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Doxycycline postexposure prophylaxis has been shown to prevent STIs in cisgender men and transgender women. In this trial involving cisgender women in Kenya, STI incidence was not lower with doxycycline than with standard care.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n  = 100), to standard of care (SOC arm, n  = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0–7 doses) for the SOC arm and 42 (IQR: 27–64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome ( P  = 2.3 × 10 −2 ) and from 4% to 15% in the metatranscriptome ( P  = 4.5 × 10 −6 ), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman’s ρ  = 0.23, P  = 9.0 × 10 −3 ) and metatranscriptome (Spearman’s ρ  = 0.55, P  = 3.7 × 10 −8 ). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223 . In participants from a randomized controlled trial, doxy-PEP use over 6 months minimally affected the gut microbiome’s taxonomic composition but increased the abundance and active expression of tetracycline antibiotic resistance genes.

Background/aims To assess the efficacy and safety of oral azithromycin compared with oral doxycycline in patients with meibomian gland dysfunction (MGD) who had failed to respond to prior conservative management. Methods 110 patients (>12 years old) with MGD were randomly assigned to receive either oral 5-day azithromycin (500 mg on day 1 and then 250 mg/day) or 1-month doxycycline (200 mg/day). They also continued eyelid warming/cleaning and artificial tears. A score comprising five symptoms and seven signs (primary outcome) was recorded prior to treatment and at 1 week, and 1 and 2 months after treatment. Total score was the sum of both scores at each follow-up. Side effects were recorded and overall clinical improvement was categorised as excellent, good, fair or poor based on the percentage of change in the total score. Results Symptoms and signs improved significantly in both groups (p=0.001). While improvement of symptoms was not different between the groups, bulbar conjunctival redness (p=0.004) and ocular surface staining (p=0.01) were significantly better in the azithromycin group. The azithromycin group showed a significantly better overall clinical response (p=0.01). Mild gastrointestinal side effects were not significantly different between the groups except for the second visit, when the doxycycline group had significantly more side effects (p=0.002). Conclusions Although both oral azithromycin and doxycycline improved the symptoms of MGD, 5-day oral azithromycin is recommended for its better effect on improving the signs, better overall clinical response and shorter duration of treatment. Trial registration number NCT01783860.

In this trial in women undergoing miscarriage surgery in low-resource countries, antibiotic prophylaxis did not result in a significantly lower risk of pelvic infection, as defined by broad criteria, than placebo. However, benefit was observed in a secondary analysis that defined pelvic infection by strict criteria (signs of infection).

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.

Background Successful H. pylori treatment requires the knowledge of local antimicrobial resistance. Data on the efficacy of H. pylori eradication regimens available in sub-Saharan Africa are scant, hence the optimal treatment is unknown. Our goals were to determine the efficacy of available regimens in Rwanda as well as evaluate the effect of treatment on health-related quality of life (HRQoL) in patients undergoing esophagogastroduodenoscopy . Methods This is a randomized controlled trial conducted from November 2015 to October 2016 at a tertiary hospital in Rwanda. Enrollees were 299 patients (35% male, age 42 ± 16 years (mean ± SD)) who had a positive modified rapid urease test on endoscopic biopsies. After a fecal antigen test (FAT) and HRQoL assessment by the Short Form Nepean Dyspepsia Index (SF-NDI) questionnaire, patients were randomized 1:1:1:1 to either a triple therapy combining omeprazole, amoxicillin and one of clarithromycin/ciprofloxacin/metronidazole or a quadruple therapy combining omeprazole, amoxicillin, ciprofloxacin and doxycycline. All therapies were given for a duration of 10 days. The outcome measures were the persistence of positive FAT (treatment failure) 4 to 6 weeks after treatment and change in HRQoL scores. Results The treatment success rate was 80% in the total population and 78% in patients with a history of prior triple therapy. Significant improvement in HRQoL in the total group (HRQoL mean scores before and after treatment respectively: 76 ± 11 and 32 ± 11, p  < 0.001) and the group with functional dyspepsia (HRQoL mean scores before and after treatment respectively: 73 ± 11 and 30 ± 9, P  < 0.001) was observed across all treatment groups. Using clarithromycin based triple therapy (standard of care) as a reference, the group treated with metronidazole had worse HRQoL ( p  = 0.012) and had a trend towards worse treatment outcome ( p  = 0.086) compared to the ciprofloxacin based combination therapies. Conclusion Clarithromycin and ciprofloxacin based combination therapies are effective and safe to use alternatively for H. pylori eradication and improve HRQoL. Among the regimens studied, metronidazole based triple therapy is likely to be clinically inferior. Trial registration The clinical trial was retrospectively registered ( PACTR201804003257400 ) with the Pan African Clinical Trial Registry database, on April 6th, 2018 in South Africa.

The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia. A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 microg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events. One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with doxycycline was well tolerated and the incidence of adverse event to doxycycline or ivermectin did not significantly deviate between treatment groups. A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin. Controlled-Trials.com ISRCTN48118452.

There is no effective therapy for Mansonella perstans , a cause of lymphatic filariasis. In this study, patients were randomly assigned to receive treatment with doxycycline for 6 weeks, targeting the endosymbiont wolbachia, or no treatment. M. perstans microfilaremia was undetectable at 12 months in 67 of 69 treated patients (97%), as compared with 10 of 63 untreated patients (16%). Patients were randomly assigned to receive treatment with doxycycline for 6 weeks, targeting the endosymbiont wolbachia, or no treatment. M. perstans microfilaremia was undetectable at 12 months in 97% of treated patients, as compared with 16% of untreated patients. The filarial parasite Mansonella perstans is endemic in central and western Africa, with a distribution that overlaps that of Wuchereria bancrofti , Loa loa , and Onchocerca volvulus . Transmitted through the bite of an infected midge (culicoides species), infective M. perstans larvae develop over the course of months into adult worms that reside in the serous cavities and mesentery and retroperitoneal tissues. Microfilariae are carried through the bloodstream, and those of M. perstans can be distinguished from those of L. loa and W. bancrofti by their small size, lack of periodicity, and the absence of a sheath. As is . . .

In randomized, double-blind trials, there was no significant difference in the health-related quality of life. Antibiotic treatment is highly effective for the acute and late septic manifestations of Lyme disease, which is caused by the tick-borne bacterium Borrelia burgdorferi . 1 However, some patients have persistent fatigue, myalgias, arthralgias without arthritis, dysesthesias or paresthesias, or mood and memory disturbances after the standard courses of antibiotics. 2 , 3 Persistent symptoms have been reported both in patients who are seropositive for antibodies against B. burgdorferi and in patients who are seronegative. Although the cause of persistent symptoms has not been determined, their temporal association with B. burgdorferi infection has led some physicians to treat patients with prolonged courses of . . .