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Parasites & Vectors Jul 2023The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated...
BACKGROUND
The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner.
METHODS
To investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment.
RESULTS
Mean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed.
CONCLUSIONS
No consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance.
Topics: Animals; Dogs; Dirofilaria immitis; Doxycycline; Dirofilariasis; Filaricides; Dog Diseases; Wolbachia
PubMed: 37491306
DOI: 10.1186/s13071-023-05858-2 -
Topics in Antiviral Medicine Dec 2023Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea,... (Review)
Review
Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea, chlamydia, and syphilis in some key populations at high risk of sexually transmitted infections. Even so, much remains unknown about the long-term consequences of doxy-PEP, and several concerns, including the potential for the development of antibiotic resistance and disturbances to the microbiome, balance the benefits. This review highlights the history of antibiotic prophylaxis for sexually transmitted infections, and the rationale, current evidence, and future directions for doxy-PEP.
Topics: Humans; Doxycycline; Sexually Transmitted Diseases; Syphilis; Gonorrhea; Antibiotic Prophylaxis
PubMed: 38198668
DOI: No ID Found -
Southern African Journal of HIV Medicine 2023South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials...
South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials have recently demonstrated high effectiveness of doxycycline post-exposure prophylaxis (PEP) for prevention of bacterial STIs in MSM, with 70% - 85% reductions in infection and syphilis, and approximately 50% reduction in infection. Doxycycline PEP was not demonstrated to be effective in reducing and infection among Kenyan cisgender women. Although no worrisome trends in antimicrobial resistance (AMR) were observed in the trials, important concerns remain about doxycycline PEP and AMR development in STIs, other pathogens, commensals, and the microbiome. Tetracycline resistance in is already widespread in South Africa, but emergence of AMR in other STIs would be concerning. Larger sample sizes of doxycycline PEP users with longer follow-up time are needed to understand the impact that doxycycline PEP may have on AMR at individual and population level. In this opinion article, we weigh the benefits of doxycycline PEP for prevention of bacterial STIs against the existing AMR concerns and data gaps in the South African context. Based on the current evidence, we conclude that it would be reasonable to offer doxycycline PEP to high-risk MSM on a case-by-case basis, provided that it is offered by experienced sexual health clinicians in settings that have access to diagnostic STI testing and ongoing AMR surveillance.
PubMed: 37795430
DOI: 10.4102/sajhivmed.v24i1.1510 -
The Cochrane Database of Systematic... Mar 2024Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic... (Review)
Review
BACKGROUND
Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review.
OBJECTIVES
To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis.
SEARCH METHODS
We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023.
SELECTION CRITERIA
We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported.
DATA COLLECTION AND ANALYSIS
During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period.
MAIN RESULTS
We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies.
AUTHORS' CONCLUSIONS
As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.
Topics: Humans; Anti-Bacterial Agents; Doxycycline; Azithromycin; Quality of Life; Chloramphenicol; Penicillins; Cephalosporins; Cefotaxime; Leptospirosis; Cross Infection
PubMed: 38483092
DOI: 10.1002/14651858.CD014960.pub2 -
The Cochrane Database of Systematic... Mar 2024Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in... (Review)
Review
BACKGROUND
Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3).
OBJECTIVES
To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis.
SEARCH METHODS
We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023.
SELECTION CRITERIA
We included randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule.
DATA COLLECTION AND ANALYSIS
We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up.
MAIN RESULTS
We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source.
AUTHORS' CONCLUSIONS
We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.
Topics: Humans; Antibiotic Prophylaxis; Doxycycline; Azithromycin; Quality of Life; Anti-Bacterial Agents; Penicillins; Leptospirosis
PubMed: 38483067
DOI: 10.1002/14651858.CD014959.pub2 -
Archivos de La Sociedad Espanola de... Oct 2023Rosacea is a chronic and inflammatory disease that primarily affects the skin, although more than half of cases also present with ocular symptoms ranging from... (Review)
Review
Rosacea is a chronic and inflammatory disease that primarily affects the skin, although more than half of cases also present with ocular symptoms ranging from blepharitis to conjunctivitis and keratitis. It represents a frequent reason for consultation with a psychosocial impact, affecting quality of life, and requires management involving ophthalmologists, dermatologists, and primary care physicians. For this paper, a search was conducted in several databases, including Medline, Embase, Cochrane, and Google Scholar, using the MeSH term "rosacea" in conjunction with other relevant keywords such as "ocular rosacea", "management", "treatment", and "guidelines". Available articles were reviewed. International and local guidelines recommend initiating the management of rosacea with lifestyle changes, including ocular hygiene and avoidance of triggers. Topical or oral treatment is recommended as the next step, with topical cyclosporine, topical azithromycin, topical tacrolimus, and oral doxycycline being the treatments most supported by evidence. Combination treatments are also recommended. Current management guidelines mainly focus on cutaneous manifestations, generating few guidelines on ophthalmologic treatment, and most recommendations are issued by experts. This work compares local and international treatment guidelines for rosacea, as well as other available medical literature, and suggests a practical and interdisciplinary treatment scheme for ocular involvement based on the reviewed bibliography.
Topics: Humans; Quality of Life; Rosacea; Doxycycline; Conjunctivitis; Cyclosporine
PubMed: 37696488
DOI: 10.1016/j.oftale.2023.09.001 -
The Journal of Antimicrobial... Jul 2023Rates of sexually transmitted infections (STIs) continue to rise across the world and interventions are essential to reduce their incidence. Past and recent studies have... (Review)
Review
Rates of sexually transmitted infections (STIs) continue to rise across the world and interventions are essential to reduce their incidence. Past and recent studies have indicated this may be achieved using doxycycline post-exposure prophylaxis (PEP) and this has sparked considerable interest in its use. However, many unanswered questions remain as to its long-term effects and particularly potentially negative impact on human microbiomes and antimicrobial resistance among STIs, other pathogens, and commensals. In this review, we discuss seven areas of concern pertaining to the widespread use of doxycycline PEP.
Topics: Humans; Doxycycline; Sexually Transmitted Diseases; Chemoprevention; Incidence; Post-Exposure Prophylaxis; HIV Infections
PubMed: 37129293
DOI: 10.1093/jac/dkad129 -
The Medical Letter on Drugs and... Feb 2024
Topics: Humans; Rosacea
PubMed: 38294765
DOI: 10.58347/tml.2024.1695b -
The Journal of Antimicrobial... Dec 2023Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP... (Observational Study)
Observational Study
OBJECTIVES
Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP diagnoses. We studied the difference in outcomes of severe CAP patients treated with doxycycline versus azithromycin in addition to β-lactam therapy.
PATIENTS AND METHODS
This was a prospective observational cohort study from March 2020 to July 2022 in a medical ICU (MICU) of an academic quaternary medical center. Adults ≥18 years admitted to the MICU receiving doxycycline or azithromycin in addition to β-lactam therapy for the treatment of CAP were included for analysis. The primary outcomes were in-hospital and 30 day mortality. Secondary outcomes were ICU and hospital length-of-stay, 30 day readmission, days of mechanical ventilation, escalation and duration of antibiotics, adverse effects such as Clostridioides difficile infection and QTc prolongation.
RESULTS
Sixty-three patients were in the azithromycin group and eighty-six patients in the doxycycline group. Both groups had similar APACHE IV and CURB-65 scores. The mean Charlson Comorbidity Index score was higher for the doxycycline group compared with the azithromycin group (P = 0.04). There was no statistically significant difference in in-hospital and 30 day mortality between the groups (P = 0.53, P = 0.57). There were no significant differences in any of the secondary outcomes.
CONCLUSIONS
MICU patients with severe CAP who received doxycycline versus azithromycin in addition to β-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.
Topics: Adult; Humans; Azithromycin; Doxycycline; beta-Lactams; Prospective Studies; Critical Illness; Drug Therapy, Combination; Anti-Bacterial Agents; Pneumonia; Community-Acquired Infections; Treatment Outcome
PubMed: 37814829
DOI: 10.1093/jac/dkad301 -
Ocular Immunology and Inflammation Sep 2023The aim of the study is to analyze visual fields defects (VFDs) in epidemic retinitis (ER).
AIM
The aim of the study is to analyze visual fields defects (VFDs) in epidemic retinitis (ER).
METHODS
Patients with ER and Humphrey's visual field (HFA) 30-2 performed after resolution were studied. VFD severity grading was performed. Patients treated with oral doxycycline (Group-A) versus doxycycline-steroids (group-B) were compared.
RESULTS
Thirty-five eyes of 25 patients were studied. Nasal, inferior, temporal and central VFD were seen in 19 (54.2%), 13 (37.1%), 7 (20%) and 6 (17.1%) eyes, respectively. Grade 0, 1, 2 and 3 VFDs were seen in 4 (11.4%), 15 (42.8%), 12 (34.2%) and 4 (11.4%) eyes respectively. Seven eyes with ≥1 year of follow-up post-resolution also showed grade 0-3 scotomas. Mean severity of scotoma was grade 1.15 (Median: 1) and 1.42 (Median: 1.5) in groups A (n = 13) and B (n = 14), respectively (p = .637).
CONCLUSION
ER can cause VFD persisting long after resolution. Treatment with oral doxycycline without steroids was non-inferior to combined treatment with respect to VFD.
Topics: Humans; Visual Fields; Doxycycline; Scotoma; Visual Field Tests; Vision Disorders; Retinitis
PubMed: 35708453
DOI: 10.1080/09273948.2022.2084422