Doxycycline Prophylaxis Research Articles

Review of doxycycline for prophylaxis of sexually transmitted infections

AbstractThe surging rates of STIs necessitate medical practitioners in the appropriate specialties to focus on rapid recognition, treatment and prevention of these conditions. Through both pre‐ and post‐exposure prophylaxis with doxycycline, dermatologists can provide up‐to‐date treatment in the field of venereology. Herein, we review the results of clinical trials in the available literature that investigate doxycycline prophylaxis in the prevention of bacterial STIs. A search was performed using the PubMED and Scopus databases which yielded six clinical trials for our review. Based on the results of these clinical trials, doxycycline prophylaxis offers significant reductions in bacterial STIs, specifically in men who have sex with men (MSM). Additional research is needed in other high‐risk groups, including females. Moreover, additional research is needed to determine the effects of doxycycline prophylaxis on tetracycline resistance in STI‐causing bacteria. As the utilization of doxycycline prophylaxis for STIs becomes more common, it is important that dermatologists become familiar with the data surrounding this prevention regimen and patient populations who may seek to know more about it. More research is needed to determine benefits in other subpopulations, antimicrobial resistance and cost effectiveness.

Acceptability of doxycycline prophylaxis, prior antibiotic use, and knowledge of antimicrobial resistance among Australian gay and bisexual men and non-binary people.

There is growing interest in novel sexually transmissible infection (STI) prevention strategies, including doxycycline post-exposure prophylaxis (doxy-PEP). We assessed interest in doxy-PEP and other STI prevention strategies among gay and bisexual men and non-binary people in Australia, as well as prior antibiotic use for STI prevention, and knowledge of antimicrobial resistance (AMR). We conducted a national, online survey in June-July 2023. Multivariable logistic regression was used to identify factors associated with the acceptability of doxy-PEP. Of 2,046 participants, 26.9% had been diagnosed with an STI in the previous year. Condoms were rated as an acceptable STI prevention strategy by 45.1% of the sample, STI pre-exposure prophylaxis by 54.0%, and doxy-PEP by 75.8%. Previous antibiotic use for STI prevention was reported by 7.5% of the sample, and 2.6% were currently using antibiotics for STI prevention. Over half the sample (62.1%) had some knowledge of AMR. Of those who knew something about AMR,76.2% were concerned about it. Interest in using doxy-PEP was independently associated with previous use of antibiotics for STI prevention (adjusted odds ratio 3.09, 95%CI = 1.78-5.35, p < 0.001), while those who were concerned about AMR were less interested in it (AOR 0.51, 95%CI = 0.36-0.72, p < 0.001). Doxy-PEP was highly acceptable to gay and bisexual men and non-binary people in Australia, and few factors distinguished between interest in using it or not. We recommend community and professional discussion and education about the effective use of doxy-PEP, AMR, and who would most benefit from doxy-PEP.

Doxycycline prophylaxis for the prevention of sexually transmitted infections: A systematic review and meta-analysis of randomized controlled trials

ObjectivesTo investigate the effects of doxycycline pre- and post-exposure prophylaxis (doxy-PrEP/PEP) on bacterial sexually transmitted infections (STIs) by conducting a systematic review and meta-analysis. MethodsPubMed, Embase, and CENTRAL were searched for randomized controlled trials (RCTs), including ongoing studies published until November 7, 2023. Our primary endpoint was the incidence of bacterial STIs measured as the number of visits with an STI per total number of visits. Random-effects model was used to estimate pooled effect sizes. The study was registered with PROSPERO, CRD42023478486. ResultsWe identified six eligible studies containing data from seven articles and four conference abstracts, enrolling men who have sex with men (MSM), transgender women (TGW), and cisgender women (CGW). The pooled analysis of 1,766 participants with 602 newly diagnosed STIs showed a 56% decrease in the overall STI incidence using doxy-PrEP/PEP (RR = 0.44; 95% CI: 0.30-0.65; I2 = 73%). For doxy-PEP, including MSM and TGW only, the RR observed for overall STI incidence was 0.40 (95% CI: 0.28-0.57; I² = 37%), 0.19 (95% CI: 0.08-0.44; I² = 39%) for chlamydia, 0.23 (0.14-0.36; I² = 0%) for syphilis and 0.55 (95% CI: 0.34-0.87; I² = 41%) for gonorrhea. No serious adverse events were reported in the studies. The certainty of evidence regarding the efficacy of doxy-PEP among MSM and TGW was graded as high. ConclusionDoxy-PEP significantly reduces the number of new cases of chlamydia and syphilis and is potentially effective against gonorrhea, influenced by local resistance patterns. Thus, it is a promising tool in the prevention of bacterial STIs among MSM and TGW.

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women

(Abstracted from N Engl J Med 2024;389:2331–2340) Around the globe, bacterial sexually transmitted infections (STIs) are increasing, with 374 million estimated annual infections of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum. The burden of STI sequelae is disproportionately endured by women, with resulting effects such as chronic pain, pelvic inflammatory disease, ectopic pregnancy, infertility, pregnancy/fetal complications, and increased risk of human immunodeficiency virus (HIV) acquisition.

Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design

Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population. ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing). Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9-18). The median age was 40 years (34-48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12-0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60-1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events. Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored. ANRS Maladies Infectieuses Emergentes. For the French translation of the abstract see Supplementary Materials section.

Doxycycline prophylaxis for bacterial sexually transmitted infections: evaluating effectiveness, risks, and challenges

Doxycycline prophylaxis for bacterial sexually transmitted infections: evaluating effectiveness, risks, and challenges

Filling in the Gaps: Updates on Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections.

Over the past two decades, cases of sexually transmitted infections (STIs) due to syphilis, gonorrhea, and chlamydia have been rising in the United States, disproportionately among gay, bisexual, and other men who have sex with men (MSM), as well as racial and ethnic minorities of all genders. In this review, we address updates about the evidence on doxycycline post-exposure prophylaxis (doxy-PEP) for prevention of bacterial STIs, including efficacy, safety, antimicrobial resistance (AMR), acceptability, modeling population impact, and evolving guidelines for use. Equitable implementation of doxy-PEP will require evaluation of who is offered and initiates it, understanding patterns of use and longer-term STI incidence and AMR, provider training, and tailored community education.

Doxycycline Prophylaxis for Skin and Soft Tissue Infections in Naval Special Warfare Trainees, United States1.

In 2015, several severe cases of skin and soft tissue infection (SSTI) among US Naval Special Warfare trainees prompted the introduction of doxycycline prophylaxis during the highest-risk portion of training, Hell Week. We performed a retrospective analysis of the effect of this intervention on SSTI incidence and resulting hospital admissions during 2013-2020. In total, 3,371 trainees underwent Hell Week training during the study period; 284 SSTIs were diagnosed overall, 29 of which led to hospitalization. After doxycycline prophylaxis was introduced, admission rates for SSTI decreased from 1.37 to 0.64 admissions/100 trainees (p = 0.036). Overall SSTI rates remained stable at 7.42 to 8.86 SSTIs/100 trainees (p = 0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p = 0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p = 0.034). Doxycycline prophylaxis was associated with decreased frequency and severity of hospitalization for SSTIs among this population.

Doxycycline in STI Prophylaxis—A Literature Review

Background: Since the implementation of pre-exposure prophylaxis (PrEP) in HIV prevention, a significant increase in the prevalence of other sexually transmitted infections (STIs) has been reported, especially among men who have sex with men (MSM). Doxycycline is being examined as a potential pharmacological agent in preventing these infections. This review aims to summarize available data on the effectiveness and potential side effects of doxycycline for the prevention of bacterial STIs. Methods: We reviewed the National Library of Medicine and the National Center of Biotechnology Information in order to find clinical trials and relevant observational studies regarding doxycycline usage in STI prophylaxis. Results: Doxycycline prophylaxis reduced the risk of acquiring chlamydia, syphilis, and, in a majority of the trials, the risk of gonorrhea. The clinical trials on doxycycline STI prophylaxis were underpowered to determine if doxycycline promotes the selection of resistance in Neisseria gonorrhoeae and Chlamydia trachomatis. Additionally, no serious side effects of this preventive measure have been reported. None of the studies aimed to compare the efficacy of post- and pre-exposure prophylaxis of STDs with doxycycline. Conclusions: The preliminary results regarding STI prophylaxis with doxycycline seem to be promising. Further research is needed to determine the potential risk of doxycycline prophylactic prescription.

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women

BackgroundDoxycycline 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.MethodsWe 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.ResultsA 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.ConclusionsAmong 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.)

Prophylaxis Failure and Successful Management of Delayed-Onset Malaria with Renal Complications: A Case Report with Oral Artemether-Lumefantrine Treatment

This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while traveling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient’s clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on thin blood smears. Due to limited access to parenteral antimalarial medications in Kosovo, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient’s recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement.

1380. Impact of Doxycycline Prophylaxis on Skin and Soft Tissue Infections in Naval Special Warfare Trainees

Abstract Background Several severe cases of SSTIs caused by salt-water associated Gram-negative pathogens (mainly Shewanella algae) among U.S. Naval Special Warfare (NSW) trainees prompted introduction of doxycycline prophylaxis during the highest risk portion of training, “Hell Week”. We present analysis of this intervention’s impact on disease incidence and hospital admission for serious SSTI. Necrotizing fasciitis caused by Vibrio harveyi in an NSW trainee during “Hell Week” prior to introduction of doxycycline prophylaxis. Methods We performed a retrospective cohort study examining data from hospital admissions for SSTI in trainees between 2013-2020. We assessed hospital admission rates for SSTIs, hospitalization rates per SSTI diagnosed at the clinic level, overall rates of SSTI, length of hospital stays and blood and wound culture data. We then compared data from pre- and post-intervention cohorts. Results 3371 NSW trainees participated in “Hell Week” training during the study period with 284 SSTIs diagnosed overall, 29 of which led to hospital admission. After introduction of doxycycline prophylaxis, admission rates for SSTI decreased from 1.37 to 0.64 admissions per 100 trainees (p=0.036). Overall SSTI rates diagnosed at the clinic level remained stable from 7.42 to 8.86 SSTI per 100 trainees (p=0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p=0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p=0.034). Blood and wound culture data showed a notable decrease in SSTI from salt-water associated Gram-negative rods (Shewanella algae and Vibrio spp.). Total number of SSTI diagnosed at Naval Special Warfare Center (NSWCEN) medical clinic each “Hell Week” training period with corresponding percentage of NSW trainees diagnosed with SSTI in each class. Date of doxycycline prophylaxis initiation labeled for reference. Wound and blood culture (Cx) data from the pre-intervention and post-intervention cohorts Conclusion Doxycycline prophylaxis during “Hell Week” training for NSW trainees was associated with decreased frequency and severity of hospitalization for SSTI, as well as near elimination of infection with invasive salt-water associated pathogens. Disclosures All Authors: No reported disclosures.

P884: POTENTIAL BENEFIT OF POST-TRANSPLANT DOXYCYCLINE IN AL ACHIEVING HEMATOLOGICAL RESPONSE AFTER AUTOLOGOUS STEM CELL TRANSPLANT – LONG TERM FOLLOW UP

Background: Systemic light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by multiorgan deposition of fibrils composed of misfolded immunoglobulin light chains. Current treatment strategies targeting the plasma cell clone do not result in immediate organ recovery, and thus effective fibril-directed therapies are needed. Doxycycline has been shown to disrupt amyloid fibril formation in preclinical models. In 2012, we reported initial results on the impact of posttransplant prophylaxis with doxycycline using data from 445 AL amyloidosis patients; prophylaxis with doxycycline was associated with improved survival compared to penicillin in those achieving hematologic response. Since then, few studies have evaluated doxycycline use in AL amyloidosis, mainly in combination with induction chemotherapy, with mixed results. We provide here updated results on outcomes of AL amyloidosis patients who received doxycycline prophylaxis post autologous stem cell transplantation (ASCT) in our institution. Aims: To evaluate the impact of doxycycline use for post-ASCT antimicrobial prophylaxis on survival in AL amyloidosis patients. Methods: We included 553 patients who underwent ASCT from July 1996 to June 2014. We excluded patients who died within 100 days of ASCT. Doxycycline 100 mg daily was substituted for penicillin prophylaxis in patients with penicillin allergy; since 2013, doxycycline has become the standard for prophylaxis in AL amyloidosis at our institution. Prophylaxis was typically continued for a year after ASCT. Antibiotic type was determined by review of medical records. The Kaplan-Meier method was used to estimate time to next treatment (TTNT) and overall survival (OS), both measured from the time of transplant; curves were compared using the log-rank test. Results: Median age was 59 and 60% were male. The median time from diagnosis to ASCT was 4 months; 90% had early ASCT (within 1 year of diagnosis) and 57% received upfront ASCT without prior induction. Penicillin was used for prophylaxis in 67% (372 patients); the rest received doxycycline. Hematologic and organ response rates were similar in the 2 groups. Median follow up from ASCT was 10.5 vs. 13.6 years in the doxycycline and penicillin groups, respectively. Among patients with early ASCT, TTNT was 5.5 (95%CI: 4.2-8.1) vs. 5.8 (95%CI: 4.7-6.8) years, respectively (P=0.95). Median OS was 12.0 (95%CI: 11.0-19.6) vs. 11.0 (95%CI: 9.6-12.7) years, respectively (P=0.17); 5- and 10-year OS rates were 81% vs. 75% and 62% vs. 54% in the doxycycline and penicillin groups, respectively. Among patients with day 100 hematologic response, there was a non-statistically significant trend towards improved OS with doxycycline, but no difference in those without hematologic response: median OS with doxycycline vs. penicillin was 21.1 vs. 14.6 years in patients with day 100 dFLC <4 mg/dL (P=0.18) Figure 1a. In patients with normal day 100 FLCr, median OS was NR vs. 12.8 years, respectively (P=0.10) Figure 1b. There was no difference between the 2 groups when OS was stratified by Mayo 2012 stage (1-2 vs 3-4), number of involved organs (1 vs. >1), ASCT period (before or after 2012), or pre-ASCT induction (Yes vs. No). Image:Summary/Conclusion: After 13 years of follow up we observed a trend towards improved OS with doxycycline as post-ASCT prophylaxis in patients who achieve a hematological response. Prospective studies are needed to elucidate whether doxycycline improves outcomes in AL amyloidosis and identify the optimal dose, duration, timing, and the subset of patients likely to benefit.

Vomiting and risk of endotracheal intubation related to preoperative doxycycline use for dilation and evacuation

ObjectiveTo describe the rate of vomiting from oral doxycycline 200 mg given the night before second trimester dilation and evacuation (D&E), proportion of anesthesia modalities, and anesthetic complications. Study DesignWe conducted a single-institution retrospective cohort study of patients presenting for second trimester D&E (14-0/7 to 23-6/7 weeks gestation) July 1, 2019-June30, 2020 following their scheduled preoperative visit as identified by billing codes. We recorded vomiting within 30 minutes of ingestion, anesthetic modality, and anesthetic complications. We tested for associations using chi-square or Fisher's exact test for categorical variables and Wilcoxon-rank sum for non-normal numeric variables. ResultsWe reviewed 702 charts, of which 461 (66%) met inclusion criteria and 420 (60%) took doxycycline as prescribed. Of those who took doxycycline as prescribed, 30 (7.14%) reported vomiting within 30 minutes of ingestion. Nulliparity, primigravida and age less than 30 were significantly associated with vomiting (p = 0.005, p < 0.001 and p = 0.03, respectively), but gestational age (p = 0.53), BMI (p = 0.93), and gastrointestinal conditions (p > 0.99) were not. Only gravidity (p < 0.001) and parity (p = 0.01) remained significant in each of their respective multivariate models. None of the 10 patients who received general endotracheal tube anesthesia (2.4%) had vomited from doxycycline preoperatively. We observed 5 (1.2%) anesthetic complications (postoperative nausea or vomiting, anaphylaxis, and aspiration) that occurred only in those without vomiting. ConclusionsVomiting rates following doxycycline were lower than those previously published. We found no significant association between doxycycline-associated vomiting and increased need for general endotracheal tube anesthesia or anesthetic complications; however, our study is underpowered to draw further conclusions. ImplicationsThe findings of this study are consistent with guidelines indicating deep sedation as an effective anesthetic modality with low complication rates. Nulliparous patients may benefit from administration of an antiemetic prior to doxycycline prophylaxis, but routine antiemetic use may not be necessary.

A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora.

ObjectivesThere is interest in doxycycline as prophylaxis against sexually transmitted infections (STIs), but concern about antimicrobial resistance (AMR). We conducted a systematic review (CRD42021273301) of the impact of oral tetracycline-class antibiotics on AMR in normal flora.MethodsWe searched MEDLINE, EMBASE, the Cochrane Library (1940–2021) and conference proceedings (2014–21) for randomized controlled trials in adults comparing daily oral tetracycline-class antibiotics to non-tetracycline controls. The primary outcome was AMR to tetracyclines; secondary outcomes included resistance to non-tetracyclines. Data were inappropriate for meta-analysis, so we analysed findings descriptively.ResultsOur search yielded 6265 abstracts of which 7 articles fulfilled inclusion criteria. Most were at moderate/high risk of bias, generally due to inadequate methodologic reporting. Studies used doxycycline, tetracycline, oxytetracycline or minocycline for 2–18 weeks. Most observed an increased burden of tetracycline resistance, including in subgingival (n = 3 studies), gastrointestinal (n = 2) and upper respiratory tract (n = 1) flora; one study of skin flora found no change in tetracycline-resistant Propionibacterium species after 18 weeks of oxytetracycline/minocycline. Four studies reassessed AMR at 2–50 weeks post-intervention and reported varying degrees of resistance. Three articles reported on the prevalence of non-tetracycline AMR after doxycycline prophylaxis, of which one found a transient increase among gastrointestinal Escherichia coli; the other two showed no difference from control.ConclusionsAlthough the effects are modest and transient, limited data from small prospective studies may suggest that oral tetracyclines for 2–18 weeks increase resistance in subgingival, gastrointestinal and upper respiratory tract flora. STI prophylaxis trials should include AMR in commensal bacteria as study outcomes.

Prophylactic use of antibiotic for incomplete and missed miscarriage, prior to medical and surgical management: a randomized controlled trial

Introduction: Miscarriage is a common gynaecological problem in day to day practice. Post miscarriage care is a challenging area coming under reproductive health. Prevention of pelvic sepsis is a main component. Effective antibiotic prophylaxis at the time of treatment for incomplete and missed miscarriage may be the answer for it. But in current practice, there is conflicting evidence and no clear guidance for the necessity of antibiotic prophylaxis. Objective: To determine the effectiveness of prophylactic doxycycline use, prior to surgical and medical evacuation of incomplete and missed miscarriage, in view of reducing the post -procedure pelvic infections. Method: Three hundred and ninety four patients were randomized into two groups. One group (n=200) received 200mg doxycycline single dose and the other group (n=194) received placebo single dose, one hour prior to the medical and surgical management. Post procedure pelvic infection was assessed by five clinical parameters within three days and two weeks later. SPSS used for the data analysis. Result: There were no statistically significant differences in the age, parity, number of children and gestational age in between the doxycycline and placebo groups. Post intervention pelvic infection was diagnosed 4% in the doxycycline group and 6.18% in the placebo group within three days, which was not statistically significant (P=0.367). It was 4.5% and 8.7% for doxycycline and placebo treated groups respectively at two weeks. It was also not clinically significant (P=0.104). There was no statistically significant difference in the type of miscarriage or the type of interventions in between the two groups. Conclusion: The study revealed that single dose doxycycline prophylaxis prior to medical and surgical management of miscarriage was not able to achieve a statistically significant reduction in post intervention pelvic infection.

Modeling the Cost-Effectiveness of Interventions to Prevent Plague in Madagascar.

Plague (Yersinia pestis) remains endemic in certain parts of the world. We assessed the cost-effectiveness of plague control interventions recommended by the World Health Organization with particular consideration to intervention coverage and timing. We developed a dynamic model of the spread of plague between interacting populations of humans, rats, and fleas and performed a cost-effectiveness analysis calibrated to a 2017 Madagascar outbreak. We assessed three interventions alone and in combination: expanded access to antibiotic treatment with doxycycline, mass distribution of doxycycline prophylaxis, and mass distribution of malathion. We varied intervention timing and coverage levels. We calculated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios from a healthcare perspective. The preferred intervention, using a cost-effectiveness threshold of $1350/QALY (GDP per capita in Madagascar), was expanded access to antibiotic treatment with doxycycline with 100% coverage starting immediately after the first reported case, gaining 543 QALYs at an incremental cost of $1023/QALY gained. Sensitivity analyses support expanded access to antibiotic treatment and leave open the possibility that mass distribution of doxycycline prophylaxis or mass distribution of malathion could be cost-effective. Our analysis highlights the potential for rapid expansion of access to doxycycline upon recognition of plague outbreaks to cost-effectively prevent future large-scale plague outbreaks and highlights the importance of intervention timing.

Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study.

The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available. We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity. We assessed the rate of treatment-related and panitumumab-related adverse events (AEs), treatment intensity, progression-free survival (PFS), and overall survival (OS). A total of 226 patients, out of the 229 enrolled in the Valentino study, were eligible for the analysis. Overall, 143 (63%) and 83 (37%) patients received or not the antibiotic prophylaxis for skin toxicity. Any grade and G3/4 panitumumab-related AEs were reported in 89% versus 92% (p = 0.650) and 27% versus 27% (p = 1.000) patients who received or not the pre-emptive prophylaxis, respectively. Any grade and G3/4 skin rash occurred in 81% versus 90% (p = 0.085) and 27% versus 25% (p = 0.876) patients receiving or not the prophylaxis, respectively. No significant differences in terms of treatment duration, treatment delays or dose reductions, PFS, and OS were observed in the two sub-populations. The adequate management of anti-EGFR-related skin toxicity is fundamental to optimize the outcome of mCRC patients, balancing the survival benefit with patients' quality of life, especially in the first-line setting.

Use of Antibiotics in Chronic Obstructive Pulmonary Disease: What is Their Current Role in Older Patients?

Chronic obstructive pulmonary disease (COPD) has considerable morbidity and mortality in the older adult population. The role of antibiotics in the management of acute exacerbations of COPD (AECOPD) is currently evolving. Despite only mild benefits, most patients with AECOPD in ambulatory settings receive antibiotics based on clinical criteria. Utilization of point-of-care C-reactive protein (CRP) has reduced antibiotic prescriptions by 20% without compromising clinical outcomes. A strict protocol allowing antibiotic use only in patients with clinical criteria and CRP ≥ 20mg/L has the potential to reduce antibiotic prescriptions for AECOPD in ambulatory settings by nearly 50%. Amoxicillin and doxycycline are commonly prescribed for AECOPD based on a favorable benefit-to-risk ratio. Prophylactic antibiotics have also been used in selected patients with severe COPD and frequent exacerbations. The use of continuous or intermittent azithromycin has demonstrated efficacy in reducing the frequency of AECOPD in this population; however, this approach has potential for the development of antibiotic resistance and adverse effects. The use of azithromycin prophylaxis in older patients with frequent AECOPD should be determined on a case-by-case basis after careful review, discussion, and counseling of the potential benefits and risks. The role of continuous doxycycline and pulsed moxifloxacin prophylaxis for frequent AECOPD remains controversial.

448. Impact of Doxycycline Prophylaxis on Skin and Soft-Tissue Infection Incidence in Naval Special Warfare Trainees

BackgroundSkin and soft-tissue infections (SSTIs) are a common complication of military training. Naval Special Warfare (NSW) training requires prolonged periods of extreme physical exertion and unique environmental exposures, including extended immersion in ocean water. A centerpiece of SEAL training is referred to as “Hell Week” (HW), a colloquial term to reflect the intense physical obstacles and exposure to extreme environmental conditions endured by candidates. Due to such environmental exposures, NSW trainees are at increased risk for SSTI due to uncommon organisms. A prior outbreak of Shewanella SSTI and bacteremia among NSW trainees led to the initiation of prophylactic doxycycline 100 mg daily during and for 7 days after HW to attempt to reduce this risk. The efficacy of this intervention is undetermined.MethodsDoxycycline prophylaxis was initiated in August 2015. We conducted a retrospective analysis of SSTI incidence presenting for medical attention among NSW trainees from April 2013 to November 2018, using case records collected prospectively at the Naval Special Warfare Center. The incidence of SSTI was calculated based on the size of a given class and the number of affected trainees. SSTI cases were then divided and analyzed as occurring during vs. after HW.ResultsThe pre-intervention cohort consisted of 1626 NSW trainees. A total of 76 trainees developed SSTI, with 20 cases during HW and 56 cases in the post-HW period. In the post-intervention cohort, 2022 trainees experienced a total of 81 cases of SSTI during HW and 83 in the post-HW period. 45% of all SSTI cases occurred in the months of June, July, and August. The incidence of cellulitis between the pre- and post-intervention cohorts during HW was 2% and 4%, respectively, and 5% and 6.4% in the post-HW period. There were no hospitalizations for invasive gram-negative infections following the initiation of doxycycline prophylaxis.ConclusionDoxycycline prophylaxis does not appear to reduce the incidence of SSTI but may reduce the incidence of certain severe infections. The choice of antibiotic prophylaxis and dosing may require further investigation. Seasonality of SSTI among NSW trainees is an unexpected finding and may provide valuable information for the prevention of future illness. Disclosures All authors: No reported disclosures.