Trimethoprim Research Articles

Prophylactic trimethoprim-sulfamethoxazole is safe in adult patients with primary central nervous system lymphoma receiving high-dose methotrexate.

This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including Cmax, clearance (CL) and AUC0-48h with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in Cmax, a 1.12-fold increase in AUC0-48h and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.

Antimicrobial Susceptibility Trends in E. coli Causing Pediatric Urinary Tract Infections in the United States

Urinary tract infections (UTIs) are among the most common pediatric infections. This study evaluated the antimicrobial susceptibility patterns of 3511 uropathogenic E. coli (UPEC) isolated from pediatric patients in the United States from 2014 to 2023. The database from the SENTRY antimicrobial surveillance program from 89 medical centers was utilized as a data source. The antimicrobial susceptibility was tested using the microbroth dilution technique against 24 antimicrobial agents. MICs were determined using the CLSI/EUCAST/FDA breakpoint criteria. All the antimicrobials reported susceptibility rates above 80% except for tetracycline (76.2%), trimethoprim–sulfamethoxazole (69.7%), and ampicillin–sulbactam (55.7%). During the study period, the susceptibility rates remained stable for most antimicrobial agents. However, significant differences were observed among age, gender, and U.S. census regions, with the Middle Atlantic showing the lowest and the Mountain region the highest susceptibility rates, for most antimicrobials. The incidence of ESBL UPEC increased from 7.1% to 10.8% between 2014 and 2023, while the prevalence of the MDR phenotype remained relatively stable. The prevalence of both ESBL and MDR phenotypes was highest among infants and young children (0–24 months), with the highest resistance rates from the Pacific region. Knowledge of the landscape of antibiotic resistance in pediatric UPEC will help healthcare providers to better tailor empiric treatment regimens for most UTI infections.

Liver cirrhosis complicated with pulmonary Nocardia infection: A case report and literature review.

Nocardia is a conditionally pathogenic bacterium found in the natural environment and is an aerobic bacterium, which causes severe pneumonia relatively rarely. The diagnosis of primary Nocardia infection is always made late due to the nonspecific clinical presentation of patients with Nocardia infection and the time required for Nocardia culture. Due to its rarity and nonspecific clinical presentation, patient survival is often compromised due to misdiagnosis. A 53-year-old woman with autoimmune cirrhosis was treated with glucocorticoids. Three and a half months later the patient developed fever, nausea, cough and sputum, treated with empirical antibiotics, and the patient occurred type I respiratory failure. Nocardia was identified by sputum culture micromorphology and Meriere matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). The patient was treated with trimethoprim-sulfamethoxazole (TMZ), and the patient's oxygen saturation recovered significantly. The patient's overall recovery was slow due to decreased albumin (ALB) and increased procalcitonin (PCT) caused by the patient's cirrhosis. Due to economic reasons, the family gave up, asked to be discharged. In our report, patients with underlying disease are immunocompromised and at increased risk of infection with conditionally pathogenic bacteria. Nocardia has no specific presentation and is often overlooked clinically. Treatment of these patients should not be limited to common bacteria or viruses, but should consider rare opportunistic pathogens, and we need to be vigilant for Nocardia infections and timely use of sulfonamide antibiotics to reduce mortality.

Antimicrobial Susceptibility Patterns and Antimicrobial Therapy of Infections Caused by Elizabethkingia Species

Background and Objectives: Elizabethkingia species have become significant sources of infections acquired in hospital settings and are commonly linked to high mortality rates. Antimicrobial resistance can be influenced by Elizabethkingia species, geographical location, antimicrobial susceptibility testing methods, and the time of bacterial isolation. There are distinct antimicrobial susceptibility patterns among species, and the investigation into potential antibiotic susceptibility variations among species is beneficial. There is no guidance on the treatment of Elizabethkingia species infections in the literature. Consequently, the purpose of this review was to elaborate on the antimicrobial susceptibility patterns of Elizabethkingia species through a scoping review of existing studies on the antibiograms of the Elizabethkingia species and on the illness caused by Elizabethkingia species. Materials and Methods: A comprehensive literature search in PubMed and Web of Science between 1 January 2000 and 30 April 2024 identified all studies, including those that examined antimicrobial susceptibility patterns and antimicrobial therapy of infections caused by Elizabethkingia species. I considered studies on antimicrobial susceptibility testing for Elizabethkingia species in which only broth microdilution methods and agar dilution methods were used. Results: The sensitivity levels of Elizabethkingia meningoseptica to piperacillin–tazobactam (5–100%), ciprofloxacin (0–43.4%), levofloxacin (30–81.8%), trimethoprim–sulfamethoxazole (0–100%), tigecycline (15–100%), minocycline (60–100%), and rifampicin (94–100%) varied. The sensitivity levels of Elizabethkingia anophelis to piperacillin–tazobactam (3.3–93.3%), ciprofloxacin (1–75%), levofloxacin (12–100%), trimethoprim–sulfamethoxazole (1.02–96.7%), tigecycline (0–52.2%), minocycline (97.5–100%), and rifampicin (20.5–96%) varied. The sensitivity levels of Elizabethkingia miricola to piperacillin–tazobactam (41.6–94.0%), ciprofloxacin (14–75%), levofloxacin (77.0–100%), trimethoprim–sulfamethoxazole (18.0–100%), tigecycline (50%), minocycline (100%), and rifampicin (66–85.7%) varied. Conclusions: The majority of the isolates of Elizabethkingia species were susceptible to minocycline and rifampin. This issue requires professional knowledge integration and treatment recommendations.

Stenotrophomonas maltophilia bacteremia in adult patients with hematological diseases: clinical characteristics and risk factors for 28-day mortality.

Patients with hematological diseases are at high risk for Stenotrophomonas maltophilia (SM) bacteremia. This study retrospectively analyzed the clinical characteristics and risk factors for 28-day mortality among 140 adult hematological patients diagnosed with SM bacteremia from January 2012 to July 2023. he overall 28-day mortality was 31.43% (44/140), with a median age of 44 years. The median hospital stay before SM bacteremia onset was 25 days, and 69.29% of patients had unresolved neutropenia. All patients had received broad-spectrum antibiotics in the past month, and 69.29% developed breakthrough bacteremia during carbapenem therapy. Independent risk factors for mortality included a Sequential Organ Failure Assessment (SOFA) score ≥5, tigecycline exposure, age ≥60, and pulmonary infection. Patients with ≥2 risk factors were stratified into the high-risk group, with a significantly higher 28-day mortality compared with the low-risk group (56.52% vs 7.04%, P < 0.001). Treatment with trimethoprim-sulfamethoxazole (TMP/SMX) (P = 0.008) or TMP/SMX combined with cefoperazone/sulbactam (CSL) (P = 0.005) was associated with survival benefits among high-risk patients. Overall, SM bacteremia usually occurs in hematological patients with prolonged hospitalization, unresolved neutropenia, and extensive use of broad-spectrum antibiotics, especially carbapenems. Patients with high SOFA scores, advanced age, pulmonary infection, or recent tigecycline exposure are at higher risk of mortality. The preferred treatment is TMP/SMX rather than fluoroquinolones, with combination therapy of TMP/SMX and CSL considered a feasible treatment option.IMPORTANCEThis study, representing the largest cohort of adult hematological patients with SM bacteremia to date, strengthens the validity of existing findings and provides new insights into its clinical management. We identify risk factors for 28-day mortality, revealing that patients with two or more risk factors experience particularly high mortality rates. This highlights the importance of early identification and targeted management of high-risk individuals. Our findings also demonstrate that TMP/SMX is superior to fluoroquinolones and suggest that combining TMP/SMX with CSL may offer additional survival benefits.

Mycotic aneurysms due to Burkholderia pseudomallei in Far North Queensland, tropical Australia: A case series and review of the literature

Since 2019, Burkholderia pseudomallei has been the most common cause of mycotic aneurysm at Cairns Hospital in tropical Australia. Among 233 culture-confirmed cases of melioidosis since this time, 8 (3.4 %) were diagnosed with a mycotic aneurysm. All 8 patients had at least 1 risk factor for melioidosis, all 8 had either established vascular disease (or risk factors for it) and all 8 presented during the local wet season or shortly thereafter. Although the patients were managed in a well-resourced, high-volume melioidosis centre, the diagnosis of mycotic aneurysm was frequently delayed. The patients had a turbulent course: 6/8 (75 %) required intensive care unit admission and 7/8 (88 %) required surgical intervention. While all 8 patients survived to hospital discharge, 2 (25 %) ultimately died as a result of their B. pseudomallei infection, a high case-fatality rate by contemporary Australian standards. Adverse drug reactions were documented in 4/7 (57 %) who commenced oral trimethoprim-sulfamethoxazole (TMP-SMX) eradication therapy; an additional 2 patients were unable to adhere to their prescribed TMP-SMX, one of whom died from relapsed melioidosis. Mycotic aneurysm is an infrequent manifestation of B. pseudomallei infection, is challenging to diagnose and has a high attributable mortality. The diagnosis should be considered in older patients who reside in, or who have travelled to, endemic areas and who present with fever and abdominal or back pain and who have risk factors for melioidosis and vascular disease. Early, comprehensive imaging, thorough microbiological evaluation, prompt vascular surgery review, targeted antimicrobial therapy, close longitudinal follow-up and strategies to ensure patients’ retention in care are crucial to achieve optimal outcomes.

Antibiotic prophylaxis reduced broad-spectrum antibiotics and length of stay in ICU patients with alcohol withdrawal induced refractory delirium tremens.

Pneumonia is a well-known complication in patients with severe alcohol withdrawal syndrome (SAWS). Antibiotic prophylaxis in ICU treated SAWS patients may be beneficial but data is lacking. The aims of this study were to investigate the effect of introduction of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, on use of broad-spectrum antibiotics and ICU length of stay (LOS) in SAWS patients with refractory delirium tremens (rDT). Retrospective observational cohort study comparing before (control group) and after the introduction of TMP-SMX prophylaxis in patients admitted to a single center ICU because of alcohol withdrawal induced rDT. A total of 108 patients were included, 53 patients in the control group and 55 patients in the TMP-SMX group. Baseline characteristics did not differ between the groups (89% male, median age 52 years). The use of broad-spectrum antibiotics was significantly lower in the TMP-SMX group than in the control group (11 vs 70%, p < 0.001). The only variable associated with decreased use of broad-spectrum antibiotics in multiple logistic regression analysis was receiving TMP-SMX (0.06, 95% CI 0.02, 0.19, p-value: <0.001). Median LOS was shorter in the TMP-SMX group than in the control group (61 vs 72 h, p = 0.004). In multiple linear regression analysis receiving TMP-SMX SMX was associated with shorter LOS (-22.7, 95% CI: -41.3, -4.1, p-value: 0.02) and having one or more comorbidities with longer LOS (37.4, 95% CI: 10.4, 64.5, p-value: <0.01). Prophylaxis with TMP-SMX in ICU-treated rDT patients was associated with reduced use of broad-spectrum antibiotics and reduced ICU LOS.

Separation of Antibiotics Using Two Commercial Nanofiltration Membranes—Experimental Study and Modelling

The widespread use of antimicrobial drugs has contributed to the increasing trace levels of contaminants in the environment, posing an environmental problem and a challenge to modern-day medicine seeking advanced solutions. Nanofiltration is one such breakthrough solution for the selective removal of antibiotics from wastewater due to their high efficiency, scalability, and versatility. This study examines the separation of antibiotics (sulfamethoxazole (SMX), trimethoprim (TMP), and metformin (MET), respectively) using commercially available membranes with an emphasis on AFC membranes (AFC 30 and AFC 80). Thus, we evaluate their efficacy, performance, and applicability in wastewater treatment processes. The data for characterizing the structural parameters of the NF membranes were determined from an uncharged organic solute rejection experiment, and the effect of various operating conditions on the retention of solutes was evaluated. All experimental data were collected using a laboratory-scale nanofiltration unit and HPLC, and rejection percentages were determined using analytical measurements. The results obtained allowed for the determination of the radius of the membrane pores using the Steric Hindrance Pore (SHP) model, resulting in values of 0.353 and 0.268 nm for the AFC 30 and AFC 80 membranes, respectively. Additionally, higher transmembrane pressure and feed flow were observed to lead to an increased rejection of antibiotics. AFC 30 demonstrated a rejection of 94% for SMX, 87% for TMP, and 87% for MET, while AFC 80 exhibited a rejection of 99.5% for SMX, 97.5% for TMP, and 98% for MET. The sieving effect appears to be the primary separation mechanism for AFC 30, as lower feed-flow rates were observed to intensify concentration polarization, thereby compromising rejection efficiency. On the contrary, AFC 80 experienced less concentration polarization due to its smaller pore sizes, effectively preventing pore clogging. Membrane performance was evaluated using the Spiegler–Kedem–Katchalsky model, based on irreversible thermodynamics, which effectively explained the mechanism of solute transport of antibiotics through the AFC 30 and AFC 80 membranes in the NF process.

Matrix Solid-Phase Dispersion Procedure for Determination of Antibiotics and Metabolites in Mussels: Application in Exposure Bioassays.

The presence of antibiotics in seafood for human consumption may pose a risk for consumers. Furthermore, some marine organisms, such as mussels, can result in appropriate bioindicators of marine contamination. In this work, a multiresidue analytical methodology suitable for the determination of antibiotics and metabolites in mussels is proposed. The target compounds include three sulphonamides and trimethoprim (TMP) and six of their main metabolites. Sample treatment involves extraction and clean-up in a single step using matrix solid-phase dispersion with acetonitrile. Analytical determination was carried out by liquid chromatography-tandem mass spectrometry. Good linearity (R2 > 0.99), accuracy (from 80.8 to 118%), and limits of quantification (lower than 5 ng g-1 (dry matter, dm)) were obtained for all selected compounds. The method was applied to the determination of antibiotics in mussel samples from an exposure assay with contaminated seawater with TMP and sulfamethoxazole (SMX). Both antibiotics were detected in the analysed samples with concentrations up to 77.5 ng g-1 dm. TMP was bioconcentrated to a higher extent than SMX, attributable to its higher hydrophobicity. None of the metabolites were detected. These results demonstrate that Mytilus galloprovincialis is a suitable bioindicator to assess marine pollution.

Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis.

The recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15-20mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (<15mg/kg/d of TMP) compared with the standard regimen in patients with PJP. We searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies. Seven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30-0.80; I 2 = 16%; P = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29-0.62; I 2 = 0%; P < 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P = 0.002), fewer patients requiring dose reductions (P = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P = 0.06). The limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.

High incidence of complications following intraoral extractions and treatment of periapical infections in the management of domestic rabbit (Oryctolagus cuniculus) dental disease (51 cases).

To describe the outcome of common medical therapies, intraoral dental procedures, extraoral surgical interventions, and resulting complications of treatment in client-owned rabbits diagnosed with dental disease. The medical records of 51 client-owned domestic rabbits presenting for veterinary care and management of dental disease from 2013 to 2023 at 2 veterinary teaching hospitals were reviewed. Of the patients managed with coronal reduction and occlusal adjustment, none developed significant complications. Of the patients that required intraoral dental extractions, 41% developed postprocedural complications, including incomplete tooth extraction. Following periapical infection and the formation of an odontogenic abscess for which surgical intervention was implemented, 25% of patients developed complications, including abscess recurrence and sepsis. Meloxicam was the most frequently prescribed analgesic medication for all procedures reviewed. Trimethoprim-sulfamethoxazole combination oral suspension was the most frequently prescribed antibiotic following coronal reduction, occlusal adjustment, and dental extractions, and parenteral penicillin G procaine was the most frequently prescribed antibiotic following periapical infection-related interventions. Seven patients had documentation of natural death or humane euthanasia secondary to progressive dental disease. The risk of postprocedural complications during the management of dental disease must be considered and discussed given the high rate of potential complications. With the increasing popularity of rabbits as companion animals, dental disease is considered one of the most common reasons for veterinary care in this species. Rabbits undergoing intraoral dental procedures and extraoral surgical interventions for the treatment of acquired and progressive dental disease are at risk of developing adverse postprocedural sequelae that must be considered before attempting intervention. This report adds to the growing body of scientific literature related to the management of this challenging disease process.

Investigation of the efficacy of siRNA-mediated KRAS gene silencing in pancreatic cancer therapy.

Pancreatic carcinoma is an aggressive cancer that progresses without many symptoms. The difficulty of early diagnosis and an inadequate response to traditional treatments also cause the survival rate of pancreatic cancer to be low. Current research is focusing on methods of diagnosis and treatment, such as gene therapy, to increase survival rates. Small interfering ribonucleic acid (siRNA) has emerged as a promising advanced therapeutic strategy for cancer treatment. This study sought to silence the KRAS gene in the human pancreatic carcinoma cell line using a complex of small interfering ribonucleic acid (siRNA) and gold nanoparticles (AuNP). In this study, 25 nM siRNA and gold nanoparticles at 0.5 mg/ml, 0.25 mg/ml, and 0.125 mg/ml concentrations were used to silence the KRAS gene in the CAPAN-1 cell line. Real-time PCR analysis, agarose gel electrophoresis, and double staining were carried out, and xCelligence real-time cell analysis (RTCA) was used to measure proliferation. The PCR analysis revealed crossing point (CP) values of actin beta (ACTB) ranging from 33.04 to 35.98, which was in the expected range for all samples. The interaction between the gold nanoparticle/siRNA complex in the double staining analysis revealed that the most effective concentration of gold nanoparticle was 0.125 mg/ml. The WST-1 technique showed that siRNA/AuPEI cells in application groups had a viability rate of over 90%, indicating no toxicity or side effects. The xCELLigence RTCA®showed that at hour 72, there was a significant difference in proliferation in the 0.5 mg/mL PEI/AuNP-siRNA, 0.25 mg/mL PEI/AuNP-siRNA, and 0.125 mg/mL PEI/AuNP-siRNA application groups compared to the control and siRNA groups (p<0.05). By hour 96, all three groups were statistically different from the control and siRNA groups in terms of proliferation (p<0.05). The results of this analysis suggest that the AuPEI/siRNA complex can be effectively used to silence the target gene, but more studies are needed to verify these results.

Efficient biochar regeneration for a circular economy: Removing emerging contaminants for sustainable water treatment

Biochar is widely known as a highly effective adsorbent for water treatment, capable of removing a wide range of pollutants. However, its saturation point limits its long-term use, but regeneration can extend its applicability. This study aims to develop a sustainable method for removing pollutants from water that aligns with the concept of the circular economy. Biochar derived from forest residue was used to remove emerging pollutants such as fipronil (FIP), venlafaxine (VEN), sulfamethoxazole (SMX) and trimethoprim (TRM). A comparative analysis of the adsorption of the studied pollutants onto biochar was performed by analyzing the kinetics, where it was found that SMX exhibited the lowest adsorption efficiency, prompting further optimization experiments. Under optimal conditions, adsorption isotherms were used to investigate the pollutant removal mechanisms. The results showed that biochar exhibited high adsorption capacities for FIP, VEN, SMX and TRM, which were 3.77, 2.09, 2.71 and 3.88 mg/g, respectively. Regeneration treatments were applied to remove adsorbed contaminants after biochar saturation. Among them, heat-activated persulfate showed the most effective regeneration, maintaining biochar's adsorption capacity after five cycles with no significant loss. Eventual morphological, structural and chemical alterations post-regeneration were assessed using different characterization techniques. The findings of this research highlight the potential of biochar for sustainable water treatment, supporting the circular economy by extending its life cycle through effective regeneration.

Pd/UiO‐66(Zr)‐2OH as a High‐Performance Catalyst for Hydrogen‐Enhanced Fenton Oxidation of Trimethoprim

ABSTRACTA novel catalyst material named Pd/UiO‐66(Zr)‐2OH was successfully developed and applied in a hydrogen‐promoted Fenton system for the efficient catalytic oxidation of the widely used antibiotic trimethoprim (TMP). The UiO‐66(Zr)‐2OH, as the carrier of catalyst in this work, was synthesized through a solvothermal method. The Pd0 nanoparticle, as the active center of the catalyst, was loaded onto its surface by the “ship‐in‐a‐bottle” strategy. The results showed that the composite Pd/UiO‐66(Zr)‐2OH demonstrated excellent catalytic performance during the reaction, achieving over 97% of TMP removal efficiency within 180 min under optimal conditions under the condition of only trace of iron without adding H2O2. This may be attributed to the fact that the [H], as a clean and efficient reducing agent, can be utilized to accelerate the regeneration of Fe2+ in the Fenton reaction, as well as in the in‐situ regeneration of H2O2. The key parameters affecting the removal efficiency of TMP, including the initial pH and concentration of Fe2+, the dosage of the synthesized material, the flow rate of H2 and the stirring speed were investigated systematically. The Pd/UiO‐66(Zr)‐2OH exhibited high stability and reusability, maintaining over 82% of its initial degradation efficiency of TMP after six reaction cycles. The mechanistic insight revealed that the system primarily relied on the generation of hydroxyl radical (·OH) and singlet oxygen (1O2) for the degradation of TMP, which was verified through quenching experiments and electron spin resonance (ESR). The degradation pathway of TMP was elucidated by analyzing intermediates and the reduction in total organic carbon (TOC). This research offers novel conceptual insights into the evolution and application of advanced oxidation technologies, efficient degradation of emerging pollutants, and expansion of pathways for hydrogen resource utilization.

Cephalosporins for Outpatient Pyelonephritis in the Emergency Department: COPY-ED Study

Study Objective.The primary objective of our study was to compare the effectiveness of oral cephalosporins versus fluroquinolones (FQ) and trimethoprim/sulfamethoxazole (TMP-SMX) for the treatment of pyelonephritis in patients discharged home from the emergency department (ED). MethodsThis was a multi-center, retrospective, observational cohort study of 11 geographically diverse US EDs. Patients ≥18 years of age diagnosed with pyelonephritis and discharged home from the ED between 1/1/2021 – 10/31/2023 were included. The primary outcome was treatment failure at 14 days defined as a composite outcome of the following, 1) recurrence of urinary symptoms, 2) repeat ED visit or hospitalization for a urinary tract infection (UTI), 3) receipt of a new antibiotic prescription for UTI. Secondary outcome was appropriateness of empiric treatment based on urine culture susceptibility. ResultsAmong the 851 patients who met inclusion criteria, 647 patients received a cephalosporin, and 204 patients received an Infectious Diseases Society of America (IDSA) guideline-endorsed first line treatment (FQs, TMP-SMX). Overall, baseline characteristics were similar between the two cohorts. Rates of treatment failure were not significantly different in the cephalosporin group compared to the FQ/TMP-SMX groups (17.2% of cephalosporin vs. 22.5% of FQ/TMP-SMX group, difference=5.3%, 95% CI -0.118-0.01). After adjusting for potential confounders, cephalosporin use was not associated with treatment failure (OR=0.22, 95% CI=0.03-1.95). There was no difference in rates of appropriate empiric treatment based on urine culture susceptibility. ConclusionOral cephalosporins were associated with similar treatment failure rates compared to IDSA guideline-endorsed treatments for the treatment of pyelonephritis in ED patients discharged home.

Investigating trends in antibiotic resistance of Escherichia coli isolated from clinical urine specimens in the Orkney Islands.

Urinary tract infections (UTIs) are extremely common, affecting people of all ages and health statuses. Although UTIs do not usually cause severe illness, in some cases they can lead to more serious complications, especially if their initial treatment is ineffective due to antimicrobial resistance (AMR). AMR is an increasing issue, exacerbated by misdiagnosis and inappropriate prescribing of antibiotics, thus facilitating further resistance. The aim of this study was to investigate the rates of AMR in Escherichia coli isolated from clinical urine specimens tested at the Balfour Hospital, Orkney, and determine trends related to patient risk factors. Antibiotic susceptibilities were tested for 100 isolates of uropathogenic E. coli using the VITEK 2 Compact (bioMérieux), and data were analysed using percentage resistance rates. Resistance rates were compared by patient sex, age and source (hospital versus community). The findings showed higher AMR in males compared with females, particularly for trimethoprim (TMP), with 52% in males and only 12% in females. AMR tended to be higher in E. coli isolated from hospital inpatients than from community specimens, except for amoxicillin (AMX) and co-amoxiclav. Finally, the study found that AMR of E. coli isolates was greater in patients aged over 50 than 18-50 years old, particularly for AMX and TMP. The highest resistance rates across all patient demographics were for AMX, implying that the use of this antibiotic for the treatment of E. coli UTIs is not appropriate.

Suspected nocardiosis in an immunosuppressed patient: a case report highlighting diagnostic challenges and management strategies

Nocardiosis is a rare but potentially fatal opportunistic infection caused by Nocardia species, predominantly affecting immunocompromised individuals. This case report details the clinical course, diagnostic workup, and management of a 63-year-old female with a history of renal transplantation. Initial investigations, including imaging studies, revealed multiple cavitary pulmonary nodules and a solitary brain lesion, raising concerns for disseminated infection. The diagnostic challenge was compounded by the broad differential diagnosis in this patient population, including fungal, mycobacterial, and other opportunistic infections. Empirical antimicrobial therapy was initiated, and subsequent microbiological confirmation of Nocardia asteroides from bronchoalveolar lavage specimens established the diagnosis. Despite initial therapeutic response, the patient developed worsening neurological symptoms indicative of CNS involvement, necessitating prolonged treatment with a combination of trimethoprim-sulfamethoxazole and imipenem. This report underscores the importance of early recognition, comprehensive diagnostic evaluation, and individualized therapeutic approaches in managing suspected nocardiosis in immunocompromised patients. Furthermore, it discusses the diagnostic pitfalls, highlights the need for a high index of suspicion, and reviews current therapeutic recommendations for both pulmonary and disseminated nocardiosis, providing a valuable reference for clinicians managing similar cases.

Multidrug-resistant Salmonella Typhi among symptomatic and asymptomatic children in informal settlements in Nairobi, Kenya

BackgroundThe emergence and persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) infections is a significant global health problem. The carrier state of typhoid makes it prudent to conduct routine surveillance for both acute cases and carriers especially those caused by MDR S. Typhi. We report on the prevalence of MDR S. Typhi, resistance phenotypes and antimicrobial resistance genes detected in symptomatic and asymptomatic children living in informal settlements in Nairobi, Kenya.Methods215 archived presumed S. Typhi isolates from stool samples provided by children ≤ 16 years collected from 2013 to 2018 were revived in May, 2022 and confirmed using culture and antisera serotyping. The Kirby Bauer disc diffusion technique was used to test the S. Typhi against 14 antibiotics. The MDR S. Typhi (resistant to ampicillin, chloramphenicol and sulfamethoxazole trimethoprim) which in addition were also resistant to either a cephalosporin or a fluoroquinolone were analyzed for Beta lactams and quinolone resistance genes using polymerase chain reaction.ResultsA total of 215 isolates were confirmed to be positively S. Typhi; of these, 105 (49%) and 110 (51%) were from symptomatic and asymptomatic children respectively. On average, S. Typhi resistance from asymptomatic and symptomatic children against 1st line drugs was observed at; 77% &70%, ampicillin; 60% & 64%, sulfamethoxazole-trimethoprim, and 45% & 54%, chloramphenicol respectively. Multi drug resistance was observed in 90 (42%) of the isolates, of these, 44 (49%) were isolated from symptomatic and 46 (51%) from asymptomatic children. Fifteen resistance phenotypes (p) were observed with, ampicillin/chloramphenicol/sulfamethoxazole-trimethoprim/nalidixic acid (amp/chl/sxt/na) as the most common among the symptomatic 43/90 (48%) and asymptomatic 55/90 (61%) children. The blaTEM−D, AMR genes were detected in 37/44 (84%) S. Typhi isolates, out of this 18 (49%) were from symptomatic while 19 (51%) were from asymptomatic children respectively.ConclusionThe carriage of MDR S. Typhi among the asymptomatic children is concerning as they can act as potential transmitters of the typhoid disease to unsuspecting children. These study findings highlight the need for continued surveillance of antimicrobial resistance and mass immunization of children living in these urban informal areas.

Multiple antibiotic resistance of Salmonella Infantis in the Peruvian poultry production chain: Detection in birds, the farming environment, and chicken carcasses

Poultry can act as a reservoir of Salmonella enterica serotype Infantis (S. Infantis) of clinical and epidemiological importance because it triggers foodborne disease outbreaks and presents antibiotic multiresistance. The present study aimed to determine antimicrobial resistance in S. Infantis isolates from poultry livers, litter and chicken carcasses from Lima, Peru, during 2022–2023. S. Infantis was isolated from 10.1 % (27/267), 4.7 % (4/86), and 8 % (2/25) of the bird, litter and carcass samples, respectively. All isolates showed resistance to nalidixic acid (NA). In addition, 94 %, 76 %, 70 %, 48 %, and 45 % of the isolates showed resistance to tetracycline (TET), amoxicillin (AMX), chloramphenicol (C), gentamicin (GEN) and trimethoprim/sulfamethoxazole (TS), respectively. All isolates showed susceptibility to imipinem and amoxicillin/clavulanic acid. Of the isolates, 93.9 % displayed multidrug resistance. The most frequent resistance pattern was C-AMX-NA-GEN-TET (24.2 %, n=8), determined even from carcass isolates, followed by C-AMX-NA-TET (18.2 %, n=6), and C-AMX-NA-GEN-TS-TET (12.1 %, n=4). The presence of these multidrug-resistant S. Infantis isolates is a threat to food safety and public health.

The characteristics and clinical course of patients with melioidosis and cancer.

Patients with an active cancer are more likely to develop melioidosis, but the characteristics and clinical course of melioidosis in patients with cancer have not been examined in detail. Trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis is prescribed to prevent melioidosis in patients receiving immune suppressing anti-cancer therapy in some jurisdictions-and is recommended in national Australian guidelines-however the risks and benefits of this strategy are incompletely defined. The study took place in Far North Queensland (FNQ) in tropical Australia. The characteristics and clinical course of patients with melioidosis diagnosed in the FNQ region between January 1, 1998, and June 1, 2023, who had-and did not have-an active cancer were compared. We also determined the subsequent incidence of melioidosis in patients receiving immune suppressing anti-cancer therapy in the FNQ region between January 1, 2008, and June 1, 2023, who did-and did not-receive TMP-SMX chemoprophylaxis for Pneumocystis jirovecii infection. An active cancer was present in 47/446 (11%) cases of melioidosis diagnosed between January 1, 1998, and June 1, 2023; there was no association between melioidosis and any cancer type. Patients with melioidosis and cancer were more likely to be older (odds ratio (OR) (95% confidence interval (CI): 1.05 (1.03-1.08) P<0.0001) and immunosuppressed (OR (95% CI): 11.54 (5.41-24.6), p<0.0001) than patients without cancer. Immune suppressing anti-cancer therapy had been prescribed to 17/47 (36%) in the 12 months prior to their diagnosis of melioidosis. Only 10/47 (21%) with cancer and melioidosis in the cohort had received no immune suppressing anti-cancer therapy and had no other risk factors for melioidosis. Twelve months after the diagnosis of melioidosis, 25/47 (53%) were still alive; 9/22 (41%) deaths were due to melioidosis and 13/22 (59%) were due to the underlying cancer. Between 2008 and June 2023, there were 4400 individuals who received myelosuppressive anti-cancer therapy in the FNQ region. There was no significant difference in the incidence of melioidosis between patients who did-and did not-receive TMP-SMX chemoprophylaxis with their myelosuppressive anti-cancer therapy (1/737 (0.15%) versus 16/3663 (0.44%); relative risk (95% confidence interval): 0.31 (0.04-2.34), p = 0.20) and no significant difference in the incidence of fatal melioidosis (0/737 versus 3/3663 (0.08%), p = 0.58). Patients with cancer are predisposed to developing melioidosis and immune suppressing anti-cancer therapy increases this risk further. However, in this region of Australia, there was no significant difference in the subsequent development of melioidosis in patients who did-and did not-receive TMP-SMX chemoprophylaxis during their myelosuppressive anti-cancer therapy.