Beta-lactam Research Articles

Diagnosis and selection of alternative antibiotics in beta-lactams hypersensitivity reactions: Current recommendations and challenges.

Beta-lactam (BLM) antibiotics , including amino-penicillin and cephalosporins, are typically the first-choice treatment for bacterial infections. However, adverse reactions to these antibiotics are frequently reported, causing non-allergist physicians to select alternative broad-spectrum antibiotics that can have harmful consequences. Patients with unclear histories of hypersensitivity reactions to BLMs should undergo an allergy workup to establish a firm diagnosis, particularly when different drugs are prescribed simultaneously. However, finding the safest, most precise, and cost-effective methods for confirming BLMs hypersensitivity and selecting the most appropriate alternative BLM is uncertain, particularly in severe delayed reactions. This review aims to provide data and recommendations on the availability and validity of skin tests (STs), drug provocation test (DPT) protocols, based on the latest published literature and guideline. To make the process more practical, we focused on cross-reactivity between BLMs and diagnostic tests. There are two main novel aspects of this document: 1) For T-cell-mediated reactions, patient stratification into high, moderate, and low-risk groups based on the mortality and morbidity of adverse drug reactions. 2) For IgE-mediated reactions, stratification of individuals with isolated limited urticarial without anaphylaxis in a low-risk group and removal of the extensive limitation.

In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia.

Multidrug-resistant (MDR) Pseudomonas aeruginosa has been declared a serious threat by the United States Centers for Disease Control and Prevention. Here, we used whole genome sequencing (WGS) to investigate recurrent P. aeruginosa bloodstream infections in a severely immunocompromised patient. The infections demonstrated unusual, progressive increases in resistance to beta lactam antibiotics in the setting of active treatment with appropriate, guideline-directed agents. WGS followed by comparative genomic analysis of isolates collected over 44 days demonstrated in host evolution of a single P. aeruginosa isolate characterized by stepwise acquisition of two de-novo genetic resistance mechanisms over the course of treatment. We found a novel deletion affecting the ampC repressor ampD and neighboring gene ampE, which associated with initial cefepime treatment failure. This was followed by acquisition of a porin nonsense mutation, OprD, associated with resistance to carbapenems. This study highlights the potential for in-host evolution of P. aeruginosa during bloodstream infections in severely immunocompromised patients despite appropriate antimicrobial therapy. In addition, it demonstrates the utility of WGS for understanding unusual resistance patterns in the clinical context.

68. Beta lactam resistant staphylococcus aureus in spinal osteomyelitis and spondylodiscitis: trends in antibiotic resistance, treatment, and complications

68. Beta lactam resistant staphylococcus aureus in spinal osteomyelitis and spondylodiscitis: trends in antibiotic resistance, treatment, and complications

Isolation and Identification of Enterobacter spp from pet Animals Ear Infections in Al-Hilla Veterinary Clinic, Iraq

Objective: To isolation and identification of Enterobactor spp. from ear infection in pet animals in Babylon province by traditional method Automated Vitek 2 system as well as determined the antibiotic sensitivity test. Methods; One hundred swab of ear infection were isolated from dogs and cats ear infections in different veterinary clinic in Babylon province, at a period between 1january to 1 July 2022. Results: The results of pet animals swab collection revealed that the percentage of gram negative was 71(71%) while the positive was 29 (29%) as well as the biochemical test showed that the enterococcal cloaca percent was (64%), Klebsiella (19%), positive bacteria (6%), E. coli 3% and no growth was 7%. The biochemical tests showed positive for Catalase, Citrate. They gave negative reaction for Urease, Oxidase, MR (Methyl Red), Indole. By the other hand, the result of isolated E. cloaca that was plated onto culture media. then subcultures on MacConkey agar (MAC) and XLD agar. The Antimicrobial susceptibility test of E.cloaca against 55 conventional antimicrobial revealed that E.cloaca varied to a large extent. The isolated bacteria showed sensitivity for the most commonly used antimicrobials for treatment of bacterial otitis media in dog and cat which were amoxycillin, amoxycillin+clavulanic acid, cephalospins, gentamicin and fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) azithromycin, clarithromycin, neomycin and ploymyxin-B. In contrast, the present study showed that E.cloaca resistant for three antibiotic belongs from beta lactam group (Cefsulodin, Loracarbet and Cefpodoxime). Conclusion: the production of inhibitor-resistant β-lactamases by E. cloacae isolates could be increasingly common in nosocomial pathogens other than E. coli or K. pneumoniae in pet animals ear infection in Al-Hilla city Babylon province, Iraq.

Lenfoma ve Solid Tümörlü Çocuklarda Febril Nötropenide Sefaperazon-Sulbaktam Monoterapisinin Etkinliği

Objective: Monotherapy with a beta lactam or a cephalosporin has become the standard of care for the treatment of febrile neutropenia (FEN). We aimed to evaluate the efficacy of cefoperazone/sulbactam (CS) as empirical monotherapy for febrile neutropenia in children with solid tumors and lymphomas. Material and Methods: Children with FEN received cefaperazone-sulbactam (80 mg/kg/day, every 8 hours). Treatment responses (a) successful, complete resolution of all signs and symptoms of infection at 72 hours and after 7 days of CS treatment; (b) success with modification, change of therapy for viral, parasitic or fungal infection or addition of glycopeptides; (c) failure was defined as the emergence of a new or resistant infection, treatment-resistant bacteremia, the need to switch to carbapenems. Results: Our study included 157 patients and 350 febrile neutropenia episodes. The most common diagnoses were osteosarcoma (35%), Ewing sarcoma (30%), non-hodgkin lymphoma (13%) and rhabdomyosarcoma (9%), respectively. The origin of fever could not be determined in 223 (64%) of FEN episodes, 79 (22%) had microbiologically documented infection (MDI), and 48 (14%) had clinically documented infection (CDI). The success rate was 65% (229), the success rate with modification was 9% (31) and the failure rate was 26% (90). SC monotherapy was successful in 33% of attacks with MDI and in 60% of attacks with CDI. However, SC monotherapy was successful in 82% of febrile episodes of unknown origin. Conclusion: Cefoperazone/sulbactam is effective and safe in febrile neutropenic children with solid tumors and lymphomas for monotherapy.

Novel Beta Lactam Antibiotics for the Treatment of Multidrug-Resistant Gram-Negative Infections in Children: A Narrative Review.

Infections due to carbapenem-resistant Enterobacterales (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes, especially in critically ill patients. Novel beta lactam antibiotics, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol, have been released in recent years to face the emerging challenge of multidrug-resistant (MDR) Gram-negative bacteria. Nonetheless, several novel agents lack pediatric indications approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), leading to uncertain pediatric-specific treatment strategies and uncertain dosing regimens in the pediatric population. In this narrative review we have summarized the available clinical and pharmacological data, current limitations and future prospects of novel beta lactam antibiotics in the pediatric population.

Latency Antibiotics in Preterm Prelabor Rupture of Membranes: A Comparison of Azithromycin Regimens.

Treatment with antibiotics at the time of preterm prelabor rupture of membranes (PPROM) has been shown to prolong pregnancy. Due to the recurrent shortage of erythromycin, azithromycin has been substituted in the traditional regimen; however, there are little data on optimal dosing. The objective of this study was to determine whether there is a difference in latency from onset of PPROM to delivery in patients who received a single dose of azithromycin compared with a 5-day course. This was a single-center, multisite, retrospective, IRB approved analysis of patients admitted with a diagnosis of PPROM. Patients were included if rupture occurred between 22 0/7 and 33 6/7 weeks of gestation and received either a single dose or a 5-day course of azithromycin along with a beta lactam. A total of 376 patients were reviewed with 296 patients included in the final analysis. There was no statistical difference in the primary outcome of latency days in patients who received the 5-day versus the single-dose course (4 vs 5 days, P = 0.641). There was a significantly higher rate of histologic chorioamnionitis in the single-dose course of azithromycin (46.4% vs 62.6%, P = 0.006). There was no difference in latency for patients who received a 5-day course of azithromycin versus a single dose for the treatment of PPROM. A higher rate of histologic chorioamnionitis was observed in those who received the single-day course. Prospective follow-up studies are needed to confirm these findings.

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Hospitals: Age-Specificity and Potential Zoonotic-Zooanthroponotic Transmission Dynamics.

Methicillin-resistant Staphylococcus aureus (MRSA) lineages are a devastating clinical and public health issue. Data on local lineage profiles are limited. We report on the frequency of community-acquired and hospital-acquired cases (CA-MRSA, HA-MRSA). We studied 147 isolates from King Khalid tertiary care hospitals (KKH), each from a case in a patient and including 33 patients at the Maternity and Children's Hospital (MCH). Of the 147 isolates, 87 males (59%) and 60 females (41%) were in KKH. The overwhelming majority (80%; n = 119/147) were CA-MRSA in KKH. Intriguingly, despite significant differences between males (70%) and females (53%), lineage-acquisition remained age-specific around 58-60 years in both genders. However, while CA-MRSA dominated early in life (0-20, 70% MCH), it increased with age in KKH adults; 21-50 (28%), >50 (59%) until the overall 80% (n = 144/180). Major specimens included skin-wounds, surgeries (70.3%), blood (13.5%), sputum (8.8%), very rarely urine (4.1%), and nasal (3.4%), albeit most patients showed severe enteritis and necrotizing pneumonia. Antibiograms showed high beta lactam resistances, including amoxicillin-clavulanate (83%), oxacillin (84%), cefoxitin FOX (100%), penicillin and ampicillin (~100%), as well as high resistance (82%) to carbapenem. Fortunately, high susceptibility was seen to non-beta lactams and, to a lesser extent, gentamicin, erythromycin, and fusidic acid; 33%, 34%, and 38%, respectively, in KKH. A similar pattern was seen in MCH except for a low resistance pattern to gentamicin CN, clindamycin CD, erythromycin E, and tobramycin TOB; 34%, 31%, 39%, and 41%, respectively, except for fusidic acid. These findings have significant clinical implications for MRSA patient management strategies. Clinical- and lineage-profiles imply host-selection and zoonotic-zooanthroponotic transmission dynamics. Future molecular typing, sequencing, and characterization of dominant clone(s) is imperative.

#5781 DRUG-INDUCED ACUTE INTERSTITIAL NEPHRITIS (D-AIN): HOW TO IDENTIFY THE RESPONSIBLE DRUG?

Abstract Background and Aims The mainstay of D-AIN treatment is the removal of the responsible drug. However, it is not always easy to identify the culprit drug as this entity mainly affects elderly patients on multiple medications, they rarely associate systemic symptoms (rash, fever), and the timeline regarding the diagnosis and the associated drug is not always clear. Therefore, the diagnosis and treatment are delayed, making full renal function recovery less likely. The lymphocyte transformation test (LTT) has demonstrated to be useful in the identification of the involved drug in other hypersensitivity-mediated lymphocyte T diseases such as Stevens-Johnson Syndrome or Dress Syndrome. For this reason, we wonder if this test could be relevant in identifying the responsible drug in D-AIN. The aim of this study is to test LTT in patients with clinical and histological diagnosis of D-AIN. Method We have conducted a retrospective observational study in which we have collected data from 2019 to 2022 from our electronic databases. Results: We have registered 9 cases of D-AIN diagnosed with histological confirmation in whom the LTT had been performed. 22.2% of these patients were men. The mean age was 48.1 years (standard deviation of 15.8). None of them had previous chronic kidney disease (CKD). Mean peak creatinine at diagnosis was 4.66 mg/dl (standard deviation of 1.95). Regarding the typical symptoms of the D-AIN, three patients (33%) presented with fever and none of them suffered from rash. 6 patients had sterile pyuria (66%). All of them received steroid treatment. Concerning the LTT results, 7 cases were positive for one of the drugs the patient was taking, and 2 were negative. Among the positive cases, the identified drugs were 1 case of beta lactams (piperacillin), 1 case of PPIs (omeprazole), 1 case of metamizole, 1 case of paracetamol, 1 case of eslicarbazepine and 2 cases of NSAIDs (dexketoprofen), while the negative cases have not been suspected of taking any culprit drug. Conclusion LTT may be a useful test to identify the responsible drug for D-AIN, especially in patients taking multiple medications in which may be included some of great importance like immunotherapy (typical cause of D-AIN) in oncological treatments. In negative cases, it could be expected that the patient had taken medications difficult to be identified in the clinical history or, in some situations, the drug hapten responsible for kidney damage might be a drug metabolite and not the drug itself, which cannot be detected by the test.

The Activity of Some Antibiotics Depend on Stereochemistry of Them (Its Structure)

The chiral carbon in biological compounds lead to its activity, for example, the beta lactam ring contains two carbon centers carbon number three and carbon number four both are chiral carbon. This chirality plays important role in the activity and bind with structures activity relationship. Also the ofloxacin act on topoisomerase which required for protein Synthesis of microorganism, the ofloxacin when become Levo isomer not only racemic mixture the activity is more than the racemic or Dextro isomer. Also, the old Antibiotics Chloramphenicol the RR’ isomers only active not the other isomers of Chloramphenicol.

Ceftazidime-avibactam with or without Aztreonam vs Polymyxin-based Combination Therapy for Carbapenem-resistant Enterobacteriaceae: A Retrospective Analysis.

Gram-negative sepsis remains one of the most difficult to treat infections in intensive care units (ICUs). Carbapenems are often considered to be robust and reliable options for treating infections due to Gram-negative bacteria. The dominance of carbapenem-resistant enterobacteriaceae (CRE) has emerged as one of the greatest challenges faced by the medical community today. Carbapenem-resistant enterobacteriaceae may be resistant to all beta lactam antimicrobials including carbapenems and often, are even resistant to other classes of drugs. There are limited studies comparing polymyxin-based therapies with ceftazidime-avibactam (CAZ-AVI)-based therapies for treating infections caused by CRE. A retrospective study comparing outcomes between patients with bacteremia caused by CRE treated with polymyxin-based combination therapy and CAZ-AVI-based therapy (with or without aztreonam). Of total 104 patients, 78 (75%) were in the CAZ-AVI group. There was no significant difference in the underlying comorbidities between the two groups. The incidence of nephrotoxicity was significantly higher in the polymyxin group (p = 0.017). Ceftazidime-avibactam-based therapy was 66% less likely to be associated with day 14 mortality (p = 0.048) and 67% less likely to be associated with day 28 mortality (p = 0.039) as compared with polymyxin-based therapy. Ceftazidime-avibactam-based therapy may be a superior option to polymyxin-based therapy for infections caused by CRE. This can have significant practical applications, in terms of optimizing therapy for the individual patient as well as sparing polymyxins and reducing the use of polymyxins in our hospitals. Prayag PS, Patwardhan SA, Panchakshari S, Sambasivam R, Dhupad S, Soman RN, et al. Ceftazidime-avibactam with or without Aztreonam vs Polymyxin-based Combination Therapy for Carbapenem-resistant Enterobacteriaceae: A Retrospective Analysis. Indian J Crit Care Med 2023;27(6):444-450.

A Rapid Method to Screen for Multi Drug Resistance (MDR) Trait in Clinical Isolates of Acinetobacter baumannii-Acyl Homoserine Lactone (AHL) Screening in CRAB and CSAB Isolates

Aims: Our proposal aimed to evaluate Acyl Homoserine Lactones (AHL) as a functional marker for Multi drug resistant (MDR) potential in clinical isolates of Acinetobacter baumannii. We investigated the AHL production potential of clinical isolates using a biosensor assay directly on a commonly used agar media.
 Place and Duration of Study: Department of Molecular Diagnostics and Biomarkers, Gleneagles Global Hospitals, Lakdikapul, Hyderabad-500004.
 Methodology: Antimicrobial drug sensitivity testing (AST) was performed on 72 clinical isolates of A. baumannii against two front-line antibiotics, Imipenem (10µg) and Meropenem (10µg), by Kirby-Bauer disk diffusion method. Production of long chain Acyl Homoserine lactone (AHLs) in the clinical isolates of A. baumannii was tested by cross streaking with the biosensor Chromobacterium violaceum mutant strain CV026 and Agrobacterium tumefaciens (NTL4pZLR4) by agar plate diffusion assay. Screening and identification of the quorum sensing mediator gene abaI was done by PCR to confirm its presence in all the 72 clinical isolates.
 Results: Out of the 72 clinical isolates, 58 were Carbapenem resistant Acinetobacter baumannii (CRAB) and 14 were Carbapenem sensitive Acinetobacter baumannii (CSAB) for AST by agar disc diffusion method. None of our isolates produced short chain AHLs whereas all the isolates could produce varying amounts of long chain AHLs. Genotypic confirmation of AHL gene was obtained by abaI gene PCR.
 Conclusion: Carbapenems are the front-line antibiotics used to treat gram negative bacterial infections in emergencies and in the critical care units of hospitals. Clinical isolates A. baumannii has innate resistance to several antibiotics due to various mechanisms, biofilms forming the first line of defense against antibiotics for the bacterium. Our study used AST to carbapenem as the leading marker for MDR, assuming the innate resistance of A. baumannii to other beta lactam antibiotics. Our study brought out certain important observations namely: a) All clinical isolates of A. baumannii produced Quorum Sensing signal molecules, the AHLs b) the clinical isolates of A. baumannii did not produce any short chain AHLs b) All the clinical isolates of A. baumannii produced long chain AHLs c) AHL production is not specific to carbapenem drug resistance because even CSAB isolates produced AHL d) AHL production is inherent to all clinical isolates of A. baumannii and it apparently indicates an underlying biofilm potential and MDR trait in these A. baumannii isolates. e) AHLs could be a universal marker for revealing MDR trait and biofilm potential in clinical microbiology AST profiling protocols.

Antibacterial effect of kitchen herbs against pathogenic multidrug-resistant E. coli isolates from calf diarrhoea.

Calf diarrhoea remains the biggest challenge both in the small and large farms. Infectious diarrhoea is associated with many pathogens, Escherichia coli being one, but majority are systematically treated with antibiotics. Since antimicrobial resistance (AMR) is a growing menace, the need to find alternative prophylactic solutions using popular kitchen herbs such as Trachyspermum ammi (carom seeds), Curcuma longa (turmeric) and cinnamon (Cinnamomum sp.) extracts is been investigated against virulent form of E. coli isolated from calf diarrhoea. The virulence factors identified in these isolates were ST (32.5%), LT (20%), eaeA (15%), stx1 (2.5%) and stx2 (5%) with the occurrence of the most common serogroups as O18 (15%) followed by O111 (12.5%). Highest resistance was seen with beta lactam + beta lactamase inhibitor (amoxicillin/clavulanic acid) followed by beta lactams (ampicillin, cefuroxime and cefepime). The zone of inhibition due to cinnamon (methanol) and carom seed (ethanol) extracts (500 to 250 μg/mL concentration) on E. coli bacteria was >19 mm, respectively. Turmeric, cinnamon and carom had the potency of inhibiting the pathogenic E. coli which maybe suggestive of its use in calf diets as prophylaxis against diarrhoea.

Essential oil and phytoconstituent (Linalool) from Homalomena aromatica Schott. rhizomes exhibit antibacterial and synergistic effects with beta-lactam antibiotics against Carbapenem-resistant Enterobacteriaceae (CRE) and Methicillin Resistant S. aureus (MRSA) pathogens

Homalomena aromatica Schott. (HA) locally known as “Sugandhmantri” in India is a perennial herb commonly found in Assam, Northeast India and popular for its aromatic and medicinal properties. The main aim of this study was to determine the phytoconstituents of the essential oil (HA-EO) extracted from the rhizomes of Homalomena aromatica, purify its major phytoconstituent (HA-EOC-L) and examine the antibacterial activity. Further the study investigated the synergistic effect of both HA-EO and HA-EOC-L with beta lactam antibiotics against a panel of multi drug resistant (MDR) bacterial pathogens comprising CRE (Carbapenem resistant Enterobacteriaceae namely Escherichia coli & Klebsiella pneumonia genetically harboring NDM/OXA enzymes that deactivates major β-lactam antibiotics including carbapenem) and MRSA (Methicillin Resistant Staphylococcus aureus harboring mecA gene that encodes PBP2a protein and attributes to antibiotic resistance). Gas chromatography – Mass spectrometry (GC-MS) analyses of HA-EO displayed a total of 177 phytoconstituents with Linalool (mono-terpene alcohol) (38.6 %), terpinen-4-ol (9.5 %), gamma terpinene, and gamma muurolene (3.6 %) as the major class. The major phytoconstituent (Linalool) HA-EOC-L of this lot was purified by fractional distillation. In vitro investigation of the antibacterial activity of HA-EO and HA-EOC-L demonstrated its potential antibacterial activity with MIC 134–1075 µg/ml and 75–606 µg/ml against MDR bacteria (CRE & MRSA) respectively. Further, testing the combinatorial activity of HA-EO and HA-EOC-L with β-lactam antibiotics [(ceftriaxone-CRO (third generation cephalosporin) and meropenem-MEP (carbapenem)], by checkerboard test and time kill assay, demonstrated its synergistic effect towards MDR bacteria with HA-EOC-L showing better adjuvant activity with fractional inhibitory concentration index values (FICI) ranging from 0.13 to 0.49. The results emphasize the significant use of HA-EO and its constituent (HA-EOC-L) as an antibiotic-adjuvant agent to combat MDR infections propounded by the MRSA and CRE indicating HA with its beneficial secondary metabolites as a useful plant that can help human health, animal health besides food and cosmetic industry to combat MDR pathogens.

2-Octylcyclopentanone Inhibits Beta Lactam Resistant Diabetic Wound Pathogens.

Microbial infection is a frequent complication of diabetic foot ulcers, with up to 82% of ulcers being infected at the initial stage of diabetes. Furthermore, the emergence of beta lactam resistant pathogens managed to eliminate the use of beta lactam antibiotics as a chemotherapeutic alternative. This further increases the amputation and mortality rate. Hence, the aim of this study is to evaluate antimicrobial efficacy of a ketone derivative 2-octylcyclopentanone against diabetic wound pathogens. The inhibitory activity of the compound was determined using disc diffusion and broth microdilution assay. Generally, 2-octylcyclopentanone showed broad-spectrum antimicrobial activity, particularly against beta lactam resistant pathogens. The compound showed comparably better antimicrobial activity than all reference antibiotics, including chloramphenicol, streptomycin, ampicillin and penicillin. In addition, the same compound also inhibits a clinically isolated Pseudonomas aeruginosa that was resistant to all reference antibiotics. The activity was microbicidal based on the low minimal lethality concentration recorded, particularly on MRSA, P. aeruginosa and Candida utilis. The killing efficiency of the compound was concentration dependent. During kill curve analysis, the inhibitory activity of 2-octylcyclopentanone was concentration and time-dependent. 99.9% of reduction of bacterial growth was observed. MRSA and P. aeruginosa, two significant diabetic wound infections, are totally inhibited by the molecule at a concentration of minimum lethality concentration. In short, 2-octylcyclopentanone exhibited significant inhibitory towards wide range of diabetic wound pathogens. Which is considered crucial since it will provide a safe and effective alternative treatment for diabetic ulcer infection.

The Current Status and Future Perspectives of Beta-Lactam Therapeutic Drug Monitoring in Critically Ill Patients.

Beta-lactams (BL) are the first line agents for the antibiotic management of critically ill patients with sepsis or septic shock. BL are hydrophilic antibiotics particularly subject to unpredictable concentrations in the context of critical illness because of pharmacokinetic (PK) and pharmacodynamics (PD) alterations. Thus, during the last decade, the literature focusing on the interest of BL therapeutic drug monitoring (TDM) in the intensive care unit (ICU) setting has been exponential. Moreover, recent guidelines strongly encourage to optimize BL therapy using a PK/PD approach with TDM. Unfortunately, several barriers exist regarding TDM access and interpretation. Consequently, adherence to routine TDM in ICU remains quite low. Lastly, recent clinical studies failed to demonstrate any improvement in mortality with the use of TDM in ICU patients. This review will first aim at explaining the value and complexity of the TDM process when translating it to critically ill patient bedside management, interpretating the results of clinical studies and discussion of the points which need to be addressed before conducting further TDM studies on clinical outcomes. In a second time, this review will focus on the future aspects of TDM integrating toxicodynamics, model informed precision dosing (MIPD) and "at risk" ICU populations that deserve further investigations to demonstrate positive clinical outcomes.

Epidemiological Description and Detection of Antimicrobial Resistance in Various Aquatic Sites in Marseille, France.

Antibiotic resistance is a worldwide public health concern and has been associated with reports of elevated mortality. According to the One Health concept, antibiotic resistance genes are transferrable to organisms, and organisms are shared among humans, animals, and the environment. Consequently, aquatic environments are a possible reservoir of bacteria harboring antibiotic resistance genes. In our study, we screened water and wastewater samples for antibiotic resistance genes by culturing samples on different types of agar media. Then, we performed real-time PCR to detect the presence of genes conferring resistance to beta lactams and colistin, followed by standard PCR and gene sequencing for verification. We mainly isolated Enterobacteriaceae from all samples. In water samples, 36 Gram-negative bacterial strains were isolated and identified. We found three extended-spectrum β-lactamase (ESBL)-producing bacteria-Escherichia coli and Enterobacter cloacae strains-harboring the CTX-M and TEM groups. In wastewater samples, we isolated 114 Gram-negative bacterial strains, mainly E. coli, Klebsiella pneumoniae, Citrobacter freundii and Proteus mirabilis strains. Forty-two bacterial strains were ESBL-producing bacteria, and they harbored at least one gene belonging to the CTX-M, SHV, and TEM groups. We also detected carbapenem-resistant genes, including NDM, KPC, and OXA-48, in four isolates of E. coli. This short epidemiological study allowed us to identify new antibiotic resistance genes present in bacterial strains isolated from water in Marseille. This type of surveillance shows the importance of tracking bacterial resistance in aquatic environments. IMPORTANCE Antibiotic-resistant bacteria are involved in serious infections in humans. The dissemination of these bacteria in water, which is in close contact with human activities, is a serious problem, especially under the concept of One Health. This study was done to survey and localize the circulation of bacterial strains, along with their antibiotic resistance genes, in the aquatic environment in Marseille, France. The importance of this study is to monitor the frequency of these circulating bacteria by creating and surveying water treatments.

Comparison of myconanoparticles and myconanoemulsion incorporated biomaterials in controlling multidrug-resistant bacterial pathogens

Green nanotechnology plays a significant role in many domains, from medicine to agriculture. Antibiotic resistance has emerged in organisms because of the continuous and indiscriminate application of various antibiotics. MDR (Multi drug resistant) bacteria, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were found to be resistant to beta- lactam antibiotics. In this study, the aqueous extract of Colletotrichum siamense was used to engineer nanoparticles (CsNps) and tea tree oil-based nanoemulsion (CsNe). Engineered CsNps and CsNe were subjected to biophysical characterization by using UV visible spectroscopy, FESEM, EDAX, FT-IR, HRTEM, SAED, and zeta potential to determine the charge, size, stability, elemental composition, topography, etc., The CsNps and CsNe were screened to detect antimicrobial activity by the zone of inhibition, MIC, MBC, and biofilm inhibition to its test potential against pathogenic E. coli, K. pnuemoniae, A. baumannii, and S. aureus. In silico studies were performed to study the binding affinity of the virulence proteins of MDR pathogens with secondary metabolites of Colletotrichum siamense. The results of both in vitro and in-silico studies of nanoparticles and nano-emulsion were observed to be more promising than beta-lactam antibiotics. Hence, in near future, these endophytic fungi, C. siamense mediated nanoparticles (CsNps) and nanoemulsion (CsNe) can be employed to develop an alternative to beta lactam antibiotics against the MDR pathogens.

Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants.

Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs. The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months. The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin-clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable. A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.

Risk Factors of Challenge-Proven Beta-Lactam Allergy in Children with Immediate and Non-Immediate Mild Cutaneous Reactions

Introduction: Beta-lactam (BL) antibiotics are the most often involved drugs in allergic reactions. Mild cutaneous reactions such as maculopapular exanthema or urticaria are the most common presenting complaints of BL allergy in the pediatric population. However, it can be challenging to distinguish BL-induced allergy from reactions due to infections or other reasons. In this study, we aimed to determine the clinical characteristics and potential risk factors of true BL allergy in children with suspected mild cutaneous reactions to BLs. Methods: We evaluated children who were admitted to our pediatric allergy clinic with suspected BL allergy in between January 2015 and March 2020. Patients with a history suggestive of immediate and non-immediate mild cutaneous reactions were included in the study. The oral challenge test (OCT) with the culprit drug was performed on all patients to confirm the diagnosis. Results: Two hundred fourteen (119 male and 95 female) patients with a median age of 4.9 years were evaluated. BL allergy was confirmed in 10.7% (23) of the patients, according to the OCT results. Most of the proven allergic reactions were of the immediate type (73.9%), and urticaria was the most common presenting complaint (60.8%) in proven BL-allergic patients. The negative predictive value of penicillin-G skin testing was 89.7% for immediate-type penicillin allergy and 93.4% for non-immediate reactions. Also, positive predictive value of penicillin-G skin testing was 50% for immediate and 25% for non-immediate reactions. In the multivariate logistic regression analysis, a history of proven drug allergy (Exp (B): 7.76, 95% CI: 1.88–31.97, p = 0.005) was found to be the risk for BL allergy. Conclusion: This study highlighted that OCTs should be performed to confirm the diagnosis in patients suspected of immediate and non-immediate mild cutaneous reactions to BLs and remove the overestimated “BL allergy” label. In these patients, a history of proven drug allergy might be a risk factor for true BL allergy.