Mass drug administration of azithromycin: an analysis

BackgroundWHO recommends mass drug administration (MDA) of the antibiotic azithromycin for children aged 1–11 months in areas with high rates of infant and child mortality. Notwithstanding the substantial potential benefits of lowering childhood mortality, MDA raises understandable concerns about exacerbating antibiotic resistance.ObjectivesIn this study, we aimed to evaluate the use of MDA using both quantitative and ethical considerations.SourcesWe performed a series of literature searches between July 2019 and June 2022.ContentWe first compared MDA with other uses of antibiotics using the standard metric of ‘number needed to treat’, and five additional criteria: (1) other widely accepted uses of anti-infectives (2) absolute use (i.e. total number), of antibiotics, (3) risk-benefit trade-off, (4) availability of short-term alternatives, and (5) the precedent for implementing similar interventions. We found that MDA falls well within a justifiable range when compared with widely accepted uses of antibiotics in terms of the number needed to treat. The other five criteria we considered provided further support for the use of MDA to prevent childhood mortality.ImplicationsAlthough better data on antibiotic use and resistance are needed, efforts to reduce antibiotic use and resistance should not start with halting MDA of azithromycin in the areas with the highest rates of childhood mortality. Improving data to inform this decision is critical. However, on the basis of the best evidence available, we believe that concerns regarding resistance should not thwart MDA; instead, MDA should be accompanied by robust plans to monitor its efficacy and changes in resistance levels. Similar considerations could be included in a framework for evaluating the benefits of antibiotics against the risk of resistance in other contexts.     

Patient-centered communication of community treatment assistants in Tanzania predicts coverage of future mass drug administration for trachoma

Objective

Prevention of Trachoma, the leading cause of infectious blindness, requires community treatment assistants (CTAs) to perform mass drug administration (MDA) of azithromycin. Previous research has shown that female CTAs have higher MDA coverage, but no studies have focused on the content of conversation. We hypothesize that female CTAs had more patient-centered communication and higher MDA coverage.

Sex differences in the response to GABA antagonists depend on the route of drug administration

 Sex differences in the responses to two GABA-related convulsants (bicuculline, picrotoxin) were studied in rats and mice following intraperitoneal (i.p.) and intravenous (i.v.) drug administration. Following i.p. administration male and female rats were equally sensitive to bicuculline, while female rats were more sensitive to picrotoxin. After i.v. infusion the threshold doses of bicuculline and picrotoxin producing running/bouncing clonus (RB clonus) were significantly lower in male than in female rats, i.e. male rats were more sensitive to both convulsants than females. Following i.p. administration, at some doses female mice were more sensitive to bicuculline and male mice to picrotoxin, although ED₅₀ values between the sexes were not significantly different. After i.v. infusion, doses of bicuculline producing RB clonus and death were significantly lower in male than in female mice, i.e. male mice were more sensitive to bicuculline. The two sexes of mice were equally sensitive to i.v. administration of picrotoxin. While sex and species differences obtained following i.p. drug administration could presumably be explained by differences in pharmacokinetics, the i.v. route of drug administration is suggested as a reliable technique in the studies of sex and species differences in pharmacodynamics. Received: 3 September 1996 / Accepted: 3 December 1996     

Streptococcus pneumoniae exposure is associated with human metapneumovirus seroconversion and increased susceptibility to in vitro HMPV infection

It remains largely unknown which factors determine the clinical outcome of human metapneumovirus (HMPV) infections. The aim of the present study was to analyse whether exposure to bacterial pathogens can influence HMPV infections. From 57 children, serum samples and colonization data for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae were collected at 1.5, 6, 14 and 24 months of age. Seroconversion rates to HMPV were determined and related to bacterial carriage. Frequent nasopharyngeal carriage (≥2 times in the first 2 years of life) of S. pneumoniae, but not of the other three pathogens, was associated with increased seroconversion rates of infants to HMPV at the age of 2 years (frequently vs. less exposed, 93% vs. 59%; p <0.05). Subsequently, the susceptibility of well-differentiated normal human bronchial epithelial cells (wd-NHBE) pre-incubated with bacterial pathogens to in vitro HMPV infection was evaluated. Pre-incubation of wd-NHBE with S. pneumoniae resulted in increased susceptibility to infection with HMPV-enhanced green fluorescent protein (EGFP), as determined by enumeration of EGFP-positive cells. This was not the case for cells pre-incubated with H. influenzae, M. catarrhalis on S. aureus. We conclude that exposure to S. pneumoniae can modulate HMPV infection.     

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film’s surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer’s degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer’s weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.     

Correlation of ANXA1 expression with drug resistance and relapse in bladder cancer

Objective: To investigate the expression of annexin a1 (ANXA1) in adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) compared with the parental cell line (pumc-91) and its relevance to the drug resistance of bladder cancer, as well as explore the relevance of ANXA1 in recurrent bladder cancer tissues as pertinent to relapse. Methods: qRT-PCR and Western blot were implemented to research the level of ANXA1 in two cell lines (pumc-91/ADM and pumc-91). Immunohistochemistry was applied to explore ANXA1 expression in bladder cancer tissues of different intervals of relapse. The association of ANXA1 with clinicopathological parameters was analyzed. Results: The expression of ANXA1 was downregulated in drug-resistant cell line pumc-91/ADM compared to pumc-91. The bladder cancer tissues recurring two years later exhibited higher ANXA1 levels. ANXA1 expression level was positively correlated with T stage, while it was not connected with histological grade strongly. The expression level and influencing factors of ANXA1 in recurrent tissues of bladder cancer were clarified for the first time. Conclusion: ANXA1 may become a promising marker to predict the recurrence and drug resistance of bladder cancer and provide guidance for surveillance.     

尼莫地平对大鼠脊髓损伤的作用研究

目的:研究尼莫地平(nimodipine)对大鼠脊髓损伤后继发性损害的保护作用。方法:成年SpragueDawley雄性大鼠24只,体重180～220 g,采用NYU脊髓撞击伤仪制成脊髓损伤模型后,随机分成尼莫地平(n=12)和生理盐水组(n=12)。两组大鼠受伤后1 h内分别经腹腔给予尼莫地平(1.0 mg/kg)或等量盐水治疗,3次/d,共1周。于受伤后1周和2周进行BBB评分和足迹实验对大鼠双后肢运动功能进行评估。受伤后2周,对损伤部位脊髓组织丙二醛(MDA)含量及脊髓过氧化物酶(MPO)活性进行检测;同时进行免疫组织化学检查确定损伤星形胶质瘢痕和所形成的坏死空洞,利用ED1观察活性小胶质细胞和巨噬细胞。结果:与生理盐水组比较,通过旷场试验(BBB评分)和足迹实验,脊髓损伤后大鼠尼莫地平组1周和2周运动功能明显改善(P<0.01)。与盐水组比较,伤后2周,尼莫地平组大鼠脊髓组织中MDA水平(nmol/g,25.6±9.7 vs 68.5±16.7)和MPO活性(U/g,252.2±63.9 vs 382.8±108.2)均明显降低(P<0.01);尼莫地平组空洞面积(mm2,4.45±1.28 vs 6.16±2.65)和ED1抗体免疫组化染色阳性面积(mm2,1.87±0.42 vs 2.86±1.01)也明显减少(P<0.01)。结论:尼莫地平可以减轻大鼠脊髓损伤后自由基的氧化损伤作用,减小空洞面积和炎症细胞浸润,具有促进脊髓损伤后的修复作用。     

Single-dose extended-release oral azithromycin vs. 3-day azithromycin for the treatment of group A β-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents: a double-blind, double-dummy study

The azithromycin immediate-release formulation (AZ-IR) provides effective treatment for group A β-haemolytic streptococcal pharyngitis in adults. Single-dose therapy with a novel azithromycin extended-release (AZ-ER) formulation could reduce treatment failure and eliminate non-compliance contributing to antimicrobial resistance. A randomized, double-blind, double-dummy, multicentre trial was conducted comparing AZ-ER (single oral 2-g dose) with AZ-IR (3 days, 500 mg once daily) for the treatment of group A β-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents ( n  = 598). The primary endpoint was bacteriological eradication at test -of-cure (TOC; day 24–28) in the bacteriological per-protocol population ( n  = 420). Bacteriological eradication was achieved in 85.4% (175/205) and 81.4% (175/215) of subjects in the AZ-ER and AZ-IR groups, respectively (95% CI  −3.1–11.1). Clinical cure at TOC occurred in 99.0% of subjects in the AZ-ER group and in 96.7% in the AZ-IR group. At long-term follow-up, bacteriological recurrence was observed in 5.5% (9/163) and 7.7% (12/156), respectively. Both treatments were well tolerated; and most adverse events (AEs) were mild to moderate in intensity. The most frequent treatment-related AE was diarrhoea, or loose stools, in 11% of both treatment groups. AZ-ER-treated and AZ-IR-treated subjects had AE burdens (AE  days/patient-year) of 7.6 days and 9.2 days, respectively. A similar trend in favour of AZ-ER was noted for treatment-related diarrhoea burden (1.9 days vs. 2.5 days). A single 2-g dose of AZ-ER is as effective and well tolerated as 3 days of AZ-IR (500 mg once daily) for treating group A β-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents.     

High prevalence of HBV and HCV infection among intravenous drug users in Korea

Although intravenous drug users are a well-known route of hepatitis C virus (HCV) and hepatitis B virus (HBV) transmission, there is no data on the prevalence of HBV and HCV infection among intravenous drug users in Korea. In order to describe the prevalence of HBV and HCV infection, and to determine HCV genotypes in the population, serum samples were collected from 107 intravenous drug users during 2005-2006. Fifty-seven percent (n = 61) were HCV RNA positive and 51% (n = 55) were HBV DNA positive. Co-infection of HBV and HCV were found in 23% (n = 25). HCV genotypes 1b, 2a/2c, 2, 2b, and 3a were found in 38% (n = 23), 44% (n = 27), 8% (n = 5), 2% (n = 1), and 3% (n = 2), respectively. Moreover, mixed infections of genotypes 1b and 2a/2c were found in 5% (n = 3). When the number of patients with HCV genotype 1b compared with that of patients with genotype 2a/2c, HBV DNA titer was not significantly different by independent t-test (t = -0.881, P = 0.392 > 0.05) between the two patient groups. These results suggest that the prevalence of HBV and HCV infection among intravenous drug users is high showing over 50% in Korea and a strategic prevention program should be performed in this group to prevent further infection into local community.     

EMS患者红细胞免疫功能与脂质过氧化的关系

目的:探讨了子宫内膜异位症(EMS)患者红细胞免疫功能的变化及其与脂质过氧化的关系。方法:应用红细胞酵母花环法测定54例EMS患者红细胞免疫功能和化学比色法测定血浆丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)含量,并与30名正常健康人作比较。结果:EMS患者红细胞免疫复合物(RBC-IC)花环率和MDA水平明显升高(P<0.05～0.01),而红细胞C3b受体(RBCC3b-RR)、SOD、GSH-PX、SOD/MDA低于正常(P<0.01)。相关分析显示,RBCC3b花环与MDA呈显著负相关(r=-0.4428,P<0.05)、RBC-ICR与MDA呈正相关(r=0.5488,P<0.05)。结论:EMS患者红细胞免疫功能降低,与活性氧代谢紊乱密切相关。     

The effect of netilmicin and vancomycin on lipid peroxidation processes in cerebrospinal fluid in children with hydrocephalus

In biological systems, it is difficult to determine free radicals because of their reactivity and their very short time of existence. On the basis of markers, which come into being as a result of radical processes, one might believe that there exist reactive oxygen species. One of the determinants of free radical activity of oxygen is the presence of malondialdehyde (MDA), a final product of lipid peroxidation. This study aimed at finding the answer to the question whether the concentration of netylmicin and vancomycin influences the amount of substances reacting with thiobarbituric acid (TBA) in cerebrospinal fluid (CSF) in children with hydrocephalus. Applying the TBA test for examinations with antibiotics added both in vivo and in vitro, we could demonstrate that increased concentration of the examined antibiotics in cerebrospinal fluid reduces the amount of MDA. The results obtained demonstrate that products of lipid peroxidation are present in the CSF samples analyzed. In this study, we found that the concentration of vancomycin and netilmicin influenced the lipid peroxidation process in cerebrospinal fluid in children with hydrocephalus, thus confirming anti-inflammatory properties of the antibiotics applied.     

Nerve growth factor and autophagy: effect of nasal anti-NGF-antibodies administration on Ambra1 and Beclin-1 expression in rat brain

Abstract

Nerve growth factor (NGF) exerts protective actions in the healthy and diseased nervous system. Intranasal administration is a suitable and safe strategy to deliver NGF to CNS neurons. We investigated whether nasal anti-NGF-antibody (ANA) administration affects neuronal autophagy, in view of its putative regulatory role in this process. We focused on olfactory bulbs (OB), neocortex (Cx), hippocampus (HF) and septal complex (SC), known to be NGF-responsive and autophagically active. Our combined molecular/morphological results demonstrate that intranasally administered ANA reaches brain NGF-target neurons and lowers the levels of endogenous NGF and its receptors. Treatment also affects – in a brain region-dependent manner – the expression of the autophagic proteins Beclin-1 and Ambra1, as well as that of proteins belonging to the Bcl2 family, namely Bax and Bcl-2, reflecting apoptotic dysregulation. This study provides a nongenetically modified, NGF-defective animal model, representing a suitable tool to investigate novel properties of the neurotrophin, especially in relation to autophagy.     

急性脑梗死患者血浆ET、Hcy水平与脂质过氧化的关系

目的：探讨了急性脑梗死患者血浆ET、Hcy水平与脂质过氧化的关系。方法：应用放免法和化学比色法对36例急性脑梗死患者进行了血浆ET、Hcy、SOD、MDA水平检测,并与35名正常健康人作比较。结果：急性脑梗死患者血浆ET、Hcy、SOD、MDA水平非常显著的地高于正常人组（P〈0.01）,而SOD水平则显著的低于正常人组（P〈0.01）,相关分析显示,血象ET、Hcy水平与MDA正相关（r=0.6018、0.6128,P〈0.01）,而SOD与MDA呈负相关（r=-0.4418,P〈0.05）。结论：急性脑梗死患者存在脂质过氧化,与ET、Hcy存在相关性。     

脑梗死患者血浆Hcy水平与脂质过氧化的关系

目的：探讨了脑梗死患者血浆同型半胱氧酸（Hcy）水平与脂质过氧化的炎系。方法：应用发光免疫分析测定54例脑梗死患者血浆Hcy水平和化学比色法测定血浆丙二醛（MDA）．超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）,并与35名正常健康人作比较。结果：脑梗死患者血浆Hcy水平和MDA水平非常显著地高于正常人组（P〈0．01）,而SOD、GSH—PX、SOD／MDA水平则低于正常人组（P〈0.01）,相关分析显示：患者Hcy水平与SOD、GSH-Px水平呈负相关（r=-0．4018、-0．4412,P〈0．01）,而与MDA水平成正相关（r=0.6012,P〈0．01）。结论：脑梗死患者血浆Hcy水平的增高与活性氧代谢紊乱有关。     

缺氧缺血性脑病患儿NO、NOS水平与脂质过氧化关系的研究

目的:探讨了缺氧缺血性脑病患儿血清NO、NOS水平与脂质过氧化的关系.方法:应用生化法对30例缺氧缺血性脑病患儿进行了血清NO、NOS测定和化学比色法测定血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)含量,并以35名正常健康人作比较.结果:缺氧缺血性脑病患儿血清NO、SOD、GSH-PX水平显著低于正常人组(P＜0.01),而NOS、MDA水平则显著高于正常人组(P＜0.01),相关分析显示:血清NO、SOD、GSH-PX水平与MDA水平呈明显负相关(r=-0.4286、-0.4125、-0.4108,P＜0.05).结论:缺氧缺血性脑病患儿血清NO、SOD、GSH-PX水平的降低与活性代谢紊乱密切相关.     

肾病综合征患者红细胞免疫功能与脂质过氧化关系的探讨

目的：探讨了肾病综合征患者红细胞免疫功能与脂质过氧化的关系。方法：应用红细胞酵母花环法测定了31例肾病综合征患者的红细胞免疫功能和化学法测定血清丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）含量,并与35名正常健康人作比较。结果：肾病综合征患者RBC-ICR花环率和MDA水平明显升高（P〈0.01）,而RBC-C3bR,SOD,GSH-PX水平则〈正常（P〈0.01）,相关分析显示：RBC-C3b花环与MDA呈显著负相关（r=-0.4786,P〈0.01）,RBC-ICR与MDA呈正相关（r=0.6702,P〈0.01）。结论：肾病综合征患者红细胞免疫黏附功能的降低与活性代谢紊乱密切相关。     

Evaluation of the microscopic observation drug susceptibility assay for detection of Mycobacterium tuberculosis resistance to pyrazinamide

The microscopic observation drug susceptibility assay (MODS) was evaluated to determine susceptibility to pyrazinamide in Mycobacterium tuberculosis, and compared with the broth microdilution method (BMM), absolute concentration method (ACM), and pyrazinamidase (PZase) determination. We tested 34 M. tuberculosis clinical isolates (24 sensitive and eight resistant to pyrazinamide) and the control strains M. tuberculosis H37Rv (ATCC 27294) and Mycobacterium bovis AN5. The MODS, BMM, ACM and PZase determination provided results in average times of 6, 18, 28 and 7 days, respectively. All methods showed excellent sensitivity and specificity (p <0.05). Of the methods studied, the MODS proved to be faster, efficient, inexpensive, and easy to perform. However, additional studies evaluating the MODS in differentiating pyrazinamide-resistant and pyrazinamide-susceptible M. tuberculosis must be conducted with a larger number of clinical isolates.     

Association of polymorphisms in pre-miRNA with inflammatory biomarkers in rheumatoid arthritis in the Chinese Han population

The aim of this study was to detect the association between 2 single nucleotide polymorphisms (SNPs), rs2910164 G>C and rs3746444 T>C, in pre-miRNA (hsa-mir-146a and hsa-mir-499) and the chronic inflammation in the Chinese Han population with rheumatoid arthritis (RA). Two hundred sixty-two Han Chinese patients with RA were recruited in this study. The SNPs were genotyped by polymerase chain reaction restriction fragment length polymorphism. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the plasma concentrations of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1) were measured. There was a significant difference in the levels of CRP and ESR among different genotypes in rs3746444 (p = 0.031 and p = 0.047, respectively). The heterozygote CT had significantly higher levels of CRP and ESR compared with homozygotes CC and TT. No significant association was observed between the SNP rs2910164 and the levels of CRP, ESR, IL-6, TNF-α, and TGF-β1 (all p > 0.05). The results of this study provided the first evidence that the SNP rs3746444 in pre-miR-499 could affect the inflammatory reaction in patients with RA. The findings were significant and might contribute to the clinical assessment of inflammatory activity, which in turn may influence therapeutic decision making.