Efficacy and Safety of Adding 6 Weeks of Doxycycline to the Essential Package of Care to Treat Filarial Lymphedema: A Double-Blind, Randomized, Controlled Trial in Southern India.

Finding additional ways to manage lymphedema due to lymphatic filariasis (LF) is a primary concern for the Global Program to Eliminate Lymphatic Filariasis. The WHO-recommended Essential Package of Care (EPC) consists of skin hygiene, elevation of affected limbs, exercise, protective shoe ware, wound care, and supportive therapy for acute phases. The care program has been successful but often hard to maintain. A double-blind study reexamined previous findings that doxycycline treatment could improve the lymphedematous changes in LF patients. The present study was carried out in a semi-urban location of Kerala, southern India, where Brugia sp. is the predominant parasite, and LF mass drug administration had ceased in many areas. Two hundred individuals (aged 14-65 years; 142 females and 58 males) with lymphedema of stages 1-3 were instructed in the EPC and were randomly administered either 200 mg doxycycline or an identical-appearing placebo daily for 6 weeks. Data were collected at 0, 3, 6, 12, 18, and 24 months and included the state of the lymphedema (size, cleanliness, skin thickness and changes), occurrence of adenolymphangitis (ADL) attacks, and patients' quality of life (QOL). The results demonstrated no difference over time between the two arms of the study; virtually all patients of both groups showed either improvement or "no worsening" in the parameters during the 2-year study period. Importantly, this rigorous trial confirmed that the EPC is of substantial benefit to lymphedema patients by reducing acute ADL and improving their QOL and clinical condition.

Adherence to Hygiene Protocols and Doxycycline Therapy in Ameliorating Lymphatic Filariasis Morbidity in an Endemic Area Post-Interruption of Disease Transmission in Ghana.

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular training on appropriate care for their affected legs, participants were randomized to receive 6 weeks of either 200 mg/day DOX (n = 117), 100 mg/day DOX (n = 120), or matching placebo (n = 119). Participants were seen every 2 months, with clinical measurements done at 6, 12, 18, and 24 months to assess the status of affected legs. There was a trend toward later appearance of acute attacks after DOX, but surprisingly, DOX showed no effect on LE stage progression. In all groups, leg LE improvement was more common (DOX 200 mg: n = 23 [20%]; DOX 100 mg: n = 23 [19.5%]; placebo: n = 32 [27.4%]) than LE worsening (DOX 200 mg: n = 2 [1.7%]; DOX 100 mg: n = 3 [2.5%]; placebo: n = 2 [1.7%]). Overall, these data show a strong benefit from adherence to a strict hygiene protocol, with some added potential benefit for DOX in preventing acute attacks.

[Neoehrlichiosis : rare tick-borne disease, also present in Switzerland]. / Neoehrlichiose : maladie rare transmise par les tiques, aussi en Suisse.

For several years, there has been increasing awareness of a novel tick-borne infection within our region: neoehrlichiosis. The causative agent, Neoehrlichia mikurensis , is an intracellular bacterium classified within the Anaplasmataceae family. Predominantly afflicting immunosuppressed individuals, its clinical presentation often involves persistent fever accompanied by vascular complications. Diagnostic protocols typically entail targeted PCR testing of blood specimens, often leading to diagnostic delays. Timely initiation of doxycycline therapy typically ensures prompt resolution of symptoms.

Depuis quelques années, nous observons une nouvelle infection, transmise par les tiques dans notre pays, la neoehrlichiose. Neoehrlichia mikurensis, la bactérie responsable de cette maladie est intracellulaire et fait partie des Anaplasmataceae. La maladie touche surtout les personnes immunosupprimées et se manifeste par une fièvre persistante et des atteintes vasculaires. Le diagnostic repose sur la recherche de la bactérie par une PCR spécifique dans le sang, ce qui explique le délai souvent conséquent avant le diagnostic. Un traitement par doxycycline permet une guérison rapide.

Scrub typhus presenting with massive splenomegaly and lobar pneumonia.

Scrub typhus is still an underdiagnosed disease despite an increase in incidence as the clinical presentation is often different, leading to a low index of suspicion among doctors. Scrub typhus, an acute febrile disease, is a cause of prolonged fever and pyrexia of unknown origin. It can have varied clinical presentations ranging from mild asymptomatic disease to fatal multi-organ dysfunction. Splenomegaly in scrub typhus has been rarely reported. We report a 30-year-old man presenting with fever, hepatomegaly, massive splenomegaly, lymphadenopathy and lobar pneumonia. Tests for malarial parasite and enteric fever were negative. Bone marrow aspiration showed normal haematopoiesis. IgM scrub was positive. Upon serological confirmation, doxycycline therapy was started followed by a rapid and complete resolution of pneumonia (both clinically and radiologically), splenomegaly and lymphadenopathy. This highlights the importance of recognizing rare clinical manifestations of this common tropical disease. An early diagnosis is required as a delay may lead to complications and a poor outcome.

Scrub typhus presenting as mitral valve infective endocarditis.

Scrub typhus presenting as infective endocarditis of the mitral valve is rare. There are few reports of infective endocarditis by scrub typhus with just one previous report of involvement of the aortic valve. An 18-year-old woman presented with prolonged fever for 1 month. Her repeated blood cultures were negative. She was finally diagnosed to have scrub typhus with scrub typhus IgM being positive and became afebrile with prolonged oral doxycycline monotherapy. Although atypical organisms such as Legionella, Mycoplasma and Coxiella are described to cause culture-negative endocarditis, vegetations were present on both the anterior and posterior mitral valve leaflets in our patient.

Effect of oral doxycycline, azithromycin and isotretinoin on haematological inflammatory markers and interleukin-17A levels in acne vulgaris: a single blinded randomised interventional study.

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32 ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216 ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17 A levels. Baseline levels of IL-17 A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated.

Sensorineural hearing loss in Lyme neuroborreliosis.

BACKGROUND: Sensorineural hearing loss (SNHL) has been suggested to occur in patients with Lyme neuroborreliosis (LNB); however, a clear association has never been documented. The present study prospectively investigated the development of SNHL in patients admitted for treatment of LNB using distortion-product-oto-acoustic emissions (DPOAE) as a measure of cochlear function. METHODS: DOAE were measured in patients with LNB on the day of diagnosis, during treatment, and 30-60 days after discharge. Frequencies were categorized as Low (1, 1.5, 2 kHz), Mid (3, 4, 5 kHz), Mid-high (6, 7, 8 kHz), and High (9, 10 kHz). Pure Tone Audiometry (PTA3) was performed at discharge and 60 days after. Patients were treated with i.v. ceftriaxone or oral doxycycline for 14 days according to guidelines. RESULTS: DPOAE measurements were obtained in 25 patients with LNB at admission and in 18 patients at follow-up. Median age was 56 years (IQR, 48-64 years), and 16 (67%) were men. Fourteen (78%) of 18 patients showed improvement in Emission Threshold Levels (ETL) from admission to follow-up in low, mid-, and mid-high frequency categories, where ETLs increased by median levels of 3.2 (-4.1 to 8.3), 7.5 (-2.8 to 9.8), and 4.7 dB (-4.3 to 10.1). A decline was observed in the high frequency category, median -3.3 dB (-9.1 to 6.7). SNHL defined by pure tone average (PTA3) >20 dB was present in 11 out of 23 (48%) at discharge and in 9 out of 16 patients (56%) 60 days after discharge, which differed significantly from matched controls (Mann-Whitney test, p = 0.036). CONCLUSION: LNB can lead to cochlear outer-hair cell dysfunction, resulting in temporary and long-term SNHL.

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis.

BACKGROUND: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children. METHODS: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ2 or Fisher's exact tests were used for group comparisons. RESULTS: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022). CONCLUSION: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Doxycycline Plus Bortezomib-Containing Regimens for the Treatment of Light-Chain Amyloidosis in the Frontline Setting: Experience from the Amyloidosis Program of Calgary.

Background: Pre-clinical and retrospective data suggest that doxycycline added to treatment regimens has benefit in AL amyloidosis. However, a recent multicenter, open-label, randomized controlled trial in AL amyloidosis patients treated with CyBorD did not demonstrate a progression-free survival (PFS) or cardiac PFS benefit with added doxycycline. Objective: The main objective of this study was to explore the role of doxycycline combined with bortezomib-containing regimens (BCRs) for newly diagnosed AL amyloidosis patients with cardiac involvement and to compare them with a cohort of concurrent patients treated with BCR only. Material and Methods: AL amyloidosis patients, newly diagnosed between January 2012 and March 2022, who were treated with BCR at the Amyloidosis Program of Calgary (APC) were evaluated. Results: Sixty-four concurrent patients were identified. Thirty-nine patients received doxycycline in addition to BCR (BCR-D) for a median of 8 months. The overall response rate was similar among the groups. No significant differences in VGPR/CR, dFLC at 1 month, time to first response, time to best response, or organ responses were noted between the BCR alone and BCR-D groups. Summary and Conclusions: Our retrospective study demonstrated that doxycycline combined with BCR failed to prolong OS, PFS, or cardiac responses compared with BCR alone in patients with cardiac AL amyloidosis.

Case report: membranoproliferative glomerulonephritis associated with Q fever causing chronic endocarditis.

BACKGROUND: Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections. CASE PRESENTATION: We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely. CONCLUSIONS: Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient.

Doxycycline-associated acute pancreatitis: a rare adverse effect of a commonly prescribed antibiotic.

In this case, a woman in her 80s presented to the emergency department with signs and symptoms of acute pancreatitis that began after starting a course of doxycycline. Common aetiologies of acute pancreatitis, including alcohol use, gallstones and hypertriglyceridaemia were ruled out. Less common aetiologies, including recent Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure, hypercalcaemia, malignancy, infection and trauma, were also ruled out, making drug-induced acute pancreatitis the most likely aetiology. After consideration of her medication list, doxycycline was determined to be the offending medication. On discontinuation and treatment with fluids and analgesics, her condition slowly improved.This case illustrates a rare but severe complication of doxycycline use. Determining the aetiology of drug-induced acute pancreatitis is more difficult in older patients due to high rates of polypharmacy. Recognition of doxycycline as an aetiology of drug-induced pancreatitis may allow earlier recognition and intervention in cases of suspected pancreatitis without a clear common aetiology in older patients with polypharmacy.

A comparative study on the effects of doxycycline, nalidixic acid and meropenem on Escherichia coli in inducing urinary tract infections.

Urinary tract infections are widely recognized as prevalent bacterial infections frequently encountered in both hospital and community settings. The most common gram-negative bacterial pathogen in humans, extra-intestinal pathogenic Escherichia coli, causes these diseases. A retrospective cross-sectional study in Karachi, Pakistan examined Escherichia coli's susceptibility to doxycycline, nalidixic acid and meropenem. One hundred isolates of Escherichia coli from urine samples of patients were collected. The Kirby Bauer disc diffusion testing method was used following CLSI guidelines. The results showed variability because of differences in patient's gender and age. 84 out of 100 samples were of females and 16 samples were of males. Infection prevalence by age showed that 15% of isolates were from children (0-12 years), 2% from adolescents (13-18 years), 52% from adults (19-59 years) and 31% from seniors. This study concluded that females and adults (aged 19-59 years) are at highest risk of prevalence. Meropenem is a potential antibiotic choice for urinary tract infections due to its demonstrated 100% susceptibility. However, in light of increasing resistance trends, the administration of doxycycline and nalidixic acid should be reserved until antimicrobial susceptibility testing has been conducted. The study ensures that antibiotics are used judiciously and effectively in combating urinary tract infections while minimizing the risk of further antimicrobial resistance development.

Clinical characterization of brucellosis in children from non-pastoral areas: a report of five cases.

BACKGROUND: Brucellosis is a global public health concern and occurs mainly in young adults and the elderly, with children having a lower incidence, thus often leading to delayed treatment. This study aimed to describe the epidemiologic features and clinical characteristics of brucellosis in children. METHODS: In this retrospective study, the clinical data of five children diagnosed with brucellosis in Anhui Provincial Children's Hospital between January 1, 2021 and December 30, 2022 were analyzed. RESULTS: All five cases were from non-pastoral areas, among which three have a history of livestock exposure and originated from the countryside. All patients had medium-high grade fever, mostly accompanied by night sweats and malaise, and three had joint pains. Laboratory tests showed that their white blood cell count was normal or mildly raised, with lymphocytes as the predominant cell population. Four patients had anemia, four had aspartate aminotransferase and alanine aminotransferase abnormality, and two had elevated ferritin levels. All blood samples were positive for Brucella culture, one of which had positive bone marrow culture, and all had positive serology test results. All patients were treated with rifampicin, in combination with sulfamethoxazole or doxycycline for 6 weeks following diagnosis. Four children had a good prognosis, but one child had recurrent joint pain. CONCLUSIONS: The epidemiologic history of children from non-pastoral areas with brucellosis is often unclear; clinical manifestations and laboratory tests lack specificity; and they are easily delayed diagnosis. Clinicians should remain vigilant regarding the possibility of this disease in children with fever of unknown origin. The epidemiological history should be investigated in detail to improve the diagnostic ability of brucellosis. We recommend emphasizing serological testing. Children with brucellosis who receive timely diagnosis and standardized treatment can expect a favorable prognosis.

Leptospirosis and melioidosis coinfection presenting as acute respiratory distress syndrome and osteomyelitis: Case report and systematic review.

INTRODUCTION: Leptospirosis and melioidosis are common in tropical and temperate climates and can be acquired by exposure to contaminated water and soil. However, concomitant leptospirosis and melioidosis infection is rarely described in the literature. We report a case of leptospirosis-melioidosis coinfection and systematically review the literature. CASE PRESENTATION: A 42-year-old male presented with fever associated with chills and rigor, dull aching pain in the right thigh, myalgia, progressive breathlessness, and dry cough for 10 days. At presentation, he was tachypneic and had tachycardia, and oxygen saturation was 46% in room air. Chest radiography and computed tomography scan showed interstitial involvement. Magnetic resonance imaging for thigh pain revealed right femur osteomyelitis. Leptospira serology was positive, and blood culture grew Burkholderia pseudomallei, confirming the diagnosis of melioidosis. Thus, a diagnosis of presumptive leptospirosis based on modified Faine's criteria and systemic melioidosis was made. He received doxycycline and intravenous meropenem and improved. RESULTS: We performed a systematic review to understand the spectrum of leptospirosis-melioidosis coinfection. We identified only nine cases of coinfection described in literature. Only one patient had septic arthritis, and our case is the only one presenting with osteomyelitis. Serology diagnosed leptospirosis, whereas melioidosis was confirmed by blood culture in most patients. The majority of coinfected patients developed some complications, and six died. CONCLUSIONS: Leptospirosis-melioidosis coinfection is rarely reported in the literature. Physicians should maintain a high index suspicion of leptospirosis-melioidosis coinfection in patients presenting with acute febrile illness following exposure to soil or freshwater, particularly in tropical and endemic regions.

Two complicated cases of severe scrub typhus, eschar- a non-negligible sign: Case reports and literature review.

RATIONALE: Scrub typhus is a mite-borne, acute febrile disease caused by Orientia tsutsugamushi. The endemic areas of scrub typhus are expanding, both globally and in China. Patients who are not treated promptly, are likely to die of multiple organ dysfunction syndrome. PATIENT CONCERNS: Case I A 61-year-old female patient complained of sudden chest tightness and shortness of breath accompanied by fever for 6 days. Case II A 54-year-old male patient complained of fever and cough for 4 days and renal insufficiency for 2 days. DIAGNOSES: Scrub typhus, multiple organ dysfunction syndrome. INTERVENTIONS: After the definite diagnosis, both patients were treated with doxycycline and various organ supports. OUTCOMES: The patient in case I was ultimately not salvageable. The patient in case II was successfully cured by the prompt administration of doxycycline along with continuous renal replacement therapy. LESSONS: With early diagnosis and treatment, patients can completely recover. Eschar, a characteristic sign of scrub typhus, is often overlooked, leading to delayed diagnosis and regrettable outcomes.

[Fever and a papule after a visit to a South-African Wild Park]. / Koorts en papel na bezoek aan Zuid-Afrikaans wildpark.

A 39-year old man presented in our emergency room with fever, lymphadenopathy in his right groin and a red papule with a dark center. He was treated with doxycycline and recovered well. Serology showed Rickettsia africae with seroconversion after a few weeks.

Septic shock and fulminant hepatic failure secondary to Q fever in a child with sickle cell disease: First case report.

Q fever is a zoonosis with a worldwide distribution that is caused by the intracellular bacterium Coxiella burnetii. Although most infections in children are asymptomatic and self-limiting, some experience severe or chronic manifestations. Its manifestations in patients with sickle cell disease are unknown, as there are no reports currently. We report the case of a 4-year-old child with sickle cell disease who was admitted to the intensive care unit with fever, septic shock and fulminant hepatic failure secondary to hepatic sequestration crisis and intrahepatic cholestasis. Coxiella burnetii infection was confirmed by molecular and serologic assays. Empiric therapy with doxycycline had a significant impact on his course, and he made an excellent recovery despite requiring extensive life-supportive measures initially. This is the first report of Q fever in a patient with sickle cell disease, demonstrating its capability to manifest as acute sickle hepatopathy with critical illness.

Sea-fan retinal neovascularization associated with rickettsial retinitis: a case report.

BACKGROUND: Rickettsial disease has been commonly associated with retinitis, retinal vasculitis, and optic nerve involvement, but the development of retinal neovascularization has been very rarely reported. We herein describe a case of rickettsial retinitis complicated with the development of sea-fan retinal neovascularization documented with multimodal imaging, including fundus photography, SS-OCT, fluorescein angiography, and SS-OCT angiography. CASE PRESENTATION: A 26-year-old female with a history of fever one week earlier presented with sudden decreased vision in the left eye. Best-corrected visual acuity (BCVA) was 20/2000 and the patient was diagnosed with rickettsial retinitis along the superotemporal retinal vascular arcade associated with serous retinal detachment and retinal hard exudates. The indirect immunofluorescence test was positive for Rickettsia conorii, and the patient was treated with oral doxycycline (200 mg/day) and oral prednisone (0.75 mg/kg/day, with gradual tapering). Four weeks after presentation, the retinal infiltrate and associated serous retinal detachment had resolved, but retinal hard exudates had increased. A large sea-fan preretinal fibrovascular neovascularization became apparent along the superotemporal retinal vascular arcade, but there was no associated retinal ischemia on fluorescein angiography. The patient received an adjunctive single intravitreal injection of 1.25 bevacizumab. Sequential follow-up examinations showed shrinking of sea-fan retinal neovascularization, a complete resolution of retinal hard exudates, and the development of a self-limited vitreous hemorrhage. On last follow-up, 30 months after intravitreal bevacizumab injection, BCVA was 20/25. CONCLUSION: Patients with rickettsial retinitis may develop a sea-fan retinal neovascularization, with subsequent vitreous hemorrhage, putatively through inflammatory mechanisms. Multimodal imaging including OCT, fluorescein angiography, and OCT-angiography, is highly useful for accurate diagnosis and reliable monitoring of the evolution of retinitis, retinal neovascularization, and other retinal changes. The use of a combination therapy with oral doxycycline and corticosteroids and intravitreal anti-VEGF can improve outcomes.

Exposure to doxycycline increases risk of carrying a broad range of enteric antimicrobial resistance determinants in an elderly cohort.

OBJECTIVES: High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic-resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood. METHODS: We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged-care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) was identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified. RESULTS: Stool samples were provided by 164 participants (median age: 88 years, IQR 81-93; 72% female). Sixty-one percent (n = 100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1-52), most commonly a penicillin (n = 55, 33.5%), cephalosporin (n = 53, 32.3%), diaminopyrimidine (trimethoprim) (n = 36, 22%), or tetracycline (doxycycline) (n = 21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q<0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q<0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30-100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q<0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q<0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n = 162, median: 3, IQR: 2-4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluoroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations. CONCLUSIONS: The gut microbiome of aged care residents is a major reservoir of antibiotic resistance. As a critical antibiotic in medical practice, a comprehensive understanding of the impact of doxycycline exposure on the gut resistome is paramount for informed antibiotic use, particularly in an evolving landscape of prophylactic applications. Near-universal asymptomatic carriage of clinically critical resistance determinants is highly concerning and reinforces the urgent need for improved management of antibiotic use in long-term aged care.