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.

Comparing efficacy and safety of high-dose and standard-dose rifampicin in the treatment of brucellosis: a randomized clinical trial.

BACKGROUND: In a few studies, higher doses of rifampicin improved the outcome of patients with TB. There is no information regarding efficacy and safety of higher doses of rifampicin in patients with brucellosis. OBJECTIVES: To compare efficacy and safety of higher and standard doses of rifampicin, each with doxycycline, in the treatment of patients with brucellosis. METHODS: Within a randomized clinical trial, clinical response and adverse events of high-dose rifampicin (900-1200 mg/day) plus doxycycline 100 mg twice daily were compared with standard-dose rifampicin (600 mg/day) plus doxycycline 100 mg twice daily in 120 patients with brucellosis. RESULTS: Clinical response occurred in 57 (95%) of patients in the high-dose group and 49 (81.66%) of patients in the standard-dose group (P = 0.04). The most common adverse events of the treatment were nausea (37.5%), skin rash (13.33%), vomiting (10%) and transaminitis (7.22%). Incidence of these events was comparable between the groups. CONCLUSIONS: The rate of clinical response in patients with brucellosis who were treated with high-dose rifampicin plus standard-dose doxycycline was significantly higher than in the patients who received the standard doses of rifampicin and doxycycline, without further adverse events. The high-dose rifampicin therefore improved clinical response in patients with brucellosis with a similar safety profile to the standard dose. If these findings are confirmed in future studies, higher doses of rifampicin may be recommended for treatment of patients with brucellosis.

Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure.

BACKGROUND: Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options. METHODS: This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019-December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline + azithromycin (1 g, day 1; 500 mg, days 2-4) and macrolide-resistant infections combination doxycycline + moxifloxacin (400 mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14-28 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections. RESULTS: Of 100 patients with macrolide-susceptible MG treated with doxycycline + azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1-97.1). Of 247 patients with macrolide-resistant MG receiving doxycycline + moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0-89.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83/D87 was associated with 98.3% cure (95% CI, 93.9-99.8) following doxycycline + moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8-77.3). Side effects were common (40%-46%) and predominantly mild and gastrointestinal. CONCLUSIONS: Combination doxycycline + azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline + moxifloxacin cured only 85%. Infections that were wild-type for S83/D87 experienced high cure following doxycycline + moxifloxacin, supporting the use of a parC-resistance/susceptibility testing strategy in clinical care.

Treatment of rosacea during pregnancy.

BACKGROUND: Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects. OBJECTIVE: Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF. METHODS: Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy. RESULTS: Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF. CONCLUSIONS: This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.

Oral antibiotics for chronic blepharitis.

BACKGROUND: Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis. OBJECTIVES: To assess the benefits and harms of oral antibiotic use for people with chronic blepharitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification. MAIN RESULTS: We included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total). The two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) -4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD -0.01, 95% CI -0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD -0.56, 95% CI -0.95 to -0.17; n = 93 (high-dose doxycycline versus placebo); MD -0.48, 95% CI -0.86 to -0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low. One study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain. One study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.

Influence of doxycycline administration on rat embryonic development during organogenesis.

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty-one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day-fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.

BreaDoxy sandwich for leptospirosis prophylaxis.

The incidence of leptospirosis is higher in resource-limited countries after the monsoon when people work in waterlogged areas after floods. Prophylactic doses of doxycycline against leptospirosis are effective but compliance is poor due to drug-induced gastritis. A cheap and effective method of improving drug compliance is presented here.

Antibiotic Exposure and Risk for Hospital-Associated Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and (ii) health care-facility-associated, community-onset CDI. We then evaluated the risk associated with antibiotic exposure, including that of specific agents, using multivariable logistic regression. A total of 2,356 cases of CDI among 506,068 admissions were identified (incidence, 46.6 per 10,000). Prior antibiotic use was the dominant risk factor, where for every antibiotic day of therapy prior to the index admission, the odds of subsequent CDI increased by 12.8% (95% confidence interval [CI], 12.2 to 13.4%; P < 0.0001). This was a much stronger association than was inpatient antibiotic exposure (odds ratio [OR], 1.007 [95% CI, 1.005 to 1.009]; P < 0.0001). The highest-risk antibiotics included second-generation and later cephalosporins (especially oral), carbapenems, fluoroquinolones, and clindamycin, while doxycycline and daptomycin were associated with a lower CDI risk. We concluded that cumulative antibiotic exposure prior to admission is the greatest contributor to the risk of subsequent CDI. Most classes of antibiotics carry some risk, which varies by drug and route. This information may be useful for antimicrobial stewardship efforts.

Safety of Combination Laser or Intense Pulsed Light Therapies and Doxycycline for the Treatment of Rosacea.

BACKGROUND: Current treatment options for rosacea include topical agents, oral therapies, phototherapy using lasers, or intense pulsed light (IPL). Combination therapy for rosacea often yields better results than monotherapy. The safety of laser/light treatments in combination with systemic doxycycline has been questioned because of the theoretical risk of photosensitivity. OBJECTIVE: The purpose of this study was to assess the incidence of phototoxicity or photosensitivity in rosacea patients receiving concomitant laser or light treatments and systemic doxycycline. METHODS: Treatment records of 36 patients receiving laser/light treatments while also being treated with standard dose or anti-inflammatory dose of doxycycline were retrospectively reviewed. RESULTS: No adverse reactions related to doxycycline combined with laser/light therapy were reported. Specifically, no photosensitivity or sensitivity to wavelengths in the pulsed dye laser (PDL), or IPL range was observed in this cohort. All patients achieved some degree of clearance. CONCLUSION: The results of this retrospective study demonstrate that doxycycline used in conjunction with laser or nonlaser light therapy is a valid combination therapy for improving signs and symptoms of rosacea. No photosensitivity reactions were observed to commonly used IPL or PDL devices.

Efficacy and safety of oral silymarin in comparison with oral doxycycline and their combination therapy in the treatment of acne vulgaris.

Two factors of oxidative stress and inflammatory processes are implicated in pathogenesis of acne vulgaris. Silymarin has antioxidant and anti-inflammatory activities. This study was done to evaluate the effect of oral silymarin in the treatment of acne vulgaris compared to doxycycline and also their combination therapy. This randomized controlled trial was performed on 60 patients with acne vulgaris were divided into three groups of 20 patients, including: Silymarin (Group 1), Doxycycline (Group 2), and both compounds (Group 3). The patients' response was monitored every month and the lesions were evaluated using photography and two methods of Global Acne Grading system (GAGS) and Acne Severity Index (ASI). According to the results, the response to silymarin was not significantly different with doxycycline in the GAGS index (p = .260), but was lower in the ASI (p = .021). In this study, the synergistic effects of silymarin and doxycycline combination have been investigated in comparison with doxycycline. Although the improvement was more favorable in combination group, there was no statistically significant difference (p = .9 in ASI and p = .5 in GAGS). The results of our study suggest that although the silymarin monotherapy is not as effective as doxycycline for the treatment of acne vulgaris, it can be a therapeutic option.

Methemoglobinemia in an Infant After Sclerotherapy With High-Dose Doxycycline.

Methemoglobinemia occurs when the heme moiety of hemoglobin (Hb) is oxidized from the ferrous to ferric state, leading to impairments in oxygen transport and delivery. Methemoglobinemia is rare in pediatric patients but has been described in the setting of congenital abnormalities in the Hb structure, inherited enzyme deficiencies, oxidative Hb injury in response to illness, and oxidative Hb injury due to toxicants. We present a 1-week-old infant born with a cervical lymphangioma who developed persistent desaturations that were unresponsive to oxygen after sclerotherapy with doxycycline. Arterial blood gas revealed a high Pao2 despite low saturations being found on pulse oximetry and a methemoglobin level that was found to be elevated. Further sclerotherapy was discontinued, the saturations eventually normalized, and the methemoglobin level decreased. This is a novel report of sclerotherapy with doxycycline associated with the development of methemoglobinemia.

Spectrophotometric analysis of discoloration and internal bleaching after use of different antibiotic pastes.

OBJECTIVES: To investigate teeth's antibiotic-induced color differences after bleaching using two different techniques. MATERIALS AND METHODS: One hundred twenty extracted maxillar human incisors were examined. The specimens were randomly divided into six groups, each receiving one of six antibiotic paste fillings: (1) triple antibiotic paste (TAP) with minocycline, (2) double antibiotic paste (DAP), (3) TAP with amoxicillin, (4) TAP with cefaclor, (5) TAP with doxycycline, and (6) no filling (control group). Spectrophotometric measurements were obtained at baseline and then during the first, second, and third weeks after paste placement. The specimens discolored by antibiotics pastes were randomly divided into two subgroups: (1) internal bleaching with hydrogen peroxide (H2O2) and (2) internal bleaching with H2O2 plus Nd-YAG laser irradiation. The ∆E value was calculated and analyzed using a two-way analysis of variance and post-hoc Tukey's test (α = 0.05). RESULTS: The ∆E for all groups showed color differences exceeding the perceptibility threshold (∆E Ëƒ 3.7) at all time points except in the control and DAP groups. Minocycline-induced TAP showed the most severe coronal discoloration (32.42). When the ∆E was examined, thermo/photo bleaching (22.01 ± 8.23) caused more bleaching than walking bleaching (19.73 ± 5.73) at every time point (P = 0.19). No group returned to the original color after bleaching (P < 0.05). CONCLUSIONS: Except for DAP, all antibiotic pastes caused discoloration. Internal bleaching with Nd-YAG laser can be useful for bleaching/removing this discoloration. CLINICAL RELEVANCE: For clinically successful final appearances, understanding the effects of bleaching procedures on antibiotic paste discoloration is important.

Efficacy of Helicobacter pylori eradication regimens in Rwanda: a randomized controlled trial.

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.

DOMINO, doxycycline 40 mg vs. minocycline 100 mg in the treatment of rosacea: a randomized, single-blinded, noninferiority trial, comparing efficacy and safety.

BACKGROUND: There is a lack of evidence for minocycline in the treatment of rosacea. OBJECTIVES: To compare the efficacy and safety of doxycycline 40 mg vs. minocycline 100 mg in papulopustular rosacea. METHODS: In this randomized, single-centre, 1 : 1 allocation, assessor-blinded, noninferiority trial, patients with mild-to-severe papulopustular rosacea were randomly allocated to either oral doxycycline 40 mg or minocycline 100 mg for a 16-week period with 12 weeks of follow-up. Our primary outcomes were the change in lesion count and change in patient's health-related quality of life (using RosaQoL). Intention-to-treat and per protocol analyses were performed. RESULTS: Of the 80 patients randomized (40 minocycline, 40 doxycycline), 71 were treated for 16 weeks. Sixty-eight patients completed the study. At week 16, the median change in lesion count was comparable in both groups: doxycycline vs. minocycline, respectively 13 vs. 14 fewer lesions. The RosaQoL scores were decreased for both doxycycline and minocycline, respectively by 0·62 and 0·86. Secondary outcomes were comparable except for Investigator's Global Assessment success, which was seen significantly more often in the minocycline group than in the doxycycline group (60% vs. 18%, P < 0·001). At week 28, outcomes were comparable, except for RosaQoL scores and PaGA, which were significantly different in favour of minocycline (P = 0·005 and P = 0·043, respectively), and fewer relapses were recorded in the minocycline group than in the doxycycline group (7% and 48%, respectively; P < 0·001). No serious adverse reactions were reported. CONCLUSIONS: Minocycline 100 mg is noninferior to doxycycline 40 mg in efficacy over a 16- week treatment period. At follow-up, RosaQoL and PaGA were statistically significantly more improved in the minocycline group than in the doxycycline group, and minocycline 100 mg gives longer remission. In this study there was no significant difference in safety between these treatments; however, based on previous literature minocycline has a lower risk-to-benefit ratio than doxycycline. Minocycline 100 mg may be a good alternative treatment for those patients who, for any reason, are unable or unwilling to take doxycycline 40 mg.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy.

AIM: To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication. METHODS: A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed. RESULTS: H. pylori eradication was achieved in < 50% of patients [per prototol (PP) = 49%; intention to treat (ITT) = 46%]. Eradication rate was higher in patients administered probiotics than in those without (PP = 55% vs 43%; ITT = 54% vs 40%). Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects. CONCLUSION: Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.

Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study.

INTRODUCTION: Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable. AIM: To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori. PATIENTS AND METHODS: This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires. RESULTS: Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%. CONCLUSIONS: Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication.

Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity.

Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.

Safety of tumescent liposuction under local anesthesia in a series of 4,380 patients.

BACKGROUND: Liposuction is increasingly performed under local anesthesia and in an outpatient setting. The term 'tumescent liposuction' has been used in the literature in patients receiving other forms of anesthesia as well, hence the confusion regarding the safety profile of liposuction performed under local anesthesia alone. OBJECTIVE: To analyze the safety of tumescent liposuction performed under local anesthesia in a larger group of patients. METHODS: Between 2003 and 2010, 4,380 consecutive patients underwent tumescent liposuction by the same surgeon. The occurrence of complications was recorded in detail. RESULTS: There were no serious complications requiring hospitalization. There were no injuries, no nerve damage or permanent lymphedema, no deep venous thrombosis or seroma. Seven patients needed closer follow-up due to large hematoma (n = 3; no drainage needed), allergic drug reaction to doxycycline (n = 2), erysipelas (n = 1) and generalized edema (n = 1). CONCLUSIONS: Tumescent liposuction under local anesthesia is a safe method, providing it is performed by an experienced surgeon and the guidelines of care for liposuction are strictly followed.

Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients.

RATIONALE: The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established. OBJECTIVES: To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease. METHODS: Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization. MEASUREMENTS AND MAIN RESULTS: Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days. CONCLUSIONS: Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.