Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic

Lysozyme is a ~14 kDa protein present in many mucosal secretions (tears, saliva, and mucus) and tissues of animals and plants, and plays an important role in the innate immunity, providing protection against bacteria, viruses, and fungi. Three main different types of lysozymes are known: the c-type (chicken or conventional type), the g-type (goose type), and the i-type (invertebrate type). It has long been the subject of several applications due to its antimicrobial properties. The problem of antibiotic resistance has stimulated the search for new molecules or new applications of known compounds. The use of lysozyme as an alternative antibiotic is the subject of this review, which covers the results published over the past two decades. This review is focused on the applications of lysozyme in medicine, (the treatment of infectious diseases, wound healing, and anti-biofilm), veterinary, feed, food preservation, and crop protection. It is available from a wide range of sources, in addition to the well-known chicken egg white, and its synergism with other compounds, endowed with antimicrobial activity, are also summarized. An overview of the modified lysozyme applications is provided in the form of tables.

Pharmacological Applications and Action Mechanisms of Phytochemicals as Alternatives to Antibiotics in Pig Production

Antibiotics are widely used for infectious diseases and feed additives for animal health and growth. Antibiotic resistant caused by overuse of antibiotics poses a global health threat. It is urgent to choose safe and environment-friendly alternatives to antibiotics to promote the ecological sustainable development of the pig industry. Phytochemicals are characterized by little residue, no resistance, and minimal side effects and have been reported to improve animal health and growth performance in pigs, which may become a promising additive in pig production. This paper summarizes the biological functions of recent studies of phytochemicals on growth performance, metabolism, antioxidative capacity, gut microbiota, intestinal mucosa barrier, antiviral, antimicrobial, immunomodulatory, detoxification of mycotoxins, as well as their action mechanisms in pig production. The review may provide the theoretical basis for the application of phytochemicals functioning as alternative antibiotic additives in the pig industry.

Acute Hemolytic Anemia Induced by Levofloxacin in A Woman With G6PD Deficiency: A Case Report

Introduction: Glucose 6-Phosphate Dehydrogenase deficiency (G6PD) is an X-linked recessive disorder recognized as the most prevalent enzyme deficiency around the world. G6PD deficiency has a high prevalence in Iran, especially in the northern regions. As we know, hemolysis in G6PD patients was not reported with levofloxacin previously. Case Report: In this report, we introduce a 54-year-old G6PD deficient woman who experienced the symptoms of hemolytic anemia following completion of treatment with levofloxacin. Result: After ruling out other causes of hemolysis, by using the Naranjo scale, levofloxacin was considered as a possible cause of hemolysis. Conclusion: Though the hemolytic anemia induced by levofloxacin is extremely rare in G6PD deficient patients, drug-induced hemolytic anemia should be considered as one of the differential diagnoses. It would be appropriate to use an alternative antibiotic instead of levofloxacin in a G6PD deficient patient.

65. Impact of an Antibiotic Side-Chain-Based Cross-Reactivity Chart on Antibiotic Use in Patients With β-lactam Allergies and Pneumonia

Background β-lactam antibiotics with dissimilar R-group side chains are associated with low cross-reactivity. Despite this, patients with β-lactam allergies are too often treated with alternative antibiotic therapy. An institutional β-lactam side-chain-based cross-reactivity chart was developed and implemented to guide in antibiotic selection for β-lactam allergies patients. Methods This single center, retrospective, cohort study analyzed the impact of the implementation of the cross-reactivity chart for patients with documented β-lactam allergies with pneumonia. Study time periods were defined as January 2013 to October 2014 prior to implementation of the chart (historical cohort) and January 2017 to October 2018 (intervention cohort) following institutional implementation and adoption. The primary outcome was the incidence of β-lactam utilization between time periods. Propensity-weighted scoring and interrupted time-series analyses compared outcomes across time periods. Results A total of 341 and 623 patient encounters were included in the historical and intervention cohorts, respectively. There was a significant increase in the use of β-lactams for treatment of pneumonia (70.4% vs 89.3%; p < 0.001) and the use of any alternative therapy decreased between cohorts (58.1% vs. 36%; p < 0.001) (Figure 1). β-lactam use per patient significantly improved between cohorts in patients with mild, Type 1 IgE-mediated hypersensitivity reactions (HSRs) and in patients with unknown reactions. There was no difference in overall HSRs between cohorts (2.4% vs. 1.45; p = 0.628), or in patients who received β-lactam antibiotics (1.3% historical group vs 1.1% intervention group; p = 0.467). Median alternative antibiotic days of therapy (3 vs. 2; p = 0.027) and duration of therapy per patient (3 days vs. 2 days; p = 0.023) decreased between cohorts. There was a significant increase in mortality while healthcare facility-onset Clostridioides difficile infections decreased between cohorts. β-Lactam vs. Alternative Therapy Use per Patients by Calendar Quarter Conclusion Implementation of a β-lactam side-chain-based cross-reactivity chart significantly increased the utilization of β-lactams in patients with pneumonia without increasing HSRs. Disclosures All Authors: No reported disclosures

250. An Assessment of the Penicillin Allergy Label in Patients Undergoing Orthopedic Procedures at a VA Medical Center

Background Approximately 10% of the population is labeled as penicillin (PCN) allergic, while only 1% of these individuals have a true IgE mediated allergy. This label influences the prescription of the most appropriate antibiotic and ultimately leads to antimicrobial resistance, hospital readmission, increased length of hospital stays, use of critical care beds, and greater healthcare costs. Post-surgical complications in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) are also increased when patients receive an alternative antibiotic due to PCN allergy. Methods A retrospective chart review identified patients who underwent a TKA or THA during the 2018-2020 calendar years at the Washington DC VA Medical Center. Multiple operations at different times on the same patient were regarded as separate events. The primary outcome was patients who were evaluable for penicillin allergy de-labeling and the secondary outcome was perioperative antibiotic choice. Results Patients in both groups were predominantly male, Black, and over the age of 60. Of a total of 317 procedures performed, we identified 28 procedures in which patients carried a PCN allergy label (PAL) and received a β-lactam alternative antibiotic for surgical prophylaxis. No patients in the PAL group received cefazolin for prophylaxis, compared to 87% of the non-PAL group who were appropriately given cefazolin. In the group carrying the PAL, 62% of patients received vancomycin and 29% of patients received clindamycin for pre-operative prophylaxis. Only one of these patients had a formal allergy consult note, but the PCN allergy was not addressed during that visit. Fewer patients (4%) required ICU admission during their hospitalization in the non-PAL group versus 10% of patients in the PAL group. Table 1. Patient Demographics and Procedure Detail Conclusion The use of alternative antibiotics in pre-procedural prophylaxis can contribute to adverse events associated with high-risk broader spectrum antimicrobials as well as increased costs associated with antimicrobials such as vancomycin. Our facility began implementation of a penicillin de-labeling program in 2018 via skin testing and direct oral challenge in collaboration with colleagues from Allergy and Immunology. Removal of PAL in this population can increase rates of appropriate prophylaxis. Disclosures All Authors: No reported disclosures

INVESTIGATION OF THE PHYTOCHEMICAL CONTENTS AND ANTIMICROBIAL EFFECTS OF TELFAIRIA OCCIDENTALISON MICROORGANISMS

The rise in several deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. Perhaps, extensive research has been dedicated to identifying alternatives to mitigating the effects of antibiotics resistance. Over the years, plants have contributed significantly to traditional medicine, proven effective in human health care, and were extensively used as alternative antibiotics in certain conditions. Thus, the current studys primary purpose is to determine the phytochemical contents and the antimicrobial activity of T. occidentalison microorganisms, including Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The result of the phytochemical analysis conducted on the leaf and seed of T. occidentalisrevealed alkaloids, tannin, steroids, flavonoids, phenol, and saponins. However, it was found that tannins and phenol were mainly deposited in the plants seed. Also, the antimicrobial analysis conducted revealed that S. aureus was more vulnerable to the ethanol, acetone, and hot aqueous extracts of T. occidentalis. At the same time, P. aeruginosa and C. Albicans showed sensitivity to ethanol and acetone exposure but failed to react to the hot aqueous extracts. The study concludes that the observed biological reactions shown by the aqueous extracts of T. occidentaliscorroborate the traditional application of this plant as an alternative antibiotic.

Lactobacillus johnsonii L531 Alleviates the Damage Caused by Salmonella Typhimurium via Inhibiting TLR4, NF-κB, and NLRP3 Inflammasome Signaling Pathways

Salmonella Typhimurium (S. Typhimurium) is an aggressive zoonotic pathogen that causes enteritis and diarrhea. Antibiotic therapy is still the primary method at present. However, the increasing emergence of multi-drug resistant bacteria weakens the therapeutic efficacy of antibiotics. Probiotics have been widely studied as an alternative antibiotic therapy. In this study, we established an IPEC-J2 cell model of S. Typhimurium infection, aiming to determine the protective effect of Lactobacillus johnsonii L531 (L. johnsonii L531) on S. Typhimurium infection. As our data showed, S. Typhimurium infection resulted in a robust inflammatory response demonstrated by promoted protein levels of the inflammatory-related pathway (TLR4, MyD88, p-IκBα, and p-p65), increased cytokine levels of IL-6, IL-1β, IL-18, and TNF-α, and activated the NLRP3 inflammasome via promoting its assembly. However, L. johnsonii L531 pre-incubation inhibited the activation of the above inflammatory signaling pathways and reduced the expression levels of pro-inflammatory cytokines. In addition, L. johnsonii L531 alleviated the damage of S. Typhimurium to tight junctions ZO-1, Occludin, and Claudin-1. In summary, our findings suggested that L. johnsonii L531 alleviated S. Typhimurium-induced tight junction injury by inhibiting the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.

Success of ceftazidime–avibactam and aztreonam in combination for a refractory biliary infection with recurrent bacteraemia due to blaIMP-4 carbapenemase-producing Enterobacter hormaechei subsp. oharae

Background. Infections due to metallo-beta-lactamase (MBL)-producing organisms are becoming a significant problem, and antibiotic treatment options are limited. Aztreonam inhibits MBLs, and its use in combination with ceftazidime–avibactam (CAZ–AVI–AZT) to inhibit other beta-lactamases shows promise. Methods. A 45-year-old woman suffered from recurrent and sustained MBL (blaIMP-4)+ Enterobacter cloacae complex bacteraemia from an undrainable biliary source, and had failed nine alternative antibiotic regimens over a 5-month period. The 10th episode was successfully treated with CAZ–AVI–AZT, and she has had no further relapses. Three of the isolates underwent whole-genome sequencing (WGS) on the MiSeq platform and were analysed with the Nullarbor pipeline. Results. A layered Etest method for synergy between CAZ–AVI and aztreonam demonstrated an MIC of 2 mg l−1 for the combination. Isolates were identified by WGS as Enterobacter hormaechei subsp. oharae . All three of the isolates had blaTEM-4 ESBL, blaOXA-1 and blaACT-25. Two of the carbapenem-resistant isolates contained blaIMP-4. Conclusion. While aztreonam inhibits MBLs, MBL-positive isolates often express other beta-lactamase enzymes. Avibactam inhibits ESBLs and other beta-lactamases, and its use in this case possibly contributed to therapeutic success due to inhibition of the concomitant blaTEM-4 in the isolates. This case demonstrates that phenotypic antimicrobial susceptibility testing (layered Etests for synergy), backed up by WGS, can produce results that allow tailored antimicrobial therapy in difficult infections. This case adds to the evidence for using CAZ–AVI–AZT in serious MBL infections.

Use of Doxycycline in a Renal Impaired Patient with Enteroccocal Sepsis

Aim: This report highlights the use of doxycycline therapy other than the more standard regimen that includes an aminoglycoside in the management of enterococcal infection in patients with renal impairment without causing further damages to the kidney due to aminoglycoside therapy. Presentation of Case: A case of enteroccocal septicemia in a 29-year-old woman who was admitted on account of acute kidney injury secondary to pregnancy induced hypertension in the setting of pre-eclampsia. She was referred from another centre where she had emergency caesarean section done on account of severe pre-eclampsia at 36 weeks gestational age. Blood culture yielded Enterococcus species. When other antibiotic regimen failed, she was started on doxycycline. Patient had good clinical response and was discharged 7 days after commencement of doxycycline. Discussion: Enteroccoci have emerged as important agent of human disease largely because of their resistance to antimicrobial agents. They are important nosocomial pathogens capable of causing serious and potentially life-threatening infections, including sepsis. The incidence of enteroccocal infections, mainly hospital-acquired, has increased over the past 2 decades and isolates with novel mechanism of resistance to antimicrobial agents are more and more frequent. Furthermore, they have great capacity for transmitting these resistances to other species and even to other genera. Conclusion: Doxycycline is a safe and effective alternative antibiotic for the treatment of enterococcal sepsis in patients with impaired renal status.