zithromax and Aortic-Aneurysm--Abdominal

Screening for abdominal aortic aneurysm (AAA) in selected groups is now performed in England, the USA and Sweden. Patients with aneurysms over 55 mm in diameter are generally considered for elective surgical repair. Patients with aneurysm diameters below or equal to 55 mm (termed 'small AAAs') are managed with aneurysm surveillance as there is currently insufficient evidence to recommend surgery in these cases. As more patients are screened, there will be an increasing number of small AAAs identified. There is interest in pharmaceutical interventions (for example angiotensin converting enzyme (ACE) inhibitors, antibiotics, beta-blockers, statins) which could be given to such patients to delay or reverse aneurysm expansion and reduce the need for elective surgical repair.. To assess the effects of medical treatment on the expansion rate of small abdominal aortic aneurysms.. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (May 2012) and CENTRAL (2012, Issue 5). Clinical trials databases were searched for details of ongoing or unpublished studies. The reference lists of articles retrieved by electronic searches were searched for additional citations.. We selected randomised trials in which patients with small AAAs allocated to medical treatment with the intention of retarding aneurysm expansion were compared to patients allocated to a placebo treatment, alternative medical treatment, a different regimen of the same drug or imaging surveillance alone.. Two authors independently extracted the data and assessed the risk of bias in the trials. Meta-analyses were used when heterogeneity was considered low. The two primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to AAA surgery in each group over the trial period.. Seven trials involving 1558 participants were included in this review; 457 were involved in four trials of antibiotic medication, and 1101 were involved in three trials of beta-blocker medication. Five of the studies were rated at a high risk of bias.Individually, all of the included trials reported non-significant differences in AAA expansion rates between their intervention and control groups.The two major drug groups were then analysed separately. For AAA expansion it was only possible to combine two of the antibiotic trials in a meta-analysis. This demonstrated that roxithromycin had a small but significant protective effect (MD -0.86 mm; 95% confidence interval (CI) -1.57 to -0.14). When referral to AAA surgery was compared (including all four antibiotic trials in the meta-analysis), non-significantly fewer patients were referred in the intervention groups (OR 0.96; 95% CI 0.59 to 1.57) than the control groups. When only the trials reporting actual elective surgery were included in a subgroup analysis, the result remained statistically non-significant (OR 1.17; 95% CI 0.57 to 2.42).For the beta-blocker trials, when all were combined in a meta-analysis, there was a very small, non-significant protective effect for propranolol on AAA expansion (MD -0.08 mm; 95% CI -0.25 to 0.10), and non-significantly fewer patients were referred to AAA surgery in the propranolol group (OR 0.74; 95% CI 0.52 to 1.05). Bronchospasm and shortness of breath were the main adverse effects from the beta-blockers. In one trial the adverse effects were reportedly so severe that the trial was stopped early after two years.. There is some limited evidence that antibiotic medication may have a slight protective effect in retarding the expansion rates of small AAAs. The quality of the evidence makes it unclear whether this translates into fewer referrals to AAA surgery, owing mainly to the small sample sizes of the studies.Antibiotics were generally well tolerated with minimal adverse effects. Propranolol was poorly tolerated by patients in all of the beta-blocker trials and demonstrated only minimal and non-significant protective effects. Further research on beta-blockers for AAA needs to consider the use of drugs other than propranolol.In general, there is surprisingly little high quality evidence on medical treatment for small AAAs, especially in relation to the use of newer beta-blockers, ACE inhibitors and statins.

Topics: Adrenergic beta-Antagonists; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Azithromycin; Doxycycline; Humans; Organ Size; Propranolol; Randomized Controlled Trials as Topic; Roxithromycin

The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms (AAAs), and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia (Cpn) infection and AAA expansion.. Nine vascular centers were included and 259 patients were invited to participate. Ten patients declined and 2 patients had chronic kidney failure, leaving a total of 247 patients. Inclusion criteria were: AAA 35-49 mm and age <80 years. Patients were randomized to receive either azithromycin (Azithromax, Pfizer Inc, New York, NY) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks, or placebo in identical tablets. The ultrasound scans were performed in a standardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months. Cpn serology was analyzed in blood samples taken at inclusion and 6 months later. Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence (MIF). Computed tomography (CT) scans were done in 66 patients at inclusion and at 1 year for volume calculations.. Thirty-four patients were excluded, ie, could not be followed for 18 months, 20 in the placebo group and 16 in the active treatment group. A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis. Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients. No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan (0.22 cm/year, interquartile range [IQR]: 0.09 to 0.34 in the placebo group vs 0.22, IQR: 0.12 to 0.36 in the treatment group, P = .85). Volume calculation did not change that outcome (10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group, P = .61). No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001.. Azithromycin did not have any effect on AAA expansion. No correlation was found between serological markers for Cpn and AAA expansion, indicating no clinical relevance for Cpn testing in AAA surveillance. However, a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

Topics: Aged; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Disease Progression; Double-Blind Method; Female; Humans; Immunoglobulin A; Immunoglobulin G; Male; Prospective Studies; Ultrasonography

Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Infected; Aortic Aneurysm, Abdominal; Azithromycin; Critical Care; Female; Humans; Infusion Pumps; Infusions, Intravenous; Male; Middle Aged; Phlebitis; Respiratory Tract Infections; Retrospective Studies; Safety; Solvents

The purpose of this study was to investigate whether Chlamydia pneumoniae (live, antigens, or polysaccharide) cause abdominal aortic aneurysm in a susceptible animal host with appropriate drug reversal.. At laparotomy, preparations of C pneumoniae (live, formalin-inactivated, and heat-inactivated) in calcium chloride were applied to the adventitial surface of the abdominal aorta of rabbits fed a cholesterol-enriched diet. Aortic diameter was measured with ultrasonography. After 3 weeks, immunohistochemistry was used to detect aortic C pneumoniae and macrophages. Presence of C pneumoniae DNA also was assessed.. At high doses (5 x 10(7) organisms) periaortic application of both live and formalin-inactivated preparations resulted in doubling of aortic diameter after 3 weeks, from 2.0 +/- 0.5 mm to 4.3 +/- 1.3 mm (P <.02). C pneumoniae DNA and antigens, together with a heavy macrophage infiltrate, were detected in the dilated aorta. In contrast, periaortic application of heat-inactivated preparations resulted in minimal macrophage influx and aortic dilatation. Treatment of rabbits with azithromycin or carprofen for 10 days after laparotomy abolished the effects of formalin-inactivated C pneumoniae on aortic dilatation. Azithromycin reduced the number of macrophages in the aortic wall more effectively than carprofen.. Because membrane antigenicity is retained in formalin-inactivated but not heat-inactivated organisms, in this experimental model, chlamydial membrane antigens (rather than live organisms) appear to cause the aneurysmal dilatation and associated macrophage recruitment. Azithromycin is likely to reverse these effects with an antiinflammatory mechanism.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Bacterial; Aortic Aneurysm, Abdominal; Azithromycin; Carbazoles; Chlamydophila pneumoniae; DNA, Bacterial; Rabbits