[The participation of the USSR in development of penicillin industry in the Eastern Europe].

The article considers on the basis of analysis of archival documents issue of rendering assistance by the Soviet Union to the countries of Eastern Europe to organize production of penicillin. It is established that by the mid of 1950s, modern powerful plants were launched in Bulgaria, Romania and Czechoslovakia by the forces of Soviet engineers . Their construction was carried out on preferential terms for countries-customers. The mutually beneficial cooperation in sphere of production of antibiotics carried out and with other countries of this region. It is demonstrated that the USSR, performing task of enormous humanitarian significance in conditions of the Cold War, simultaneously implemented another goal - formation of loyalty of population of these countries and organization of coalition of friendly states on its Western borders.

Delabelling beta-lactam allergy.

Background: Hypersensitivity to beta-lactam (BL) antibiotics is one of the most frequent reported drug allergies. In our population, it is common to find labels of BL allergy in electronic medical records (EMRs) that have not been assessed. The objective of our study was to detect patients with beta-lactam allergy labels in their EMRs and to assess how many of them are false after a correct diagnostic evaluation. Methods: A multicentre prospective study was performed with patients labelled as allergic to BLs in their EMRs in the previous 5 years. Demographical and clinical data, as well as variables regarding the BL allergy label and the characteristics of the index reaction from clinical history and EMRs, were recorded. Then, diagnostic assessments including clinical history, skin tests (STs), and drug provocation tests (DPTs) were conducted in order to confirm or exclude the diagnosis of BL allergy. Results: A total of 249 patients completed the study, of which 160 (64.3%) were women with a median age of 57 years (interquartile range [IQR], 45-68). The most frequent BL allergy labels detected were for penicillin (124), amoxicillin/clavulanic acid (61), and amoxicillin (54). Of the 204 patients who underwent STs, 20.1% were positive. DPTs were performed in 224 patients, showing good tolerance in 87.1% of cases. After the allergy diagnosis work-up, 186 patients (74.7%) were diagnosed as non-allergic to BL antibiotics. Conclusion: In our study population, the number of patients labelled as allergic to BLs in their EMRs was similar to that in previously published studies, with proportions near to 75%-80% being falsely labelled as allergic to BLs.

Fully closed conformation of penicillin-binding protein revealed by structure of PBP2 from Acinetobacter baumannii.

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for ß-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections.

True Rate of Allergy among Pediatric Inpatients with Penicillin Allergy Labels (TRIAL).

Background: Penicillin allergy is a common drug allergy diagnosis in pediatric patients; however, upon appropriate allergy testing, many of these patients are found not to have a true allergy. For patients with a reported allergy, alternative antibiotics are prescribed, which are less effective, more toxic, or more expensive. There is a lack of data evaluating allergies in hospitalized children and comparing allergy assessments conducted by pediatric allergists and pharmacists. Objective: To estimate the percentage of pediatric patients admitted with reported penicillin allergy who did not have a true penicillin allergy. Methods: This single-centre prospective cohort study included inpatients between 6 months and 17 years of age, with a documented penicillin allergy, who were admitted to the general pediatric and oncology units of a tertiary care children's hospital between November 2019 and March 2023. The allergy history, evaluation, and risk categorization were performed by pharmacists. The history was reviewed with the allergist, and the patient was then referred, underwent skin testing, or received oral amoxicillin challenge with monitoring for 1 hour. Results: Thirty patients were included, of whom 29 (97%) had delabelling of their penicillin allergy. Four patients (13%) had delabelling on the basis of history alone, without risk assessment. Twenty-five (83%) of the patients were assessed as having low risk; 24 of these had delabelling following oral challenge, and 1 did not complete the oral challenge because of transfer to another hospital. One patient (3%) was assessed as having moderate risk, with delabelling on the basis of results of skin testing and oral challenge. The pharmacist's and allergist's risk assessments were in agreement in 29 (97%) of the 30 cases. Conclusions: Pediatric patients, including those with oncologic malignancies, are often mislabelled as having a penicillin allergy. Pharmacists are able to accurately determine true allergy risk and delabel penicillin allergies for pediatric patients in the hospital setting.

Contexte: L'allergie à la pénicilline est un diagnostic d'allergie médicamenteuse courant chez les patients pédiatriques; cependant, après des tests d'allergie appropriés, bon nombre de ces patients ne présentent pas de véritable allergie. Pour ceux présentant une allergie signalée, des antibiotiques alternatifs sont prescrits, moins efficaces, plus toxiques ou plus coûteux. Peu de données permettent d'évaluer les allergies chez les enfants hospitalisés et de comparer les évaluations des allergies réalisées par les allergologues pédiatriques et les pharmaciens. Objectif: Estimer le pourcentage de patients pédiatriques admis avec une allergie à la pénicilline signalée, mais qui n'avaient pas de véritable allergie à la pénicilline. Méthodologie: Cette étude de cohorte prospective monocentrique comprenait des patients hospitalisés âgés de 6 mois à 17 ans, présentant une allergie documentée à la pénicilline, qui ont été admis dans les unités de pédiatrie générale et d'oncologie d'un hôpital pour enfants de soins tertiaires entre novembre 2019 et mars 2023. Les antécédents, l'évaluation et la catégorisation des risques de l'allergie ont été renseignés par les pharmaciens. L'anamnèse a été revue avec l'allergologue, et le patient a ensuite été référé, a subi un test cutané ou a reçu une provocation orale à l'amoxicilline avec surveillance pendant 1 heure. Résultats: Sur 30 patients inclus, 29 (97 %) ont vu un désétiquetage de leur allergie à la pénicilline. Quatre patients (13 %) ont bénéficié d'un désétiquetage sur la seule base de leurs antécédents, sans évaluation des risques. Vingt-cinq (83 %) patients ont été évalués comme présentant un faible risque; 24 d'entre eux ont bénéficié d'un désétiquetage à la suite d'une provocation orale, et 1 n'a pas terminé la provocation orale en raison d'un transfert vers un autre hôpital. Un patient (3 %) a été évalué comme présentant un risque modéré, avec un désétiquetage basé sur les résultats des tests cutanés et de la provocation orale. Les évaluations des risques par le pharmacien et l'allergologue concordaient dans 29 (97 %) des 30 cas. Conclusions: Les patients pédiatriques, y compris ceux atteints de cancers malins, sont souvent étiquetés à tort comme ayant une allergie à la pénicilline. Les pharmaciens sont en mesure de déterminer avec précision le risque réel d'allergie et de désétiqueter les allergies à la pénicilline chez les patients pédiatriques en milieu hospitalier.

An infant with acral peeling of skin: A curious case of congenital syphilis.

Congenital syphilis (CS) is a vertically transmitted infection caused by the spirochete Treponema pallidum. It is seen rarely due to proper antenatal screening. Signs and symptoms appear within the first 2 years of life in early CS and after 2 years in late CS. Failure to diagnose and treat CS in its early stages can result in higher morbidity and mortality. Skin manifestations can guide toward the diagnosis of CS at an early stage. Here, we report a 2-day-old neonate who presented with acral peeling of skin along with respiratory distress and hepatosplenomegaly. Clinical suspicion of CS was made and subsequently confirmed by a positive venereal disease research laboratory test in both mother and child. The child was treated with aqueous crystalline penicillin G as per the CDC guidelines.

Primary Cutaneous Actinomycosis Mimicking Cutaneous Leishmaniasis.

Actinomycosis is a chronic suppurative bacterial infection commonly seen in the tropics, caused by gram-positive, anaerobic bacilli of the genus Actinomyces. There are very few reported cases of primary cutaneous actinomycosis. It can mimic mycetoma, tuberculosis, nocardiosis, and botryomycosis. A high index of clinical suspicion is required for diagnosis in the absence of sinuses. Even with repeated attempts, cultures are mostly negative; and hence, histology reveals the diagnosis in most cases. Here, we report an unusual case of primary cutaneous actinomycosis in a 21-year-old female patient, following a road traffic accident (RTA). A positive Splendore-Hoeppli phenomenon and special stains demonstrated the ray fungus and helped us reach the diagnosis. The patient was started on oral penicillin G and showed good response.

Management and Implications of Beta-Lactam Allergies.

Beta-lactam antibiotics are essential components in the current antimicrobial treatment strategy, playing a crucial role in ambulatory patients and hospitalized patients. Despite their prominent therapeutic index, the use of beta-lactam can lead to adverse effects, with allergic reactions being the most concerning because of their severity. Additionally, the phenomenon of cross-reactivity may occur among various beta-lactam families, with side chains significantly contributing to immunological recognition, making these structures often responsible for the cross-allergic reactivity of beta-lactams. Tools to assess beta-lactam allergy include taking a patient's medical history, performing skin tests, and conducting provocation tests. This research aims to analyze the relevant aspects related to the safe administration of beta-lactam antibiotics in hospitalized patients as well as provide knowledge on the proper management of patients with such hypersensitivity, by doing systemic research. This research was made using Google Scholar and keywords such as "Beta-lactam allergy," "Hypersensitivity," "Cross-reactivity," "Desensitization," and "Beta-lactam allergy management." In conclusion, substituting a beta-lactam antibiotic with an alternative antibiotic may not always be the best management option for these patients, as it may lead to more adverse effects, be less effective, and prolong hospitalization time. It may also result in higher rates of antibiotic-resistant infections and increased medical costs, as these alternatives are often more expensive. However, an alternative within the beta-lactam family can be sought by conducting the appropriate analyses. Although cross-reactivity does not always occur among all beta-lactams, potential cross-reactivity should always be considered.

Novel ratiometric electrochemical aptasensor based on broad-spectrum aptamer recognition for simultaneous detection of penicillin antibiotics in milk.

To effectively monitor multi-residues of penicillin antibiotics (PENs) in milk, we developed a novel ratiometric electrochemical aptasensor enabling simultaneous detection of PENs. The aptasensor employed a broad-spectrum aptamer as a recognition element, niobium carbide functionalized with methylene blue (Nb2C-MB) as a reference signal generator, and a ferrocene-labeled aptamer (Fc-Apt) as an output signal. Electrodes were modified with Fe-N-C doped carbon nanotubes (Fe-N-C-CNTs) to amplify detection signals further. During detection, Fc-Apt binding to PENs decreased Fc current intensity (IFc) and increased MB current intensity (IMB). The simultaneous detection of PENs was achieved using IMB/IFc as a quantitative signal. Under optimal conditions, a good linear relationship between IMB/IFc and antibiotic concentration was observed, indicating the aptasensor had a robustness. The limits of detection of aptasensor for four penicillin antibiotics and their mixed targets were 0.093-0.191 nM. This work provides a new approach to multi-residue detection of the same class of antibiotics.

Safe Penicillin Allergy Delabeling in Primary Care: A Systematic Review and Meta-Analysis.

BACKGROUND: Ten percent of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient delabeling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and nonallergist delabeling. OBJECTIVE: To assess the safety of delabeling low-risk adults by means of dDC in primary care. METHODS: We searched the MEDLINE, Embase, and Cochrane Library databases from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal were performed by 1 reviewer, and we pooled the results in a meta-analysis. RESULTS: Of 2138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated delabeling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely delabeled. Ten patients (<1%) developed an immediate reaction: 3 had self-limiting reactions and 7 needed antihistaminics, steroids, epinephrine, and/or salbutamol. CONCLUSIONS: No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of 1 recent report, these studies are of low to moderate quality. Nonspecialist delabeling is promising, but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.

The Safety of Aztreonam Versus Ceftazidime in Patients Labeled With Penicillin Allergy: A Cohort Study.

PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

Harnessing biotechnology for penicillin production: Opportunities and environmental considerations.

Since the discovery of antibiotics, penicillin has remained the top choice in clinical medicine. With continuous advancements in biotechnology, penicillin production has become cost-effective and efficient. Genetic engineering techniques have been employed to enhance biosynthetic pathways, leading to the production of new penicillin derivatives with improved properties and increased efficacy against antibiotic-resistant pathogens. Advances in bioreactor design, media formulation, and process optimization have contributed to higher yields, reduced production costs, and increased penicillin accessibility. While biotechnological advances have clearly benefited the global production of this life-saving drug, they have also created challenges in terms of waste management. Production fermentation broths from industries contain residual antibiotics, by-products, and other contaminants that pose direct environmental threats, while increased global consumption intensifies the risk of antimicrobial resistance in both the environment and living organisms. The current geographical and spatial distribution of antibiotic and penicillin consumption dramatically reveals a worldwide threat. These challenges are being addressed through the development of novel waste management techniques. Efforts are aimed at both upstream and downstream processing of antibiotic and penicillin production to minimize costs and improve yield efficiency while lowering the overall environmental impact. Yield optimization using artificial intelligence (AI), along with biological and chemical treatment of waste, is also being explored to reduce adverse impacts. The implementation of strict regulatory frameworks and guidelines is also essential to ensure proper management and disposal of penicillin production waste. This review is novel because it explores the key remaining challenges in antibiotic development, the scope of machine learning tools such as Quantitative Structure-Activity Relationship (QSAR) in modern biotechnology-driven production, improved waste management for antibiotics, discovering alternative path to reducing antibiotic use in agriculture through alternative meat production, addressing current practices, and offering effective recommendations.

Penicillin V versus amoxicillin for pneumonia in children-a Swedish nationwide emulated target trial.

OBJECTIVES: Although most countries recommend amoxicillin for paediatric pneumonia, there is a long tradition of treatment with penicillin V (PcV) in Sweden, thus not empirically covering Haemophilus influenzae. There are, however, large regional differences in treatment practice. The aim was to compare clinical outcomes (treatment failure and severe complications), in children aged 1-59 months treated with PcV vs. amoxicillin for pneumonia. METHODS: This population-based emulated target trial included all children born in Sweden between 2001 and 2021, using national health, sociodemographic, and population registers. All pneumonia cases from hospitals and paediatric outpatient clinics in children aged 1-59 months treated as outpatients with PcV or amoxicillin between July 2005 and December 2021, were identified. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for treatment failure (newly dispensed antibiotic prescription or pneumonia-associated hospitalization day 1-14) and severe complications (lung complications, an invasive bacterial disease, admission to intensive care unit or death day 1-28) were calculated with logistic regression analysis. RESULTS: PcV was prescribed in 14 766 cases and amoxicillin in 10 566. Treatment failure occurred in 7.7% with PcV vs. 4.7% with amoxicillin, aOR 1.76 (95% CI: 1.54-2.00). Severe complications were rare, with no significant difference between PcV and amoxicillin (0.3% vs. 0.2%, aOR 0.96, 95% CI: 0.53-1.73). Sensitivity and interaction analyses showed consistent results. DISCUSSION: PcV treatment compared with amoxicillin, was associated with an increased risk for treatment failure but not for severe complications. The absolute risks for adverse outcomes were low in both groups suggesting a minor role of H. influenzae in paediatric pneumonia.

[Penicillin allergy: A label that is not forever]. / Alergia a la penicilina: una etiqueta que no es para siempre.

Self-reported penicillin allergy is highly prevalent. Different studies estimate that 10% of the population is labeled as such. This label, confirmed or suspected, forces us to take precautions and replace the antibiotic treatment of choice (frequently beta-lactams) with other 2nd or 3rd choice alternatives with worse overall results: side effects, resistance, costs, etc. The penicillin allergy label, once placed, remains in the medical record. It is only confirmed in less than 5% of patients, either because it has been placed inappropriately or because over time the sensitivity decreases and may disappear. Penicillin Allergy Decision Rule -PEN-FAST- is a validated and simple clinical prediction rule that estimates the risk of presenting an allergic reaction. Its use, together with algorithms that involve primary care in the study and delabeling of low-risk patients, can change our clinical practice.

The appropriateness of penicillin allergy de-labelling by non-allergist clinical ward teams.

OBJECTIVES: We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin. METHODS: Opportunistic, prospective observational study of usual clinical care, between 16 May 2023 and 14 August 2023, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history. RESULTS: Of the 123 patients admitted with a PenA (or sensitivity record) and exposed to a penicillin, data were collected for 50. Their PenA records were grouped follows: eligible for DDL 34 (68%), eligible for DOC 11 (22%), high risk 4 (8%) and unable to obtain history 1 (2%). In 14/50 (28%) patients there was no evidence of a current PenA assessment in the medical notes. CONCLUSIONS: Using the allergy risk tool, most patients with PenA records were exposed to penicillin appropriately. However, patients meeting high-risk criteria were also exposed to penicillin when the tool excluded them. PenA assessment needs to be carried out with appropriate training and governance structures in place.

Pharmacotherapies for multidrug-resistant gram-positive infections: current options and beyond.

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.

Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation.

Introduction: Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation. Methods: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the gluteal muscles of 6 horses for 3 days. Single IV administration of sodium BP was performed to the same horses with a dose of 22,000 IU BP/kg bwt 39 weeks after last IM injection. BP plasma concentrations were determined by UPLC assay coupled with mass spectrometry and a PK/PD analysis was conducted to predict the efficacy of various dosing regimens by estimating values of the fT>MIC index for different minimum inhibitory concentrations (MIC). Tolerance at the site of IM injection was monitored by creatine kinase activity quantified with a validated chemistry system and clinical scorings. Results and discussion: Except one neurological reaction following one administration of penethamate hydriodide, the tolerance was good. Procaine BP alone, procaine BP/benzathine BP combination or penethamate hydriodide intramuscular administrations at a dosage of 22,000 IU BP/kg bwt q24h for 5 days would yield plasma concentrations that should be effective against bacteria with MIC of ≤0.256, 0.125 or 0.064 mg/L respectively. Of all the tested treatments, the use of a sodium BP by IV Constant Rate Infusion (CRI) for 10 hours a day was deemed to be the most efficient. All the formulations tested in this study are adequate to treat infections with susceptible Streptococcus equi.

A potential space-making role in cell wall biogenesis for SltB1and DacB revealed by a beta-lactamase induction phenotype in Pseudomonas aeruginosa.

Pseudomonas aeruginosa encodes the beta-lactamase AmpC, which promotes resistance to beta-lactam antibiotics. Expression of ampC is induced by anhydro-muropeptides (AMPs) released from the peptidoglycan (PG) cell wall upon beta-lactam treatment. AmpC can also be induced via genetic inactivation of PG biogenesis factors such as the endopeptidase DacB that cleaves PG crosslinks. Mutants in dacB occur in beta-lactam-resistant clinical isolates of P. aeruginosa, but it has remained unclear why DacB inactivation promotes ampC induction. Similarly, the inactivation of lytic transglycosylase (LT) enzymes such as SltB1 that cut PG glycans has also been associated with ampC induction and beta-lactam resistance. Given that LT enzymes are capable of producing AMP products that serve as ampC inducers, this latter observation has been especially difficult to explain. Here, we show that ampC induction in sltB1 or dacB mutants requires another LT enzyme called MltG. In Escherichia coli, MltG has been implicated in the degradation of nascent PG strands produced upon beta-lactam treatment. Accordingly, in P. aeruginosa sltB1 and dacB mutants, we detected the MltG-dependent production of pentapeptide-containing AMP products that are signatures of nascent PG degradation. Our results therefore support a model in which SltB1 and DacB use their PG-cleaving activity to open space in the PG matrix for the insertion of new material. Thus, their inactivation mimics low-level beta-lactam treatment by reducing the efficiency of new PG insertion into the wall, causing the degradation of some nascent PG material by MltG to produce the ampC-inducing signal. IMPORTANCE: Inducible beta-lactamases like the ampC system of Pseudomonas aeruginosa are a common determinant of beta-lactam resistance among gram-negative bacteria. The regulation of ampC is elegantly tuned to detect defects in cell wall synthesis caused by beta-lactam drugs. Studies of mutations causing ampC induction in the absence of drug therefore promise to reveal new insights into the process of cell wall biogenesis in addition to aiding our understanding of how resistance to beta-lactam antibiotics arises in the clinic. In this study, the ampC induction phenotype for mutants lacking a glycan-cleaving enzyme or an enzyme that cuts cell wall crosslinks was used to uncover a potential role for these enzymes in making space in the wall matrix for the insertion of new material during cell growth.

The Genetic Landscape of Antimicrobial Resistance Genes in Enterococcus cecorum Broiler Isolates.

Enterococcus cecorum is associated with bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Prophylactic treatment with antimicrobials is common in the poultry industry, and, in the case of outbreaks, antimicrobial treatment is needed. In this study, the minimum inhibitory concentrations (MICs) and epidemiological cutoff (ECOFF) values (COWT) for ten antimicrobials were determined in a collection of E. cecorum strains. Whole-genome sequencing data were analyzed for a selection of these E. cecorum strains to identify resistance determinants involved in the observed phenotypes. Wild-type and non-wild-type isolates were observed for the investigated antimicrobial agents. Several antimicrobial resistance genes (ARGs) were detected in the isolates, linking phenotypes with genotypes for the resistance to vancomycin, tetracycline, lincomycin, spectinomycin, and tylosin. These detected resistance genes were located on mobile genetic elements (MGEs). Point mutations were found in isolates with a non-wild-type phenotype for enrofloxacin and ampicillin/ceftiofur. Isolates showing non-wild-type phenotypes for enrofloxacin had point mutations within the GyrA, GyrB, and ParC proteins, while five amino acid changes in penicillin-binding proteins (PBP2x superfamily) were observed in non-wild-type phenotypes for the tested ß-lactam antimicrobials. This study is one of the first that describes the genetic landscape of ARGs within MGEs in E. cecorum, in association with phenotypical resistance determination.

ß-Lactam allergy delabeling is safe and saves costs in Primary Care.

OBJECTIVE: To determine whether the ß-lactam allergy delabeling was safe and cost-saving in Primary Care (PC) patients. DESIGN: We have conducted a retrospective chart review of PC patients with ß-lactam allergy label evaluated in our Allergy Unit between 2017 and 2022. SITE: Allergy Department. Hospital Virgen del Rocio (Sevilla). PARTICIPANTS: A total of 391 patients labeled for ß-lactam allergy in PC were studied. MAIN MEASUREMENTS: (a) Outcome evaluation of a ß-lactam allergy delabeling procedure. (b) A ratio between the total e-prescribed antibiotic cost and the number of treatment days (the experimental daily antibiotic cost or EDAC) before and after delabeling was analyzed in delabeled and truly allergic patients. RESULTS: The results of skin testing were positive in 9.2% of the reported cases (36 of 391 patients). The reactions to oral provocation challenge (OPC) occurred in 2.14% of the patients who underwent negative skin testing to offending ß-lactam (in 15 of 699 OPC). A total of 307 patients (78.5%) were delabeled; 70 (17.9%) had a ß-lactam selective response and 14 (3.59%) reacted to both penicillin and cephalosporin. The EDAC before and after the procedure in delabeled patients was significantly lower (0.88 € vs 0.62 €, p<10-3), than that observed in truly allergic group (0.87 € vs. 0.76 €, p=not significant). CONCLUSION: To delabel ß-lactam allergy in Primary Care patients is safe in most patients, cost-saving in antibioticotherapy, and allows identify the main clinical ß-lactam allergy phenotypes that benefit from this procedure.