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Medical research on azitrocin
Azithromycin for treating uncomplicated typhoid and paratyphoid fever (enteric fever).
Cochrane Database Syst Rev. 2008; CD006083
Effa EE, Bukirwa H
BACKGROUND: Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease. OBJECTIVES: To compare azithromycin with other antibiotics for treating uncomplicated enteric fever. SEARCH STRATEGY: In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company. SELECTION CRITERIA: Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI). MAIN RESULTS: Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug-resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting. AUTHORS' CONCLUSIONS: Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone.
Drugs for treating uncomplicated malaria in pregnant women.
Cochrane Database Syst Rev. 2008; CD004912
Orton LC, Omari AA
BACKGROUND: Women are more vulnerable to malaria during pregnancy, and malaria infection may have adverse consequences for the fetus. Identifying safe and effective treatments is important. OBJECTIVES: To compare the effects of drug regimens for treating uncomplicated falciparum malaria in pregnant women. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (February 2008), CENTRAL (The Cochrane Library 2008, Issue 1), MEDLINE (1966 to February 2008), EMBASE (1974 to February 2008), LILACS (February 2008), mRCT (February 2008), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and pharmaceutical companies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of antimalarial drugs for treating uncomplicated malaria in pregnant women. DATA COLLECTION AND ANALYSIS: Two authors assessed trial eligibility and risk of bias, and extracted data. We performed a quantitative analysis only where we could combine the data. We combined dichotomous data using the risk ratio (RR) and presented each result with a 95% confidence interval (CI). MAIN RESULTS: Ten trials (1805 participants) met the inclusion criteria. Two were quasi-randomized, seven did not describe allocation concealment, and all adjusted treatment failure to exclude new infections. One trial reported fewer treatment failures at day 63 with artesunate plus mefloquine compared with quinine (RR 0.09, 95% CI 0.02 to 0.38; 106 participants). One trial reported fewer treatment failures at day 63 with artesunate plus atovaquone-proguanil compared with quinine (RR 0.14, 95% CI 0.03 to 0.57; 80 participants). One trial reported fewer treatment failures at day 28 when amodiaquine was compared with chloroquine (RR 0.20, 95% CI 0.08 to 0.46; 420 participants) and when amodiaquine plus sulfadoxine-pyrimethamine was compared with chloroquine (RR 0.02, 95% CI 0.00 to 0.26; 418 participants). Compared with sulfadoxine-pyrimethamine given alone, one trial reported fewer treatment failures at delivery (or day 40) with artesunate plus sulfadoxine-pyrimethamine (RR 0.15, 95% CI 0.04 to 0.59; 79 participants) and azithromycin plus sulfadoxine-pyrimethamine (RR 0.27, 95% CI 0.10 to 0.76; 82 participants). AUTHORS' CONCLUSIONS: Data are scant. Some combination treatments appear to be effective at treating malaria in pregnancy; however, safety data are limited.
Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).
Cochrane Database Syst Rev. 2008; CD004530
Thaver D, Zaidi AK, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA
BACKGROUND: Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever (enteric fever), but how they compare with other antibiotics and different fluoroquinolones is unclear. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different durations of fluoroquinolone treatment. SEARCH STRATEGY: In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, mRCT, conference proceedings, and reference lists. SELECTION CRITERIA: Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trials' methodological quality and extracted data. We calculated odds ratios (OR) for dichotomous data with 95% confidence intervals (CI). We analysed trials with greater than 60% children separately from trials of mostly adults. MAIN RESULTS: Of 38 included trials, 22 had unclear allocation concealment and 34 did not use blinding. Four trials included exclusively children, seven had both adults and children, and three studied outpatients. ADULTS: Among primary outcomes (clinical failure, microbiological failure, and relapse), compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical failure (594 participants) or microbiological failure (378 participants), but they reduced clinical relapse (OR 0.14, 95% CI 0.04 to 0.50; 467 participants, 6 trials). We detected no statistically significant difference versus co-trimoxazole (82 participants, 2 trials) or azithromycin (152 participants, 2 trials). Fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 95% CI 0.01 to 0.45; 120 participants, 3 trials), but not microbiological failure or relapse. Versus cefixime, fluoroquinolones reduced clinical failure (OR 0.05, 95% CI 0.01 to 0.24; 238 participants; 2 trials) and relapse (OR 0.18, 95% CI 0.03 to 0.91; 218 participants, 2 trials). CHILDREN: In children with high proportions of nalidixic acid-resistant strains, older fluoroquinolones increased clinical failures compared with azithromycin (OR 2.67, 95% CI 1.16 to 6.11; 125 participants, 1 trial), with no differences using newer fluoroquinolones (285 participants, 1 trial). Fluoroquinolones and cefixime were not statistically significantly different (82 participants, 1 trial). Trials comparing different durations of fluoroquinolone treatment were not statistically significantly different (889 participants, 9 trials). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials). AUTHORS' CONCLUSIONS: Trials were small and methodological quality varied. In adults, fluoroquinolones may be better for reducing clinical relapse rates compared to chloramphenicol. Data are limited for other comparisons, particularly in children.
BMC Microbiol. 2008 Oct 8; 8(1): 173
Hall-Stoodley L, Nistico L, Sambanthamoorthy K, Dice B, Nguyen D, Mershon WJ, Johnson C, Hu FZ, Stoodley P, Ehrlich GD, Post JC
ABSTRACT: BACKGROUND: Streptococcus pneumoniae is a common respiratory pathogen and a major causative agent of respiratory infections, including otitis media (OM). Pneumococcal biofilms have been demonstrated on biopsies of the middle ear mucosa in children receiving tympanostomy tubes, supporting the hypothesis that chronic OM may involve biofilm development by pathogenic bacteria as part of the infectious process. To better understand pneumococcal biofilm formation six low-passage encapsulated nasopharyngeal isolates of S. pneumoniae were assessed over a six-eight day period in vitro. RESULTS: Multiparametric analysis divided the strains into two groups. Those with a high biofilm forming index (BFI) were structurally complex, exhibited greater lectin colocalization and were more resistant to azithromycin. Those with a low BFI developed less extensive biofilms and were more susceptible to azithromycin. dsDNA was present in the S. pneumoniae biofilm matrix in all strains and treatment with DNase I significantly reduced biofilm biomass. Since capsule expression has been hypothesized to be associated with decreased biofilm development, we also examined expression of cpsA, the first gene in the pneumococcal capsule operon. Interestingly, cpsA was downregulated in biofilms in both high and low BFI strains. CONCLUSIONS: All pneumococcal strains developed biofilms that exhibited extracellular dsDNA in the biofilm matrix, however strains with a high BFI correlated with greater carbohydrate-associated structural complexity and antibiotic resistance. Furthermore, all strains of S. pneumoniae showed downregulation of the cpsA gene during biofilm growth compared to planktonic culture, regardless of BFI ranking, suggesting downregulation of capsule expression occurs generally during adherent growth.
Clin Ther. 2008 Sep; 30(9): 1639-50
Solans A, Izquierdo I, Donado E, Antonijoan R, Peña J, Nadal T, Carbó ML, Merlos M, Barbanoj M
Background: Rupatadine is an oral active antihistamine and platelet-activating factor antagonist indicated for the management of allergic rhinitis and chronic urticaria in Europe. Objective: The purpose of this study was to describe the effect of the concomitant administration of azithromycin and rupatadine on the pharmacokinetics of rupatadine and its metabolites after repeated doses. Methods: This was a multiple-dose, randomized, open-label, 2-way, crossover, Phase I study in which healthy male and female volunteers received rupatadine 10 mg once a day for 6 days either alone or with azithromycin 500 mg on day 2 and 250 mg from day 3 to day 6. Treatments were administered after a fasting period of 10 hours with 240 mL of water, and fasting conditions were kept until 3 hours postmedication. A washout period of at least 21 days between the 2 active periods was observed. Blood samples were collected and plasma concentrations of rupatadine and its metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examination, electrocardiograms, and laboratory screen controls at baseline and the final study visit. Results: Twenty-four healthy volunteers (15 males, 9 females; mean [SD] age, 25.67 [5.58] years; weight, 65.96 [8.57] kg) completed the study. Except for maximum observed concentration during a dosing interval (C(max,ss)) of 3-hydroxydesloratadine, on average, there were no statistically significant differences in mean plasma concentrations in any of the main pharmacokinetic parameters of rupatadine, desloratadine, and 3-hydroxydesloratadine when administered in combination with azithromycin or alone. The C(max,ss) ratio was 111 (90% CI, 91-136) and area under the plasma concentration-time curve during a dosing interval (AUC(0-tau)) ratio had a value of 103 (90% CI, 91-117). The corresponding ratios for the rupatadine metabolites were 109 (90% CI, 100-120) for C(max,ss) and 103 (90% CI, 96-110) for AUC(0-tau) for desloratadine and 109 (90% CI, 103-115) for C(max,ss) and 104 (90% CI, 100-108) for AUC(0-tau) for 3-hydroxydesloratadine. Point estimates for C(max,ss) ratios using paired data were 111% for rupatadine, 109% for desloratadine, and 109% for 3-hydroxydesloratadine. The 90% CIs were included in the interval 80% to 125% for desloratadine and 3-hydroxydesloratadine, whereas 90% CI for rupatadine was shifted to the right of the interval used for comparing bioavailability of the drugs. A total of 5 subjects reported 9 AEs; 5 of these were thought to be related to the drug administration and all were categorized as mild or moderate. The reported AEs were somnolence (1/24 in the rupatadine group and 1/24 in the rupatadine plus azithromycin group), diarrhea (1/24 in the rupatadine plus azithromycin group), and gastric discomfort (2/24 in the rupatadine plus azithromycin group). Four AEs were considered not to be related (2 episodes of headache, 1 anemia, 1 cheilitis). All were resolved spontaneously. No serious AEs were reported. Conclusions: The results of this study in these healthy volunteers found no significant differences in pharmacokinetic parameters other than C(max,ss) of 3-hydroxydesloratadine between rupatadine 10 mg administered alone or with azithromycin 500 mg on day 2 and 250 mg from day 3 to day 6. The administration of rupatadine compared with rupatadine plus azithromycin met the regulatory definition of bioequivalence in terms of exposure and rate parameters; however, C(max,ss) of rupatadine was outside the conventional confidence interval.
Epidemiol Infect. 2008 Oct 8; 1-7
Nair D, Dawar R, Deb M, Capoor MR, Singal S, Upadhayay DJ, Aggarwal P, DAS B, Samantaray JC
SUMMARYThe first of several cases of meningococcal meningitis was reported in April 2005, in New Delhi, India. Subsequent to this the Government declared an outbreak, which persisted for two periods, from April-July 2005 and January-March 2006. The National Institute of Communicable Diseases (NICD) recommended using WHO criteria for diagnosis of disease. During the outbreak 380 clinically suspected cases were investigated. Of 55 cases diagnosed as confirmed/probable the mortality rate was 14.6%. Meningitis was reported in 60% of cases and meningococcaemia in 40%. Microscopy of petechial rash was positive in 87.5%, CSF Gram stain positive in 68.3%, and latex agglutination test of CSF positive in 64.9% of samples. Neisseria meningitidis (serogroup A) was isolated from 37.7% of cases, 57.7% from CSF. Blood culture was positive in 10.4% of cases. CrgA polymerase chain reaction for N. meningitidis confirmed the isolates. All isolates were susceptible to third-generation cephalosporins, azithromycin and rifampicin, with increasing resistance to ceftriaxone. Penicillin resistance was encountered in 15.4% of strains. Resistance to quinolones was very high at 100% for levofloxacin, 84.6% for ofloxacin and 65.4% for ciprofloxacin. All patients with penicillin-resistant organisms (4) or intermediate sensitivity (4) succumbed to the disease. These patients also had a higher minimum inhibitory concentration to ceftriaxone.
Community Dent Health. 2008 Sep; 25(3): 170-2
Pomarico L, Czauski G, Portela MB, de Souza IP, Kneipp L, de Araújo Soares RM, de Araújo Castro GF
OBJECTIVE: The aim of this work was to analyze pH and sugar concentration in seven antiretroviral and three antibacterial medications frequently prescribed to HIV infected paediatric patients. METHOD: Sugars (sucrose, glucose, lactose and fructose) and pH were measured from every one of ten medications with different serial numbers in two samples. The pH was determined by a previously calibrated digital pHmeter (Beckman). Analysis of free sugars was performed using thin-layer chromatography (TLC). The pH results and the amount of sugar originated from the two samples in each lot were added. The arithmetic mean of these results were computed. RESULTS: Two antiretrovirals (Zidovudin and Abacavir Sulphate) had pH below critical level (3.55 and 3.93, respectively). All three antibacterials analyzed had pH above 5.5, and one of them (Azithromycin) had the highest pH level of the ten medications examined (9.28). Sugar was present in seven out of 10 of the medications analyzed. The antibacterials contained the highest concentration of sucrose, ranging from 40% to 54%. Glucose was found in one of the ten, sucrose was present in seven of them and none showed lactose. Fructose was not observed with the technique used. CONCLUSIONS: A number of medications frequently used by HIV-infected children may cause a significant risk of both caries and dental erosion.
Braz J Infect Dis. 2008 Jun; 12(3): 202-9
Rubio FG, Cunha CA, Lundgren FL, Lima MP, Teixeira PJ, Oliveira JC, Golin V, Mattos WL, Mählmann HK, Moreira ED, Jardim JR, Silva RL, Silva PH
Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.
Atomic force microscopy of supported lipid bilayers.
Nat Protoc. 2008; 3(10): 1654-9
Mingeot-Leclercq MP, Deleu M, Brasseur R, Dufrêne YF
Supported lipid bilayers (SLBs) are widely used in biophysical research to investigate the properties of biological membranes and offer exciting prospects in nanobiotechnology. Atomic force microscopy (AFM) has become a well-established technique for imaging SLBs at nanometer resolution. A unique feature of AFM is its ability to monitor dynamic processes, such as the interaction of bilayers with proteins and drugs. Here, we present protocols for preparing dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DOPC/DPPC) bilayers supported on mica using small unilamellar vesicles and for imaging their nanoscale interaction with the antibiotic azithromycin using AFM. The entire protocol can be completed in 10 h.
Effects of various drugs on alcohol-induced oxidative stress in the liver.
Molecules. 2008; 13(9): 2249-59
Popovic M, Janicijevic-Hudomal S, Kaurinovic B, Rasic J, Trivic S
The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group) reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group), while other groups had similar effects on the studied parameters.