Combined Antibiotic Treatment Research Articles

Gallic acid synergistically enhances the antibacterial activity of azithromycin in MRSA.

The rise of antibiotic resistance in existing pathogens has been identified as a major threat to global healthcare in the twenty-first century. This resistance has consequences such as increased cost and prolonged hospital stays, treatment failure, and ultimately increased risk of patient mortality. It is therefore imperative to develop strategies to combat drug resistance. Combined treatment of common antibiotics and natural compounds is one of the most effective methods against resistant bacterial infections. Gallic acid (GA) is a natural secondary metabolite abundantly found in plants and has significant medicinal effects in various aspects of health. In this research, the antibacterial effects of azithromycin (AZM) and GA alone and in combination with each other were investigated on planktonic and biofilm forms of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the combination of AZM/GA had an additive effect against MSSA and P. aeruginosa and a synergistic effect against MRSA. In addition, combining these two agents significantly reduced the minimum biofilm inhibitory concentration (MBIC) of AZM and GA in the MRSA strain. Finally, the level of ROS generation in the effect of AZM plus GA was evaluated in the bacteria. Among the studied strains, ROS production was significantly increased in combination treatment compared to AZM alone in MRSA. The results show that the combination of AZM and GA has a significant effect against MRSA and can be considered as an effective treatment option.

Efficacy of Intravenous Colistin Monotherapy Versus Colistin Combined With Meropenem in Patients With Multidrug-Resistant Infections: A Retrospective Observational Study.

Background Intensive care units frequently contend with infections caused by highly drug-resistant organisms, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE), which often lead to high mortality rates. Colistin (colomycin) is employed to treat infections, notably extremely drug-resistant (XDR) bacteria. Antibiotic combination treatment is a frequently used tactic in this endeavour. However, the widespread use of antibiotics in synergy could result in the emergence of resistance and a rise in side effects, such as those linked to Clostridium difficile infection. The aim of the study was to assess and contrast the clinical results of intravenous colistin monotherapy with the combination of colistin and meropenem in patients experiencing MDR bacteremia resulting from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). Methods In this retrospective observational study, an analysis spanning two years, from June 2021 to June 2023, was conducted at a teaching hospital located in Karachi, Pakistan. The research involved the retrospective examination of medical records from 132 patients who had been diagnosed with MDR bacteremia. Patients were divided into two categories based on their treatment regimen, either intravenous colistin monotherapy or intravenous colistin combined with meropenem. Among the 132 patients included in the analysis, 66 underwent colistin monotherapy, while the other 66 received a combination of colistin and meropenem. The primary focus of evaluation in this study centered on the 14-day all-cause mortality, while secondary outcomes encompassed clinical success and microbiologic cure. Results The mean age of patients in both groups was comparable, and there were no noteworthy gender differences. Additionally, the distribution of infection types and the isolated pathogens showed no substantial distinctions between the two groups. The study revealed no statistically significant disparities in 14-day mortality, improvement in Sequential Organ Failure Assessment (SOFA) score, or the proportion of patients who were cured and survived between the two treatment groups. Conclusion The findings from this study lead to the conclusion that there exists no significant disparity in the efficacy of colistin monotherapy compared to the combination of colistin with meropenem in the treatment of MDR bacteremia stemming from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). The results provide a basis for future research and underscore the significance of ongoing endeavors to refine antibiotic treatment strategies in response to the worldwide issue of antibiotic resistance.

Management of the human hair follicle microbiome by a synthetic odorant

BackgroundHuman scalp hair follicles (HFs) engage in olfactory receptor (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® up-regulated HF antimicrobial peptide expression of dermcidin (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands. ObjectivesTo understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner. MethodsDCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this treatment affected the HF microbiome. ResultsSynthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs ex vivo. Combined antibiotic and odorant treatment, during an ex vivo dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured Staphylococcus epidermidis and Malassezia restricta over S. aureus and M. globosa, while exhibiting antimicrobial activity against Cutibacterium acnes. These effects were reversed by co-administration of Phenirat®. ConclusionsWe provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases.

Воздействие бовгиалуронидазы азоксимера на бактериальные биопленки в эякуляте пациентов с хроническим простатитом.

Introduction. The use of molecular biological methods in the analysis of bacterial diversity (metataxonomics) of prostate secretion and ejaculate to assess the male microbiota made it possible to identify the bacterial diversity of the microbiota in chronic prostatitis. At the same time, many strains of uropathogens identified in chronic prostatitis show the ability to form biofilms, while there are no generally accepted methods for treating infections caused by bacterial biofilms. Purpose of the study. To study the effect of bovhyaluronidase azoximer in chronic prostatitis, which may be due to the enzymatic action of hyaluronidase on the matrix of bacterial biofilms, which increases the bioavailability of antibiotics, leading to the transition of bacteria into a planktonic state. Material and methods. An electron microscopic study of the ejaculate of 42 patients with chronic prostatitis was performed, of which 32 randomly selected patients received combined antibiotic treatment (4-6 weeks) together with bovhyaluronidase azoxymer (12 weeks) (group I), 10 patients received only antibiotic therapy according to clinical guidelines (group II). On ultrathin sections, the number of bacterial microcolonies and neutrophilic leukocytes per 100 spermatozoa was counted. Results. In the semen of 30 patients, bacterial biofilms with a characteristic morphology were detected: the presence of heterogeneous microorganisms in one microcolony and the presence of a fibrous matrix in which bacteria are immersed. After therapy, in group I, a decrease in the number of bacterial microcolonies, the disappearance of the extracellular matrix, and isolated single bacteria (planktonic state) were detected, in some cases, damage to the bacterial cell wall was detected. In group II quantitative changes in the content of microcolonies and neutrophilic leukocytes were also revealed, however, the morphology of microcolonies in group II did not change. Conclusions. electron microscopy in the study of the ejaculate of patients with chronic prostatitis allows us to reveal the features of the structure of bacterial biofilms. In combined antibiotic therapy together with bovhyaluronidase azoxymer, the biofilm matrix changes and the bacteria transform into a planktonic form.

Antibiotics use patterns in end-of-life cancer patients and medical staff's perception of antimicrobial stewardship programs.

While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff's perceptions of antibiotics in cancer patients with EOL. Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient's right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

Mutators can drive the evolution of multi-resistance to antibiotics.

Antibiotic combination therapies are an approach used to counter the evolution of resistance; their purported benefit is they can stop the successive emergence of independent resistance mutations in the same genome. Here, we show that bacterial populations with 'mutators', organisms with defects in DNA repair, readily evolve resistance to combination antibiotic treatment when there is a delay in reaching inhibitory concentrations of antibiotic-under conditions where purely wild-type populations cannot. In populations of Escherichia coli subjected to combination treatment, we detected a diverse array of acquired mutations, including multiple alleles in the canonical targets of resistance for the two drugs, as well as mutations in multi-drug efflux pumps and genes involved in DNA replication and repair. Unexpectedly, mutators not only allowed multi-resistance to evolve under combination treatment where it was favoured, but also under single-drug treatments. Using simulations, we show that the increase in mutation rate of the two canonical resistance targets is sufficient to permit multi-resistance evolution in both single-drug and combination treatments. Under both conditions, the mutator allele swept to fixation through hitch-hiking with single-drug resistance, enabling subsequent resistance mutations to emerge. Ultimately, our results suggest that mutators may hinder the utility of combination therapy when mutators are present. Additionally, by raising the rates of genetic mutation, selection for multi-resistance may have the unwanted side-effect of increasing the potential to evolve resistance to future antibiotic treatments.

Multiple heteroresistance to tigecycline and colistin in Acinetobacter baumannii isolates and its implications for combined antibiotic treatment

BackgroundWe investigated the presence of heteroresistance against both tigecycline and colistin in Acinetobacter baumannii and then evaluated the effectiveness of combined antibiotic treatment given the existence of discrete tigecycline- and colistin-resistant subpopulations.MethodsWe performed population analysis profiling (PAP) to evaluate the degree of composite heteroresistance in A. baumannii isolates, with the extent of this resistance quantified using subsequent antibiotic susceptibility testing. We then evaluated the amino acid sequence of PmrBAC and the relative mRNA expression levels of pmrB. Finally, we investigated the combined antibiotic efficacy of tigecycline and colistin in multiple-heteroresistant isolates using dual PAP and in vitro time-killing assays.ResultsAll tigecycline-heteroresistant A. baumannii isolates, with the exception of one colistin-resistant isolate, were also heteroresistant to colistin. Evaluations of the colistin-resistant subpopulations revealed amino acid alterations in PmrA and PmrB and increased expression of pmrB. All tigecycline-resistant subpopulations were susceptible to colistin, and all colistin-resistant subpopulations were susceptible to tigecycline. Dual PAP analysis using tigecycline and colistin showed no heteroresistance, and in vitro time-killing assays revealed that a combination of these two antibiotics effectively eliminated the bacterial cells.ConclusionOur results suggest that multiple heteroresistance to tigecycline and colistin is highly prevalent among A. baumannii clinical isolates and that these resistant subpopulations exist independently in single multiple heteroresistant isolates. Therefore, our findings may explain the success of combined antibiotic therapies in these infections.

Antibiotic prescription patterns during last days of hospitalized patients with advanced cancer: the role of palliative care consultation.

Issues regarding antibiotic use in end-of-life patients with advanced cancer present a challenging ethical dilemma in academic referral centres. This study aimed to investigate the role of palliative care consultation on antibiotic prescription patterns among hospitalized patients with advanced cancer during their last days of life. This retrospective cohort study included adult patients with metastatic solid cancer admitted to a tertiary referral hospital for at least 4 days and subsequently died and who were given antibiotics 4 days before death between January 2018 and December 2021. Patients were divided into palliative care consultation (PC) and non-consultation (non-PC) groups. The outcomes were the proportion of patients who received antibiotic combination treatment, antibiotic escalation and antibiotic de-escalation within 3 days of death. Propensity score analysis with the inverse probability of the treatment weighting method was used to compare the outcomes. Among the 1177 patients enrolled, 476 (40.4%) received palliative care consultation and 701 (59.6%) did not. The PC group received considerably less antibiotic combination treatment (49.0% versus 61.1%, adjusted OR: 0.69, 95% CI: 0.53-0.90, P = 0.006) and antibiotic escalation (15.8% versus 34.8%, adjusted OR: 0.41, 95% CI: 0.30-0.57, P < 0.001) than the non-PC group. Additionally, the PC group reported significantly higher antibiotic de-escalation (30.7% versus 17.4%, adjusted OR: 1.74, 95% CI: 1.28-2.36, P < 0.001). Receiving palliative care consultation may minimize aggressive antibiotic prescription patterns in the last days of patients with advanced cancer in an academic referral centre setting.

Assessment of CD200R Activation in Combination with Doxycycline in a Model of Melioidosis.

Antimicrobial resistance continues to be a global issue. Pathogens, such as Burkholderia pseudomallei, have evolved mechanisms to efflux certain antibiotics and manipulate the host response. New treatment strategies are therefore required, such as a layered defense approach. Here, we demonstrate, using biosafety level 2 (BSL-2) and BSL-3 in vivo murine models, that combining the antibiotic doxycycline with an immunomodulatory drug that targets the CD200 axis is superior to antibiotic treatment in combination with an isotype control. CD200-Fc treatment alone significantly reduces bacterial burden in lung tissue in both the BSL-2 and BSL-3 models. When CD200-Fc treatment is combined with doxycycline to treat the acute BSL-3 model of melioidosis, there is a 50% increase in survival compared with relevant controls. This benefit is not due to increasing the area under the concentration-time curve (AUC) of the antibiotic, suggesting the immunomodulatory nature of CD200-Fc treatment is playing an important role by potentially controlling the overactive immune response seen with many lethal bacterial infections. IMPORTANCE Traditional treatments for infectious disease have focused on the use of antimicrobial compounds (e.g. antibiotics) that target the infecting organism. However, timely diagnosis and administration of antibiotics remain crucial to ensure efficacy of these treatments especially for the highly virulent biothreat organisms. The need for early antibiotic treatment, combined with the increasing emergence of antibiotic resistant bacteria, means that new therapeutic strategies are required for organisms that cause rapid, acute infections. Here, we show that a layered defense approach, where an immunomodulatory compound is combined with an antibiotic, is better than an antibiotic combined with a relevant isotype control following infection with the biothreat agent Burkholderia pseudomallei. This approach has the potential to be truly broad spectrum and since the strategy includes manipulation of the host response it's application could be used in the treatment of a wide range of diseases.

Synthesis and Characterization of Nitric Oxide-Releasing Ampicillin as a Potential Strategy for Combatting Bacterial Biofilm Formation

Biofilm formation on biomaterial interfaces and the development of antibiotic-resistant bacteria have decreased the effectiveness of traditional antibiotic treatment of infections. In this project, ampicillin, a commonly used antibiotic, was conjugated with S-nitroso-N-acetylpenicillamine (SNAP), an S-nitrosothiol compound (RSNO) used for controlled nitric oxide (NO) release. This novel multifunctional molecule is the first of its kind to provide combined antibiotic and NO treatment of infectious pathogens. Characterization of the molecule included NMR, FTIR, and mass spectrometry. NO release behavior was also measured and compared to pure, unmodified SNAP. When evaluating the antimicrobial efficacy, the synthesized SNAPicillin molecule showed the lowest MIC value against Gram-negative Pseudomonas aeruginosa and Gram-positive methicillin-resistant Staphylococcus aureus compared to ampicillin and SNAP alone. SNAPicillin also displayed enhanced biofilm dispersal and killing of both bacterial strains when treating a 48 h biofilm preformed on a polymer surface. The antibacterial results combined with the biocompatibility of the molecule show great promise for infection prevention and treatment of polymeric interfaces to reduce medical device-related infections.

Efficacy of Vascularized Submental Lymph Node Transfer with Decongestive Therapy and Antibiotics for Early-Stage Lower Limb Filarial Lymphedema.

Filarial lymphedema (FLE) is the most common cause of secondary lymphedema, with endemic prevalence in developing countries. FLE traditionally has been managed with antibiotics and decongestive therapy (DCT) in the early stage or excisional surgery at the late stage. Results of vascularized lymph node transfer (VLNT) in postoncologic lymphedema have been encouraging, and VLNT is a widely accepted surgical treatment. The authors advocate that the combined treatment of antibiotics, DCT, and vascularized submental lymph node (VSLN) transfer could produce objective and subjective improvement of early-stage lower limb FLE. Between January of 2019 and January of 2020, patients with early-stage lower-limb FLE who underwent VLNT were retrospectively reviewed. VLNT was harvested from the submental region in all patients. Outcomes were assessed using volume improvement, frequency of cellulitis, and lymphoscintigraphy, along with subjective scoring questionnaire. Three men and one woman with an average age of 27 years (range, 25 to 29 years) were included. Two patients presented bilateral lymphedema. One patient was lost at 3-month follow-up and not included in the analysis. Patients showed an initial decrease in circumferential measurements after antibiotics and DCT of 2074 ± 471 cc (39% ± 9%). At a mean follow-up of 12.3 ± 6.2 months, further improvement of limb volume of 2389 ± 576 cc (45% ± 10%) was achieved following VSLN transfer. Lymphoscintigraphy demonstrated dye uptake by the VLNT with reduced dermal backflow and none of the patients had episodes of postoperative cellulitis. Patients reported excellent outcome on subjective scoring (average score, 9 ± 1) and returned to their daily activities without wearing compression garments. The authors' early experience showed that VSLN transfer may represent an effective treatment option in the multimodal approach to early-stage lower limb FLE.

Ocular microbiota promotes pathological angiogenesis and inflammation in sterile injury-driven corneal neovascularization

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b+Ly6C+ and CD11b+Ly6G+ myeloid cells, not Foxp3+ regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation.

Granulicatella elegans infective endocarditis: A case report

Granulicatella elegans is a rare cause of infective endocarditis, accounting for 1–2% of all cases. It is well recognized that this pathogen can present in association with negative blood cultures. There are higher rates of both relapse and mortality compared with endocarditis caused by other bacteria. Microbiological diagnosis can be especially challenging because many conventional blood culture media lack pyridoxal, which can be found in automated blood culture broths like BACTEC™ or BACT/ALERT® and thus they may require ‘helper’ bacteria to be culture the organism. This current case report describes a 66-year-old male patient with a 10-year history of post-inflammatory combined aortic valve disease (moderate aortic stenosis and mild aortic regurgitation). He presented with a 3-month history of recurrent fever and general deterioration. Despite targeted, prolonged, combined antibiotic treatment with intravenous penicillin and gentamicin, surgery was eventually required. An aortic prosthetic valve implantation was performed with good results. In case of subacute endocarditis, especially when a causative organism proves difficult to detect, G. elegans should be considered. Identification is greatly enhanced by using polymerase chain reaction methods and this test should be considered in all cases of culture negative endocarditis.

Impact of disturbance and dietary shift on gastrointestinal bacterial community and its invertebrate host system.

The gut microbiome is one of the most important sites of host-microbe interactions, however, mechanisms governing the responses of host-associated microbes to changing environmental conditions are poorly understood. To address this, we investigated individual and combined effects of dietary changes and increase in salinity (from freshwater to salinity 3) or antibiotic concentration on the gastrointestinal bacterial community of the aquatic snail Ampullaceana balthica. In parallel, the energy reserves of the host were quantified. A change of natural food source to biofilm forming green algae Scenedesmus obliquus as well as the combined treatment of salinity and S. obliquus decreased the richness and changed the composition of the A. balthica gastrointestinal bacterial community. In these treatments Pseudomonas became the dominant bacterium. However, energy reserves of the host were higher in these treatments compared to the reference aquaria specimens and the combined treatment of antibiotics with S. obliquus. The presence of antibiotics inhibited the dominance of Pseudomonas and resulted in lower energy reserves despite S. obliquus feeding. Therefore the host seems to be able to adapt and replace its bacterial community composition to respond to mild changes in salinity and food source. Antibiotics in the water can disturb this self-regulating mechanism. Our study underlines the ability of aquatic macroinvertebrates to respond to sudden changes in food source and mild shifts in salinity. Moreover, it emphasizes the strong impact of the food source on the gastrointestinal microbiome and the importance of generalists during disturbance.

ATP Bioluminescence Assay To Evaluate Antibiotic Combinations against Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa.

ABSTRACTTime-kill curves are used to study antibiotic combinations, but the colony count method to obtain the results is time-consuming. The aim of the study was to validate an ATP assay as an alternative to the conventional colony count method in studies of antibiotic combinations. The cutoff point for synergy and bactericidal effect to categorize the results using this alternative method were determined in Pseudomonas aeruginosa. The ATP assay was performed using the GloMax 96 microplate luminometer (Promega), which measures bioluminescence in relative light units (RLU). To standardize this assay, background, linearity, and the detection limit were determined with one strain each of multidrug-resistant P. aeruginosa and Klebsiella pneumoniae. Twenty-four-hour time-kill curves were performed in parallel by both methods with 12 strains of P. aeruginosa. The conventional method was used as a “gold” standard to establish the pharmacodynamic cutoff points in the ATP method. Normal saline solution was established as washing/dilution medium. RLU signal correlated with CFU when the assay was performed within the linear range. The categorization of the pharmacodynamic parameters using the ATP assay was equivalent to that of the colony count method. The bactericidal effect and synergy cutoff points were 1.348 (93% sensitivity, 81% specificity) and 1.065 (95% sensitivity, 89% specificity) log RLU/mL, respectively. The ATP assay was useful to determine the effectiveness of antibiotic combinations in time-kill curves. This method, less laborious and faster than the colony count method, could be implemented in the clinical laboratory workflow.IMPORTANCE Combining antibiotics is one of the few strategies available to overcome infections caused by multidrug-resistant bacteria. Time-kill curves are usually performed to evaluate antibiotic combinations, but obtaining results is too laborious to be routinely performed in a clinical laboratory. Our results support the utility of an ATP measurement assay using bioluminescence to determine the effectiveness of antibiotic combinations in time-kill curves. This method may be implemented in the clinical laboratory workflow as it is less laborious and faster than the conventional colony count method. Shortening the obtention of results to 24 h would also allow an earlier guided combined antibiotic treatment.

Impact of adopting non-antibiotic dry-cow therapy on the performance and udder health of dairy cows.

On dairy farms, the prophylactic use of antibiotics at drying-off is being increasingly challenged. The objective of this study was to examine the effect of antibiotic dry-cow therapy (DCT) or non-antibiotic DCT on dairy cow performance and udder health. Holstein cows (n=285) with low risk of intramammary infection (<200,000cells/ml) were assigned to one of two treatments, either antibiotic DCT (A+TS; antibiotic treatment in combination with internal and external teat sealants) or non-antibiotic DCT (TS; internal and external teat sealant only). There was no statistically significant (p>0.05) difference between treatments for mean cow milk yield, composition or energy corrected milk yield. Mean somatic cell count was 0.16 loge higher in the TS treatment (95% confidence interval [CI]: -0.00 loge to -0.33 loge ) compared to A+TS treatment (p = 0.047). A 50% increase in the number of mastitis cases was observed in the A+TS treatment compared to TS treatment (odds ratio=1.5, 95% CI: 0.80%-3.01%), although this was not significant. There was no statistical evidence (p>0.05) that treatment had any effect on colostrum quality and composition. Results indicate that non-antibiotic DCT can be adopted in 'low-risk' cows who were offered grass silage-based diets in cubicle accommodation, with low risk of adverse effects on performance or udder health.

Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study.

ObjectivesTo assess efficacy and safety of the combined treatment of antibiotics (3rd-generation cephalosporin and azithromycin) and antiviral agents (lopinavir/ritonavir or hydroxychloroquine) on moderate COVID-19 patients in South Korea.MethodsA retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 299 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were used to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with either CA/LoP (cephalosporin, azithromycin, and lopinavir/ritonavir) (n = 57), CA/HQ (cephalosporin, azithromycin, and hydroxychloroquine) (n = 25) or standard supportive care (n = 217). We analyzed the association between treatment group and standard supportive group in terms of three endpoints: time to symptom resolution, time to viral clearance, and hospital stay duration. Using propensity-score matching analysis, three rounds of propensity-matching analysis were performed to balance baseline characteristics among three cohorts.ResultsKaplan-Meier curves fitted using propensity score-matched data revealed no significant differences on time to symptom resolution, time to viral clearance, hospital stay duration among the three treatment arms (CA/LoP vs Standard, log-rank p-value = 0.2, 0.58, and 0.74 respectively for the three endpoints) (CA/HQ vs Standard, log-rank p-value = 0.46, 0.99, and 0.75 respectively). Similarly, Cox regression analysis on matched cohorts of CA/LoP and standard supportive group showed that hazard ratios of time to symptom resolution (HR: 1.447 [95%-CI: 0.813–2.577]), time to viral clearance(HR: 0.861, [95%-CI: 0.485–1.527]), and hospital stay duration (HR: 0.902, [95%-CI: 0.510–1.595]) were not significant. For CA/HQ and standard supportive group, hazard ratios of the three endpoints all showed no statistical significance (HR: 1.331 [95%-CI:0.631–2.809], 1.005 [95%-CI:0.480–2.105], and 0.887, [95%-CI:0.422–1.862] respectively). No severe adverse event or death was observed in all groups.ConclusionsCombined treatment of 3rd cephalosporin, azithromycin and either low-dose lopinavir/ritonavir or hydroxychloroquine was not associated with better clinical outcomes in terms of time to symptom resolution, time to viral clearance, and hospital stay duration compared to standard supportive treatment alone. Microbiological evidence should be closely monitored when treating SARS-CoV-2 patients with antibiotics to prevent indiscreet administration of empirical antimicrobial treatments.

The gut microbiome contributes to splenomegaly and tissue inflammation in a murine model of primary biliary cholangitis

BackgroundSplenomegaly is not just a consequence of numerous chronic and acute conditions but may also contribute to their severity, due to the interaction of the spleen with the gut microbiome. This study aimed to explore the effect of the gut microbiome on splenomegaly.MethodsWe used p40−/−IL-2Rα−/− mice as a murine model of primary biliary cholangitis (PBC) as per our previous study. Splenomegaly was evaluated by spleen weight. Severity of liver inflammation was evaluated by hepatic mononuclear cell (MNCs) number and pathological score. Changes of immune cells in the spleen and liver were detected by flow cytometry. The effects of the gut microbiome on splenomegaly and liver inflammation were observed by combined antibiotic treatment in p40−/−IL-2Rα−/− mice.ResultsA proportion of p40−/−IL-2Rα−/− mice developed splenomegaly. The results revealed that liver mononuclear cells infiltration, histological scores of hepatic inflammation, and bile duct damage were positively correlated with the degree of splenomegaly. Hepatic CD4+ and CD8+ T cells numbers were significantly higher in mice with splenomegaly, and this was particularly observed in activated effector memory CD4+ T and CD8+ T cells. A proportion of some other immune cells including granulocytes, B, natural killer (NK), and CD8+ T effector memory cells were also altered in the enlarged spleen. More importantly, administration of quadruple antibiotics to deplete gut microbiota relieved the splenomegaly of p40−/−IL-2Rα−/− mice, significantly alleviated liver inflammation, and caused a significant reduction of liver and spleen T cell accumulation and activation; however, single antibiotics did not induce these changes.ConclusionsSplenomegaly was associated with more severe liver inflammation in our PBC murine model, and this effect was reversed by quadruple antibiotic treatment.

Synergistic efficacy of meropenem, ciprofloxacin and colistin antibiotics against planktonic and biofilm forms of Myroides odoratimimus bacterial isolates

PurposeIn this study, it was aimed to investigate the combined synergistic efficacy of colistin (CT), meropenem (MEM), and ciprofloxacin (CIP) antibiotics on planktonic and biofilm forms in Myroidesodoratimimus strains isolated from various clinical specimens. MethodsAntibiotic susceptibility was determined by the Kirby-Bauer disk diffusion method. In addition, minimum inhibitory concentrations (MIC) of CIP, MEM, and CT were studied using the standardized broth microdilution method. In vitro synergistic activity of antibiotics against M. odoratimimus planktonic bacteria strains was studied by the Micro Broth Checkerboard method. The microtiter plate (MtP) method was used to determine the effectiveness of antibiotics on M. odoratimimus biofilm formation. ResultsA zone of inhibition was not observed against other antibiotics used except amikacin and linezolid in all strains. While CT/MEM and CT/CIP combinations have a synergistic effect on all strains, the combination CIP/MEM has an additive effect. According to the biofilm inhibition results, all three antibiotics inhibited biofilm formation. However, the efficacy of MEM (60.3–76.5%) and CIP (60.2–77.8%) was approximately two times higher than that of CT (25.4–34.5%). In addition, the effectiveness of combinations of antibiotics on biofilm formation was examined and the percentage of inhibition was 30.8% when CT was used alone, while the biofilm inhibition rates of CT/MEM and CT/CIP were 92.4% and 91.7%, respectively. MEM/CIP combination was inhibited biofilm formation by 75.7%. ConclusionsThis study is the first report showing the efficacy of CT, MEM and CIP antibiotics, which are frequently used in clinical practice, in combination on M. odoratimimus planktonic and biofilm forms. The findings of our study are particularly guiding for combined antibiotic treatment options in immunosuppressed patients admitted to an intensive care unit (ICU). The CT/MEM combination is currently used frequently. In addition, these results are important in terms of supporting in vitro that CT/CIP and MEM/CIP combinations can also be used as a treatment option in M. odoratimimus related infections.

Surgical Treatment of Nontuberculous Mycobacterial Pulmonary Disease and a Combination of Nontuberculous Mycobacterium Pulmonary Disease and Pulmonary Tuberculosis

ObjectivesNontuberculous mycobacterial pulmonary disease (NTMPD) is an important health system problem worldwide. Surgical treatment experience is limited, and the safety of such operations is still unclarified. Therefore, improving our knowledge of NTMPD is important. DesignIn this retrospective observational study, we analyzed the medical records of 2,432 patients operated on from January 2011 through December 2017 in our hospital. There were 20 patients with NTMPD in group 1 and 23 patients with combined NTMPD and pulmonary tuberculosis in group 2. Patients received antibiotic treatment before and after surgery as per Russian Federal clinical guidelines and individual drug susceptibility. ResultsPostoperative complications occurred in 2 (10%) cases in group 1 and 4 (17.4%) in group 2, and intraoperative complications occurred in 2 (8.7%) cases in group 2. There was no 30-day mortality in both groups. After 1 year, all 40 traced patients had neither bacterial excretion nor cavities in the lungs. After 3 years and 5 years, the efficacy among 32 and 13 traced patients was 100%, respectively. ConclusionsModern surgery for small NTMPD forms is safe - helping improve outcomes for ineffective antibiotic treatment. Combined surgery and antibiotic treatment are acceptable in both the short and long term.