Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

First-line treatment with ceftriaxone for Neisseria gonorrhoeae infection less likely to be prescribed to patients with a penicillin allergy label: a retrospective audit of medical records.

Background Gonorrhoea notifications have increased substantially in Australia over the past decade. Neisseria gonorrhoeae is already highly resistant to several antibiotics and so, alternatives to first-line treatment are generally strongly discouraged. The penicillin allergy label (AL) on patient medical records has previously been shown to influence prescribing practices, to the detriment of best-practice management and antimicrobial stewardship. This study aimed to understand how the penicillin AL influences antibiotic selection for gonorrhoea treatment at Canberra Sexual Health Centre. Methods A retrospective chart audit of gonorrhoea cases treated at Canberra Sexual Health Centre between January 2020 and October 2023 (n =619 patients, n =728 cases). Antibiotic selection was assessed according to penicillin AL status. Ceftriaxone selection was assessed according to penicillin allergy severity reported in the medical records and as determined using a validated antibiotic allergy assessment tool. Results Cases with a penicillin AL were more likely to receive antibiotics other than ceftriaxone (n =7/41, 17.1%) than cases without the label (n =8/687, 1.2%, P n =28/41, 68.3%) to apply the assessment tool. Those reported as low-severity in the records were more likely to receive ceftriaxone (n =21/22, 95.5%) than those reported as moderate-high (n =7/11, 63.6%) or unreported (n =6/8, 0.75%). Conclusions Treatment of gonorrhoea in outpatient settings requires an understanding of penicillin allergy, and the ability to quickly and accurately identify penicillin-AL patients who can safely tolerate ceftriaxone. Institutionally endorsed penicillin allergy de-labelling protocols and access to easy-to-navigate prescribing advice within national sexually transmitted infection management guidelines would support this.

[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.

[Penicillin allergy-Truth or duty?] / Penicillinallergie ­ Wahrheit oder Pflicht?

The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show a negative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play a central role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and a risk stratification for the identification of patients with a penicillin allergy. This overview article presents a possible delabelling algorithm within the framework of the clarification of a beta-lactam antibiotic allergy. The focus is on a structured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score.

Identification of antibiotic induced persister cells in Streptococcus agalactiae.

Antibiotic persistence is a phenomenon, where a small fraction of a bacterial population expresses a phenotypic variation that allows them to survive antibiotic treatment, which is lethal to the rest of the population. These cells are called persisters cells, and their occurrence has been associated with recurrent disease. Streptococcus agalactiae is a human pathobiont, able to cause invasive infections, and recurrent infections have been reported to occur in both newborns and adults. In this study, we demonstrated that S. agalactiae NEM316 can form persister cells when exposed to antibiotics from different classes. The frequency of persister cell formation was dependent on bacterial growth phase and the class of antibiotics. The ability to form persister cells in response to penicillin was shown to be a general trait among different clinical S. agalactiae isolates, independent of sero- and sequence-type. Taken together, this study shows the existence of antibiotic tolerant S. agalactiae persister cells, which may explain why this bacterial species frequently persists after treatment of invasive infection and can be associated with recurrent disease.

Attaching Metal-Containing Moieties to ß-Lactam Antibiotics: The Case of Penicillin and Cephalosporin.

Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C6 and cepham C7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b, which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.

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.

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.

Thyroglobulin specific IgE and a possible link to suspected penicillin induced allergic skin manifestations - cross sectional study.

Porcine thyroglobulin was important in the discovery of alpha-Gal allergy. Here, the linkage of porcine thyroglobulin-specific IgE with IgE positivity to routinely assessed allergens and to the incoming diagnosis within a population of suspected atopic individuals is explored. IgE, IgA, total IgG and IgG subclasses to porcine thyroglobulin, IgE to bovine, human thyroglobulin and meat extract were measured with ELISA. The following correlations were observed in IgE binding to porcine and bovine thyroglobulin (r = 0.910, p = 1x10-17), porcine and human thyroglobulin (r = 0.635, p = 4x10-6), human and bovine thyroglobulin (r = 0.746, p = 6x10-9) and porcine thyroglobulin and meat extract (r = 0.482, p = 0.0009). Only one out of ten samples which showed binding to porcine thyroglobulin in ELISA tested positive with ImmunoCAP alpha-Gal, implying different epitope/s. Increased IgE binding was detected towards a more electronegative fraction of porcine thyroglobulin separated according to charge and the binding could be partially inhibited by galactose. Anti-thyroglobulin IgE was found in 29.7% of the population, in subjects who were significantly younger, p < 0.0001 and it occurred more frequently in patients referred for testing penicillin specific IgE (OR 2.48, p = 0.0059) and were negative. IgE specific to porcine, bovine and possibly human thyroglobulin may be implicated in post-infectious skin manifestation misinterpreted as penicillin allergy.

Antistreptococcal treatment of psoriasis: a systematic review.

Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.

Alexander Fleming: a second look.

In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.

Evaluation of patients labeled with a penicillin allergy to promote antimicrobial stewardship in dental practice.

BACKGROUND: Approximately 10% of the US population self-reports a penicillin allergy history or are labeled as penicillin allergic. However, from 90% through 99% of these patients are not allergic on formal evaluation. CASE DESCRIPTION: Patients labeled as penicillin allergic receive broader-spectrum and sometimes less-effective antibiotics, thereby contributing to increased treatment failures, antibiotic resistance, and adverse drug reactions. Self-reported penicillin allergy can be eliminated or classified as low-, medium-, or high-risk after a careful review of patient history. This allows these patients to be delabeled; that is, having any reference to their penicillin allergy history or of having an allergy to penicillin eliminated from their health records. PRACTICAL IMPLICATIONS: Oral health care professionals are ideally placed to partner in both antibiotic stewardship interventions by means of recognizing pervasive mislabeling and aiding in the process of delabeling.

Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial.

PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

Penicillin Allergy: Mechanisms, Diagnosis, and Management.

Allergy to penicillin can occur via any of the 4 types of Gel-Coombs hypersensitivity reactions, producing distinct clinical histories and physical examination findings. Treatments include penicillin discontinuation, and depending on the type of reaction, epinephrine, antihistamines, and/or glucocorticoids. Most beta-lactams may be safely used in penicillin-allergic patients, with the possible exception of first-generation and second-generation cephalosporins. Penicillin testing includes skin testing, patch testing, and graded challenge. The selection of the type of testing depends on the clinical setting, equipment availability, and type of hypersensitivity reaction. Desensitization may be used in some cases where treatment with penicillins is essential.

What Is Strep Throat?

This JAMA Patient Page describes strep throat, its signs and symptoms, diagnosis, treatment, and potential complications.

Development of Penicillin-Based Carbonic Anhydrase Inhibitors Targeting Multidrug-Resistant Neisseria gonorrhoeae.

The development of antibacterial drugs with new mechanisms of action is crucial in combating the rise of antibiotic-resistant infections. Bacterial carbonic anhydrases (CAs, EC 4.2.1.1) have been validated as promising antibacterial targets against pathogens such as Helicobacter pylori, Neisseria gonorrhoeae, and vancomycin-resistant enterococci. A multitarget strategy is proposed to design penicillin-based CA inhibitor hybrids for tackling resistance by targeting multiple bacterial pathways, thereby resensitizing drug-resistant strains to clinical antibiotics. The sulfonamide derivatives potently inhibited the CAs from N. gonorrhoeae and Escherichia coli with KI values in the range of 7.1-617.2 nM. Computational simulations with the main penicillin-binding protein (PBP) of N. gonorrhoeae indicated that these hybrid derivatives maintained the mechanism of action of the lead ß-lactams. A subset of derivatives showed potent PBP-related antigonococcal effects against multidrug-resistant N. gonorrhoeae strains, with several compounds significantly outperforming both the lead ß-lactam and CA inhibitor drugs (MIC values in the range 0.25 to 0.5 µg/mL).

Penicillium chrysogenum: Beyond the penicillin.

Almost one century after the Sir Alexander Fleming's fortuitous discovery of penicillin and the identification of the fungal producer as Penicillium notatum, later Penicillium chrysogenum (currently reidentified as Penicillium rubens), the molecular mechanisms behind the massive production of penicillin titers by industrial strains could be considered almost fully characterized. However, this filamentous fungus is not only circumscribed to penicillin, and instead, it seems to be full of surprises, thereby producing important metabolites and providing expanded biotechnological applications. This review, in addition to summarizing the classical role of P. chrysogenum as penicillin producer, highlights its ability to generate an array of additional bioactive secondary metabolites and enzymes, together with the use of this microorganism in relevant biotechnological processes, such as bioremediation, biocontrol, production of bioactive nanoparticles and compounds with pharmaceutical interest, revalorization of agricultural and food-derived wastes or the enhancement of food industrial processes and the agricultural production.

The effects of leptin and cannabinoid CB1 receptor agonist/antagonist in cerebral tissues of epileptic rats.

OBJECTIVE: In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model. METHODS: Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 µg), ACEA (7.5 µg), AM251 (0.25 µg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method. RESULTS: MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels. CONCLUSION: It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.