Doxycycline Added to Prednisolone in Outpatient-Treated Acute Exacerbations of COPD: A Cost-Effectiveness Analysis Alongside a Randomised Controlled Trial.

BACKGROUND: Most patients with mild to severe chronic obstructive pulmonary disease (COPD) experience exacerbations, which are also associated with increased healthcare costs. Despite limited evidence of antibiotics' benefits for exacerbations in outpatients, antibiotics are frequently prescribed. The aim of this study was to investigate whether doxycycline added to prednisolone is cost-effective compared to placebo plus prednisolone for the treatment of COPD acute exacerbations. METHODS: An economic evaluation from the societal perspective was performed alongside a 2-year randomised trial in 301 COPD patients in the Netherlands. The primary outcome was cost per quality-adjusted life year (QALY). The secondary outcome was cost per exacerbation prevented. Healthcare utilisation and loss of productivity were measured using retrospective questionnaires and clinical report forms. Missing data were imputed using multiple imputations by chained equations. Bootstrapping was employed to estimate statistical uncertainty surrounding cost-effectiveness outcomes. A sensitivity analysis from the healthcare perspective was performed. RESULTS: On average, costs in the doxycycline group were €898 higher than in the placebo group [95% confidence interval (CI) - 2617 to 4409] for the 2 years of follow-up. QALY values were higher in the doxycycline group (0.03; 95% CI - 0.00 to 0.06), but patients in this group suffered 0.01 more exacerbations than patients in the placebo group (95% CI - 0.14 to 0.11). Cost-effectiveness acceptability curves showed that the probability of doxycycline being cost-effective compared to placebo was 61% and 43% at a willingness-to-pay threshold of €34,000 per QALY and per exacerbation avoided, respectively. The sensitivity analysis showed similar results from the healthcare system perspective. CONCLUSIONS: In patients with mild to severe COPD treated for exacerbations in an outpatient setting, doxycycline added to prednisolone is not cost-effective compared to prednisolone plus placebo over a 2-year period.

Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease.

BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not been investigated. METHODS: This prospective economic evaluation, adhering a societal perspective, was performed alongside the PLEASE study, a multicenter, placebo-controlled, double-blind 1:1:1 randomized clinical trial in which all patients received open-label intravenous ceftriaxone for two weeks before the 12-week randomized blinded oral antibiotic regimen (doxycycline, clarithromycin plus hydroxychloroquine, or placebo). Between 2010 and 2013, patients (n = 271) with borreliosis-attributed persistent symptoms were enrolled and followed for one year. Main outcomes were costs, quality-adjusted life years, and incremental net monetary benefit of longer-term versus shorter-term antibiotic therapy. RESULTS: Mean quality-adjusted life years (95% CI) were not significantly different (p = 0.96): 0.82 (0.77-0.88) for ceftriaxone/doxycycline (n = 82), 0.81 (0.76-0.88) for ceftriaxone/clarithromycin-hydroxychloroquine (n = 93), and 0.81 (0.76-0.86) for ceftriaxone/placebo (n = 96). Total societal costs per patient (95% CI) were not significantly different either (p = 0.35): €11,995 (€8,823-€15,670) for ceftriaxone/doxycycline, €12,202 (€9,572-€15,253) for ceftriaxone/clarithromycin-hydroxychloroquine, and €15,249 (€11,294-€19,781) for ceftriaxone/placebo. Incremental net monetary benefit (95% CI) for ceftriaxone/doxycycline compared to ceftriaxone/placebo varied from €3,317 (-€2,199-€8,998) to €4,285 (-€6,085-€14,524) over the willingness-to-pay range, and that of ceftriaxone/clarithromycin-hydroxychloroquine compared to ceftriaxone/placebo from €3,098 (-€888-€7,172) to €3,710 (-€4,254-€11,651). For every willingness-to-pay threshold, the incremental net monetary benefits did not significantly differ from zero. CONCLUSION: The longer-term treatments were similar with regard to costs, effectiveness and cost-effectiveness compared to shorter-term treatment in patients with borreliosis-attributed persistent symptoms after one year of follow-up. Given the results of this study, and taking into account the external costs associated with antibiotic resistance, the shorter-term treatment is the antibiotic regimen of first choice.

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial.

BACKGROUND: The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. METHODS: Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. DISCUSSION: This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. TRIAL REGISTRATION: Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849 . (Registered on April 17, 2013).

Assessment of parasitological findings in heartworm-infected beagles treated with Advantage Multi® for dogs (10% imidacloprid + 2.5% moxidectin) and doxycycline.

BACKGROUND: Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles. METHODS: This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer's recommendations and read using a spectrophotometer at 490 nm. RESULTS: All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10-12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0-2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001). CONCLUSIONS: This study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

Characteristics and clinical assessment of antibiotic delivery by chitosan sponge in the high-risk diabetic foot: a case series.

OBJECTIVE: The local delivery of antimicrobials is attractive for a number of reasons. Chitosan, a biodegradable polysaccharide sponge material, has been proposed as medium to deliver antibiotics directly to wounds. In this report we evaluate the safety and practicality of antimicrobial delivery via chitosan sponge. METHOD: We present the clinical course and systemic absorption characteristics of three cases of people with diabetic foot wounds treated with antibiotic soaked chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN). The antibiotic sponge was made by reconstituting 1.2g tobramycin or 100mg doxycycline in 10-15ml saline and saturating the sponge with the solution. The sponge was then applied to the wounds. Serum levels of each respective antibiotic were evaluated after application. Additional in vitro studies were conducted evaluating elution of antibiotics from the chitosan sponge at established minimum inhibitory concentrations (MIC) for Staphylococcus aureus over 28 days. RESULTS: No patient experienced adverse local or systemic effects due to the sponge treatment. The measured serum levels applied antibiotics remained far less than established minimums after intravenous therapy. Each patient required further treatment, however local infection or contamination resolved during the course of their hospital stay after the chitosan/antibiotic application. CONCLUSION: The use of antibiotic-impregnated chitosan sponges appears a safe and effective mechanism of local delivery of antimicrobials in wounds. Future studies and clinical trials are ongoing to confirm these results and to guide clinical applications.

Cost of Medications Recommended by Canadian Acne Clinical Practice Guidelines.

BACKGROUND: Acne affects a large proportion of the Canadian population and has psychosocial and financial consequences. OBJECTIVE: We provide cost information for treatments recommended by the Canadian acne guidelines. METHODS: Highest level recommendations were selected for 3-month usage cost. RESULTS: Three-month estimated treatment costs were as follows: topical retinoids ($14.40-$73.80), benzoyl peroxide (BPO; $6.75), fixed-dose BPO-clindamycin ($40.95-$44.10) and BPO-adapalene ($73.80), oral antibiotics ($25.20 for tetracycline 250 mg qid; $52.20 and $52.74 for doxycycline 50 mg bid and 100 mg od, respectively), and hormonal therapy ($26.46-$37.80 for ethinyl estradiol [EE] 0.030 mg/drospirenone 3mg and $75.60-108.99 for EE 0.035 mg/cyproterone acetate 2 mg). Oral isotretinoin 3-month costs ranged from $393.96 to $478.80. CONCLUSIONS: Awareness of costs of recommended treatments may facilitate improved outcomes by increasing procurement and adherence.

Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: a randomized, controlled pilot study.

BACKGROUND: Incident syphilis infections continue to be especially prevalent among a core group of HIV-infected men who have sex with men (MSM). Because of synergy between syphilis and HIV infections, innovative means for controlling incident syphilis infections are needed. METHODS: Thirty MSM who had syphilis twice or more since their HIV diagnosis were randomized to receive either daily doxycycline prophylaxis or contingency management (CM) with incentive payments for remaining free of sexually transmitted diseases (STDs). Participants were tested for the bacterial STDs gonorrhea (Neisseria gonorrhoeae), chlamydia (Chlamydia trachomatis) and syphilis at weeks 12, 24, 36, and 48 and completed a behavioral risk questionnaire during each visit to assess number of partners, condom use, and drug use since the last visit. Generalized linear mixed models were used to analyze differences between arms in STD incidence and risk behaviors at follow-up. RESULTS: Doxycycline arm participants were significantly less likely to test positive for any selected bacterial STD during 48 weeks of follow-up (odds ratio, 0.27; confidence interval, 0.09-0.83) compared with CM arm participants (P = 0.02).There were no significant self-reported risk behavior differences between the doxycycline and CM arms at follow-up. CONCLUSIONS: Daily doxycycline taken prophylactically was associated with a decreased incidence of N. gonorrhoeae, C. trachomatis, or syphilis incident infections among a core group of HIV-infected MSM at high risk for these infections. Safe and effective biomedical tools should be included in the efforts to control transmission of syphilis, especially in this population. A randomized clinical trial should be conducted to confirm and extend these findings.

Doxiciclina para tratamento da doença inflamatória pélvica / Doxycycline for treatment of pelvic inflammatory disease

CONTEXTO: A Doença Inflamatória Pélvica (DIP) é uma síndrome clínica atribuída à ascensão dos microorganismos do trato genital inferior, com comprometimento do endométrio, trompas, anexos uterinos e/ou estruturas contíguas. Os microorganismos mais comumente envolvidos são Neisseria gonorrhoeae e Chlamydia trachomatis. A Organizaçao Mundial da Saúde (OMS) estima a ocorrência de 1.967.200 casos de clamídia e de 1.541.800 casos de gonorreia na população sexualmente ativa no Brasil, por ano. Dentre mulheres com infecções não tratadas por clamídia e/ou gonorreia, 10 a 40% desenvolvem doença inflamatória pélvica (DIP). A doxiciclina é um dos medicamentos recomendados pelo Ministério da Saúda para tratamento da DIP, mas ainda não é disponibilizado no SUS para essa indicação. TRATAMENTO RECOMENDADO: De acordo com o Manual de Controle das DST (2006)2, do Ministério da Saúde, os tratamentos recomendados para DIP leve, sem sinais de peritonismo ou febre (tratamento ambulatorial), deve ser realizado da seguinte forma: -Esquema 1: Ceftriaxona 250 mg, IM, dose única + Doxiciclina 100 mg, VO de 12/12 horas, por 14 dias + Metronidazol 500 mg, VO, de 12/12 horas, por 14 dias; -Esquema 2: Ofloxacina 400 mg, VO de 12/12 horas por 14 dias Ou Ciprofloxacina 500 mg 12/12horas por 14 dias + Doxiciclina 100 mg, VO de 12/12 horas por 14 dias + Metronidazol 500 mg, VO de 12/12 horas, por 14 dias. CONSIDERAÇÕES FINAIS: A doxiciclina é uma opção de tratamento para a doença inflamatória pélvica (DIP). As estimativas de impacto orçamentário anual resultante da ampliação de uso da doxiciclina no SUS, para tratamento da DIP provocada por clamídia e/ou gonorreia, variaram de R$274.528,36 até R$ 1.098.113,45. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 11/06/2015 deliberaram, por unanimidade, recomendar a ampliação de uso da doxiciclina 100mg, em comprimido, para tratamento da doença inflamatória pélvica (DIP). DECISÃO: PORTARIA Nº 56, de 1 de outubro de 2015 - Torna pública a decisão de incorporar a doxiciclina 100mg comprimidos para tratamento da doença inflamatória pélvica (DIP), conforme normas técnicas definidas pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS.

Doxiciclina para tratamento da donovanose / Doxycycline for treatment of donovanose

CONTEXTO: A donovanose é uma doença progressiva e crônica, freqüentemente associada à transmissão sexual, provocada pela bactéria Klebsiella granulomatis e acomete principalmente a pele e as mucosas das regiões genitais, perianais e inguinais. É pouco frequente, com incidência de aproximadamente 5%, entre as DST. A doxiciclina é um dos medicamentos recomendados pelo Ministério da Saúda para tratamento da donovanose, mas o medicamento ainda não é disponibilizado no SUS para essa indicação. TRATAMENTO RECOMENDADO: O Ministério da Saúde recomenda, no Manual de Controle das DST (2006)2, os seguintes tratamentos para donovanose: -Doxiciclina 100mg, via oral, de 12 em 12 horas por, no mínimo, 3 semanas ou até a cura clínica; ou -Eritromicina (estearato) 500mg, via oral, de 6 em 6 horas por, no mínimo, 3 semanas ou até a cura clínica; ou -Sulfametoxazol+Trimetoprima (800+160mg), via oral, de 12 em 12 horas, por, no mínimo, 3 semanas ou até a cura clínica; ou -Tetraciclina 500mg, de 6 em 6 horas por, no mínimo, 3 semanas ou até a cura clínica; ou -Azitromicina 1g, via oral, em dose única, seguido por 500mg via oral por 3 semanas ou até cicatrizar as lesões. CONSIDERAÇÕES FINAIS: A doxiciclina é uma opção de tratamento para a donovanose. Na comparação entre o custo de tratamento com a doxiciclina 100mg e com os outros medicamentos recomendados pelo Ministério da Saúde e incorporados ao SUS (estolato de eritromicina 500mg, sulfametoxazol+trimetoprima 800+160mg, tetraciclina 500mg e azitromicina 500mg), o custo da doxiciclina foi o menor de todos. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 02/04/2015 deliberaram, por unanimidade, recomendar a incorporação da doxiciclina 100mg, em comprimido, para tratamento da donovanose. DECISÃO: PORTARIA Nº 55, de 1 de outubro de 2015 - Torna pública a decisão de incorporar a doxiciclina 100mg comprimidos para tratamento de donovanose, conforme normas técnicas definidas pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS.

Doxiciclina para tratamento da sífilis / Doxycycline for treatment of syphilis

CONTEXTO: A sífilis é uma doença sexualmente transmissível, causada pela bactéria Treponema Pallidum, infecciosa e sistêmica, a partir de sua manifestação. A OMS estima a ocorrência de 937.000 casos anuais de sífilis na população sexualmente ativa no Brasil. A penicilina é o tratamento de primeira escolha para a sífilis; entretando, alguns indivíduos apresentam reações alérgicas à penicilina e não podem utilizá-la. A doxiciclina, na forma farmacêutica comprimido e na concentração de 100mg, já é disponibilizada pelo SUS, para outra indicação terapêutica. TRATAMENTO RECOMENDADO: A primeira escolha para o tratamento da sífilis é a penicilina benzatina. No caso de pacientes com história comprovada de alergia à penicilina, o Ministério da Saúde recomenda dessensibilização desses pacientes ou tratamento com: eritromicina (na forma estearato ou estolato) 500 mg, via oral, de 6 em 6 horas, por 15 dias para sífilis recente e por 30 dias para sífilis tardia; ou com tetraciclina, na mesma dose; ou ainda doxiciclina 100mg, por via oral, de 12 em 12 horas, por 15 dias na sífilis recente e por 30 dias na sífilis tardia. A tetraciclina, a doxiciclina e o estolato de eritromicina são contraindicados na gestação. CONSIDERAÇÕES FINAIS: A doxiciclina é uma opção de tratamento para a sífilis em pacientes com alergia confirmada à penicilina. Na comparação de custos de tratamento da sífilis entre a doxiciclina 100mg e o estolato de eritromicina 500mg, o custo da doxiciclina foi 7,6 vezes inferior ao do estolato de eritromicina 500mg. Portanto, a escolha da doxiciclina, ao invés da eritromicina, geraria uma economia no orçamento do SUS. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 02/04/2015 deliberaram, por unanimidade, recomendar a incorporação da doxiciclina 100mg, em comprimido, para tratamento da sífilis em pacientes com alergia confirmada à penicilina. DECISÃO: PORTARIA Nº 54, de 1 de outubro de 2015 - Torna pública a decisão de incorporar a doxiciclina 100mg comprimidos para tratamento de sífilis, conforme normas técnicas definidas pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS.

Clinical assessment of post-adulticide complications in Dirofilaria immitis-naturally infected dogs treated with doxycycline and ivermectin.

This study shows that a combination of doxycycline (10mg/kg/sid for 30 days) and ivermectin (6 µg/kg/every 15 days for 6 months) is well tolerated for the treatment of canine heartworm disease (HWD). Monthly echocardiography showed that 84% of treated dogs either progressively improved parameters indicative of pulmonary hypertension or, following slight worsening, resolved all signs. Thoracic radiography showed the persistence of interstitial inflammation, even though also in this case, approximately 70% of the dogs steadily improved or worsened but then improved by the end of the study.

Evaluation of single-dose azithromycin versus standard azithromycin/doxycycline treatment and clinical assessment of regression course in patients with adult inclusion conjunctivitis.

BACKGROUND: Single-dose azithromycin (AZT) has been proved efficient in treating various human Chlamydia infections. However, it has not been thoroughly tested in patients with adult inclusion conjunctivitis (AIC). It is the aim of this study to perform a comparative evaluation of efficacy and safety of one-day AZT with long-term AZT and doxycycline (DOX) regimens in AIC and to present a clinical profile of regression course of the disease. MATERIALS: Eighty-three consecutive adults, with symptoms and signs of chronic conjunctivitis and positive Polymerase Chain Reaction (PCR) for chlamydia, were randomly assigned in four treatment groups; AZT 1-day 1000 mg orally, AZT 500 mg daily 9 and 14 days and DOX 200 mg 21 days orally. Follow-up visits were scheduled 1 and 2 weeks, 1, 3 and 6 months after treatment completion. PCR was repeated at the 2nd post-treatment week to confirm elimination of infectious agent. Detailed record of subjective symptoms and objective signs was performed at all visits. Retreatment rate among groups was evaluated as primary outcome. Regression rate of symptoms/signs among groups was recorded as secondary outcomes. RESULTS: All treatment groups provided statistically equivalent results of retreatment rate. Statistically significant regression of symptoms/signs was documented, initially from the 1st post-treatment week in general, but 1 month was required for complete patients' relief. Follicles were the most common clinical sign with the earliest regression after successful treatment. CONCLUSION: Single-dose azithromycin should be considered as equally reliable treatment option, comparing to long-term alternative regimens for AIC. Patients should wait for one week, until first signs of significant regression become obvious and should consider approximately one month to total relief. Follicles could be reasonably used as a key sign for clinical assessment of treatment success.

Systematic review and meta-analysis of randomized clinical trials in the treatment of human brucellosis.

BACKGROUND: Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. METHODS AND FINDINGS: A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. CONCLUSIONS: Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice.

An open-label, community-based, 12-week assessment of the effectiveness and safety of monotherapy with doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads).

Rosacea is a common inflammatory disorder of the skin of middle-aged and older adults. A unique 40-mg formulation of doxycycline (30-mg immediate-release and 10-mg delayed-release beads) developed for its anti-inflammatory properties is the only US Food and Drug Administration-approved oral medication for the disorder. This report describes the results of the Oracea for Rosacea: A Community-Based Assessment (ORCA) trial, a phase 4 trial of the 40-mg formulation as monotherapy in adults with mild to severe papulopustular rosacea. A total of 1197 participants were enrolled in the monotherapy arm of the 12-week open-label study at 271 community-based investigational sites. The primary outcome measure was a change in the 5-point investigator global assessment (IGA) score from baseline to end point (week 12). Secondary outcome measures included change in the 5-point clinician erythema assessment (CEA) score from baseline to end point, IGA success, and adverse events (AEs). The monotherapy per-protocol (PP) population was selected a priori as the primary analysis population and safety assessments were performed on all participants who received at least 1 dose of the study drug. In the PP population of 826 monotherapy participants who completed the trial, approximately 75% of participants with mild to severe rosacea at baseline were clear or near clear by week 12, according to IGA scores. Furthermore, approximately 75% of participants had CEA scores reflecting none or mild erythema after 12 weeks. In the safety population of 1196 participants, treatment-related AEs were reported in 6.7% of participants that were mainly mild or moderate in severity. Adverse events that occurred in more than 1% of the safety population included diarrhea (1.2%), nausea (1.3%), and headache (1.0%). The incidence of fungal and yeast infections was 0.4%. The results of the ORCA trial support the effectiveness and safety of the 40-mg formulation of doxycycline in patients with papulopustular rosacea.

Management of neurobrucellosis: an assessment of 11 cases.

OBJECTIVE: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy. PATIENTS AND METHODS: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases. RESULTS: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection. CONCLUSIONS: Parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.

Cost-effectiveness of alternative outpatient pelvic inflammatory disease treatment strategies.

OBJECTIVE: Effectiveness differences between outpatient pelvic inflammatory disease (PID) treatment regimens are uncertain, but significant differences in cost exist. GOAL: To examine the influence of antibiotic costs on PID therapy cost-effectiveness. STUDY DESIGN: The authors used a Markov decision model to estimate the cost-effectiveness of recommended antibiotic regimens for PID and performed a value of information analysis to guide future research. RESULTS: Antibiotic costs vary between USD 43 and USD188. Pairwise comparisons, assuming a hypothetical 1% relative risk reduction in PID complications with the more expensive regimen, showed economically reasonable cost-effectiveness ratios. Value of information and sample size considerations support further investigation to detect 10% PID complication rate differences between regimens with >or=USD 50 cost differences. CONCLUSIONS: Within the cost range of recommended regimens, use of more expensive antibiotics would be economically reasonable if relatively small decreases in PID complication rates exist. Further investigation of effectiveness differences between regimens is needed.

Persistence and relapse in brucellosis and need for improved treatment.

Treatment failure and relapse are major problems in the management of brucellosis. In developing countries, treatment with the oral combination doxycycline/rifampicin is preferred because of its convenience. However, its efficacy is lower than that of the doxycycline/streptomycin regimen and is likely further reduced when compliance is poor. Alternative regimens should be investigated in well designed clinical trials to determine whether treatment can be improved. Use of DNA detection as a marker for treatment success and for the prediction of relapse requires confirmation. In the absence of simple and effective treatment regimens, patient education to promote compliance is essential.

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis.

BACKGROUND: Therapeutic guidelines for treatment of late manifestations of Lyme borreliosis have not yet become well established. Patients with symptoms suggesting central nervous system involvement are often treated with courses of intravenous ceftriaxone. This is an expensive treatment approach with potentially severe side effects. We compared the efficacy, side effects and costs of doxycycline and ceftriaxone in the treatment of such patients. PATIENTS AND METHODS: Adult patients qualified for the study if they had nonspecific symptoms suggesting central nervous system involvement for more than six months (but without overt clinical signs of the involvement), had positive serum borrelial antibody titers and/or erythema migrans prior to the onset of symptoms, had not been previously treated with antibiotics and did not have pleocytosis in the cerebrospinal fluid. Patients were given either 100 mg of oral doxycycline twice daily for 4 weeks (23 patients) or 2 g of intravenous ceftriaxone daily for 2 weeks followed by 100 mg of doxycycline twice daily for another 2 weeks (23 patients). Clinical outcome was assessed during a 12-month follow-up period. RESULTS: Improvement in the frequency and/or the intensity of symptoms was reported by more than two-thirds of the 46 patients enrolled in the study. The two treatment regimens were found to be correspondingly effective. Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone. Treatment with doxycycline proved to be much cheaper than with ceftriaxone. CONCLUSIONS: In patients with previously untreated chronic Lyme borreliosis with symptoms suggesting central nervous system involvement but without overt clinical signs of it, and without pleocytosis in the cerebrospinal fluid, treatment with doxycycline is as effective as with ceftriaxone. Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.