Use Of Broad-spectrum Antibiotics Research Articles

Improved use of antibiotics following implementation of antimicrobial stewardship in a neonatal intensive care unit.

Inappropriate antibiotic use in infants can have multiple adverse effects and contribute to the development of bacteria resistant to antimicrobials. Antimicrobial stewardship programs can reduce unnecessary antibiotic use in children. The aim of this study was to evaluate the effect of an antimicrobial stewardship program implemented in 2017 in the Neonatal Intensive Care Unit (NICU) at The Children's Hospital Iceland. The study included all infants who were admitted to the NICU during the study period (January 1st 2012-October 31st 2020). Data was collected from hospital records. Three periods were defined: preimplementation (2012-2014), peri-implementation (2015-2016) and postimplementation (2017-October 2020). Antibiotic use was quantified using days of therapy (DOT) per 1000 bed days (BD). For statistical analysis the pre- and postimplementation periods were compared. Antibiotics were administered in 38.6% (1372) of admissions to the NICU during the study period. Antimicrobial use per year decreased from 584.6 to 317.1 DOT/1000 BD per year (P < 0.001). Use of broad-spectrum antibiotics decreased significantly. The average number of BD per month decreased from 297.8 to 220.9 BD/month (P = 0.0096). There were no significant changes in the length of stay for each infant or the proportion of readmissions or retreatment. Increased awareness of appropriate use of antimicrobials in the NICU led to shorter treatments and less use of broad-spectrum antibiotics. No increase in adverse effects such as readmissions or retreatment was observed.

Exploring comparative analysis of antibiotic resistance patterns in E.coli bacterial strains through the agar plate method

Abstract Introduction Antibiotic effectiveness varies across classes and bacteria, complicating the fight against infections. Utilising E. coli as a model organism offers insights into the microbial response to antibiotics. The agar plate method is crucial for visualising and assessing antibiotic resistance efficacy1. The looming threat of antibiotic resistance, with a potential death toll of 10 million by 2050, emphasises the urgency2. Investigating E. coli's role in gut health and its interaction with antibiotics via agar plate assays informs the selective use of broad-spectrum and narrow-spectrum antibiotics, vital for medical and agricultural applications3. Aim This study aims to explore the differential efficacy of broad-spectrum and narrow-spectrum antibiotics, including ampicillin, chloramphenicol, cefoxitin, and erythromycin, against E. coli using the agar plate method. The study aims to evaluate the effects of different antibiotics on E. coli to identify patterns of resistance and susceptibility, providing insights into the bacterial response to these drugs. Methods To maintain aseptic conditions, all equipment was sterilised, and a sterile workspace was established, as illustrated. The agar plates were carefully labelled with the specific bacterial strains and antibiotics slated for evaluation. Employing sterile techniques, the E. coli strains were swabbed onto these agar plates to ensure an even distribution. Antibiotic discs were then methodically placed onto the agar, spaced appropriately to prevent overlap, and gently pressed to ensure contact with the medium. These plates were subsequently incubated at 37°C for 24-48 hours, allowing for bacterial growth and antibiotic diffusion. Post-incubation, the diameters of the inhibition zones around each antibiotic disc were meticulously measured. Following the experimental procedures, biohazard materials were disposed of in accordance with safety protocols, and equipment was re-sterilised. To uphold the experiment’s validity and reliability, it was repeated over four weeks, with the average results compiled and analysed. Results This study evaluates the antibacterial effectiveness of four antibiotics over four weeks, measuring the area of inhibition against E. coli. Ampicillin's inhibition varied significantly, with a peak of 2358.58 mm² in Week 3 after a drop to 1468.46 mm² in Week 2. Chloramphenicol also showed variability, peaking at 897.27 mm² in Week 3. Cefoxitin displayed a consistent increase in effectiveness, with an inhibition area of 2317.44 mm² in Week 2. Erythromycin showed no inhibitory effect throughout the study. The data emphasises the dynamic bacterial response to these treatments. Discussion or Conclusions This study provides valuable insights into the relationship between antibiotic use and bacterial resistance in E. coli strains, utilising the agar plate method to assess antibiotic effectiveness and predict future resistance trends. By analysing inhibition zone patterns over time, the study identifies emerging resistance, suggesting this method’s utility in forecasting bacterial evolution. However, the approach is limited by its focus on in vitro conditions, which may not fully capture in vivo complexities, and it does not consider genetic mutations or environmental influences. These limitations highlight the need for more comprehensive research. The study advocates for integrated global strategies, combining judicious antibiotic use with novel antimicrobial developments.

Diagnostic uncertainties in patients with bacteraemia: impact on antibiotic prescriptions and outcome.

To establish a formal diagnosis in infectious disease is not an easy task. Our aim was to characterize diagnostic uncertainty (DU) in patients for whom blood cultures were positive (PBC) and to determine its impact on both the antibiotic therapy and the outcome. This was a prospective multicentre study including PBC for 6 months. The laboratory gave the PBC result to the infectious disease (ID) specialists in real time (24/7). The latter analysed all data from electronic patient charts and gave therapeutic advice to the physicians in charge of the patient to either initiate an antibiotic therapy, or to modify or to pursue continuing antimicrobial treatment. A DU was defined as no diagnosis of ID after thorough reading of the patient's chart, or more than two diagnoses despite two medical opinions obtained before PBC. An unfavourable outcome was defined by the occurrence of death during hospitalization. One hundred and nighty-nine PBCs were communicated to ID specialists, including 93 DUs (47%). In multivariate analysis, DU was associated with hospitalization in medical wards: [adjusted odds ratio (AOR) (95% CI): 6.94 (3.41-14.28)], the advice to initiate an antibiotic treatment: [3.89 (1.56-9.70)] and piperacillin-tazobactam use [3.75 (1.56-9.00)]; ICU requirement at initiation of care was a protective factor [0.38 (0.17-0.84)]. An unfavourable outcome was observed in 22 cases, and in a second logistic regression showed that DU was associated with the latter [AOR (95% CI): 5.07 (1.60-16.12)]. DUs were frequent during infections proved by PBC, and were associated with admission in medical wards, broad-spectrum antibiotic use and a high rate of unfavourable outcomes.

Evaluation of infectious agents in the pediatric palliative care unit

Aim: The use of broad-spectrum antibiotics, changes in patient profile, prolonged life expectancy, increased use of medical devices and technologies such as catheters, intravenous fluids, gastrostomy and tracheostomy have led to changes in the number and types of microorganisms isolated from infections and cultures. There are no data on infections seen in pediatric palliative care. The aim of this study was to determine the frequency of infections and the pathogens produced in culture, to identify the sites of growth and to review what should be done. Materials and Methods: This was planned as a cross-sectional, retrospective study between 11/18/2018 and 09/01/2023. Sociodemographic data, reason for hospitalization, number of hospitalizations, primary diagnoses, comorbid conditions, medical devices and technology used, time and place of culture, number of cultures, microorganisms grown and factors associated with culture growth were examined. Statistical analysis was performed with the SPSS 18.0 program. p

Clinical manifestations and treatment of candidemia caused by different Candida species: a retrospective study

ObjectiveCandidemia leads to higher mortality and longer hospital-stay. While the studies about the clinical manifestations of candidemia caused by different Candida species and the relationship between the antifungal drugs and prognosis were rarely performed.MethodsThis retrospective study enrolled all 94 patients diagnosed as candidemia from January 2020 to July 2023 in BTCH. Demographic information, comorbidities, laboratory parameters, medications and prognosis were collected and analyzed.ResultsC. albicans was the most common specie of candidemia. There was no significant difference in age, gender and hospital-mortality in different species groups. Higher-level and longer duration of broad-spectrum antibiotic use, lower BMI, hypoalbuminemia, longer duration of PN and history of G+ coccemia were conclusive about mortality. The C.tropicalis group had higher SCRE levels (F = 8.40, P = 0.03) and shorter TTP (F = 5.03, P < 0.01) than other species. No distinction was found in different antifungal drugs groups including triazoles and echinocandins after 7 days treatment (χ2 = 0.05, P = 0.81). The efficacy was no difference between triazoles and echinocandins in the different species groups. (χ12 = 1.20, P1 = 0.75; χ22 = 0.05, P2 = 0.81).ConclusionC. albicans accounts the most among candida induecd candidemia.The C.tropicalis group had higher SCRE levels and shorter TTP than other groups. Elder, hypoproteinemia, lower BMI, longer duration and higher-level of broad-spectrum antibiotic use, longer PN support and G+ coccemia increase risks for candidemia. The efficacy of triazoles and echinocandins are the same when blood culture turned negative in 7 days.

Rapid laboratory diagnosis of urinary tract infection, with or without antibiotic decision support-a small pilot study investigating accuracy and clinical impact.

The study evaluated the accuracy and clinical impact of rapid diagnostics (RD) with or without antibiotic decision support (ADS) for hospitalized patients with urinary tract infections. A two-centre prospective intervention was conducted with 230 patients divided into three groups: RD-only (n = 59), RD plus ADS (n = 56) and a control group (n = 115). Mean laboratory turnaround time for RD was 10 h and 50 min. Of 115 microorganisms, 108 were correctly identified. The error rate for rapid susceptibility determination was 0.85%. Total antibiotic consumption, measured in defined daily doses (DDD), was lower in the intervention groups compared to the control group (ADS: 10.3 DDD, p = 0.01; RD: 10.9 DDD, p = 0.06; control: 13.0 DDD). No significant differences were observed in the use of broad-spectrum antibiotics (p = 0.816). Adherence to antibiotic guidelines was significantly better in the ADS group compared to the control group (p = 0.015) (RD vs control; p = 0.261). The ADS group also received fewer doses of ineffective antibiotics (ADS: 1.8 doses, p = 0.012; RD: 2.4 doses, p = 0.195; control: 3.4 doses). Length of hospital and ICU stays or 30-day readmission rates did not differ across groups. No in-hospital mortality was observed in any group.

Timely empirical antibiotic therapy against sepsis in a rural Norwegian ambulance service: a prospective cohort study

BackgroundEarly diagnosis and antibiotic therapy in patients with sepsis reduce morbidity and mortality, thus pre-hospital management is likely to affect patient outcomes. Pre-hospital administration may increase the risk of unnecessary use of broad-spectrum antibiotics, but identification of an infectious focus enables more targeted antibiotic therapy. The aim of this study was to investigate how paramedics, with or without the assistance of general practitioners, can administer empiric intravenous antibiotic treatment against sepsis in a timely manner.MethodsCohort study of patients with suspected sepsis that received pre-hospital intravenous antibiotics and were transported to hospital. The setting was mainly rural with long average distance to hospital. Patients received targeted antibiotic treatment after an assessment based on clinical work-up supported by scoring systems. Patients were prospectively included from May 2018 to August 2022. Results are presented as median or absolute values, and chi-square tests were used to compare categorical data.ResultsWe included 328 patients. Median age was 76 years (IQR 64, 83) and 48.5% of patients were female. 30-days all-cause mortality was 10.4%. In cases where a suspected infectious focus was determined, the hospital discharge papers confirmed the pre-hospital diagnosis focus in 195 cases (79.3%). The presence of a general practitioner during the pre-hospital assessment increased the rate of correctly identified infectious focus from 72.6% to 86.1% (p = 0.009). Concordance between pre-hospital identification of a tentative focus and discharge diagnosis was highest for lower respiratory tract (p = 0.02) and urinary tract infections (p = 0.03). Antibiotic treatment was initiated 44 min (median) after arrival of ambulance, and median transportation time to hospital was 69 min. Antibiotic therapy was started 76 min (median) before arrival at hospital.ConclusionsPre-hospital identification of infectious focus in suspected sepsis was feasible, and collaboration with primary care physicians increased level of diagnostic accuracy. This allowed initiation of intravenous focus-directed antibiotics more than one hour before arrival in hospital in a rural setting. The effect of pre-hospital therapy on timing was much stronger than in previous studies from more urban areas.

Impact of Antibiotic Stewardship on Treatment of Hospitalized Children with Skin and Soft-Tissue Infections

Background: Skin and soft-tissue infections (SSTIs) are common infectious syndromes in children. Overusing broad-spectrum antibiotics has contributed to rising antibiotic resistance, complicating treatment outcomes. To address this issue, antimicrobial stewardship programs (ASPs) have been implemented to optimize antibiotic use. This study evaluated the impact of a multifaceted ASP on antibiotic prescribing practices for SSTIs in a pediatric acute care setting over eight years. Methods: We conducted a quasi-experimental study at the Pediatric Acute Care Unit of the Padua University Hospital, including children admitted with SSTIs from October 2014 to September 2022, to evaluate the impact of a multifaceted ASP implemented in October 2015. The study was divided into three periods: pre-implementation (October 2014–September 2015), post-implementation (October 2015–March 2020), and COVID-19 (April 2020–August 2022). Data on antibiotic prescriptions and microbiological results were collected and analyzed. Results: The implementation of the ASP led to a significant reduction in the use of broad-spectrum antibiotics, particularly third-generation cephalosporins (from 40.4% to 9.8%) and glycopeptides (from 21.1% to 1.6%). There was a notable increase in the prescription of Access antibiotics, from 30% in the pre-implementation to over 60% in the post-implementation and 80% during COVID-19. No increase in the hospital length of stay was observed. Microbiological results showed no significant changes in bacterial profiles over time. Conclusions: The use of the ASP effectively improved antibiotic prescribing practices, reducing reliance on broad-spectrum antibiotics even during the COVID-19 pandemic. These findings highlight the value of ongoing stewardship efforts and suggest the need for similar programs in ambulatory settings to further address antibiotic resistance.

Extended Spectrum β-Lactamase: Tackling Antibiotic Resistance and Overcoming Treatment Challenges

Antibiotics, also known as antibacterials, kill or inhibit bacterial growth but are ineffective against viruses, fungi, or parasites, often leading to misuse. They are categorized by molecular structure, mode of action, and spectrum of activity. Antimicrobial Resistance (AMR) occurs when pathogens no longer respond to antimicrobial drugs, arising naturally or through acquisition. Resistance mechanisms include enzymatic (most common), genetic and physical. Bacteria produce various β-lactamases, such as Extended Spectrum β-lactamases (ESBLs), AmpC enzymes, and carbapenemase to exert resistance to Beta-Lactam (βL) class of antibiotics. ESBL families include TEM, SHV, and CTX-M, with E. coli being the most prevalent host. Any Gram-Negative Bacteria (GNB) can be an ESBL producer, but most common ones are the Enterobacteriaceae including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis. ESBL-producing Enterobacteriaceae (ESBL-E) resist penicillin, aztreonam, and cephalosporins except cephamycins and carbapenems, posing a significant public health risk. Genetic resistance mechanisms involve random mutations and horizontal gene transfer through either of the following processes namely conjugation, transformation, transduction. Physical mechanisms include efflux pump production and decreased porin channels. In some microbiological laboratories, ESBL production are often not determined, rather resistance based on MIC values to third generation Cephalosporins are considered as resistance due to ESBL production. Antibiotic use in agriculture and medicine has increased Multi-drug resistant (MDR) ESBL-producing E. coli and evidenced in retail meat and among meat shop employees. Community-acquired ESBL-E infections are a growing concern, with hospital transmission primarily occurring among patients sharing rooms with ESBL carriers. Empirical and definitive therapies for ESBL-E infections must be adjusted based on Antibiotic Susceptibility Testing (AST). The MERINO trial identified urinary tract infections as the most common source of ESBL-E bacteremia, with E. coli being predominant. For critically ill patients with non-urinary tract infections, Meropenem or Imipenem-cilastatin are recommended. For uncomplicated UTIs, Nitrofurantoin, Cotrimoxazole, and Piperacillin-Tazobactam (Pip-Taz) are effective, while Cotrimoxazole, Fluoroquinolones, and Ceftolozane-tazobactam are suitable for complicated UTIs. New β-lactamase inhibitors like avibactam, vaborbactam, and relebactam are promising for treatment. Misuse of antibiotics, such as inappropriate dosing and duration, contributes to AMR, a growing global challenge. Deaths from AMR, estimated at 1.27 million in 2019, could reach 10 million by 2050. ESBLs drive the use of broad-spectrum antibiotics, accelerating resistance development. Inadequate therapy exacerbates infections, leading to prolonged hospital stays, complications, and increased mortality. Balancing new drug development with resistance emergence is crucial to combat AMR.

Guidelines to practice in hospitals at home: penicillin infusion pumps in erysipelas treatment

Abstract Background Hospitals at home are increasingly offering outpatient parenteral antimicrobial therapy (OPAT) in an attempt to reduce costly inpatient care, but these settings favor broad-spectrum antibiotics that require less frequent dosing than penicillin. Benzyl penicillin could be delivered via continuous infusion pumps (eCIP), but studies on their safety and efficacy in OPAT are scarce, and it remains unclear how much the availability of eCIPs increases penicillin use in real-life settings. Methods We examined 462 electronic healthcare records of erysipelas patients treated between January 2018 and January 2022 in a large Finnish OPAT clinic. Average marginal effects from logistic models were estimated to assess how the introduction of eCIPs in December 2020 affected penicillin use, and to compare clinical outcomes between patients with and without eCIPs. Results Introduction of eCIPs increased the predicted probability of penicillin treatment by 36.0 percentage points (95% confidence interval 25.5-46.5). During eCIP implementation, patients who received an eCIP had 73.1 (58.0-88.2) percentage points higher probability than patients without an eCIP to receive penicillin treatment. They also had about 20 percentage points higher probability to be cured at the time of discharge and three months after it. Patient and nurse satisfaction regarding eCIPs was very high. Conclusions Benzyl penicillin eCIP treatment is effective and safe, and substantially increases the use of penicillin instead of broad-spectrum antibiotics. To reduce the risk of antimicrobial resistance, eCIPs could increasingly be promoted for use in OPAT clinics, and there should be adequate education and support in their implementation. Key messages • Continuous infusion of benzyl penicillin via elastomeric infusors substantially decreases broad-spectrum antibiotic use among erysipelas patients treated at home. • When erysipelas patients can be treated with outpatient parenteral antibiotic therapy, the use of elastomeric benzyl penicillin infusors is safe and effective and should thus be increasingly promoted.

Therapy of Aspiration: Out-of-Hospital and In-Hospital-Acquired.

Therapeutic considerations for aspiration pneumonia prioritize the risk of multidrug-resistant organisms. This involves integrating microbiological insights with each patient's unique risk profile, including the location at the time of aspiration, and whether it occurred in or out of the hospital. Our understanding of the microbiology of aspiration pneumonia has also evolved, leading to a reassessment of anaerobic bacteria as the primary pathogens. Emerging research shows a predominance of aerobic pathogens, in both community and hospital-acquired cases. This shift challenges the routine use of broad-spectrum antibiotics targeting anaerobes, which can contribute to antibiotic resistance and complications such as Clostridium difficile infections-concerns that are especially relevant given the growing issue of antimicrobial resistance. Adopting a comprehensive, patient-specific approach that incorporates these insights can optimize antibiotic selection, improve treatment outcomes, and reduce the risk of resistance and adverse effects.

Copper-based photocatalysts with natural organic ligands for efficient removal of tetracycline under visible light

The excessive use of broad-spectrum antibiotics, such as tetracycline, presents a significant challenge to human survival and development. Oxygen vacancies (OVs) metal-organic framework (MOF) materials were synthesized using natural organic acids (L-malic acid, L-aspartic acid, and L-asparagine) with similar structures but different charge densities, along with copper as the metal linking agent. The presence of oxygen vacancies in the catalyst provides abundant active sites for photocatalytic reactions. The employment of flexible straight-chain organic ligands devoid of rigid polycyclic rings, combined with the incorporation of different substituents to induce variations in charge density, the resulting catalysts exhibit distinct photocatalytic activities under visible light. Density functional theory calculations confirm that L-asparagine exhibits the largest electron density difference, and the Cu-based MOF (Cu-ASU) synthesized as an organic ligand exhibits the highest photocatalytic activity under visible light excitation. The catalyst displayed remarkable photocatalytic activity against tetracycline antibiotics under identical conditions (with removal rates of 93.5 % for tetracycline, 81.4 % for terramycin, and 95.6 % for chloramphenicol hydrochloride). This provides a novel approach for the design and synthesis of photocatalysts for the removal of antibiotics from water.

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study

ObjectiveTo determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.DesignMulti-centre observational cohort study using data from 2009 to 2018 clinical records.SettingCanadian...

Antibiotic Appropriateness for Urinary Tract Infections in Children.

We examined local prescribing patterns across the entire treatment course for children treated for uncomplicated urinary tract infection (UTI) to determine opportunities for antibiotic stewardship initiatives. We conducted a retrospective review of emergency department and inpatient encounters for febrile and afebrile UTI in a children's hospital from 2021 to 2022. An antibiotic spectrum ranking was established, and providers' choices were assessed for appropriateness on the basis of the individuals' urine culture (UCx). Groups were stratified by fever presence and compared using χ2, Fisher's exact, and Mann-Whitney U tests. Of 172 encounters (83% emergency department), 99 (58%) had a positive UCx. Eighty (80%) grew Escherichia coli, with 67 (84%) being susceptible to cefazolin (minimum inhibitory concentration ≤16 mg/L). There were 229 antibiotic regimens and 39 (17%) were appropriate. Inappropriate antibiotic choices included unnecessary use of broad-spectrum antibiotics and misdiagnosed UTI. Grouping by encounter, at least 1 dose of a third cephalosporin was given in 51% of encounters, and 80% of these received it unnecessarily because of UTI misdiagnosis or suitability of a narrower-spectrum antibiotic. The median prescribed antibiotic duration was 7 days (interquartile range 7-10). Of 73 encounters with UCx growing mixed flora or a nonuropathogen, only 29 (40%) had antibiotics discontinued. Confirmed UTI was associated with fever and nitrite positivity. Our study revealed high prevalence of inappropriate antibiotics, particularly unnecessary prescribing of third cephalosporin, prescriptions not supported by laboratory data, and prolonged treatment courses. Our results identify factors that can be used to support UTI treatment pathways and ensure antibiotic stewardship.

Discovery of highly potent triazole derivatives with broad-spectrum antifungal activity based on Iodiconazole

The widespread use of broad-spectrum antibiotics, the growing number of immunocompromised individuals, and the emergence of drug-resistant strains have resulted in the increasing incidence and mortality of invasive fungal infections. Azole drugs are the primary treatment for invasive fungal infections, and Iodiconazole is a potent azole drug with strong antifungal activity, but its stability is poor. In order to improve stability, a series of triazole compounds containing ethynyl group were designed and synthesized. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound 20l showed excellent inhibitory activity against pathogenic fungi and drug-resistant fungi. Importantly, and the stability of 20l (T1/2 = 30.2 min) was obviously improved compared with Iodiconazole (T1/2 = 4.39 min). In addition, the preferred compound 20l can prevent fungal phase transition and the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound 20l was almost non-toxic to mammalian HUVEC cell and 293T cell. In vivo pharmacokinetic studies showed that 20l had acceptable pharmacokinetic properties. These results strongly demonstrate that compound 20l was worth further investigation as a potential antifungal inhibitor.

Institutional insights into engraftment syndrome: A cohort study on allogeneic transplantation outcomes

BackgroundEngraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD). ObjectiveTo investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution. Study designThis retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria. ResultsOf the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (P < 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (P = 0.01; Student's t-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (P < 0.05, Pearson's chi-squared test). ConclusionsThe general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES.

Species distribution, antifungal susceptibility pattern and associated factors of Candida blood stream infections in Sri Lanka from 2018 to 2022

Introduction: Candidemia can be life-threatening in immunocompromised individuals thus, prompt diag-nosis and treatment with antifungal agents is mandatory for successful outcome.Surveillance data on species distribution, antifungal susceptibility and associated factors of candidemia is utmost important to decide on empiric antifungal therapy, to impose infection control measures as well to promote antifungal stewardship in a country.Therefore, this study was aimed at retrospective review of data on candidemia at Mycology Reference Laboratory in Sri Lanka for 5 years duration to identify the species causing candidemia, their antifungal susceptibility pattern and associated factors.Results: A twofold rise in candidemia cases were seen during this 5-year duration compared to previous 7 years (2011-2017). Predominant species causing candidemia was C. tropicalis (35%) followed by C. parapsilosis (33%). C. albicans was the 3rd commonest species causing candidemia in Sri Lanka.There were 3% C. glabrata cases, 2% C. guilliermondii and 1% C. famata and C. krusei cases. Importantly two sequencing confirmed C. auris cases were identified for the first time in Sri Lanka in 2021.Overall good antifungal susceptibility was seen for both fluconazole and amphotericin B and there were only 7%and 1.6% resistance respectively.Long term hospital stay (47%) was commonly seen in this study group followed by use of broad-spectrum antibiotics (24%) and involvement of gastro-intestinal tract (21%).Conclusion: Candida tropicalis is the commonest species causing candidemia in Sri Lanka. Common Candida species had good susceptibility to antifungals. Long term hospital stay was associated with candidemia in majority of patients.

Neonatal Infectious Disease: A Major Contributor to Infant Mortality Requiring Advances in Point-of-Care Diagnosis.

Neonatal infectious disease continues to result in high rates of infant morbidity and mortality. Early- and late-onset disease represent difficult to detect and difficult to treat illnesses, particularly when antimicrobial resistant pathogens are present. Newborns are immunodeficient and are at increased risk of vertical and horizontal infection, with preterm infants increasingly susceptible. Additional risk factors associated with infection include prolonged use of a central catheter and/or ventilation, congenital abnormalities, admittance to intensive care units, and the use of broad-spectrum antibiotics. There is increasing recognition of the importance of the host microbiome and dysbiosis on neonatal infectious disease, including necrotising enterocolitis and sepsis in patients. Current diagnostic methods rely on blood culture, which is unreliable, time consuming, and can result in false negatives. There is a lack of accurate and reliable diagnostic tools available for the early detection of infectious disease in infants; therefore, efficient triage and treatment remains challenging. The application of biomarkers, machine learning, artificial intelligence, biosensors, and microfluidics technology, may offer improved diagnostic methodologies. Point-of-care devices, such diagnostic methodologies, may provide fast, reliable, and accurate diagnostic aids for neonatal patients. This review will discuss neonatal infectious disease as impacted by antimicrobial resistance and will highlight novel point-of-care diagnostic options.

Antibiotic Prescribing Trends in Dentistry during Ten Years' Period-Croatian National Study.

Prescribing antibiotics is a regular part of daily dental practice. Antibiotics have a significant but a limited role in general dental practice due to the threat of emergence of antimicrobial resistance (AMR). As such, the aim of this study was to assess prescribing trends in dental antibiotics use from 2014-2023 in Croatia. Data on antibiotic prescribing practices for this study were provided by the Croatian Health Insurance Fund. The analysis included the number of prescriptions, packages, cost, and the World Health Organization's defined daily dose per 1000 inhabitants (DID) per day as an objective utilization for comparison. Over the 10-year period, dentists in Croatia prescribed an annual average of 357,875 antibiotic prescriptions, representing an annual average of 78.7% of all dental prescriptions. The most commonly prescribed antibiotic was the combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid, which made up 58.54% of antibiotics and 46.1% of all dental prescriptions. This was followed by amoxicillin (12.61%), clindamycin (12.58%), and metronidazole (9.96%). The trend showed two discontinuations, the first for the pandemic years, and the second caused by disruption in amoxicillin production. The rise in the use of broad-spectrum antibiotics needs to be addressed and regulated to ensure patients and dentists understand that antibiotics are not a substitute for dental treatment. Dentists should always begin treatment with narrow-spectrum antibiotics regardless of possible exceptional circumstances.