. Assessment of stakeholder positions uncovers diverse expectations, collaborative challenges, and resource considerations. “Actor mapping” identifies key stakeholders, emphasizing the importance of high-interest and high-power actors. (4) Conclusions. This SA approach not only provides insights into the present stakeholder landscape in Belgium, it can also serve as a blueprint for other countries in the process of developing OH reports. Full article

Sepsis can trigger acute respiratory distress syndrome (ARDS), which can lead to a series of physiological changes, modifying the effectiveness of therapy and culminating in death. For all experiments, male Wistar rats (200–250 g) were split into the following groups: control and sepsis-induced by endotoxin lipopolysaccharide (LPS); the control group received only intraperitoneal saline or saline + CEF while the treated groups received ceftriaxone (CEF) (100 mg/kg) IP; previously or not with sepsis induction by LPS (1 mg/kg) IP. We evaluated respiratory mechanics, and alveolar bronchial lavage was collected for nitrite and vascular endothelial growth factor (VEGF) quantification and cell evaluation. For pharmacokinetic evaluation, two groups received ceftriaxone, one already exposed to LPS. Respiratory mechanics shows a decrease in total airway resistance, dissipation of viscous energy, and elastance of lung tissues in all sepsis-induced groups compared to the control group. VEGF and NOx values were higher in sepsis animals compared to the control group, and ceftriaxone was able to reduce both parameters. The pharmacokinetic parameters for ceftriaxone, such as bioavailability, absorption, and terminal half-life, were smaller in the sepsis-induced group than in the control group since clearance was higher in septic animals. Despite the pharmacokinetic changes, ceftriaxone showed a reduction in resistance in the airways. In addition, CEF lowers nitrite levels in the lungs and acts on their adverse effects, reflecting pharmacological therapy of the disease. Full article

The symbiotic community of microorganisms in the gut plays an important role in the health of the host. While many previous studies have been performed on the interactions between the gut microbiome and the host in mammals, studies in fish are still lacking. In this study, we investigated changes in the intestinal microbiome and pathogen susceptibility of zebrafish (Danio rerio) following chronic antibiotics exposure. The chronic antibiotics exposure assay was performed on zebrafish for 30 days using oxytetracycline (Otc), sulfamethoxazole/trimethoprim (Smx/Tmp), or erythromycin (Ery), which are antibiotics widely used in the aquaculture industry. The microbiome analysis indicated that Fusobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in the gut microbiome of the zebrafish used in this study. However, in Smx/Tmp-treated zebrafish, the compositions of Fusobacteria and Proteobacteria were changed significantly, and in Ery-treated zebrafish, the compositions of Proteobacteria and Firmicutes were altered significantly. Although alpha diversity analysis showed that there was no significant difference in the richness, beta diversity analysis revealed a community imbalance in the gut microbiome of all chronically antibiotics-exposed zebrafish. Intriguingly, in zebrafish with dysbiosis in the gut microbiome, the pathogen susceptibility to Edwardsiella piscicida, a representative Gram-negative fish pathogen, was reduced. Gut microbiome imbalance resulted in a higher count of goblet cells in intestinal tissue and an upregulation of genes related to the intestinal mucosal barrier. In addition, as innate immunity was enhanced by the increased mucosal barrier, immune and stress-related gene expression in the intestinal tissue was downregulated. In this study, we provide new insight into the effect of gut microbiome dysbiosis on pathogen susceptibility. Full article

To solve the problem with pan-drug resistant and extensively drug-resistant Gram-negative microbes, newly approved drugs such as ceftazidime/avibactam, cefiderocol, plazomicin, meropenem/vaborbactam, and eravacycline have been introduced in practice. The aim of the present study was to collect carbapenemase-producing clinical Enterobacterales isolates, to characterize their carbapenemase genes and clonal relatedness, and to detect their susceptibility to commonly used antimicrobials and the above-mentioned newly approved antibiotics. Sixty-four carbapenemase producers were collected in a period of one year from four Bulgarian hospitals, mainly including Klebsiella pneumoniae (89% of the isolates) and also single Proteus mirabilis, Providencia stuartii and Citrobacter freundii isolates. The main genotype was bla_NDM-1 (in 61%), followed by bla_KPC-2 (23%), bla_VIM-1 (7.8%) and bla_OXA-48 (7.8%). Many isolates showed the presence of ESBL (bla_CTX-M-15/-3 in 76.6%) and AmpC (bla_CMY-4 in 37.5% or bla_CMY-99 in 7.8% of isolates). The most common MLST type was K. pneumoniae ST11 (57.8%), followed by ST340 (12.5%), ST258 (6.3%) and ST101 (6.3%). The isolates were highly resistant to standard-group antibiotics, except they were susceptible to tigecycline (83.1%), colistin (79.7%), fosfomycin (32.8%), and aminoglycosides (20.3–35.9%). Among the newly approved compounds, plazomicin (90.6%) and eravacycline (76.3%) showed the best activity. Susceptibility to ceftazidime/avibactam and meropenem/vaborbactam was 34.4% and 27.6%, respectively. For cefiderocol, a large discrepancy was observed between the percentages of susceptible isolates according to EUCAST susceptibility breakpoints (37.5%) and those of CLSI (71.8%), detected by the disk diffusion method. This study is the first report to show patterns of susceptibility to five newly approved antibiotics among molecularly characterized isolates in Bulgaria. The data may contribute to both the improvement of treatment of individual patients and the choice of infection control strategy and antibiotic policy. Full article

The opportunistic human fungal pathogen Candida albicans produces and releases into the surrounding medium extracellular vesicles (EVs), which are involved in some processes as communication between fungal cells and host–pathogen interactions during infection. Here, we have conducted the isolation of EVs produced by a clinical isolate of C. albicans during biofilm formation and proved their effect towards the ability of the Gram-negative bacterial pathogen Klebsiella pneumoniae to adhere to HaCaT cells and form a biofilm in vitro. The results represent the first evidence of an antagonistic action of fungal EVs against bacteria. Full article