A case report of acute renal failure caused by anti-brucellosis treatment.

RATIONALE: Rifampicin, as a main chemotherapy drug treating brucellosis, is widely used in clinical practice. Rifampicin-associated ARF is not rare, especially in those rifampicin re-exposure patients. However, this was rare complication of severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium, and few studies have reported it. PATIENT CONCERNS: A 59-year-old male presented to our hospital with acute renal failure (ARF) caused by anti-brucellosis treatment with rifampicin (675 mg/day), gentamicin (320 mg/day), and doxycycline (200 mg/day). He had a contrast-enhanced CT of the upper abdomen before the onset of. After stopping rifampicin and undergoing integrated therapy, the patient's renal function gradually recovered. DIAGNOSES: Considering that the patient had a history of using rifampicin for pulmonary tuberculosis in the past, based on the examination results, the patient was diagnosed with rifampicin-associated ARF. INTERVENTIONS: Symptomatic treatment such as hemodialysis, and anti-brucella treatment with doxycycline and moxifloxacin were given. OUTCOMES: The patient had significant anuric and polyuric periods and acute tubular necrosis is considered. After treatment, his renal function and urine volume returned to normal, and Brucella melitensis was not isolated from blood cultures. LESSONS: The case reveals that severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium. Misdiagnosis and mistreatment can deteriorate the patient's condition. Renal function should be closely monitored in the susceptible patients. Early recognition can provide appropriate therapy to patients. If unexplained renal failure during the use of rifampicin, especially in those rifampicin re-exposure patients, rifampicin-associated ARF should be considered.

Antibiotic prophylaxis for leptospirosis.

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.

Antibiotics for treatment of leptospirosis.

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; I2 = 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; I2 = 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; I2 = 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.

Efficacy and safety of therapeutic strategies for human brucellosis: A systematic review and network meta-analysis.

BACKGROUND: Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA). METHODOLOGY: A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO. RESULTS: Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01-0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27-3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence. CONCLUSIONS: This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies.

Pharmacokinetics of single dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections.

BACKGROUND: Clinical trials showed a single oral dose of doxycycline taken after sex protects against STIs among men who have sex with men (MSM) but not women. Pharmacokinetic data at vaginal, rectal and penile sites of STI exposure are lacking. We examined vaginal, rectal and urethral doxycycline concentrations in men and women to better inform STI prevention. METHODS: Doxycycline pharmacokinetics in male and female participants 18-59 years of age were evaluated in blood and urine and on rectal and vaginal swabs collected at 1, 2, 4, 8, 24, 48, 72, 96 and 168 h after receiving a 200 mg oral doxycycline dose in a non-randomised single dose open label single centre study in Atlanta, Georgia. Rectal, vaginal, and cervical biopsies and male urethral swabs were collected 24 h after dosing (Trial registration: NCT04860505). Doxycycline was measured by liquid chromatography-mass spectrometry. FINDINGS: Eleven male and nine female participants participated in the study. Doxycycline concentrations on rectal and vaginal swabs collected up to 96 h after dosing were approximately twice those of plasma and remained above minimum inhibitory concentrations (MICs) for at least four, three, and two days for Chlamydia trachomatis, Treponema pallidum, and tetracycline-sensitive Neisseria gonorrhoeae, respectively. Geometric mean doxycycline concentrations in male urethral secretions (1.166 µg/mL; 95% CI 0.568-2.394 µg/mL), male rectal (0.596 µg/g; 0.442-0.803 µg/g), vaginal (0.261 µg/g; 0.098-0.696 µg/g) and cervical tissue (0.410 µg/g; 0.193-0.870 µg/g) in biopsies collected 24 h after dosing exceeded MICs. Plasma and urine doxycycline levels defined adherence markers up to four and seven days postdosing, respectively. No adverse events were reported in this study. INTERPRETATION: Doxycycline efficiently distributes to the rectum, vagina and urethra. Findings can help explain efficacy of STI prevention by doxycycline. FUNDING: Funded by CDC intramural funds, CDC contract HCVJCG-2020-45044 (to CFK).

A Case of Doxycycline-Induced Pancreatitis.

INTRODUCTION: Acute pancreatitis is a common cause of hospitalizations in the United States, causing approximately 230 000 to 275 000 annual admissions We present the case of a patient with acute pancreatitis likely due to doxycycline. CASE PRESENTATION: A 64-year-old male was admitted after developing acute epigastric pain radiating to his back, a lipase of 6611 (units/L), and a computed tomography scan showing moderate peripancreatic inflammation. He had no recent alcohol use, his gallbladder was surgically absent, and he had no gallbladder pathology on evaluation; however, he had been started on doxycycline 10 days prior. While hospitalized, he was treated with pain medications, fluids, and antibiotics for aspiration pneumonia. His acute symptoms resolved, except for minor intermittent abdominal pain 2 months after discharge. DISCUSSION: Doxycycline-induced pancreatitis has been reported within 3 to 17 days of medication initiation. Given the temporal correlation and lack of other inciting etiologies, we determined the most likely etiology was doxycycline. CONCLUSIONS: Further study is needed to understand the pathophysiology and incidence of doxycycline-induced pancreatitis.

Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Doxycycline induces mitochondrial dysfunction in aortic smooth muscle cells.

The antibiotic doxycycline is known to inhibit inflammation and was therefore considered as a therapeutic to prevent abdominal aortic aneurysm (AAA) growth. Yet mitochondrial dysfunction is a key-characteristic of clinical AAA disease. We hypothesize that doxycycline impairs mitochondrial function in the aorta and aortic smooth muscle cells (SMCs). Doxycycline induced mitonuclear imbalance, reduced proliferation and diminished expression of typical contractile smooth muscle cell (SMC) proteins. To understand the underlying mechanism, we studied krüppel-like factor 4 (KLF4). The expression of this transcription factor was enhanced in SMCs after doxycycline treatment. Knockdown of KLF4, however, did not affect the doxycycline-induced SMC phenotypic changes. Then we used the bioenergetics drug elamipretide (SS-31). Doxycycline-induced loss of SMC contractility markers was not rescued, but mitochondrial genes and mitochondrial connectivity improved upon elamipretide. Thus while doxycycline is anti-inflammatory, it also induces mitochondrial dysfunction in aortic SMCs and causes SMC phenotypic switching, potentially contributing to aortic aneurysm pathology. The drug elamipretide helps mitigate the harmful effects of doxycycline on mitochondrial function in aortic SMC, and may be of interest for treatment of aneurysm diseases with pre-existing mitochondrial dysfunction.

Long-Term Safety Profiles of Macrolides and Tetracyclines: A Systematic Review and Meta-Analysis.

Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine.

D-PLEX100 (D-PLEX) is a novel product candidate made of a polymer-lipid-based matrix (PLEX platform) which contains doxycycline that is being released at a constant rate for 30 days. D-PLEX was developed to prevent surgical site infections, which are a major global health challenge. Previous studies have shown its safety in adult humans, adult swine, and adult rabbits. The aim of this study was to assess the toxicity and safety of D-PLEX also in juvenile animals to support future clinical trials in pediatric patients. Yucatan miniature swine were selected as a model, primarily due to their relatively larger mass. D-PLEX or placebo (formulation without doxycycline) was administered locally to abdominal incisions, and the animal's safety parameters were followed for 9 months and compared to sham-control swine. There was no evidence of any systemic safety concern or local toxicity at the incision site in D-PLEX-treated animals. D-PLEX was detected after 1 month and was fully resorbed at the 3-month time point. The surgical incision sites were fully healed at the 6-month time point in all D-PLEX-treated animals. Toxicokinetic (TK) assessments revealed that doxycycline exhibited low Cmax and therefore minimal systemic exposure following a single dose of local administration. This study provides evidence for the safety of D-PLEX and PLEX-based formulation in juvenile miniature swine and supports its further testing in clinical pediatric population. In addition, it can be used as a reference for future preclinical studies aiming to evaluate the safety of other PLEX-based product candidates for the pediatric population.

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.).

Seasonal Patterns in Tetracycline-Associated Hyperpigmentation Among Patients With Acne Vulgaris.

BACKGROUND: Oral tetracyclines (TCNs) are commonly prescribed for acne, but they have been shown to increase the risk of hyperpigmentation, particularly in the setting of sun exposure. OBJECTIVE: We evaluated seasonal trends in TCN-associated hyperpigmentation incidence in addition to Google search trends for hyperpigmentation-related terms. METHODS: We performed a retrospective review of acne patients seen at Massachusetts General Brigham and Women’s Hospital between 1992 and 2022. We calculated the incidence of new hyperpigmentation diagnoses for each drug cohort. We also analyzed search volume of hyperpigmentation-related terms extracted from Google Trends. RESULTS: Seasonal differences in new hyperpigmentation diagnoses were identified among acne patients prescribed doxycycline (P=0.016), with peak incidence in April. In the control group of patients who had never received a TCN, diagnoses peaked in May. There were no significant seasonal differences among patients prescribed minocycline (P=0.885). There was greater search volume for hyperpigmentation-related terms in spring and summer compared to fall and winter (P<0.001). Limitations of this study include its retrospective nature and reliance on prescription and diagnosis coding data. CONCLUSIONS: Our findings support the seasonal periodicity of acne-related hyperpigmentation, underscoring the importance of photoprotection counseling for patients with acne. Additionally, doxycycline may be associated with an earlier onset of hyperpigmentation, suggesting a potential benefit of considering minocycline or other alternatives to doxycycline. J Drugs Dermatol. 2023;22(11):e9-e11    doi:10.36849/JDD.7409e.

ß-Lactams plus doxycycline versus azithromycin for treatment of severe community-acquired pneumonia in critically ill patients.

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 ß-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 ß-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 ß-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.

Doxycycline for the Treatment of Lyme Disease in Young Children.

BACKGROUND: Doxycycline is considered the first-line treatment of Lyme disease in adolescents and adults, but largely disproven concerns of permanent tooth staining prevented its use and evaluation in children <8 years old. We sought to describe short-term adverse effects and treatment failures among young children receiving oral doxycycline for Lyme disease. METHODS: We completed a 2-pronged evaluation of children with Lyme disease treated with doxycycline. We performed a retrospective case series of patients <8 years old who were diagnosed with Lyme disease and treated with doxycycline. We then performed a telephone follow-up survey study of the patients' parents to gather additional details regarding clinical outcomes and adverse reactions to doxycycline. Descriptive statistics were calculated. RESULTS: A total of 32 patients were identified through the retrospective case series and 18 participated in the follow-up survey. The most common clinical diagnosis (22/32; 69%) was single erythema migrans. Seven (22%) had neurological Lyme disease. Three patients (9%) stopped doxycycline treatment prematurely due to adverse effects. During telephone follow-up, 2 children were reported to have dental staining. No patients were identified with treatment failure during the retrospective case series. On telephone follow-up, 3 patients had residual symptoms after treatment, though none were convincing of treatment failure. CONCLUSIONS: Our study suggests that doxycycline is generally well-tolerated and an effective treatment of Lyme disease in young children. Prospective, observational studies with long-term assessment of dental staining and clinical outcomes are needed. Alternative antibiotics, principally amoxicillin, remain the preferred treatment of non-neurological Lyme disease manifestations in young children, but doxycycline is likely a safe and effective alternative when needed.

Severe Ureaplasma urealyticum infection in a patient with ocrelizumab-induced hypogammaglobulinaemia.

Infections caused by Ureaplasma urealyticum in immune-competent people are typically simple and uncomplicated. However, in cases of immunosuppression, severe disseminated infections can occur.This case report describes the case of a severe, disseminated infection caused by U. urealyticum in a young female with unacknowledged humoral immunosuppression due to treatment with ocrelizumab for multiple sclerosis.The patient was admitted due to a recurrent episode of a tubo-ovarian abscess. Throughout the following 2 months of hospitalisation, treatment with several types of antibiotics and the placement of various drains led to no improvement. As extensive investigations indicated hypogammaglobulinaemia, U. urealyticum was suspected, and tests came back positive. Treatment with doxycycline and moxifloxacin led to a full recovery.This demonstrates how humoral immunosuppression is a risk factor for severe disseminated infections and how these may be avoided through monitoring of immunoglobulin levels in patients treated with ocrelizumab.

Efficacy of supramolecular salicylic acid in combination with doxycycline in the treatment of acne.

To determine the efficacy of supramolecular salicylic acid combined with doxycycline on acne, totally 70 patients with acne treated in our dermatology department from May 2020 to May 2021 were enrolled and randomized (1:1) into control or experimental groups using the random number table method. The control group was given doxycycline for oral administration while the experimental group was given oral doxycycline combined with supramolecular salicylic acid for topical administration. The overall effective rate of treatment was significantly higher in the experimental group versus control group (97.14% vs. 82.86%, P<0.05). Patients in the control group had significantly longer mean acne regression time after treatment versus experimental group (P<0.05). After treatment, patients in the experimental group had significantly lower self-rating depression scale (SDS) scores and self-perceived burden (SPB) scores than the control group, while Short Form 36-item health survey (SF-36) scores were significantly higher than the control group (P<0.05). The overall incidence of adverse reactions was significantly lower in the experimental group versus control group (5.71% vs. 17.14%, P<0.05). Supramolecular salicylic acid in combination with doxycycline in the treatment of patients with acne is an optimal option, as it could better promote acne regression, reduce the level of depression and reduce the patient's self-perceived burden.

Efficacy and safety of doxycycline versus iodopovidone for pleurodesis through an intercostal tube in malignant pleural effusions: a randomized trial.

PURPOSE: The search for an inexpensive agent for chemical pleurodesis in malignant pleural effusion (MPE) continues. We aimed to compare the efficacy and safety of iodopovidone versus doxycycline for pleurodesis in MPE. METHODS: We randomized consecutive subjects with recurrent symptomatic MPE (1:1) to undergo pleurodesis with either doxycycline or iodopovidone administered through an intercostal tube. The primary outcome was the success rate of pleurodesis at 30 days. The secondary outcomes were the time to pleurodesis, chest pain (assessed using visual analog scale [VAS]) after pleurodesis, and complications (hypotension, acute respiratory failure, empyema). RESULTS: We randomized 52 and 58 subjects to receive either doxycycline or iodopovidone. The mean (standard deviation [SD]) age of the study population (51% women) was 54.1 (13.6) years. Lung cancer (≥ 60%) was the most common underlying cause of MPE. We observed a similar frequency of success in the doxycycline vs. the iodopovidone group (complete response: 43 (82.7%) vs. 46 (79.3%) subjects; partial response: 7 (13.5%) vs. 10 (17.2%) subjects; p = 0.3). The mean (SD) time to pleurodesis was 1.5 (1.9) days and 1.9 (5.4) days in the doxycycline and iodopovidone groups, respectively. While the VAS for chest pain was significantly higher with iodopovidone (mean [SD] VAS: doxycycline, 31.9 [20.9]; iodopovidone, 41.3 [21.8]; p = 0.017), it did not reach the minimal clinically important difference. The complication rates were similar between the two groups. CONCLUSION: Iodopovidone was not superior to doxycycline for pleurodesis in MPE. TRIAL REGISTRATION NUMBER/DATE: clinicaltrials.gov (NCT02583282) / October 22, 2015.

Pulsed Oral Azithromycin vs 6-Week Oral Doxycycline for Moderate to Severe Meibomian Gland Dysfunction: A Randomized Clinical Trial.

Importance: The treatment of moderate to severe meibomian gland dysfunction (MGD) with oral doxycycline requires a 6-week course of treatment and has frequent adverse effects (AEs), which may be associated with poor compliance. Objective: To determine if the AEs of a 3-week course of oral azithromycin were equivalent to the AEs of a 6-week course of oral doxycycline. Design, Setting, and Participants: This double-masked randomized clinical trial was conducted at a referral center in Thailand from September 2018 to May 2022. Participants with moderate to severe MGD judged unresponsive to conservative management were included. Interventions: Patients were randomized 1:1 to receive oral azithromycin (1 g once per week for 3 weeks) or oral doxycycline (200 mg daily for 6 weeks). Main Outcomes and Measures: After initiating therapy, the study team assessed the total MGD score and Ocular Surface Disease Index (OSDI) score at the initial visit, at 6 weeks, and at 8 weeks, and assessed AEs at 6 weeks and 8 weeks. The prespecified equivalence margins for MGD score and OSDI score were set at ±2 and ±9, respectively. Results: A total of 137 eyes from 137 patients were randomized into groups, 68 eyes in the azithromycin group and 69 eyes in the doxycycline group (female, 66.4%; mean age, 62.0 [SD, 15.1] years). The adjusted mean difference of total MGD scores between groups at week 6 and week 8 were -0.33 (95% CI, -1.70 to 1.03; P for equivalence = .01) and 0.13 (95% CI, -1.59 to 1.84; P for equivalence = .02), respectively. The adjusted mean difference of OSDI between groups score at week 6 and week 8 was -1.20 (95% CI, -5.31 to 2.91; P for equivalence < .001) and -1.59 (95% CI, -5.73 to 2.55; P for equivalence < .001), respectively. In addition, patients treated with azithromycin had fewer gastrointestinal AEs (4.4% vs 15.9%; risk difference, 11.5%; 95% CI 1.6%-21.4%; P = .03). Conclusions and Relevance: These data support an equivalency of effects of azithromycin as compared with doxycycline for MGD score and OSDI score at both follow-up times. The study did not show more gastrointestinal AEs in the azithromycin group. The reduced dosing and potentially fewer gastrointestinal AEs associated with azithromycin support its use as an alternative to doxycycline for at least 6 weeks. Trial Registration: ThaiClinicalTrials.org Identifier: TCTR20180810001.

A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia.

BACKGROUND: Doxycycline and minocycline are brain-penetrant tetracycline antibiotics, which recently gained interest because of their immunomodulatory and neuroprotective properties. Observational studies have suggested that exposure to these drugs may decrease the risk to develop schizophrenia, but results are inconsistent. The aim of this study was to investigate the potential association between doxycycline use and later onset of schizophrenia. DESIGN: We used data from 1 647 298 individuals born between 1980 and 2006 available through Danish population registers. 79 078 of those individuals were exposed to doxycycline, defined as redemption of at least 1 prescription. Survival analysis models stratified for sex with time-varying covariates were constructed to assess incidence rate ratios (IRRs) for schizophrenia (ICD-10 code F20.xx), with adjustment for age, calendar year, parental psychiatric status, and educational level. RESULTS: In the non-stratified analysis, there was no association between doxycycline exposure and schizophrenia risk. However, men who redeemed doxycycline had a significantly lower incidence rate for schizophrenia onset compared to men that did not (IRR 0.70; 95% CI 0.57-0.86). By contrast, women had a significantly higher incidence rate for schizophrenia onset, compared to women that did not redeem doxycycline prescriptions (IRR 1.23; 95% CI 1.08, 1.40). The effects were not found for other tetracycline antibiotics (IRR 1.00; 95% CI 0.91, 1.09). CONCLUSIONS: Doxycycline exposure is associated with a sex-dependent effect on schizophrenia risk. The next steps are replication of the results in independent well-characterized population cohorts, as well as preclinical studies to investigate sex-specific effects of doxycycline on biological mechanisms implicated in schizophrenia.