Beta-lactam Antibiotics Research Articles

Revisiting mutational resistance to ampicillin and cefotaxime in Haemophilus influenzae

BackgroundHaemophilus influenzae is an opportunistic bacterial pathogen that can cause severe respiratory tract and invasive infections. The emergence of β-lactamase-negative ampicillin-resistant (BLNAR) strains and unclear correlations between genotypic (i.e., gBLNAR) and phenotypic resistance are challenging empirical treatments and patient management. Thus, we sought to revisit molecular resistance mechanisms and to identify new resistance determinants of H. influenzae.MethodsWe performed a systematic meta-analysis of H. influenzae isolates (n = 291) to quantify the association of phenotypic ampicillin and cefotaxime resistance with previously defined resistance groups, i.e., specific substitution patterns of the penicillin binding protein PBP3, encoded by ftsI. Using phylogenomics and a genome-wide association study (GWAS), we investigated evolutionary trajectories and novel resistance determinants in a public global cohort (n = 555) and a new clinical cohort from three European centers (n = 298), respectively.ResultsOur meta-analysis confirmed that PBP3 group II- and group III-related isolates were significantly associated with phenotypic resistance to ampicillin (p < 0.001), while only group III-related isolates were associated with resistance to cefotaxime (p = 0.02). The vast majority of H. influenzae isolates not classified into a PBP3 resistance group were ampicillin and cefotaxime susceptible. However, particularly group II isolates had low specificities (< 16%) to rule in ampicillin resistance due to clinical breakpoints classifying many of them as phenotypically susceptible. We found indications for positive selection of multiple PBP3 substitutions, which evolved independently and often step-wise in different phylogenetic clades. Beyond ftsI, other possible candidate genes (e.g., oppA, ridA, and ompP2) were moderately associated with ampicillin resistance in the GWAS. The PBP3 substitutions M377I, A502V, N526K, V547I, and N569S were most strongly related to ampicillin resistance and occurred in combination in the most prevalent resistant haplotype H1 in our clinical cohort.ConclusionsGradient agar diffusion strips and broth microdilution assays do not consistently classify isolates from PBP3 groups as phenotypically resistant. Consequently, when the minimum inhibitory concentration is close to the clinical breakpoints, and genotypic data is available, PBP3 resistance groups should be prioritized over susceptible phenotypic results for ampicillin. The implications on treatment outcome and bacterial fitness of other extended PBP3 substitution patterns and novel candidate genes need to be determined.

Mycobacterium tuberculosis F-ATP Synthase Inhibitors and Targets

Mycobacteria tuberculosis (Mtb) infection causes tuberculosis (TB). TB is one of the most intractable infectious diseases, causing over 1.13 million deaths annually. Under harsh growing conditions, the innate response of mycobacteria is to shut down its respiratory metabolism to a basal level, transit into a dormant, non-replicating phase to preserve viability, and establish latent infection. Mtb utilizes non-canonical regulatory mechanisms, such as alternative oxidase pathways, to survive in low oxygen/nutrient conditions. The bacterium’s survival in its native microenvironmental niches is aided by its ability to evolve mutations to drug binding sites, enhance overexpression of various enzymes that activate β-lactam antibiotics hydrolysis, or stimulate efflux pathways to ward off the effect of antibiotics. Bedaquiline and its 3,5-dialkoxypyridine analogs, sudapyridine and squaramide S31f, have been shown to be potent Mtb F1FO-ATP synthase inhibitors of replicating and non-replicating Mtb and have brought oxidative phosphorylation into focus as an anti-TB target. In this review, we attempt to highlight non-canonical structural and regulatory pathogen-specific epitopes of the F1-domain, ligand development on such sites, structural classes of inhibitors targeting the Fo-domain, and alternative respiratory metabolic responses that Mtb employs in response to bedaquiline to ensure its survival and establish latent infection.

Identifying the Molecular Fingerprint of Beta-Lactams via Raman/SERS Spectroscopy Using Unconventional Nanoparticles for Antimicrobial Stewardship

Background/Objectives: Beta-lactam antibiotics, derived from penicillin, are the most used class of antimicrobials used for treating bacterial infections. Over the years, microorganisms have developed resistance mechanisms capable of preventing the effect of these drugs. This condition has been a significant public health concern for the 21st century, especially after predictions that antimicrobial resistance could lead to 10 million deaths annually by 2050. The challenge of developing new antimicrobials brings with it the need to ensure the efficacy of existing ones, hence the importance of developing fast and low-cost monitoring techniques. Methods: In this study, we present an alternative based on nanophotonics using Surface-Enhanced Raman Spectroscopy (SERS) mediated by nanoparticles for the detection of antimicrobials, with emphasis on some beta-lactam antibiotics commonly prescribed in cases of critically ill patients. It is a sensitive and accurate technique for drug monitoring, allowing for rapid and specific detection of its molecular signatures. This approach is crucial to address the challenge of antimicrobial resistance and ensure the therapeutic efficacy of existing treatments. Results: Our experiments demonstrate the possibility of identifying spectra with characteristic vibrations (fingerprints) of these antimicrobials via SERS. Conclusions: Our results point to new strategies for molecular monitoring of drugs by optical techniques using unconventional nanoparticles.

Sensitivity Pattern in Children Respiratory Bacterial Infections

Background: Bacterial respiratory infections are a major health concern, especially in underdeveloped and developing countries. This study aims to evaluate the prevalence of Gram-negative and Gram-positive bacteria in respiratory infections and assess the efficacy of antibiotics. Methods: A prospective, observational study was conducted from July 2010 to July 2011. Patients with respiratory infections were categorized by age, bacterial pathogen, disease type, and season of infection. Diagnostic methods, including throat swabs, blood cultures, and antibiograms, were used to identify pathogens and determine antibiotic resistance profiles. The infection rate was calculated using standard epidemiological formulas. Results: Gram-negative bacteria accounted for 84.7% of infections, with Acinetobacter baumannii (26.4%) being the most common pathogen. Gram-positive infections, primarily caused by Streptococcus pneumoniae (77%), were also prevalent. The highest infection rates were observed in the spring, particularly among children under one year and those aged 1-6 years. Pneumonia was the most common diagnosis (43.5%). Ampicillin resistance was widespread, but Acinetobacter baumannii, E. coli, and Klebsiella pneumoniae showed sensitivity to Sulbactam, Cefoperazone, and Piperacillin/Tazobactam. Conclusion: Acinetobacter baumannii was the predominant cause of respiratory infections, especially in young children and during spring. Ampicillin resistance was common, but Sulbactam, Cefoperazone, and Piperacillin/Tazobactam were more effective. These findings highlight the importance of targeted antibiotic therapy, particularly for Gram-negative bacterial infections.

Overview of β-Lactam-Resistance Genes in Pandemic Multidrug-Resistant Acinetobacter baumannii: A Troublesome Pathogen in the Indian Intensive Care Unit

Objectives: Acinetobacter baumannii is responsible for many infections in admitted patients, especially in the intensive care unit (ICU). Several risk factors may lead to an enhanced risk of A. baumannii colonization and infections. β-lactam antibiotics are frequently administered to treat Gram-positive and Gram-negative bacterial infections due to their minimum side effects, but the acquisition of β-lactamase genes has been the most challenging and troublesome situation and an imminent threat to the world as it increases mortality, medical expenses, and hospital stays. Hence, the present systematic review focused on the screening of β-lactam resistance genes that have been identified in the A. baumannii isolates’ genome and the nosocomial infections they cause in the Indian ICU. Material and Methods: This review has been done according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline 2020. After screening, 317 genomes were included in this systematic review. We downloaded data from the bv-brc.org website on an Excel spreadsheet for statistical analysis. We presented categorical data in percentages (%) and in the form of a graph and pie chart. Results: Among the 317 isolates, pneumonia was caused by 189 strains (59.62%), bacteremia was caused by 109 strains (34.38%), respiratory infection by 12 isolates (3.79%), sepsis by 5 isolates (1.58%), and wound infection by 2 isolates (0.63%), which indicated that A. baumannii strains are highly involved in pneumonia followed by bacteremia. We did comparative genome analysis and found 26 β-lactamase genes; among them, the ADC2 gene was found to be in higher frequency (312) and was identified in 98.42% of A. baumannii isolates, followed by the OXA23 gene (303), which was found in 95.58% of isolates. The NDM-1 gene was identified in 181 (57.09%) isolates. OXA66 was found in 156 (49.21%) isolates. Our findings show a higher frequency of the ADC2 gene, followed by the OXA23 gene, in all these nosocomial infections. We have found that NDM-1, ADC2, OXA23, and OXA-66 genes coexisted in higher frequency in the A. baumannii isolates (137; 43.21%), followed by OXA23, OXA-66, and ADC2 (52; 16.40%). Conclusion: A. baumannii is a notorious pandemic pathogen, designated as a “priority of concern” by the World Health Organization. Our study indicates a high prevalence of the ADC2 gene, which gives resistance against the cephalosporin group and co-existence of β-lactamase genes (ADC2, OXA23, OXA66, and NDM-1) in various A. baumannii isolates’ genomes. This is a worrisome situation. Global molecular surveillance and the “One Health Concept” are crucial, as are research studies on plant extracts’ in vitro and in vivo efficacy against A. baumannii. Combating multidrug-resistant A. baumannii requires a multifaceted approach that involves infection control measures, antimicrobial stewardship, surveillance, education, research, and collaboration. Implementing these strategies and staying vigilant in the face of this resilient pathogen is essential to minimize its impact on health-care systems and public health.

Analysis of spontaneous reports from a pediatric population: Stevens–Johnson syndrome and toxic epidermal necrolysis induced by antibacterial drugs

Relevance. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are cutaneous hypersensitivity reactions that can be induced by drugs and are particularly severe in children.Objective. To study the structure of antibacterial drugs (ABs) involved in the development of SJS and TEN in pediatric populations.Methods. Retrospective pharmacoepidemiologic study of spontaneous reports (SRs) entered into the Russian National Pharmacovigilance database during the period 01.04.2019 – 31.12.2023.Results. The majority of suspected drugs were β-lactams (76.0%), with penicillin accounting for 47.4% and cephalosporins — for 52.6%. Amphenicols (12.0%), macrolides (8.0%), and fluoroquinolones (4.0%) were less frequently reported.Conclusion. The most common group of ABs that induce SJS and TEN in children is the group of β-lactam antibiotics.

Whole-Genome Analysis of Multidrug-Resistant Klebsiella pneumoniae Kp04 Reveals Distinctive Antimicrobial and Arsenic-Resistance Genomic Features: A Case Study from Bangladesh.

Multidrug-resistant bacteria, particularly extended-spectrum-beta-lactamase-producing (ESBL) bacteria, pose a significant global public health challenge. Klebsiella pneumoniae (KPN) is frequently implicated in cases of this resistance. This study aimed to investigate the presence of drug and metal resistance genes in clinical K. pneumoniae isolate Kp04 and comparative genomics of clinical KPN isolates characterized from Bangladesh. A total of 12 isolates were collected. Disk-diffusion assay showed that all five isolates were resistant to 14 out of 21 tested antibiotics and sensitive to only three-tigecycline, imipenem, and meropenem. KPN Kp04 was positive for both blaSHV and blaCTX-M ESBL genes in PCR. All five isolates produced PCR amplicons of the correct size for ampicillin (ampC), tetracycline (tetC), fluoroquinolone (qnrS), and aminoglycoside (aadA) resistance genes. The whole genome of Kp04 was sequenced using the MiSeq Platform (V3 kit, 2 × 300 cycles). We utilized different databases to detect Antibiotic-Resistant Genes (ARGs), virulence factor genes (VFGs), and genomic functional features of the Kp04 strain. Whole-genome sequencing identified 75 ESBL, virulence, and multiple drug-resistant (MDR) genes including blaSHV, tetA, oqxA, oqxB, aadA, sul1-5, and mphA in KPN Kp04 isolate. Pan-genomic analysis of 43 Bangladeshi KPN isolates showed similarities between Dhaka and Chattogram isolates regarding virulence and antibiotic-resistant genes. Our results indicate the transmission of similar virulent KPN strains in Dhaka and Chattogram. This study would provide valuable information about drug sensitivity, antibiotic, and metal resistance features of K. pneumoniae circulated among hospitalized patients in Bangladeshi megacities.

Antimicrobial Susceptibility Profiles of Salmonella spp. Isolates from Clinical Cases of Waterfowl in Hungary Between 2022 and 2023

The global spread of antimicrobial resistance is one of the most significant challenges of the 21st century. The waterfowl sector is an economically decisive part of the poultry industry, yet it remains under-researched, and its antibiotic usage is less monitored. Our study aimed to determine the antimicrobial susceptibility of avian pathogenic Salmonella strains, which are still prevalent in ducks and geese, against antibiotics critical for both animal and human health, and to compare these findings with human resistance data. We analyzed 71 Salmonella strains, collected by the National Reference Laboratory from samples originating from 29 settlements across Hungary between 2022 and 2023, using the minimum inhibitory concentration (MIC) method. Notably, the duck strains (n = 52) exhibited 57.7% resistance to potentiated sulfonamides, 28.8% resistance to doxycycline, and 25% resistance to cefotaxime. Among the geese strains (n = 19), 52.6% showed resistance to potentiated sulfonamides, followed by 26.3% resistance to doxycycline and amoxicillin–clavulanic acid, and 15.8% resistance to cefotaxime, ceftiofur, and ceftriaxone. When compared to human resistance data, we found significantly lower resistance levels for amoxicillin in ducks (20.0%) and geese (8.3%) in the Dél-Alföld region, compared to ampicillin resistance in human samples (45.4%), in which amoxicillin analog is an antibiotic in human medicine. Resistance to ciprofloxacin was only observed in ducks (2.0%), whereas pefloxacin resistance in human medicine was notably higher (22.3%). Overall, the results for the waterfowl sector in the Dél-Alföld region of Hungary align with the international literature in several aspects. Further investigation using next-generation sequencing to identify the genetic basis of multi-resistant strains is warranted.

Microalgae-mediated bioremediation: Metabolomic profiling and adaptive responses under amoxicillin-induced stress

This study examines the effects of varying concentrations (25, 50, 100, and 150 mg/L) of Amoxicillin-3000 (AMOX), a widely prescribed beta-lactam antibiotic, on the growth of the microalga Chlorella sorokiniana UUIND6. Results revealed that low AMOX concentration (25 mg/L) stimulated best algal growth, prompting further exploration of AMOX degradation processes, identification of transformation products, biochemical composition of microalgae. Photodegradation, both direct (light) and indirect (induced by microalgae) was examined. LCMS identified similar transformation product in both the photodegradation with a m/z ratio of 367.1. Moreover, microalgae-induced c photodegradation resulted in negligible zone of inhibition after 96 h, achieving an impressive 98.8 % degradation, significantly surpassing the 85.5 % degradation observed with light alone. Modifications in abiotic factors also influence the stoichiometry of microalgae cells, resulting in significantly higher lipid (31.24 ± 2.93 %) and protein (44.12 ± 1.75 %) content compared to control cells (lipid 23.6 ± 2.4 %, protein 31.62 ± 1.52 %), indicating notable metabolic alterations (p<0.05) under AMOX-induced stress. Additionally, increased reactive oxygen species (ROS) scavenging activity (48.89 ± 2.51 %) suggests photosynthetic impairment and a decrease in TPC and TFC content, aiding in the prevention of oxidative stress. Overall, this study highlights the advantages of Chlorella-induced bioremediation of AMOX via photodegradation over light-driven processes. It presents a practical, sustainable approach for mitigating ecological risks in freshwater ecosystems and provides insights into antibiotic removal mechanisms and performance in microalgae-based systems under environmentally relevant conditions.

Machine learning models for coagulation dysfunction risk in inpatients administered β-lactam antibiotics

The β-Lactam antibiotics represent a widely used class of antibiotics, yet the latent and often overlooked risk of coagulation dysfunction associated with their use underscores the need for proactive assessment. Machine learning methodologies can offer valuable insights into evaluating the risk of coagulation dysfunction associated with β-lactam antibiotics. This study aims to identify the risk factors associated with coagulation dysfunction related to β-lactam antibiotics and to develop machine learning models for estimating the risk of coagulation dysfunction with real-world data. A retrospective study was performed using machine learning modeling analysis on electronic health record data, employing five distinct machine learning methods. The study focused on adult inpatients discharged from 1 January 2018, to 31 December 2021, at the First Affiliated Hospital of Shandong First Medical University. The models were developed for estimating the risk of coagulation dysfunction associated with various β-lactam antibiotics based on electronic health record feasibility. The dataset was divided into training and test sets to assess model performance using metrics such as total accuracy and area under the curve. The study encompassed risk-factor analysis and machine learning model development for coagulation dysfunction in inpatients administered different β-lactam antibiotics. A total of 45,179 participants were included in the study. The incidence of coagulation disorders related to cefazolin sodium, cefoperazone/sulbactam sodium, cefminol sodium, amoxicillin/sulbactam sodium, and piperacillin/tazobactam sodium was 2.4%, 5.4%, 1.5%, 5.5%, and 4.8%, respectively. Machine learning models for estimating coagulation dysfunction associated with each β-lactam antibiotic underwent validation with 5-fold cross-validation and test sets. On the test set, the optimal models for cefazolin sodium, cefoperazone/sulbactam sodium, cefminol sodium, amoxicillin/sulbactam sodium, and piperacillin/tazobactam sodium yielded AUC values of 0.798, 0.768, 0.919, 0.783, and 0.867, respectively. The study findings suggest that machine learning classifiers can serve as valuable tools for identifying patients at risk of coagulation dysfunction associated with β-lactam antibiotics and intervening based on high-risk predictions. Enhanced access to administrative and clinical data could further enhance the predictive performance of machine learning models, thereby expanding pharmacovigilance efforts.

Occurrence and Phenotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in Emergency Medical Service Ambulances as a Potential Threat to Medical Staff and Patients

Introduction: An ambulance used by an emergency medical service team is the workplace of specialised medical personnel, providing daily transportation for patients in life-threatening conditions, from all walks of life, with numerous diseases and injuries. MRSA (methicillin-resistant Staphylococcus aureus) strains are classified as Gram-positive cocci, characterised primarily by their multidrug resistance. Infections caused by S. aureus have a low treatment success rate and are associated with persistent carrier state. This study aimed to isolate MRSA and MSSA (methicillin-sensitive Staphylococcus aureus) in the emergency vehicle and determine drug resistance of these isolates. Materials and Methods: This study involved an ambulance vehicle operated in central Poland. A total of 39 swabs were taken and evaluated from inside the ambulance on permanent duty. The isolates were analysed using catalase and coagulase assays, Gram staining, culturing on Chapman medium, growth evaluation on agar with 5% sheep blood, and assessing the strains’ sensitivities to selected antibiotics. Material was collected from 13 designated points located in the medical compartment and driver’s cabin. Results: S. aureus bacteria were detected in 51.28% of the samples, 40% of which were MRSA strains. Despite the application of high disinfection standards for the interior of the ambulance, it was not possible to kill all S. aureus strains, which may be because the pathogens in question produce a biofilm that effectively allows them to survive on various surfaces, including those disinfected. Almost 100% of the MRSA isolates were resistant to antibiotics from the β-lactam group (penicillin, ticarcillin, cefotaxime, and cefoxitin), the macrolide group (erythromycin) and the lincosamide group (clindamycin). However, only a few MRSA strains proved resistant to streptomycin (12.5%) and ciprofloxacin (37.5%). β-lactam antibiotics, such as cefotaxime (100% resistant strains) and penicillin (58% resistant strains), were also ineffective against MSSA. Although MSSA isolates showed slight resistance to ticarcillin and erythromycin (33.3%) and clindamycin (25%), the remaining antibiotics proved effective (no resistant strains). Conclusions: Among the isolated strains, the greatest resistance to β-lactam antibiotics and erythromycin was observed. Multidrug-resistant strains of S. aureus were found in the emergency medical system. Even the MSSA strains detected in the studied ambulance showed resistance to some of the antibiotics used. The prevalence of S. aureus strains within ambulances indicates the need for a high hygiene level in daily prehospital work with patients.

RESISTÊNCIA A BETALACTÂMICOS: UMA REVISÃO SISTEMÁTICA DOS MECANISMOS E IMPLICAÇÕES CLÍNICAS

Introduction: Beta-lactam antibiotics are commonly administered drugs for the treatment of bacterial infections. They act as inhibitors of bacterial cell wall synthesis, which is essential for the bacteria's survival. Bacterial resistance, especially to the class of β-lactam antibiotics, is a growing public health problem that impacts the efficacy of treatments and increases hospital costs. Objective: This work aims to conduct a systematic review on beta-lactam resistance, addressing its mechanisms and clinical implications. Methods: A systematic review was conducted following PRISMA criteria, selecting 15 complete articles published between 2014 and 2024, obtained from the BVS and MedLine databases. The articles were critically analyzed, and relevant data were organized into tables to discuss antibiotic resistance to β-lactams and address its causes, mechanisms, and clinical implications. Results: The reviewed studies indicated that bacterial resistance is influenced by genetic factors and interactions with the intestinal microbiota, in addition to the inappropriate use of antibiotics. Innovative interventions are necessary to address resistance, focusing on specific strains and mechanisms of action. Conclusion: Bacterial resistance requires a multifaceted approach, including an understanding of the mechanisms involved and the implementation of new treatment strategies. The research highlights the importance of effective interventions to combat resistant infections and improve clinical outcomes.

Peroxyacetic acid activated sulfite process: Generation of reactive species and degradation of β-lactam antibiotics

Sulfite advanced oxidation process is a new chemical oxidation technology with strong development potential and can effectively produce many reactive species for the degradation of emerging contaminants (ECs). This study used the peracetic acid activated sulfite advanced oxidation process (PAA/S(IV) process) with no additional energy input and no heavy metal used to degrade typical β-lactam antibiotics. 79.68 % of amoxicillin (AMX) was rapidly degraded in the PAA/S(IV) process within 5 min, and the reaction pH of 7.0∼9.0 is the best degradation effect. In the PAA/S(IV) process, SO4•-, •OH and CH3C(O)OO• that degrade AMX can be produced, and the contribution rates to the AMX degradation were 58.80 %, 22.24 %, and 18.96 %, respectively. The presence of HCO3– and HA cleared •OH and SO4•- affected the formation of CH3C(O)OO• and then delayed the AMX degradation, while the effect of Cl- on the AMX degradation was negligible. Under the action of the reactive species, the β-lactam ring is broken, and five degradation paths are proposed.

Production of Natural Penicillin-Binding Protein 2 and Development of a Signal-Amplified Fluorescence Polarization Assay for the Determination of 28 Beta-Lactam Antibiotics in Milk

Production of Natural Penicillin-Binding Protein 2 and Development of a Signal-Amplified Fluorescence Polarization Assay for the Determination of 28 Beta-Lactam Antibiotics in Milk

Temporal control of Staphylococcus aureus intracellular pH by sodium and potassium.

Adaptation to environmental change during both colonization and infection is essential to the pathogenesis of Staphylococcus aureus. Like other bacterial pathogens that require potassium to fulfill nutritional and chemiosmotic requirements, S. aureus has been shown to utilize potassium transport to modulate virulence gene expression, antimicrobial resistance, and osmotic tolerance. Recent studies examining the role for potassium uptake in mediating S. aureus physiology have also described its contribution in mediating carbon flux within central metabolism and generation of a proton motive force. Here, we utilize a pH-sensitive green fluorescent protein to examine the temporal regulation of S. aureus intracellular pH by potassium and sodium under various environmental conditions, including extracellular pH and antibiotic stress. Our results distinguish unique conditions and transport mechanisms that utilize these ions to modulate cytoplasmic pH homeostasis, and they identify these processes as a novel mechanism of intrinsic ampicillin resistance in S. aureus.

Assessment of the Safety of Alternative Antibiotics in Children with Confirmed Beta-Lactam Antibiotic Allergy

Introduction: Beta-lactam antibiotics (BLAs) are the most common cause of drug hypersensitivity reactions in children, and it is important to find safe alternative antibiotics for these children. This study evaluates the selection, safety to alternative antibiotics in patients with confirmed BLA allergies based on diagnostic tests. Methods: At the Pediatric Immunology and Allergy Clinic of Ankara Bilkent City Hospital, a retrospective evaluation of diagnostic tests (including skin prick, intradermal, and drug provocation tests) was conducted to identify alternative antibiotics for patients with confirmed BLA. Patients were also contacted by telephone to assess their use of these alternative drugs. Results: The study included 80 patients with confirmed beta-lactam allergy (BLA). The BLAs causing reactions were categorized into two groups: penicillins (75%, n = 60) and cephalosporins (25%, n = 20). Among the penicillins, amoxicillin-clavulanic acid (ACA) was the most common at 68.8%, while among the cephalosporins, ceftriaxone was the most common at 16.3%. Of the 55 patients with ACA allergy, 53 underwent controlled administration with clarithromycin, with 52 showing no reaction. In addition, no reaction was observed in patients who received DPT with cefuroxime (n: 16), phenoxymethyl penicillin (n: 9), cefdinir (n: 1), and cefixime (n: 1), while there was no reaction in the controlled administration with clindamycin. Alternative treatments were tested in 13 patients with a confirmed ceftriaxone allergy. No adverse reactions were observed in 9 patients who underwent DPT with ACA and in 10 patients who were exposed to clarithromycin under controlled conditions. Finally, 54 of the 80 patients (67.5%) were successfully contacted and none reported a reaction to the alternative drugs. Conclusion: For patients with confirmed BLA, macrolides may be considered as preferred alternatives. In addition, beta-lactams with different side chains may be safe alternatives after diagnostic evaluation, taking into account the risk of cross-reactivity.

Antibiotic prescribing practice in urological departments in Germany: results of across-sectional study

The patterns and intensity of inpatient antibiotic prescribing vary according to medical specialty. Analysis of recent data on antibiotic use density in hospital departments of urology in Germany. Annual surveillance data of 107 departments for the period 2022/2023 were evaluated. We used adaily dose definition adapted for adult hospitalized patients (recommended daily doses, RDD), and 100 patient days as the denominator (RDD/100). The overall median antibiotic use density was 71RDD/100 with awide range between 15.9and 138.7 RDD/100 but no significant differences according to hospital size. Fluoroquinolones (median 6.0RDD/100) were prescribed as the fourth most frequent antibiotic class after broad-spectrum cephalosporins (median 16.2RDD/100), aminopenicillin/beta-lactamase inhibitor combinations (median 10.8RDD/100), and broad-spectrum penicillins (piperacillin-tazobactam and piperacillin) (median 8.9RDD/100). The ratio between penicillin and cephalosporin RDD per hospital ranged from 6:94 to 98:2 (overall 52:48). The proportion of aminoglycosides (< 1%) and parenteral fosfomycin (< 0.1%) was very small. Cotrimoxazole (median 4.0RDD/100) was less frequently prescribed than fluoroquinolones. The proportion of oral agents was 44.7% overall, with only small differences according to hospital size. Oral fosfomycin, pivmecillinam, nitrofurantoin, and nitroxoline were much less frequently prescribed than oral beta-lactams, fluoroquinolones, and cotrimoxazole. The overall antibiotic use density in urological hospital departments varied substantially in 2022/2023. Beta-lactam antibiotics were the most frequently used antibiotics, while fluoroquinolones (often as oral agents) continued to be prescribed with alarge range similar to overall antibiotic use and independent of hospital size. Inpatient prescribing of the agents recommended and typically used for uncomplicated cystitis was rare. Penicillins and cotrimoxazole should more often be considered as the treatment option. Aminoglycosides and parenteral fosfomycin should be discussed in cases of otherwise drug-resistant pathogens.

Microbiological and Clinical Features of Patients with Cellulitis in Tropical Australia; Disease Severity Assessment and Implications for Clinical Management.

Australian guidelines for the treatment of cellulitis are informed by data from temperate, metropolitan centers. It is uncertain if these guidelines are equally applicable in tropical Australia, where the population, access to healthcare, and array of potential pathogens are quite different. This retrospective study examined adults admitted to Cairns Hospital in tropical Queensland, Australia, who were treated with intravenous antibiotics for a principal diagnosis of cellulitis in 2019. The study aimed to describe the epidemiological, clinical, and microbiological findings in these cases and the resulting implications for patient management. There were 305 episodes of cellulitis; a potential pathogen was identified in 93/305 (30%), most commonly Staphylococcus aureus (45/93, 48%) or Group A Streptococcus (16/93, 17%). There was one case of Burkholderia pseudomallei. Initial treatment was most commonly with narrow spectrum β-lactam antibiotics with flucloxacillin prescribed in 170/305 (56%) and cefazolin prescribed in 74/305 (26%). Overall, 4/305 (1%) died or were admitted to the intensive care unit (ICU) within 30 days, 123/305 (40%) had an inpatient stay >48 hours, and 63/305 (21%) were readmitted to hospital within 30 days. Every patient who subsequently died or required ICU admission had an elevated early warning score (EWS ≥3) on admission. An EWS ≥3 on admission also predicted an inpatient stay of >48 hours (odds ratio [OR]: 3.2, 95% CI: 1.7-6.0; P <0.001) and 30-day readmission (OR: 2.3, 95% CI: 1.2-4.6; P = 0.01). The etiology of cellulitis in tropical Queensland, Australia, is very similar to that seen in temperate regions, enabling the use of standard management algorithms for patients with cellulitis in the region.

Prevalence, Antimicrobial Susceptibility, and Resistance Genes of Extended-Spectrum β-Lactamase-Producing Escherichia coli from Broilers Sold in Open Markets of Dakar, Senegal.

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) poses a significant public health concern due to its widespread prevalence and resistance to multiple antibiotics. This study aimed to assess the prevalence, resistance profile, and carriage of ESBL-encoding genes in ESBL-Ec isolates from broilers in two markets of Dakar, Senegal. Sampling over a one-year period revealed that 61.7% of broilers carried ESBL-Ec in their cecum. Antibiotic susceptibility testing of 186 ESBL-Ec isolates showed high resistance to β-lactam antibiotics, including ampicillin, ticarcillin, and third-generation cephalosporins. Notably, all isolates were susceptible to imipenem. Multidrug resistance was frequent, with 91.4% of the isolates displaying this phenotype. Comparison between the two markets revealed variations in resistance to quinolones. PCR analysis detected blaCTX-M genes in all isolates, with blaCTX-M-1 being the most prevalent subgroup. Additionally, blaTEM and blaOXA genes were found in 26.3% and 2.7% of isolates, respectively, while no blaSHV genes were detected. Combinations of ESBL genes were common, with blaCTX-M15-blaTEM being the most frequent. These findings highlight the widespread prevalence of ESBL-Ec in broilers from Dakar markets, indicating a potential risk of transmission to humans through the food chain. Effective surveillance and intervention strategies are crucial to mitigate the spread of antimicrobial resistance in humans and animals.

Computational approach towards repurposing of FDA approved drug molecules: strategy to combat antibiotic resistance conferred by Pseudomonas aeruginosa

Antimicrobial resistance is recognized as a major worldwide public health dilemma in the current century. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, causes nosocomial infections like respiratory tract infections, urinary tract infections, dermatitis, and cystic fibrosis. It manifests antibiotic resistance via intrinsic, acquired, and adaptive pathways, where efflux pumps function in the extrusion of antibiotics from the cell. MexB protein, part of the tripartite efflux pumps MexAB-OprM present in P.aeruginosa, expels the penems and β-lactam antibiotics, thereby enhancing Pseudomonas resistance. The current study was intended to screen around 1602 clinically approved drugs to understand their ability to inhibit the MexB protein. Amongst them, the top 5 drug molecules were selected based on the binding energies for analyzing their physio-chemical and toxicity properties. Lomitapide was found to have the maximum negative binding energy followed by Nilotinib, whereas Nilotinib’s number of hydrogen bonds was higher than that of Lomitapide. ADMET study revealed that all 5 drug molecules had limited solubility. Also, Lomitapide and Venetoclax showed low bioavailability scores, while Nilotinib, Eltrombopag, and Conivaptan demonstrated higher potential for therapeutic levels. A molecular dynamic simulation study of the 5 drugs against MexB was carried out for 200 nanoseconds. The RMSD, RMSF, Hydrogen bond formation, Radius of gyration, SASA, PCA, DCCM, DSSP and MM-PBSA binding energy calculation along with demonstrated high stability of the MexB-Nilotinib complex with lesser distortions. Our study concludes, that Nilotinib is a potential inhibitor and can be developed as a therapeutic agent against MexB protein for controlling P. aeruginosa infections.