Long-term Antibiotic Use Research Articles

Severe Dehydration Due to Low Intake in Patients with Oral Candidiasis in Malignancy: A Case Report

Oral candidiasis is an infection in oral cavity caused by Candida albicans. This disease is frequently caused by immunological suppression, which can be local or systemic, caused by immunosuppression due to extremes of age (newborns and the elderly), diseases that impair immunity, such as in infection of human immunodeficiency virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), long-term systemic steroid use, and long-term systemic antibiotic use. Oral candidiasis could lead to low-intake condition due to swallowing difficulties. This case report aimed to present a patient with severe dehydration due to oral candidiasis that needs to be hospitalized.

Systemic antibiotics increase microbiota pathogenicity and oral bone loss

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.

Evaluation of surgical antibiotic prophylaxis

Surgical prophylaxis is one of the areas where antibiotics are used commonly. In this study it is aimed surgical prophylaxis appropriateness and determination of cost analysis in our hospital. The study was performed November 30-15, 2018. 108 patients who underwent surgery in general surgery, orthopedics and neurosurgery clinics have been included in this prospective study. Patient selection was based on the classification of clean and cleancontaminated. Demographics, features of the surgery, applied prophylactic antibiotics and surgical prophylaxis appropriateness were recorded in the forms. All patient information forms were evaluated by infectious disease specialists using the surgical prophylaxis guide. The costs of unnecessary antibiotics were determined. Mean age of 108 patients who underwent a surgical procedure was 52.4 years and 39.8% of the patients were male and 60.2% were female. Of the surgery procedures 75.9% (n:82) were clean and 24.1% (n:26) clean-contaminated. Preoperative 58.3% (63) unnecessary antibiotic prophylaxis was detected. Continuing prophylaxis at a prolonged time were used in 99 (91.7%) patients in the postoperative period. Cefazolin is the most commonly used agent for surgical prophylaxis. The cost of unnecessary and long-term antibiotic use was determined as ₺6983,69. In this study, the time of antibiotic prophylaxis were to be a big problem. Prophylaxis often starts very early and continues for days. The wrong practices in surgical prophylaxis lead to unnecessary antibiotics treatment to the patients and also burden to the budget of the country.

Role of nanotechnology in mastitis treatment for dairy cows: a mini review

Mastitis is among the most popular ailments in dairy cow that results in the greatest financial losses for dairy farms. Different strains of bacteria, fungus, and algae are responsible for causing mastitis. Mostly this disease is typically caused by bacteria that grow in the udder and lymph nodes, causing damage to the udder parenchyma. Antibiotics are the primary method of treatment for mastitis. However, long-term use of antibiotics has caused pathogens that cause mastitis to become more resistant to antibiotics. As a result, various strategies for eliminating pathogenic bacteria that cause mastitis are being researched. Researchers have looked for alternative therapeutic modalities to antibiotics for the treatment of mastitis. These efforts are helped by the innovative invention of nanotechnology for mastitis therapy and management. As a result, nanotechnology may become the primary type of mastitis treatment in the near future. In vitro-In vivo research of alternative remedy for mastitis have indicated that many microorganisms responsible for this disease can be successfully inhibited and destroyed. The current review article discusses different nanoparticles for mastitis treatment in dairy cow herds.

Recent progress in nanozymes for the treatment of diabetic wounds.

The slow healing of diabetic wounds has seriously affected human health. Meanwhile, the open wounds are susceptible to bacterial infection. Clinical therapeutic methods such as antibiotic therapy, insulin treatment, and surgical debridement have made great achievements in the treatment of diabetic wounds. However, drug-resistant bacteria will develop after long-term use of antibiotics, resulting in decreased efficacy. To improve the therapeutic effect, increasing drug concentration is a common strategy in clinical practice, but it also brings serious side effects. In addition, hyperglycemia control or surgical debridement can easily bring negative effects to patients, such as hypoglycemia or damage of normal tissue. Therefore, it is essential to develop novel therapeutic strategies to effectively promote diabetic wound healing. In recent years, nanozyme-based diabetic wound therapeutic systems have received extensive attention because they possess the advantages of nanomaterials and natural enzymes. For example, nanozymes have the advantages of a small size and a high surface area to volume ratio, which can enhance the tissue penetration of nanozymes and increase the reactive active sites. Moreover, compared with natural enzymes, nanozymes have more stable catalytic activity, lower production cost, and stronger operability. In this review, we first reviewed the basic characteristics of diabetic wounds and then elaborated on the catalytic mechanism and action principle of different types of nanozymes in diabetic wounds from three aspects: controlling bacterial infection, controlling hyperglycemia, and relieving inflammation. Finally, the challenges, prospects and future implementation of nanozymes for diabetic wound healing are outlined.

Listening to enteric bacteria from the perspective of antibiotic alternatives in animal husbandry

<p>Antibiotic alternatives are urgently needed to combat the gut dysbiosis and antibiotic resistance due to the long-term use of antibiotics in farm animals and the slow growth of discovery of novel antibiotics. Interfering with bacterial cell-to-cell communication, known as quorum sensing (QS) is a promising strategy. QS inhibitors, or quenchers, can suppress various social activities and physiological processes, including the production of virulence factors and biofilm formation without inducing antibiotic resistance. There are dense microbes in the gut of animals, which communicate with each other as well as the hosts. The phenomena of QS in gut pathogens of farm animals is a novel area that deserves intense interest and further research. However, a few of studies have investigated QS changes in gut pathogens of farm animals, and validation of quenchers in animals is lacking. Combining antibiotic alternatives and antibiotics could achieve a synergistic effect, and improving our understanding of QS targets and developing databases for precision medicine could lead to more effective and safe use of quenchers. In this review, we summarized recent development of QS in farm animals and the mechanism of quencher used as antibiotic alternatives. Furthermore, the review concluded the advantage of using QS to fight against bacteria and put forward some perspectives for the future development of QS in antibiotics.</p>

Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection.

The barrier function of host cells enables intracellular bacteria to evade the lethality of the host immune system and antibiotics, thereby causing chronic and recurrent infections that seriously threaten human health. Currently, the main clinical strategy for the treatment of intracellular bacterial infections involves the use of long-term and high-dose antibiotics. However, insufficient intracellular delivery of antibiotics along with various resistance mechanisms not only weakens the efficacy of current therapies but also causes serious adverse drug reactions, further increasing the disease and economic burden. Improving the delivery efficiency, intracellular accumulation, and action time of antibiotics remains the most economical and effective way to treat intracellular bacterial infections. The rapid development of nanotechnology provides a strategy to efficiently deliver antibiotics against intracellular bacterial infections into cells. In this review, we summarize the types of common intracellular pathogens, the difficulties faced by antibiotics in the treatment of intracellular bacterial infections, and the research progress of several types of representative nanocarriers for the delivery of antibiotics against intracellular bacterial infections that have emerged in recent years. This review is expected to provide a reference for further elucidating the intracellular transport mechanism of nanocarrier-drug complexes, designing safer and more effective nanocarriers and establishing new strategies against intracellular bacterial infection.

Dual-Nozzle 3D Printed Nano-Hydroxyapatite Scaffold Loaded with Vancomycin Sustained-Release Microspheres for Enhancing Bone Regeneration

Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects. Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation. The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 μg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration. Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.

Essential Oils in the Treatment of Various Types of Acne—A Review

Acne is a chronic, common disease that poses a significant therapeutic, psychological and social problem. The etiopathogenesis of this disease is not fully understood. Drugs used in general and external therapy should have anti-seborrhoeic, anticomadogenic, bactericidal, bacteriostatic, and anti-inflammatory properties. Acne treatment is often associated with the long-term use of antibiotics, contributing to the global antibiotic resistance crisis. In order to solve this problem, attention has been paid to essential oils and their terpene components with potent antimicrobial, anti-inflammatory, and antioxidant properties. Research shows that certain essential oils effectively reduce inflammatory acne lesions through mechanisms related to the sebaceous glands, colonization of Cutibacterium acnes, and reactive oxygen species (ROS). An example is tea tree oil (TTO), a more commonly used topical agent for treating acne. TTO has antimicrobial and anti-inflammatory activity. The paper presents the latest scientific information on the activity and potential use of specific essential oils in treating acne. Evidence of antibacterial, anti-inflammatory, and antioxidant activity of several essential oils and their main components was presented, indicating the possibility of using them in the treatment of acne.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

LAPAROSCOPIC MESH EXPLANTATION FOR MESH INFECTIONS FOLLOWING INTRA PERITONEAL ON-LAY MESHPLASTY (IPOM): A CASE SERIES

The introduction of synthetic mesh has become the standard of care in the management of abdominal wall hernias [1,2]. However, the slightest of breach in the sterility chain can lead to mesh infection and biolm formation which often requires a prolonged stay in hospital with long term use of antibiotics and need for multiple interventions. Incidence of mesh infection is dependent on both Intra-operative events as well as pre-existing modiable risk factors in the patient. Mesh infection can present as abscess, chronic discharging sinus and sepsis [1] However, in most cases, mesh explantation is required. In this paper, we present a series of 5 patients who underwent laparoscopic mesh explantation following IPOM mesh infection with good outcomes.

1983. Impact of postoperative antibiotics duration on prognosis in patients with infective endocarditis

Abstract Background Infective endocarditis (IE) remains a major medical problem with high morbidity and mortality. Appropriate antibiotic treatment in patients with IE lowers the risk of embolism, recurrence, and long-term mortality. However, there are concerns about renal toxicity and an increase in the incidence of resistant strains due to long-term use of antibiotics. In this study, we compare the difference in overall mortality according to the duration of postoperative antibiotics therapy in patients with IE for each group. Methods From 2005 to 2017, we retrospectively reviewed 416 patients with IE at a 2400-bed tertiary hospital in South Korea. A total of 239 IE patients who underwent valve surgery and appropriate antibiotics duration were enrolled. The primary endpoint was long-term overall mortality. The secondary endpoints were reoperation rate, recurrence rate, and postoperative complications, such as new-onset heart failure, paravalvular and embolic complications. Results The median follow-up duration was 71 (interquartile range, 46–109) months. The duration of postoperative antibiotic therapy was less than 2 weeks in 67 patients (28.0%) and more than 2 weeks in 127 patients (72.0%). The median age was 53 years. The overall mortality was 13.0% (31/239). There were no statistical differences in overall mortality (13.4% vs. 12.8%, p=0.894), reoperation (6.0% vs. 4.1%, p=0.507), and recurrence (7.5% vs. 2.9%, p=0.148) between patients with postoperative antibiotic therapy for ≥2 weeks and less than 2 weeks. The duration of postoperative antibiotic therapy based on 2 weeks in the Kaplan-Meier curve was not associated with overall mortality (log-rank test, p=0.971). Conclusion In conclusion, there was no statistically significant difference in the overall mortality, recurrence, and reoperation rate according to the duration of postoperative antibiotic therapy. When surgery and recommended total antibiotics duration are properly performed according to guidelines, the effect of duration of postoperative antibiotic therapy on overall mortality, recurrence rate, and reoperation rate is reduced to a statistically insignificant extent. Disclosures All Authors: No reported disclosures.

Genetic and Environmental Investigation of a Novel Phenylamino Acetamide Inhibitor of the Pseudomonas aeruginosa Type III Secretion System.

Traditional antibiotics target essential cellular components or metabolic pathways conserved in both pathogenic and nonpathogenic bacteria. Unfortunately, long-term antibiotic use often leads to antibiotic resistance and disruption of the overall microbiota. In this work, we identified a phenylamino acetamide compound, named 187R, that strongly inhibited the expression of the type III secretion system (T3SS) encoding genes and the secretion of the T3SS effector proteins in Pseudomonas aeruginosa. T3SS is an important virulence factor, as T3SS-deficient strains of P. aeruginosa are greatly attenuated in virulence. We further showed that 187R had no effect on bacterial growth, implying a reduced selective pressure for the development of resistance. 187R-mediated repression of T3SS was dependent on ExsA, the master regulator of T3SS in P. aeruginosa. The impact of 187R on the host-associated microbial community was also tested using the Arabidopsis thaliana phyllosphere as a model. Both culture-independent (Illumina sequencing) and culture-dependent (Biolog) methods showed that the application of 187R had little impact on the composition and function of microbial community compared to the antibiotic streptomycin. Together, these results suggested that compounds that target virulence factors could serve as an alternative strategy for disease management caused by bacterial pathogens. IMPORTANCE New antimicrobial therapies are urgently needed, since antibiotic resistance in human pathogens has become one of the world's most urgent public health problems. Antivirulence therapy has been considered a promising alternative for the management of infectious diseases, as antivirulence compounds target only the virulence factors instead of the growth of bacteria, and they are therefore unlikely to affect commensal microorganisms. However, the impacts of antivirulence compounds on the host microbiota are not well understood. We report a potent synthetic inhibitor of the P. aeruginosa T3SS, 187R, and its effect on the host microbiota of Arabidopsis. Both culture-independent (Illumina sequencing) and culture-dependent (Biolog) methods showed that the impacts of the antivirulence compound on the composition and function of host microbiota were limited. These results suggest that antivirulence compounds can be a potential alternative method to antibiotics.

1773. Evaluation of Fluoroquinolone Prophylaxis in Preventing Bacterial Infection in Neutropenic Afebrile Patients Without Leukemias or HSCT: A Systematic Review

Abstract Background Per 2010 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer, routine use of fluoroquinolone (FQ) chemoprophylaxis in low-risk populations (defined as those with solid tumors or lymphoma undergoing chemotherapy) is not recommended to prevent febrile neutropenic episodes as it was not found to impact all-cause mortality. Since these guidelines were published, there have been additional randomized trials (RCTs) of FQ chemoprophylaxis in patients with cancer. Our objective was to assess the efficacy of FQ vs placebo in preventing probable or confirmed bacterial infection in patients with cancer who did not have leukemias or hematopoietic stem cell transplant (HSCT). Secondary outcomes of interest included febrile episodes, mortality, and adverse effects of antibiotic use. Methods Medline via PubMed, The Cochrane Central Register of Controlled Trials, and SCOPUS from inception through 2/17/2022 were searched. We included RCTs in English comparing FQ to placebo in preventing neutropenic fever and bacterial infections in patients with cancer who did not have leukemias or HSCT. Results We included 5 RCTs (N= 3158). The rates of probable or confirmed bacterial infection in patients with cancer revealed 541/1562 (34.6%) infections in the FQ group and 679/1560 (43.5%) in the placebo group (OR: 0.68, 95% CI:0.59,0.79, I2 = 57%, p=0.002). In evaluating development of febrile episodes, 300/1566 (19.2%) events were noted in the FQ group and 407/1555 (26.2%) in the placebo group (OR: 0.58, 95% CI:0.41,0.83, I2 = 0%, p< 0.001). Mortality events in the FQ group were 113/1597(7.1%) and 124/1508 (8.2%) in the placebo group (OR: 0.76, 95% CI:0.53,1.1, I2 = 7%, p=0.15). Adverse events associated with antibiotic use in the studies were more frequent in the FQ group. Figure 1Forest Plot of Mortality in included studiesFigure 2Results on Development of Fevers in included studies.Figure 3Forest plot of Probable or Proven Infection in included studies. Conclusion Although evidence does not show that FQ prophylaxis provides mortality benefit, it did show a decrease in development of bacterial infections and febrile episodes. This suggests that treatment may still provide clinical benefit to this population of patients, but must be weighed against risks and consequences of long-term antibiotic use, which were not reported by the included studies. Disclosures All Authors: No reported disclosures.

Long-term oral antibiotic use in people with acne vulgaris in UK primary care: a drug utilization study.

The inappropriate use of antibiotics is understood to contribute to antimicrobial resistance. Oral antibiotics are regularly used to treat moderate-to-severe acne vulgaris. In practice, we do not know the typical length of oral antibiotic treatment courses for acne in routine primary care and what proportion of people receive more than one course of treatment following a new acne diagnosis. To describe how oral antibiotics are prescribed for acne over time in UK primary care. We conducted a descriptive longitudinal drug utilization study using routinely collected primary care data from the Clinical Practice Research Datalink GOLD (2004-2019). We included individuals (8-50 years) with a new acne diagnosis recorded between 1 January 2004 and 31 July 2019. We identified 217 410 people with a new acne diagnosis. The median age was 17 years [interquartile range (IQR) 15-25] and median follow-up was 4.3 years (IQR 1.9-7.6). Among people with a new acne diagnosis, 96 703 (44.5%) received 248 560 prescriptions for long-term oral antibiotics during a median follow-up of 5.3 years (IQR 2.8-8.5). The median number of continuous courses of antibiotic therapy (≥ 28 days) per person was four (IQR 2-6). The majority (n = 59 010, 61.0%) of first oral antibiotic prescriptions in those with a recorded acne diagnosis were between the ages of 12 and 18. Most (n = 71 544, 74.0%) first courses for oral antibiotics were for between 28 and 90 days. The median duration of the first course of treatment was 56 days (IQR 50-93 days) and 18 127 (18.7%) of prescriptions of ≥ 28 days were for < 6 weeks. Among people who received a first course of oral antibiotic for ≥ 28 days, 56 261 (58.2%) received a second course after a treatment gap of ≥ 28 days. The median time between first and second courses was 135 days (IQR 67-302). The cumulative duration of exposure to oral antibiotics during follow-up was 255 days (8.5 months). Further work is needed to understand the consequences of using antibiotics for shorter periods than recommended. Suboptimal treatment duration may result in reduced clinical effectiveness or repeated exposures, potentially contributing to antimicrobial resistance.

Risk Factors and Outcomes of Multidrug-Resistant Bacteria Infection in Infected Pancreatic Necrosis Patients.

The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40-70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients. Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed. IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381-12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502-4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109-6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients. We identified common infectious strains and risk factors for MDRB infection in IPN patients.

A sublingual nanofiber vaccine to prevent urinary tract infections.

Urinary tract infections (UTIs) are a major public health problem affecting millions of individuals each year. Recurrent UTIs are managed by long-term antibiotic use, making the alarming rise of antibiotic resistance a substantial threat to future UTI treatment. Extended antibiotic regimens may also have adverse effects on the microbiome. Here, we report the use of a supramolecular vaccine to provide long-term protection against uropathogenic Escherichia coli, which cause 80% of uncomplicated UTIs. We designed mucus-penetrating peptide-polymer nanofibers to enable sublingual (under the tongue) vaccine delivery and elicit antibody responses systemically and in the urogenital tract. In a mouse model of UTI, we demonstrate equivalent efficacy to high-dose oral antibiotics but with significantly less perturbation of the gut microbiome. We also formulate our vaccine as a rapid-dissolving sublingual tablet that raises response in mice and rabbits. Our approach represents a promising alternative to antibiotics for the treatment and prevention of UTIs.

When more can lose more: Comments to the long-term use of prophylactic antibiotics for very low birth weight infant resulting in the adverse outcomes.

When more can lose more: Comments to the long-term use of prophylactic antibiotics for very low birth weight infant resulting in the adverse outcomes.

Long-term use of broad-spectrum antibiotics affects Ly6Chi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy.

The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A+ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6Chi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.