Short-Term Exposure to Ambient Air Pollution and Antimicrobial Use for Acute Respiratory Symptoms.

Importance: Ambient air pollution and antimicrobial resistance pose significant global public health challenges. It is not known whether ambient air pollution is associated with increased consumption of antimicrobials. Objective: To assess whether a short-term association exists between ambient air pollution levels and antimicrobial consumption among the general population seeking primary care consultations for acute respiratory symptoms. Design, Setting, and Participants: This 2-stage cross-sectional ecological time series analysis study using data on daily ambient air pollution and antimicrobial consumption was conducted in the 11 largest cities in Catalonia, Spain, from June 23, 2012, to December 31, 2019, among all inhabitants aged 12 years or older. Statistical analysis was performed from November 2022 to December 2023. Exposures: Daily ambient air pollution (particulate matter of 10 µg/m3 [PM10], particulate matter of 2.5 µg/m3 [PM2.5], and nitrogen dioxide [NO2]). Main Outcomes and Measures: The main outcome was antimicrobial consumption associated with primary care consultations for acute respiratory symptoms in the 30 days before and after the dispensing of the antimicrobial. Antimicrobial consumption was measured as defined daily doses (DDDs) per 1000 inhabitants per day. Results: Among 1 938 333 inhabitants (median age, 48 years [IQR, 34-65 years]; 55% female participants), there were 8 421 404 antimicrobial dispensations, with a median of 12.26 DDDs per 1000 inhabitants per day (IQR, 6.03-15.32 DDDs per 1000 inhabitants per day). The median adjusted morbidity score was 2.0 (IQR, 1.0-5.0). For the 1 924 814 antimicrobial dispensations associated with primary care consultations for acute respiratory symptoms, there was a significant correlation between increases of 10 µg/m3 in the concentration of the 3 pollutants studied and heightened antimicrobial consumption at day 0 (PM10: relative risk [RR], 1.01 [95% CI, 1.01-1.02]; PM2.5: RR, 1.03 [95% CI, 1.01-1.04]; NO2: RR, 1.04 [95% CI, 1.03-1.05]). A delayed association emerged between increases in PM2.5 concentration and antimicrobial consumption between day 7 (RR, 1.00 [95% CI, 1.00-1.01]) and day 10 (RR, 1.00 [95% CI, 1.00-1.01]) after exposure. Conclusions and Relevance: In this 2-stage cross-sectional study using ecological time series analysis, short-term exposure to air pollution was associated with increased antimicrobial use associated with primary care consultations for acute respiratory symptoms in the general population. This finding could contribute to informing policy decisions aimed at reducing air pollution and its associated risks, thereby promoting respiratory health and reducing antimicrobial use.

Observational, retrospective real-world evidence study demonstrates safety, performance and usefulness of antimicrobial central venous catheters.

OBJECTIVE: To collect real-world data to demonstrate the safety and performance of Arrowg+ard Blue® /Arrowg+ard Blue Plus® (AGB/AGB+) central venous catheters (CVCs). METHODS: This observational, retrospective study involved patients who required AGB/AGB+ CVCs at designated general hospitals in USA (22), UK (19) and Germany (2). Data were extracted from electronic medical records. There were no specific inclusion/exclusion criteria. Primary endpoint was successful treatment without an adverse event (AE). Secondary endpoint was rate of AEs. RESULTS: In total, 384 cases were included from 43 centres and most patients (74%) were >35 years of age. A success rate of 99%, and an overall AE rate of 0.8% were observed. Moreover, the overall infection rate was lower than typically reported for standard catheters. In addition, power injection of contrast media was successful in all 51 cases. CONCLUSIONS: This study indicates the AGB/AGB+ CVCs perform as intended with a high success rate and few AEs. Further large-scale, controlled studies are required to confirm our findings.

Metronidazole-induced encephalopathy in a patient with spondylodiscitis.

INTRODUCTION: Metronidazole-induced encephalopathy is an uncommon but potentially severe complication of metronidazole treatment. Although the exact pathophysiology remains elusive, proposed hypotheses include RNA binding, neurotoxicity from free radicals, and modulation of neurotransmitter receptors. Most cases demonstrate improvement upon discontinuation of metronidazole, highlighting the importance of early recognition. Magnetic resonance imaging plays a critical role in diagnosing metronidazole-induced encephalopathy, with characteristic imaging findings frequently observed in the dentate nuclei and corpus callosum. CASE SUMMARY: A 63-year-old man treated with metronidazole for lumbar spondylodiscitis developed neurological symptoms consistent with metronidazole-induced encephalopathy. IMAGES: Magnetic resonance imaging revealed characteristic bilateral hyperintense lesions in the cerebellar dentate nuclei, corpus callosum, and brainstem. Prompt recognition and discontinuation of metronidazole led to symptom resolution. CONCLUSION: This case underscores the importance of clinicians and radiologists being aware of this condition and emphasizes the pivotal role of magnetic resonance imagining in establishing the diagnosis.

Safety and efficacy of outpatient parenteral antimicrobial therapy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy. METHODS: We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy. We included studies without restrictions on language or publication year. Eligibility was reviewed independently by two assessors, and data extraction was cross validated. We evaluated bias risk via the Cochrane tool and determined the evidence certainty using GRADE. Meta-analysis was conducted using a random effects model. The protocol of this review was registered on PROSPERO (CRD42023460389). RESULT: Thirteen RCTs, involving 1,310 participants were included. We found no difference in mortality (Risk Ratio [RR] 0.54, 95% Confidence Interval [CI] 0.23 to 1.26; P = 0.93), treatment failure (RR 1.0, CI 0.59 to 1.72; P = 0.99), adverse reaction related to antimicrobials (RR 0.89, CI 0.69 to 1.15; P = 0.38), and administration device (RR 0.58, CI 0.17 to 1.98; P = 0.87) between outpatient and inpatient parenteral antimicrobial therapy. The overall body of evidence had a low level of certainty. CONCLUSION: Existing evidence suggests OPAT is a safe and effective alternative to inpatient treatment. Further RCTs are warranted for a thorough comparison of inpatient and outpatient parenteral antimicrobial therapy with a high level of certainty.

Moderate and serious adverse reactions to antimicrobials among hospitalized children: A systematic review.

AIMS: This systematic review aimed to investigate the occurrence of moderate and severe adverse drug reactions (ADRs) to antimicrobials among hospitalized children. METHODS: The PubMed/Medline, Cochrane Library, Embase, Web of Science, Scopus, Lilacs and CINAHL databases were searched in April 2023 to systematically review the published data describing the characteristics of moderate and severe ADRs to antimicrobials among hospitalized children. The search was carried out without date restrictions, up to the search date (April, 2023). RESULTS: At the end of the selection process, 30 articles met the inclusion criteria. Cutaneous reactions were the primary serious clinical manifestations in most articles (19/30), followed by erythema multiforme (71 cases), Stevens-Johnson syndrome (72 cases), and toxic epidermal necrolysis (22 cases). The main antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the primary outcomes, 30% (9/30) of the articles reported deaths, and 46.7% (14/30) of studies reported increased lengths of hospital stay, need for intensive care, and transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication substitution or prescription of specific medications for the symptomatology. CONCLUSIONS: The findings of this review could be used to identify areas for improvement and help health professionals and policymakers develop strategies. In addition, we emphasize the importance of knowing about ADRs so that there is adequate management to avoid undesirable consequences.

When Should Patients at the End of Life Get Antimicrobials?

Although antimicrobial medications are commonly prescribed to patients at the end of life (EOL), clinicians might not discuss the benefits and harms of antimicrobials with their patients in the advance care planning process. This commentary on a case discusses challenges and strategies in antimicrobial decision making for patients at the EOL. As antimicrobial use can harm some patients, and as antimicrobial resistance remains an urgent public health issue, this article advocates for ethical reasoning to guide antimicrobial decision making for patients at the EOL.

Quantitative and qualitative evaluation of antimicrobial usage: the first step for antimicrobial stewardship.

The identification of antimicrobial use patterns is essential for determining key targets for antimicrobial stewardship interventions and evaluating the effectiveness thereof. Accurately identifying antimicrobial use patterns requires quantitative evaluation, which focuses on measuring the quantity and frequency of antimicrobial use, and qualitative evaluation, which assesses the appropriateness, effectiveness, and potential side effects of antimicrobial prescriptions. This paper summarizes the quantitative and qualitative methods used to evaluate antimicrobials, drawing insights from overseas and domestic cases.

Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double-blind, placebo-controlled trial.

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study.

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Pharmacogenomics and adverse effects of anti-infective drugs in children.

Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.

Caracterização de cubossomos não-iônicos em presença de proteínas modelo: uma abordagem estrutural e funcional / Characterization of non-ionic cubosomes in the presence of model pro­teins: a structural and functional approach

Uma área de pesquisa que vem ganhando muita atenção nos últimos anos é a nanome­dicina, com especial atenção para os sistemas com entrega controlada de fármacos, ou drug delivery. Dentre as diversas nanopartículas utilizadas para este fim, destacam-se os sistemas formados por lipídeos e polímeros, como por exemplo os lipossomos e os cubossomos. Neste trabalho, é estudada a influência estrutural da lisozima e da curcumina, proteínas modelo. A lisozima é uma enzima antimicrobiana produzida por animais e que faz parte do sistema imunológico. Ela é uma hidrolase glicosídica que catalisa a hidrólise dos componentes da parede celular de bactérias gram-positivas. Esta hidrólise, por sua vez, compromete a integridade das paredes celulares, causando a lise (e como consequência a morte) das bactérias. Curcumina é um composto cristalino de cor amarelada brilhante, encontrada no caule da Curcuma longa (ou açafrão), que tem sido utilizada como corante ou até mesmo como aditivo alimentar. Este composto tem sido uma grande aposta no tratamento de doenças crônicas como inflamação, artrite, síndrome metabólica, doença hepática, obesidade, doenças neurodegenerativas e principalmente canceres, sendo também utilizada em estudos como potencial agente antibacteriano. O principal objetivo deste trabalho é construir sistemas nanoestruturados com potencial de atuarem como sistemas antimicrobianos, com a liberação controlada de ambos dos fármacos. Estes sistemas são compostos por cubossomos de fitantriol (PHY) em ausência e presença da lisozima, da curcumina e de suas combinações, a fim de analisar ação antimicrobiana conjunta da lisozima e da curcumina. As técnicas biofísicas utilizadas para caracterizar essas partículas são SAXS (espalhamento de raios-X em baixos ângulos), DLS (espalhamento dinâmico de luz), Cryo-TEM (criomicroscopia eletrônica de transmissão) e NTA (análise de rastreamento de nanopartículas). Foi possível verificar que as formulações lipídicas são eficazes na formação de estruturas cúbicas com estabilidade desejável. As nanopartículas cúbicas demonstraram alta capacidade de encapsulação da lisozima e da curcumina. A cinética de liberação desses medicamentos mostrou-se promissora, sugerindo que a encapsulação dos fármacos é eficaz, bem como a liberação controlada e direcionada. Duas linhagens de bactérias foram estudadas, sendo que a E. coli, não sofreu nenhum dano citotóxico, enquanto a Bacillus subtilis sim. Tal resultado indica o potencial antimicrobiano do sistema para alguns tipos de bactérias

An area of research that has gained significant attention in recent years is nanomedicine, with a particular focus on drug delivery systems. Among the various nanoparticles used for this purpose, lipid and polymer-based systems, such as liposomes and cubosomes stand out. This study investigate the structural influence of encapsulating lysozyme and curcumin, model compounds. Lysozyme is an antimicrobial enzyme produced by animals and is part of the immune system. It is a glycosidic hydrolase that catalyzes the hydrolysis of components in the cell walls of gram-positive bacteria. This hydrolysis compromises the integrity of cell walls, leading to the lysis (and consequently the death) of bacteria. Curcumin is a bright yellow crystalline compound found in the stem of Curcuma longa (or turmeric), commonly used as a dye or even as a food additive. It has been a significant focus in the treatment of chronic diseases such as inflammation, arthritis, metabolic syndrome, liver disease, obesity, neurodegenerative diseases, and especially cancers. It is also studied as a potential antibacterial agent. The main objective of this study is to construct nanostructured systems with the potential to act as antimicrobial agents, with controlled release of both drugs. These systems consist of phytantriol (PHY) cubosomes in the absence and presence of lysozyme, curcumin, and their combinations to analyze the joint antimicrobial action of lysozyme and curcumin. Biophysical techniques used for characterization include Small-Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS), Cryo-Transmission Electron Microscopy (Cryo-TEM), and Nanoparticle Tracking Analysis (NTA). It was observed that lipid formulations are effective in forming cubic structures with desirable stability. Cubic nanoparticles have demonstrated a high encapsulation capacity for lysozyme and curcumin. The release kinetics of these drugs have shown promise, suggesting that drug encapsulation is effective, as well as their controlled and targeted release. Two bacterial strains were studied, with E. coli showing no cytotoxic damage, while Bacillus subtilis did. This result indicates the antimicrobial potential of the system against types of bacteria

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

The Effects of Antimicrobial Mouthwashes on Systemic Disease: What Is the Evidence?

The potential association between antimicrobial mouthwash use and systemic health has gained attention in recent years with reports highlighting how some common systemic conditions are influenced by the use of different types of mouthwashes. In this context, links between mouthwash use and cardiovascular disease, diabetes mellitus, oral cancer, Alzheimer's disease, and preeclampsia have been proposed, albeit with limited levels of evidence. Chlorhexidine mouthwash in particular has been the most widely studied agent while available data on other types of over-the-counter mouthwashes are generally scarce. Furthermore, there is currently no evidence-based recommendations on the appropriate use of mouthwashes during pregnancy. This article will present the current evidence on the association between mouthwash use and the aforementioned conditions with emphasis on the mechanisms that may underlie such an association.

Use of a taurolidine containing antimicrobial wash to reduce cardiac implantable electronic device infection.

AIMS: TauroPace (Tauropharm, Bavaria Germany), a taurolidine solution for combating cardiac implantable electronic device (CIED) infection, was compared with a historical control of 3% hydrogen peroxide (H2O2) in a prospective observational study. METHODS AND RESULTS: The device pocket was irrigated, and all hardware accessible within (leads, suture sleeves, pulse generator) was wiped with H2O2, TauroPace, or taurolidine in a galenic formulation during any invasive CIED procedure at the study centre. Only CIED procedures covered by TauroPace or H2O2 from 1 January 2017 to 28 February 2022 were included for analysis. Patients who underwent >1 procedure were censored for the last treatment group and reassigned at the next procedure. The primary endpoint was major CIED infection within 3 months. The secondary endpoints were CIED infection beyond 3 months, adverse events potentially related to the antimicrobial solutions, CIED system, procedure, and death, till the end of follow-up. TauroPace covered 654 procedures on 631 patients, and H2O2 covered 551 procedures on 532 patients. The TauroPace group had more patient risk factors for infection than the H2O2 group (P = 0.0058) but similar device and procedure-specific risk factors (P = 0.17). Cardiac implantable electronic device infection occurred in 0/654 (0%) of the TauroPace group and 6/551 (1.1%) of the H2O2 group (P = 0.0075). Death occurred in 23/654 (3.5%) of the TauroPace group and 14/551 (2.5%) of the H2O2 group (P = 0.33). Non-infection related adverse events were rarer in the TauroPace (3.8%) than the H2O2 (6.0%) group (P = 0.0802). CONCLUSION: TauroPace is safe but more effective than H2O2 in reducing CIED infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05576194.

The expert clinical pharmacological advice program for tailoring on real-time antimicrobial therapies with emerging TDM candidates in special populations: how the ugly duckling turned into a swan.

INTRODUCTION: The growing spread of infections caused by multidrug-resistant pathogens makes the need of tailoring antimicrobial therapies by means of a 'patient-centered' approach fundamental. In this scenario, therapeutic drug monitoring (TDM) of emerging antimicrobial candidates may be a valuable approach, but expert interpretation of TDM results should be granted for making them more clinically useful. The MD Clinical Pharmacologist may take over this task since this specialist may couple PK/PD expertise on drugs with a medical background and may provide expert interpretation of TDM results of antimicrobials for tailoring therapy on real-time in each single patient based on specific both drug/pathogen issues and patient issues. AREAS COVERED: This article aims to highlight the main key-points and organizational aspects for implementing a successful TDM-based expert clinical pharmacological advice (ECPA) program for tailoring antimicrobial therapies on real-time in different hospitalized patient special populations. EXPERT OPINION: TDM-based ECPA programs lead by the MD Clinical Pharmacologist may represent a way forward for maximizing clinical efficacy and for minimizing the risk of resistance developments and/or toxicity of antimicrobials. Stakeholders should be aware of the fact that this innovative approach may be cost-effective.

Longitudinal effects of oral administration of antimicrobial drugs on fecal microbiota of horses.

BACKGROUND: Antimicrobial drug-associated diarrhea (AAD) is the most common adverse effect in horses receiving antimicrobials. Little information on how oral administration of antimicrobials alters intestinal microbiota in horses is available. OBJECTIVE: Investigate changes of the fecal microbiota in response to oral administration of antimicrobials. ANIMALS: Twenty healthy horses. METHODS: Prospective, longitudinal study. Horses were randomly assigned to 4 groups comprising 4 horses each: group 1 (metronidazole); group 2 (erythromycin); group 3 (doxycycline); group 4 (sulfadiazine/trimethoprim, SMZ-TMP); and group 5 (control). Antimicrobials were administered for 5 days. Fecal samples were obtained before (day 0) and at 1, 2, 3, 4, 5, 6, and 30 days of the study period. Fecal microbiota was characterized by high throughput sequencing of the V4 region of the 16S rRNA. RESULTS: Horses remained healthy throughout the study. Richness and diversity in doxycycline, erythromycin, and metronidazole, but not SMZ-TMP groups, was significantly lower (P < .05) at multiple time points after administration of antimicrobials compared with samples from day 0. Main changes in the microbiota were observed during the time of antimicrobial administration (day 2-5; weighted and unweighted UniFrac PERMANOVA P < .05). Administration of erythromycin, doxycycline and, to a lesser extent, metronidazole produced a pronounced alteration in the microbiota compared with day 0 samples by decreasing the abundance of Treponema, Fibrobacter, and Lachnospiraceae and increasing Fusobacterium and Escherichia-Shigella. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral administration of antimicrobials alters the intestinal microbiota of healthy horses resembling horses with dysbiosis, potentially resulting in intestinal inflammation and predisposition to diarrhea.

Risk of venous thromboembolism in outpatient parenteral antimicrobial therapy (OPAT): A systematic review and meta-analysis.

The risk of venous thromboembolism (VTE) in outpatient parenteral antimicrobial therapy (OPAT) is not fully understood and the optimal strategy for thromboprophylaxis remains unclear. This systematic review investigated the incidence of VTE in OPAT settings (PROSPERO CRD42022381523). MEDLINE, CINAHL, Emcare, Embase, Cochrane Library and grey literature were searched from earliest records to 18 January 2023. Primary studies reporting non-catheter-related VTE or catheter-related thromboembolism (CRT) events in adults who received parenteral antibiotics in home or outpatient settings were eligible. In total, 43 studies involving 23 432 patient episodes were reviewed, of which 4 studies reported non-catheter-related VTE and 39 included CRT. Based on generalised linear mixed-effects models, pooled risk estimates of non-catheter-related VTE and CRT were 0.2% [95% confidence interval (CI) 0.0-0.7%] and 1.1% [95% CI 0.8-1.5%; prediction interval (PI) 0.2-5.4%]. Heterogeneity was largely attributed to risk of bias by meta-regression (R2 = 21%). Excluding high-risk-of-bias studies, CRT risk was 0.8% (95% CI 0.5-1.2%; PI 0.1-4.5%). From 25 studies, the pooled CRT rate per 1000 catheter-days was 0.37 (95% CI 0.25-0.55; PI 0.08-1.64). These findings do not support universal thromboprophylaxis or routine use of an inpatient VTE risk assessment model in the OPAT setting. However, a high index of suspicion should be maintained, especially for patients with known risk factors for VTE. An optimised protocol of OPAT-specific VTE risk assessment should be sought.